Albert Baird Hastings : an oral history [sound recording]
Page  [i]

ALBERT BAIRD HASTINGS National Library of Medicine Bethesda, Maryland 1969

Page  [ii] TABLE OF CONTENTS Introduction Curriculum vitae of Albert Baird Hastings Bibliography of Albert Baird Hastings Transcript Index Appendix: tape-transcript correlation i - LV v - x XL - 1 - 668 - 705 - XXXIV 667 704 706

Page  i Introduction This oral history memoir is the culmination of a series of tape recorded interviews held with Dr. Albert Baird Hastings in La Jolla, California, in December, 1967, and February and May, 1968. This transcript is the final edited copy which resulted from roughly 39 hours of interview. After each visit to La Jolla, the initial "verbatim" transcript was prepared from the magnetic tape and edited first by the interviewer (chiefly for correction of typographical errors and punctuation) and then by Dr. Hastings, who made minor changes generally for clarification. Deletions of portions of the transcript were extremely rare. As a result the memoir retains a great deal of spontaneity and candor. All of the interviews were held in Dr. Hastings1 office at the Scripps Institute of Oceanography (temporary home of the Department of Neurosciences, School of Medicine) at the University of California, San Diego, in La Jolla, California, with the exception of one interview held in Dr. Hastings1 study in his home in La Jolla, The memoir is not intended to resemble a document written for publication; it is intended to be a transcript of the spoken word. In retrospect, it is very easy to justify the selection of Dr. Hastings for the Oral History Program of the National Library of Medicine. When Dr. Martin M. Cummings, Director of the National Library of Medicine, first approached Dr. Hastings in August of 1967 to participate in the Oral History Program, it was on the basis of Dr. Hastings1

Page  iiii career in biochemistry as related to medicine at several distinguished institutions and in the company of numerous equally outstanding physicians and scientists. As the interviews progressed, it was soon obvious that a rich vein of knowledge had been tapped. Through this autobiographical memoir, one may gain significant insight into "what makes Albert Baird Hastings tick" as well as a better understanding of this important period in the development of contemporary medicine from a qualitative to a quantitative science. Dr. Hastings has divided his discussion chronologically and by the laboratories and institutions with which he has been associated. In each instance, he speaks in depth and with candor about the scientific research carried on by himself and his colleagues, about the environment in which he worked, and about his students, colleagues, and associates in his active scientific career. His long association with the Federal Government through service on numerous scientific committees and councils is amply covered. It is my impression that the weaknesses of this interview where present can best be attributed to the shortcomings of the interviewer and his preparation. The location of Dr. Hastings1 papers in La Jolla ruled out ready access between interviews. Though the interviewer was trained in medicine and clinical chemistry, the discussions of Dr. Hastings' scientific contributions would have benefited by the presence of one more knowledgeable in biochemistry. In spite of this, the vigor, enthusiasm, and articulate nature of Albert Baird Hastings have produced a document which truly supplements the written record and

Page  iiiIll provides insight into and new information about many of the areas discussed. The original copy of this memoir is to be housed with Dr. Hastings' sizeable collection of personal papers in the National Library of Medicine. Materials consulted in preparation for these interviews included the following: 1) The publications listed in Dr. Hastings1 bibliography. 2) Dr. Hastings1 personal papers contained in 18 filing drawers and consisting of correspondence, lecture notes, manuscripts, etc. 3) Corner, G. W. A History of the Rockefeller Institute. New York, Rockefeller Institute Press, 1964. 4) Medicine in the Division of Medical Sciences, University of Chicago, edited by F. C. McLean and N. Gorgas. Methods and Problems of Medical Education, 19th Series. New York, The Rockefeller Foundation, 1931. 5) Baxter, J. P. Scientists Against Time. Boston, Little, Brown, 1946. 6) Advances in Military Medicine, Vols. I and II, edited by E. C. Andrus, D. Bronk, et al. Boston, Little, Brown, 1948. 7) Stewart, I. Organizing Scientific Research for War. Boston, Little, Brown, 1948. Finally, any individual who wishes to listen to a particular portion of the tape recording must identify from the transcript the number and side of the reel on which the particular passage occurs. He then must estimate roughly where the passage would appear, advance

Page  ivIV to that location on the tape and begin listening while checking the transcript. The only portion of the transcript which has been transposed from its original location is Dr. Hastings1 "closing statement" and evaluation of his career, which appears on tape at the end of Reel 18, Side I and in the transcript has been moved to the end of the memoir. The listener should also be aware that beginning with Reel 4, the tapes are numbered consecutively from the first reel of the first interview in December, 1967, and should not be confused by the designation of reel number cited at the beginning of each tape, as this refers to the reel number for that particular series of interviews. Peter D. Olch, M.D. Deputy Chief History of Medicine Division National Library of Medicine

Page  vV CURRICULUM VITAE A(lbert) Baird Hastings Born: November 20, 1895; Dayton, Kentucky Education: Shortridge High School, Indianapolis B.S., University of Michigan, 1917 Ph.D., Columbia University, 1921 Diplomate, American Board of Clinical Chemists, 1952 Honorary Degrees: SCoD., University of Michigan, 1941 Sc.D., Harvard University, 1945 Sc.D., Oxford University, 1952 SCoD., Boston University, 1956 Sc.D., St. Louis University, 1965 Sc.D., Columbia University, 1967 The President's Medal for Merit, Committee on Medical Research, Office of Scientific Research and Development, 1948 Honorary Professorship, University of San Marcos, Lima, Peru, 1957 Distinguished Service Award, Medical Alumni Association, University of Chicago, June, 1961 The Banting Medal of the American Diabetes Association, June, 1962 American College of Physicians, 1964 Award U.SoP.H.So citation for service, consultation and advice (1917-1964), 1964 Modern Medicine Distinguished Achievement Award, 1965 A. Baird Hastings Symposium, "Metabolic Regulation in Heterogeneous Systems," University of Michigan, Ann Arbor, Michigan, October 23-24, 1965 Massachusetts Institute of Technology, silver plaque citation, Boston, 1965 Brookhaven National Laboratory, citation for service, 1965 Sesquicentennial Award, University of Michigan, Ann Arbor, 1967 Citation, Department of Physiology, Columbia University, 1967 Positions 1917 - 1921 1921 - 1922 1922 - 1926 1924 (Summer) 1925 Chemist, U.S. Public Health Service Assistant, Rockefeller Institute for Medical Research Associate, Rockefeller Institute for Medical Research Lecturer, University of Southern California Visiting Scientist, Kaiser Wilhelm Institute for Biology, Berlin

Page  viVL 1926 - 1928 1928 - 1935 1930 - 1931 1935 - 1958 1950 1952 (June-Dec.) 1954 1957 (July-Nov.) 1959 1959 - 1962 1959 - 1966 1962 - 1966 1962 (Sept.-Nov.) 1966 1966 1967 (Nov.) Professor of Physiological Chemistry, University of Chicago Professor of Biochemistry, University of Chicago Visiting Professor of Biochemistry, Peiping Union Medical College, Peiping, China Hamilton Kuhn Professor of Biological Chemistry and Head of Department, Harvard Medical School Visiting Scientist, Carlsberg Laboratory, Copenhagen Fulbright Lecturer, Oxford University, Oxford, England Member, U.S0 Delegation to the International Conference on Peaceful Uses of Atomic Energy, Geneva Visiting Professor, John Curtin School for Medical Research, Australian National University, Canberra Professor Emeritus, Harvard Medical School Director of the Division of Biochemistry, Scripps Clinic and Research Foundation, La Jolla, California Research Associate, University of California, San Diego, Department of Marine Biology Head, Laboratory for Metabolic Research, Scripps Clinic and Research Foundation, La Jolla, California Guest Investigator, U.S. Naval Medical Research Unit No. 2, Taipei, Taiwan Member Emeritus, Scripps Clinic and Research Foundation, La Jolla, California Research Associate, University of California, San Diego, Department of Neurosciences, School of Medicine Visiting Professor, School of Medicine, Pahlavi University, Shiraz, Iran Lectureships 1937 (November) 1940 (December) 1957 (November) 1962 (June) 1964 (April) 1965 (May) Benjamin Knox Rachford Lectureship, University of Cincinnati Harvey Lecture John P. Peters Memorial Lecture, Yale University Banting Memorial Lecture, American Diabetes Association Lecture for 1964 American College of Physicians Award Black Memorial Lecture, Los Angeles Academy of Medicine

Page  viiVLL Academies American Academy of Arts and Sciences, 1936- American Philosophical Society, 1941- National Academy of Sciences - National Research Council, 1937- Royal Danish Academy of Sciences and Letters, 1951- Professional Societies American Association for the Advancement of Science, 1920; Vice President, 1965 Chairman, Medical Sciences Section, 1965 American Association for Cancer Research, 1946-American Association of Clinical Chemists, 1965-American Bureau for Medical Aid to China, American Chemical Society, 1917-American Institute for Nutrition, 1940-American Physiological Society, 1927-American Society of Biological Chemists, 1921- Treasurer, 1936 - 1940 Vice President, 1943 - 1944 President, 1945 - 1947 Association of American Physicians, 1936-Association of Harvard Chemists, 1962-Biological and Medical Sciences Research Club of San Diego, 1963- President, 1963 - 1964 The Biochemical Society, 1949-Central Society for Clinical Research, 1928-The Endocrine Society, 1955-The Gerontological Society, Inc., 1945-The Harvey Society, 1921-Radiation Research Society, 1958-San Diego Academy of Medicine, 1965-San Diego Zoological Society, 1963-Society of Chemistry of Peru, 1957-Society of Columbia Chemists, 1961-Society for Experimental Biology and Medicine, 1920- Vice President, 1943 - 1945 President, 1945 - 1947 Society for the Study of Development and Growth, 1948-Taipei International Medical Society, 1962-Western Association of Physicians, 1960-The Yu Wang Fu Association, 1931-Los Angeles Academy of Medicine, 1965- Editorships American Journal of Physiology, 1956 - 63

Page  viiiVLLL Endocrinology, 1963- Handbook of Physiology, 1959 - 66 Journal of Applied Physiology, 1956- Journal of Biological Chemistry, 1941 - 1954; 1955 - 1959 Physiological Reviews, 1932 - 1935 Proceedings of the Society for Experimental Biology and Medicine, 1935 -Geriatrics, 1965- Advisor to Committee on The Handbook of Biological Data, American Institute of Biological Sciences, 1949 - 1953 Advisory Board, Biochemical Preparations, 1945-Advisory Board, Comprehensive Biochemistry, 1957 Advisory Board, Methods of Biochemical Analysis, 1953 - 1960 Advisory and Consultative Activities to Governmental Agencies Associated Universities, Inc., Brookhaven National Laboratory Trustee, 1948 - 1951 Visiting Committee to the Medical Department, 1956 - 1964; Chairman, 1962 - 1964 Consultant, 1959 - 1964 Research Collaborator, 1964- Atomic Energy Commission Member, Board of Review, 1947 Member, Committee on Biology and Medicine, 1947 - 1950 Consultant, Director, Division of Biology and Medicine, 1950 - 1963 Member, Oak Ridge Nat. Lab. Advisory Committee for Biology, 1955 - 1957 Member, Committee on Medical Research, Office of Scientific Research and Development, 1941 - 1947 (Presidential Appointee) National Academy of Sciences - National Research Council, 1937- Member, Division of Medical Sciences, 1937 - ; Member-at- large, 1964 - ; Executive Committee, 1964 - ; Fellowships Board, 1937 - 1954; Chairman, 1951 - 1954 Member, Division of Biology and Agriculture, 1944 - 1955 Member, Board of Food and Nutrition, 1944 Committee on Growth, 1945 - 1946 Advisory Committee on Atomic Bomb Casualties, 1951 - 1959 Advisory Committee to evaluate the NIH General Research Support Program, 1965 U.S. Army Quartermaster Research and Development Command Member, Advisory Board, 1955 - 1958

Page  ixIX U.S. Army, Walter Reed Institute of Research Member, Scientific Advisory Board, 1956 - 1962 U.S. Public Health Service, National Institutes of Health Member, National Advisory Cancer Council, 1943 - 1946 Member, National Advisory Health Council, 1947 - 1948 Member, National Advisory Arthritis and Metabolic Diseases Council, 1956 - 1960 Member, National Advisory Heart Council, 1960 - 1964; National Heart Council, Israel Research Survey, 1962 Consultant, National Heart Institute, 1964-Program Consultant, National Institute of Child Health and Human Development, 1964 - 1965 Training Review Committee for Aging, National Institute of Child Health and Human Development, 1965 - 1969 Additional Advisory Activities Advisory Council, Life Insurance Medical Research Fund, 1946 - 1950 Associate, John Winthrop House, 1947 - 1959 Board of Directors, American Bureau for Medical Aid to China, 1963 - 1965 Board of Scientific Advisors, Merck Institute for Therapeutic Research, 1957 - 1962 Board of Syndics, Harvard University Press, 1936 - 1946; 1947 - 1951; 1953 - 1955; 1956 - 1958 Consultant, The Regents of the University of California, Laboratory for Nuclear Medicine and Radiation Biology, 1959-Consultant in Chemistry, Peter Bent Brigham Hospital, 1935 - 1959 Faculty Advisory Committee, Nieman Fellow, 1949 - 1959 Member, Advisory Council, Children's Hospital Research Foundation, Cincinnati, 1946 - 1959 Member, Executive Committee of the Growth Society, 1945 - 1946 National Advisory Board, Physiological Research Laboratory, Scripps Institution of Oceanography, 1963 - ; Chairman, 1963 - 1965 National Scientific Advisory Committee, Oklahoma Medical Research Foundation and Institute, 1963 - ; Chairman, 1964 Overseers' Committee to visit the Harvard University Press, 1959 - 1965 Research Council, San Diego Zoological Society, 1963-Scientific Advisory Board, Cancer Research Institute, New England Deaconess Hospital, 1949-Scientific Advisory Board, Massachusetts General Hospital, 1951 - 1954 Scientific Advisory Board, McLean Hospital, 1945 - 1959 Scientific Advisory Committee, The Nutrition Foundation, 1947 - 1961

Page  xX Trustee, Protein Foundation (presently Blood Research Institute), 1959-Trustee, Worcester Foundation for Experimental Biology, 1950 - 1954 Member, National Advisory Board, Scripps Clinic and Research Foundation, 1965- Professional Organizations Aesculapian Club of Boston, 1936- Alpha Chi Sigma (Chemistry Fraternity), 1916- Alpha Omega Alpha (Honor Medical Society), Harvard Chapter, 1936- Cambridge Scientific Club, 1946- Examiner Club, 1951 - 1958 Harvard Faculty Club, 1935 - 1958 Harvard Medical Alumni Association of Southern California, 1959- La Jolla Torch Club, 1959- Medical Exchange Club, Boston, 1943- Navy League of the United States, 1959 - 1960 Phi Chi (Medical Fraternity), 1918- Phi Mu Alpha (Sinfonia) (Music Fraternity), 1916- R. C. R. C. (Roxbury Clinical Reading Club), Boston, 1941- Sigma Xi (Honorary Scientific Research Fraternity), 1917- The Sumner Club, La Jolla, 1959- Service Organizations La Jolla Town Council, 1960- Library Association of La Jolla, 1959 - 1964 Social Clubs Century Association, 1948-Chicago Literary Club, 1931-Cosmos Club, 1942-Harvard Club of Boston, 1940-1961 Harvard Club of New York City, 1940-1958; 1961-St. Botolph Club, Boston, 1946-1958 Harvard Club of San Diego, 1965-Cuyamaca Club of San Diego, 1966-

Page  xiXL Bibliography of Albert Baird Hastings A single asterisk (*) designates those articles Dr. Hastings felt were significant contributions. A double asterisk (**) designates those scientific contributions that Dr. Hastings felt were important in his career. [Though numbered 2-283, this is a complete bibliography as of December 1968] * 2. A. B. Hastings. Effect of fatigue on bicarbonate content of plasma. Am. J. Physiol., 49, 134 (1919). 3. F. H. Pike, H. C. Coombs, A. B. Hastings. Changes in the concentration of C02 of the blood following changes in the circulation through the medulla oblongata. Proc. Soc. Exp. Biol. Med., 16_, 49 (1919). 4. A. B. Hastings. An investigation of changes in the blood and urine resulting from fatigue. Pub. Health Reprint 546 (Aug. 1, 1919). 5« E. L. Scott, A. B. Hastings. Some phases of protein catabolism and fatigue. Pub. Health Reprint 617 (Oct. 15, 1920). 6. E. L. Scott, A. B. Hastings. Sugar and oxygen relationships in the blood of dogs. Proc. Soc. Exp. Biol. Med., 17, 67 (1920). 7. E. L. Scott, A. B. Hastings. A study of the sugar and oxygen relationships in the blood of dogs during exercise. Proc. Soc. Exp. Biol0 Med., 17_, 120 (1920). 8. A. B. Hastings. The lactic acid in the blood of dogs in exercise. Proc. Soc. Exp. Biol. Med., 18, 306 (1921). * 9. Ae B. Hastings, H. A. Murray, Jr. Observations on parathyroid-ectomized dogs. J. Biol. Chem., 46, 233 (1921). 10. A. B. Hastings, C. D. Murray, H. A. Murray, Jr. Certain chemical changes in the blood after pyloric obstruction in dogs0 J. Biol. Chem., 4£, 223 (1921). * 11. A. B. Hastings. The physiology of fatigue. Pub. Health Reprint 117 (May, 1921).

Page  xiiXll 12. A. B« Hastings. A hydrogen electrode vessel adapted for titrations. J. Biol. Chem., 46, 463 (1921). 13. Ac B. Hastings, H. C* Coombs, F. H. Pike. The changes in the concentration of the carbon dioxide resulting from changes in the volume of blood flowing through the medulla oblon-gatao Am. J. Physiol., 57., 104 (1921). 14. G. E. Cullen, A. B. Hastings. A comparison of colorimetric and electrometric determinations of hydrogen ion concentrations in solutions containing carbon dioxide. J. Biol. Chem., 5£, 517 (1922). 15c A. B. Hastings, D. D. Van Slyke. The determination of the three dissociation constants of citric acid. J. Biol. Chem., 53>, 269 (1922). 16. J. He Austin, Go E« Cullen, A. B. Hastings, F. C. McLean, J. P. Peters, D. D. Van Slyke. Studies of gas and electrolyte equilibria in the blood„ I. Technique for collection and analysis of blood, and for its saturation with gas mixtures of known composition. J» Biol. Chem., 54, 121 (1922). 17. D. D. Van Slyke, A. B. Hastings, M. Heidelberger, J. M. Neill. Studies of gas and electrolyte equilibria in the blood. III. The alkali binding and buffer values of oxyhemoglobin and reduced hemoglobin. J. Biol. Chem., 54, 481 (1922). 18. D. D. Van Slyke, A. B. Hastings, J. M. Neill. Studies of gas and electrolyte equilibria in the blood. IV. The effect of oxygenation and reduction on the bicarbonate content and buffer value of blood. J. Biol. Chem., 54, 507 (1922). 19. Co A. L. Binger, A. B. Hastings, J. M. Neill. Edema associated with moderate bicarbonate administration during convalescence from pneumonia. Arch. Int. Med., 31, 145 (1923). 20. A. B. Hastings, A. Hopping. A criticism and modification of the McLean blood sugar method. Proc. Soc. Exp0 Biolo Med., 2£, 254 (1923). 21. A. B. Hastings, J. M. Neill, H. J. Morgan, C. A. L. Binger. The acid-base balance in pneumonia. Proc. Soc. Exp. Biol. Med., Zl, 66 (1923). 22. A. B. Hastings, D. D. Van Slyke, J. M. Neill, M. Heidelberger, C. R. Harington. Studies of gas and electrolyte equilibria in the blood. VI. The acid properties of reduced and oxygenated hemoglobin. J. Biol. Chem., 60, 89 (1924).

Page  xiiiXL1L 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. H. A. Salvesen, A. B. Hastings, J. F, Mclntosh. Blood changes and clinical symptoms following oral administration of phosphates. J. Biol. Chem., 60, 311 (1924). H. A. Salvesen, A. B. Hastings, J. F. Mclntosh. The effect of the administration of calcium salts on the inorganic composition of blood. J. Biol. Chem., 60, 327 (1924). A. Be Hastings, J0 Sendroy, Jr., C. D. Murray, M. Heidelberger. Studies of gas and electrolyte equilibria in the blood. VII. The effect of carbon monoxide on the acidity of hemoglobin. J. Biol. Chem., 61, 317 (1924). A. B. Hastings, J. M. Neill, H. J0 Morgan, C. A. L. Binger. Blood reaction and blood gases in pneumonia. J. Clin. Invest., i, 25 (1924). A. B. Hastings, J. Sendroy, Jr. Studies of acidosis. XX. The colorimetric determination of blood pH at body temperature without buffer standards. J. Biol. Chem., 61, 695 (1924). J. M. Neill, A. B. Hastings. The influence of the tension of molecular oxygen upon certain oxidations of hemoglobin. J. Biol. Chem., 63., 479 (1925). C. D. Murray, A. B. Hastings. The maintenance of carbonic acid equilibrium in the body with special reference to the influence of respiration and kidney function on C0«9 HCO^1, and COo" concentrations in plasma. J« Biol. Chem., 65,, 265 (1925). A. B. Hastings, J. Sendroy, Jr., W. Robson. Studies of acidosis. XXI. The colorimetric determination of the pH of urine. J. Biol. Chem., 65_, 381 (1925). A. B. Hastings, J. Sendroy, Jr. The effect of variation in ionic strength of the apparent first and second dissociation constants of carbonic acid. J. Biol. Chem,,, 65, 445 (1925). D. D. Van Slyke, A. B. Hastings, C. D. Murray, J. Sendroy, Jrc Studies of gas and electrolyte equilibria in the blood. VIII. The distribution of hydrogen, chloride and bicarbonate ions in oxygenated and reduced blood. J. Biol. Chem., 65., 701 (1925). 33. H. J. Stewart, J. H. Crawford, A. B. Hastings. The effect of tachycardia on the blood flow in dogs. I. The effect of rapid irregular rhythms as seen in auricular fibrillation, J. Clin. Invest., 3., 435 (1926).

Page  xivXIV * 35 36 37 38, 39, 40, 41, A. B. Hastings, C. D. Murray, J. Sendroy, Jr. Studies of the solubility of calcium salts. I« The solubility of calcium carbonate in salt solutions and biological fluids. II. The solubility of tertiary calcium phosphate in salt solutions and biological fluids. III. The solubility of calcium carbonate and tertiary calcium phosphate under various conditions. (Sendroy and Hastings, II and III). J. Biolc Chem., 7i, 723 (1927). A. B. Hastings, H. Ac Salvesen, J0 Sendroy, Jr., Do D0 Van Slyke Studies of gas and electrolyte equilibria in the blood. IX. The distribution of electrolytes between transudates and serumc J. Gen. Physiol., 8_, 701 (1927). C. A. L. Binger, A. B« Hastings, J. Sendroy, Jr. A further study of blood reaction and blood gases in pneumonia. J. Exp. Med., 45_, 1081 (1927). A. B. Hastings, H. B. Van Dyke. The importance of the carbonate ion in physiological activity. Proc. Soc0 Exp. Biol. Med., 24, 831 (1927). A. B. Hastings. The role of hemoglobin in the blood. Symposium Monograph (1928). Colloid Ho B. Van Dyke and A. B. Hastings. The response of smooth muscle in different ionic environmentSc Am. J0 Physiolc, 83., 563 (1928). D. D. Van Slyke, J. Sendroy, Jr., A. B. Hastings, J» M. Neill. Studies of gas and electrolyte equilibria in the blood. X. The solubility of carbon dioxide at 38° in water, salt solution, serum and blood cells. J. Biol. Chem., 78, 765 (1928). 42. A. B. Hastings, J. Sendroy, Jr., D. D. Van Slyke. Studies of gas and electrolyte equilibria in the blood. XII. The value of pK1 in the Henderson-Hasselbalch equation for blood serum. J0 Biol0 Chem., 79, 183 (1928). 43. A. B. Hastings, J. Sendroy, Jr., J. F. Mclntosh, D. D. Van Slyke, Studies of gas and electrolyte equilibria in the blood. XIII. The distribution of chloride and bicarbonate in the blood of normal and pathological human subjects. J. Biol. Chem., 79., 193 (1928). 44. D. D. Van Slyke, A. B. Hastings, A. Killer, J. Sendroy, Jr. Studies of gas and electrolyte equilibria in the blood. XIV. The amounts of alkali bound by serum albumin and globulin. J. Biol. Chem., 7.9, 769 (1928).

Page  xvXV * 45. J. Sendroy, Jr., A. B. Hastings. The activity coefficients of certain acid-base indicators. J. Biol. Chem., 82, 197 (1929). * 46. N. W. Shock, A. B. Hastings. A microtechnique for the determination of the acid-base balance of the blood. Proc. Soc. Exp. Biol. Med., 26_, 780 (1929). 47. A. E. Koehler, Ac B. Hastings. Metabolic studies following the administration of suprarenal extracts. Am. J. Physiol., 90, 418 (1929). 48. R. DC Barnard, A. B. Hastings. Attempts to demonstrate combination between ethylene and hemoglobin. Anesthesia and Analgesia, 9., 234 (1930). 49. C. P. Miller, Jr., A. B. Hastings. A synthetic substitute for ascitic fluid in a medium for the cultivation of gonococ-cus. Proc. Sec. Exp. Biol. Med., 27., 748 (1930). * 50. A. B. Hastings, E. L. Compere. Effect of bilateral suprare-nalectomy on certain constituents of the blood of dogs. Proc. Soc. Exp. Biol. Med., 28_, 376 (1931). 51. J. E. Davis, A. B. Hastings. Effect of suprarenalectomy on muscle tissue respiration. Proc. Soc» Exp. Biol. Med., 2£, 378 (1931). 52. Jc E. Davis, A. B. Hastings. Effect of thyroidectomy and suprarenalectomy on muscle tissue respiration. Proc. Soc. Exp. Biol. Med., 2£, 747 (1931). 53. A. B. Hastings. Description of Biochemical Research Laboratories at the University of Chicago Clinics. Contribution to "Methods and Problems of Medical Education: 19th Series." Rockefeller Foundation (1931). 54. S. H. Liu, A. B. Hastings. Acid-base paths in human subjects. Proc. Soc. Expo Biol. Med., 2j8, 781 (1931). 55. He N. Harkins, A. B. Hastings. A study of electrolyte equilibrium in the blood in experimental acidosis. J. Biol. Chem., 9£, 565 (1931). * 56. H. H. Roseberry, A. B. Hastings, J. K. Morse. X-ray analysis of bone and teeth. J. Biol. Chem., 9£, 395 (1931). 57. A. B. Hastings, A. H. Steinhaus. A new chart for the interpretation of acid-base changes and its application to exercise. Am. J. Physiol., 96, 538 (1931).

Page  xviXVI 58. A. Bo Hastings, H. B. Van Dyke. Studies of bromide distribution in the blood. I. In vitro experiments of bromide and chloride distribution. J. Biol0 Chem., 9£, 13 (1931). 59. H. Be Van Dyke, A. B. Hastings. Studies of bromide distribution in the blood. II. The distribution of bromides and chlorides in the blood of dogs following the administration of sodium bromide. J. Biol. Chem., 92, 27 (1931). 60. B. F. Avery, A. B. Hastings. A gasometric method for the determination of lactic acid in the blood. J. Biol. Chem., 94, 273 (1931). 61. L. J. Bogert, A. B. Hastings. The calcium salts of bone. J. Biol. Chem., 94, 473 (1931). 62o A. B. Hastings, H. N. Harkins, S. K. Liu. Blood and urine studies following bromide injection. J. Biolc Chern., 94, 681 (1932). 63. C. P. Miller, Jr., A. B. Hastings, R. Castles. Influence of inorganic salts on the multiplication of gonococcus. J. Bacteriol., 24, 439 (1932). 64. M. S. Mishkis, E. B. Ritchie, A. B. Hastings. Bromide and chloride distribution between serum and cerebrospinal fluid. Proc. Soc. Exp. Biol. Med., 3£, 473 (1933). 65. C. Be Huggins, A. B. Hastings. Effect of calcium and citrate injections into cerebrospinal fluid. Proc. Soc. Exp. Biol, Med., 3(), 459 (1933). 66. A. B. Hastings, G. B. Huggins. Experimental hypocalcemia. Proc. Soc. Exp. Biol. Med., 3£, 458 (1933). 67. E. S. G» Barren, A. B. Hastings. Studies on biological oxidations. II. The oxidation of lactic acid by alpha-hydroxy-oxidase. J. Biol. Chem., 100, 155 (1933). 68. F. C. McLean, A. B. Hastings, L. Eichelberger, J. L. Hall. On the ionization of calcium citrate. Proc. Soc. Exp. Biol. Med., 3£, 1136 (1933). 69. H. B. Hanson, A. B. Hastings. The effect of smoking on the carbon monoxide content of the blood. J.ACM.A0, 100, 1481 (1933). 70. F. W. Schlutz, AB B. Hastings, M» Morse. Changes in certain blood constituents produced by partial inanition and muscular fatigue. Am. J. Physiol., 104, 669 (1933).

Page  xiiXVI1 71. 72. 72a, 73. 74. ** 75. ** 76. ** 77. 78. 79. 80, * 81, Fo Co McLean, A. B. Has tings . The concentration of calcium ions in biological fluids. Proc. Soc. Expc Biol. Med., 30, 1344 (1933). E. B. Bay, F. C. McLean, A. B. Hastings. Electrical and mechanical changes in isolated heart following changes in calcium content of the perfusing fluid. Proc. Soc. Exp. Biol. Med., 3£, 1346 (1933). F. C. McLean, E. B. Bay and A. B. Hastings. Electrical changes in heart of the rabbit following changes in potassium content of perfusing fluid. ProCo Am. J. Physiol., 105, 72 (1933). Jc Eo Davis, A. B. Hastings. The relationship of the adrenal and thyroid glands to excised muscle metabolism. Amc J. Physiol., 105, 110 (1933). F. C. McLean, A. B. Hastings, containing fluids. Proc, (1934). State of calcium in protein-Soc. Exp. Biol. Medc, 31, 529 N. W. Shock, A. B» Hastings. Studies of the acid-base balance of the blood. I. A microtechnique for the determination of the acid-base balance of the blood. J. Biol. Chem., 104, 565 (1934). A. B. Hastings, N« W. Shock. Studies of the acid-base balance of the blood. II. A nomogram for the calculation of acid-base data for blood. J. Biol. Chem., 104, 575 (1934). N. W. Shock, A. B. Hastings. Studies of the acid-base balance of the blood. III. Variation in the acid-base balance of the blood in normal individuals. J. Biol. Chem., 104, 585 (1934). L. Drastich, W. E. Adams, A. B. Hastings, C. L. Compere. The effect of exercise on the acid-base balance and oxygen of the blood following atelectasis and pneumectomy0 J. Thoracic Surgery, 3_, 341 (1934). J. E. Davis, A. B. Hastings. The measurement of the oxygen consumption of immature rats. Am. J. Physiol., 109, 683 (1934). F. C. McLean, A. B. Hastings. A biological method for the estimation of calcium ion concentration. J. Biol. Chem., 107, 337 (1934). A. B. Hastings, F. C. McLean, L. Eichelberger, J. L. Hall, E. DaCosta. The ionization of calcium, magnesium and strontium citrates. J. Biol. Chem., 107, 351 (1934).

Page  xviiiXV1LL 82. J. E. Davis, E. DaCosta, A. B. Hastings. The effect of thyroxin on the tissue metabolism of excised frog heart. Am. J. Physiol., 110, 187 (1934). * 83. E. S. G. Barron, A. B. Hastings. Studies on biological oxidations. III. The oxidation-reduction potential of the system lactate-enzyme-pyruvate. J. Biol. Chem., 107, 567 (1934). 84. F. C. McLean, B. 0. Barnes, A. B. Hastings. Influence of thyroparathyroidectomy and of parathyroid hormone upon the state of calcium in the serum of the cat. Proc. Socc Exp. Biol. Med., 32., 253 (1934). * 85. F. C. McLean, A. B. Hastings. The state of calcium in the fluids of the body in health and in disease. Trans. Assn0 Am. Phys., 49., 76 (1934). * 86. F. C. McLean, A. B. Hastings. The state of calcium in the fluids of the body. I. Conditions affecting the ionization of calcium. J. Biol. Chem., 108, 285 (1935). 86a. A. B. Hastings. Salts and Edema, in The Kidney in Health and Disease, Chap. XXXII, Lea and Febiger, Publishers, Philadelphia (1935). 86b. A. B. Hastings and H. B. Van Dyke. Edema in dogs following sodium bromide administration, in, The Kidney in Health and Disease, Chap. XXXIII, Lea and Febiger, Publishers, Philadelphia (1935). 87. A. B. Hastings. Chemical analysis of otoliths and endolymphatic sac deposits of ambylystoma tigrinum. J. Comp. Neur., 61, 295 (1935). 88. F. W. Schlutz, A. B. Hastings, M. Morse. Certain blood changes associated with physical exhaustion in the normal dog. Am. J. Physiol., Ill, 622 (1935). 89. F. C. McLean, A. B. Hastings. Clinical estimation and significance of calcium ion concentrations in the blood. Am. J0 Med. Sci., 189, 601 (1935). 90. J. E. Davis, A. B. Hastings. Metabolism of tissues in cerebro-spinal fluid and other media. Proc. Soc. Exp. Biol. Med., 32_, 1449 (1935). 91. E. L. Compere, F. C. McLean, A. B. Hastings. State of calcium in the fluids of the body. II. Calcium in the blood in rickets. Am. J. Dis. Children, 50, 77 (1935).

Page  xixXIX 92. F. C. McLean, B. 0. Barnes, A. B. Hastings. The relation of the parathyroid hormone to the state of calcium in the blood. Am. J. Physiol., 113, 141 (1935). 93c F. W. Schlutz, M. Morse, A. B. Hastings. Acidosis as a factor of fatigue in dogs. Am. J. Physiol., 113, 595 (1935). ** 94. N. W. Shock, A. B. Hastings. Studies of the acid-base balance of the blood. IV. Characterization and interpretation of displacement of the acid-base balance. J. Biol. Chem., 112, 239 (1935). 95. J. E. Davis, A. B. Hastings. The effect of thyroxin on the tissue metabolism of excised limulus heart. Am. J. Physiol., 114, 618 (1936). 96. EC G. Weir, A. B. Hastings. The ionization constants of calcium proteinate determined by the solubility of calcium carbonate. J. Biol. Chem., 114, 397 (1936). ** 97. A. B. Hastings, L. Eichelberger. The exchange of salt and water between muscle and blood. I. The effect of an increase in total body water produced by the intravenous injection of isotonic salt solutions. J. Biol. Chem., 117. 73 (1937). * 98. L. Eichelberger, A. B. Hastings. The exchange of salt and water between muscle and blood. II. The effect of respiratory alkalosis and acidosis induced by overbreathing and rebreathing. J. Biol. Chem., 118, 197 (1937). * 99. L. Eichelberger, A. B. Hastings. The exchange of salt and water between muscle and blood. III. The effect of dehydration. J. Biol. Chem., 118, 205 (1937). 100. A. B. Hastings. Factors governing the calcium equilibria in the body. N. E. J. Med., 216, 377 (1937). 101. EC H. Stotz, A. B. Hastings. The components of the succinate-fumarate-enzyme system. J. Biol. Chem., 118, 479 (1937). 1020 A. A. Browman, A. B. Hastings. Solubility of aragonite in salt solutions. J. Biol. Chem., 119, 241 (1937). 103. F. W. Klemperer, 0. A. Bessey, A. B. Hastings. Oxidation-reduction potentials of certain synthetic flavins. Proc. Soc. Exp. Biol. Med., 37., 114 (1937). 104. B. Alexander, A. B. Hastings. Use of cerebrospinal fluid and synthetic salt solutions in studies of tissue metabolism. Proc. Soc. Exp. Biol. Med., 37, 268 (1937).

Page  xxXX * 105. F. J. Mullin, A. B. Hastings, W. M. Lees. Neuromuscular responses to variations in calcium and potassium concentrations in the cerebrospinal fluid. Amc J. Physiol., 121, 719 (1938). 106o H. I. Chu, A. B. Hastings. A note on the state of calcium in high protein serum. J. Clin. Invest., 17, 167 (1938). * 107. J. F. Manery, I. S. Danielson, A. B. Hastings. Connective tissue electrolytes. J. Biol. Chem., 124, 359 (1938). 108. A. B. Hastingso Trends in preclinical teaching. The Harvard Medical School - Seminar held at the 41st Annual Meeting of the Associated Harvard Clubs, Chicago (1938). 109. M. Kiese, A. B. Hastings. Reversible inactivation of phos-phatase. Science, 88_, 242 (1938). 110. H. I. Chu, A. B. Hastings. The effect of para-amino benzene sulfonamide on the oxygen consumption of tissue and certain pathogenic bacteria. J. Pharm. Exp. Therap., 63, 407 (1938)o 111. F. W. Klemperer, H. C. Trimble, A. B. Hastings. The uricase of dogs, including the Dalmatian. J. Biol. Chem., 125, 445 (1938). * 112. J. F. Manery, A. B« Hastings. The distribution of electrolytes in mammalian tissues. J. Biol« Chem,,, 127, 657 (1939). 113. D. J. Cohn, A. Tannenbaum, W. Thalhimer, A0 B. Hastings. Influence of oxygen and carbon dioxide on the blood of normal and pneumonic dogs. J. Biolc Chem., 128, 109 (1939) 114. Me Kiese, A. B. Hastings. The dissociation constant of hypo-bromous acid. J. Am. Chem. Soc., 61, 1291 (1939). 115. A. B. Hastings, J. M. Muus, 0. A. Bessey. Tissue metabolism in vitamin deficiencies. I. Effect of deficiencies in riboflavin and other heat-stable vitamin B components. J. Biol. Chem., 129, 295 (1939). 116. J. M. Muus, S. Weiss, A. B. Hastings. Tissue metabolism in vitamin deficiencies. II. Effect of thiamine deficiency. J. Biol. Chem., 129, 303 (1939). * 117. E. G. Weir, A. B. Hastings. The distribution of bromide and chloride in tissues and body fluids. J. Biol. Chem., 129, 547 (1939).

Page  xxiXXL 118. I. S. Danielson, A. B. Hastings. A method for determining tissue carbon dioxide. J. Biol. Chem., 130, 349 (1939). 119c Ic S. Danielson, H. I. Chu, A. B. Hastings,, The pKj of carbonic acid in concentrated protein solutions and muscle„ J. Biol. Chem., 131, 243 (1939). 120. A. B. Hastings, H. L. Blumgart, 0. H. Lowry, D. R. Gilligan. Chemical changes in the heart following experimental temporary coronary occlusion. Trans. Assoc. Am. Physc, 54, 237 (1939). 121. N. Drinker, A. A. Green, A. B. Hastings. Equilibria between calcium and purified globulins* J. Biol. Chem., 131, 641 (1939). 122. J. F. Taylor, A. B. Hastings. Oxidation-reduction potentials of the methemoglobin-hemoglobin system. J. Biol. Chem., 131, 649 (1939). 123. Mo Kiese, A. B. Hastings. The catalytic hydration of carbon dioxide. J. Biol. Chem., 132, 267 (1940). 124. M. Kiese, A. B. Hastings. Factors affecting the activity of carbonic anhydrase0 J. Biol. Chem., 132, 281 (1940). 125„ A. B. Hastings, C. W. Eisele. Diurnal variations in the acid-base balance. Proc. Soc. Exp. Biol. Med., 43, 308 (1940)0 126. D. D. Van Slyke, A. Hiller, D. A. MacFadyen, A. B. Hastings, F. W. Klemperer. On hydroxylysine. J. Biolc Chem., 133, 287 (1940). ** 127. A. B. Hastings, G. B. Kistiakowsky, R. D. Cramer, F. W. Klemperer, A. K. Solomon, B. Vennesland. Liver glycogen from lactic acid containing radioactive carboxyl carbon. Science, 9l_, 421 (1940). 127a. A. Bo Hastings, G. B. Kistiakowsky. Biological studies with radioactive carbon. Bull. Conf. on Applied Nuclear Physics, Cambridge, Mass., p. 51 (1940). 128. D. G. Friend, A. B. Hastings. Studies of drugs in tissue metabolism. I. Method for measuring metabolism of tissue in serum. Proc. Soc. Exp. Biol. Med., 45, 137 (1940). 1290 H. N. Christensen, A. B. Hastings. Phosphatides and inorganic salts. J. Biol. Chem., 136, 387 (1940).

Page  xxiixxii ** 130. J. B. Conant, R. D. Cramer, Ac B. Hastings, F. W. Klemperer, A. K. Solomon, B. Vennesland. Metabolism of lactic acid containing radioactive carboxyl carbon. J. Biol. Chem., 137, 557 (1941). 131. B. J. Jandorf, F. W. Klemperer, A. B. Hastings. A manometric method for the determination of diphosphopyridine nucleo-tide. J. Biolc Chem., 138, 311 (1941). 132. J. 0. Hutchens, B. J. Jandorf, A. B. Hastings. Synthesis of diphosphopyridine nucleotide by Chilomonas paramecium. J. Biol. Chem., 138, 321 (1941). ** 133. A. K. Solomon, B. Vennesland, F. W. Klemperer, J. M. Buchanan, A. B. Hastings. The participation of carbon dioxide in the carbohydrate cycle. J. Biol. Chem., 140, 171 (1941). * 134o A. B. Hastings. The electrolytes of tissues and body fluids. Harvey Lectures, XXXVI, 91 (1940-41). * 135. B. Vennesland, Ac K. Solomon, J. M. Buchanan, R. D. Cramer, A. B. Hastings. Metabolism of lactic acid containing radioactive carbon in the OC or position. J. Biol. Chem., 142. 371 (1942). ** 136. B. Vennesland, A. K. Solomon, J. M. Buchanan, A. B. Hastings. Glycogen formation from glucose in the presence of radioactive carbon dioxide. J. Biol. Chem., 142, 379 (1942). 137. L. C« McGee, A. B. Hastings. The carbon dioxide tension and acid-base balance of jejunal secretions in man,, J. Biol. Chem., 142, 893 (1942). * 138. 0. H. Lowry, A. B. Hastings. Histochemical changes associated with aging. I. Methods and calculations. J. Biol. Chem., 143, 257 (1942). * 139. 0. H. Lowry, A. B. Hastings, T. Z. Hull, A. N. Brown. Histochemical changes associated with aging. II. Skeletal and cardiac muscle in the rat. J. Biol. Chem., 143, 271, (1942) * 140. 0. H. Lowry, C, M. McCay, A. B. Hastings, A. N. Brown. Histochemical changes associated with aging. III. The effects of retardation of growth on skeletal muscle. J. Biol. Chem., 143, 281 (1942). 141. F. W. Klemperer, A. B. Hastings, D. D. Van Slyke. The dissociation constants of hydroxylysine. J. Biol. Chem., 143, 433 (1942).

Page  xxiiiXX1LL 142. 0. H. Lowry, 0. Krayer, A. B. Hastings, R. P. Tucker. Effect of anoxemia on myocardium of isolated heart of the dog. Proc. Soc. Exp. Biol. Med., 49_, 670 (1942). 143. 0. H. Lowry, D. R. Gilligan, A. B0 Hastings. Histochemical changes in the myocardium of dogs following experimental temporary coronary arterial occlusion. Am. J. Physiol., 136, 474 (1942). 144. J. F. Taylor, A. B. Hastings. The equilibrium between oxygen and hemoglobin in concentrated urea solution. J. Biol. Chem., 144. 1 (1942). * 145. W. M. Wallace, A. B. Hastings. The distribution of the bicarbonate ion in mammalian muscle. J. Biolo Chem., 144, 637 (1942). 146. 0. H. Lowry, A. B. Hastings. Histochemical changes in aging. "Problems of Ageing," 2d Ed., Chap. 27, Williams and Wilkins (1942). 147» C. B. Anfinsen, 0. H. Lowry, A. Be Hastings. The application of the freezing-drying technique to retinal histochemistry. J. Cell. Comp. Physiol., 2jO, 231 (1942). * 148. J« M. Buchanan, A. B. Hastings, F. B. Nesbett. Glycogen formation from pyruvate in vitro in the presence of radioactive carbon dioxide. J« Biol. Cheme, 145, 715 (1942). ** 149. A. B. Hastings, J. M. Buchanan. The role of intracellular cations on liver glycogen formation in vitro. Proc* Nat. Acad. Sci., 2£, 478 (1942). 150. H. Tabor, A. B. Hastings. The ionization constant of secondary magnesium phosphate. J« Biol. Chem., 142, 627 (1943). 151. J. MO Buchanan, A. B. Hastings, F» B. Nesbett. The role of carboxyl-labeled acetic, propionic, and butyric acids in liver glycogen formation. J. Biol. Chem., 150, 413 (1943). 152. W. W. Westerfeld, J. R. Weisiger, B. G. Ferris, Jr., A. B. Hastings. The production of shock by callicrein. Am. J. Physiol., 142. 519 (1944). 153. L. C. McGee, A. B. Hastings. The osmotic pressure of fasting jejunal secretions in man. Gastroenterology, 4_, 243 (1945) 154. Y. Subbarow, A. B. Hastings, M. Elkin. Chemistry of anti-pernicious anemia substances of liver. "Vitamins and Hormones," III, 237-296 (1945). Academic Press.

Page  xxivXXIV * 155. J. M. Buchanan, A. B. Hastings« The use of isotopically marked carbon in the study of intermediary metabolism. Physiol. Rev., 2£, 120 (1946). ** 156. A. B. Hastings, M. B. Shimkin. Medical research mission to the Soviet Union. Science, 103, 605, 637 (1946). 157. 0. H. Lowry, A. Bo Hastings, Co M. McCay, A. N. Brown. Histo- chemical changes associated with aging. IV. Liver, brain, and kidney in the rat. J. Gerontology, !_, 345 (1946). 158. H. Wo Deane, F. B. Nesbett, A. B. Hastings. Improved fixation for histological demonstration of glycogen and comparison with chemical determination in liver. Proc. Soc« Exp. Biol. Medo, 63., 401 (1946). 159o W. K. Rieben, A. B. Hastings. Chemische und biologische Studien uber Tartronsaure. Helv. Physiol. Acta, £, C52 (1946). 160. A. B. Hastings. Chemical sectors of medicine's frontier. Clin. Bull. School of Medicine of Western Reserve Univc, 1£, 34 (1946). 161. C. B. Anfinsen, A. E. Beloff, A. B. Hastings, A. K. Solomon. The in vitro turnover of dicarboxylic amino acids in liver slice proteins. J. Biol. Chem., 168, 771 (1947). 162. H. W« Deane, F. B. Nesbett, J. M. Buchanan, A. B. Hastings. A cytochemical study of glycogen synthesized from glucose or pyruvate by liver slices in vitro. J. Cell. Comp. Physiol., 30, 255 (1947). A. B. Hastings, C. B. Anfinsen, R. G. Gould, I. N. Rosenberg, A. K. Solomon. In vitro observations on C Q£ incorporation in liver glycogen. Fed. Proc., 6_9 259 (1947). R. G. Gould, I. N. Rosenberg, F0 M. Sinex, A. B. Hastings. Rate of C 62 excretion following intraperitoneal administration of isotopic bicarbonate and acetate. Fed. Proc», 7, 156 (1948). 165o R. B. Singer, A. B. Hastings. An improved clinical method for the estimation of disturbances of the acid-base balance of human blood. Medicine, 27, 223 (1948). 166« 0. H. Pearson, A. B. Hastings, J. H. Currens, F. D. Whitcomb. Electrocardiographic changes in potassium-deficient rats. Trans. 17th Conf. on Metabolic Aspects of Convalescence. Josiah Macy, Jr., Foundation, p. 54-66 (1948). * 163. 164,

Page  xxvXXV 167. R. G. Gould, F. M. Sinex, I. N. Rosenberg, A. K. Solomon, A. B. Hastings. Excretion of radioactive carbon dioxide by rats after administration of isotopic bicarbonate, acetate, and succinate. J. Biol. Chem., 177, 295 (1949). * 168. A. B. Hastings, A. K. Solomon, C. B. Anfinsen, R. G. Gould, I. N. Rosenberg. Incorporation of isotopic carbon dioxide in rabbit liver glycogen in vitro. J. Biol. Chem., 177, 717 (1949). * 169. R. G. Gould, A. B. Hastings, C. B. Anfinsen, I. N. Rosenberg, A. K. Solomon, Y. J. Topper. Metabolism of isotopic pyruvate and acetate in rabbit liver slices in vitro. J. Biol. Chem., 177, 727 (1949). C. A. Villee, 0. H. Pearson, A. B. Hastings. In vitro utilization of C -labeled acetate and pyruvate by rat diaphragm muscle. Fed. Proc., 8_, 263 (1949). S. Cobb, 0. H. Pearson, A. B. Hastings. Inhibitory effects of pteroyl glutamic acid preparations. Proc. Soc. Exp. Biol. Med., 7£, 595 (1949). C. A. Villee, A. B. Hastings. Metabolism of C -labeled glucose by the rat diaphragm in vitro. J. Biol. Chem., 179, 673 (1949). Y. J. Topper, A. B. Hastings. A study of the chemical origins of glycogen by use of C -labeled carbon dioxide, acetate, and pyruvate. J. Biol. Chem., 179, 1255 (1949). J. M. Buchanan, A. B. Hastings, F. B. Nesbett. The effect of the ionic environment on the synthesis of glycogen from glucose in rat liver slices. J. Biol. Chem., 180, 435 (1949) J. Me Buchanan, A. B. Hastings, F. B. Nesbett. The effect of the ionic environment on the synthesis of glycogen and total carbohydrate from pyruvate in liver slices. J. Biol. Chem., 180, 447 (1949). 176. W. R. Christensen, A. B. Hastings. Acid-base balance of rats exposed to reduced barometric pressure. J. Aviation Med., 2£, 221 (1949). 177. 0. H. Pearson, A. B0 Hastings, H. Bunting. Metabolism of cardiac muscle: utilization of C -labeled pyruvate and acetate by rat heart slices. Am. J. Physiol., 158, 251 (1949). 170. 171. 172. ** 173. 174. 175.

Page  xxviXXVI 178. 0. H. Pearson, C. K. Hsieh, C. H. DuToit, A. B. Hastings. Metabolism of cardiac muscle: utilization of C -labeled pyruvate and acetate in diabetic rat heart and diaphragm. Am. J. Physiol., 158, 261 (1949). 179. C. A. Villee, A. B. Hastings. The utilization in vitro of C^-labeled acetate and pyruvate by diaphragm muscle of rat. J. Biol. Chem., 181, 131 (1949). 180. C. A. Villee, H. W. Deane, A. B. Hastings. The synthesis of glycogen in vitro by rat diaphragm muscle. J. Cell. Comp. Physiol., 34-, 159 (1949). 181. C. T. Teng, F. M. Sinex, A. B. Hastings. Factors affecting glycogen formation in vitro. Fed. Proc., £, 237 (1950). 182o A. B. Hastings. The college teacher and professional societies, in "A Handbook for College Teachers," ed. by Bernice Brown Cronkhite. Chap. XI, p. 172, Harvard University Press (1950). * 183. J. W. Raker, I. M. Taylor, J. M. Weller, A. B. Hastings. Rate of potassium exchange of the human erythrocyte. J. Gen. Physiol., 33,, 691 (1950). 184. C. A. Villee, V. K. White, A. B. Hastings. Studies on carbohydrate metabolism in mammalian muscle. Biol. Bull., 9£, 312 (1950). * 185. E. B« Flink, A. B. Hastings, J. K. Lowry. Changes in potassium and sodium concentrations in liver slices accompanying incubation in vitro. Am. J. Physiol., 163, 598 (1950). 186. C. T. Teng, A. B. Hastings, F. B. Nesbett. Metabolism of C -labeled pyruvate by rat liver in vitro. Fed. Proc., 10, 258 (1951). 187« C. Bo Mueller, A. B. Hastings. The rate of transfer of phosphorus across the red blood cell membrane. J. Biol. Chem., 189, 869 (1951). 188. C. Bo Mueller, A. B. Hastings. Glycolysis and phosphate fractions of red blood cells. J. Biol. Chem., 189, 881 (1951). 189. C. P. Lyman, A. B. Hastings. The total CCL, plasma pH and pCC-2 of hamsters and ground squirrels during hibernation. Am. J. Physiol., 167, 633 (1951). * 190. A. B. Hastings, C. T. Teng, F. B. Nesbett, F. M. Sinex. Studies on carbohydrate metabolism in rat liver slices. I. The effect of cations in the media. J. Biol. Chem., 194, 69 (1952).

Page  xxviiXXV11 191. C. T. Teng, F. Me Sinex, H. W. Deane, A. B. Hastings. Factors affecting glycogen synthesis by rat liver slices in vitro. J. Cell. Comp. Physiolo, 39.» l (1952). 192. C. A. Villee, V. K. White, A. B. Hastings. The metabolism of C -labeled glucose and pyruvate by rat diaphragm muscle in vitro. J. Biol0 Chem., 195, 287 (1952). 193. I. M. Taylor, J. M. Weller, A. B. Hastings. The effect of cholinesterase and choline acetylase inhibitors on the potassium concentration gradient and potassium exchange of human erythrocytes. Am* J. Physiol,, 168, 658 (1952). 194. A. B. Hastings, C. T. Teng, F. B. Nesbett, A. E. Renold. Further observations on potassium and carbohydrate metabolism. Fed. Proc., 1A, 227 (1952). 195. F. M. Sinex, J. MacMullen, A. B. Hastings. The effect of insulin on the incorporation of carbon-14 into the protein of rat diaphragm. J. Biol. Chem., 198, 615 (1952). 196. A. B. Hastings. Factors affecting the metabolism of glucose and pyruvate in vitro. In "Carbohydrate Metabolism. A Symposium on the Clinical and Biochemical Aspects of Carbohydrate Utilization in Health and Disease." V. A. Najjar, Ed. Johns Hopkins Press, pp. 59-75 (1952)0 197. A. B. Hastings, Rc A. Peters, R. W. Wakelin. A study of the inorganic ion environment on the convulsions induced in pigeons by fluorocitrate. Proc. of the Physiol. Soc., 20-21, J. Physiol., 120 (1953). 198. C. T. Teng, M. L. Karnovsky, B. R. Landau, A. B. Hastings, F. B, Nesbett. Metabolism of C -labeled glycerol and pyruvate by liver in vitro. J. Biol. Chem,,, 202, 705 (1953). 199. R. Z. Dintzis, A. B. Hastings. The effect of antibiotics on urea breakdown in mice. Proc. Nat. Acadc Sci., 39, 571 (1953). * 200. A. E. Renold, C. T. Teng, F. B. Nesbett, A. B. Hastings. Studies on carbohydrate metabolism in rat liver slices. II. The effect of fasting and of hormonal deficiencies. J. Biolc Chem., 204, 533 (1953). * 201. A. B0 Hastings, A. E. Renold, C. T. Teng. Cationic and hormonal influences on carbohydrate metabolism of rat liver in vitro. Trans. Assoc. Ame Physicians, LXVI, 129 (1953).

Page  xxviiiXXVL11 202. 203. 204. * 205. * 206. 207 208. 209. * 210, 211. 212. A. E. Renold, A. B. Hastings. Modifications du metabolisme des hydrates de carbone dans le foie d'animaux diabe-tiques et dans le foie d'animaux traites a la cortisone. Acta Endocrinologica 14, 47 (1953). J. Ashmore, A0 E. Renold, F. B. Nesbett, A. B. Hastings. Metabolism of glycerol-flt-C ^ by normal and diabetic rat liver slices. Fed. Proc., 13, 176 (1954). E. Calkins, I« M. Taylor, A. B. Hastings. Potassium exchange in the isolated rat diaphragm; effect of anoxia and cold Am. J. Physiol., 177, 211 (1954). Ac EC Renold, A. B. Hastings, F. B. Nesbett. Studies on carbohydrate metabolism in rat liver slices. III. Utilization of glucose and fructose by liver from normal and diabetic animals. J. Biol. Chem., 209, 687 (1954). Ashmore, A. B. Hastings, F. B. Nesbett. The effect of diabetes and fasting on liver glucose-6-phosphatase. Nato Acad. Sci., 4£, 673 (1954). Proc, Ac B. Hastings, E. J. Cohn. Year Book of the American Philosophical Society, 336, (1953). A. E. Renold, A. B. Hastings, F. B. Nesbett, J. Ashmore. Studies on carbohydrate metabolism in rat liver slices. IV. Biochemical sequence of events after insulin administration. J. Biol. Chem., 213. 135 (1955). B. R. Landau, A. B. Hastings, F. B. Nesbett. Origin of glucose and glycogen carbons formed from C -labeled pyruvate by livers of normal and diabetic rats. J« Biol. Chem., 214, 525 (1955). J. Ashmore, A0 E. Renold, F. B. Nesbett, A. B. Hastings. Studies on carbohydrate metabolism in rat liver slices- V. Glycerol metabolism in relation to other substrates in normal and diabetic tissue. J. Biolc Chem., 215, 153 (1955) Ac B« Hastings, R. A. Peters, R. W. Wakelin. The effect of subarachnoid injection of fluorocitrate into cerebrospinal fluid of rabbits. Q. J0 expc Physiol. XL, 258 (1955). R. Bullwinkle, R. H. Fallen, T. C. Fleming, A« B. Hastings. Note on the acid-base balance of the blood of rabbits following the intracerebral injection of fluorocitrate. Q. J. exp. Physiol. XL, 269 (1955).

Page  xxixXXIX 213. * 214. 215. 216. 217. * 218 * 219. * 220. 221. 222. 223. J. Ashmore, F. B. Nesbett, A. B. Hastings. Hormonal induced changes in glucose-6-phosphatase activity in rat liver. J. Clin. Endocrinology and Metabolism, 15, 897 (1955). A. B. Hastings, A. E. Renold, C. T. Teng. hormones on carbohydrate metabolism. Hormone Research. Vol. XI, (1955). Effect of ions and Recent Progress in A. B. Hastings. The Use of Isotopes in Biochemical and Medical Research. A/Conf. 8/P/178. International Conference on the Peaceful Uses of Atomic Energy (1955). L. Tobian, W. I. Morse, A. B. Hastings. Intracellular potassium concentration in normal and diabetic rat liver0 Proc. Soc. Exp. Biol. andMed., Vol. 90, 97-99 (1955). A. Ames, III and A. B. Hastings. Studies on water and electrolytes in nervous tissue. I. Rabbit retina incubated in vitro; Methods and interpretation of analytical data. J. of Neurophysiology, 10:201-212 (1956). J. Ashmore, A. B. Hastings, F. B. Nesbett and A. E. Renold. Studies on carbohydrate metabolism in rat liver slices. VI. Factors influencing glucose-6-phosphatase. J. Biol. Chem., 218, 77 (1956). J. Ashmore, J. Kinoshita, F. B. Nesbett, and A. B. Hastings. Studies on carbohydrate metabolism in rat liver slices. VII. Evaluation of the Embden-Meyerhof and phosphogluco-nate oxidation pathway. J. Biol. Chem., 220, 619 (1956). A. Eo Renold, J. Ashmore, and A. B. Hastings. Regulation of carbohydrate metabolism in isolated tissues. Vitamins and Hormones., Vol. XIV, p. 139 (1956). J. Ashmore, G. F. Cahill, Jr., A. B. Hastings,, Pathways of glucose metabolism in diabetic liver. Fed, Proc. 15, 213, (1956). J. Ashmore, G. F. Cahill, Jr., S. Zottu, and A. B. Hastings. Effect of hormones and ions on the in vitro synthesis of liver glycogen. J. Clin. Endocrinology and Metabolism, !£, 213 (1956). A. B. Hastings, J. Ashmore, G. F. Cahill, Jr. Intracellular ionic environment and enzyme activities; carbohydrate metabolism in liver„ Archives Biochem. and Biophys,,, 65, 78 (1956).

Page  xxxXXX 224. * 225 * 226. 227. 228. * 229. 230. * 231. * 232. * 233. 233a. 234. J. Ashmore, G. F. Cahill, Jr., A. B. Hastings. Inhibition of glucose-6-phosphatase by hypoglycemic sulfonylureas. Metabolism, 5_, 774 (1956). J. Ashmore, G. F. Cahill, Jr., A. B. Hastings and S. Zottu. Studies on carbohydrate metabolism in rat liver slices. VIII. Effect of ions and hormones on pathways of glucose-6-phosphate metabolism. J. Biol. Chem. , 224, 225 (1957). G. F. Cahill, Jr., J. Ashmore, S. Zottu, and A. B. Hastings. Studies on carbohydrate metabolism in rat liver slices. IX. Ionic and hormonal effects on phosphorylase and glyco-gen. J. Biolc Chem., 224, 237 (1957). G. F. Cahill, Jr., A. B. Hastings, and J. Ashmore. Effects of substituted sulfonylureas on rat diaphragm and liver tissue. Diabetes, Jan. -Feb., 1957, Vol. 6, No. 1, p. 26-27 D. Elwyn, J. Ashmore, G. F. Cahill, Jr., S. Zottu, W. Welch and A. B. Hastings. Serine metabolism in rat liver slices. J. Biol. Chem., 226, 735 (1957). Harvard Medical Science, A. B. Hastings. Atoms in the Medical School. Alumni Bulletin, April 1957. A. B. Hastings,, E. S. G. Barren, Medical Biochemist. Nov. 8, 1957, Vol. 126, No. 3280, p. 964. G. F. Cahill, Jr., A. B. Hastings, J. Ashmore and S. Zottu. Studies on carbohydrate metabolism in rat liver slices. X. Factors in the regulation of pathways of glucose metabolism. J. Biol. Chem., 230, 125 (1958). R. G. Spiro, J. Ashmore, and A. B. Hastings. Studies on carbohydrate metabolism in rat liver slices. XII. Sequence of metabolic events following acute insulin deprivation. J. Biol. Chem., 230, 761 (1958). R. G. Spiro and A. B. Hastings. Studies on carbohydrate metabolism in rat liver slices. XI. Effect of prolonged insulin administration to the alloxan-diabetic animal. J. Biol. Chem., 230, 751 (1958). R. G. Spiro. Studies on Carbohydrate Metabolism in rat liver slices. XIII. Influence of the pituitary on the insulin-deficient state. J. Biol. Chem., 230, 773 (1958). G. F. Cahill, Jr., J. Ashmore, A. E. Renold, and A. B. Hastings. Blood glucose in the liver. Am. J. Med., 26, 264 (1959).

Page  xxxiXXX1 235. ** 236. 237. 238. 239. 240. ** 241. 242. 243. * 244. B. R. Landau, A. B. Hastings and S. Zottu. Studies on carbohydrate metabolism in rat liver slices. XIV. Metabolic alterations associated with dietary variations. J. Biol. Chem., 233, 1257 (1958). J. Ashmore, M. L. Karnovsky and A. B. Hastings. Intermediary Metabolism. Radiation Biol. and Med., 29^, 738 (1958). J. Ashmore, G. F. Cahill, Jr., and A. B. Hastings. Effect of Hormones on Alternate Pathways of Glucose Utilization in Isolated Tissues. 1959. (Given at Laurentian Hormone Conference.) J. Ashmore and A. B. Hastings. Use of C in quantitative studies of alternate metabolic pathways. Proc. Second U. N. Conf. on Peaceful Uses of Atomic Energy, 25, 64 (1959). W. C. Shoemaker, R. Mahler, J. Ashmore, D. E. Pugh, and A. B. Hastings. The hepatic glucose response to insulin in the unanesthetized dog. J. Biol. Chem., 234, 1631 (1959). A. B. Hastings. The Parathyroids. Editors, R. 0. Creep and R. V. Talmage, Charles C. Thomas, Publisher, pp. 5-6, 260-261 (1961). A. B. Hastings and E. B. Dowdle. Effect of CC^ tension on synthesis of liver glycogen, in vitro. Trans. Assoc. Am. Physicians, 73., 240 (1960). B. R. Landau, R. Mahler, J. Ashmore, D. Elwyn, A. B. Hastings and S. Zottu. Cortisone and the regulation of hepatic gluconeogenesis. Endocrinology, 70, 47 (1962). A. B. Hastings. Symposium on hormone transport mechanisms. (XIV Meeting of Protein Foundation), Vox Sanguinis, 5_, 62 (1960). B. R. Landau, J. Ashmore, A. B. Hastings, and S. Zottu. Studies on carbohydrate metabolism in rat liver slices. XV. Pyruvate and propionate metabolism and C0« fixation in rat liver slices in vitro. J. Biol. Chem., 235. 1856 (1960). 245. A. B. Hastings. Biochemistry's first century. The Quarterly Bulletin of the Indiana University Medical Center, 21, 40 (1959). 246. J. E. Richmond and A. B. Hastings. Distribution of sulfate in blood and between cerebrospinal fluid and plasma in vivo. Am. J. Physiol., 199, 814 (1960).

Page  xxxiiXXX11 247. J. E. Richmond and A. B. Hastings. Distribution equilibria of sulfate in vitro between red blood cells and plasma. Am. J. Physiol., 199, 821 (1960). 248. A. B. Hastings. Research in the basic sciences. The Boston Medical Quarterly, 12, 1 (1961). 249. A. B. Hastings. Address at Tenth Anniversary Dinner, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health. The NIH Record, 13, 3 (1961). 250. A. B. Hastings. Introductory Remarks at Conference "Biological Aspects of Metal-Binding." Fed. Proc., 2£, 1 (1961). 251. A. B. Hastings, T. A. Mahowald, D. D. Fanestil. Environmental carbon dioxide concentration and carbohydrate metabolism in liver. Science, 134, 1429 (1961). * 252. A. B. Hastings. C0£ concentration versus carbohydrate metabolism in livero Robert A. Welch Foundation Conference, V., Chap. XX, 261 (1962) (1965). 253c A. B. Hastings, T. A Mahowald, D. D. Fanestil and W. J. Longmore. Effect of C0£ concentration on carbohydrate metabolism in rat liver. Fed. Proc., 21, 82 (1962). 254. R. B. Singer and A. B. Hastings. Acid-base values, blood and plasma: Man. "Standard Values in Blood", Handbooks on Biological Data, American Institute of Biological Sciences, National Research Council, Washington, D.C., p. 124 (1952). 255. R. B. Singer and A. B. Hastings. Acid-base values in man and other species. "Blood and Other Body Fluids", Biological Handbooks, Federation of American Societies for Experimental Biology, Washington, D.C., pp. 177-190 (1961). 256. A. B. Hastings. In search of our medical future. Baylor University College of Medicine Commencement Address. The Bulletin, ^, 4 (1962), and The Pharos, 2£, 78 (1963). ** 257. A. B. Hastings. "Ah, Sweet Mystery ——" A biochemist's myopic viewpoint. The Banting Memorial Lecture, Am. Diabetes Assoc., Diabetes, rL, 361 (1962). * 258. D. D. Fanestil, A. B. Hastings, T. A. Mahowald. Environmental C02 stimulation of mitochondrial adenosine triphosphatase activity. J. Biol. Chem., 238, 836 (1963). 259. B. R. Landau, A. B. Hastings and S. Zottu. Substrate concentration and metabolic pathways in liver slices in vitro. Biochem. et Biophys. Acta, 74, 621 (1963).

Page  xxxiiiXXXL1L 260. B. R. Landau, A. Bc Hastings and S. Zottu. Pyocyanin and metabolic pathways in liver slices in vitro. Biochem. et Biophys. Acta, 74, 629 (1963). 261. H. N. Christensen, B. H. Feldman and A. B. Hastings. The Con-centrative and reversible character of intestinal amino acid transport. Amer. J. Physiol., 205, 255 (1963). 262. W. Jo Longmore and A. B. Hastings. Factors affecting metabolism of glycerol-C by liver in vitro. Fed. Proc., 22, 472 (1963). 263. A. B. Hastings and D« D. Fanestil. Effect of COo concentration on glucose-C ^ metabolism by rabbit kidney cortex and medulla, in vitro0 Festband Warburg, Biochemische Zeitschrift, 338, 276 (1963). 264. A. Bo Hastings. Donald D. Van Slyke - The Twentieth Century latro-Chemist. Federation Proceedings, 23 (3), 586 (1964). 265. A. B. Hastings. Chester Scott Keefer, M.D., D. Sc., Physician and Teacher, Extraordinary. The Boston Medical Quarterly, 14, 89 (1963). * 266. W. J. Longmore, A. B. Hastings and T. A0 Mahowald. Effect of Environmental C02 and pH on Glycerol Metabolism by Rat Liver, In vitro. J. Biol. Chem., 239, 1700 (1964). 267. W. J. Longmore and A. B. Hastings„ Glycerol Metabolism in Choline Deficient Rats. J. Nutrition, 83 (2), 103 (1964). ** 268. A. B. Hastings. Intermediary Metabolism — Before and After Isotopes. Amu Int. Med., 61 (5), I, 966 (1964). ** 269. W. J. Longmore, A0 B. Hastings and Elizabeth So Harrison. The effect of physiological variation in pH and C02 concentration on acetate-l-^C metabolism. Proceedings of the National Academy of Sciences, 52 (4), 1040 (1964). * 270. A. B. Hastings and W. J. Longmore. Carbon dioxide and pH as Regulatory Factors in Metabolism. Enzyme Regulation, Vol. Ill, Pergamon Press, Oxford, England, pp. 147-159 (1965). * 271. A. B. Hastings. Acids and Bases in Biological Systems — Introductory Remarks. * 272. A. B. Hastings. The Heterogeneous Man. Perspectives in Biology and Medicine, VIII (1), 84 (1964).

Page  xxxivXXX LV 273. 274. 275. 276. W. J. Longmore, A. B. Hastings, E. S. Harrison and H. H. Liem. Environmental factors affecting conversion of acetate-1- 14 C to fatty acids and cholesterol by liver in vitro. A. Federation Proceedings, 24 (2), 476 (1965). B. Hastings. Autobiographical sketch for Encyclopedia of Science and Technology, Biographical Supplement, McGraw-Hill, p. 213 (1966). A. B. Hastings. William Mansfield Clark. Memoir for Yearbook, American Philosophical Society, 1965. W. J. Longmore, A. B. Hastings and E. S. Harrison. The effect of environmental pH and CC^ concentration on mitochondrial ATPase activity of rabbit kidney cortex and medulla. (Introduction by A. Baird Hastings; A case for carbon dioxide.) Hvalradets Skrifter (Oslo), Essays in Marine Physiology, No. 48, 178 (1965). 277. A. B. Hastings. The metabolic role of C0£ in liver metabolism (Abstract), VII Chemical Congress of Peru. 278. A. B. Hastings. My life with CC>2 and postdoctoral fellows from St. Louis University. (Not yet published) 279. W. J. Longmore, A. B. Hastings, E. S. Harrison and H. H. Liem. Effect of COo and cations on fatty acid and cholesterol synthesis by liver in vitro. American Journal of Physiology, 212, 221 (1967). 280. A. B. Hastings. Effect of THAM and other buffers on cellular metabolism; Introductory remarks. Annales De L'Anesthe-siologie Francaise, 7_, (3), 579 (1966). 281. A. B. Hastings. Remarks from "Molecular Medicine," address at Life Sciences Symposium, Massachusetts Institute of Technology on December 2, 1965. (Not published) 282. A. B. Hastings. Intracellular pH: Introductory Remarks. Proc. 3rd International Congress on Nephrology. Vol. 1, p. 158 (1966). 283. W. J. Longmore, B. R. Landau, E. S. Baker, A. B. Hastings, D. L. Lum, H. R. Williams: Effect of pH and C02 concentration on glucose metabolism by rat adipose tissue, in vitro. Am. J. Physiol., 215, 582 (1968).

Page  1 Dr. Olch: The date is December 18, 1967 and we are in the office of Dr. A. Baird Hastings at the Scripps Institute of Oceanography, University of California, San Diego, in La Jolla, California. Dr. Hastings: Well, I want to get the record straight about my place of birth. I was born on November 20, 1895 in Dayton, Kentucky, and my father recorded this fact in the Hastings' family Bible. There were no birth records kept in Kentucky at that time. As I grew up, for some reason unknown to me at the present time I got the idea that I was born in Bellevue, Kentucky. Now Bellevue and Dayton are contiguous; they are separated only by a street. The record is now clear that, though I was born in Dayton, Kentucky, my parents moved within a few months after I was born across the street into Bellevue, Kentucky. I don't know the address either of where I was born in Dayton or in Bellevue. Dr. 00: Is it now known as Bellevue-Dayton, Kentucky or are they still two separate communities? Dr. H»: I don't know. I think they are separate communities, for the simple reason that they were both listed in an atlas when I once looked them up a few years ago. Dr. 0.: What large community is this near? Dr. H.: Covington. It's just across the river from Cincinnati. My father and mother met in Cincinnati.

Page  2But this lack of accurate information, at least recorded information? of just where and when I was born was only resolved last year, because in applying for my Social Security and not having a birth certificate they were unwilling to take the affidavit which my mother had given when I got my first passport because in hunting up the records of the 1900 census--it is recorded in the 1900 census that I was born on November 20, 18961 Not 1895. It required all the efforts of my brother, who was a lawyer in Florida who has the family Bible, and some kind of state official taking affidavits stating that he had seen the family Bible and so forth. Plus the fact that my brother had to go through the correspondence between my father, who was a traveling salesman, an^ my mother prior to November 20, 1895 in which fortunately he referred to the forthcoming baby and then in the letters of February and March of 1896, which have their stamp on the envelope--all of these fortunately were preserved—which refer to the baby as having been born. At long last after 15 months of struggling with this with the Social Security people, they have finally acknowledged that I was born November 20, 1895. Fortunately, both my mother's affidavit for my passport and the record in the Bible state Dayton, Kentucky. It is only providential that gome of these letters were addressed to Bellevue after I was born, and to Dayton before I was born. This made me realize what probably happened. My problem has been through the years though, that having started high school and college, putting Bellevue, Kentucky as my birthplace, and I continued this through American Men of Science and Who's Who. But fliy

Page  3passport has always been in terms of Dayton, Kentucky„ At one stage I wanted to get Dayton in there, so I wrote Bellevue-Dayton. Dr. 0.: Yes, that is how it is in the American Men of Science. Dr. H.: At any rate, I don't know what to do at this stage of my life; I think I will do nothing, probablyI Whenever I have to swear where I was born, it will be DaytonI Dr. Oc: What field of endeavor was your father in, Dr. Hastings? Dr. H.: For most of his life, he worked for a wholesale coffee and tea house and was a traveling salesman. He had a business college education and only once was he in business for himself, which was when he and his father opened a grocery store in Richmond, Indiana and they failed and he went back to being a traveling salesman. He was a very fine man, really. Dr. 0.: Hastings, I gather, is an English name. Dr. H.: It's English and Quaker. [Dr. Hastings then referred to a family album of candid pictures of his family and his childhood.] Unfortunately, these were all after he had been taken ill. He died when I was in high school in my second year, of tuberculosis. [Browsing through the album] Otis Luther Hastings; my brother is named Otis Lowell Hastings.

Page  4Dr. 0.: Your father's name is Otis Luther Hastings and your brother Otis Lowell Hastings. You have one brother? Dr. H.: One brother. He is seven years younger and he is a lawyer. This was our house in Indianapolis, Indiana. Dr. 0.: When did your family actually move from Bellevue, Kentucky? Dr. H.: Well, within the first year of my life they moved from Kentucky to Dayton, Ohio; from Dayton, Ohio to Piqua, Ohio. The next move was to Richmond, Indiana which is a region of Indiana—Cambridge City, Dublin--where a Quaker community had settled many, many years ago. It was regarded as rather the home base of the Hastings family. Dr. Oc: Your parents had been Quakers prior to moving to this place. Dr. H0: My father had been, not my mother„ Then when I was six years old--that would make it 1901--they moved to Indianapolis, Indiana and lived there until I went to college, so I grew up there in Indianapolis. All my memories that I have really are of Indianapolis, Indiana. We lived at that address [referring to the album], I see; I had forgotten what it was. Dr. 0.: 952 West 33rd Street, Indianapolis. Dr. H.: This was real country at that time. This was a lot from a farm that we bought. I remember so well, my father built that house for $1800.

Page  5Dr. 0.: Oh my! One couldn't buy a few square feet of land for that these days. Dr. H.: Well, it's true. We couldn't have both a furnace and a bathroom for the first year or so, so we took the furnace, and the bathroom a year or so later. But that is where we lived and where he died. Dr. 0. : What did you find as a young boy in high school—how did you generally spend your free time? Were you interested in fishing then as you are now, I gather? Dr. H.: Oh, I fished on the White River a little, but I was a stinking grind, you see. Dr. 0.: You were interested in books and studying at this age? Dr. H.: Yes. My mother, a most remarkable person, had educated herself and didn't even go to high school. She became quite an important person after my father died, later in life, but both of them always just expected one to do his best. The only thing I remember my father saying the day he actually died, to me, was, "Son, whatever you are asked to do, always do it as well as you can and a little bit more." I think if I have any motto that I have lived by all my life, it's that. Things don't come easily for me; I'm not a smart fellow, but I'm a hard working fellow and nothing short of perfection would satisfy me. So much so that I got all A-pluses in Shortridge High School1 Dr. 0.: Shortridge High School? In Indianapolis?

Page  6Dr. H. : That's a very famous high school, particularly famous for its excellent teachers. So much so that even Jim Conant found it still one of the best high schools in the United States. Dr. 0.: In his survey---Dr. H.: Yes, he told me so. But I did make all A-pluses and I was the first male to ever do that at Shortridge. Well anyhow, you asked me what I did in my spare time; there wasn't much spare timel The spare time I did have was used to take care of a coffee and tea route that I started when I was seven years old. Dr. 0.: Distributing some of the products that your father was selling? Dr. H.: Yes, virtually that. I wanted to have a paper route. I had substituted for a neighbor, and I could have had one and my father said, "Of course you can have a paper route if you want to, but you might consider having a coffee and tea route instead because I can arrange for you to fill your orders at the wholesale coffee and tea company (the Bright Company) and I will give you your first capital and from then on you are on your own." He got a little suitcase--about the size of that one as I remember [referring to Dr. Olch's attache case]--cardboard, of course, and he filled it with spices and extracts and tea--no coffee in that one, but it was full though and he said, "You can start in the neighborhood and see if you can dispose of this and I will tell you what they should sell for and that will be your capital." I didn't really

Page  7start out to handle coffee, but the neighbors probably said, "Can you get us coffee too," so it became mostly a coffee route. I would take my orders every Friday afternoon, if I didn't have them already, by telephone. Saturday morning I would go down and fill the orders. I had a big wire basket in the front and back of my bicycle. I lived five miles I suppose from the wholesale coffee company--it seems like that in retrospect--maybe it was only three. Then I would deliver my coffee or tea or whatever it was. By the middle of Saturday afternoon I was through my work and I had made several times as much money as I would have made having a paper route. And indeed, it shows my lack of business ambition or acumen, that I would only let this route grow large enough to take care of my needs, my financial needs. I never had an allowance. I always earned it by my coffee and tea route. If I had any ambition I would have been able to retire much before I did I At any rate, except for one accident where I had been breaking the rules of not hanging onto the back of automobiles to save energy coming back from this coffee company--it was an intersection and the car stopped but I sailed into the intersection. Except for the scar above my eye, there is nothing to show for it anymore. Coffee was all over the intersection1. And so was my bicycle I Dr. 0.: In school, did you find yourself becoming interested in science at this stage? What were your favorite subjects? Dr. H. : I suppose I might as well be frank with you. The answer is no1. I'd had a smattering of Latin in eighth grade public school and so I

Page  8registered for Latin and also since the teacher was going to give Greek that year, for Greek. And then I took mathematics and English; can1t remember what else. I had decided that I wanted to be a teacher of Latin and Greek, a classics teacher. This was stimulated by the most wonderful high school teacher named Miss Ella Marthens. I just happen to have the school yearbook. [pause] There she is. She only died a few years ago, well up in her nineties. A very sylph-like figure, who lived with Miss Rousseau McClellan who was head of biology. She had a Master's Degree from Indiana University. These two, plus Miss Marthen1s sister, had a big house on Meridian Street and they were such a wonderful pair. They stimulated innumerable boys in the high school class to try and amount to something. Without any doubt, if it hadn't been for those two women, I would never have gone to college. I wouldn't even have had the ambition, let alone the thought. Shortridge High School had a number of such outstanding teachers. Indeed, I personally feel that you are made or broken by the kind of high school teachers you have rather than college teachers. Dr. 0.: You feel it effects one earlier than college? Dr. H.: Yes, at least I am perfectly sure myself, and I can point to a very large number of my classmates and members of classes just before and just after mine, who have become very important people in America's scene. Of course we are getting a little old now, but during the war it was amazing how many Shortridge graduates I ran into in Washington, in judgeships, abroad, in Congress, and even my associate (I'm jumping

Page  9ahead now) on the Committee on Medical Research of OSRD--the Committee on Medical Research consisted of four civilians and a general, an admiral, and the head of the Public Health Service. Of those four civilians, one was A. N. Richards, the Chairman; one was Lewis Weed, the Vice-Chairman--- Dr. 0«: The anatomist? Dr. H.: Yes, at Hopkins. Richards was Vice-President for Medical Affairs at Pennsylvania and Weed at Hopkins--and then two "privates" as we called ourselves--Alphonse Raymond Dochez and Baird Hastings. Dochez is the one who, with Avery, did the typing of pneumococci and preceding the Dicks, made scarlet fever vaccines and had it traced to the streptococcus. Dr. 0.: Which of this group was also from Shortridge? Dr. H.: Dochez1 Dochez surprised me one night as we were getting acquainted, because he was older than I wasc I had grown up with everybody else's idea that he'd never been west of the Hudson River, that he was strictly Parisian, boulevardier, because he always had a waxed moustache and spats and carried a cane, and the name. I practically collapsed on the patio of the Shoreham Hotel that nice Saturday night that we were there early in the war--I had happened to mention that I had gone to Shortridge High School, and he leaned back in his chair and said, "Well, I went there tool" He said, "Did you ever read Seventeen?" I said, "Oh my yes, of course, that's an

Page  1010 American classic." He said, "Well, do you remember the incident described there, where the freshman younger brother in high school was persuaded to put on a top hat, white tie, and tails to go to the freshman dance?" I said, "Oh yes, the agony that that fellow went throughI It is the most poignant incident I have ever read; I practically weep everytime I think about it." He said, "Well, that was meI My two older brothers were the same age as Booth Tarkington, who lived across the street, and these rascals got me to do this I" I have often thought that "Do" put on that white tie and tails and never took them off1. Well, that has nothing to do with me, really. Dr. 0.: That is a remarkable aside, really. Dr. H.: Let me say something more about this business of how a biochemist is made. I did well, as I told you, in Latin and Greek. It is very unusual that a high school gives Greek, and it is very unusual for anybody to take it if they do I But this was the tail end of the period when Princeton, Harvard, and Yale required Latin and Greek to be considered for admission, so Indianapolis boys who thought they wanted to go to Princeton or these other places had to have some Greek. But that isn't the reason I took it. I took it because I liked Latin and I liked Greek even more. Well, in my second year, when my father died, and we having no means of income, I prepared to leave high school and get a job. Miss McClellan said, "Don't do that. We want you to stay in high school and indeed go on. I have friends (they all turned

Page  1111 out to be graduates of Shortridge) in business here (heads of department stores and various things) and I am sure we can find after hours work for you. Next fall, in your junior year, if you will take zoology, I will also make you laboratory assistant (it was the second assistant; she had a senior assistant and one who was supposed to collect earthworms and frogs, leaves for botany, etc.)*" So they kept me in high school by this. I worked as a special delivery boy on a bicycle for one of the department stores after school hours. I kept my coffee route going Fridays and Saturdays, and in the fall became second assistant in biology. Now, I also took physics. You had to take something, but I took no chemistry in high school, no chemistry whatsoever. I took four years of Latin and two years of Greek, so I got no German and no French. I took history and English for four years and math right through solid geometry. Well, in my senior year, the question came now—what is Baird going to do next year? I had a great crony who was my biggest competitor for perfection all through this period—a boy named Alan Boyd. He is a very prominent lawyer in Indianapolis now, a corporation lawyer, very successful. Smart as a whip, always was—sharp! But I kept up with him by sheer hard work and indeed beat him now and then. We were great cronies. We met together at Miss Marthens1 and Miss McClellanfs home one evening, and the only decision that I had made was, that if I was to go to college at all, it had to be the University of Michigan. The reason was that only two members of the Hastings family--and they were

Page  1212 first cousins of my mothers, Bairds--had gone to college. James Baird and Charles Baird; they had gone to Michigan. Charles Baird had stayed there as sort of manager of athletics. Jimmy Baird had been captain of the football team twice in the f90's and then went out as a civil engineer and helped build the Flatiron Building in New York and then became first vice-president and then president of the George A. Fuller Construction Company. After he retired from that, formed his own company. While with the Fuller Construction Company, he built the Lincoln Memorial, which is the finest thing in the country, I think, architecturally,, His own company kept spending as much money as they had to build the Cathedral. Dr. 0.: When you say "the Cathedral," you refer to the Washington Cathedral? Dr. HC: Yes. He is dead now, of course, but they are still building on it. Well, with this decision to go to Michigan, we had written for a catalog The only other decision that had been made was, if I do go to college, I must take courses that would prepare me to earn a living quickly to take care of my mother and send my brother at least through high school and hopefully, through collegec In our naive way, we four sitting there, decided Baird should be an engineer. There was money in engineering and you could get a good job as soon as you graduated in engineering. So we got this catalog—a big thick thing—and started leafing it through. It seems like yesterday we did this together,

Page  1313 these two teachers, Al Boyd, and me. First was Civil Engineering. No, that's not Baird's forte. Mechanical Engineering. Oh no! He isn't any good at machinery. Then came Electrical Engineering, and that was even further out! In the end came a section called Chemical Engineering, and since none of us knew really what this was, we decided Baird would be a chemical engineer. I borrowed a hundred dollars, signed notes for them from each of these two cousins and another hundred from some old great uncles, who had made money in the orange business in Florida, and with these three hundred dollars, I registered for Chemical Engineering at the University of Michigan in the fall of 1913. I'm wasting our time with these details---- Dr. 0.: No, these details are important. They are not a waste of time at all. Dr. H.: I guess I'm getting old! But these things are coming back. Anyhow, I went and I had been only accepted on probation on the grounds that I hadn't any modern language and I hadn't had trigonometry. So, before being accepted even provisionally, I had to meet Dean Mortimer E. Cooley. He was one of the great mechanical engineers as well as educators in this century, at least at Michigan. I can see Dean Cooley now. He called for my file and he opened this up and he looked at me--I was of course skin and bones; in those days I was 5' 11" and weighed 1201 I was a skinny, rather sallow and pale kid, and he looked over

Page  1414 his glasses and said, "Mm-mm-mm. Four years of Latin, two years of Greek. No German; no French; no trigonometry; mm-mm-mm. Well, if you will make up your trigonometry and get some German and French on the side, we'll take a chance. Who knows, this may be our requirement some years hence!" This was the important thing that that guy said. Anyhow, he did accept me and I struggled through wood shop and machine shop. I got my first B in my life out of the wood shop, so I struggled so hard with the bellows and the iron and the making of these things, that I got an A out of the machine shop!! I mean the iron or metal shop. I decided then and there that if I could get an A out of that, I could do anything in life! But obviously I had to take chemistry, my first course in chemistry after going there, and I didn1t like it very much to tell you the truth. The first year in chemistry is, in those days anyway, mostly made up of learning a new language and not a very systematic one. Latin and Greek were very much more systematic as languages than chemistry. Dr. 0.: Who was your Professor of Chemistry? Dr. H.: A man named Bigelow. Ifve forgotten his first name; an old Boston Bigelow family and had a good Boston accent—and a beautiful teacher, I might say—he was also a professor of physical chemistry. You see, if you can just get by that first year of chemistry, you'll find it's lovely, I mean even with Qual. and Quant. [Qualitative Analysis and Quantitative Analysis], it begins to be something you can manipulate. Today, I am sure the first year in chemistry must be very

Page  1515 interesting because--well heavensI--they have all had chemistry in high school by the time they get to college and start right in with the structure of the atom and all of those kinds of things. But in those days, it was learning the elements and just strict roteI But I got A1s in it; they didn1t give A-pluses. I was going along in my second year toward my chemical engineering degree. I was working out of hours to earn money, of course. I had a letter from Charlie Baird that gave me an entree to being a dishwasher at Prettyman's big eating establishment. I graduated from that to having a table of my own to service as a waiter. Saturdays I would go to the YMCA and they would have all the odd jobs. I've done everything from cut down trees on State Street, keeping a garden for a man, helping people move trunks from the attic. I don't know how one does these things, but I did. I came out that first year all right. My mother was unable to help me, of course. She had gone back into the millinery business. She had been in the millinery business when she met my father. She and our next door neighbor set up a little hat shop near our home and made a go of it, but not enough. I mean it simply kept up the house* At the end of that second year though in Michigan, my mother married again. A man named Morris Baird, a very distant relative, and they moved to Evanston, Illinois. He wasn't very wealthy, but he was successful, and he helped me with the rest of my college education, so I didn't have to borrow anymore and I paid back these hundred dollars—the first three hundred dollars that I got--to pay these people who helped me get started.

Page  1616 Well, I went to summer school between my second and third year at Michigan because I had had to take these extra courses. I took physical chemistry among other things that summer. I liked it very much. It was a course given by Professor Floyd Bartell. His job was primarily, during the academic year, to give the laboratory course in physical chemistry. Professor Bigelow gave the lectures. He had also developed a course in colloid chemistry and he was interested in membranes as his research problem. Well, I enjoyed the course and did well in it, the summer course, and at the end of the course Professor Bartell asked me if I would like to be the assistant in physical chemistry at the University of Michigan. Now this was the second best assistantship in the department of chemistry. It paid $175 a year and the best one paid 200, but the best one—you were assistant to the head of the department, who was a very famous analytical chemist by the name of Professor Campbell, who had been blinded many years before by a Kipp generator that had blown up, but he kept on working every day. His assistant called for him, the assistant took him home, and in between classes he was available to conduct experiments in the laboratory under Professor Campbell1s direction. Well, the assistant in physical chemistry had to prepare the apparatus for the students, the solutions for the students, help when they were in the laboratory with the instruction, and, among other things, he had a laboratory of his own—twenty by twenty laboratory of his own—which adjoined the professor's laboratory which adjoined the professor's office. And on one side was the student laboratory.

Page  1717 This was the fall of 1915, and from that moment until last fall—last September, a year ago--I have had a laboratory of my own and this has conditioned everything I have done. Well, there was a proviso with strings tied to this offer of assistantship. It would require that I major in chemistry and transfer from the School of Engineering to the Arts School, which I agreed to do very readily. I went to the Dean at the beginning of the semester and told him I wanted to transfer to the Arts School, and he called for my folder because lots of fellows want to transfer from the Engineering School to the Arts School because they were full of D's and E'sl He looked at my grades, and there was only one B and he said, "Oh no, you don't want to do this; this is just a passing fancy of yours. No, no, no, no, but take whatever you want to, Hastings, whatever Bartell wants you to take, go ahead and take it, but don't transfer officially, you would be back." So I didn't do it that fall. Well, by the spring, I tried to do it again, and again the next fall. It wasn't until the year after the fall that this transpired, that by then I had failed to take certain required engineering courses because I had to take all of these physical chemistry courses and organic and so forth. And so I couldn't have graduated in the class anyhow, so he finally, still with some reluctance, let me transfer. The only thing that gripes me about this whole business; even in the University of Michigan, all of these A's got transferred officially as C's and this kept me out of Phi Beta Kappa! Bartell nearly blew his top when this happened, the lack of election to Phi Beta Kappa. Well, of course we've forgotten all that

Page  1818 now. I made Sigma Xi as an undergraduate, so I have made up for it some. So I transferred and majored in physical chemistry. I took all the courses in physical chemistry there were, graduate and undergraduate. As an undergraduate, and at the end of the year, 1916 I guess it was, Bartell asked what was I going to do after I graduated? I said, "I guess I'll get a job, I suppose." It really was very easy for people to get jobs in those days. They were recruiting undergraduates in chemistry in industry. He said he thought I ought to go on and do graduate worko I said, "You mean work for a Ph.D.?" He said, "Yes, that's what I mean." I said, "That's ridiculous; only very brilliant people can ever get Ph.D.s. You've got to be a van't Hoff or somebody like him to do this." "Well," he said, "I've watched you through this year or so and I find that you work hard and are resourceful." This is a thing that has been another byword with me, and ever since he said I was, I have tried to be resourceful in the lab; and it has stood me in good stead. So, since I had gotten ahead with my credits by now by working summers, I was able to enter the graduate school in January, at the beginning of the second semester in 1917 as a graduate student in physical chemistry. Since Bartell was interested in membranes and osmosis, I started doing some beginning, sort of preliminary research work on permeability of collodion membranes. It's kind of interesting, because membrane studies was the beginning of my interest in heterogeneous systerns«> The other thing that was helpful at that moment, for what happened afterwards, was that Bayliss's Principles of General

Page  1919 Physiology, a brand new type of book, had just come out and Bartell, this physical chemist, got himself a copy and showed this to me. He was studying it and he let me study it from time to time, which was my first contact with a biological subject. Dr. 0.: When I was in medical school, we not infrequently still would look to Starling and Bayliss for certain points. Dr. H.: Yes. Well, it was a remarkable book and later editions are not as good as the original one, but it fulfilled a great need at that time and, I am sure, stimulated my interest toward biological things because really, as of that time, I wasn't really interested in biology-I was strictly a physical chemist! My first semester in the graduate school, I had elected to take, since there was no more physical chemistry to take, some advanced quantitative chemistry and some mineralogy and bacteriology under F. G. Novy. I had no biological subjects in college and one course in zoology in high school. And then came World War I. April 6, we went in. Everybody left to go to camp and I tried to leave to go in along with everybody else, but I was too skinny! I got turned down in my first attempt to get into the first officers training camp. All my friends in the fraternity went. (I had, by then, been elected as a junior to a musical fraternity. I am not musical. They elected me because I couldn't play anything or sing, and everybody else could. So I was elected as an audience that

Page  2020 had to listen to the other boys. This is the professional music fraternity, Sinfonia, Phi Mu Alpha, which was a general fraternity. It ran all the big things, the musical plays, glee clubs, Michigan Daily—a very active group.) I couldn't stand this so when the boys got on the train to go to Chicago to Fort Sheridan, outside of Chicago, I just went with them to see what would happen, and I was sitting there in the adjutant's office that first afternoon when they were being inducted, when the then Colonel Bullard, afterwards General, an artillery man, came out and read a telegram to this effect: "Can use forty good men if they arrive before (2 days from then)." Signed, whoever it was, the Commandant at Fort Logan H. Roots, Arkansas, which is at Little Rock. Well, I signed up and went, but I was just as thin there as I was in Chicago and——— Dr. 0.: At this time you had your Bachelors Degree. Dr. H.: Yes, I had my Bachelor's Degree and I was registered graduate student. It hadn't been awarded; it would be awarded in June, but--— Dr. Oo: Everybody dropped everything and went off to the war. Dr. H.: That's right. I had finished all of the work toward my degree. There was a guy there as the medical officer at Fort Logan H. Roots, who afterwards was declared insane. That's the reason he wasn't accepting anybody; he only accepted one person out of ten that came through. "Open your mouth! Turn around, open your buttocks! Rejected!" Well, because

Page  2121 I had gotten there the night before this next physical exam came off, I had been assigned to an artillery company where there was a fellow, the captain, who was so delighted to find somebody with an engineering background, that he signed a waiver for me to stay in camp as a regular student officer on the grounds that I might be able to pass my physical examination at the end of the course. I ran trigonometry courses every evening after mess in the mess hall for these boys from Arkansas, Mississippi, Texas, who filled up the camp and didn't know trigonometry, let alone calculate a firing angle. I earned a commission. I could have been a second lieutenant in the regular or a first lieutenant in the reserves, but this same medical officer wouldn't pass me on my physical exam. By then they had to hold a hearing you see; I had to have someone pleading my case and so forth. Anyhow, I had an honorable discharge for physical disability from the army in late July, 1917. Dr. 0.: So actually, you were just there for a period of months. Dr. H.: Months, right. May, June, and July. But it makes me a veteran of World War I, but I still get furious every time I think of this guy, because I was just underweight. I was very healthy. A guy who was very fat and flabby, a jeweler from Little Rock, had gotten into camp and he screamed all the time about how he couldn1t do the work, and on a forced march, I carried his pack as well as mine, and another guy carried his rifle. Well, he got a first lieutenantship! Anyhow, you have no idea how my generation of that time felt it was encumbent upon us to save the world for democracyI Really! I couldn't bear living

Page  2222 with myself or anybody else unless I could get in there. I went back to Michigan to help Bartell with his course as his instructor in the fall of '17. He was about to go in the service and take a commission in the Chemical Warfare Service and said he would get me in somewhere. Meantime, from time to time, I would go line up and try to get in the Air Force; they just had to make an average weight and height during any one day. But I never made it. Then I finally wrote to Jimmy Baird, who was then building the Quantico camp and finishing up the Lincoln Memorial, and he said he knew all the colonels and generals, of course, and to come on down and he would see what he could do for me. So I went down to Washington for a few months. He gave me a nominal job as assistant paymaster on the Quantico camp job, which meant that I had to go up to Washington and get the money once a week with an armed guard with bayonets I My actual job during the week was counting the deliveries made by the subcontractors — the number of elbows and pipes and things that they were delivering. I lived with the Bairds, but again, this darn weight-height business came up. Not even the generals could do anything about it. So again, I went back to Michigan and while I was there, "Hec" Britton, who afterwards became president of the American Chemical Society, had a summer job with the Public Health Service as a chemist. I donft know how he happened to hear about it or get it, but the Public Health Service was making a study of fatigue in 8 and 12-hour plants. They had chosen the Scoville Brassworks in Bridgeport, Connecticut as a 12-hour plant and the Ford Motor Company as the 8-hour plant. They had a very fancy and very large and diversified board--

Page  2323 economists, physiologists, psychologists, and others. For the most part, it was evaluating the amount of work done per unit of time, and subjective fatigue signs. There were two American physiologists who were consultants to this study and they had instituted some objective criteria. But the man officially in charge, from the Public Health Service, was named J. W. Schereschewsky. Dr. 0.: Schereschewsky. Yes, I know the name well from my association with the National Cancer Institute. Dr, H.: He was really quite a scholar in medicine and extremely broad in his interests. He had the idea that there were certain chemical things that could be studied in relation to fatigue and they had hired Britton, who had one more year to go to finish his Ph.D. in organic chemistry, to do certain chemical analysis of morning and evening urine of people on different kinds of operations. They had, among other things, the idea that there might be more protein breakdown and therefore nitrogen excretion would be important to do. Then somebody thought there might be more absorption of toxins from the gut. I don't know who thought of this, but anyhow this was in the picture already. So they did free and conjugated phenols and somebody else said, if you want to get an idea of protein breakdown, you ought to do the sulfur to nitrogen ratioo So Britton was doing total and ethereal sulfates and free sulfates. These were done on both the morning and evening samples of urine. Well, they had finished at the Scoville Brassworks and had moved to the Ford Motor Company when "Hec" Britton--thatf s Hector—decided the

Page  2424 draft was breathing down his neck. He was married and had a child and decided that he had better get his Ph.D. thesis wound up before he found himself a doughboy. So he came into my lab at Michigan one night and said, "How would you like to take over my job?" He knew--everybody around knew--I was struggling hard to get back into uniform. I said, "Is it war work?" He said, "Yes." Well, I was getting kind of discouraged about getting into uniform and I was ready for any kind of war work. "Hec" said, "They now have decided in Washington, that fatigue is due to acidosis and that they have got to have somebody to measure hydrogen ion concentrations. I thought of you because I know you have been setting up these hydrogen ion experiments for the students with the Hildebrand electrode, and you know all about it, at least as much as anybody does." Well, I have now finished the story of my life! I got this job with the United States Public Health Service, officially as of November 1, 1917, and I was hired to measure hydrogen ion concentrations of a body fluid—in this case urine--and I've been doing work related to hydrogen ion concentration ever since. [End of Side I, Reel l] [Beginning of Side II, Reel 1] Well, I had been setting up the Hildebrand hydrogen electrode which was the only one which was then described. This was a couple of years after it had been first described by Joel Hildebrand. I had this assignment to measure the hydrogen ion concentration of morning and evening urine in men at the Ford Motor Company engaged in different kinds of physical

Page  2525 operations. You must realize I had had no physiology up to this time, human or any other kind, and in an effort to get started quickly as of November 1, I went from Detroit back to Ann Arbor and got Eberbach and Son to give me two calomel cells, that is, the glass part of it with the platinum wires fused in. I told them I would see that the government would repay them. Total value about $5.50. This was the only thing missing from my set up because I had located a Type K potentiometer that had never been out of its box out at the Dearborn plant. I had a galvanometer, of course, and I had made my own bubbling hydrogen electrode, so all I needed were the calomel cells. I was so pleased with myself, I wrote to Washington and told Dr. Schereschewsky, "Would you please reimburse Eberbach and Son $5.50." There came back, in a few days, three typewritten pages, single spaced, of all the laws that I had brokenl Dr0 0.: From Dr. Schereschewsky? Dr. H.: Well, a short one from Schereschewsky and a long one from Beuchler, W. C. Beuchler, who was Disbursing Officer---- [Searching through some of his early letters] I wish I knew what I had done with that original letter. It's around here some place. But I apparently had violated the law of the land because I had not gotten bids from three different companies and gotten official Washington approval. And the fact that I, being so scared, offered to pay for it myself, made no impression on them at all. I had broken the law1. And they let me cool on this, worry about it for some time before they then

Page  2626 wrote and said that there are ways to mend this and we will allow you to get these bids in retrospect, even though the Eberbach and Son bid may not be the lowest, it may be possible to arrange to pay them—this thing didn't get resolved until the following April! There's my beginning! Dr. 0.: That was your introduction to the Government red tape. [See also p.277 ] Dr. H.: Yes, as long as I survived that, I've had no trouble getting along with it since then. They dug this all up and read copies at a meeting they held in my honor when I retired from the National Heart Council in 1964, and gave me this big citation signed by four living Surgeons-General. Dr. Terry couldn't be there; he was out in San Francisco and he sent the Assistant Surgeon-General and he read all this correspondence to all these people and it just brought down the house! Well, this, as I say, started November 1, 1917, and by the middle of December I had been reading about urine and kidneys and I wrote a letter to Professor Frederic S. Lee, the head of physiology at Columbia and consultant to the USPHS, under whom I was supposed to be working. He was in charge of my research activity. Schereschewsky was not directly in charge; I answered to Frederic S. Lee. I wrote him to the effect that I had discovered to measure the hydrogen ion concentration or anything else in morning and evening urine was a great waste of time, Mind you, I was also at this time doing Kjeldahls and free and

Page  2727 conjugated phenols and three kinds of sulfurs on all these same samples. So hydrogen ion determinations were not all I was doing. Dr. 0.: Did you have adequate laboratory facilities provided for you? Dr. H.: Yes. We did quite well as a matter of fact at the Ford lab. No thanks to Henry Ford personally, because he didn't believe in this kind of thing. But there was a good metallurgical lab and the chief chemist let me set up shop there. There are a lot of amusing stories involving the Ford Motor Company and its inefficiency in those days that I could go off on, but I am not going to. The fact that I had an appointment in the Public Health Service was very interesting in those days. It made people not know whether to—well, they were scared not to let me do anything I asked to do. I represented the government. Dr. 0.: This was the Ford Motor Company reacting to the fact that you were a government official in their presence. Dr. H.: That's right. The fact that I could get these various workers (over 40 of them) to pee in a bottle twice a day--I don't think a fellow coming from a university could have done it. Dr. 0.: It is a very interesting point. Dr. H.: I didn't know that at that time; it is in retrospect. Anyhow,

Page  2828 I got complete cooperation from everybody, everybody. (Ford himself, was off on a Peace ship at that time.) Do you remember the Peace ship? Dr. 0.: No, I fear I don't. Dr. H.: He took a ship and delegation to stop the war in the fall of 1917. Yes. It was a great event. Anyhow, he raised hell when he got back to the Ford Company. Well, what I am getting around to saying is that I wrote this letter to Frederic Lee and said that this was no way to study fatigue; it was a waste of the government's money and a waste of my time, that unless the government was prepared to study fatigue in animals under controlled conditions in a laboratory, I didn't want to do it. And out of that came then, orders to me to go to Columbia University, in the Department of Physiology, where Frederic Lee was the head of the department, and carry out the research. Dr. 0.: This was 1918. Dr. H.: This was 1918, January 1918 when I moved to Columbia. I really just had to learn to do these things myself though; there was nobody in the department that had ever bled an unanesthetized dog. They were used to anesthetizing cats and putting in cannulas and that sort of thing. To start with, the only thing we had was what they called a cat wheel, a wheel for fatigue, but you couldn't get blood from a cat. I don't know if you have ever tried to get blood from an unanesthetized cat. They are real rascals you know. The wheel wasn't big enough for dogs, so that's why I had to build a treadmill. There's a picture of my

Page  2929 treadmill in my thesis. [Turning to his bookshelf to get the bound volume of reprints] There are a lot of firsts in here. I must find that manuscript of that thesis. I am terribly sorry; I certainly wanted to save it as that is the only manuscript that I had ever typed myself1 [The manuscript was subsequently located.] [Coming across the EKGs in his thesis] People are more interested in those EKGs than they are anything else in this thing now though, because these were taken before, during, and after I was sticking a big trocar through the chest of these dogs, just quieting them down, and puncturing the left or right ventricle to get arterial or mixed venous blood. Ho B. Williams, who was the man who brought the string galvanometer to this country, took the EKGs. During this period, he was the only man who supplied the strings for the string galvanometer. The strings were all drawn and silvered in his private laboratory and he wouldn't let anyone else know how it was done at that time except his personal assistant. Dr. 0.: Where was he located? Dr. H.: He was in the Department of Physiology. He was an associate professor and later, after a little interregnum after Lee retired as head, he became the head* He was a physicist type. Oh, they had a great bunch of fellows in that department of physiology. Nobody has ever had better tutorial training than I had in those three and a half years, '18 to '21.

Page  3030 Lee was the head, German trained, a wealthy and highly cultured person, and lived just off 5th Avenue on 65th Street. These other professors, F. H. Pike, the neurophysiolegist, who was a contemporary of A. J . Carlson, Burton-Opitz, a cardiovascular physiologist, and Ernest L. Scott, well-trained in chemistry. [End of the 1st day of interviewing] Dr. 0.: The date is December 19, 1967, and again we are in the office of Dr. A. Baird Hastings at the Scripps Institute of Oceanography in La Jolla, California, for the moment fortunately, without rainl Dr» H.: I thought it might be well to mention that at the close of World War I, Dr0 E. L. Scott--Ernest L. Scott--who was an assistant professor of physiology but was also a biochemist, returned from France where he had been in service, and resumed the supervision of the research work which I was doing for the United States Public Health Service in the Department of Physiology. Dr. Scott, before he entered the service, had been engaged in the study of the sulfur and phenol metabolism carried out by Dr. Britton in his absence and taken over by me. We completed this work together, and it was published in the Public Health Reports. Meantime, I went on with the study of what we would now call changes in the acid-base balance as the result of exercise. Dr. Scott was my immediate thesis supervisor after I had accepted Professor Frederic Leefs invitation to take my Ph.D. in physiology. This came about one day when the war was over, Dr. Lee called me into his office and asked me what I was going to do now that the war was over. I said

Page  3131 that I was going back to the University of Michigan and go on with my studies toward the Ph.D. in physical chemistry with Professor Bartell. He said, "Why don't you stay here and take your Ph.D. in physiology?" I said, "But I haven't had any physiology; I'm a chemist." Dr. 0.: This was the question I was going to ask. Was it somewhat unusual in those days for a man to switch disciplines, as it were, for his Ph.D.? Dr. H. : Well, I presume so. I was a pretty innocent fellow in those days. I didn't know how people got Ph.D.s. My main objective was to earn a living because I had been married May 31, 1918 and on May 14, 1919 our son, Alan Baird Hastings, was born. When Dr. Lee asked me if I wouldn't like to take my Ph.D. in physiology, I said I didn't know any physiology. He said, "Well, you know chemistry and we can teach you the physiologyI" Since I was going to get $1200 a year as a salary as an instructor at the University of Michigan, and I was receiving $2400 a year plus a dollar and a half per diem allowance as long as I was away from my official station in Washington at the Hygienic Laboratory, and since I had a wife and baby, I decided it would be foolhardy not to become a physiologist. It had nothing to do with the desire to be a physiologist. So I did register in the graduate school and in those days, Columbia University was very generous. They wrote to the University of Michigan and gave me credit for the courses I had started in February, 1917, but had left for Officers Training Camp in April. I hadn't really completed

Page  3232 the courses, but they recorded them as credit for everybody that did that, and Professor Lee also arranged for me to get retroactive credit, as much as they allowed, for the research that I had already been doing for the government in the department. It only left me the problem of getting some credits on the record in physiology and in biochemistry. I actually assisted in the physiology lab course while I was taking it and got credit for it that way. For biochemistry, since I couldn't spare much time from my research activity for which I was being paid, I took a course which was given all day Saturday in the second semester of the year for those medical students who had flunked the course in biochemistry the semester before! Well, that is all the formal biochemistry I ever had. Now my thesis work was partly on the changes in the acid-base balance following exercise and partly on the changes of the fragility of red cells of the blood with exercise. This latter problem was suggested to me by Dr. Scott. It yielded positive results immediately. After exercise, the circulating red cells were less fragile, statistically speaking, than they were under control resting conditions. This turned out to be due to the fact that with exercise, dogs developed a hemoglobinemia, particularly if they have not been run for several days (the more fragile cells had been broken up by the severe exercise)0 It turned out that one could, by exercising the dogs mildly, regularly every day, that this phenomenon disappeared and led to the conclusion that after a prolonged period of no exercise, the blood accumulates a

Page  3333 lot of old and about to be broken up red cells which then, on whipping them around as we did with really violent exercise (eight miles an hour was nothing for these dogs to do), just simply broke up those red cells faster than the spleen could take them out. This led to a really pink plasma. The other thing that we got into in connection with this work on exercise on the blood, was the effect of oxygenation and reduction and the effect of C02 addition and subtraction on the fragility of the red cells. Because this seemed to involve osmotic pressure changes, we even got into the study of the distribution of chlorides and bicarbonate, in other words, a very early study of the effect of Donnan equilibrium on the distribution of ions. This was undertaken in very much greater detail later at the Rockefeller Institute, but it is all in the thesis. It seems as if the consideration of equilibria in heterogeneous systems, that is, where the membranes are involved, is a subject that has set the framework for practically everything I have done. In those days, even the composition of the red cells was not very well determined. Methodology was still pretty inadequate, particularly for small amounts of blood. It's hard for us to remember now that prior to the Van Slyke volumetric apparatus which permitted one to do carbon dioxides and r- oxygen on one or two cc. samples of blood, it used to take 500 cc'sc of blood to make an accurate oxygen determination. This was done with a thing called a PfltTger pump. I remember they had one in the department of physiology at Columbia. I never tried to use it.

Page  3434 I actually didn't know that the Van Slyke volumetric apparatus existed when I undertook the study of the alkali reserve of the plasma in relation to exercise and fatigue. I adapted a titration hydrogen electrode that had been described by J. F. McClendon, of the University of Minnesota, to titrate the plasma and as a measure of the alkali reserve, i.e. how much acid it took to bring the pH to normal. This adaptation and this particular electrode led to my writing it up. Dr. 0.: Yes, in 1921. [#12]* Dr. H.: Having written it up with the idea that maybe it might be published, I asked my friend, Dr. G. E. Cullen, who was Van Slyke's first assistant at the hospital of the Rockefeller Institute, whether he thought it was worthy of publication. He was pleased with it when I took it over to the Rockefeller Institute and said, "Wait a minute I" and he went into Van Slyke's office. Pretty soon he came out and said, "Dr. Van Slyke wants to see you." Van Slyke, who was then editor of the Journal of Biological Chemistry, accepted it for publication then and there. That was March 9, 1921. Then he said, "What are you going to do when you get your Ph.D.?" It was supposed to come off in June. I said, "I have been asked by Dr. Schereschewsky to come down to Washington and start a physiological research laboratory in the Hygienic Laboratory." They had no department of physiology. They had just that year persuaded Dr. William Mansfield Clark to leave the Bureau of Animal Husbandry where he had been ever since his Ph.D., and transfer to the jr. _. Throughout this memoir, the number in the square brackets [J will refer to Dr. Hastings' bibliography which appears at the beginning of the memoir.

Page  3535 Public Health Service and head the department of chemistry in the Hygienic Laboratory in Washington. Van said, "Well, that would be a fine thing to do, but perhaps there's another alternative." (I should have said that they were still holding an appointment at Michigan at this point.) Well, he said that he thought it would be very much better for me to go down and be near William Mansfield Clark, who was a great friend of Van Slyke and indeed they had worked together at Woods Hole. He said, "There might be still another alternative, but I can't tell you anything about it now. Just don't do anything until you hear from me!" This was March. Well, March went by and I didn't hear from him, April went by and I didn't hear from him, and in--well, I've forgotten the exact dates; you can check in the Schereschewsky correspondence if you want the exact dates--anyhow, it was getting mighty close to June and I had to make some kind of a decision. I called him one day and asked him if there was any reason why I shouldn't tell Dr. Schereschewsky that I would come down to Washington, and he said, "I can't tell you just this minute, but I will let you know in a day or so." It was true. He called me over and offered me a job as Glen Cullen's successor, as his first assistant. The reason he couldn't speak earlier was because Cullen was dickering to go to the University of Pennsylvania as a research professor and these things had to be settled first. Also, he had to get Dr. Flexner's permission because Flexner, as the Director of the Rockefeller Institute, never let even the members hire anybody unless he himself had interviewed them. I didn't get interviewed by

Page  3636 him (Flexner) before, which was a very rare thing, but I did shortly after Van had told me I was to be appointed. Well of course this was a tremendous opportunity! It meant that I was in charge of Van's research laboratories. We planned the experiments together, but the execution and the organization of who would do what was in my hands. I felt very badly, and do to this day, that I let Schereschewsky down. He left me there at Columbia to finish my Ph.D. so I could come down and start their department of physiology and then I didn't goj Dr. 0.: Had there been some discussion to this effect early on, or was this something that came up shortly before 1921 when you got your Ph.D.? Dr. H.: No. This was part of the plan from 1919 on. The grounds on which Schereschewsky left me there after the war was that I would take my Ph.D. and then come down. So there was nothing committed to writing on what my position would be; it was a gentlemen's agreement if you will This guilt feeling on my part accounts for the fact that from that moment to this I'd do anything the Public Health Service asked me to do. Dr. 0.: You certainly have been involved with them ever since that time. Dr. H.: I certainly have and I'll do anything they ask me' Trying to overcome this feeling that I let them down.

Page  3737 I went to Van's department in the fall, i.e. Van Slyke's department at the Hospital of the Rockefeller Institute and everything good that has happened to me from that time to this was because of that. They started calling me a biochemist when I went there, so even though in my heart I have known I wasn't, I sort of rolled with the punch as it were. It was my good fortune to get there just the year after Van Slyke, at F. C. McLean's instigation, had undertaken to work on the blood as a physicochemica1 system. McLean had been at the Rockefeller Institute before the war and worked with Van Slyke and had, after the war, become the first Director and Professor of Medicine at the Peking Union Medical College, the famous PUMC. He was there for eight years in that capacity until he then went to Chicago and started the full time school there. They got every third year off, two years there and at least part of the third year off, and McLean had gone with this same fellow, Dr. H. A. Murray, whom we were talking about yesterday [off the tape], and spent some time in L. J. Henderson's laboratory trying to prove that there is a chloride shift when you oxygenated or reduced blood at constant pH, This was predicted by Henderson and the methodology that they had available at that time was inadequate; they couldn't prove or disprove it. So McLean, before he went back to his job in Peking, persuaded Van Slyke to undertake this study. It needed a gasometric method for determining carbon dioxide and oxygen that was more accurate than the volumetric method which had been worked out for clinical purposes.

Page  3838 It was as a result of that that Van Slyke invented the manometric method which gave an accuracy of .04 of a millimole per liter in the C02 determinations instead of about a half a millimole; about ten times more accurate than the previous method. The year before I went, in 1920-21, McLean, John P. Peters, Harold Austin, G. E. Cullen, and Van Slyke had attempted to study the effect of oxygenation and reduction on CO^ absorption curves. I should also say they were stimulated to do this because Yandell Henderson, the Professor of Physiology at Yale, had with some young associate in his department at Yale, published a paper in the Journal of Biological Chemistry in which they claimed that there was no difference in the C02 absorption curves of oxygenated and reduced blood, if the blood was oxalated. This of course turned out not to be true and again was due to inadequate methodology in Yandell Henderson1s hands. The methods of equilibration which Peters and Austin had devised to study this subject in 1920, 21, were both cumbersome and inadequate, so when I went there in the fall of 1921, they had not been able to get a completely successful series of experiments, largely because of the methodology of equilibration which didn't yield four good equilibration points. You might get two or you might get three but it wasn't enough to draw definitive curves. James Neill had come to the Institute, though trained in bacteriology and ultimately destined to be a professor of bacteriology at Cornell

Page  3939 and to work at the Institute with Avery, the bacteriologist, had been farmed out to Van Slyke to learn more chemistry. Van brought him in immediately on the perfection of this new manometric apparatus and Neill did the major part of the actual experimental testing of it and perfecting it0 So the manometric apparatus is always known as the Van Slyke and Neill apparatus. Cullen overlapped me for a few months„ He didn't leave for Pennsylvania until January. Dr. 0.: He later went to Vanderbilt, did he not? Dr. H.: He later went to Vanderbilt and then from Vanderbilt he went to Cincinnati, where he was head of biochemistry in the Children's Hospital Medical Research Foundation, which was sort of a Rockefeller Institute for Children. He died in 1940--a huge and able biochemist with a heart as big as his body. When Cullen left in January, we were still trying to make this method of equilibration work that Neill and I had inherited. We couldn't do any better than they did. So one day after having had an unsuccessful experiment, we decided, "Let's get out in the fresh airl" I think it was early in March perhaps, but it was warm for a March day. We went to Central Park and climbed up on the highest rock they had, and then Jimmy Neill, who was a little, short, Pittsburgh-stogey smoking fellow, who had a terrific vocabulary when it came to profanity--swore to the high heavens I Literally! And when he got through, one of us said to

Page  4040 the other, "You know what we really want to do is get this blood equilibrated with the gas phase and then simply cut the blood from the gas." Our whole problem had been that you would get an equilibration and then the problem was to get your blood out or your gas out without changing the equilibrium you had set up, and this had become such a Rube Goldberg business of trying to do it that it had failed. With that statement, we said, "Why not?1." We went back and sketched out what we wanted and Van thought it was a good idea so we did just that. [Referring to a drawing on p. 129 in the publication No. 16 in the Hastings' bibliography] Our contribution was to change one big equilibration vessel into one big and one little vessel connected with a flexible rubber tubing. We would carry out the equilibration, and then without taking the vessel out of the bath, we'd put it in a vertical position and then we would simply let the blood drain into the little vessel. Then we would put two clamps on the rubber tubing, lift it out of the water bath, take some scissors and cut the rubber in between the two clamps. Then we hitched the little vessel up to a mercury reservoir and we hitched the gas up to the mercury reservoir, and we could sample each of them, and from that moment on, every experiment we did came out perfectly! We rolled out enough for three papers in a matter of two months'. Believe me, these were long experiments; I would stay in the Rockefeller hospital the night before and start the experiment at seven o'clock and have samples ready for analysis at 8:30, when the rest of the gang

Page  4141 would turn up. Often we would be plotting our data by 10 or 11 o'clock the same night. Our data were so good that if, in plotting it, there was one point that suddenly was off the straight line, we knew there was an error in calculation—not ana lysis--some place1. Van Slyke still says that this was the happiest and most productive time of his life, and it certainly was for me. [Referring to one of the publications resulting from this experimental work] You can see it is so good--that is one with ten equilibrations--every point is on the line. One way to describe this work is C0« titration curves of oxygenated and reduced hemoglobin. The problem was how much were they separated at the same pH, because that was the basis for making the calculation of how much the pK of hemoglobin shifted on oxygenation and reduction. You couldn't get all that data published today, you know. Dr. 0.: That's right, you'd have a devil of a time. Dr. H.: These data were praised by L. J. Henderson because this permitted one for the first time to calculate, with any degree of accuracy, the shift in the pK of an ionizable group of hemoglobin on oxygenation and reduction. The data that I'm talking about, that we were able to get immediately on changing this technique, is illustrated in this paper which you might like to make a note of.

Page  4242 Dr. 0.: Yes, that is publication No. 17 in your bibliography, Van Slyke, Hastings, Heidelberger, and Neill. Dr. H. : Nobody had been able to get data on the partial reduction of hemoglobin before, such as we got in experiments like this one, so we could plot the degree of oxygenation against the change in the bicarbonate at constant pH. These points all lie on a straight line. Nobody knew, up to that time, what kind of line it would be. Now seeing Heidelberger1 s name on this, I must interject something about Heidelberger. May I? Dr. 0. : Please do. Dr. H. : The same time that I came to the Rockefeller Institute, in the fall of '21, Michael Heidelberger joined Van Slyke1 s department temporarily. Jacobs and Heidelberger--that ' s Walter Jacobs and Michael Heidelberger — were organic chemists at the Rockefeller Institute (not the hospital), and for some years their job had been to synthesize and discover a chemical that would be a "magic bullet" for trypanasomiasis which was the subject on which Louise Pearce and Wade Brown had been spending many years. After many false leads and the synthesis of many compounds with no therapeutic value at all against the trypanasome, they " encountered (1919) what is known as tryparsamide. This was proven Tryparsamide: Jacobs and Heidelberger, 1919 OH ONa

Page  4343 effective in the field by Louise Pearce, and I think was actually patented by the Rockefeller Institute, though it has been made available, of course, for the medical profession. Before I went to the Institute, Dr. Flexner had called Jacobs, who was the senior of the two, and Heidelberger into his office, and though I wasn't there in effect, it's my understanding that he said, "Gentlemen, you have had to synthesize many compounds before you finally got one that was effective. This has cost the Institute so many thousands of dollars. I think that if you undertook another subject like this you might not be so lucky1. I think this is not a profitable direction for the Institute to take. Jacobs, you are senior, we'll keep you. Heidelberger, I'll give you one year with pay to go any place you want to and get further experience." At that time, Heidelberger was an organic chemist, not a biochemist; he wasn't a bacteriologist; he had even written a small textbook on organic chemistry. Well, Heidelberger decided that he ought to learn more biochemistry, and that the opportunities were greater in biochemistry than in organic chemistry, and because Van Slyke was, even then, the senior biochemist who would be apt to hear about any jobs, Michael elected to spend that year with Van Slyke to pick up some biochemistry and hopefully Van would get him a job before the end of the year. He came over and Van accepted him. Van actually assigned him for the first few weeks he was there, to Alma Hiller, who was Van's clinical chemist. The M.D.s who came circulating through the department and

Page  4444 were assistant residents in the hospital were under Alma Killer as far as their doing laboratory work was concerned. So the first time I laid eyes on Michael Heidelberger, he was in this clinical chemical lab doing Kjeldahls, creatines, creatinines, and acetone bodies in the blood, urine, and so forth. I have often wondered what he thought, since he was an experienced and senior organic chemist. When I arrived and we got going on the blood as a physicochemical system, and we decided we wanted to work with hemoglobin as such, Van asked Michael to devise a method for preparing pure, active hemoglobin. He owned a horse--a big horse--in the department and I was the horse bleeder. I could stick that trocar in his jugular vein and get out 500 cc. of blood in no time flat, a liter if necessary. Dr. 0.: Did you keep the animal at the Institute or did you have to go over to Princeton? Dr. H.: Ours was kept at the Institute in New York. They had several, but ours was the oldest and the king of the lot. The rest, they all made work from time to time on the gardens and grass. But our horse would refuse to do any work, quite above it. Michael devised what I still think is probably the best possible method — the best method yet devised—for preparing pure, salt free, isoelectric, active hemoglobin. All of our work was done with

Page  4545 hemoglobin that Michael prepared. I won't go into the method; it is on record, of course. Now comes the interesting point. Michael was already an Associate at the Rockefeller Institute. The lowest rank was Fellow, the next rank was Assistant, the next rank was Associate which was a three year appointment and repeatable, and above that, Associate Member and Member, both of which carried tenure. Technically, I was over Michael since I was in charge of, or the first assistant to Van Slyke; Michael, though an Associate and outranked me, nevertheless was a visitor in the department. As Cullen was cleaning his desk preparatory to leaving on January 1 for Pennsylvania and to turning his little office over to me, he came upon a vial--that would hold about 50 ccs. It was about half full of some tannish noncrystalline gunk. He said, "By the way, this is some material that represents an acetone precipitate from broth cultures of pneumococci" (I can't remember if it was Type I, II, or III at this time). "It contains a thing which Avery calls a specific soluble substance." "The 'Fess,'" which is what they always called Avery, "is such a wonderful fellow and you will enjoy knowing him, that I urge you, in your spare time, to go on working on this because the 'Fess' will come up after I have gone and ask you if I told you of the work I was doing with him and he will draw you a little bean-shaped thing and he'll put a little halo around it and he will say, 'if we just can find out what that little halo is; there's where the secret of type specificity resides.'"

Page  4646 I said, "Glenn, I'm a physical chemist, if anything, and I know so little organic chemistry it would be a shame for me to even attempt to do anything with this material. But Michael Heidelberger is here and this is right up his alley. He is the one who ought to go on working on this." So I went out in the corridor because Michael was working in Van Slyke's own lab which was on the corner of the 7th floor, and this little office was across from it. I came out in the middle of this corridor and said, "Michael, come here. I've got a present for you1." He came and I told him what Glenn had told me and handed him this little bottle. [End of Side II, Reel l] [Beginning of Side I, Reel 2] Dr. H.: After Glenn had gone, Avery came and asked me about this work that he said Cullen had been doing with him, and I said that I had turned it over to Michael Heidelberger who was an organic chemist and could work on this problem much more effectively than I could. So he went in and, according to Michael, did just what Glenn said he would; drew his little pneumococcus with the halo around it and sufficiently interested Michael so that in his spare time, when he wasn't making hemoglobin for us, he started doing some routine qualitative determinations as to just what sort of substance it was. When he did a Molisch reaction, which even I could have done, he got a strong positive reaction indicating carbohydrate. This is a qualitative

Page  4747 reaction for carbohydrate that is done by every medical student on the first day in biochemistry. It stood out magnificently purple, which meant there was lots of some kind of carbohydrate there and that interested Michael, and in the course of a very few weeks, he had pure material from the then different types of pneumococci. This was the specific soluble substance from the smooth pneumococci--Type I, Type II, Type III. When he examined them by polarimetry and by analysis, they were obviously large polysaccharides with sugar acids. I titrated some of them when he had gotten them pure, and found that they had pKs down between 2 and 3. The sugar acids, glucuronic and gluconic acids had pKs around that neighborhood. In the titration, I was also able to pick up an amino group which eventually turned out to be glucosamine as part of a polysaccharide of Type I pneumococcus. The important thing is, that I want to get on the record; when I passed this little bottle from my hand to Michael Heidelberger1s hand, immunochemistry was born1. That was the beginning of immuno chemistry I It's not often that you know exactly when something begins. He is Mr. Immunochemistry, number I1.--in the world1. Growing out of this, he got Walter Goebel to come with him. Obviously, Dr. Flexner never called to his attention that he had only one year. He stayed then at the Rockefeller Institute for some years, going for a short time then to Mt. Sinai, and then shortly after, was called to Columbia where he stayed until he retired. He then went to Rutgers and had a series of years there after he retired from Columbia, and now I believe he is at

Page  4848 New York University. He will be 80 next April, is still working, and should have long since been a Nobel laureate. The fact that there are these specific and chemically identifiable compounds that are characteristic of this specific soluble substance, then led Avery, McLeod, and McCarty to the transforming factor. Avery was able to transform a rough one to a smooth type of a different species, and that led to the transforming factor which turned out to be DNA, and that led to the whole darn business of getting Nobel Prizes today. It is a very exciting history! It's medical history, but it isn1t Hastings history. But what a break it was that Michael was there; that Flexner had broken up the Jacobs-HeideIberger team. Oh, it would have happened some other way I suppose, in the future, but this is the way it did happen! Well, to go back to the Institute, my job for the five years I was there was mostly to run the experiments on the study of blood as a physicochemical system, though we did a number of things on the side, which I am kind of proud of. For instance, as part of the business of seeing whether you could account for the precipitation and solution of the calcium salts of bone by physical chemical laws along; in other words, what was the solubility constant for bone salt--in our naivity we thought it was a mixture of calcium carbonate and calcium phosphate, tertiary calcium phosphate because that is what your chemical analyses

Page  4949 told you. We couldn1t study that unless we had the dissociation constants for carbonic acid at 38 degrees centigrade and at the ionic strength of body fluid, and of the dissociation constants of phosphoric acid under the same conditions. The physical chemists, who had put such constants in the physical chemical literature, never worked at body temperature and seldom worked at salt concentrations that were equivalent to those in the body. So just after the Debye-Huckel theory appeared (1923) which accounts for the change in activity coefficients of ions in salt solution, Sendroy and I (Sendroy was my technician at that time) undertook to study the effect of changing ionic strength at 38 degrees on the first and on the second dissociation constant of carbonic acid. We needed the second in order to get the CCL ion concentration, in order to get at the bone problem. I believe we were the earliest people to put in the literature the effect of varying ionic strengths and apply the Debye-Huckel theory to the change in the activity coefficient of weak electrolytes (1925). E. J. Cohn did a bigger job on the phosphate ion activities, but that was later (1927) than we did it on the bicarbonate and carbonate ions. Because it was published in the Journal of Biological Chemistry, the physical chemists have never noticed it. Although I have no reprints of that paper left, they were almost the last ones to be exhausted. And yet of all my papers, I am proudest of that job--a purely physical chemical job—because it was done accurately and elegantly and many years later. Duncan Maclnnes, a

Page  5050 famous physical chemist of the Rockefeller Institute, now dead, did a very comprehensive study and much more elaborate than ours and over wider ranges of temperature, ionic strength, etc., but the extrapolated value of his dissociation constants to zero ionic strength which is the true pK, is within .01 of a pK value of the one we put in the literature many years before. I get a great kick out of this because his are the data that are always quoted1. [#35] That done, we went back to the business of studying the solubility of CaGO^. We used those data on the study of the solubility of the bone salt and factors that affected it, and those three papers were published in the Journal of Biological Chemistry. Dr. 0.: Yes, in 1927, Hastings, Murray, and Sendroy. That's item No. 35 in your bibliography. Dr. H. : That represented 123 pages — those three papers. Dr. 0.: I was very aware of the amount of data that appeared in papers of this period. Dr. H.: Yes, you can't get anything like that published anymore. It's too bad. Dr. 0.: Can I ask you--I gather there was a very close association between Dr. Henderson's laboratory at Harvard and Dr. Van Slyke's laboratory.

Page  5151 Dr. H.: They were-well, I wouldn't say intimate friends, but good friends and intimate, professionally. Henderson had this great mind, but he couldn't do an experiment to save his soul. He never did an experiment; never attempted to do an experiment after he worked in Strassburg as a young man. Dr. 0.: You will pardon my naivity. Is this when he was associated with Hasselbalch? Dr. H.: No, he never was associated with him physically. It has just become customary to call it the Henderson-Hasselbalch equation because Henderson1 s great contribution—probably his greatest—was to realize that as far as biological phenomena are concerned, the interesting thing and the significant thing about any weak electrolyte, whether it's carbonic acid or phosphoric acid or acetic acid or lactic acid, is not how much is there, but how much of what is there is partly ionized and partly not. Another way of stating this is that analytical chemists are only interested in end points of titration. They're interested in the beginning and the end--to find out how much of the acid is present. Henderson introduced, back in about 1908 or 1909, the concept that what you should be interested in is everything between the beginning and the end. Though he did not introduce the idea of buffer, he really was talking about the ability of weak electrolytes in the presence of their salts to be buffers. He concentrated on the mass law equation, [H j [A ]= K, as being the physiologically ~THA] interesting part, and the ratio of the ionized to unionized acid is

Page  5252 what sets what the hydrogen ion concentration is. Now Hasselbalch took the logarithm of this equation after S^renson had introduced the concept of pH. The Hasselbalch contribution is simply converting the mass law equation in its simplest form to a logarithmic form so you can plot H"*concentration on a logarithmic scale. This is not significant because if you tried to plot a titration curve against hydrogen ion, you can't get it on a reasonable sized piece of paper, but if you plot the degree of dissociation against pH, then you get a symmetrical S-shaped curve and the position of it on the pH scale is determined by whatever the pK is, i.e., the negative logarithm of the ionization constant. (Henderson-Hasselbalch equation: pH = pK+log[A*]) [HA] The second year that I was with Van Slyke he got me promoted to an Associate, and he went off to China for several months to the Peking Union Medical College at McLean1s invitation. He and McLean and Hsien Wu, Professor of Biochemistry at the Peking Union Medical College, worked together while he was there. So Van Slyke, Wu, and McLean, during this period that Van Slyke was in China, extended the work that I have just been describing on the blood that we did in the spring of 1922, to the application of the Donnan equilibrium to the distribution of the diffusible ions, chloride, bicarbonate, hydrogen ion between cells and serum. He left me, during that period, to get the definitive ionization constants of hemoglobin which I was showing you a little earlier. That was the job I did while he was in China. When he came back, much of this work that they had done out there had

Page  5353 to be redone, at least Van Slyke wanted it redone because he never wanted anything to go out in the literature unless it was the best you could make it. He decided that the chlorides were not very accurate and he developed a better chloride method, and we redid the experiments after he got back from China. There was something else I was going to mention, but I got off the track--about the China trip. Dr. 0.: You make reference in the address which you gave at the dinner in Dr. Van Slyke1s honor, to a letter he apparently sent back, a longhand letter in which he essentially wrote the paper. Dr. H.: If I can find it, Ifll let you see it. He wrote this paper on the boat going over and it was practically complete except for the constants that he would need to put in. Dr. 0«: Which is the work he did there in China. Dr. H.: Yes. It is really quite a classic. I hope somebody gets his papers. I think you better go after them. Dr. 0.: I just assumed that they already had been obtained by somebody; in fact, I am amazed that the Rockefeller would let them loose. Dr. H.: He has been away from there for a long time. Of course, they have sort of rediscovered him. They gave him an honorary degree last June.

Page  5454 In the spring of 1925, I was called to Flexner's office one day and he said, "Professor Otto Warburg is coming over to the Institute. He is going to be here two weeks. He's going to bring this apparatus which he has devised to measure tissue respiration. He's published a series of papers using this, and it is of interest to us here because we have various people working on cancer. He has found what he calls a high aerobic glycolysis in malignant tumors--experimental transplanted tumors. Instead of having him demonstrate this to the people who are doing cancer research, I've decided to assign you to Warburg as his laboratory assistant--his technical assistant—while he is here. You are the only person who will have access to him. I want you to learn all about the use of this apparatus, and then after he goes, I will expect you to teach anybody from the cancer research laboratories, such as Murphy or Carrel or Rous or any of their people. For this, you may have this apparatus, if you care to use it." It was very smart of him because if he had picked anybody from any of the other people doing cancer research; there was jealousy among them, they worked behind locked doors. Dr. 0.: Carrel, I gather, was a rather difficult person to work with. Dr. H.: So I was assigned, while he was there, to Otto Warburg, whom I had never met, and I hadn't ever been in Germany so I didn't speak German, but I could read it--scientific German. I remember so well the very first morning. Warburg could speak English

Page  5555 though he didn't like to, but he could and certainly could understand it. He laid out the reprint of how I should make up the solutions in preparation for doing an oxygen consumption on some tumor tissue, or liver I guess we used — slices of liver. He had a way, which most of us have used ever since, of making up a lot of isotonic solutions-sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium bicarbonate; and then you know you are isotonic no matter how you mix them. By putting so many ccs. of each of these solutions in, you can end up with an isotonic solution which has the right concentration of bicarbonate, and the right concentration of calcium, potassium, magnesium, and sodium chloride makes up the rest, then you put in glucose of course. Well he said, "Now we will put in so much sodium bicarbonate and we'll bubble 5 per cent CC^ and 95 per cent oxygen through this before we add the calcium and magnesium so it won't precipitate, and then we'll have sieben comma vier." I said, "Nein, Herr Professor, sieben comma eins'." This was one subject which I knew forwards and backwards and he couldn't fool me on the fact that if you only put in 12 and a half millemoles of bicarbonate and bubble 5 per cent COo through it, you are going to have a pH of 7.1! The blood plasma has 25 millemoles of bicarbonate per liter and 40 millimeters CQj* That is equivalent to 5 per cent C0£ in gas. I had measured too many of these things. Warburg had never measured a pH in his life1. He calculated them, only he was too damn smart for himself. You see he had an M.D. and a Ph.D.

Page  5656 in chemistry and had worked in physics; his father was a great physicist For some reason or another, he had gotten into his head so firmly that carbonic acid, being a dibasic acid, could contribute two hydrogen ions. This has nothing to do with the price of eggs if you stay below pH 8 or 9--I mean that second one doesn't dissociate if the pH is around 7, you seel But he had just decided that everybody--Henderson, Hasselbalch, everybody--had been making a mistake through these years and he, by George, was not going to make the mistake, but nobody had ever taken him up on this before—nobody!--and all his papers prior to 1925, and he had been publishing for 15 years, I guess, his phs were wrong as published! By 0.3 of a pHl Well, it suddenly dawned on him, even with my poor German, what he had been doing! The result was that he recognized and acknowledged his mistake. He went back to Germany and published a one-page correction and thanks to me in the Biochemische Zeitschrift. Birgit Vennesland put it into the Hastings 70th Anniversary Symposium. It's not published in the proceedings, but I've got a copy of it which she showed as a slide. The result of this was that when he left, he invited me over to work with him. I think I was the first American to work in his lab; I wasn't there long, I left in May and came back in October. This was 1925. I spent a long summer there with my wife and baby. It just happens that I didn't do much work on respiration in his lab,

Page  5757 but I did do my first work with radioactive isotopes. He had an idea-it was a screwy idea, I guess--that narcotics worked by way of their solubility in membranes, and he had decided that one way to study this--explore it anyhow--would be to take a substance like an inert gas and then see how its solubility was changed if you put in thymol, let's say. As an easy way to study solubility of an inert gas, he suggested that we use radon. So I set up an apparatus, which I still have pictures of--never published it and I kick myself for not doing it--and I determined the solubility of radon, the solubility coefficient of radon in yeast cells and in red cells that summer. We used an electroscope--a very fancy one, a fine big German one--we got from the department of physics. It was very accurate; still probably a sure way of measuring radioactivity to this day, and certainly simpler--foolproof. Nothing but a gold leaf and a stop watch; you can't go wrong! Dr. Oc: One of the letters I came across that I found very interesting was from Dr. Murray--"Mike"--at this time when you were about to leave for Germany, and he had a rather amusing comment about Dr. Warburg which goes along with what you just said; that is, he was rather pompous and opinionated. Dr. H.: Oh he was very opinionated! If you'd get around to reading any of those messages from people who came to my 70th anniversary symposium party in Ann Arbor in the fall of '65, you'll find a telegram

Page  5858 there from Warburg that goes something like this: "Congratulations on your 70th anniversary. Sorry I cannot be present. You have made good as I always knew you would and I am always right." Dr. 0.: He hasn't changed with age, has hel Dr. H.: On his 70th anniversary, Conant was then High Commissioner to Germany and he happened to tell me, one day when I ran into him in New York, he was going up to Berlin to make a speech at the celebration of Warburg's 80th birthday. Well, I hadn't kept track and I hadn't written him in a long time, so I sat down and wrote him a real nice letter congratulating him on his 80th birthday and he wrote back that I was 10 years early; it was his 70th birthdayI Dr. 0.: Among your papers, I have found a letter dated February 11, 1922 in which you invited Professor W. M. Bayliss, of London, England, to visit what you refer to as the Junior Bayliss Club in New York and meet with you one evening. I wonder if you could expand on this for me. Dr. H.: While I was still at Columbia and working for the Public Health Service and for my Ph.D., a small group of us in our 20's, attached to different medical school departments, decided to form a Junior Bayliss Club and each obtain a copy of Bayliss' Principles of General Physiology, study it together and meet together regularly every two weeks as mutual students teaching each other. We had been doing this for a couple of years when we learned that

Page  5959 Professor Bayliss was coming to give a series of lectures in New York under the auspices, I believe, of New York University. I was delegated to write him and ask him if he would dine with us while he was in New York. He accepted the invitation, and we arranged to have dinner in a private dining room at Keenfs Chop House where they were famous for their large and luscious lamb chops. When we picked up Professor Bayliss at Dr. Wallace1s home, he turned out only to have a very few teeth left and was quite unable to enjoy and masticate these specially large and luscious lamb chops. He had a small pipe with a well-chewed stem that he puffed on instead,. Nobody could have been more charming, more interested, and interesting to us than Professor Bayliss was that evening. It was one of the high spots of our lives. A year later when Dr. Cullen and his wife and I and my wife were crossing the street at Piccadilly Circus, who should we encounter but Professor Bayliss! This was the first trip of either of our families to England or abroad at all. Bayliss promptly invited us out to his very large and fancy home at Hempstead. He showed us the bench under the tree he had built, where he had written the book, and had fresh fruit from his own gardens for dinner, of which we had had none of since we arrived; again, he could not have been more charming or more considerate. Dr. 0.: Another letter, on a totally different subject, but I thought rather interesting because in a sense it appears to be your first contact

Page  6060 with oceanography; a letter which makes reference to a cable you received from William Beebe in March of 1925. The letterhead says "the Putnam Syndicate." You might expand on this as it seems to be a rather unusual set of circumstances. Dr. H.: William Beebe, as you well know, was in the habit of making expeditions to strange places and making scientific observations of a sort. In this year, 1925, his expedition was to the Sargasso Sea. Prior to leaving, he sent one of his girls on the staff who was going on the expedition, named Miss Kopoloff, to the Rockefeller Institute to learn how to measure pHs colorimetrically; since this was a subject on which we had worked for some time and indeed were still working, Dr. Van Slyke referred her to me, and I taught her how to measure pHs over a wide range using dyes, acid-base indicators as standards. We fixed her up with the standards and stock solutions. To my surprise, I suddenly received, via Mr. Putnam, this cable which in effect says, "What concentration of bromcreosol green did you tell me to use?" The surprising thing is to receive that as a query from the Sargasso Seal To have had the opportunity, immediately after getting my Ph.D. at Columbia, to spend 5 years in the laboratory of Dr. Van Slyke at the Hospital of the Rockefeller Institute is by all odds the most important experience--scientifically and otherwise—that I have ever had. Van Slyke himself is one of the two men who made biochemistry bloom in this

Page  6161 country; the other being Otto Folin, my predecessor at Harvard. Van Slyke was always on an informal basis with all of his associates in the laboratory and he was known as "Van" to all of them. His standards of analysis and of research were the highest attainable. He never would let any paper go out for publication in which there was any feeling on his part that some of it could be done better. As an example, every year for the five years I was there, we made measurements of the solubility coefficient of carbon dioxide in water, salt solutions, plasma, and red cells. At the end of each year he would say, "Now Baird, go write this up," and I would write it up and then, as happened all five years, he would say, "I think I will put this away in my desk until fall and look it over again; we might think of some way of improving this." This paper was actually not published until 1928— two years after I had left. [#4l] The other thing that was very important as far as my own future life was concerned was that I was in an environment in the hospital where Van and I were but two biochemists among half a dozen clinicians, all of whom were doing research of course. This means that I, very early in my life, was thrown intimately with clinical investigators and learned not only to respect but to be sympathetic with them and their problems. This, perhaps more than what I learned specifically in biochemistry, determined my future. Too often, and particularly today much too often, biochemists look down on clinicians and clinicians are scared of biochemists. This is most unfortunate.

Page  6262 Dr. 0.: Along these lines, may I ask, did you experience among any of the staff of the Rockefeller Institutions any element of looking down by the Ph.D. on the M.D. or vice versa? Is this anything that ever entered into one's relations, where you had M.D.s and Ph.D.s working side by side? Dr. H.: Well, I was not conscious of it ever. Dr. Cole, the director of the hospital, regarded all of the staff of the hospital as part of his^ family! It didn't make any difference whether you had a Ph.D. or and M.D. We operated at the hospital with open doors, with complete exchange of information--good and bad--at all levels. This was very different from the rest of the Institute. There, each member, which meant he was the head of his particular department, operated behind closed doors! There was a great deal of jealousy; there was very little mixing from one Member's group to another Member's group. It was almost as if we at the Hospital of the Rockefeller Institute belonged to a rather exclusive club, and we were very proud of this. This isolation has broken down pretty well now I found, when I visited there last week. They don't have this same feeling at allo It is probably because they have too many young people milling around among them. You can* t keep them confined under your own wing and not talk about your work, if you get young people. Perhaps I ought also to say, in that connection, that it shouldn't be thought that the Rockefeller

Page  6363 Institute only started to be an educational institution after Dr. Bronk took over as president. Van Slyke alone, I think, must have had about 100 men--mostly M.D.s—who we would call today postdoctoral fellows. There was always a certain number of people who, by registering at Columbia and doing their research at the Institute, were taking their Ph.D.s. This was true of Cullen, Sendroy, Ida Rolf, under Levene; it's true of Henry Simms and there may be others. It has been regularized, but it did exist before. Dr. 0. : This is a little aside, but I think it would be interesting,, Could you give an estimate of what was generally available at this period of time when you were at the Rockefeller Institute, to the physician in the city of New York. Not at the Rockefeller Hospital, but any of the hospitals in the city as far as clinical chemistry or clinical pathology? How knowledgeable was he about these procedures? Were any sorts of determinations done at this time as routine procedures? Certainly we were doing hemoglobins then. Dr. H. : Well, at that period of my life, it was the period when one cco methods for blood sugars were developed. Folin's method, Benedict's method, Myer's method, and, of course, this is what made it possible to not only get insulin, but make it stick. There were at least three people, two of whom I know, who discovered insulin before Banting and Best. My mentor at Columbia, E. L. Scott, was one. Work that he had done at the University of Chicago before he came to Columbia; in retrospect, it is perfectly obvious that he had

Page  6464 insulin. But it took 50 ccs. of blood to make one blood sugar determination, therefore, when it was not readily accepted at the Society for Experimental Biology and Medicine meeting where he reported on this, he dropped the subject, but it's perfectly obvious today that he had insulin. And Murlin had it before too, but there were no one cc. blood sugar methods. Dr» Oo: So really it was a little too early for these new methods to become generally available. Dr. H. : Then they began to use these methods and make determinations at hospitals. Van Slykefs original volumetric gasometric method made it possible to determine blood oxygen and CO^. He gave us the first sensible, rational quantitative method for determining the degree of acidosis in diabetes. Folin was developing his many blood colorimetric methods at the same time. This was a big revolution. This period turned medicine from being qualitative symptomatology to quantitative facts. The big revolution in medicine in this country occurred because it was made quantitative. Dr. 0.: I suppose it was after 1930 that some of these methods became relatively routine in the better hospitals. Dr. H.: Yes, you might say between 1925 and 30. I don't really know the extent to which they were, but people began to have clinical laboratories that had facilities for quantitative determinations.

Page  6565 There is another contribution that the Rockefeller Institute made in that period under Dr. Cole which should always be remembered. Not only did he have as his staff Van Slyke, Avery, A. E. Cohn, Swift, who were the Members, but they turned out people; they turned out the people who became the sort of first generation of clinical investigators who were Professors of Medicine. Palmer at Columbia is a case in point; Robertson, McLean, Miller, Austin, Peters, Stadie, etc. These were very important contributions, and clinical investigation--the quantitative study of patients--was really born at the Hospital of the Rockefeller Institute. Well, I had better be careful what I say in the presence of a Hopkins1 man! Certainly it was going on at Hopkins too. This was a real product of the Rockefeller Institute—people. I listed a good many of them in that article on Van Slyke. [Midday break for lunch] Dr. H.: While Van Slyke was in China, a man appeared, who had a limp, and said his name was C. R. Harington, and he had arrived to work with Van Slyke. Van hadn1t told me that he was coming, but there he was. With Dr. Cole's agreement, we took him in as one of our team in studying the blood as a physicochemical system, titration of hemoglobin, and he stayed on through the year and was an author with us. Ifve got to correct something; it wasn't the year Van Slyke was in China. It couldnft have been, but Van Slyke was away on an extended trip because this had to be in the last year I was at the Institute—*25-*26.

Page  6666 At that time we lived at Croton-on-the-Hudson. We had moved every year further north from 172nd Place where we started married life, and in the last year lived at Croton-on-the-Hudson. Harington was staying with Dakin, the great biochemist, who lived at Scarborough. When we were through at night, we would take the train—usually a local—and he would get off at Scarborough; but this gave us ample time to get well acquainted and talk about things. It developed that when he went back to England, he was to take over a new job at University College, London, as Professor of Pathological Chemistry. He said, one night as we were going home, "I want to pledge you to secrecy on what I am going to tell you, but I have been talking it over with Dakin," and he said, "You know, Kendall has had ten years since he got crystalline thyroxine and he still hasn't got the right formula. He's been trying to make it compatible with a tryptophane, an iodinated tryptophane derivative. I know where he has gone wrong, and my first job when I get back to England is to get the right formula for thyroxine." I didn't tell anybody about this conversation. Later in that next year in the spring, Professor McNee, I think his name was, the bile man--he was Professor of Medicine at University College—came through the Rockefeller Institute and I said, "Oh, how's Harington?" "Oh," he said, "Harington, you know, was a great disappointment. This fellow went into the laboratory we provided for him and he closed his door and we've never seen him since! I think we are going to have to discontinue this arrangement next year." r

Page  6767 Well, McNee hadnft left the United States very long, when we suddenly heard that C. R. Harington had opened this laboratory door and announced that the right structure for thyroxine was tetraiodothyronine! But he wasn't able to synthesize it alone. He had to go up to Edinburgh and get the help of Professor Barger, his old Professor, to synthesize the thing. I tried for many years after that to get the Nobel Prize given to Kendall, Harington, and Barger, and the Nobel committee, in those days, would only accept two nominees. They kept trying to get me to knock one off of the three, and I didnft feel that you could be justified. So Harington never got recognized for this. He later became the Director of the National Institute for Medical Research. [End of Side I, Reel 2] Dr. 0.: This is Side II, Reel 2. It is still December 19. I believe at this point you were going to speak about the period when you were finishing up at the Rockefeller Institute and about to leave for the University of Chicago. Dr. H.: By the time 1926 came, I had rather unconsciously developed the habit of thinking of the whole organism—indeed man--as a heterogeneous system with gas-fluid phases, the lung and blood plasma; the liquid-liquid systems where one liquid is separated from another by a membrane which will let water and various ions or solutes through, such as plasma and interstitial fluid or any of the other extracellular fluids, or interstitial fluid and intracellular fluid as exists in every cell; or the heterogeneous system consisting of solids and liquid, such

Page  6868 as exists between the bone salts and interstitial fluid. With this kind of an unconscious feeling about the--at least not overtly planned feeling--about the kind of physicochemical system one had that one might study for purposes of understanding physiological processes; as, I say, by 1926 we knew so much about the plasma--erythrocyte heterogeneous system; the electrolyte composition, very accurately, of both the extracellular fluid, the plasma and the intracellular fluid; we knew so much about hemoglobin--its physicochemical constants; how many charges there would be per molecule at the pH inside the cells. We knew the intracellular fluid of the red cell was a high potassium solution with magnesium and some sodium, but practically no calcium. The extracellular fluids were essentially high sodium solutions with small concentrations of potassium and calcium and magnesium--indeed a diluted sea water. The behavior of the red cell in its extracellular fluid environment as a transporter of oxygen and carbon dioxide was completely understandable in the terms of the physical chemical constants which we had determined, and that as a result, the idea that there was anything mysterious about the unequal distribution of ions or that chloride ions went "uphill," if you will, when you changed the C(>2 concentration; this was all now understandable in terms of recognized physical chemical constants and physical chemical laws'. So that this is what I took with me to Chicago. Indeed, the first thing I attempted to do in collaboration with Harry Van Dyke, who was then Associate Professor of Pharmacology, was to simply extend what we had done with

Page  6969 chloride distributions as a function of pH to bromide distributions. [#40, 58, 59] It was nothing new in the way of concepts; it was simply applying what I knew. Then when I decided to stay at Chicago in my second year and move over to the department of medicine---- Dr. 0.: You went there originally not in the Department of Medicine? Dr. H.: No. I went there as a full Professor of Physiological Chemistry in the fall of 1926. I was 30. Dr. 0.: Was there some question of your leaving? You say when you finally decided to stay after that first year in Chicago. Dr. H.: Yes. I didnft like Chicago very much. We didn't like living in Chicago very much, to tell you the truth. I wasn't very well welcomed in the Department of Physiological Chemistry because I went there at a salary of $6500 and the man who was acting head of the department, F. C. Koch, many years my senior, only got $5000, and this is not a good situation. And also, it was in the records of the Board of Trustees, as well as the offer to me, that I would be provided with a technician, and no professor at the University of Chicago had ever had a full time technician paid by the university before; so these two things sort of got me off to a bad start and I, being so much younger than the other professors like Carlson and Koch--— Drc Oo: Was the attraction—I know you were so very happy at the Rockefeller--when you went to the University of Chicago though, was

Page  7070 it the idea you expressed earlier this morning about wanting to get out and spread your own wings? Dr. H.: I don't think when you are 29 years old and offered a full professorship at the University of Chicago that you turn it down! It's true that they were dickering with me at Yale for the Professorship of Physiology; Peters had the idea that—you know, this sounds like hell if we are recording; it sounds as if I am bragging all the time—but really, I am just being as factual as I know how. Dr. Oc: We have documents to back all this. Dr. H.: Peters was hell-bent on my becoming the Professor of Physiology. Winternitz had transferred Yandell Henderson from the Professorship of Physiology to the Department of Applied Physiology. He made him take a Professorship of Applied Physiology; that left the Professorship of Physiology open and Peters was strong for my coming and I might have been, but the wheels ground too slowly and McLean got the official invitation from Chicago in first and I took it, to tell you the truth. That was before John Fulton was made Professor of Physiology. I think I would have been happy enough; I mean I wasn't too unhappy at the University of Chicago when I went there. I just wasn't as happy as I was at the Rockefeller Institute, and if L. J. Henderson hadn't produced an invitation to go to Harvard in 1928 and, I am told, though I have no evidence for this, that (you see, Flexner disliked Henderson and Henderson disliked Flexner) news reached Flexner some way or other

Page  7171 that Henderson had arranged for me to take a professorship at Harvard; he instructed Dr. Cole to get on the phone and offer me an associate membership and my own department if I would come back to the Institute. Dr. 0.: This was at the time you were leaving Chicago to go to Harvard? Dr. H.: No, this was 1928. I had been in Chicago a year and a half. I was just a pawn; I've always been just a pawn1. Anyhow, I make the most of it; I have a lot of fun out of it. I don't have any enemies, I hope. Anyhow, while I was enjoying being wanted at two places, this Lasker Foundation money came in. Incidentally, Albert Lasker and his first wife—the present Mary Lasker is his third wife; the present Lasker Foundation has nothing to do with the Lasker Foundation that I ran for seven years at the University of Chicago. He gave a million dollars to be used in the Department of Medicine to set up a research unit within the Department of Medicine to study degenerative diseases. McLean said, "You can study anything you want to," at the time he was at the top and powerful, so at that point I moved over from the Department of Biochemistry across the court to the research laboratories of the Billings Hospital. Have you been to Billings Hospital? Dr. 0. : No. Dr. H.: Well, the Billings Hospital, one wing is surgery and one wing is medicine and pathology is across the back, and then there is a little court and then physiology and biochemistry.

Page  7272 On the first floor of the Department of Medicine's quarters was a suite of laboratories that I had helped design for McLean to use before I knew I would be at Chicago. It was when he was still at Peking and making his transition and he said, "You lay out what you think would be the ideal laboratory suite." It had one big room and we had special hot rooms and cold rooms and balance rooms and dark rooms, an organic lab, an analytical lab, a gas analysis lab, a physiology animal lab, Kjeldahl rooms----- Dr. 0.: This was in the Department of Medicine'.? Dr. H.: Oh, this was done up right; each four medical students would have an individual laboratory of their own from the time they entered their third year. It was to be their headquarters. The faculty soon usurped them; they don't exist anymore, but that is the way it was built I Supposed to accommodate 40 students; ten such rooms with four in a room, equipped for everything—microscopic, chemical, pathological, Well, I moved over there and had a staff of three. I had 50,000 cold hard dollars a year to spend. We were always in the black, even in the height of the depression. We didn't have to take salary cuts, but the rest of the university did so we did too. That was where I decided to leave the blood and get into factors effecting water and electrolyte distribution in tissues. Studying the blood was like--as I put it in one lecture—paddling up and down White River in Indianapolis and deducing from what went by in the muddy

Page  7373 little stream, what went on on shore. I decided to make a direct attack on muscle tissue. The very first efforts were not very productive because I was so imbued with the idea that the Donnan equilibrium would account for all the distribution of ions, that I always tried to fit the data we were getting into this and they didnft fit! It's funny that when we threw all my preconceived ideas out the window and started at the other end with the assumption that muscle cells are impermeable and don1t have any chloride in them by and large, that we got on the right track, though we wasted perhaps the better part of a year before we did any significant experiments. It is one thing to have blood that you can centrifuge and take the plasma off and analyze cells, and another one to try and figure out first, what percentage of a hunk of tissue that you have done some careful analyses on, is extracellular and what part is intracellular. This was so early that we didn't even know whether or not we should treat the interstitial fluid as an ultrafiltrate of blood plasma. We could analyze plasma and calculate what the ultra-filtrate composition would be. We got in in the nick of time because Wallace Fenn and Jack Peters were also worrying about this thing, so was Dan Darrow. So the four of us sort of reached the same conclusion about the same time; the objective being, what is the composition of the intracellular fluid or at least muscle and any other tissue you could treat similarly, like liver. Only two tissues can be treated so simply—liver and

Page  7474 muscle. When you come to the kidney, when you come to the brain, you can't do it; you can't yet I Heart muscle, skeletal muscle, liver, you can. There were about five years of work on water and electrolytes in tissues, the extra and intracellular phases; what makes the cells swell or shrink?--we had a whole series of papers with Eichelberger on this. She stayed right with this subject; right up until the time she retired last year. She's done similar studies on every tissue on the body with clinicians, with surgeons, and her work on that is really classic. Dr. 0.: Was she a graduate student of yours? Dr. H.: No, she had taken a Ph.D. with Stieglitz in chemistry. Here are her collected reprints and practically all of them are electrolyte studies growing out of those first ones. Dr. 0.: I was thinking that you had said that you really didn't start to teach until Harvard, but that was medical students. You did have some Ph.DO candidates at Chicago; Drc Harkins I know was one of them. Dr. H.: Oh yes, Dr. Harkins, and then a man named Mishkis, a Russian, and J. EC Davis, Miss Browman, Shock, Weir; these were all Ph.D. graduates at Chicago„ Dr. 0.: Do you know whether this Weir was any relation to the surgeon in New York?

Page  7575 Dr. H.: No, he was a mulatto as a matter of fact. A very fine man with very delicate features, who was awfully good and awfully smart and went to Howard. The people there were so damn jealous of him that he had to leave and he is practicing medicine in California, near Sacramento. He came down and visited me a couple of years ago; I hadn't seen him for years; I had known that they just ganged up on him because he was too good. It was a very sad thing. He was as good as any man I have ever had. Too bad. Where are we? I'm rambling. Dr. 0.: I asked you about your Ph.D. candidates. Dr. H.: Oh I know, I did deliberately decide to go from the heterogeneous system which was the blood to the heterogeneous system which is a tissue and the cells their extracellular fluid. So now I moved to tissues, soft tissues. As I say, that is what Lillian Eichelberger and I did, but at the same time we had two other kinds of problems going there which is how I sort of got going into metabolism. There was a brief flurry with trying to make an active adrenal extract. This was before any active extract had yet been obtained. The only criteria you had to see whether or not the extract you had was active, were adrenalectomized dogs, and see if you had made something to keep them alive. We tried to get something faster than this, of course. We adrenalectomized mice and had a brief flurry with the late Alfred Koehler [#47], who was the one who was most interested in this problem--

Page  7676 in an active extract, but at one stage we kept the inactive fraction and threw the other down the sink. But in the course of this, I did hook up with Compere, an orthopedic surgeon, and he adrenalectomized dogs.[#50] This is when I decided that Koehler's criteria were wrong and we would have to find something better, so this was independent of Koehler. I did what I suppose you would call shotgun chemistry; I don't think it shows any great brains, but I combed the literature for all the things which had been implicated as changing in the blood after bilateral adrenalectomy. I found it had been said that calcium changes, so we did plasma calciums and then to balance this, plasma potassiums. There was said to be low bicarbonate, so I did bicarbonates and pHs. There was said to be low blood sugar, so I did blood sugars and lactic acids. By then, I had invented a gasometric lactic acid method. I wanted to give it an airing anyhow. People said that creatinine and creatine climbed, so we did that too. I think that was all we did. Oh yes, I guess we did phosphates too. The main thing that we did discover (and it was before Harrop and Loeb found a drop in sodium, which is now regarded as characteristic of adrenal insufficiency), was that serum potassium doubles within the first 48 hours after adrenalectomy and goes on climbing until it gets to 20 millemoles--it starts at five, you know, normal—and when it gets to 20 the dogs die. When you inject potassium salts intravenously in normal dogs, 20 millemoles is the lethal concentration of potassium in your extracellular fluids. So if nothing else happens after adrenalectomy, the high potassium does kill them.

Page  7777 We also found that lactic acid goes down and this has not been explained by anybody yet. Potassium increase is now well recognized and I think is more important than the drop in sodium, physiologically. That work on adrenal function included work on tissue metabolism, using a Warburg apparatus. It got me into metabolism as well as electrolyte changes in tissues. We wanted to determine intracellular environment in which metabolism goes on and then what is going on there. We also had a mouse colony which we were following to see what happened to metabolism with age. This was the beginning of my interest in the physiology of aging. E. S. G. Barren came from Johns Hopkins in 1931 to be my first assistant, He had been working with Michaelis and he was interested in electron transport and oxidation and reductions and so was I because of my interest in what William Mansfield Clark was doing. So we undertook to study heme potentials and hemochromagen potentials. But the most important thing we did at that time was to determine for the first time, with accuracy, the potential of the lactate: pyruvate system at different pHs. So I had three kinds of problems going in my laboratory for those last few years at the University of Chicago: (1) tissue electrolytes, (2) tissue metabolism and (3) biological oxidations. It was also during that period that Nathan Shock took his Ph.D. with me and this permitted us to develop and use the micro acid-base pipette which Shock made.[#75] Thomas and Fisher both made them later, but he

Page  7878 made the first ones himself. This pipette permits you to do the pHs, CC^s, and hematocrits (which you need to get your hemoglobin concentration) on 0.1 cc. of blood; all on the same 0.1 cc. of blood1. As a result of that, we were able to determine the acid-base pathways after disturbance of the acid-base balance from normal. This was something we were never able to do at the Rockefeller Institute and nobody has determined the acid-base pathways with so many points on the pathways since then. We could get as many as 20 points in a single experiment. We were not able to get the whole thing published in the JBC; they cut us down to a few simple examples, but---- Dr. 0.: Again, primarily based on the fact that you were able to use such minute quantities of blood. Dr. Ho: [Referring to a chart in item #76 or #94 of his publications] I will explain them to you someday, but not now, about the triaxial coordinate paper which we used to display our data. It is so ideal for plotting x, y, z equations which is what the mass law is, but it is not popular with anybody but me. Shock and I both feel that it separates what we call the pulmonary acid-base function from the kidney acid-base function at a right angle1. It is just cross-section paper, and it puts the CC^ tension and the bicarbonate and the pH in equal geometric relation with each other so you don't think of one as subordinate to the other. As you can see, each path was determined by a large number of points, and everyone of those represents duplicate or triplicate determinations. Now, nobody has ever done anything like

Page  7979 that! We had 39 males and 19 females as subjects. It is clear from the data that the body doesn't really care whether it keeps the pH within the physiological limits that we work in, but it cares tremendously whether it keeps the CC^ tension at 40 millimeters; the average of all the data we collected through the years shows that the body is twice as interested in keeping the carbon dioxide tension at 40 millimeters as it is the pH at 7.4! This is pretty much ignored by physiologists and clinicians. I mean they still teach the body wants to keep the pH at 7.4 and you can't get it out of their heads! Thereby hangs another tale. My last eight years at the Scripps Clinic and Research Foundation have been devoted to showing that the C0« concentration is quite as important as pH in their effects on the synthesis of glycogen, the phosphorylation of glucose and fructose and glycerol, and many times — four or five times—as important as pH on fatty acid synthesis by liver. Now these are just two examples we have worked on. It is sort of a wide open field for somebody to take this and work on it in vivo. I mean my stuff is all in vitro. It needs to be extended in vivo. Well, I am way off the subject, except that this all began actually through our not being able to make the decision of whether the body preferred to keep the pH or CC^ tension of the blood constant. Now, the work we did at the Rockefeller Institute on bone salt solubility was carried out on the assumption that there was calcium

Page  8080 carbonate either in the form of aragonite or calcite in bone salt because by chemical analysis, bone salt is 15 per cent calcium carbonate, 85 per cent calcium phosphate. Our results led us to conclude that blood plasma was in equilibrium with bone salt. Going on at the same time were experiments at Columbia by the late Victor Lamer, the physical chemist, L. Emmet Holt, the pediatrician, and Chown, who shook plasma with tertiary calcium phosphate taken from a bottle. The plasma calcium concentration went down, and they concluded that blood plasma is supersaturated with respect to the bone salt. Then, while I was at Chicago, there suddenly appeared a paper by Shear and Kramer, who had shaken blood plasma with secondary calcium phosphate, CaHPOA, and there they found the calcium went up. They concluded that the plasma was undersaturated with respect to bone salt. In describing this dilemma to a physicist at lunch at the Quadrangle Club one day, he said, "Why don't you find out what the solid phase of bone is?" And I said, "But it's not crystalline!? And he said, "Oh hell, everything is crystalline to X rays'. Come on over and we'll settle this." So I went over and he made me powder the bone and we made these powder photographs which took a week to be exposed before they would develop--! beg your pardon1.--it's in the record; the exposure was approximately 45 hours'. Seemed like a week'. Out of this came the clear evidence that the bone salt is a carbonate apatite; that there is no separate phase of secondary calcium phosphate or

Page  8181 calcium carbonate, either in the aragonite or calcite form. The carbonate that's there is part of the crystal. So all three of us who had studied the solubility of the three calcium salts without biological relevance, whereas our experiments were all right, our conclusions had no justification as far as biology is concerned. But there still was another problem about calcium, even though we now knew what the solid phase was--a carbonate apatite--the question of what is the calcium ion concentration in body fluids? Particularly of blood plasma. All clinicians know that the normal calcium concentration is ten milligrams per cent; if it goes down to seven, you get tetany; if it goes up to 12 or 14, you have hyperparathyroidism. They also know that in certain kinds of nephrosis and low proteins, you can have seven or eight milligrams per cent without tetany. Well, Franklin McLean, who had been the builder of the University of Chicago full time school and the Professor of Medicine and the Dean of the school, came on evil days as an administrator. He was such a good administrator, made so many decisions that he finally angered the majority of the faculty and they got him out as Dean. I saw this coming and decided to save Franklin McLean for science because he was a darn good scientist and I cooked up an experiment, ostensibly to study edema of an excised rabbit heart with a Loewi type perfusion. I carried it up to a point and then went into McLean1s office and said, "Franklin, I need your help in the lab." I got him out--he had worked with Loewi once--and said, "Tell us what we are doing wrong." I put

Page  8282 him into a lab coat, and he has never taken it off to this day1. That was in 1932. (He lasted just eight years as an administrator at the University of Chicago Medical School. That!s why I say the half life of a good dean is eight years.) Well, we went on from this beginning and studied the effect of ions on excised rabbit hearts. By back perfusion through the coronaries, we measured the mechanical work of the heart and we brought Emmet Bay in because he was an electrocardiograph man. We hooked the heart up, through the ceiling, to the clinical EKG, and we were taking very nice records of the effects of changing potassium ion concentrations, calcium ion concentrations, and hydrogen ion concentrations. [#72a] This was all carried out in a 38 degree room which was saturated with water vapor and we could keep the rabbit heart going for several hours. In the course of an experiment, McLean and I lost so much salt and water ourselves that we would be severely dehydrated. Actually, we got very good records of the effect of potassium ion changes on the EKG much before anybody else did, but it never got published for reasons I am about to tell you. Well, we were going along fine one day when suddenly I was called to Dr. Frank Lillie's office, then Dean of Biological Sciences, who said that George Dick had just accepted the Professorship of Medicine with the proviso of his taking it that Franklin McLean be physically

Page  8383 outside (not be physically within) the precincts of the Department of Medicine of the University of Chicago. Of course, these labs were the ones I had designed for Franklin and were now occupied by me but were part of the Department of Medicine., I blew sky high, but it didn't do any good. McLean just took it on the chin. He just felt that what had happened to him was sort of a professional hazard--! can't think of the technical phrase we use today. As soon as this became known, Carlson promptly offered to bring him into his department of physiology as Professor of Pathological Physiology. You see, they could take his salary away, they could take his deanship away, but they couldn't take his professorship away. So Franklin and I moved over to the Department of Physiology to continue our experiments. But we couldn't work on the rabbit heart anymore because I had the 38 degree room and Carlson didn't have any such room in his department. So we said there was nothing to do but see what we could learn by studying the frog heart. We went back to the old fashioned way of studying the frog heart and, by gosh, we found the frog heart is really a calcium ion electrode'. It will respond to changes in calcium ion concentrations and not to calcium that is there in any other form. We also found that it is ten times more sensitive to the calcium ion concentration than to the potassium ion concentration, We used to use an old fashioned kyomgraph, and you can detect 0.1 of a millimole per liter change in calcium ion. The magnesium doesn't effect it. Well, it just turned out to be wonderful1. With this then, we started measuring calcium ion concentrations in biological fluids0

Page  8484 Then Franklin got the idea that well, maybe the relation to protein is simply a very simple ionization of calcium proteinate and it turned out to be just that! The calcium protein salt ionizes; there is a dissociation constant and we determined it by plotting [Ca ] as a function of total plasma calcium and total protein we prepared the McLean and Hastings nomogram that is widely used now. It's a plot of • » _ o o o the equation [03***] x [Trot"]- 10~J' . You need to know the total [Ca Prot] protein, you need to know the total calcium and you read off your calcium ion concentration. It is accurate except in such things as multiple myeloma where you get big increases of some globulins. In later years with Nancy Drinker, we used the Cohn plasma protein fractions to determine the pK of Ca proteinate for each of the proteins Whereas there is a difference between the euglobulins and the gamma globulins and albumin, they are not of very large magnitude. With these two things, one, how to get the calcium ion (we already knew how to get the phosphate ion concentrations) and, knowing what the solid phase was — this now being about 1934--we were in a position to take up, again, the question of whether or not the plasma is in equilibrium or supersaturated with respect to the calcium salts of bone Prior to this it was really pretty irrelevant; I mean by that, we didn't know what the calcium ion concentration was! We didn't know what the solid phase was! Unless you know what the solid phase is, you don't know what kind of ions you should multiply together to get a solubility product! Anyhow, this was all done at Chicago in the last two or three years and was perhaps, from the standpoint of

Page  8585 medicine—bones anyhow and parathyroid problems, the most important thing that we have done. [#80, 81, 84, 85, 86, 89, 91 92] McLean stayed right in the calcium field. He is now Mr. Calcium, No. 1, you know*. He has published three or four books, and is still publishing. He has been honored by medals, degrees, and symposia here and abroad. Last year he retired completely from the University of Chicago; and moved to the University of Illinois Dental School. He goes to work everyday over there. He will be 80 on February 29 next! Isn't that interesting though about how the measurement of the calcium ion concentration came about? We might not have gotten that calcium ion concentration solved--maybe nobody would have; many people had tried and I had tried again and again with my physical chemical knowledge to find some way of measuring calcium ion concentration,, Calcium amalgum electrodes, second order electrodes; diffusion through a collodion membrane or any other kind of membrane didn't prove the point because if you put in, say, nitrate for instance, you'll have nonionized calcium, but it would be diffusible so you can't solve it by ultrafiltration or diffusion. And yet, if we had stuck with the rabbit heart, if Dick hadn't insisted that McLean get out of my laboratory in medicine, we would never have gone to the frog heart in a month of Sundays I We might be more famous for what we discovered about potassium and calcium ions which we never got finished with, the rabbit heart and EKGs etc., but the frog heart thing was really a Godsend to the whole calcium problem'. It's the standard wayc We

Page  8686 even put physical chemical constants into the physical chemical literature; the ionization constants for calcium citrate and for strontium citrate. Oh, that was great fun. McLean is another one you should get. I don't know what he has done about his biography or papers. He and Canby Robinson were the two white haired boy-deans in medicine. Canby at Vanderbilt and Hopkins, who ended up at Cornell; McLean at the Rockefeller Hospital, PUMC and Chicago. A fantastic guyI Dr. 0.: His contributions to science as well as medical education were so important. Dr. He : Well, that would wind up me in Chicago, I guess. We had a good time there. We got so we liked it after three years, very much, because the people were so fine. I never had any problems, very frankly, even though I was one of the so-called "Rockefeller gang" that McLean had brought out« Dr. 0.: Was there sort of an anti-Rockefeller group? Dr. H.: Well, the fact that they thought that this big octopus of a medical school, being set up full-time on the campus, was taking Rockefeller Foundation money out of their mouths that they would otherwise get; this was when we first opened, and of course the practicing physicians in the Jackson Park branch were dead set against it and, indeed, they got the staff canned from the Jackson Park branch which

Page  8787 meant they couldn't belong to the AMA for quite a number of years. You see, the University set up a full time teaching hospital from the start so they were in competitive business with the clinics. On top of that, the west side—there was the Cook County and the Presbyterian on the west side of Chicago--oh dear, what is the name of the original University of Chicago Medical School? Dr. 0.: Rush? Dr. H. : Rush1. Rush Medical College. You see, those professors were very distinguished people, but "dollar a year" professors, and they didn't want us either, so everybody was "agin us!" Fortunately, I was exempt. That was one time I was glad I didn't have an M.D. because they couldn't consider me as competitive. So I got along all right with all of these folks. Dr. 0.: I wonder if I might ask you about Dr. Harkins. He was in surgery by then I gather, was he not? Dr. H.: No, this was prior to his going into surgery; this was prior to going into medicine. Well, he was registered in the medical school—when do you suppose he finished his bachelors? Dr. Oc : Oh my——— Dr. H.: [consulting American Men of Science] Henry N. Harkins got his B.S. at Chicago in '25. He is listed here as a Scholar in '25 and '26,

Page  8888 M.S. in '26, Smith Fellow '26 to '28--he was a Douglas Smith Fellow while he was working with me--he got his Ph.D. in '28 and his M.D. at Rush in '31. Henry got a Douglas Smith Fellowship at the medical school in 1926, originally to work with McLean, but McLean turned him over to me because McLean wasn't working in the lab; he was building the school. I was then—being the first year out from the Institute — interested in trying to find out what the acid-base pathways were. That's how Henry came to study the acid-base pathways in dogs after you displaced the acid-base balance as much as you could with HCL and get away with it. [referring to a paper written with Dr. Harkins, #55] Some of these pHs we got immediately after injecting--in this case 32 ccs. of normal hydrochloric acid as fast as we could--that is within two minutes, 6.3 I guess that is. Here's another, 6.2, 6.1--it only stays there momentarilyo The idea was to get some points on the way out and then what was the pathway back. Even that shows that it goes along a C09 tension line pretty much. This was when I first picked up that triaxial paper. This was its first use to plot acid-base data. Dr. 0.: Dr. Harkins then was really headed for a career in chemistry following in his father's footsteps, do you think? Dr0 H.: No. This was a Ph.D. in medicine. It was a degree that they had created before they created the school. This was to make scholars in medicine, and they offered a Ph.D. in medicine and this was the

Page  8989 first, last, and only Ph.D. in medicine ever given at the University of Chicagoo Dr. 0.: I'll be darnedl You can get a PhoDo in surgery at the University of Minnesota, but you get it in physiology or something of this sort. Dr. H.: His examination was one of the funniest things in the world because here was this young man who hadn't seen a patient at all yet. He's registered and at the end of his second year in medical school, but McLean, who was head of the Department of Medicine at that time, invited all of the Professors of Medicine to be there. I don't know whether Carlson came, but of course I came and I think H. G. Wells, the pathologist, came. Drs. Capps and Miller, very famous clinicians, came. When it came their turn to quiz Henry, I remember Dr. Miller said, "Mr. Harkins, what are the symptoms of typhoid fever?" Henry knew all about Donnan equilibrium and the transport of oxygen and CO and hemoglobin but he didn't know anything about anything clinical,, Well, the time came to discuss his performance after he had left the room, and they shook their heads and said this man must learn more clinical medicine, but they let him through. Henry went out to Rush to finish. He didn't stay at the Chicago south side school,, You see, at that time you could choose which you went to, and he went to Rush and it must have been there that he got into surgery. Dr. 0.: I notice that while you were at Chicago you did finally get to Peking,,

Page  9090 Dr. H.: Yes, they invited me out there in 1930. I went out as actually a Visiting Professor in the Department of Medicine. But Professor Hsien Wu, of biochemistry, had said that I was going to be Visiting Professor in the Department of Biochemistry. When I go there, I found that I had two offices and planned my work so that I did research with Wu in the mornings and research with Francis Dieuaide, head of the Department of Medicine, in the afternoon. I got a lot done It's a wonderful place to study edema and the effect of acid-base balance on edema. They could get these patients to come in and put them on the same amount of the same food and same fluid day after day after day, and we did a three-months study on three patients there,. We would have a week control, then we would put them on sodium bicarbonate for a week with everything the same, and then we would put them on ammonium chloride for a week and we did water balance studies as well as acid-base studies. With Wu we started on muscle electrolyte studies. I didn't get a publication out of the work I did with him, but I got a lot of experience that stood me in good stead when we--Lillian Eichelberger and I—afterwards went into the same business of studying electrolytes and acid-base balance in tissues. Another thing I haven1t mentioned during that period was the in vitro action of thyroxine. Now, people had claimed that before, meaning that they would take some tissue slices and put them in a Warburg apparatus and have some thyroxine in the side arm and then dump it in. There were quite a few reports in the literature that the oxygen consumption

Page  9191 went up! Every time one of these reports came out, I'd repeat it and I couldn't confirm it. I never was able to find any acute effect by adding thyroxine to a tissue on oxygen consumption. I think this happened because even doing Warburg measurements which are not terribly difficult, are very tricky and you've got to work with the technique for a year so that you don't let yourself get fooled! So we never had been able to get an in vitro effect of thyroxine. When I searched the literature at the time we made this publication [#82], I found there were just as many other people who couldn't get a thyroxine effect on C>2 consumption as there were people who claimed it. I just picked out ten of each! Our experiments came about this way. While McLean and I were using the frog heart for calcium ion assay, we found that we could set it up one day and get our determinations, and usually we could stick that frog heart in Ringer's solution in a test tube and stick it in the icebox overnight and take it out the next day and use it some more. It was still viable. The problem of measuring the effect of thyroxine over a long period of time in a warm-blooded tissue was the fact that it dies on you. Suddenly one day, it occurred to me that this tissue is staying viable for 48 hours if we wanted it to, by keeping it in the icebox at five degrees. So Davis--James Davis--and I proceeded to use the frog heart to study the effect of thyroxine on metabolism. [End of Side II, Reel 2]

Page  9292 [Beginning of Side I, Reel 3] Dr. 0.: Item No. 82 in your bibliography. Dr. H.: [Referring to the article] The top numbers here are the change from the control in oxygen consumption in each pair of frog hearts. Itfs quite a lot of thyroxine. It's one mg. per 100 ccs. of the solution. We kept them in the icebox; we'd take them out and measure their oxygen consumption then put them back. As you see, we had lots of pairs; this was a differential Warburg method so we could measure the oxygen consumption and the CC^ production. After three hours, the metabolism had gone down in both the hearts with and without thyroxine. After ten hours, it had gone down about the same in the controls, but it was not so low in the hearts with thyroxine; after 15 hours, there was a 70 per cent difference and it lasted right on up to 42 hours. I am told it takes about ten hours after the administration of thyroxine to affect the metabolism of man. At least that's Boothby's observation. Anyhow, it fits with experience—you don't get a quick effect of thyroxine. Something has to happen in the way of enzyme induction, which they think now. This was the first clean-cut evidence, using the frog heart technique, to demonstrate the in vitro action of thyroxine. An amusing thing happened when we reported this at the physiology-biochemistry seminar we always had every Friday afternoon at Chicago. Carlson said, "Well, how do you know it is not acting on the nerve endings in the heart?" And we said well of course we don't. Carlson said, "Well, why don't you go to

Page  9393 Woods Hole and repeat this with the limulus heart with and without its ganglion." The limulus heart is what made Carlson famous as a very young man. So I sent Davis to Woods Hole the next summer and he repeated this work on the limulus heart, with and without the ganglion and got the same results. I'm tired. Suddenly I'm very tired. This is Dr. Olch interviewing Dr. A. Baird Hastings. The date is December 22, 1967. It's a delightful cool, sunny morning in La Jolla, California and we1re just a stones throw again from the surf of the Pacific Ocean. Our discussion this morning is going to roughly cover the period, actually, from the end of Dr. Hastings academic stay in the University of Chicago and moving on to Harvard University. Drc H.: Well, in introducing my Harvard period, I think I should say first that I had been offered a professorship and had verbally accepted it, from Mr. Lowell in 1928--a professorship of biophysical chemistry. We said that there would be no hitch about it, but that it was necessary at Harvard for a professorial appointment to be brought before the Board of Overseers at one meeting and lay over until the next meeting, and that it could not be official until it had been confirmed at the second meeting of the Board of Overseers. Between that first meeting and the second meeting of the Board of Overseers, I had this offer from the Rockefeller Institute and then the offer from the University of

Page  9494 Chicago to be Research Professor of Biochemistry in the Department of Medicine, under the Lasker Foundation. Since I had not had a confirmed appointment from Harvard, and since I decided to stay at Chicago, I wrote and told them thank you very much, I'm going to stay here. Under these circumstances, I should think that a university would never offer a fellow a professorship again. Dr. 0.: It is rather unique. Dr. H.: But in 1935, and after Professor Folin had died in the fall of 1934, I received a wire from President Conant, while I was attending the Atlantic City meeting of the Association of American Physicians, asking me to meet him in New York and discuss taking over the chairmanship—headship, not chairmanship--of the Department of Biological Chemistry--the Hamilton Kuhn Professorship. Well, I met him and I discussed the possibility with him, but I felt really inadequate to take over the teaching and responsibility for the whole department, and told him so. Dr. 0.: Was this basically because you had been in research for so many years and not teaching? Dr. H. : That's right. I knew a great deal about a few things, but nothing about most of the aspects of biochemistry. And I remember so well that I said to Conant, I said, "You know, biological chemistry now has become so much a special subject of organic chemistry"--which was different from the way it was even ten years before, 15 years before,

Page  9595 when physical chemistry was supposed to be the panacea for the problems of biochemistry. So I said, "I don't know any organic chemistry, Jim," and he said, "Oh, donft let that worry you!" He said, "Organic chemistry is easy to learn. I111 send you one of my textbooks I" Which he did. And he said, "And besides, you can always hire somebody to supply your organic chemistry." Well anyhow, he said, "Go on up and look it over." So I did. In Boston, I met with Dr. Edsall who was finishing his last year as Dean. Dr. 0.: That's John Edsall? Dr. H. : No, that's his father—John Edsall is his son. The dean was David L. Edsall. He told me what the budget would be, told me the department was pretty run down, and took me over and introduced me to Dr. Cyrus Fiske, who was an associate professor in the department, but already, of course, one of the most famous biochemists in the world. He and his graduate student, Subbarow, had discovered phosphocreatine and had after that discovered ATP, though they seldom get the credit for it because a German discovered it simultaneously and reported it before they did. So he introduced me to Fiske, and Fiske was feeling very low. I remember so well; he sat there in his chair pulling on his pipe and saying nothing for several minutes, then he took his pipe out of his mouth and said, "Well, it's all very badI" This was my introduction to the department. Dr. 0.: An encouraging introduction to Harvard!

Page  9696 Dr. H.: Well, it had been a rough year on him because ever since Folin had died, the rumor was around that he would succeed Folin. But he had had an accident--an automobile accident—and ever since then he'd been "a little queer," as people said, and he had periods of depression, I don't think they ever really seriously considered giving him the responsibility for running the department, but he'd already had an Associate Professorship and tenure. I had told Conant in the first interview in New York that certainly one thing I would insist on, if I were to take the job, and that was that both E. J. Cohn and Cyrus Fiske must be elevated to full Professorships — they were both Associate ProfessorshipSo Cohn was not in the Department of Biological Chemistry, He was in the research department of physical chemistry in the school of medicine—a research unit- —- Dr. 0.: But no teaching responsibilities. Dr. H.: No teaching responsibilities, and administratively quite separate and physically quite separate. He was on the floor on top of the Physiology Department separate from the Biological Chemistry Department. I must be careful to always refer to it as the Biological Chemistry Department—it is not the Department of Biochemistry; that's something else again. Anyhow, I insisted that if I were to come they would have to both be made full professors because I didn't want to start with that millstone around my neck; they were both much more distinguished scientists than

Page  97 I was. And I then went around the department and it is true, it was physically in terrible shape; nothing had been done to it for years and years — not just paint, but plumbing and lighting—everything in very poor state. The department staff consisted solely of Fiske, an Associate Professor, Trimble, an Assistant Professor, an Associate, Logan, who was really running the department. Then there was one instructor named Danielson who had just finished his Ph.D., and there was Subbarow who had been there for ten years; he was a research fellow. And that's all there was to the teaching staff. Well, I went back from this visit to Chicago and I felt I'd be a damn fool to give up this suite of labs which I designed there the way I wanted it, in Chicago. I had fifty thousand dollars a year to do nothing with except do research. There was a staff of three senior people in basic research and two in clinical research. My problems were going well and--oh, my budget--my total basic budget at Harvard was twenty-five thousand dollars a year, guaranteed, and then the Dean from his pocket, supplemented this so that he told me he would add twenty thousand dollars and I would have forty-five thousand dollars to teach 125 medical students, 45 dental students — this was a separate class—whatever graduate students there were, pay for the help, pay the salaries, etc. Well, I realized this was going to be a terrific challenge and practically impossible with a budget like that in a run-down show, and the more I thought about it the more I thought I'd be a damn fool. So one day

Page  9898 about a week after I came back, I decided I couldn't delay any longer and I was sitting there at my desk after lunch in Chicago, thinking how I could write a nice letter of declination to Dean Edsall, and I heard some footsteps coming down the corridor because the door was open and they1re terrazo floors, so they click--it was obviously a woman. I had been looking out the window while I was thinking about this before putting pen to paper, and then the footsteps stopped. I swung around and there in the doorway was a fine looking young lady in an intern1s uniform, and I said, "Oh, you're Dr. Folin," and she said, "How did you know?" I said, "Well, come in, what would you like?" She said, "I just heard you'd been offered my father's job and I thought I'd come and see what you looked like." And I said, "Come in and take a good look." She sat down. Well, the result of that was that after a half, three quarters of an hour talking with Teresa Folin (now Mrs. Jonathan Rhoads) who was serving as an intern in the Children's Hospital, I wrote a different letter. I had not yet met Teresa, but I knew she was there. I hadn't laid eyes on her yet. This was a--I just didn't--! don't know, things clicked so I took a chance and it was right. By the time that half or three quarters of an hour were over, she had so described her life and her father's life in Boston and in New Hampshire in the summer and the Cannon's, and the nice things and the bad things that the Harvard job suddenly took on some meaning. It wasn't just an impossible chore; it became a challenge with the possibility of having a fine, new, exciting

Page  9999 life like her father had had1. So instead of writing the letter that I was going to write, I wrote quite a different letter and outlined the numerous things that I felt had to be resolved some way or other, if one was going to make a good department out of it and that I would like to come back again and spend some time and make a list--an estimate—and see to what extent Harvard University could meet these requirements. I went, and I did, and they did and I went I And again it turned on one of these small things—Teresa Folin. I see her every year or so in Philadelphia. She laughs about how she made a Harvard professor! So then I went in the fall of 1935, having gone to Russia in the summer between Chicago and Harvard. Dean Edsall had asked whether to not reappoint any of the people that were now there, and I said no, not at all. I'd much prefer to live with them, and I did, and was successful in developing each of the men that I inherited, so that they eventually went off and got good jobs and had good careers, all except Dr. Trimble who was then 50, and he was invaluable to me though I had to fight every three years with Conant to get a reappointment--a three-year appointment—because Conant was against that after two three-year appointments. He had the up or out principle0 Dr. 0.: In other words, if you didn't achieve tenure after two three-year appointments, you had to go elsewhere? Dr. H.: Yes. I think you were allowed to have, at the medical school,

Page  100100 a total of eleven years as temporary appointments, instructorships and assistant professors. I'm sure this was good for the school. On the other hand, there were always exceptions. I managed to get my way in this case, however, so that I didn't have to turn Harry Trimble out on the street. I tried hard to get him other jobs, but he was too old and hadn't published for too long. Well, I brought just one man with me from Chicago. That was Dr. Friedrich Klemperer, the son of a very famous clinician, head of one of the two great clinics at Berlin. He was a scholar, who was head of the Moabit Clinic, and had been the physician of Emil Fischer and of Lenin. Dr. 0.: Personal physician for these people? Dr. H»: Personal, yes. Dr. Klemperer, Sr. had four sons and they all went into different things and were successful, but the second son, Friedrich, had his medical work with Thannhauser in Freiburg, and then the whole family had moved out of Germany after Hitler came in. Dr. 0.: Was there any relation—was one of the sons the Otto Klemperer, the conductor? Dr. H.: I think he was the brother of the clinician. He belonged to the other, the older generation. Dr. 0.: I see. So he was an uncle to the gentleman that was with you. Dr. H.: I think so. The Klemperer, who's a pathologist in New York, is another--cousin, I think--too; they're all related. Well, Friedrich

Page  101101 had been with me a year in Chicago and was very smart and very resourceful, very ingenious. He set up my laboratory for me and we worked together until World War II came along, and he moved down to Massachusetts General Hospital so he could participate actively in medicine. He felt that he ought to end up there sooner or later and he stayed there for some years with Walter Bauer. Well, so except for Klemperer, I didn't add anybody, and—this is the department picture in June 1936. It includes everybody, the storeroom man, the dishwasher---- Dr. 0.: Right. For the sake of the record, these are two photographs, a group shot of the 1934 staff of the Department of Biological Chemistry and of the 1936 staff. Dr. H.: In the 1934 picture, there are Folin, Fiske, Logan, and Trimble, Danielson, and that's all there was to the staff. In '35, there is no picture--they didn't take any. In the spring of '36--I came in the fall of '35--you see there's Klemperer, Fiske and me, Trimble, Logan, and that was Stotz. Stotz was in there as a graduate student, but he hadn't been put on his thesis work yet. He came to me and asked to be able to do his thesis with me. Dr. 0.: Stokes, forgive me, how do you---- Dr. H.: Elmer Stotz--S-t-o-t-z--he was my first Harvard graduate student, and he did his Ph.D. thesis in one year; he'd been there three years and Fiske hadn't given him a thesis problem yet. He got

Page  102102 this thesis out and now, of course, he's the head of biochemistry at the University of Rochester. He's also the co-editor of this Comprehensive series of biochemistry. Dr. 0.: Ah yes, Florkin and Stotz Comprehensive Biochemistry. Dr. H.: Twenty volumes have appeared. Dr. 0.: And he was your first graduate student at Harvard. Not actually your first graduate student because you did have some at Chicago. Dr. H.: Oh no, I had six at Chicago and one at the Rockefeller Institute—Sendroy at the Institute. Dr. 0.: I just want to get that on the record. Dr. H.: Well, if you really do put this in shape sometime, it might be nice to make a list of the graduate students and what's happened to them. It's the thing I'm proudest of. I'm much prouder of my Ph.D's and my postdoctoral fellows than I am of my publications. They live I They're your immortality. They go on producing other people. In my office I always had all their pictures up in front of me when I sat at my desk. My papers were behind me, because when things get put in cellulose they're dead'. That first year at Harvard was a very rough year for me because I knew that I couldn't lecture very well to medical students, but that I must start out and try from the beginning, because if I sat back and waited

Page  103103 for Logan or some of the other fellows who were in the habit of doing it every year to start the course, I never would screw up my courage to tackle the medical student. So I gritted my teeth and gave the first twelve lectures. Dr. 0.: In reference to that, I did find a comment made by you in a letter to Dr. Ebert, currently the Dean, September 1, 1965, in which you referred to this first year, and you have in parenthesis in your letter, "if you want to laugh, ask Franny Moore how terrible I was that first year. I wanted to use Peters and Van Slyke's Quantitative Clinical Chemistry as a textbook." Dr. H.: Yes, it was a little unrealistic. The boys in this class of 1939 were gentle with me. I've kept all the Aesculapiad1s. Dr. 0.: That's the student medical—or the yearbook for Harvard Medical School. Dr. H.: [Leafing through the Aesculapiad] This class of 1939 was most distinguished. There's so many professors in it--men that have made their names now in all fields. Dr. 0.: Do you remember Franny Moore as a first year student? Dr. H.: Very well. Yes, he was very good. He was smart, a man of many talents. Of course, everybody knows such people as Stanbury---- Dr. 0. : Who went out into biochemistry-Stanbury?

Page  104104 Dr. H.: Yes, and endocrinology; Balboni has become quite a well-known surgeon. There's John Dingle who's become famous at Western Reserve; Vince Dole, a member of the Rockefeller Institute. I was much too scared of them all so they treated me very gently. They were very nice. They just laugh about it now; they didn't laugh about it then. I gave them some very good lectures on the body as a physicochemical system, physical chemical laws that apply, and a great deal about hemoglobin, acid-base balance--— Dr. 0.: Sounds very similar to the type of course really that Dr. Clark used to give at Johns Hopkins--a strong component of physical chemistry. Dr. H. : I kept up this form of introducing students—medical or graduate students--to the biochemistry of the body, because I still think it is a good logical way to present the physicochemical structure, the chemical composition, the relative size of the different phases involved. If you know how much extracellular fluid, how much intracellular fluid, how much bone and the composition of each--chemically--you then have accounted for all the constituents of the body. And the whole question is how small do you break down these different phases. Until you have that picture of it, it isn't, to me, very logical to start worrying about enzymes and metabolism. Enzyme action and metabolism go on intra-cellularly, and if you have what happens in one tissue affecting another tissue, then you have to consider transport through membranes into other fluid phases and through capillaries into the blood stream and back out and so forth. So I still think it's the best way to start

Page  105105 thinking about the chemistry of the body. Dr. 0.: These were first year students who were the---- Dr. H.: First year medical students. They had just finished their anatomy, and I must say that I don't believe that the quality of the Harvard medical students has changed materially when you consider the composition of the class as a whole through the years. They're all smart students. They're top students--this is true--but there was then and is now, roughly, a third of the class who has had minimum physical and biological science, and this amounts to one year of physics, one year of biology and two years of chemistry, and that represents 25 per cent of a student's college life. On the other end of the scale, there was a third of the class which had majored in chemistry or had majored in biology and probably had taken over half their college courses as science, or some science. And then there was the middle third which had a little more than the two years of chemistry and maybe some qualitative and quantitative analysis, seldom physical chemistry, sometimes a couple of courses in biology. And we had to—since we could only give one course—set our course for this middle third. And then we had to work intensively for the first month, the first few weeks, with those students who hadn't had any quantitative laboratory experience at all because our course was entirely quantitative in the laboratory. Then at the end of that month, after we brought them up to this middle third, we could give our attention to the specially well-trained third and give them special things to do—harder things to do--which would

Page  106106 challenge them. And thatfs the way I organized and ran our course. Since our medical course was given entirely in one semester—February 1 to June 1--I insisted from the beginning, and throughout my tenure as head of the department, that when the medical students came in, research in our department went out the window—if continued, it was extracurricular. They did it nights and Saturdays and Sundays on their time because I said, "You're going to have the other eight months of the year to do research if you want to and on top of that, it!s darn good for you to take off and have to look at your subject in relation to the whole field of biochemistry." So my people all had to come to all the lectures—just as I went to them. We all participated in trying to make the lab work as meaningful as we could, and I kept deviling the Dean and the President for more teaching support so that instead of five teaching staff that were there in 1935, there were about 35 in 1958 when I became emeritus. So it was seven times the size when I left and much more troublesome to run. But we did get it up to the point where I could assign one senior and one junior man as something like an Assistant Professor and Teaching Fellow to each twenty students which meant that a staff member was intimately associated throughout a whole semester day after day with ten students! Dr. 0.: Yes, and by telling them that during this eight month period or rather during this semester, they were to devote their full time to teaching the students and their research had to be set aside, I!m sure you were able to keep them really always on hand and in the laboratory to be of assistance.

Page  107107 Dr. H.: You bet. I believe in this so firmly that I--if you get anything in the record, that's what I want. After the first year, I found that I could manage the job and settle down to plan the development of the department, not just in bodies but in what kinds of people, minds one would want there for the next five years, so that the active areas of biochemistry were well represented. At that time, I went to the Dean and said, "I want to get funds and people to cover physical biochemistry, organic biochemistry, enzymology, and nutrition." Later, I substituted quantitative histo-chemistry, the kind that Kai Linderstrgfm-Lang and Lowry did, for the physical chemistry. We were responsible for teaching nutrition in the School of Public Health as well as medical students, but we didn't have a man for it. I finally got Otto Bessey, who transferred from pathology-he was Bessey of Bessey and King fame—and that was fine until they started this Public Health Research Institute in New York City and Glenn King persuaded Bessey to go and run this, and he then took Lowry with him and that gave them a fine start. At that point, I went with Cecil Drinker down to the Rockefeller Foundation—International Health Division—and from Sawyer we got $125,000; $25,000 a year for five years to start a Division of Nutrition within the Department of Biological Chemistry. I think this was 1941 or '42. I'm skipping a little bit to get this in here. At that point, I wrote many of my friends, professors, for suggestions, and one of the suggestions that came, sort of reluctantly from Philip Shaffer, who's r

Page  108 the famous Dean, who built Washington University twice, and was continuously the head of biochemistry and had been Folin's early student--Shaffer wrote me a long letter outlining the virtues of about four different people in detail and he signed his name, and then in ink underneath, he said, "PoS. I suppose you ought to also consider Fred Stare." And so this tipped me off that his own conscience wouldn't let him send that letter without mentioning Fred Stare but also it was the last thing in the world he wanted to do. Dr. 0.: He didn't want to lose the man. Dre H.: Yes. So--well, he wanted him to succeed him. But Fred had an M.D. and a Ph.D. and was made for the job and he came in 1942 as a member of our department, and I designated it sort of unofficially as the Division of Nutrition of the Department of Biological Chemistry. You could do things like that at Harvard. He got Hegsted to come with him from Wisconsin, and they quickly outgrew the department and when General Simmons, after the war, came to be the Dean of the School of Public Health, he made as a condition to his coming to Harvard that Stare and Hegsted and Nutrition be transferred as a full department to the School of Public Health. Fred Stare has progressed from there on to having the biggest Department of Nutrition in the country, so to speak. He's a real go-getter and good, and this is a very good department. Well, you see I am not progressing at all logically or chronologically. The business of how we developed the Department of Biochemistry--! can

Page  109109 sit down and do that, not very excitingly--but at least do it, any time you want to do it, but I get more interested when I think of the University of Chicago, or Harvard, or here, in my extracurricular activities than in my teaching and research. Sure, my job was to develop the research department in Chicago, develop and do good research—teaching and research—at Harvard, but some how or other, I always seem to get a tremendous thrill out of certain kinds of extracurricular activities. In Chicago, I was put on the Board of Publication of the University of Chicago Press; I was on there for eight years. This is the board that decides what manuscripts will be published and what ones won't, and you get involved in the whole making and merchandising of books as a result of that experience. So Conant put me on the Board of Syndics of the Harvard University Press the first year I came, and at that time the Harvard University Press was a very inferior press. Perhaps it was the worst of all the university presses, whereas Chicago was the top. They didn't have any series of monographs, for instance, in medicine and public health like we had in Chicago, which I sort of thought was ridiculous considering the distinction of the medical people and the scientists at Harvard. It was run like a pleasant little tea party, and it always lost money and Conant didn't like it and he tried to shut it up. He and I used to have great fights over this--good-natured, sure--but it's one thing I disagreed with him entirely. He was all for closing down the press at one stage after I had been there for four or five years. Well, I just fought it tooth and nail, and along with Paul Sachs, who comes from this famous Sachs

Page  110110 family of Goldwin Sachs, but he became an authority on art. He established the Fogg Museum and was the Associate Director; he never would let them make him the Director, and he spent his life in the arts, and the Fogg Museum is one of the choice museums in the country. He was a member of the Board of Syndics too, and at one stage we took matters into our own hands and reorganized it and saved the Press and eventually got a very fine Director in Tom Wilson, a man whofs both a scholar and had business acumen which nobody else had had before. He built the Harvard University Press into the greatest press in the country, I guess. The products are just simply amazing, like the Adams papers and the Emerson papers. They have a bigger number of books put out per year than most commercial presses. Well, I was a member, a syndic, of the Harvard Press every year that was legitimate for me for the 23 years I was there. I think it added up to 18 altogether because, though I'd have to be off a year, they'd not fill the job and put me back on the next year. Well, that was one kind of an extracurricular activity. Another kind was after the tercentenary. As part of it, Conant, instead of establishing a School of Journalism; he was offered a lot of money to establish a School of Journalism and he didn't want it, but instead he set up what they call the Nieman Fellowships. These are reporters or writers for magazines who are selected by their paper or magazine-nominated by them--and then the final selection is made by a committee, some Harvard, some non-Harvard, and some publication people that make

Page  111Ill the selection of up to 15 people per year. These fellows come with their families and are paid whatever salary they got with their paper or other publication, and they're given the run of Harvard University for a year. They work harder than any undergraduate student. They don't have to do a thing. The only thing they have to do is meet together on Monday nights for dinner; they usually would have a speaker, but otherwise they don't have to do anything. The result is that they all vie with each other in taking a heavier course of study than regular students do and they take the exams. It's the damnedest thing in the world and---- Dr. 0.: What sort of things do they usually take? Dr. Hoi Well, very few of them take science; about one in 30 or 40 will turn out to be a man whose ambition is to be a science writer„ I mean one year out of three—they' re very rare. But mostly they go in for history or economics or sociology and it succeeded too well at the end of the, I think it was the first ten years. So many had gone back to their papers, but within a year had gone out and bought their own paper, that the publishers were about to refuse to send men to be Nieman Fellows any longer„ Dr. 0.: Well, you were, I gather, on the Board---- Dr. H.: So I was on the Faculty Advisory Committee representing science for these people. I represented science and one thing I always did was, once a year, in the spring, invite all the Nieman Fellows over to my

Page  112112 department at Harvard Medical School, and we'd sit around my office first and chat. I'd have one or two of the interesting young fellows of my department in too, to chat with them and then I'd turn them loose in the department and they'd scatter around and sit down in the different laboratories where experiments were under way. It was a thrilling thing to watch these fellows sit down with no knowledge of the science that was going on, but, sit on the stool, and say to one of these fellows, "What are you doing that for?" Well, it was also the best possible thing for these young graduate students; they were first shocked and then they tried to justify what they were doing. It was the first time they had been asked such a question. Dr. 0.: Explain it in language these people understandc Dr. H.: So I used to think of it as having a double advantage; it showed these reporters a part of the world they might otherwise never have seen and also let our boys see them. Then we did have some quite successful men turn up who wanted to be science writers. Then, I was their mentor. I helped them select their courses and sort of acted as tutor for them. It is fun to see their names in by-lines around the country. Then another thing that I think of--I guess I wouldn1t call it extracurricular—but it wasn't part of my job as head of biochemistry. That was the development of the Biophysical Laboratory at the Harvard Medical School. We got involved in isotopes starting in the summer of

Page  113113 1939. Conant asked Kistiakowsky and me to come over for lunch one day, which had happened before, but this time it was over the fact that the Harvard cyclotron was nearing completion and what was going to be done with it. It was out of that luncheon conversation that we decided we could find a way to do something about it, using Carbon 11, though Kistiakowsky, Conant, and I didn't know what we were letting ourselves in for. None of us had ever worked with Carbon 11 or any other isotope. It was out of that luncheon that grew this plan to label lactic acid with Carbon 11 and study its metabolism, particularly its conversion to glycogen. So we did undertake this and brought in quite a lot of other fellows. Have I been over this before? Dr. 0.: No, not on tape. Dr. H.: It seems that I've talked about this some time before more recently. Well, this involved getting quite a lot of people because Carbon 11 only has half-life of 20 minutes, and that means within five hours after you've taken your boron oxide target off the cyclotron, you haven't anything to measure anymore. Every 20 minutes there are only half as many radioactive C atoms as you had 20 minutes ago. It's sort of a miracle that we were able to get this work done, but it was because I had such fine young people with me as Birgit Vennesland, who's now Professor at Chicago, and Friedrich Klemperer and Jack Buchanan, now Professor at MIT, and Arthur Solomon, who's the Harvard biophysicist. We had also, for awhile, the help of an organic chemist named Cramer who's now with Du Pont. When the time came to write up

Page  114114 the first paper [#130], we had so many names that I certainly didn't want my own name first and Kistiakowsky didn't want his first, and I suddenly had a bright idea and put them alphabetical, and then in order to start them off with a senior name, in which everybody knew he hadn't done any of the lab work, I put Jim Conant's name on and wrote and told him; I called him up after I had it on the manuscript and said, "I hope you don't mind." He said, "Oh, I don't belong on thereI" I said, "Well, it will save me a lot of trouble, if you'll just let me put it on and after all, we started this at luncheon at your house." I think he actually has been secretly very pleased with it because it solved the problem for me, and it was the first one of that series, and it was a really historic series because then the work on the lactic acid was good and interesting and exciting and new, and upset the previous ideas about the conversion of lactate to glycogen. The really exciting thing happened in doing a control experiment. We were already to publish that lactic acid paper when I said, "Well now, let's run through exactly the same experiment we've been doing only give nonradioactive lactic acid in the same amount and then inject some isotopic sodium bicarbonate--C labeled—and we'll go through all the operations, and if our technique is perfect then we'll come out with zero counts in the glycogen." We had to do something like that because, of the lactate, the carboxyl labeled lactate, we'd put into the rat, over 50 per cent of it came out in the first half hour as carbon dioxide. It was partly metabolized to carbon dioxide, so there was the possibility

Page  115that the radioactivity we were measuring in the liver glycogen was trapped CO you see, and wasn't the conversion of the lactate molecule, but was simply trapped carbon dioxide molecule0 So this was to be a control proving that you could believe what we said about lactate going to glycogen. Well, we had radioactivity in the glycogen'. Dr. 0.: So you had radioactivity? Dr. H.: Yes, we turned up with radioactivity in the liver glycogen, and it hadn't been any place in that rat's body except as carbon dioxide. Dr. 0.: Here opens another whole avenue. Dr. H.: And well, we didn't believe it, of course. I mean we were skeptical. We thought, Oh my God'. Our technique's terrible, and we've got to do this again more carefully. We've got to isolate the glycogen, dissolve it, add some nonradioactive bicarbonate and then acidify it and sweep out the COo and reprecipitate the glycogen and count it, in less than five hours. It was hard to do because there wasn't much time to do all this. But we did it, and finally Birgit Vennesland was actually able to hydrolyze the glycogen and make osazones and still find the radioactivity undiminished. From that moment on we believed it. But this means, you see, that as you sit here about eight to ten per cent of the carbons in your liver glycogen have had a history of being carbon dioxide in your body'. This was the first evidence—first proof--that C02 is fixed and used metabolically in mammalian organisms.

Page  116116 Bacteria were known, of course, to fix CCL but this was the first proof in mammals and it just meant there wasn't a clear division between plants and animals. The enzymes are there to fix CO^ in you and me, just as they are in daisies'. Well, that didn't happen until 1940. The cyclotron suddenly disappeared in '42, and it wasn't until long after that I learned that it was shipped to Los Alamos and was the cyclotron that helped with the first atomic bomb, and is still there; it never came back. But after the war when Kistiakowsky came back and Solomon came back from England where he's spent most of the war, I wanted to get back into isotope work and Kistiakowsky advised me to get hold of Louis Hempelmann. You want to change the tape? [End of Side I, Reel 3] Dr. 0.: This is the discussion of December 22 and it is Side II, Reel 3. You were just beginning to say how you were anxious to get back into isotope work at the end of the war. Somebody had advised you to get hold of a gentleman by the name of Hinkleman? Dr. H.: Hempelmann. Louis Hempelmann, he's a Professor now at Rochester He'd been at Los Alamos during World War II. I tried to get him to come and join us at Harvard, but he, at that time, wanted to go to Washington University, St. Louis. But he did come and advised me, that if we were going to get into the isotope business at Harvard — this was now November '45 you see; this is as soon as it was possible for the boys at Los Alamos to even get permission to leave it to come to Boston--

Page  117117 and he said that you should have a good physicist, atomic physicist, and you should have a good biochemist experienced in the isotope field, and you should have a medical man who has had experience in the field. This would be the irreducible minimum nucleus to start an isotope research unit at any institution. Well, I persuaded Solomon to come back to the medical school to be the physicist of the team. Dr. Oo: You had had him with you before, had you not? Drc H.: Yes, in a very nominal capacity. He was a Research Associate at that time. Otherwise I didn't know whom we would get because Hempelmann didn't want to come. But I knew we had to have enough money to have three Assistant Professors. I got Solomon as an Assistant Professor at $5,000 a year in 1946. Just at this time the university, the President and Fellows had put up $450,000 to the Department of Physics to build another cyclotron. They expected to recover something from the government in payment for their own, but it was going to take more money anyhow. Conant set up a multidisciplinary committee to be responsible for the building and the use of the cyclotron. This is a Harvard stunt they use very regularly for big instrumentation that has multiple uses. This committee was a large one. It was headed by Buck, the Provost, and it had the key people in physics including Bainbridge, who triggered the first bomb at Los Alamos; it had Kistiakowsky from chemistry; it had Shields Warren and Joe Aub and me from the medical school; I think it had somebody from biology too, but it was heavily weighted with physicists. They weren't quite sure either what style

Page  118118 cyclotron they wanted, or just when they would have it ready and so forth. So I spoke up and said, "Look, how about our medical school committee borrowing $25,000 a year for five years from this committee and we'll pay it back if it's necessary, while you're waiting around on how to use this $450,000." I don't know whether we'd have got it or not, but Conant had happened to attend that meeting, and he was sort of sitting in the back of the room and he spoke up and said, "Well, I think that's a pretty good idea," and then he got up and left the room1. I'm showing you a great deal of what a politician, schemer that Baird is sometimes without really meaning to be. Anyhow, they gave us that money, and actually, we only used it for three years when they found other uses for it, but by then we were under way. This meant that we could get started, and it provided Solomon's salary and then I got DeWitt Stetten as our biochemist. I tried to get Waldo Cohn, but he didn't want to leave Oak Ridge. Dr. 0»: Walter- Dr. H.: Waldo Cohn. He's quite famous for his work on nucleic acids, and during the war he was very much involved in developing chromatog-raphy; he was very good. But Stetten, DeWitt Stetten, came. Dr. 0.: Yes, I certainly know who he is--at NIH for many years. Dr. H.: I couldn't find the atomic physician, but I finally, just through an accident, encountered Seymour Gray who had been at the University of Chicago and had some experience with isotopes. He came

Page  119119 to Boston and was at the Peter Bent Brigham on the GI service. I hired him on a half-time basis to join with Solomon and Stetten as the isotope team. Of course, in a sense, he paid his way before anybody else because he introduced the chromium tagging of red cells which is now one of the generally used ways. It's about the only thing he did with our isotope group. Later he dropped out. And after a year (1948), Stetten had an offer to go to the Public Health Research Institute (Bessey and Lowry had left the PHRI), so I lost Stetten after a year. So from then on I supplied the biochemist from my own department. First, Yale Topper, who is now at the NIH, and following him, Anfinsen, and following Anfinsen, Karnovsky. Their main job, they were the organic chemist type, was to make labeled compounds for the rest of us to use—well, they could also use them too, and did, very effectively, but it meant their labs were across the court from Building C-2, the biochemistry department. We took over, first, a few rooms on the first floor of Building D-2 at the Harvard Medical School, then we spread both ways and took over the whole floor and we took over the other side and around the corner. And this has been known, Conant wouldn't let us call it the isotope lab or the atomic medicine lab or anything like that. He said, "No," he said--at this meeting where this was discussed and set up--he said, "We111 call this the Biophysical Laboratory and it will be administered, not as a separate department, but by a Committee on Biophysics in relation to medicine." I was the chairman of this committee and Solomon was the secretary, and then we'd have such people as Aub and Warren, and usually Landis, head of physiology, and maybe one

Page  120120 other person from Cambridge--biology. This kept going that way from that time until I left in 1958. I was the chairman of this and Solomon and I together built this whole enterprise; it became, and is a great training ground. You see, what I'm talking about are my extracurricular activities, and I take a great deal of pride in them, I must say. Oh, I also started the Harvard Monographs in Medicine and Public Health. They didn't have any such series at the Harvard Press, and I thought this was terrible and I kept talking it up and talking it up; it always takes money, the question was how to get some money. Finally one night, this was after we'd been there two or three years, I was at dinner one evening at Arlie Bock's house, and both Dean Burwell and Dean Drinker were there and the Bursar, for dinner--!'ve forgotten his name for the moment. I went into my song and dance, when the men separated from the ladies afterwards, and told them what a crime it was we didn't have a Monograph series in Medicine and Public Health; that I was perfectly sure that there were oodles of fine manuscripts lying around or going off to commercial publishing houses that ought to be published by the Harvard University Press, from our large and distinguished medical faculty* Well, Drinker was always a doer and he said, "How much do you need to get started?" and I said, "Well, if I could have $5,000 just as a subsidy to underwrite publication costs, I will see if we can get some of these manuscripts," because it always takes some money and the Press doesn't have any money to subsidize us« Well, he said,

Page  121121 "Sidney, I don't see why we shouldn't each let Baird have $2,500, do you Sidney?" Sidney said, "No, I don't," and Cecil said to the bursar, "You don't see why we can't do this, do you?" "No." And so I went back to the Syndics of the Press and got their official approval to start this series. I appeared before the next faculty meeting and made a statement and then within a week I had three manuscripts on my desk. Well, this went on for about ten years, as a matter of fact, and we still had the $5,000 left--it was rotating. Almost all the monographs made some money. Some of them were classics, like Schoenheimer's book on the Dynamic State of Body Constituents. It consisted of his Dunham lectures which he wrote, and then committed suicide in 1941 before he gave them. Professor Hans T. Clarke had to come and give them. This made a little book, though; the first book on intermediary metabolism using isotopes, heavy isotopes, N and deuterium. The whole thing was laid out there, and this went through many printings and I think they could sell another edition if they put it out today. Sir Macfarlane Burnet, the Australian scientist who won the Nobel Prize, delivered the lectures in 1944 and these were published in the series as Virus as Organism. I was also Chairman of the Dunham lectureship committee for ten years so I helped pick the lecturer, and get the manuscripts for the series0 The Dunham committee had a lot of money so they'd help underwrite publication., It was another way to save this other fund. I got a lot of fun out of juggling things like this and

Page  122122 making them work; it's the way you learn to do at Harvard. It's all legal and all above board. So I had a busy time even before the war came along. When the war came, certainly life was even busier. Drc 0.: You and Dr. Burwell actually arrived at Harvard at the same time, or I should say, Dr. Burwell became Dean in 1935 when you joined the faculty. Dr. H.: Yes, and we used to say we were freshmen in the medical school together, though he had graduated actually from the Harvard Medical School in 1919. Burwell had a great deal to do with making key appointments at the medical school while he was the Dean. He made some of the most important and highly successful appointments that were made. Among the professional appointments which come to mind are: Landis in Physiology, Mueller in Bacteriology, Ball in Biochemistry, Bauer in Medicine (MGH), Thorn in Medicine (PBBH), Castle in Medicine (BCH), Moore in Surgery (PBBH), and Denny-Brown in Neurology (BCH). He was scholarly, interested in the history of medicine, wrote very well, and, indeed, later after he retired, he undertook to write the definitive history of the Harvard Medical School from the early part of the 19th century when the last history left offc He didn't get it completed before he died, but it was pretty well under way« He was also a very kind and very gentle fellow, very good clinician and even though he was Dean, he kept up his service for a part of each year and kept a laboratory with respiratory and cardiovascular research going at the Brigham throughout his deanship. He, particularly during the

Page  123123 war when so many of the faculty went off to war, and it was very hard to keep the school going, and yet he managed to do it, he brought back some retired professors and did a valiant job of keeping the school under way. He was criticised after the war by not being vigorous enough, by not being a good money getter, but I look on Sidney Burwell as a very great administrator for Harvard Medical School. I have nothing but praise for him. Dr. 0.: One of the things I noticed in the brief time I've had to look through some of your correspondence with people associated with Harvard; I noticed in some of the correspondence, for instance in a letter to Dr. George Packer Berry in February of 1961, you made the statement, "If we had differences about curriculum changes at times, they were about techniques and timing, not objectives,," And a letter to Dr« Ashmore in March of 1962 in response to some statement he had made, I think relative to a position elsewhere, you stated, "I quite agree that I would never care to be responsible for teaching without the authority to do it my way." And then in parenthesis, "that was what took the fun out of my Harvard job." I wondered if you could just make some comment about your feelings about the curriculum, of the basic sciences of medical school as related to the clinical sciences and what, perhaps, you found that you disagreed with in the changes that were being brought about at Harvard. Dr. Hoi Well, I don't want to generalize on this. I will comment freely about my own experience, my own ideas. But what might work, and r

Page  124124 I think would be best for me and my students at Harvard, I might not feel would be right for other people. Throughout most of my career at Harvard, the source of my satisfaction with teaching turned out to be the fact that I and my teaching staff were able to plan what we were going to teach and how we were going to teach it, in detail. We started our planning for our second semester teaching in the first semester of each year. Each week we did something toward this; we didn't wait until January to plan the course. We started planning it in October for the new year. We took into account criticisms that we ourselves could see, improvements we could make. We took into account the comments that the students had made to us, some of which were very important and useful. We took into account money, if we'd been able to get it, to get new equipment that would improve the kind of experiments we were doing. We had one hundred and twenty-five medical students in a laboratory at one time, and it's a big investment to add a single piece of equipment—even a pipette, anything cost a hundred dollars, two hundred dollars to get one more pipette for everybody! So you don't change radically; you evolve as you can get funds and see needs. The responsibility for the teaching of biochemistry was given to me personally by Harvard University in 1935; it was my responsibility. President Conant said, "You'll get so much money and your responsibility is to teach the students; now how you do that or how you spend the money is up to you." Well, that's the way we had done it from 1935 to 1956, I think. Then Dean Berry decided to make a frontal attack on the curriculum and

Page  125125 get a lot of money and do an experiment, not as a radical as they did at Western Reserve, but have integration of teaching. This was the key word, and there's money in those words; you get money from foundations if you do an experiment. Ifm not against integration when you've got something to integrate, but you don't just start with an integrated curriculuml You just can't do it'. You have to teach some physiology, you have to teach some anatomy, you have to teach certain facts of biochemistry until you have something that you can put together. A muscle! OK, you can describe the anatomy of the muscle, you can describe the way it works, you can describe the chemistry that goes on, but first you've got to know certain language, certain facts, and I see no way to get around that. Physiology and biochemistry had already integrated our teaching. First Cannon and I, and when he retired, Landis and I, had an integrated area of teaching, first in the field of pulmonary physiology and chemistry. This was taught as a unit. A quarter of the class was taken two weeks at a time and this was repeated three more times each year. (I read this in here already.) Dr. 0.: No, you mentioned it last night. We don't have this on tape and I think we should. Dr. H.: Well, I've been telling it to somebody recently and it seems as if I've already dictated it. Cannon would assign one of his senior instructors. They were such people as Davenport at one time, who's now Professor of Physiology at Michigan, and Johnny Pappenheimer, who's sort of the most distinguished physiologist now active, and others whose

Page  126126 names have eluded me. I always assigned two people from my group, junior faculty, graduate students or postdoctoral fellows. The four of us would work with the students everyday for two weeks at a time. The first week we'd take an eighth of the class in the biochemistry department and an eighth in the physiology department on one day, then alternate departments the next. We owned 20 Van Slykes and they owned Haldanes. The staff in the physiology department taught the physical aspect of respiration and we taught the chemical„ But the important thing as far as the lab work was concerned; after one week of learning techniques, learning how to manipulate Van Slyke machines, Haldanes, spirometers and so forth, the second week was devoted entirely to doing team experiments where each student would have individual assignments of responsibility. These were so rewarding. We'd end up with the students doing acid-base balance studies on themselves; get their own blood and one fellow would take ammonium chloride and one would take sodium bicarbonate and one would rebreathe and one would overventilate and they did all this themselves and they did it with accuracy that would be publishable if it weren't already published. In many instances they showed enough interest in the section so that we did absolutely new experiments, research experiments. It was a great success. It was integrated teaching, but it was planned and sensible and rational and they were ready for it I This other plan was not thought out that way. It was worked out this way. The dean, I presume knowing that he'd find a great deal of opposition on my part, or at least I wouldn't go along with it too easily, set up a committee made up of Assistant

Page  127127 Professors from each of the departments, the basic science departments, and we heads of the departments were not present at the committee meetings at all. He did it on the grounds that we were much too busy to devote our time to committee meetings and each of us had a chance to nominate our own representative. I had Karnovsky representing our department, which meant I knew every move that was made. They brought out an integrated first year curriculum which ended up by having a smattering of anatomy that ran through the first semester and then the other time was taken up by a bob-tail, short, superficial course of biochemistry and physiology. No one of these being enough to provide the student with enough basic knowledge in all three subjects. In the second semester, they attempted to have completely integrated courses. They had the semester divided into three areas: Area 1 devoted to physical chemical problems, respiration, kidney, acid-base balance; Area 2 was the neurosciences and Area 3 the hormones, endocrines, special metabolism. Well, these were taught all at once and people from each of the departments of anatomy, physiology, biochemistry and biophysical chemistry participated. Very ambitious and a few students got a great deal out of it, but many, too many of them were just at the edge of a group of people doing things and didn't know what the hell was going on. Well, it broke my heart, because it meant that this course within a course on respiratory physiology and biochemistry of mine that we'd worked so hard through the years to evolve, went out the window with

Page  128128 this, and the other thing that offended me so was the fact that no longer did I feel that 1^ had the responsibility for seeing that these students were getting the best biochemistry for their practice of medicine! If it hadn't been for my continuing group of postdoctoral fellows through these difficult years with me, I would have really gone off the deep end, I guess, I was so unhappy about it. Dr« 0.: Do you feel that this is a manifestation of what, I gather, has happened at many medical schools over the past 10 to 15 years in that they are more and more becoming, they are more and more coming under the control, .administrative control, curriculum-wise and everything else, of the Dean which was not the case, at least it's my impression it was not the case for many years; when the department head, as you did, had the responsibility and the authority to teach that course in the way you wanted to teach it. And nowadays the Dean seems to be the man that calls the shots as far as--— Dr. H. : Well, I don't like to generalize because I don't know that much about it really, you see, but this is something that did happen at Harvard, and of course I'm sure I made George Berry unhappy too by resisting this. We had great debates at the faculty meetings. Indeed, ordinarily the faculty meetings had no interesting business. There would be a handful of people that didn't know what else to do who would come; not enough to make a double row. All would just sit around the big long table, but it soon got around that there might be fireworks. So most of the faculty tried to crowd into the faculty room; they brought

Page  129129 all the folding chairs, they sat all over the floor to listen to these debates between George Berry and Baird. Well, he won because he was Dean! It was a good show. So we had a chance to try the new curriculum, but it didn't work. It really rocked them on their heels when I left, you see, because many people thought I left because of this and I didn't disillusion them. I really left because I had a chance to work in a lab again, and I couldn't be let off the hook as head of the department. I still wouldn't have taken the job here in La Jolla if I'd had to resign from Harvard—that's something else again. I wouldn't have thought of doing it, but they let me retire as emeritus, because I had gone to Harvard when I was 40 years oldc I'd taught 25 classes, and 25 and 40 is 65, and when you're 65 you're allowed to ask for retirement. You must retire in the academic year you're 66. You may request retirement—at least that's been the rule and the fact that I had taught those 25 classes in 23 years because of the speed-up——- Dr0 0.: During the war. Dr. H.: -——simply meant that I'd done my 65 year old Harvard job, only I was only 63. The other thing was that when Conant left the Presidency to become High Commissioner to Germany, in order to save him from resigning as President, they changed the rules in the book (so I understand), to the effect that a permanent officer which is what a Professor or a President is, he may request retirement any time after

Page  130130 he's 60, and he must retire in the academic year he's 66. They changed this for Conant and I happened to know that that was on the books though it wasn't widely advertised. So they let me retire with honor for having finished my Harvard job, but there are lots of people, as I say, that think I was fed up with the way things had been going and left. As a matter of fact, they took a hard look at the curriculum after this; they searched themselves. Dr. 0.: Well, you achieved something by doing this. Dr. H.: Actually, I achieved a great deal for the department. George then had to shell out enough money to redo the department for the incoming professor, my successor, which otherwise he thought he wouldn't have to do for another couple of years. As soon as he got there, together with Bernie Davis in bacteriology and Fawcett in anatomy, those three fellows wouldn't have anything to do with the integrated way of teaching, so it's back about where it was. Dr. 0.: Now it's back very similar to the situation when you were there. Dr. Ho: Well, they are teaching biochemistry in the first semester instead of the second, but as far as I know that's the main thing. Dr0 0. : Well, I gather the big drive that brought you out here—well to a place where you could get back to the lab, was the fact that you felt that for 25 years you, in a sense, had been physically removed much of the time from the laboratory--in other words, doing with your own hands your own research.

Page  131131 Dr. H.: Not quite that. Up to the war, I was very much in the lab, probably all but these four months of teaching, two-thirds of the time; I only had to spend a third of the time in administration, so I had really a great deal of time for lab work. I always have felt that my papers and my ideas and my productivity in my Harvard years were even better than during my Chicago years when I had full time for lab work. Partly because I did have to plan my experiments and what I was going to do more carefully. I couldn't be wasteful of time. When you've got a full time research professorship, you get—well, I don't know whether I should say lazy-but at least you're relaxed. If something doesn't work one day, you leave it and you don't worry about it too much because there's tomorrow and tomorrow and tomorrow, and when you're a teacher and an administrator you can't afford that kind of extravagant waste, you use your time and the result is you think harder about planning your experiments, you don't just kind of follow your nose. Dr. 0.: Right. That's an excellent point, which leads us into another area and I know you've said to me off tape and your professional career has certainly shown this, that you feel that it is very important for a man to be both a teacher and a research scientist, and that this idea of having an individual in a medical school who is strictly doing research or one who is strictly doing teaching and really doesn't have a research interest and capability, is not fulfilling the full requirement of a good teacher. Dr. H.: Yes, I think I have about as much right to pass a comment on

Page  132132 that subject as anybody in the world. At the University of Chicago, I was a research professor of biochemistry in the Department of Medicine, and had full time for research activities. Teaching was extracurricular. Immediately across the court from me was Professor Koch, who was head of the Department of Physiological Chemistry at the University of Chicago and as such taught medical students and graduate students. I was a Mary and he was a Martha. He had a terrible time getting money, getting time to do research, and I just had nothing to do but research. But he made a big contribution in teaching young people and I only saw very few of them--the graduate students. When I went to Harvard there was Edwin Cohn in a full-time research professorship. He never saw medical students and very few graduate students — full-time research, lots of money for it, and there was me with less money and many more responsibilities. Here, he was the Mary and I was the Martha. That's why I say I have run my own control. Now, I know that I wouldn1t trade my career as Martha for that of Mary for anything in this world. It makes your research better to have to take off every once and awhile and consider your whole subject; it makes your research better to be surrounded by young, questioning men and bite every kind of thing you have to give them, and who can pick out a weak spot in your argument and don't hesitate to say so very easily. They keep you on your toes; they make you look at your own problem in different ways in your attempt to describe it to them; to teach them. Altogether the relation between a scientist in a laboratory and his fellow man--in this case the students--is one of those things that is essential for research and for

Page  133133 success and for progress. You'll get in such a rut otherwise. You learn more and more about less and less. If it hadn't been for World War II, Edwin Cohn would have gone to his grave continuing to measure the dielectric constants of amino acids and proteins to another decimal of accuracy! We saved him literally-not because we wanted to save Edwin—but because at the beginning of World War II, Cannon, who was chairman of the committee, came to me and said, "How do you suppose we can get somebody to prepare pure beef albumin?" We went up to Edwin Cohn's office together and asked him about this and he reached back into his reprints and opened up one of his fine Morocco-bound volumes and said, "Well, if you use such and such an ionic strength, such and such temperature, such and such alcohol concentration, such and such pH, you'll come out with your albumin." All the other proteins like gamma globulin and that sort of thing—they were to be thrown away. They were the by-products. I have jumped over into the wartime, but I didn't mean to. I was only wanting to describe how Edwin Cohn was saved from being known only for the accuracy and completeness with which he had documented the properties of amino acids and proteins. Dr. 0.: Well, as far as your involvement in the war effort and so on, I think when I come back in February, I really want to endeavor to go into these various things, because I think they're very important. Dr. H.: Yes, I want you to spend a day or so on that locked file there,

Page  134134 I think that's another story, and it was almost another life. So you'll come back and pump me about it. Sometimes when I'm lying awake nights thinking about some of the nice things that have happened in my life, I think of the individuals who, because of my accidental intervention, have had good things happen to them. The first instance of that kind is Franklin McLean, whom I rescued in the nick of time as a scientist, and he has been a leading figure in calcification of bone now for so many years that people have completely forgotten that he was ever an administrator. The second was at the start of the Atomic Energy Commission, immediately after the war, when I was a member of the Committee on Biology and Medicine of the AEG. The first act that we agreed on was that we must have a Director of the division, and I proposed and then had to work diligently on Shields Warren to get him to even look at the job, let alone take the job. He was ideal for that position which he held 1947-1952. He built the program of the Atomic Energy Commission for Biology and Medicine. The third one was when Francis Dieuaide, who had been the head of medicine at the Peking Union Medical College for, I think, about 14 years, came back to this country. First, I took him into my laboratory for a year to rejuvenate him as a scientist. Then there were arrangements made at the Massachusetts General Hospital so that he had a job of sorts for seven years. Then came the war and he was a colonel in the Surgeon General's Office. But after the war he didn't know what he was going to do. Just at that time, the Life Insurance

Page  135135 Medical Research Fund was formed. Francis Blake of Yale was chairman of the Advisory Committee, which was set up to support medical research and medical fellowships particularly in the field of cardiovascular diseases. Our first act was to decide who was to be the Director of the Life Insurance Medical Research Fund, and I said I know just the person for you, for us--Francis R0 Dieuaide. Dr0 0. : How do you spell DeWade? Dr. H. : D-i-e-u-a-i-d-e. Dieuaide. He's very scholarly, very mild, very self-effacing, and very bright and very good and doesn't miss a trick. He built that program of the Life Insurance Medical Research Fund so that it is a model towards which every other medical research, cancer research, cardiovascular heart fund and so forth, might well model themselves. And then the last one may have been the most important of all. Again, after the war, the university physicists who had been part of the Manhattan District, wanted to have a reactor to work with, to smash their atoms—and yet, since the cost was so prohibitive, no university could afford a reactor. So nine of the eastern universities banded together to form a corporation—Associated Universities, Inc. --Harvard, Yale, MIT, Columbia, Princeton, Pennsylvania, Cornell, Rochester, and Johns Hopkins, and then they entered into a contract with the Atomic Energy Commission to build and run a reactor and associated big atom smashing machines, big cyclotron, synchotron and so forth. For a place,

Page  136136 they obtained the use of old Camp Yaphank in the middle of Long Island, Upton, Long Island. They started building their reactor there and converted the barracks into laboratories. The physicists and the chemists got off to a good start. Oh, I should also say that this corporation which had the responsibility of running the show which was to be paid for by the Atomic Energy Commission, was composed of 18 trustees, two from each university. One trustee would be a faculty man, and one would be a business vice-president or the equivalent. When this corporation was first founded, Kistiakowsky was the faculty appointee by Conant, and Reynolds was the vice-president for financial affairs at Harvard. These were our two trustees. After one meeting, Kistiakowsky said, "I'm not going to do this. I've had enough of this sort of thing; I want to get out of it entirely," and so Conant made me the faculty trustee from Harvard instead of Kistiakowsky. I found at the very first meeting that I attended that the physicists and chemists were going to run off with the whole show, and there was only one other nonphysical science man there from any of the faculties. He was from Yale, and he was a botanist and he was dead set against anything connected with medicine. He'd already expressed this, so that they were in the mood to have nothing to do with medicine and only a little bit with biology. Meantime, as soon as they had gotten started, they had offered jobs to a certain number of biochemists and biologists and had been unable to get any good ones to take a job. I sent two of my very good postdoctoral

Page  137137 fellows down to look it over, and I thought it would be a very good place for them to go next, but they came back and said, "No, there's nobody there in the middle of this wasteland of Long Island; we'd be isolated, scientifically." I'm talking about the Brookhaven National Laboratory at its start—that1 s what I'm talking about—and I couldn't get any of them to go. Dr. 0.: It wasn't known as this at that time, was it? Dr. H.: Yes, I think it was called this from the beginning. Almost coincident with this, however, Donald Van Slyke's wife died. A woman we were devoted to. He went into a tailspin after this; life to him wasn't worth living after her death. He lost all his spark, lost all his interest in everything. We were all very worried about him. This coincided with his, what was then obligatory retirement, at least active participation as a Member of the Rockefeller Institute. He could have stayed on with restricted funds and restricted laboratory and office space. At any rate, the combination of these things made me go down to New York; he had then moved to an apartment on West End Avenue, and I told him about this budding institution, the Brookhaven National Laboratory. I guess it had been going a year at this time and their inability to get really good biological and medical scientists there and would he please, for my sake, go to the Brookhaven National Laboratory and take on the responsibility and the title of Associate Director for Biology and Medicine under the physicist, Lee Hayworth, who was the Director. We needed him to build those departments of biology

Page  138138 and of medicine because I knew darn well, until we got somebody with the name and a reputation and a stature such as Donald Van Slyke, we wouldn't be able to get off the ground I I was so right. He says to this day, whenever he mentions this, that I ordered him to go there and I accept this statement because I did! From where I sat, it was the only feasible solution for Brookhaven. He came; he did work long enough at this job of Associate Director to pick out H. J. Curtis as the head of biology and Lee Farr as the head of medicine. Oh, he and I both tried very hard on Jim Shannon; we thought we had him hooked, but it was shortly before he got the job as Director [of NIH] and has been the Director ever since. So he decided he had rather do that than be at Brookhaven, otherwise Jim would be there. Hefd sold himself to the trustees and he was all set. Then Van got Lee Farr, who was then at the A. I. Du Pont Institute, and had, before the war, been with Van Slyke at the Rockefeller Institute. Anyhow, from that moment on with Van there, Curtis and Farr had little difficulty staffing their departments. Van, pretty soon, got working in the lab again. He'd taken his old technician with him, John Plazin, who had been with him since 1906. John's ambition was to be the best technician in the world and he was. He and Van worked there together in the labs and pretty soon Van developed a much better way to measure Carbon 14 with greater accuracy, greater sensitivity. He earned his way as a scientist too, but I not only saved the biology and medicine for the Brookhaven National Laboratory by that move, but I saved Van Slyke, and I think that's as important as anything I've done—probably more so

Page  139139 than all the rest of the things I've ever done. Van is still there and working productively—age 84. [End of Side II, Reel 3]

Page  140140 [Reel 4, Side l] The date is February 5, 1968 with Dr. Olch in the office of Dr. Albert Baird Hastings at the Scripps Institute of Oceanography in La Jolla, California for the start of our second week of interviews. Dr. 0.: I think we agreed to begin this series of interviews with a discussion of your scientific work while at Harvard, that's 1935 to 1958. Dr. H.: When I moved from the University of Chicago to Harvard in the fall of 1935, I undertook to expand and extend some of the problems that I had been working on while at the University of Chicago. I had as an associate in that early period only Dr. Friedrich Klemperer, whom I have mentioned previouslyc I really had three scientific laboratory interests at the time. One was tissue electrolytes, in particular, an interest in extending what the mass and electrolyte composition of the extra cellular and intra cellular phases were of tissues other than the blood. We had completed, at Chicago, studies of the skeletal muscle with respect to the extra cellular and intra cellular phases in this regard. I hoped to extend this to other tissues. The second problem was further studies on calcium metabolism and particularly factors which affected calcification and decalcification. And thirdly, the extension of our work with Shock on acid-base balance. As it happened, however, the first problem that Klemperer and I undertook was to measure the oxidation-reduction

Page  141141 potentials of a number of synthetic flavins; that is, flavins which were closely related to riboflavin which is known also as Vitamin B,~. I mention this only because we found on measuring these oxidation-reduction potentials at different pH's that the curves indicated that there was, at certain pH's, a transition from a two electron transfer reaction in one step to a two electron transfer reaction in two separate steps. This indicated that there was the appearance of a free radical. Dr. 0.: This information was published in article Number 103 in your bibliography. Dr. H.: If we had pursued this further and realized its importance, we would probably have been one of the earliest to demonstrate the importance of free radical formation, in such substances as the flavins, which was so definitively worked out by Michaelis and his colleagues at the Rockefeller Institute. In the second year that I was in Harvard, Dr. Oliver H. Lowry who had just completed his M.D. and Ph.D. at Chicago joined our department. I was fortunate in interesting him in the further exploration of tissue electrolytes. About the same time, Dr. Jeanne Manery joined my laboratory as a research fellow, a National Research Council fellow, and she also was interested in this subject. With Dr. Manery we published in 1939, [# 112] a paper representing her work while in the department, on the distribution of electrolytes in a large number of mammalian tissues and demonstrated that in all the tissues that we analyzed except the red blood cells, cartilage and gastric mucosa, the

Page  142142 sodium and the chloride that is in any soft tissue is essentially almost entirely extra cellular—and that the ratio of their concentrations corresponds closely to that of plasma. About the same time, Dr. Lowry studied the rate of change in distribution of ions between intracellular and extracellular fluid of liver and muscle when incubated in vitro. In a word, he observed as others had done before him, that the exchange of intracellular potassium for extracellular sodium in muscle is very slow, but that in liver, it is very rapid indeed. So rapid, indeed, that you couldn't accurately measure the rate with the methods then at our disposal. Parenthetically, I should say that this work preceded the availability of isotopes. But this observation of Lowry's on the very rapid exchange of intracellular potassium in liver for extracellular sodium was one of the most important observations for most of the scientific work that I and my colleagues carried on from then to the present time. Earlier I have referred to the fact that when we worked with Carbon 11 in 1940 and studied the conversion of lactate to glycogen in liver, we had to work with whole animals. We had to study this in intact rats because there was no in vitro method whereby you could study the conversion of even glucose let alone lactate, to liver glycogen. We had made valiant efforts ourselves to incubate liver slices in an artificial extracellular fluid, such as an ultrafiltrate of plasma, made up artificially. But we were never able to demonstrate the in vitro conversion of glucose to glycogen in liver slices. After Lowryfs results were available, it became apparent at once that

Page  143143 shortly after we put our liver slices into an extracellular medium, such as a modified Ringer's solution, that the high intracellular potassium concentration of the liver cells was promptly converted to a high intracellular sodium concentration. This gave me the very simple and obvious suggestion that we should see what would happen if we put our liver slices in a simulated intracellular medium, namely, one that was 120 millimolar potassium and 20 millimolar magnesium instead of one that was essentially a solution of sodium chloride and bicarbonate. From the first experiment that we did with glucose in a potassium-magnesium medium we found more glycogen at the end of the incubation than we had started with. The technique that developed from this has kept me in the manner in which I like to live ever since! That was a four star development. Such a simple thing as that. Why other people hadn't done it before, God knows. It only works on liver, of course. It works simply because the liver cells are so permeable, and exchange cations and small anions, so readily with those in the extracellular environment. Well, we did not know this when we were doing our Carbon 11 work. At least we didn't know it until just the very end of it. The first paper that we published on this finding was actually published with John Buchanan, who came to me as a graduate student and took his Ph.D. with me. This paper was published in the Proceedings of the National Academy of Sciences in 1942. Dr. 0.: That's item #149 in your bibliography.

Page  144144 Dr. H.: There was a good bit of preliminary work that I did both with Klemperer and Dr. Vennesland before these experiments were done which formed that publication. Dr. Buchanan, Frances Nesbett and I also used this solution in some preliminary experiments showing that carbon dioxide using C C>2 could be incorporated into liver glycogen in vitro when pyruvate was the substrate. [#148] Because of my absence from Boston for about half of each week from '41 to '46 .... Dr. 0.: That was when you were involved with OSRD .... Dr. H.: That's right. And very little further work was done during the war years in which I participated personally on this subject. But after the war, when Carbon 14 became available, and we had established a biophysical laboratory at Harvard with Arthur Solomon, which I have previously described, we took up the subject again. One of the first things that we did was to see whether we could confirm and extend the C02 incorporation into liver glycogen in vitro. This was published in 1947 [item #163] with Anfinsen, Gould, Rosenberg, and Solomon. In a series of about a dozen experiments, we established quite convincingly that about 8% of the glycogen carbons of liver have had a history of being carbon dioxide in the animal's body. From 14 that moment, we undertook to study metabolic pathways using C labeled substrates.

Page  145145 Dr. 0.: May I interject a question here? Was this finding readily accepted by your colleagues? I ask, primarily on basis of the statement that we both agreed upon in our last series of interviews, that even today every textbook seems to push the importance of the pH and this idea of the importance of carbon dioxide still hasn't permeated literature in the way that one would expect. Dr. H.: I would say that in biochemical circles it is completely accepted. It is usually described as an extension of the discovery of Wood and Werkman. It is called the Wood-Werkman reaction, in which they discovered before we did this liver glycogen work, that bacteria will fix CO^ just like plants will, and they worked out the chemical reaction involved. That is a carboxylation of pyruvate to make oxalacetate, and that's how COo gets into the Krebs cycle intermediates. Our work, when it is cited, is cited as a confirmation of this sort of reaction. We did not discover the reaction. We did first demonstrate that CC^, as C02 in the body, can be and is incorporated into organic material in a mammalian organism. Having demonstrated that we could carry on this study of carbohydrate metabolism in rat liver in vitro by using what I like to call the intracellular ionic medium for incubation with a high concentration of potassium and magnesium, we have studied many of the pathways which 14 a C labeled substrate such as glucose, fructose, glycerol, pyruvate, lactate, or acetate follow in their eventual conversion to such substances as glucose, glycogen, carbon dioxide and water, lactic acid, fatty acids, and to some extent proteins. As the different possible

Page  146metabolic pathways that glucose, for instance, may take before it all appears as carbon dioxide and water,--as these different pathways and the enzymes involved--were worked out, a succession of colleagues and I undertook to evaluate quantitatively the extent to which these labeled substrates followed one pathway versus another. We called this series of studies Factors Affecting Alternate Metabolic Pathways. Obviously, none of them could be complete, but we were able to do such things as determine how much glucose was phosphorylated to glucose-6-phosphate per unit of liver per hour. Then, what percent of the glucose-6-phosphate that was formed would be metabolized to pyruvate via the Meyerhof-Embden glycolytic pathway; how much was further metabolized via the Krebs citric acid pathway to carbon dioxide and water; how much was diverted through the pentose phosphate pathway; how much was converted to glycogen via the UDPG pathway, uridine diphosphate glucose pathway; and how much was simply hydrolyzed again by glucose-6-phosphatase, which the liver contains and no other tissue does, to glucose and inorganic phosphate. Having established those percentages for normal animals, we could then study how these pathways were altered quantitatively in livers taken from diabetic animals, for instance. And how much they were altered by the administration of insulin. We also studied them after adrenalectomy and after diabetes plus adrenalectomy and the affect of some of the sterols. This was rewarding in one way, because by making similar studies with labeled pyruvate in normal and diabetic animals, it developed that we could resolve, at least for rats, the old argument of whether diabetes

Page  147147 was due to underutilization of glucose or overproduction of glucose. This was an argument that I had heard go on year after year at the Association of American Physicians in Atlantic City. Each had its proponents and each had good evidence that they were right. Well, it turned out they were both right because the diabetic animal has muscle which, in the absence of insulin, cannot take up glucose as readily as the normal one. Therefore, there is underutilization of glucose. But we could not study the question of whether the liver, which is our glucose producer, had a greater or lesser rate of glucose production until we had isotopes available, and even then we needed to devise experiments which permitted us to have our livers in paired vessels, both containing glucose and pyruvate. One contained isotopic glucose. The other isotopic pyruvate. It was from the data on pyruvate metabolism that we determined glucose production. Dr. C. T. Teng and Dr. F. Marott Sinex were associated with me in this work. Since we had no means of having two carbon isotopes and studying them in the laboratory, we devised a means of doing the equivalent of that, which, as I said, was to set up faired flasks for each experiment we 14 did. We had C labeled pyruvate and unlabeled glucose in one and C^ labeled glucose and unlabeled pyruvate in the other. Otherwise, everything was the same. From the data we got, we were able to calculate both glucose production and glucose utilization. It developed that in the diabetic liver there is both a decrease in glucose utilization

Page  148148 and a very large increase in glucose production. Administration of insulin corrects both these abnormalities. As I ended my paper when I reported this to the Association of American Physicians, "so, we have worked for three years and all we have to show for it is that we have converted a two-letter word 'or* to a three-letter word 'and1!11 (LAUGHTER) At this point, I would like to pay tribute to the numerous colleagues in the Department of Biological Chemistry, at the Harvard Medical School who, between 1947 and 1958, worked with me on this problem of factors affecting intermediary metabolism, in the liver and other tissues. In addition to Klemperer, Buchanan, and Vennesland whom I 14 have already mentioned, there was, after C became available, Anfinsen, Sinex, Teng, Renold, Cahill, Ashmore, Landau, and Spiro. Altogether, we published 56 papers on this subject. Dr. 0.: Is this the same Dr. Renold who is to be here this week? Dr. H.: That's right. Practically all of those whom I have mentioned are now professors someplace in this country-- Dr. 0.: Or abroad. There are some abroad-- Dr. H.: They're all in this country except Renold. He is in Geneva, Switzerland.

Page  149149 This was not all that was going on in my laboratory in the Department during this period. Lowry extended his study of electrolytes in normal tissues to a study of the change in the mass and composition of muscle, heart, liver, brain, and kidney--in relation to aging. Dr. 0.: Changes in mass and composition of tissues with aging --- Dr. H.: That's right. This is also the period when Richard Singer worked with me for two years and devised the Singer-Hastings acid-base nomogram, which clarified the problem of how acid-base data should be interpreted clinically. Although there have been modifications of this nomogram proposed in recent years by Astrup and Siggaard Andersen with a different nomogram, the information obtained from the Siggaard Andersen nomogram is identical to that which one gets from the Singer-Hastings nomogram. Dr. 0.: I'm certainly familiar with the Singer-Hastings nomogram from medical school and clinical chemistry. Dr. H.: The reprint of the nomogram article which was published in Medicine is still in demand I'm proud to say. It's No. 165 in my bibliography. It was published in 1948. I'd like to emphasize again that by using the Shock-Hastings so-called acid-base pipette, one can obtain on 1/10 of a cc. of whole blood, the necessary and sufficient data to characterize the acid-base balance accurately and quantitatively. One obtains the hematocrit, the carbon

Page  150150 dioxide concentration, and the pH of the plasma by this method, from 1/10 of a cc. of blood, which means that one can gather these data from finger blood. No calculations are necessary. All that one needs is the Singer-Hastings nomogram and you can read off the C02 tension of what amounts to the arterial blood, and the buffer base. By comparing that with normal values, you know accurately how much the carbon dioxide tension is changed from normal, and how much titration of the blood with fixed acid or fixed base has occurred in milliequavelents per liter. Dr. 0.: I'm just curious. Was Dr. Singer a clinician? Dr. H.: Yes, he was an M.D. from the University of Pennsylvania. He was well-trained in mathematics and in chemistry, and took the M.D. at the University of Pennsylvania. He went back there after his fellowship with me and had the appointment of Assistant Professor in Biochemistry and in Medicine. Because he was in two departments, his promotion was neglected and eventually he left academic life and became the Medical Director of a life insurance company. This is another example of how difficult it is to have an academic career unless you are definitely identified as on the academic ladder of one department. Dr. 0.: Yes. This is an interesting example of that. Dr. H.: There are many of them, unfortunately; it's too bad. The same things happened to Landau.

Page  151151 Dr. 0.: Bernie Landau? Drc Ho: Bernie Landau. He left me to become an Associate Professor of Biochemistry and of Medicine at Western Reserve, and prospered mightily--did magnificently, but the time came when he decided that he couldn't wait any longer, and so he is now Director of Biochemical Research at the Merck Institute for Experimental Therapeutics. I'm sure he's one of the best trained men in the country; a Ph.D. in organic chemistry, an M.D. from Harvard——— Dr. 0.: Yes, I worked with Bernie at the National Institutes of Health in the Cancer Institute when he was with Roy Hertz. Dr. H.: He was just wonderful when he was with me. He could do many things none of the rest of us could do, because he was so well trained in organic chemistry0 I'd like to mention Yale J. Topper, who is now at the National Institutes of Health. He did one of the earliest studies of alternate metabolic pathways. He preceded Bernie, who later redid and extended the work on the degrading of the carbons and getting their specific activities. Yale Topper, of course, has prospered too. He was an organic chemist from Woodward. Well, to go back to this work in metabolism, I should have--at the time I was talking about factors affecting the intermediary metabolism, also mentioned that we quite naturally made several sets of experiments

Page  152152 and published papers on the role of ions in metabolism. Dr. 0.: Yes. I know there is a large block of your bibliography that's on this topic. Dr. H.: Nor did I neglect hemoglobin entirely, though most of my hemoglobin work was done at the Rockefeller Institute. Dr. 0.: I don't mean to make a pun, but in a sense, you had it in your blood.' Drc H.: Okay. That's right. It does seem as if I had never been able to get rid of a problem that I once worked on. Dr. John Taylor came to me with a National Research Council Fellowship after receiving his Ph.D. from Johns Hopkins under William Mansfield Clark. He completed a definitive study of the oxidation-reduction potential of the hemoglobin-methemoglobin system. This was done successfully and over a wide pH range for the first time, because we used one of the stunts that Barron and I had used at Chicago, namely, to put in a small amount of a dye whose potential would be somewhere near that of the hemoglobin potential. This facilitated the establishment of an equilibrium oxidation-reduction potential rapidly, and thus, permitted the acquisition of much more data than Conant and his colleagues had been able to present in the earlier attempt to measure such potentials. Dr. 0.: That's a publication in 1939, Journal of Biological Chemistry, [#122]

Page  153153 Dr. H.: Another series of experiments that we were able to do because of the availability of isotopic potassium and isotopic phosphorous was the study of the rate of exchange of potassium between red cell and plasma and between muscle and plasma. The former was carried out with postdoctoral fellows, John Weller, I. M. Taylor, John Raker, the latter with Evan Calkins. The study of the exchange of phosporous from red cells to plasma was carried out with C. B. Mueller. It is of interest that as of today, Mueller is a professor of surgery, Raker is a professor of surgery, Taylor is a Professor of Medicine and Dean at North Carolina, Weller is a Professor of Medicine at Michigan, and Calkins is a Professor of Medicine at Buffalo. Oh, yes! I should not neglect to mention Ed Flink who spent a year with me and studied the potassium exchange in muscle. Flink is now a Professor of Medicine at West Virginia. Dr. 0.: A number of these are professors in the department but not necessarily heads of the departments. Dr. H.: Yes. Dr. 0.: Throughout your active career, you have had a fair number of clinicians who have spent a number of years doing basic research. Dr. H. : This is the joy of it.1 In fact, I found that it was highly important for these young men with M.D.'s who had not had previous research experience to amount to anything, to spend not less than two

Page  154154 years in the department. The only ones whom I ever had, and I think there were only two, who spent but one year, got practically nothing out of it. Itfs customary for them to sort of flounder around for the first few months, and live with us until they felt like biochemists, and then by June of the first year, they would just be getting into something interesting. So I tried to insist that people would spend two years if they spent any0 Someday I must make a list of these people, a complete list, because I once did a rough count and in the post war years before I left Harvard for La Jolla at the end of '59, I had about 60 M.D.*s who had worked in our department with me. Perhaps, just for completeness sake, I should mention that calcium still pursued me, though not as actively as it had in my previous laboratories. My last Harvard Ph.D., a lovely young German girl named Michaela Smits did, as her thesis, a study of the interaction of citrate with the bone minerals. Michaela later married one of Edwin Cohn's Ph.D.'s, Tommy Thompson, and has since been producing and raising a lovely family. She has never written up her thesis for publication, unfortunately. Dr. 0.: One of the hazards, I imagine, of females in science. Dr. H.: I haven't done very well by my scientific point of view. I don't think I've done justice to it, but let me see if I can get it into it's perspective. Will the recorder pick me up if I walk around? Dr. 0.: Yes, sure.

Page  155155 Dr. H.: In retrospect, I feel that it was most fortunate that I began my scientific activities even while I was at Columbia taking my Ph.D., and at the Rockefeller Institute, on the determination of the mass and composition—electrolyte wise, between cells and their environment. It is true that it was limited to the blood for the first few years and then was extended to tissues. Had it not been for this, I would never have had this concept of approaching man as a heterogeneous system made up of a number of heterogeneous systems, but which one can group into the following: Heterogeneous system 1. A gas-liquid system. This would be represented by the blood and the alveolar gases. 2. A liquid-liquid system represented by the red blood cells and the plasma, as one example. The mass and composition of the plasma and the interstitial fluid, separated by the capillaries is another example of heterogeneous system #2. [ End of Reel 4, Side I ]

Page  156156 [Reel 4, Side II recorded on February 5, 1968] Dr. H.: Another example of heterogeneous system #2 is the interstitial fluid and intracellular fluid which is represented in the variety of soft tissues. And system #3 fluid-solids is represented by the bone salt and its interstitial fluid. To get a quantitative idea of man: "A heterogeneous system." One can plot the composition of each phase vertically and the relative mass of each horizontally on a piece of cross-section paper and thereby portray quantitatively the composition and mass of the several main phases in the body. This is what I started out every teaching lecture or series of lectures with! Until one gets the feeling that one is dealing with cells with an optimum intracellular environment, surrounded by an extracellular environment of optimum mass and composition, one can't really approach sensibly and quantitatively, the metabolic events that are occurring there. Intracellular metabolism does not occur in a Ringer's solution! If I had not had the previous experience with tissue electrolytes before I got involved in studying intermediary metabolism, I would never had had this realization that metabolic events and environmental events, such as, exchange of ions across cells, are intimately interrelated. These two branches of research-tributaries suddenly came together at Harvard in one stream and I've never left either since. Dr. 0.: It has been a common stream ever since.

Page  157157 Dr. H.: I have neglected to discuss the work of Claude Villee, who is now a Professor in a Department of Biological Chemistry, and who has become literally world famous for having developed a field of human fetal biochemistry. I have neglected to mention Jytte Muus, who came with me during my first year at Harvard from Copenhagen on a fellowship and did some work with me on calcium binding, and on the affect of vitamin deficiencies on heart muscle metabolism and who, now for many years, has been Professor of Biochemistry at Mount Holyoke. I also neglected to mention the beautiful work of Manfred Kiese, a pharmacologist from Berlin who came in 1937, I guess, and who was with me two years. The first year we worked on carbonic anhydrase, preparing very pure samples and testing them for every metal except zinc, which was later discovered by Keilin and Mann to be the important metal of this enzyme! The kinetic studies that he carried out were very elegant and are very important even today. The second year, he worked on sulfhydryl-oxidation and showed the relation between the pKs of the sulfhydryl groups of four sulfhydryl compounds cysteine, cysteinyl cysteine, glutathione and isoglutathione. He showed the relation between the pKs of the sulfhydryls of these compounds and their rate of oxidation when catalyzed by minute amounts of iron. Then there was Bernard Jandorf, who took his Ph.D. with me in 1942 on DPN, diphosphopyridine nucleotide. He worked up a new method for its isolation. He worked up a new method for its manometric determination,

Page  158158 and he studied its distribution in different animal tissues. He also was from Germany originally. He is now chief of the Biochemical Division of the Chemical Center at the Edgewood Arsenal in Maryland. Altogether, I have the feeling looking back on what I call Phase Two of my life, which means from 1935 to 1959, as both a very happy and productive one. It was made so, by the flow of such a wonderful group of young men and women who as I always told them—if they once became members of the Department, whatever the capacity, they could never resign' So thatfs why I still get letters from them pretty regularly and certainly always when they need a new job or recommendation for a grant or a fellowship. Hal Christensen was my second Harvard Ph.D., Stotz having been the first. He is the one, that in many respects, I'm proudest of. This is because he took the time to have the experience, after taking his Ph.D., of working with clinicians. This made it possible for him when he was asked to head the Department at Tufts, to develop a department that the clinicians felt was good, and that the medical students felt was relevant to their careers, and this, in turn, made him the natural for the position of Head of Biochemistry at Michigan. He is the one of my boys whom I regard as most like me in his point of view toward teaching, research, and biochemistry in relation to medicine. He has never lost this point of view. I do want to put in a piece about Eric Ball because he and I ran the Department together after he came to Harvard in 1940. I guess I have VI 'A

Page  159159 already recorded that in 1935 we were a very small department. I made no changes initially. They came about naturally by people taking other jobs. When Logan left to become Professor of Biochemistry at the University of Cincinnati, this opened up a senior academic position in the Department. I had for some years had my eyes on Eric Ball. I met him first in 1932 in Italy and heard him give a paper there. It was so magnificent that I said to myself, "If ever I have the chance to get this young man, I am certainly going to do it." The opportunity opened up in 1940. I wrote to Bill Clark and asked him for permission to approach Eric, and Bill, being the gentleman that he was, gave me permission to approach him, but with great reluctance. It was Bill's hope that Eric would succeed him at Hopkins when he retired. I found that in order to get his appointment through promptly, I could not offer him more than Assistant Professorship because to get an Associate Professorship through at Harvard takes a year after you start to work on it. I didn't want to risk losing him, so I offered him an Assistant Professorship at a big increase of salary over what he was getting at Hopkins. Bill Clark certainly did not want him to leave Hopkins for less than an Associate Professorship with tenure, because Eric had already established himself. He had become very well known for his work on oxidation-reduction potentials of biologically important substances. I simply had to tell him that if he would come as an Assistant Professor I would get him an Associate Professorship immediately--at least do my best to do so. Fortunately,

Page  160160 I was able to deliver the goods. He had such a good reputation, that it was one of the few cases where I was able to also enlist Edwin Cohn's support on what I wanted to do. With both of us backing it and Conant being familiar with his work, it really was no problem in getting this promotion to Associate Professor. In 1942 or '43 when I was away half time in Washington, I found that, though Eric was taking care of things as I would do, nevertheless he needed the authority to take action when I was not there, and so we officially made him Acting Head of the Department until I returned full time. From then until I left in '58, we just ran the Department together. A Settee instead of a Chair! I would never take any action unless I asked him about it, and vice versa. After the war (1946), he was still an Associate Professor and Joe Wearn decided that he wanted Eric to be head of Biochemistry at Western Reserve. They offered him the job. When Joe had asked me for suggestions, I had, of course, recommended Eric--I couldn't do less. Nevertheless, I warned Joe that I was going to keep Eric if I could. When I took it up with Burwell and Conant, they agreed that we should offer him a full Professorship, and Conant did a very smart thing. He said, "In doing this I also am going to insist that his salary not be on your budget, but on a separate budget, and that he will have an amount along with his salary of $5,000 to help with having an assistant, secretary, technicians, etc." He said, "If we do it this way, and if something happens to you, Baird, suddenly, and we have to look for another person, the other person isn't necessarily going to have to have Eric

Page  161161 if he doesn't want to, like you had to have Fiske." He said, "This need make no difference in the relationship as long as you and Eric get along well, but this always gives him independence in case you do have a falling out, or if it seems better to go some place else in the University. If he can find another department in the University where he would be happier and more effective, he can pick up his marbles and go." This was a very good thing to do and it worked out well. It gave us the opportunity to be very frank with each other. Eric didn't always approve of decisions that I would make, and he would tell me so, very frankly. Sometimes I would take his advice and sometimes I wouldn't but this had nothing to do with our academic relationship because he wasn't beholden to me, academically at all, as head of the Department. I was still head of the Department. I could act unilaterally if I had to, but I didn't. I'd like to emphasize this. I just think that having a head of an academic department should have some continuity to it. Where you have short term rotation of chairmanships every three or four years, there is no real incentive to plan ahead. You don't keep your eyes open for bright young men that are coming along, keep track of them until you have an opening for them, so that the department can build up its weaknesses. I think our department was a very good department, not because I was good, but because I worked hard to have as many better young people it it as I could find and accommodate; better biochemists

Page  162162 in it than I was, that would make it a well rounded department, working at the important peripheries, and could supply the best possible biochemical teaching for the medical students. This was my goal! If you get good people like that, you don't need to worry about their bibliographies, you know, that comes naturally. One more secret: Eric and I, in all our years together would never add anybody to the staff unless we had met their wives. We laugh about it when we are together now. We have subsequently decided that part of our success during those years was because we picked good wives! Drc 0.: This can make a world of difference. Dr. H.: You can smell out in one dinner party with a prospective fellow and his wife, whether his wife really wants to come, or really is willing to have her husband work late nights and Saturdays and Sundays in the lab. Particularly the young ones. Or whether they want him to go out and get a good job with a lot of money, and so forth. Ifm telling you all of my secrets! Dr. 0.: They may prove useful to me some day. Dr. H.: We always started to revise our Biochemistry course in October of the year although we didn't start our medical school teaching until February 1. As I think I have recorded already, we had a departmental meeting every Monday at twelve o'clock in my office, where

Page  163163 we discussed anything that was on anybody's mind. This included everybody from professor to teaching fellows, if we had any teaching fellows. We seldom had more than two of them. This way I kept in pretty close touch with what was on people's minds, and often caught problems, such as whether a storeroom man was really doing his job, what we were really running out of and I would have to find some more money, before these things became critical. I am pleased to know that they have continued having these departmental meetings on Mondays even nine years after I've left. Before then, Folin had never had any kind of a meeting. He went into his lab and shut his door in the morning, and Fiske went in his lab. There were never any seminars, never any departmental meetings. Never a departmental secretary! He used the librarian next door to type letters when he had to. When the students came in for their semesters, hefd give his lectures, Fiske would give his, Logan would give his. Logan would have a teaching fellow or so who would work in the laboratory, and that was that. But we fought out--with great arguments, I might say--what the content of the course should be. Up to the last four years, I gave the first ten or twelve lectures .... then my department colleagues decided that my introductory lectures which treated the body as a physico-chemical system were passe. I'd start out with man as a heterogeneous system, and then work through each of these kinds of systems. The gas-liquid system would bring me right to the blood and the transport of oxygen and CC>2 and the liquid-liquid system would bring me right into osmotic things and the Donnan

Page  164164 equilibrium, and I could get in sodium metabolism. Then the extra-cellular-intracellular system would get me into potassium and magnesium metabolism. The acid-base balance was a big section while we were studying the blood0 Dr. 0.: You still have, I believe, in your files all the lectures that you gave. Dr. H.: Yes. I gave five of those ten lectures in Shiraz. To finish these remarks on our course; I would end with the solid-liquid system, the bone, and extracellular fluid, and that would get me into calcium and phosphorous metabolism. That would set the stage for the other boys, usually starting with Eric, who would give them the overall metabolic picture, and electron transport and then we would go through carbohydrates, lipids, proteins, hormones. But there were always new things coming in. I believe Villee, who was a biologist originally, introduced biochemical genetics to our medical students before other medical schools did. He got his Ph.D. working on fruit flies and always kept up to date on genetics as well as biochemistry. Incidentally, he wrote a textbook of biology which is now in its 5th edition and is a widely accepted college textbook of biology. The full citation for this book is Villee, Claude A. Textbook of Biology, Saunders, Philadelphia, 5th ed., 1967. I understand that he gets more out of his royalties from this than he gets as a professor at Harvard! He is a

Page  165165 beautiful lecturer, so clear, and writes so clearly on the board. We always gave him the metabolic cycles to teach because he did it so well. We had mimeographed sheets of lecture outlines and supplementary notes that we revised each year and distributed to the students. Dr. 0.: Did you have a lab manual of procedures? Dr. H.: Oh yes. It went through 6 editions during my tenure. We would never publish it because it fitted our course and what we wanted to do, and the minute you publish it then you get people who want you to put this and that in and to change it, so we only published enough for the medical students and staff and maybe fifty more for a few friends. This manual matched our facilities. No one else had 20 Van Slykes. They couldn't do the acid-base studies we did. I don't suppose that they use it anymore because they have a brand new kind of a course. We redid the manual every three or four years. We worked hard at this business and hoped we were giving the best course in biochemistry for medical students in the country. Not all of my colleagues in the department were as enthusiastic as I was about doing this0 But I insisted that we try. After all our medical student course only took 4 months out of 12. Dr. 0.: Many of them were probably more wrapped up in their own research.

Page  166166 Dr. H.: Oh yes. It's gotten much more so now, I understand. By and large, they liked me, and by and large they trusted me. We had a fine family relationship. If they didn't fit in the family, they didn't stay I guess. I don't think I had anybody leave in a huff. I left out such wonderful people as Westerfeld, for instance, who was in the department for a long time. I have only talked about people who were really related to me and my own research work. Dr. Westerfeld is one of the great professors of biochemistry in the country. (PAUSE) Dr. 0.: The two following vignettes on Dr. Moses Gomberg and Dr. Paul De Kruif go back really to the Michigan and Rockefeller Institute era. Dr. H.: When I was at the University of Michigan, I took organic chemistry under Professor Moses Gomberg, who was born in 1866. After having been educated in Munich, Heidelberg and Michigan, he became an Instructor in 1893 at the University of Michigan. He was Professor from 1904 until he retired in 1936. Though born in Russia, he emigrated to the United States while a young man. He made the important discovery about 1900 of the first organic free radical, triphenylmethyl. This means that though carbon has four bonds, only three of them were combined with phenyl groups, and it lacked the fourth bond being

Page  167167 satisfied. Van Slyke took his Ph.D. with Gomberg on an extension of this work with free radicals. Today, organic free radicals are one of the most important items dealt with by organic and biological chemists. Personally, he was one of the gentlest, most self-effacing persons imaginable. He would never go through a doorway before a colleague or a student. He retired from his professorship in 1936. He proudly took Van Slyke and me through his organic chemistry laboratories in order to show us the new equipment and improvements that he had installed that year. He said, "Just so my successor will have a good department to start with." What a difference that was to the usual inactivity that characterizes the last year of a professor's tenure. Dr. 0.: Paul De Kruif was a controversial figure, in a sense. Perhaps maligned by some, misunderstood by many. Dr. H.: Well, I knew Paul De Kruif quite well, particularly in his early years and mine, because he was taking his Ph.D. under Professor Novy in the Department of Bacteriology at Michigan at the same time that I was working as an assistant in physical chemistry. Since we both worked very late at night, we formed a habit of going to which ever laboratory the light was still on when we turned out our own. Paul De Kruif is known today primarily for his books written for the layman on medical or scientific subjects and for having been the science writer for Reader *s Digest. Actually, he was a very able scientist in

Page  168168 his youth. In 1915, he was working on his thesis, the subject of which was "The dissociation of microbic species." This was the forerunner of the recognition of type specificity by bacteria, which was, in a sense, the forerunner of Avery's, MacLeod's, and McCarty's discovery of the transforming factor which is found to transform one type specific pneumococcus into another. The transforming factor was found to be DNA. So you might say that the transforming factor was the forerunner of DNA, RNA, the amino acid codes and Nobel Prizes. He was a big bear of a man of Dutch ancestry from that part of Michigan, Zeeland and Holland, Michigan, which was settled by the Dutch. I think his home was in Zeeland. I have often described him as the Paul Bunyan type of man—large, muscular, vigorous, full of excitement about science and literature and women and life. During one of these sessions late at night when he's come to my lab, he'd just discovered H. G. Wells. He introduced me to the books of H. G. Wells. He also first told me about a promising Michigan graduate at the Rockefeller Institute named Donald Van Slyke, who was a "comer" as Paul said. It's the first time I ever heard the name. It was while I was still at Michigan--! think it was 1917-- that he finished his thesis and submitted it for acceptance by his thesis committee. At Michigan, theses had to be approved by someone from the Department of English. He had been flunked in Freshman English by an instructor named Brum. Dr. Brum, at the time Paul finished his thesis, was, I believe, an Associate Professor. So Paul asked that Dr. Brum be put on his thesis committee so he could show him he might

Page  169169 flunk him in Freshman English, but, by gosh, he was going to get his Ph.D. So it went to Brum for reading, and it came back all marked up with blue pencil with the statement that it would have to be rewritten. I was in the laboratory that Saturday morning when Paul got the news. He was a great friend of Bartell and came storming into the physical chemistry quarters, which were all connected from the student lab at one end to the professor's lab at the other end with connecting doors. Just like a bull in a china shop, he went stomping and cursing to the high heavens from one end of the lab to the other until we thought he had practically gone out of his mind, Finally, Bartell quieted him down, got hold of Gomberg and Novy, and after several days of cooling off, finally persuaded him to let them exchange Brum for another member--professor of the Department of English--on his committee. Then, with a compromise on the amount of the writing that had to be done, Paul eventually did get his Ph.D. But then he went off to the wars in Paris and had a high old time for himself, so that when he came back, he was divorced and eventually married again--a very fine woman. When he came back, through Van Slyke's influence, he got an opportunity to work with Dr. Flexner who kept a laboratory going even though he was Director of the Rockefeller Institute. Paul took up more work, as I remember, on the study of bacterial mutations. He had the habit of working at night, all night, and soon met the literary group including George Nathan

Page  170170 and Mencken, the famous Baltimore author of the American Dictionary. Paul had written an article published in the old Century Magazine, entitled "Our Medicine Men" in which he took the medical profession apart, and it had made quite a commotion, but it was well written and Mencken and Nathan and others said he was a born writer and that he should devote himself to writing popular science. He got acquainted with Norman Hapgood, whom, I believe, was the editor of Hearst International Magazine. Norman Hapgood wanted to expose medical quackery and so Paul did come out to California and wrote some articles about one of the kinds of quackery that was going on here--putting drops of blood in a machine that really didn't do anything and then saying that they could make diagnoses this way. As I remember, there was a series of two or three articles and one last one. I remember it was called "Ponce de Leon and the Ring-tailed Monkey." And this was about monkey glands. Somehow or other, I can't remember the details, he brought into it some correspondence that some pharmaceutical house had had with the Rockefeller Institute. When this was called to Flexner's attention, he fired him on the spot and told him never to come back. Dr. 0.: So all the while he was writing this material, he was still actively on the staff. Dr. H.: Actively on the staff and---Dr. 0.: Doing research at that time?

Page  171171 Dr. H.: Doing good research between midnight and dawn or 8 o'clock in the morning. Yes, he was very able and it has always seemed a shame to me that Paul as a scientist had this ending though I am sure he did a great service in a way. He may have laid the groundwork for the public's being willing for us to spend so much money in medical research—basic medical research—because such books as the Microbe Hunters, which was his first book after he left the Institute and others in this series, made a great impression on everybody and were popular books. Most people, of course, don1t realize that Arrowsmith, for which Sinclair Lewis gets the single credit, was really written by De Kruif and Lewis. That is, the first two-thirds of Arrowsmith--is what Paul De Kruif dictated to Sinclair Lewis when they teamed up to write this book. I believe it was dictated in England where they had gone to write. Dr. 0.: There is no indication of this in the publication itself. Dr. H.: I don't believe it is. I believe he was given a $10,000 retainer to collaborate with Lewis on this book by the publishers. Though I don't know whether this was in the original contract, he did get the movie rights. He told me this himself. The first two-thirds of Arrowsmith are so true to Paul's life and experience, that I can identify most of the characters. A few he names at the Rockefeller Institute, like Jack Northrop and Van Slyke. But the hero, Dr. Gottlieb, is described physically as Professor Novy. You can identify Professor Novy's physique, but his scientific ability is the combination of Novy

Page  172172 and Jacques Loeb, whom Paul worshipped. He sat at Loebfs table at every luncheon and for as long as Loeb would talk. The "McGurk Institute" is something like the Rockefeller Institute. The book begins at the "University of Winnemack," which is reminiscent of the University of Michigan, and in almost the first chapter, you encounter an English instructor who's named "Brumfit." And this instructor is painted as kind of an unsavory character, who tells questionable stories. He couldn't resist getting even with Brum again! Dr. 0.: Brumfit! Yes, I see. Dr. H.: I often wondered why Lewis or De Kruif didn't get sued by Brum. Dr. 0.: What was the reaction around the Rockefeller when this came out? Dr. H.: I don't know. I wasn't there. It was after I had left. I was in Chicago, I think. It was fascinating to read. As I said, the first two-thirds were very identifiable. I later saw Paul and he was about to take on the business of helping with the movie. I met him on the train coming from Bronxville to New York one day. We hadn't seen each other for many years. He told me that he certainly wasn't going to let it end the way Arrowsmith had ended, because he said it wasn't the way he had left it all. He dictated about three times as much as was published and then Sinclair Lewis left for the Riviera and said he'd whip it into shape. However, Lewis stopped after two-thirds

Page  173173 and invented the whole last third of Arrowsmith. You can tell if you read it today; the last third isn1t as good; it doesn't ring quite as true. So Paul finally had his chance in the movie to put his own ending back on Arrowsmith. Dr. 0.: This is interesting because that book even today is required reading for the Freshmen medical students at Johns Hopkins in Professor Owsei Temkin's course in the history of medicine. Dr. H.: Well, in a sense, you see, if you take those first two-thirds, it's one of your living biographies. Dr. 0.: I'll have to read this again. It's been many years since I read Arrowsmith. Dr. H. : Well, I'll end this by saying what a pity it was that Paul dropped out of science the way he did. I think the world lost a very good scientist. After the war, I ran into him in Boston and we sat out there on the lawn in front of our building, and I told him that I had seen his son down at Yale in connection with some of the war work. "Oh," he said, "How is he? I haven't seen him since he has grown up." He ended by saying, well, he'd guessed he'd made a mess out of his life. And that's the last time I saw Paul. Dr. Oo: I think one of the things we might talk about with some profit is for you to discuss your experiences and your work and the people you worked with in your various visiting professorships and some

Page  174174 of the foreign laboratories in your career. Dr. H.: I think I'll begin by mentioning some of my relations with Copenhagen because, as of today, I have now been there a total of seven different times. The first time was only for a weekend, but that was during my first trip abroad for working purposes which was in Berlin in 1925. I went up to Copenhagen to visit Professor Christen Lundsgaard who had just become the Professor of Medicine and with whom I had worked when he was in Van Slyke's department at the Rockefeller Institute. I fell in love with Copenhagen and the Danes that inhabit it on that occasion and I am still in love with Copenhagen. I didn't get a chance to actually work there for any extended period, i.e., for more than a few months at a time, but whenever we went abroad for any purpose, we were inclined to go first to Copenhagen and then decide where we would go from there, if anyplace. Sometimes, we did and sometimes we didn't. In 1939, I was invited by Professor Linderstr^m-Lang, who was then the Director of the Carlsberg Laboratory, to spend all the summertime I could spare in his laboratory. So, my wife, and son and I did spend about four months in Copenhagen on that occasion. That time I worked with Linderstr^m-Lang on developing a very micro-micro method for doing nitrogens on very minute amounts of organic material or tissues or cells. This, of course, was the year the war broke out and on more than one weekend during that

Page  175175 summer, it was rumored that the Germans would take over Copenhagen that weekend. There was a constant flux of scientists coming through from Eastern Europe. They were convinced that war was on its way. [End of Reel 4, Side IIJ

Page  176176 [Reel 5, Side l] Dr. H.: It was with a great deal of feeling that we parted with the Linderstr^m-Langs in August of 1939 because by then, I was as close to Kaj as if he were my own brother. We knew so well that it would be years before we'd see each other again. Linderstr^m-Lang was one of the leading biochemists of the world. It is a shame that he never received the Nobel Prize for his work. He belongs to that select category of people who are ineligible for the Nobel Prize because they do too much too well. He was first and foremost a great physical chemist. He made very important contributions to the theory of electrolytes and he did pioneer work on proteins, enzymes, protein structure, and then with his colleague, Heinz Holter, developed a whole new system of quantitative histochemistry. They developed the methods that give accurate quantitative results on pieces of tissue of histological dimensions. And out of this development, has come the present-day school which is best represented by Lowry on the use of quantitative histochemistry at the cellular, or indeed subcellular level, now. But Lang was more than a very great scientist. He was such a good violinist at the time he was the assistant to S^renson, who was his predecessor as director of the Carlsberg Laboratory, that he didn't know whether he wanted to be a concert violinist or a scientist. The decision was made for him by an accident in the laboratory where, when

Page  177177 he was holding his hand under a red hot porcelain crucible to carry it from one bench in the lab to the other, it slipped from the tongs and he had a contracture of his third finger, and was never able to play the violin again until 1947. He loved to sing, and sang very badly but very loudly. He knew all the Swedish and Danish folk songs. He would sit at the piano and play and translate these as he went along. During the war, when he had to keep himself occupied, he took up painting and he painted some of the most remarkably fine things—very serious, but very fine paintings. I don't know what has happened to them. He could draw caricatures. At meetings, he would always turn up with a bunch of caricatures. I have in my files one of me. He was a most remarkable fellow. Dr. 0.: Was he permitted to continue on in his position at the Carlsberg Institute by the Germans? Dr. H.: Carlsberg. Yes. He managed it. He managed it. But just! He was very much involved in the underground. He had such an open expression that apparently he succeeded. The Carlsberg Laboratory was above reproach and he dissembled well enough so that he was not even under suspicion until very late in the war. Both Lowry and Anfinsen were in the laboratory to learn the histo-chemical techniques in 1939, and '40. They were there in April 1940 when the Germans took over, Copenhagen, Denmark. One morning shortly

Page  178178 after that and I can't remember the date on this, but it was during the occupation, Lang told me that as he came from his home which was attached by an areaway to the laboratory, he glanced out the window at the back of the laboratory where there was a big walled garden, and there was a big black car that he recognized. It was the car of the local German official representative of the German government. I forget the name. Well, he promptly got hold of the man who was as much a colleague as he was his chief technician and ran the shop that made all the difficult apparatus for Lang, who said quite frankly that he was coming to work and he had found it downtown unattended, so he drove it out to the lab.1 Dr. 0.: Oh, my.1 Oh, my.1 Dr. H.: He said, "I was really scared." So he said, "Well, get it out of here as fast as you can!" The Germans never learned of this escapade. But I know another story about wartime in Denmark. In 1943, they were spiriting Nils Bohr out from Denmark to Sweden. He then went from Sweden to England, and from England to the United States so he could help work on atomic energy. I learned of his reaching England in December of 1943 when I was there, but I did not meet Bohr myself at that time. Lang, after the war, told me that the arrangements to spirit him away involved him. He was to pick him up at his house which was near the Carlsberg Laboratory and escort him to the place where the boat was. There they would row him across to the nearest Swedish island.

Page  179179 It had been decided that Linderstr^m-Lang should walk 50 feet or more in front of Bohr, so if a sentry were encountered, Bohr could duck in the bushes. Lang said, "I went along at this rate and I didn't know whether Bohr was behind me or not, but I assumed he was and when I came to the place where he was to duck down the path to the boat, I then went my 50 paces, and suddenly I found myself going (whistle)." He said, "I just couldn't let Bohr go without saying good-bye!" He said, "Then I ran.'" (LAUGHTER) This has nothing to do with me or science or anything else, but LinderstrtfSm-Lang was such a great person. I didn't see him again, of course, until 1950. No, that's not quite right. He did come over here around 1950. He made his first trip after the war to the United States about this time and then we went there and spent several months, four or five. We rented a house this time though ordinarily, we stayed with them at their house. There, I worked on a problem that he had also been interested in. The problem was to locate the site of the enzyme, gastrointestinal urease, but since there turns out to be no gastrointestinal urease except in the bacteria that are there, this later turned out to be a misnomer. Following that 1950 visit during which I had been asked to give an address at the Royal Danish Academy of Arts Sciences, I was elected to the Academy. Dr. 0.: The date of your election to the Danish Royal Academy was 1951,

Page  180180 Dr. H.: Most of our other trips were sort of social and I haven't recorded them on this chart. Dr. 0.: Am I correct in my impression that the Danes have made a great contribution to clinical chemistry in general as opposed to some other areas of the sciences. Dr. H.: They have developed a very sophisticated methodology for chemical analysis of large numbers of blood samples that works very well, but I don't believe that I would think of them as having made original contributions to clinical chemistry any more than, or as much as, I would think of Van Slyke's or Folin's contributions. Of course, 0. Siggaard-Andersen and P. Astrup are Danes and they have made an important contribution to acid-base balance technology which is good and practical. I'm delighted that it is beginning to be widely used. But you do have to have a very expensive piece of apparatus with a radiometer in order to do it their way. I can't help but feel that the fact that it is necessary to have this expensive piece of equipment, and you have to get people to learn how to use it that has contributed to its popularity. Once they learn how to use it, it's such an expensive piece that they've got to use it. Money for the purchase of such an apparatus in the United States has been available through the Public Health Service. Yet it was all unnecessary, because you get just the same results with the Shock-Hastings micro-acid-base method where all you have to do is have a gross of Wasserman tubes, and

Page  181181 select those with the same internal diameter. Then spend half a day making up solutions of phenol red and alkali and acid in accurately measured concentrations and sealing these tubes. You have practically permanent pH standards. (See Biblio. Ref. #75, 94.) Dr. 0.: Don't you think part of the attraction is that it is a new gimmick? Dr. H.: Yes, and the fact that it is an expensive gimmick. Also, I think the other thing is that it has come along when there are Professors of Medicine, who are capable now of understanding what it is all about and using it for diagnosis and guiding treatment. Actually, I'm amused, that every time I turn around, I get a new article or book or something in the mail on acid-base balance in medicine. Acid-base balance has come of age, and credit for its accurate measurement rightfully belongs to the Danes because the first accurate blood pH measurements were made by Lundsgaard and Hasselbalch before anybody else in this country did it. So, it's only fitting that they should do it. It's so nice to know that they do get a great deal of the credit, because so much of the work on the theory of electrolytes in physical chemistry has been done in Scandinavia. Arrhenius in Stockholm, of course; Bjerrum, Br nsted and Linderstr^m-Lang in Copenhagen are the great names in the physical chemistry of electrolytes. I might pick up the story with my one and only sabbatical, at Oxford, at this point. In 1952, I applied for leave of absence from Harvard

Page  182182 to take a sabbatical year. At Harvard, the rule was that a professor is entitled to a half year with full pay or a full year with half pay every seven years if it doesn't cost Harvard anything to have you on leave, and "if it can be arranged." I was never able to arrange it before. First, I had to get another professor in the department, so that meant I had to have a fellow like Eric Ball which I did in 1940. But I never could seem to find a block of a half year when I could be away without having to hire somebody else to do what I did. But Eric came to me one day in 1951 and said, "Look, I am eligible for a sabbatical, and if you're not going to take yours, I'm going to take it.'" So that made me arrange to get a leave of absence for the first semester of 1952 and be back in time to teach the second semester. I applied for a Fulbright professorship—or rather the Oxford people asked for me, Sir Rudolph Peters asked for me. So Mrs. Hastings and I went to Oxford in July and stayed until January. They were six glorious months. They were a great experience. In the course of which I received an honorary Doctor of Science from Oxford which pleased me very much. Dr. 0.: You were teaching there as well as doing research? Dr. H.: I taught and I gave all of the series of lectures that I gave to the Harvard medical students. That year, I had to give them twice, once at Oxford and once at Boston. Dr. 0.: Did you find a great contrast in the medical students at the two places?

Page  183183 Dr. H.: Very much. In the first place, they don't have to go to lectures there. So Peters warned me, he said, "Don't be surprised if there aren't any students there." He said, "There'll be some people there from the department, of course. But, the students don't have to go to lectures here. And if they go to one, they don't have to come back." So I was always very pleased that most of the students came. I don't know how many, I never took attendance. One of the great thrills I got out of lecturing there particularly on the transport of oxygen and the transport of CC^ was to do it in the same lecture hall and on the same floor and at the same blackboard and with the same bench in front of me that J. S. Haldane had used. Well, I was affiliated with Trinity College while I was there and after arguing a year after I had left, they sent me a notice the following year, in December of 1953, that I had been elected a permanent honorary member of the Senior Common Room. This is a very small honor in a way, because in actual fact it only meant that any time I go back to Oxford, I am entitled to pay for my meals at Trinity College. But, it also is something they don't do for everybody, so I took advantage of it when I was recently in Oxford in December 1967. The nice part of it was that this 1952 sabbatical gave me an extended period to see whether I liked to work in the lab again because from 1941 until then, that means ten years, I hadn't been in the lab to do any extended work. Dr. 0.: You: had been teaching and spending your time in Washington.

Page  184184 Dr. H.: Yes, and running the department. Peters took me right in on his problem of the toxicity of fluoro-acetate which he was still working on. He had already made the discovery that the metabolism of fluoro-acetate is converted to fluoro-citrate. The reason fluoro-acetate is a war gas and rodenticide and is very toxic, is not because it is fluoro-acetate, but because the cells don't seem to tell the difference between acetic acid and fluoro-acetic acid. They condense the fluoro-acetate and oxalo-acetate and make, instead of citrate as the next compound in the Krebs cycle, fluoro-citrate. It turns out that fluoro-citrate hitches on to the next enzyme, aconitase, and won1t get off and thereby stops the Krebs cycle. Then everything runs down and you get no more ATP, the potassium leaks out and all hell breaks loose. You get convulsions and death in pigeons and in rats. I understand that in dogs it is the heart that stops first. Anyhow, this is what happens. I had had experience with changing ions in the cerebrospinal fluid so I studied the effects of minute amounts of fluoro-citrate intracranially and placed within the cisterna. I found that placing the fluoro-citrate in the cerebrospinal fluid was very effective in producing convulsions. I developed a means of recording the onset of these convulsions. It takes them 30 minutes to come on. I did some other things on the side too, but it was the fun of being able to work concentratedly all day without interruption. Indeed it was Peters who, when we were working

Page  185185 over a rabbit one day, suddenly said he would have to go to London for some meeting and back off from the table and off he1d go. I would look up as he left and grin! And he would ask, "What is amusing?" And I would say, "Well, there but for the grace of God go ll" I found I liked to work in the lab again. Peters, the next year or so after that, having been head of the Department of Biochemistry i at Oxford for 35 or 36 years, decided to take a full-time job at the Agricultural Research Institute in Babraham, which is near Cambridge. He jumped the gun and became Emeritus before he had to at Oxford and took on this full-time job at Babraham which he held until he was 70. Two things were important to me; finding that I liked to work in the lab and then in 1958 having the opportunity to retire at Harvard and take up full-time research in La Jolla. His having jumped the gun at Oxford gave me the courage to do it too. Oxford was so full of exciting people and historic culture even if it was most uncomfortable to live through a winter there, that my wife wished mightily that I were younger and eligible to succeed Peters. She's never quite enjoyed any place as much as she did Oxford. I think I may have told you but I may as well read it into the record that when we first came out here to La Jolla and went to a cocktail party, I heard her reply to somebody, who said, "Well, isn't it wonderful that you and Baird have reached beautiful La Jolla!"--! heard her say, 'Veil, I think Baird went 3,000 miles in the wrong direction!" (LAUGHTER)

Page  186186 Dr. 0.: Her heart belongs to Oxford, there's no question of that! Dr. 0.: The date is February 6, 1968. We are again in the office of Dr. Hastings at the Scripps Institute of Oceanography in La Jolla. This morning we are going to begin our discussion of Dr. Hastings' multiple roles with the government. Dr. H.: Well, you see, my first contact with the U. S. Government in any official capacity began in November of 1917 when I became an Assistant Sanitary Chemist in the U. S. Public Health Service. I have already recorded those years up to 1921 when I was an employee of the Public Health Service, and under whose auspices I was to receive a Ph.D. degree. Having not gone on with my career with the government as a member of the Hygienic Laboratory in Washington, but having gone to the Rockefeller Institute instead, I have always felt a sense of responsibility to do anything that the Public Health Service ever wanted me to do. I suppose this carried over into other fields of government service, because my sense of gratitude and my sense of having not gone on and worked for them after I received my degree. However, I had very little to do officially with any form of government except for occasional ad hoc meetings that were called, until 1941. The year before, 1940, it was true that I had undertaken to do some wartime research on means of combating gas warfare, specifically lewisite and mustard gas, under the auspices of NDRC. That's the National Defense Research Committee which was formed, I believe in

Page  187187 1940. The NDRC was a committee of scientists which included such men as Vannevar Bush, Chairman, James Bryant Conant, Karl Compton, Richard C. Tolman, and the President of the National Academy of Sciences, Frank Jewett. The NDRC also had representatives of the military forces. It was initiated by Bush and some of his associates because they felt that neither the National Academy of Sciences, nor the National Research Council, an operating agency of the National Academy, were constituted to get the kind of current research done as was necessary to advance better means of conducting a war. Even though we were not, ourselves, yet in the war, they felt that it was essential that we get under way. This organization, the NDRC, had no responsibility for conducting medical research. In 1941, President Roosevelt authorized the formation of a more formal organization which would include the responsibility for medical research as well as for research in the physical sciences and engineering This organization was called the Office of Scientific Research and Development, known as OSRD. It was actually composed of two rather independent operating parts. Vannevar Bush was the Director of OSRD. One part, the continuing NDRC, under Conant, had the responsibility of doing research and development on all forms of waging war. The Committee on Medical Research, known as the CMR under A. N. Richards, had the responsibility of initiating and developing means of combating the effects of disease and injury as a result of military action.

Page  188188 My first knowledge of the Committee on Medical Research and my connection with it was obtained in a most mysterious manner. One day in June, 1941, the exact day I can't remember, I had an outside visitor in my department at the Harvard Medical School who, after lunch, wanted to see the Harvard cyclotron which was in Cambridge. I proceeded from Vanderbilt Hall in Boston after lunch with this visitor--!'m sorry I can't remember who it was--to Cambridge by taxi without informing my secretary that I was going anywhere. We went to the cyclotron and after inspecting it, being a hot June day, Dr. Arthur Solomon, who was there at the cyclotron, suggested we walk over to his house which was only a few blocks away, because he said the blinds had been drawn and it would be cool inside and that he had some beer on ice. So the three of us walked over there and were sitting comfortably sipping beer in Art Solomon's house. At that time he was not married. He had bachelor quarters. The phone rang in the middle of the afternoon. Art answered it, came in and said, "Baird, it's for you." I went to the phone and the voice at the other end said, "Baird, this is Jim Conant. I just wanted to warn you that you are going to get a call from Vannevar Bush to ask you to be a member of the newly formed Committee on Medical Research. I think this is something that you would not want to turn down. It will be a Presidential appointment!" To this day, I haven't the foggiest idea how he ever found out where I was; how his secretary or my secretary tracked us there, because Art didn't say anything when we

Page  189189 left to anybody at the cyclotron where we were going. But anyhow, this is what happened. Dr. 0.: Is it your impression that Dr. Conant had essentially suggested you as a member of this committee? Dr. H.: I am sure it must have been that way, though I have no direct evidence. Well, I did get the call and subsequently the Presidential appointment. From memory I can't remember when we held our first meeting, but the composition of the Committee on Medical Research as it was formed was Alfred Newton Richards, Vice President for Medical Affairs at the University of Pennsylvania, Chairman; Lewis Weed, Dean of Johns Hopkins Medical School, Vice Chairman; Alphonse Raymond Dochez, Head of Bacteriology at Columbia University; myself; Colonel J. S. Simmons, of the Division of Preventive Medicine, Office of the Surgeon General of the Army; Rear Admiral Harold Smith, from the Bureau of Medicine and Surgery of the Havy, and Dr. L. R. Thompson, Director of the National Institutes of Health. Parenthetically, a year later in 1942, Dr. Rolla E. Dyer replaced Louis Thompson as Director of NIH and as a member of our committee. Dr. 0.: I was rather interested in the composition of this group. I certainly understand the involvement of the various military services, and the fact that there was a bacteriologist, Dochez; a pharmacologist, Richards; biochemist, yourself; and the only appointment that I questioned was Dr. Weed as an anatomist.

Page  190190 Dr. H.: Weed was appointed because he was and had been for some time the chairman of the Division of Medical Sciences of the National Research Council. During the year between 1940 and 1941, when there was no representation of medicine in the NDRC, he had been very active in establishing wartime committees and had really mobilized the Division of Medical Sciences in such a way that if they had money, they were ready to get the wartime research done. It was a very important item and I am glad you brought that out. Dr. 0.: Well, that answers my question. Dr. H.: Indeed, in many respects, the fact that there had been these committees with very distinguished American medical scientists heading them and on them, gave us immediately, on our formation, a very large agenda of problems that had been identified as worth undertaking. This was a most amazing experience, of course, because we virtually had a blank check. The problem was how could we use it wisely—how to use the money wisely and get the most out of it in the shortest period of time. Our problem became one of setting priorities, almost more than whether we could do it. I might just as well stop at this moment because I might forget it, to introduce the fact that I have felt ever since my wartime experience as a member of the Committee on Medical Research that we may have been

Page  191191 responsible for the tremendous post-war expansion in medical research, in this country. And indeed, it may not have been an unmixed blessing, for the following reason. Because of the sense of urgency that we all felt, particularly after December 7, 1941, we attempted to get as much good research done as was humanly possible, as fast as possible, when a problem was identified, and when we had been assured by the Armed Services that it was a problem which they wanted done (technically we couldn't undertake anything unless they asked for it). Then, if one of the university scientists was identified as able and willing to undertake this research problem, a contract was drawn between OSRD and the university. There were occasions in which we felt the budget proposed by the scientist was too modest and that the work would go on at a more rapid rate if the budget were larger. We would say, "Look, if we give you a larger amount of money, can't you get this work done in a shorter time." This has been on my conscience ever since, because I think it has, sometimes, led scientists to get so much money for their research activities that they hired too many technicians and acquired too much apparatus for optimum progress. The very scientist whom we wanted to bear down and expend his best energy and capability on a research problem was virtually removed from personal activity on the problem. He became the administrator of a large operation instead of a personal laboratory investigator. Dr. 0.: This is very interesting, because I had the feeling in preparing for this session that perhaps this was really the first instance where the scientific community received large sums of money from the

Page  192192 government, which was, of course, continued after the war in the form of the NIH extramural program of the grant mechanism and so on. I'm very interested about your comments that you have mixed feelings about the way this had to be done, because of the necessity of the times. Dr. H.: May I make another insertion as it occurs to me? It has been reported and it was not denied either by Bush or by Richards when I asked them later whether this was a true story that prior to Conant's calling me, Bush had called Richards in Philadelphia. (Bush was head of the Carnegie Institution at that time) Bush, who always talked through his pipe and clipped his words as a good down East Yankee should, said, "Richards"--"Yes."--"The President has authorized me to ask you to be Chairman of the Committee on Medical Research under me, the head of OSRD." Bush said that. There was a long silence, and then he heard coming over the phone--"Jesus Christ!" And Bush said, "Not him, You!" Dr. 0.: While we are just getting started on this basic committee of CMR, may I ask candidly, did the group work well together, Weed, Dochez, yourself, Richards, et al? Dr. H.: I would say--all things considered--they worked very well together. I think that there is no doubt about it, although Weed initially was disappointed that he was not selected as the chairman. But there were apparently too many people that didn't approve of Weed's appointment as chairman of CMR. Weed was already chairman of

Page  193193 the Division of Medical Sciences of the National Research Council. Of course, nobody could have been a more wonderful companion on a committee than Dochez. He and I, though we hadn't known each other at all well before, promptly became very well acquainted and shared the same office all during the war. Dr. 0.: You have told me the story of how both of you discovered that you both had graduated from Shortridge High School.

Page  194194 [Reel 5, Side II] Dr. H.: Yes. That knit us together very quickly. The service representatives were very faithful in their attendance at the meetings, which were held every week. Simmons representing the Army, though he said very little, was attentive; Rear Admiral Harold Smith had been called back to active duty because he was known as "Research Smith" and though he said very little, he always sat next to me, and he would have had the projects that we were going to take up reviewed by other officers in the Bureau of Medicine and Surgery and he would have the written opinions of these reviews. As the research proposals came up, he would always slide these reviews over to me and then if there was discussion, I would say, "Dr. Richards, Admiral Smith has something he would like to say." He would never speak up on his own account. Thompson was only with us through the first year, but there is a footnote about him that I would like to enter. In the last year of my service as an Assistant Sanitary Chemist in the Public Health Service from 1920-21, he was one of the succession of Junior Public Health Service officials who inherited me as his administrative responsibility. So I had remembered him as the Senior Surgeon of the Public Health Service, who when he inherited me had come to New York to see whether I was working hard, and putting in my proper 48 hours a week for the Public Health Service. I had never seen him from that day until we both turned up as Presidential appointees on the Committee on Medical Research.

Page  195195 As members of C. M. R. we took our responsibilities very seriously right from the very beginning and if we hadnft, Richards would have insured that we did because he had a great sense of responsibility of not misusing public funds in any way, shape, or form. We attempted to be as careful and meticulous about reviewing and insuring the competence of investigators and the relevance of the problems as if we were acting for a Foundation--like the Rockefeller Foundation. Once approved by our Committee, it still had to be approved by Bush. He had the final authority. No contracts could be let--these were contracts and not grants—except over Busies signature. We, as a Committee, were very proud at the end of the war that of the 595 contracts that were approved by the Committee on Medical Research, that is roughly from July 1, 1941 to January of !46--of those 595, 593 were approved by Bush. There were two contracts disapproved by Bush. One of these was a contract to study the use of penicillin for mastitis in cows1 udders. The other was to investigate the problem of avoiding air embolism in cavities in aviators when they were at high altitude. Bush has subsequently said that it wasn't so much that he disapproved these two, though he did say that they had a low priority at the time, but he did not want it to be in the record that he had approved 100 per cent of the CMR recommended contracts, and that if he was going to disapprove any, these were the ones he was going to disapprove. A two-volume history of the scientific activities of CeM.R, was published after the war.

Page  196196 Dr. 0.: There was a whole array of things that CMR was involved in. Those that are perhaps best publicized in the published works that have been written about OSRD and CMR are the work on anti-malarials, blood and blood substitutes, penicillin. In December when I was here, you went into some detail off the tape on the very fascinating and important story of the development of the penicillin work under CMR which I hope that you will incorporate into your discussion. Dr. H.: Yes. Our involvement with penicillin was quite early. It was August, 1941 when Professor Howard Florey of Oxford, now Lord Florey, came to this country and called on Dr. Richards. Florey had taken up the study of penicillin after Fleming, who had discovered penicillin in 1928, had dropped further research on it. Florey had a brilliant chemist working with him, Ernst Boris Chain, who, I think, was originally Russian though he had also worked in Germany. Chain asked to work with him at Oxford, and Florey had suggested that he take up the problem of how to isolate the active substance, which we now know as penicillin, from the culture in which the Penicillium notatum mold was grown. Chain had been successful in making concentrates, though by no means pure preparations of penicillin, and these concentrates had been sufficiently active to be dramatically effective when applied topically on burns to prevent infection, and in maintaining the survival of mice, which had been infected with lethal doses of staphylococci. Florey and his two or three colleagues in his laboratory

Page  197197 had rigged up a bathtub and various home-made apparatus in which to process cultures of the mold. Actually, they grew the mold in bottles, but to do the extraction on a large scale, they had to resort to all sorts of home-made things. The British pharmaceutical houses were much too busy with their war activities and in maintaining their normal activities in the midst of the war to take on the development of a new substance. So Florey was advised to come to the United States and see if there wasn't some American pharmaceutical houses that might be interested such as Merck, for instance. Since A. N. Richards had for many years been a consultant to the Merck Research Institute, he was contacted. Well, Florey made such an impression on both Weed and Richards at this visit, at which I was also present, that Richards said that he would undertake to see what the Committee on Medical Research could do toward the development of penicillin production on a large scale. To this end, he consulted his good friend, George Merck, President of the Merck Company, and through him arranged to have a meeting of several presidents of leading pharmaceutical houses and their directors of research in New York. We met there in the fall of '41. All but one of these pharmaceutical houses agreed to undertake collaborative work on developing penicillin as a therapeutic agent. They were not to be reimbursed by the government for any of the development costs. They would have access to all the information from the government and the government laboratories, such as the Peoria laboratories, where mold research went on very actively.

Page  198198 We assured them that we would get them priorities for construction, that we would pay for any clinical trials for any of the products that they produced. Dr. 0.: Off hand, do you remember why that one pharmaceutical company elected to not participate in this? What were their reasons? Dr. H. : Well, they simply thought they could go it alone and either get penicillin themselves or some other antibiotic. Dr. 0.: I assume that you don't feel at liberty to give the name of that pharmaceutical company. Dr. H.: Oh, I don't think it is any secret; you can figure it out from the records. It was Lederle. It was more or less a kind of disappointment for me because Dr. Y. Subbarow (formerly of Harvard) was the Director of the Biochemical Research Laboratory of Lederle. Mr. Bell, the President of Lederle, who I knew very well, had brought Subbarow with him to the New York meeting. It was, I presume, a decision based on Subbarow's confidence that he was already well on the way toward its production and that they could do it with the facilities that they had and perhaps it would be less cumbersome than being involved with collaborative studies where they had to share all the information they had, and with no prospect of any patents being permitted. None of these companies, you see, engaged in the collaborative research, could have any patent rights of their own.

Page  199199 Dr. 0.: Did Lederle stick to their guns? Did they stay out of this collaborative work with penicillin? Dr. H.: Well, you are asking me something I really don't know for sure. As far as I know, they did. They weren't against having government relations, at all, I'm sure they had others. It was just that at this time, they didn't, anyhow. The other companies are a matter of record--! can't recall them all. All of these companies went very actively to work on this problem. At that time, the only way to grow the Penicillium notatum mold was in flat 250 cc. bottles and they had to be sterile at the beginning and sterile at the end, otherwise, no penicillin would be produced. They had to incubate for seven days before you harvested the cultures, and extracted the penicillin from it. This made work go very slowly to simply handle thousands and thousands of bottles so they promptly got to work on trying to adapt big tanks for the growth of the mold. It had to be aerated and aerated steriley. They experienced tremendous difficulties when they undertook this. So that as I look at this graph of penicillin production, I see that the first million units was produced and turned over for use in a patient by all these collaborating companies in about the spring of 1942. It was from the fall of 1941, until the spring of 1942 before the first million units, which is one therapeutic dose, was produced. Dr. 0.: The cost of that first million units must have been tremendous

Page  200200 Dr. H.: It must have been tremendous; I sometimes say it must have cost a million dollars. That's probably an exaggeration, but the first 100,000 units must have cost an awful lot. I should say that the first million units was used by Dr. Francis Blake, who was then the head of the Committee on Medicine of the National Research Council and he used it on one of his patients at Yale, a woman who was dying of septicemia. She survived as a result of this. But the rate of production did not get to the point where systematic clinical trials could begin until about June of 1942. At that point, the rate of penicillin production had reached only about two million units per month. [Refer to chart of Penicillin Production Rate] But Dr. Keefer was, at that time, an Executive Medical Director and he was given the responsibility of arranging the clinical trials. I can't remember exactly when he was put into that position, but this was a very important date. From that moment on, the rate of penicillin production began to increase logarithmically, at an accelerating rate. By January, 1943, the rate of penicillin production had gone up from one million units per month to ten million units per month. The reason I have these data in my possession is because all penicillin produced by anybody in any way in the United States had to be reported to Dr. Keefer. We had all the data up to the end of 1943, when the business of keeping records became so large that it was turned over to the War Production Board Allocation Order and they kept the records. After the war, I got their records and matched them with our records

Page  201201 and I have all of them. By the spring of 1943, the rate had reached 100 million units per month and Keefer decided that instead of using all of the penicillin that was produced on civilian cases, in order to determine the spectrum of its use and the optimum dosage and the toxicity which, at that time, was still zero, Keefer decided it was time to get penicillin used in military cases. But we had no luck in interesting the military in its use. We were feeling pretty frustrated. One night, one Tuesday night before I left to take the Federal to go down to Washington for my weekly three days in Washington, in the spring of 1943--I probably could even identify the date, if I went back to the diaries--Chester Keefer who lived nearby and customarily came over after dinner to give me the latest news, on this evening said, "Baird, when you get there tomorrow morning, you go right into Richards1 office and pound on his desk" and Chester pounded on the coffee table and said, "You say, Chief, we've got to get our penicillin out to Bushnell General Hospital, in Ogden, Utah." He said, "I have just had a letter from an old friend of mine from out there, a medical officer, who said we've just got these boys pouring in from the South Pacific with the most terrible osteomyelitis and you've got to get me penicillin. I've heard about what results you are getting with it." Chester said, "Tell the Chief to call the Surgeon General, and tell him we've got to send a man out there who knows how to handle penicillin." He said, "If he gets this far, tell him that Champ Lyons will go and he'll go tomorrow afternoon if he is ordered to go." So,

Page  202202 the next morning, I did. I walked in and pounded on the Chief's desk, and he looked up over his glasses, and he said, "What's that for?" I said, "Because Chester told me to do that."1 He said, "Why did Chester tell you to do that?" And I said, "Because we've got all these osteomyelitis cases out at the Bushnell General Hospital that have returned from the South Pacific and that penicillin would take care of their infections. He wants you to get permission from the Surgeon General to send somebody out there with penicillin to demonstrate what this can do, so that we can, now with enough production rate, start using it on military cases." Richards said, "I suppose you won't get out of here until I do that, will you?" I said, "No, sir." So rather reluctantly he picked up the phone and called the Surgeon General's office, and he didn't get the Surgeon General because he wasn't there, but he got a colonel who was Deputy Surgeon General--! think a man from Louisville; I can't remember his name either—but he said, "Okay, yes, you can send somebody. Who do you suggest?" I said, "Champ Lyons." The colonel said, "When could he go?" I said, "Chester says he can go this afternoon." And that was that! Champ did go and the result, the way this cleaned up the osteo cases was so dramatic, was from that moment on, difficult to keep enough penicillin for a continuation of our research on its spectrum of use and dose, or for, hopefully, chemical work.

Page  203203 I must put on record that I still had doubts at this time—this was by now the spring of 1943, late spring—that we could ever get production by biological methods up to a rate where it would be enough for the great mass of wounds that would occur when we really got involved. I rather nagged at Richards, because he wouldn't entertain the idea of allocating any of this penicillin for chemical studies. I had the naive idea, as a chemist, that the chemist had a chance on enough material to resolve the structure, and since we had all these tremendous organic synthetic chemists available to us at the pharmaceutical companies that the way to get a lot of penicillin fast was to get it synthesized. Fortunately, Richards didn't buy my solution, and stuck to his guns. Actually, chemical studies were not undertaken, except in whatever small sort of bootleg ways the different laboratories may have done, until late 1943, when the rate of production had gotten up to a thousand million units per month. Then something like one or two per cent was allotted to go to the chemists. This curve of penicillin production rate continued to rise so that by the middle of spring of 1944, we were able to release enough to hospitals generally, with directions for its use. By June, 1944, when D-day came, the production rate was up to 100,000 million units per month, enough for all casualties. To complete this, by the end of spring of 1945, the rate of production was up to a million million units per month and it was allocated for civilian use.

Page  204204 Dr. 0.: Perhaps I might make a copy of this graph with your permission, and we can incorporate it into the manuscript. Dr. H.: Yes. When I collected these data and plotted the rate of penicillin production against time, beginning August 1941, I had to plot it as the logarithm of million units per month. When I did this, it came out a perfectly smooth "S" shaped curve. This is the picture of the birth, growth, and development of an industry! It may be the only one in existence.' Because all the power, all the people and all the industries, all the scientists that could be usefully put on this problem to produce as much penicillin as it was humanly possible to produce, were doing it from 1941 to 1946 when this curve ends. I have a formula for this curve, and if I had only had had the formula in 1943, I could have predicted when it was safe to have D-day and enough penicillin for all the injuries., Dr. 0.: At what point in this development did the pharmaceutical companies turn to the brewing industry for the elucidation of this problem of mass production. Dr. H.: I'd have to look it up someplace, because I don't have it here. Dr. 0.: Certainly before the rapid rise of that curve.

Page  205205 Dr. H.: Yes. It is probably in late '42 or early '43, I would think. Dr. 0.: No. The actual date isn't really that important. I was interested by the comment that you had made off the tape in December, that it occurred to somebody that the brewing industry is accustomed to working with these large vats of fermenting material and their knowledge would be useful. Dr. H.: They had the know-how on how to keep enormous vats of fermenting yeast sterile for long periods of time. Their know-how was, I'm sure, of crucial importance in licking this problem. Some of the brewing industries so enjoyed getting into the business of making a therapeutic agent that they wanted to stay in after the war. Dr. 0.: Were some of the brewing companies producing penicillin, or at least growing or culturing penicillin, or did they merely provide the technical know-how? Dr. H.: No, I think they were making penicillin. Again, this is something I can't remember but I'm sure it's on record. Dr. 0.: I gather the pharmaceutical companies were not overly happy about the competition that might develop if this other industry became involved in making penicillin. Dr. H. : Well, not after the war. They were delighted to have them cooperate at the time. I must pay a great tribute to the pharmaceutical

Page  206206 industry, and to all those who collaborated with them in this effort, because there really wasn't any holding back. It was magnificent the way they exchanged information! Of course, the British did get into the act also. I can't remember exactly when they did and I don't know whether the data are available to plot a similar curve for the British industry. All I know is that when I made the trip, which I will describe as a separate section, to Russia in 1944 with Florey, he was able to bring some penicillin for use on patients in Russia, as was I. We had the feeling that maybe he brought almost all that was available to him, whereas, I brought only a very small fraction. So they were in the business of making it, and there was an exchange of information with certain of the British pharmaceutical houses. There would have been anyhow because some of these were subsidiaries of American pharmaceutical houses, or at least had a working arrangement with them. Before going on with the activities of the Committee on Medical Research, I'd like to stop long enough to pay a tribute to probably the greatest man from my point of view whom I've ever met and worked with. I say this deliberately, because until I started working with Richards, obviously it was Van Slyke. Dr. 0.: I'm very interested to hear you say this.

Page  207207 Dr. H.: Alfred Newton Richards was a person of such humility, such intellectual greatness and integrity and magnanimity, that I rate him one of the great men of the 20th Century. This doesn't mean that he was without human frailty. He loved his Manhattans and he loved to have undignified fun with his colleagues under the proper circumstances. But these were very rare occasions. He wrote the King's English almost Shakespearian with a touch of the Bible. He was such a perfectionist that I was never able to write a letter on his behalf, in an attempt to take some of the load of correspondence, that he didn't alter. We shared adjoining offices and Keefer would try to steer correspondence and appealed to me for decisions on things that we felt we could make equally well in order to remove the load from Richards. Everything was handwritten with him, he seldom dictated to the secretary. If one goes through my correspondence with Richards, you will find even for the simplest question or short letter, a sense of elegance about the phrasing, which is the way he thought. He, of course, was a great scientist in the first place. He and his young colleague at that time, Joe Wearn, in the twenties, were the first to cannulate the frog glomerulus and analyze the few micro-liters of glomerular fluid with micro methods that they devised long before biochemists got interested in micro methods. They proved the correctness of the Cushny hypothesis, that plasma is filtered in the glomerulus. For this, he should have received the Nobel Prize.

Page  208208 He was a magnificent teacher. He was a leader of a very distinguished group, as head of pharmacology at the University of Pennsylvania and when he became an administrative officer as the Vice President for Medical Affairs, he guided the University of Pennsylvania Medical School to greatness. No better selection could have been made as the leader of wartime medical research. Bush worshipped him as I did. Dr. 0.: He sounds like a remarkable man. Dr. H.: He died only last year, age 90. I was not there, but Joe Wearn was there the day before he died, which was his 90th birthday. Joe has told me that "the Chief," as we always called him, took his hand and said, "Well, Joe, I made it!" Having this close and almost continuous association with A. N. Richards for almost five years, without any doubt, was the great experience of my life. I remember one evening after we had worked late and were going to the Cosmos Club for dinner and walking along--- Dr. 0.: Massachusetts Avenue? Dr. H.: H Street it was. I was berating him for not letting some of that penicillin, which was being produced, assigned to chemists to solve the problem! And I felt this very strongly. I kept, as we were walking, trying to persuade him to see it my way. Finally, Richards said, "Baird, don't you think I have any feelings, whatever?" Which shut me up.

Page  209209 May I put another story in? Dr. 0.: Please do. Dr. H.: Another winter night when Richards, Wearn, and I had worked late, we came out of the National Academy of Science Building where we had our offices, and picked up a cab with a Negro driver. The driver said, when the three of us got in, "Where to, boss?" And Richards said, "To the Cosmos Club." Upon which the driver took his hands off the wheel and leaned back and said, "Can't take you there boss, that am a house of pleasure!" (LAUGHTER) This was during the period when you were not supposed to take taxis to any place of amusement. And it developed much later, I did pass a place that was spelled Kosmas Club, which was obviously, a "house of pleasure." I always meant to send that story to the New Yorker. Dr. 0.: Oh, yes. You certainly should have. Dr. H.: Particularly as at that time, in the old Dolley Madison House, many that frequented it were bearded, craggy old men. Dr. 0.: That's before the Cosmos Club moved to its present quarters. Dr. H.: It didn't move until after the war. Dr. 0.: That's a wonderful story. Anybody from Washington would appreciate that.

Page  210210 Dr. H.: I have before me, one of the drafts of the history of the CMR. I have before me the breakdown of the GMR-OSRD contracts and the expenditures for the five years that the OSRD was in existence. The total for CMR was just under 24 million for the five years, which is in sharp contrast to the 2 billion and more expended by our Big Brother, the NDRC, for the same period,, However, they got atomic bombs and we got penicillin and DDT and plasma fractionation, and anti-malarials, and blood preservation. Who knows which has done the human race the more good. I have just done a quick totaling of the expenditure assigned to the development and clinical testing in chemical exploration of penicillin. And it amounts to $2.3 million, of which $1.8 million was expended in the clinical testing and evaluation. So, less than half a million was expended on the research and development of penicillin. Dr. 0.: That really isn't much money when you consider what they came up with and compare it as you say with the budget of NDRC. Dr. H.: As my eye runs down here, I see we had contracts, with no funds from OSRD, on the chemical structure of penicillin for the following companies, Squibb, Pfizer, Merck, Abbott, Lilly, Parke-Davis, Upjohn, and Winthrop. They were official contracts. They did chemical research on isolation, structure, and so forth, and contributed to it and pooled their information, and were not reimbursed

Page  211211 one cent. The only sizeable university chemical research contract was with du Vigneaud at Cornell University, who received $166,000 for chemical studies of penicillin. Dr. 0.: There really was very little spent on synthesis until quite late. Dr. H.: Otherwise, I think it's of interest that the six divisions in which the contracts of CMR fell, spent between 2 and 5 million dollars a piece during the whole five years. In medicine, $3.8 million; surgery, $2.8 million; aviation medicine, $2.4 million; physiology, $3.9 million; chemistry, $2.3 million and malaria, $5.6 million. Dr. 0.: There really is an amazing amount of what we have today that are developments that came out of this funding of money. Dr. H.: Yes, even the preliminary work on adrenal steroids, though cortisone was not synthesized until after the war0 The groundwork was laid, and many of the substances that made its synthesis possible, were carried out as part of the wartime research. Also the development of gamma globulin and other blood plasma proteins was the direct result of the wartime work. [End of Reel 5, Side II]

Page  212212 [Reel 6, Side I, recorded February 6, 1968] Dr. H.: Five years after we started, in January 1947, the existence of the Office of Scientific Research and Development came to an end by order of President Truman, who sent those of us who had been appointed by President Roosevelt, a letter which said, "I should like, as we thus come to the formal conclusion of that undertaking, namely, the Office of Scientific Research and Development, to recall and repeat my expression of last January, of appreciation for your service to the country as a voluntary appointee of the Committee on Medical Research. Very truly yours, Harry Truman." We met at the White House for what was a very, to me, moving ceremony, simple though it was. Bush simply said, "Mr. President, on behalf of myself and my colleagues, we thank you for the privilege of having served our government," and the President said something to this effect, "I don't know how to thank you on behalf of the government and I don't know what we are going to do to enlist men like you to serve us in the future." (As we know now, twenty years later, the partnership of universities and government is stronger than ever). Dr. 0.: Wasn't there an attempt made, or I should say, wasn't there a program set up whereby there would be some sort of continuing committee of individuals such as yourself and the members of the Committee on Medical Research, when the OSRD was demobilized? It seems that I have come across a memo from Vannevar Bush in which he

Page  213213 states there would be something to keep this unified science concept in this country as a continuing working group, in one sense or another, even in peace time, because it had worked so well during the war? Dr. H.: Yes, and some of us were members of that rather short-lived committee. Dr. 0.: The name of that short-lived committee, apparently was the Research Board for National Security, which I gather lasted about a year. This letter which you received from the President of the National Academy of Sciences, dated March 25, 1946, merely states that the Secretaries of War and Navy have withdrawn their requests for the formation of such a committee. Do you have any further impressions as to why the committee was so short-lived? Dr. H.: No, not in the slightest, t modified by comments beginning p. 219] Dr. 0.: Well, that is very interesting. Dr. H.: It may be a chapter in itself, if we ever get to write it. This folder here is all about it. I will have a bit more to say about it when I finish discussing OSRD. We had one marvelous party at the close of the existence of the OSRD, on January 19, 1947 which was held at the Carlton Hotel, and all the

Page  214214 generals and admirals came who were accessible to Washington. Eisenhower was there. I sat next to Admiral King, they were all there. Vinegar Joe Stillwell, his general cronies, whom he hadn't seen for years and the Presidential appointees of OSRD. It was a very gay occasion in which all of us planned and contributed something. My contribution was a glass-blown gadget accompanied by a legend in rhyme. Somebody else, all of these are seemingly nameless, contributed a pocket addition of the history of OSRD or the Taming of the Shrewd. At the end of this fake ceremony, Bush was presented with the award, Doctor of Profane Letters. This citation is perhaps worth recording because it isn't anyplace else. Dr. 0.: Yes, I would like for you to narrate it here. Dr. H.: "To Vannevar Bush, Master of Differential Analysis and Human Integration, Persistent Prodder of Medical Minds, Enthusiastic Proponent of Penicillin for Cow's Udders, (that's the one he wouldn't approve), Expert Manipulator of the Administrative Needle, Leader in Research on Low Living and High Life, Intrepid Explorer of Nuclei (and I don't mean cells), Proud Possesser of the Illegible Hand and the Unmailable Vocabulary. For these manifold virtues and accomplishments, extraordinary, I have the honor to confer upon you the Degree of Doctor of Profane Letters and admit you to the company of Temporal Men." I have a sneaky idea that this was written by Richards. It

Page  215215 sounds so much like him. Dr. 0.: Could I get you to read into the record your contribution which is entitled "Final CMR Report". Dr. H.: O.K. Everyone had his chance to have fun. I produced a piece of glassware which Oliver Lowry had presented to me on a previous Christmas and that I regarded as one of my proud possessions It was a Rube Goldberg sort of blown glassware with attached circles, spirals, sidearms, deadends and with different colored fluids in different places. I took off the labels that had previously been on that were apropos for Biochemistry and starting at the bottom, I labeled the lower bulb from which all the rest of it stemmed, "The OSRD Retort" and then as it went up to a microcondenser, I labeled that "Still In". That was in honor of Steve Simmons, who, at each Committee meeting of CMR, produced some sort of cartoon. His prize one was on receiving orders from Bush to begin to de-escalate our program because Bush knew something we didn't know in July of 1945, namely, that things were going to be over by the end of the year. This offended Simmons and the rest of us tremendously, so he drew a rather scurrilous cartoon that day, representing the "Great Withdrawal." But then, to go on with this description, there is one sidearm that went around in circles, called the "Runaround" and there was the "Screwball Trap" and there was the "Army-Navy Merger," and

Page  216216 there was a "Manhattan Cocktail" and then there were channels and there was a "Vicious Circle" and there was the "C. W. Last Resort" and then the exit of this tube was the "Pen-is-still-in." To accompany this, when I presented it to Bush at this great farewell dinner, I read the following legend. "Sir, this is my final CMR Report. The greatest need of a Science Director is to have at hand a screwball detector, a means to smell from far away, the crank who has an egg to lay, the answer quick to Army's plea or Navy's wish to span the sea, to Gal-Tech Scientists who wish to make a submarine from fish, to doctors who would sterilize all insects which give birth to flies, to physicist who wish to fly, by fourth dimension through the sky, to inventors of all calculators of weasels, ducks, and alligators, t'was said, t'is not a chemist's war, so they hitched atoms to a star, they've labored long and labored well, and now they've blown the world to hell! You'll find the means in this machine to answer questions, great or mean. Insert into OSRD, the product comes out signed, V. B." Dr. 0.: That's beautiful. Dr. H.: Now you can see this, this was Steve Simmons' product for this final dinner. Dr. 0.: Do you have an extra copy? We will incorporate that also in the transcript.

Page  217217 Do any of the problems of this de-escalation or demobilization of OSRD, as far as the Committee on Medical Research is concerned, do any of the major problems stick out in your mind that were involved in this sudden change, from the all out effort to, either terminating the contract or transferring them to the Military Services? Dr. H.: Well, we did it very simply. I really don't know how the NDRC did theirs, but in January 1946, when we were ordered to close down, we held a succession of meetings and I don't remember how many active contracts we had at that time, maybe 200 or 225. We went right through them one by one and the routine was, Dr. Richards would say, "General Simmons," who was now a general instead of a colonel, "Does the Army want this contract?" "No." He said no to almost all. Then he would say, "Admiral Smith, does the Navy want this contract," and Admiral Smith said no to all of them, one by one, because he knew they were in the business of developing ONR. That was going to be their program which was not yet underway. Dr. 0.: Office of Naval Research. Dr. H.: Office of Naval Research. So then he would say, "Dr. Dyer, do you want this program?" and he said "Yes." So by the time we had gone through all of them, Dr. Dyer had almost all of them. Dr. 0.: Many of these then came under the National Institutes of Health? Dr. H.: These became the responsibility of the National Institutes of

Page  218218 Health and the National Institutes of Health were ready to take them over because Dr. Parran and Dr. Dyer had the year before, had an enabling act put through Congress which was really a very simple bill. It was the Cancer Act which had been enacted back in 1935 or 1936, and they crossed out "cancer" and inserted "medical" and this was a very broad act. It entitled them to do everything they have done since. All they needed was money and of course we could keep these going for a while with funds that were already appropriated so we simply transferred funds from the OSRD, when it passed out of existence, to the National Institutes of Health, Public Health Service. Those that were good were continued and those that weren't were dropped out. They promptly set up appropriate administrative machinery They already had a National Cancer Council which I had served on, or was serving on, I forget the dates of that, but then they set up a National Health Advisory Council, which I then became a member of after the Cancer Council. C. J. Van Slyke, the N.I.H. cardiologist who just died had a great deal to do with suggesting the study section and review procedures. I would like to put on the record that from its inception, Parran and Dyer and Van Slyke had the conviction, and indeed they put into operation, this conviction, that the Public Health Service should only be the agency whereby the scientists of this country were able to fund those research problems that they, the scientists felt were worth doing. At no time, did the thought that the Public Health Service would run the scientists of this

Page  219219 country, and what they did, ever enter into their thoughts. Dr. 0.: So that, from the very beginning, there was this study section concept. Dr. H.: Yes, that the people would apply to the N.I.H. for funds but they would be judged by their peers and then if their peers judged it worthy, it was simply the Public Health Service's responsibility to go to Congress and get the money and be the means of disbursing it. Dr. 0.: This has continued up to the present time. Dr. H.: Yes, this is hopefully the way it still operates now. It is very difficult to do it because of the size of the program. It is very difficult to satisfy the business-minded people in Congress that you can administer such a large sum of money without waste or overlap or mis-use of funds. Every investigating committee that has looked into this has been astounded by the small amount of mis-use, or inefficient use of funds that you can find. Dr. 0.: You actually were a member of one of these study committees, or investigating committees, in the 1950's was it? Dr. H.: Yes, that was the so-called "Long Report." Dr. H.: These remarks will be in reference to a short-lived organization called the Research Board for National Security, which was

Page  220220 initiated in November 1944 by a letter to the President of the National Academy of Sciences and signed by Stimson, Secretary of War and Forrestal, the Secretary of the Navy. The President of the Academy, Dr. Jewett, proceeded to act on this letter to set up such an organization. I was intimately involved in the beginning of the formation of this Board and discussed several aspects of it with Dr. Jewett. This Board was to be composed both of civilians and representatives from the Armed Services. It was undoubtedly stimulated by the realization that the scientists of the country had much to offer in research and development that would be essential for the future protection of our Nation. I was asked to head a Division of Biological Sciences in June 1945 and I proceeded to set up panels. However, in the Fall, I found that my academic responsibilities would of necessity take precedence over further such active participation in Washington affairs, and I found it necessary to resign. I don't remember the date of that resignation. Dr. 0.: I knew that you had written in November, but I haven't found the statement as yet. Dr. H.: The Board itself was disbanded in March of 1946 at the request of Forrestal and Patterson, who succeeded Stimson as Secretary of War. Meantime, however, in early 1945 in February, Dr. Dochez, who was also a member of the Board, and I exchanged memoranda on what

Page  221221 such a responsibility would require and what activities would be necessary to discharge such a responsibility. What struck me at that time was the fact that unless our Nation was geared to training and developing scientific personnel who were competent to make discoveries in the basic science areas, we perhaps would not be able to keep abreast of those nations who were continuing the output of scientists even in the face of the war. I was particularly alerted to this problem ever since I!d made my trip to Russia because whereas in the United States, we had been unable to have graduate students work for the Ph.D. degree in the basic sciences during the war, the Russians were deliberately identifying such men, even at the height of the war, namely January 1944, and preventing them from being in active service and requiring them to go back to universities for their training in their special fields such as physics and chemistry and biology and indeed even medicine. So I once put my thoughts down on paper to this effect, that it would be in the interests of national security to make sure that in any government support of scientific research, that there be provision for the training of scientific personnel in order to insure an adequate pool of basic scientists and good investigators. This was because through the activities of both the NDRC and the CMR in war time, we had really taken them off basic work and put them on applied work, in other words they engaged primarily in development and not research. In a sense therefore, we had dissipated one of our most important national

Page  222222 resources, the pool of investigators in the basic sciences and this indeed, required replenishment. The result of this was that as soon as my efforts in Washington on the CMR were no longer required, I spent a great deal of my extracurricular effort in trying to encourage the establishment of Fellowships, both pre-doctoral and post-doctoral, under both governmental and non-governmental agencies. I served on a committee of the Public Health Service which fortunately, Dyer also highly approved of, and called, to establish the Fellowship program of the United States Public Health Service, under NIH. In those early days the Public Health Service was reluctant to get into the business of establishing pre-doctoral Fellowships for fear they would run into conflict with the mission of the Department of Education. However, they did have a few, a very few pre-doctoral Fellowships. Fortunately, they did establish post-doctoral Fellowships in medical sciences which have been, life-saving to this country, One reason I was particularly sensitive to the need for Fellowships was because I was a member of the Fellowship Board of the Division of Medical Sciences of the National Research Council from 1937 to 1954. This Fellowship Board administered the funds provided by the Rockefeller Foundation, and it was the only money we had in medical sciences for many years. This permitted only 10 or 12 Fellowships to be made for the whole medical sciences from anatomy to surgery, in the whole United States.

Page  223223 Dr. 0.: This was in the 50's? Dr. H.: This was from the 30's on. This was the contribution of the Rockefeller Foundation. The Rockefeller Foundation never had any medical Fellowships under their name. The National Research Council Fellowship Board administered these funds which came entirely from the Rockefeller Foundation. So, that meant that before the war, there were very few available. Indeed, they were so rare that people regarded having had one as a high honor that they always put in their curriculum vitae and was a recommendation so high that it resulted in many people getting a chance at Professorships over their colleagues who were just as good. Well, I didn't limit myself to this activity. When I was made a member of the Advisory Council of the newly formed Life Insurance Medical Research Fund in 1946, most of my efforts at the committee meetings were to establish Fellowship programs, both pre and postdoctoral and they were established at that time and are still continuing, Indeed they are taking on more importance now than their grant program. Though I never served on the Merck Fellowship Board, I nagged at George Merck every time I could get ahold of him during this period to set up a Fellowship program and they did, particularly for chemists. When we established the Committee on Growth, for the American Cancer Society, again, I advocated the Fellowship program as more important

Page  224224 than the grant program because I believed as did Conant that if you can train good people, you get good research done. Somehow or other if they've really got good ideas, they'll get them done. They will get the money to do whatever it is their ideas prompt them to do, but you can't buy good people.1 You just have to make them.' Later this hobby of mine was continued when the Nutrition Foundation was founded and I was on its scientific advisory committee. It is still my conviction that the training of able scientists is the way to have progress in science. I must confess that I am personally much prouder of the M.D.s and Ph.D.s that I have had the privilege of helping with their scientific educations and research activities than I am of the papers I have published myself. I like to have my students' pictures on the wall in front of me at my desk and my reprints at my back. Dr. 0.: That's a beautiful expression, you've used that before. Dr. H.: In addition to having spent the six years working half-time as a member on the Committee on Medical Research of OSRD, I had other activities in Washington that gave me association with different governmental agencies. In 1943 I was made a member of the National Advisory Cancer Council, and in this period, our activities were restricted to very small amounts of money for grants to scientists. There was really hardly any extramural program under the Cancer

Page  225225 Council worthy of the name. I have forgotten the exact amount but it was not much in excess of 10 or $20,000. Dr. 0.: Dr. Ewing was on that Council was he not? Dr. H.: No. He was Federal Security Agency Administrator--1947-52. Hektoen was on, and Ivy was on, and Doisy was on. I remember these people. That membership terminated in 1946, but I was immediately put on the National Advisory Health Council which had recently been formed in order to set up the machinery for the Public Health Service's operation of the research programs which they had inherited from the Committee on Medical Research. Subsequently, to complete my story of activities for the Public Health Service up to the present time, I was a member of the National Arthritis and Metabolic Disease Council from 1956 to 1960. Incidently, this council is the lineal descendent of the Hygienic Laboratory with whom I started my scientific life officially in 1917. Dr. 0.: I've never really thought of it that way. Dr. H.: Yes, they re-named the Hygienic Laboratory, the Experimental Biology and Medicine Institute and then in the 50's when, after Congress had set up the Heart Council and Cancer Council, I presume there were a lot of the members of Congress who had neither cancer nor heart trouble but had arthritis trouble, and they wanted the

Page  226226 Public Health Service to build a new institute, under Sebrell's administration as Director of N.I.H. (1950-55). Finally to avoid having to build a new institute, he re-named the Institute for Experimental Biology the National Arthritis and Metabolic Disease Institute. Dr. H.: When that term was over in 1960, I was appointed a member of the National Advisory Heart Council. I remember so well that at the first meeting of the Heart Council that I attended, I found myself in the presence of a number of men whom I did not know, whereas in the Arthritis Council I had become quite intimate with all my fellow members. So I felt rather strange and not at home. As I swung around in my chair, I saw the secretaries of the several study sections sitting in a satellite row of seats, and I suddenly felt very much at home because I had lived with these same people for the four previous years. I swung back to the table and interrupted whatever conversation was going on, with the statement "Oh.1 I now feel very much at home here because I am really surrounded in this row with the people who provide the continuity for all our programs]" and this endeared me to the hearts of all these study section secretaries and they sent me a message that they were very pleased that their efforts were appreciated by somebody. Dr. 0.: I am sure they sometimes don't get that feeling.

Page  227227 Dr. H.: Well my service on the Heart Council was up in '64 which made this at that time, a record for having been a member of four NIH Councils. I guess it is now surpassed by Mary Lasker and maybe other people. My service to the Councils and the Public Health Service was recognized by a surprise presentation of a very handsome and large framed citation for service for 47 years to the Public Health Service, and it was signed by the four living Surgeon Generals, Parran, Scheele, Leroy Burney, and Luther Terry. That being over, I was then appointed as a consultant to the NICHD and a member of the training committee for the Aging Program, a position which I continue to hold. Meantime, at the close of the war in 1946, the Manhattan District became the Atomic Energy Commission's responsibility. One of the first actions of the Atomic Energy Commission, was to authorize the formation of a Committee on Biology and Medicine to create a program of research in atomic energy in relation to biology and medicine. I was first a member of the Board of Review which met every day, all day for a week and listened to members from the biology and medicine areas who had been involved in the Manhattan District. At the end of that week, we brought out a report, submitted it to Lilienthal, Chairman of the Atomic Energy Commission, to the effect that they should have a strong program. I was a member of the first committee that was set up for a three-year term. From then, until 1963, I remained a Consultant to the Director of the Division of Biology and

Page  228228 Medicine in Washington and was frequently used and asked to come down and help him with his problems. The Director that I refer to, of course, was Shields Warren whom I previously described, as to how he became the Director. Also, from 1955 to the end of '57, I was for two years a member of the Advisory Committee of the Oakridge National Laboratory in Biology. Then there was the appointment as one of the two Harvard trustees to the Associated Universities, which was created to form and manage the Brookhaven National Laboratory. This was one of the most interesting extra-curricular jobs that I ever had. It was in this period that I was able to help them by persuading Van Slyke to come as Deputy Director for Biology and Medicine. There was a gap then, of no association with Brookhaven until 1956, when I was appointed to the Visiting Committee to the medical department and served in that capacity for 2 terms, in other words until 1964. I was chairman for the last two years. I am still a research collaborator on their rolls, but I never seem to get there to do any research. I had two brief contacts with the Army. One was on an advisory board to the Quartermaster Research and Development Department, from 1955 to 1958, and from 1956 to 1962 I was a member of the Advisory Board to the Walter Reed Institute for Research. This again I found very rewarding because during this period, Colonel Richard Mason was the

Page  229229 Director of the Institute, and he was making valiant efforts to establish distinguished departments in the Walter Reed Institute that would be headed by distinguished civilians that would provide a core Research Institute unit that would make the circulation of medical officers of ability a profitable experience as well as to conduct important research relevant to the health of army personnel. Unfortunately, he was rotated from this position and his successors have not maintained the same kind of spirit around the place, so practically all of these good people that he had assembled have left. This completes my strictly official government activities but perhaps in this connection, it should be mentioned that as a member of the National Academy of Sciences which is a quasi government institution, since 1939, I have been involved in various activities that the National Academy of Sciences has been asked to undertake on behalf of the government. I have also been a member of the Fellowship Board of the National Research Council which is the operating body for the National Academy from 1937 to 1954, and chairman from 1951 to 1954. This was the period during which I developed my conviction that we needed nationally a much larger program, both post-doctoral and pre-doctoral for Fellowships. Dr. 0.: So this really started before World War II. Dr. H.: Yes. Heavens, we used to get a hundred applicants of brilliant people running all the way from, as I said, anatomy to

Page  230230 surgery and we could only pick one in ten. That's all the money there was. I was also a member of the Division of Biology of the National Research Council from '44 through '55. This was in order to give liaison between the Division of Medical Sciences and the Division of Biology with our activities on the Committee on Medical Research. Perhaps I failed to mention in describing my activities on the Committee of Medical Research, that I was the leg man. I was young at that time. At least I went in young, and I came out old, but I was the one who had to chase around and do things. Richards couldn't, Weed couldn't because he had too many other things to do. Dochez couldn't because he never did move around much. I even was a member of the Board of Food and Nutrition there for a while. Another thing I always like to remember, probably not of great importance in my life but I still think it has something to do with other peoples' lives was the following: One early Spring day in '45, I was sitting between "Dusty" Rhoads, C.P. Rhoads and Milton Winternitz, who was head of our division of treatment of war gas injuries. Rhoads and Winternitz both wanted to exploit the new steroids and new chemical agents, the nitrogen-mustards, in the study of cancer. Out of this conversation they had thought maybe I could get Richards to give them permission to have these two groups of chemicals for research prior to the termination of OSRD. Well Richards said no. But out of this conversation grew the idea that we ought to have, within the

Page  231231 N. R. C. Division of Medical Sciences, under Weed a Committee on Abnormal Growth, which would include not only cancer research but other growth abnormalities. So the three of us went to Weed and asked Weed if he didnft think this was a good idea to form a Committee on Abnormal Growth. He did because he could do that with a stroke of a pen and each of us agreed to form a panel. I was interested, very frankly, in capitalizing on the developments that were coming in quantitative histochemistry, for which I knew Lowry was so good. Gersh was another one, and I wanted to enlist Frank Schmitt's interest. I undertook to form the panel on histochemistry and Rhoads on nitrogen-mustards. I've forgotten the names of the panels exactly. Before we were able to even hold a meeting of our panels, Weed was waited on by representatives of the American Cancer Society, who asked him to form a committee within his division for the disbursement of cancer society funds for research and training. They wanted this to be called the Committee on Growth.

Page  232232 [Reel 6 - Side III Dr. H.: As I said, Weed had been asked to form a committee to administer the funds of the American Cancer Society, which they now had available in large amounts for basic research and training of people. They wanted it to be called the Committee on Growth and Weed said, "I have just formed such a committee" and then informed us that our name was changed from Committee on Abnormal Growth to Committee on Growth and then he made certain additions, so it was a larger and a more representative committee. Murphy and Little were among those added. Dr. 0.: Murphy of the Rockefeller? Dr. H.: Yes. At any rate, I stayed as a member of the Committee on Growth in charge of the sub-panel on biochemistry for two years, '55 to '57. I note looking down this chart that I have in my hand that I had five Washington, government activities all at once, from '45 to '47. There was one other important NRC committee that I must make note of, and that was in 1951, I became a member of the Committee on Atomic Bomb Casualties, (ABCC). This had been formed immediately after the war by the National Research Council to carry on under contract for the AEG, follow-up studies on the survivors of Hiroshima and Nagasaki bombs. At that time I was a member of the Committee on Biology and

Page  233233 Medicine, AEG, so I knew the problems of the initiation of the enterprise from the AEG standpoint. I was glad to be a member of this committee and use my experience as a member on the very large problems that came from trying to staff this study in Hiroshima with sufficiently competent, medically trained people because it was largely routine examinations of well people in large numbers and itfs not really a very challenging experience. In that connection, perhaps I should mention that in 1956 when I was still a member of the Atomic Bomb Committee, there was a crisis in which the then Director of the Casualty Commission in Hiroshima had fired one of the young doctors who against his orders had started some research that the Director said he couldn't start. He had no authority to either hire or fire, because only the National Academy of Sciences could hire or fire and they had delegated this responsibility to Dr. Keith Cannon, who was Chairman of the Division of Medical Sciences. Keith had wired back, "You can1t fire him." Upon which it was decided that Cannon should go out and that I, representing the National Academy, should go with him to try and get this straightened out as amicably as possible. We flew out there together, and over the first weekend we were there—we were there just two weeks, I had gone home with the chief of the medical department, an internist from Stanford. He lived in the compound where all the rest of the staff lived and after dinner on Saturday night, his next door neighbor, a Nisei, who was a staff doctor, came over and in the

Page  234234 conversation learned that I was an avid fisherman. The compound, I should say, was at the edge of the Inland Sea and there was a sea wall within less than 100 yards of where we were living. So this Nesei doctor said if I would like to, he would show me how to fish Japanese style the next morning. After breakfast, Sunday, I went out with him and he supplied me with a long, very flexible bamboo pole, and it had on it a very, very fine filament. I wouldn't use it as a leader, it was so fine. At the end of that he tied a much finer sort of spiderweb leader and then a tiny little gold hook, which he then proceeded to cover with lots of little earthworms. So you couldn't see the gold hook, it looked like a little gob of worms floating in space. Indeed it almost did. Then very deftly he taught me to flick it out as far as it would go and pretty soon I got a tug and pulled in a little fish. The fish varied from 3" long to, at the most 5" long. As soon as he saw I had the hang of it, he left me there and I proceeded, at the edge of this stone parapet, to enjoy myself, very much. Then I was conscious that somebody was standing at my shoulder. It was one of the staff that I had met the day before. I kept on fishing, and said something like, how are things going and that was all that was needed for him to tell me how things were going, from his point of view. When he got through, he went back to his house. After a respectable interval, somebody else came out of their house, came and stood at my shoulder and I kept fishing. I never had to look at these fellows at all. I'd give a little leading question now and then. Anyhow, in about an hour I had had about four such interviews

Page  235235 behind my back instead of face-to-face. Having collected all the information I needed, I rolled up my line, took my fish and went back and said well my job is done and I can go home. The thing that impressed itself on me is that I had wondered how I was going to get this information, and I had considered having them assign an office to me and then call these fellows in one by one. I never would have been able to get near as much, nor would I have had the feeling that I was getting the low-down as I did with this experience. I am a great believer in what fishing does for people. Dr. 0.: It bares the soul! (PAUSE) Dr. H.: This will be a brief account of what I like to call the Micro-mission on Medical Research to Moscow. It started in the late Spring, 1943, when the activities of the Committee on Medical Research were at their height. I identify it in my mind as the period in which our penicillin production had reached the point where we wanted to get it to try it out in military sources. It was during our period of acceleration as an agency for getting war research done; I couldn't have been busier. The United States government, meaning, I guess, the State Department, received an invitation from the Soviet Government to exchange information on certain medical problems which were considered of mutual

Page  236236 interest. This invitation was referred to Bush and by him to Richards, who was Chairman of our Committee on Medical Research. After a long drawn out series of exchanges, which I was never a party to, it was decided that ten subjects of mutual interest could be discussed by approved representatives from the United States, Great Britain and Canada. I was asked by Bush to represent the United States. I went to Canada and discussed with the Chairman of the Canadian Research Council, whom they would like to send along, and after some consideration they decided that they would leave it to a British representative and me. Then there was a protracted attempt to get Great Britain to name a representative. Mellanby who was then Executive Secretary, which was the highest officer of the British Medical Research Council, I think it is called, procrastinated on naming anyone. Meantime, the ten reports were written by the authorities in the subjects which were being studied under contract with OSRD. These ten subjects were British Antilewisite, BAL, which was a discovery by Sir Rudolph Peters and his colleagues in the Department of Biochemistry at Oxford. I might say, a biochemically tailored and logically developed discovery, not just an accident. Penicillin which we had developed but had no share in discovery; typhus vaccine, in which we used egg chick embryo as the source for growth; plasma fractionation which developed from the work of E. J. Cohn; the treatment of malaria with atabrine, because we had

Page  237237 no other substitute for quinine at that time; surgical problems, how the wounds, burns and shock were treated; insecticides, because by then it had been found that DDT was remarkably effective. The eighth subject was sterilization of air; the ninth one was how to combat athletes foot, and lastly the advances then made in military goggles, particularly for aviators. Well anyhow, we had these ten extended reports prepared; they made a big thick volume about three inches. These were then cleared with the various military associates and they were of course, sent to and modified as our Canadian and British colleagues suggested. I think I was alerted from August or September on, I can't remember without looking up a diary. There was the problem of just how we would go and when we would go. Part of this was due to the fact the British had not let Bush know whom they would nominate to go with me. In November--! had had all my shots, I had my special passport, I was ready to go at anytime but I had gone down to Washington for a routine meeting of the CMR. Then Bush said, "I've decided not to wait any longer for the British. I am going to send you." I called my wife and said I needed some clothes and she brought them down that night. Shimkin and I, who was a member of the Public Health Service, at that time working on cancer research for the National Institutes of Health, took off at 2:00 p.m. on November 24, 1943. Dr. 0.: Was Dr« Shimkin along primarily as an interpreter? You were really carrying the message.

Page  238238 Dr. H.: Yes, he was my assistant and interpreter. This had been a last minute thing that had only come about a week before we left when we were called by Chip Bohlen, now Ambassador Bohlen but who was then in charge of the Russian Desk at the State Department. He said they just had a message from the Russians that I would be permitted to bring my own Russian interpreter. Could I find one? Well the Russians that I knew or the scientists that speak Russian were very few. The ones I knew, I would not want to travel with on a mission like this and Dyer suggested Shimkin to me. I interviewed Shimkin, who seemed all right to me and I took him over to the State Department. I donft know whether Bohlen gave him an adequate examination in Russian, because I don't know how good his Russian was although he had spent a term in Russia. However, he declared that Mike Shimkin was suitable and could serve as an interpreter for me. So without knowing Shimkin at all, we took off. I might as well say that I was terribly annoyed with him on the very first leg of our trip. We did stop at New York, took off from there at 5:30 that same day but the next stop was Stephenville, Newfoundland, where we arrived at 3:30. As soon as we took off on this next leg, Mike started wandering around the plane and talking in a very loud voice and sometimes belligerent manner to the Colonels and military who were also on the plane. Since we were travelling under secret

Page  239239 orders, nobody was to know that we were going to Russia. Particularly since I didn't know him very well, I was both worried and annoyed, so I asked him to come back to his seat. This wasn't a bucket seat job; it was a DC-4, but very primitive. I said, "Mike, from now until we land in Washington, I'm the boss and you are not to discuss anything with anybody unless I say you can." So from that moment to this day, he always calls me "boss". I'd brought a little pocket chess set along, to keep us amused, and I said, "Do you play chess?" and he said, "Yes, a little," and with that, he checked me within about three or four moves and we set it up again and after the third time, he beat me three games very easily. I'm not a good chess player, but I am an average, irregular chess player. I said, "Good Lord, MikeI Why didn't you tell me you were an expert? Where did you learn?" "Oh," he said, "I was captain of the chess team at the University of California!" I said, "Well, this isn't going to be any fun for you or me; do you know any card games?" He said, "Yes, I know cribbage," so we started cribbage and we kept a record and played thousands of games and I came out about five ahead. Well now, this isn't getting us to Russia is it? We landed in Prestwick, Scotland in late afternoon. It was practically dark, about 5:45 p.m. on Thanksgiving day and parenthetically I should say that we were the last plane to take the northern route and get through. The one behind us never did get through and they ferried through the Azores from there on. We had Thanksgiving dinner with the Air Force

Page  240240 in Prestwick then went on to London the next day. There began one of the most irritating experiences of my life. We had started with a 2 priority on our transportation, and were raised to a 1 priority by a Dispatching Officer, a Major in London when he discovered I was traveling with a letter from Roosevelt. This Major said 'Veil you have got to get on your way.111 and raised our priority to a 1, but still we couldn't move and we didnft get away from London until the 16th of December. That's 20 days. Dr. 0.: Primarily because of weather? Dr. H.: No, this was because, unbeknownst to us, the Tehran Conference which was held between November 28 and December 1, 1943 was on. It was followed by the conference in North Africa. In any event, they were unwilling to let anybody start toward Tehran which was to be next destination until the conference was all over and everybody was back home safely. Dr. 0.: Security reasons. Dr. H.: Security reasons. Of course I didn't even know the conference was on until it was all over. Finally we took off. But before that I should say that I went to Mellanby, Sir Edward Mellanby in his office with Dr. Joseph Ferrebee, who was our CMR representative in London at the time and an old friend. When I arrived, Mellanby said, "Well it looks as if you people are serious about carrying out this

Page  241241 medical research mission to Moscow. Of course I don't approve of it, because I never had any use for those Russians ever since they confiscated all the property of the British there when they took over." He probably lost some himself. He said "Florey has just gotten back from North Africa, I'll see if he would like to go along with you." Dr. 0.: So that is why there had been no action on it. He had just been sitting on it on his own. Dr. H.: Yes, he wasn't going to do anything unless he was forced to. There was another reason why I found myself in London because I don't think I really told the story of leaving Washington quite straight. The week before I actually left, Bush had said, "You are going to go even if you have to go alone." When I got down the next week, he said, "Instead of your going straight across to North Africa and on by yourself, I've got a job for you to do on the way in London. We don't seem to be able to get things straight in our relations on patent rights and distribution on potential antimalarials which are being made by British houses and American houses." He said, "I've got John Conner here who is our attorney," (the one who used to be the Secretary of Commerce and formerly President of Merck but he was a young fellow who was the OSRD attorney) "and he will brief you on the problem". It was a problem of how to both protect the British companies and the American companies and still have exchange of information. Bush wanted to draw up something that was legally business-like

Page  242242 and typed, but he couldn't get a firm statement out of anybody in Britain as to whom he should deal with, who had the authority to sign for the government as his opposite over there. Well, this is the main reason that I turned up in Mellanbyfs office. I explained to him that Bush had to know who was his opposite and who could legally sign for Britain if he could get the different pharmaceutical companies together to consider the proposal of the Americans so they could get things shipshape. Mellanby said, "Well I don't know whether I've got authority to sign for the government or not. Wait a minute, I'll find out." He picked up the telephone and called one of the cabinet ministers who had the responsibility for the Medical Research Council and said, "I say, Vannevar Bush, Head of the OSRD wants to negotiate an arrangement, a binding legal arrangement with our companies about these potential antimalarials which they are developing. Do I have authority to sign as representative of the Government for that or not?" So he hung up the phone and said, "He says I do.'" I really got a kick out of that! Well, I got that job done though I later had toh ave a meeting with Sir Robert Robinson of Oxford, C. R. Harington, Head of the Medical Research Institute and Heilbron, Professor of Chemistry, Imperial College. After that we had to twiddle our thumbs trying to keep warm. I got a bad case of influenza and bronchitis. We took off, in a bucket-seat job, from Prestwick, on the 19th of December, 1943. Dr. 0.: You went back to Prestwick?

Page  243243 Dr. H.: We had to go back to Prestwick to take off. We were there for two days, from the 17th to the 19th. That was a God-awful experience. We couldn't get warm at that time of year in Scotland, you know. It was saturated with water-vapor and just above freezing. We took off, with our destination, Marrakesh, Morocco. The night before we left, at dinner, I sat next to an American Army Colonel who had just gotten back from Marrakesh and when he identified me he said, "Oh, when you get to Marrakesh be sure and look up Elliott Cutler. Colonel Cutler was the Chief Medical Officer for the American Expeditionary Force and was in charge of medical affairs for the army whenever they decided to make the trip across the Channel. Pete Churchill, (Edward D.) who was Professor of Surgery at the Massachusetts General Hospital, as Elliott Cutler was Professor of Surgery at the Peter Bent Brigham Hospital, had been in charge of all the medical operations in the North African affair. Of course, by that time they were on Sicily and I guess indeed had a foothold on Italy. Pete had seen a lot of action, and indeed he was screaming for whole blood. He didn't care about these Cohn fractions, all he wanted was whole blood! That was because the Army wasn't supplying enough whole, at that time, blood. We (CMR) hadn't done much of anything on it either. I think it was a big oversight on our part. Anyhow Cutler was stuck in Marrakesh because he couldn't get himself more than a #3 priority, and a #3 priority didn't get you anywherel

Page  244244 This Colonel at Prestwick had said, "There is no telling how long he will be stuck down there, you had better look him up when you get to Marrakesh." Also, on this plane, a bucket seat, as fellow passengers were half a dozen fellows who spoke French and hovered to themselves in one part of the plane and didn't mix with either Mike or me. If you couldn't mix with Mike, you just didn't mix, because he was the "mixingest" guy you ever saw. He tried to make passes at these fellows to see who they were and where they were going and what it was all about. By then he had learned better than to tell them where we were going and Ihad come to have confidence in him. I got so I liked Mike very much. I had a miserable time because the pilot had decided the best way to get to Marrakesh whole was to keep in the clouds and sometimes this meant going very high and there wasn't any oxygen. They gave me a walking tank to breathe in. I had such spasms of coughing. I kept sampling this little pot of oxygen. It came out afterwards, the reason he did this dodging into clouds was because the plane just ahead of us had been shot down by the Germans. They thought they were getting somebody high in the government but they only got a very famous actor, Leslie Howard. He was in the plane ahead of ours, A great loss! Dr. 0.: Oh yes, I can remember when that happened, very well.

Page  245245 Dr. H.: Well anyhow, that was why our pilot was flying as high as necessary to keep in the clouds. In the morning, at 7:15 (Mike kept all these records) we landed at Marrakesh in brilliant sunshine and I must say, nothing had ever looked better to me in my life. Clear, brilliant Arab sunshine, a great concrete apron. Nothing there except our quarters that we'd built, but the place was milling with Arabs in their fezzes and long "nightgowns" and gaily dressed French officers, British, Canadians, Australians, Americans. I thought we would probably layover there a day or so and warm up but as soon as the dispatching officer saw the #1 priority, he said, "You get out of here on the next plane. You have an hour." So, I called up Elliott Cutler at his hotel and he said, "Oh, come in and see me!" and I said, "I can't, I'm on my way in an hour." I didn't say where to. Well he said, "I will come right out and see you and mind you, you must picture this; two fellows, Hastings and Shimkin, dressed in old clothes. Each one with a regular issued big duffle bag stuffed full of Arctic clothing issued by the Army, thinking we might need it. Another one partly full of cans of C-rations in case we were dropped in the middle of the steppes. Each of us had a suitcase of his own with decent clothes in it, and we had 8 pieces of different kinds of packages and boxes. I had an official pouch sealed by the State Department with our classified reports in it. We had a box about 18" cubic which contained all the different samples of Cohn

Page  246246 fractions in their different forms. We had another package of penicillin. I've forgotten what all we had, but it made a big mound of material which we stacked together and never left. At least, if one left, the other guarded it. We had set up this pyramid of stuff after I got my orders for the next plane in the middle of this great big empty barn of a room, which was the waiting room. It had, a hundred people milling around in it, of different nationalities and different color and clothes. As I stood there by this mound of baggage, really not very relaxed about this whole trip in the middle of the war because I was in a war area at that moment, I caught sight of Elliott Cutler, who was a very good surgeon but he was a very much better General. He was born for the Army.1 He loved it; he was dressed in the finest tailored uniform and his boots were shined to high heaven. I saw Elliott come to the edge of this big open space and he spotted me through this crowd, at the center of this crowd, upon which he threw his arms into the air and in an enormously loud voice said, "Ah, Baird, so I hear you are going to Russia!" Dr. 0.: Oh my Lord.1 Dr. H.: Upon which it was as if an electric current had gone through everybody's feet and everything stopped like that for the instant.' People quit milling. Dr. 0.: Good Lord, how did he learn this?

Page  247247 Dr. H.: Some people knew this and didn't know it was under wraps. I don't know why it should have really been under wraps except that we tended to put things under wraps and since we were traveling with classified documents and one of them was marked SECRET, it was enough to make everything about our trip secret. Well anyhow, he made his way over to me and I got ahold of Mike and I said, "You watch this stuff, I've got to get Elliott out of here! I was by then, properly impressed about secrecy and probably went to great lengths to maintain my clearance, at least my freedom. I took him by the arm and we went out on this great concrete apron in the sunshine, and we walked up and down. Elliott had heard it from somebody who had come through from Washington so we discussed things. He told me I must spend a night in Algers and see Pete Churchill. As we were walking back and forth along this big apron, and I wasn't paying much attention to who was passing, one way or another, suddenly Elliott drew himself up, squared his shoulders, pulled in his stomach and gave a most magnificent salute to a funny little man that didn't come up to his shoulder in a dark blue, dusty mussed uniform and wearing a box cap which I hadn't noticed. Elliott said, "It's not often you have a chance to salute a 5-star General.1" This was General de Latray de Tassigny, who had been spirited out of France the night before on a submarine. Dr. 0.: For heaven's sake.

Page  248248 Dr. H.: Just to finish this off quickly, they called my plane and after I had discovered how hard it was to get #1 priority, I always assumed that I took precedence over everyone else, so I started off with all my bags and things over my shoulders, hands full, towards the plane and as I went along, I got a tug on my arm from a chap who was obviously the pilot. He said, "Dr. just stand here with me a second will you?" and they did the same with Mike, so we stood there. They had made a little double line and along comes this little General, just so high. His staff were the boys who had come down with us on the plane the night before. They were having their rendezvous with the General at Marrakesh. They had on their finest robin egg blue uniforms and the big red band and the box hats. It was magnificent.' So they went on the plane and we followed. Well, at this rate, we won't get to Russia very fast. Dr. 0.: This is probably a good place to stop for tonight. Dr. 0.: The date is February 7, 1968. We are again in the office of Dr. Hastings at the Scripps Institution of Oceanography and will continue our discussion where we left off yesterday afternoon with Dr. Hastings' medical mission to Moscow. Dr. H.: After taking off from Marrakesh on the 20th of December, we stopped briefly at Casablanca and then at Oran, Algeria where General

Page  249249 de Latray de Tassigny and his staff disembarked. We proceeded to Alger, Algeria where we spent the night in a blacked-out tent encampment and where we found Pete Churchill (Colonel Eo D. Churchill), and Drc Henry Beecher, who I believe had the rank of Major and who had just arrived. The next morning we took off for Cairo but were unable to land because of a sand storm and turned back to a place called Marble Arch. It is named because there is a marble arch on the border of Libya and Cirenaica in the middle of the Sahara Desert, which Mussolini had erected. There was a British camp there and they entertained us as best they could. They were particularly delighted because we had two American nurses aboard, because they had not seen any women for a long time. Because the mine fields around the camp had not yet been cleared, we were restricted to a few yards of the camp. Perhaps I should mention in this connection, that at Alger we had picked up some British aid American officers, who were enroute to Cairo and one young lieutenant, whom I got to talking with, was named James Tullis. He was taking a well needed rest from active service in the fighting in Italy. He was very glad to see me and he described his interest in the metabolism of the white blood cells and I rashly said, "Well, when this war is over give me a ring and I111 see what I can do for you." His home was in Cleveland. Perhaps just to

Page  250250 finish this up, shortly after the end of the war two years later, I suddenly got a telephone call in Boston, long distance from Cleveland, "This is James Tullis," he said, "I was just discharged yesterday. I am at my parents1 home and I remembered your invitation." I said, "Well, it's still good. Come to Boston when you get a chance and I'll see what I can do for you." He arrived the next morning upon which I called up first Bill Castle at the Thorndike Laboratory and he said he had no openings at the moment for such a young man. I then called Shields Warren at the New England Deaconess and he said, "Oh, that is most fortunate because Drc Schramm, who is the executive officer for a small cancer foundation, was just talking to me about wanting to support a fellow. Send him over." He (Tullis) came back by noon with his Fellowship assured and by evening he had rented a house. He came back to Boston and he has been there ever since. He spent two years working partly for Shields Warren and partly with me and then during the post-war period when plasma fractionation and preservation of cells became important, he transferred to the Protein Foundation where he is the key man in the country on the preservation of red cells, white cells and platelets. Dr. 0.: All stemming from--— Dr. H.: All stemming from this plane ride and the fact that we were spending the night at Marble Arch, Libya.

Page  251251 Well, to go back to the itinerary, we took off at 8 o'clock on December 25, 1943 and arrived over Cairo at noon. There were broken clouds and the airport was at times covered and unidentifiable. We were riding in a C-43. Our pilot was a civilian American Airlines pilot in peacetime with the rank of Major. He'd never landed at the Cairo Airport. His co-pilot was a full Colonel who was along as a "dead-head", for the ride. We circled quite a while and then suddenly our pilot saw a hole in the clouds and an airport and he swooped for it. He landed successfully, but barely so, on a very short airstrip. Almost immediately a group of fezzed Egyptians poured out of the building waving their hands in a manner to say, "go away! go away.1" It turned out that we had inadvertently landed at the civilian airport of Cairo, The American Air Force landing field was a scant half mile or mile away. We all wanted to get out even if it was the civilian airport but our pilot had no success in convincing the Egyptians that we could. We said to a British Brigadier and a British Admiral, who were aboard, "This is your baby, you get us off of here.1" So the British Brigadier put on his coat with its red lapels and he took his swagger stick and he put his monocle in his eye and he and the Admiral went off to argue with the Egyptians. In about 15 minutes they came back saying, "It's no soap. We've got to take off." So reluctantly our pilot zoomed up our old C-43 and barely got up over the fence that was all around the field and made this

Page  252252 short, sort of big jump, across the fence to the American Airport I was sitting close to the doorway and when he came out the sweat was pouring off his face and he said, "My God, I made it but I never thought I couldJ" Well, we disembarked. Both Mike Shimkin and I were pretty-much the worse for wear because this was now noon of December 22nd. [End of Reel 6, Side II]

Page  253253 [Reel 7, Side I,] continuation of recording on February 7, 1968 Dr. H.: As I say, we arrived in Cairo at the right airport on noon of December 22, 1943. We had taken off from Marrakesh about noon on the 20th and we had had practically no sleep during that period of 2 days. We were rumpled because we were in our GI clothing and looked pretty disreputable. We got our duffle bags around our shoulders, and our several other bags distributed about us, and staggered into the cafeteria that was part of this American Air Force installation. In the center of the room, in which we unloaded our bags beside a table, I recognized Tracy Mallory, Professor of Pathology at the Massachusetts General Hospital at Harvard. Now remember, we'd just left Churchill and Beecher; before that we'd just left Cutler and before that at Prestwick, I'd run into some Harvard fellows--John Gordon—people like this to whom I'd introduced Shimkin. While we were floating around England during that three or four weeks, we ran into a number of Harvard colleagues. As I unloaded my bag and said, "Hello, Tracy' Mike, this is Tracy Mallory," of the MGH in a very casual tone. Upon which Mike removed his GI furlined hat that we both were wearing, slammed it on the floor and said, "My God, have I got to go all the way to Moscow meeting nobody but Harvard menj" Dr. 0.: Harvard was well represented. Dr. H.: I never recorded this story before, though I've told it to friends a good many times, because during the McCarthy era, I was glad

Page  254254 that it wasn't on record, for both Mike's sake and mine particularly when McCarthy was investigating Harvard faculty. Well, we were held up in Cairo from noon on the 22nd until 8 o'clock on Christmas day, December 25, 1943. During that time, we had an opportunity to visit with Dr. John Snyder and Dr. Andrew Yeomans, who were in charge of the Typhus unit—both of them in uniform, Andy in the Army and John in the Navy. We also visited Dr. John Paul who was in the hospital with infectious hepatitis. We made a couple of false starts for Abadan, Iran--one on the 24th and one on the 25th--before we finally got away. On one of these we returned from having gotten over the Suez Canal and then turned around and came back. We missed the landing strip by several yards and dropped on the sand, bounced in the air forty feet, and then finally, after a number of smaller bounces, happened to hit the concrete strip. As the pilot came out--he was a big tall Iowa boy, towheaded--he was laughing to beat the band. Behind him was a little, short, red-headed, freckle-faced fellow from Purdue, the co-pilot and he was cursing the pilot to high heaven. As they went past me to open the door, the pilot said, "He'd never landed one of these things before. I thought it was time he learned." And this little fellow said, "You told me she wouldn't stall till 65 and she stalled at 85!" Well, anyhow, my heart was in my mouth. I thought that was the end of this mission to Moscow.

Page  255255 We got to Abadan, Iran on the night of the 25th and had our Christmas dinner there with the American contingent. Again we were stalled for three days. Fortunately, there was an incoming chief surgeon to the Persian Gulf Command, named Colonel John McDill, who was to relieve Col. Ostrander in Tehran. Probably, because there were so few civilian Americans in evidence in this part of the country at that time, Col. McDill took no chances on whether we were important or not. He treated us as important.' As a result, I traveled with him to all the American hospital installations that were within automobile distance from Abadan--and this was repeated after we got to Tehran. So I had the rather unique experience of seeing quite a lot of Iran, that even Col. Simmons, who made a brief trip there, did not see. After three days we took off for Tehran and arrived there on the 28th of December. Florey was met by a car from the English Embassy and whisked off to the British Embassy. A sergeant in a jeep and the most junior of all the people on the staff of our Embassy met us. This chap, whose name I've forgotten, was lame and was unable to get in the armed services so he had volunteered his services to the State Department. They had sent him to the Iranian Embassy as a volunteer. He did much of the leg work for the Embassy. A very fine fellow whom I saw occasionally in after years. There being no instructions to take us to the Embassy, he took us to one hotel after the other but we couldn't get in any of them. Finally, he took us to Camp Amirabad,

Page  256256 which was the American installation in Iran. We met Col. Ostrander and Col. Fry, who was head of medicine of the Jefferson Medical School unit. Col. Fry offered to take me in with him and other arrangements were made for Shimkin. We spent from December 28 to January 13 in Tehran waiting for the Russians to take us on to Moscow. These's a great deal I could say about this but I must not take the time to do so now. If there is time at a later date, I would like to contrast my experience in Iran, in this period of '43-'44, with the experience I've lust had there in '67. Because the contrast is so great I would like to do it justice. Perhaps I can record one of the many things that happened during this sixteen-day wait, because it has its amusing aspects. Florey was wined and dined and treated as a most distinguished guest of the British Embassy, whereas, I never saw our Ambassador or any senior person in the embassy. I was not invited to our Embassy while I was in Tehran. Florey however occupied the bed that Churchill had just gotten out of at the Tehran conference. Dr. 0.: Was there any explanation for this as far as our Embassy, or were they still wrapped up in the Tehran conference or was it just one of those things? Dr. H.: No, I think we had a Minister, not an Ambassador and I'm not sure he was in the city. The secretaries whom I did meet in the Embassy office seemed to be very third rate fellows. Whereas the British Embassy staff were on their toes, indeed. Our dealings

Page  257257 with the Russians to get our transportation finally all had to be done through the British boys. It seemed to me at that time that our people were incompetent. I shouldn't say that should I? Dr. 0.: Well, I think it's important as it's an interesting commentary on the way we handled our Middle East embassies. Dr. H.: I began to get a very low opinion of our Middle East Embassy staff, at that time. Dr. 0.: Well, I think this is true; it's true. It's one of our problems. Dr. H.: The British knew the ways to get things done. But Florey saw that Shimkin and I got invited to some of these dinners that they had. Of course he was much better known than I, because the news of penicillin had already reached this part of the country. You see, technically, Florey was under my orders. I was the head of this mission, if there was a head. But it was amusing later to find, in dispatches about us that had come back to England (I have one in my files, from the newspapers) that Professor Florey had been in Tehran, Iran and had lectured on penicillin there and he was accompanied by an American dermatologist called Hastings.1 Dr. 0.: If they were going to make you an M.D., the least they could have done was to make you something other than a dermatologist

Page  258258 Dr. H.: Actually, it was this nice boy from Princeton. I forgot to say that he was a Princeton lad, who had met us at the plane and took care of us. On the 12th, I expect it was; it might have been the llth of January, we were notified that the Russians were prepared to take the four of us, that is Florey and his colleague, Sanders, and me and my colleague, Shimkin, to Moscow. In the evening after dinner, I was called to the phone and Sanders was on and he said, "You know, Florey is very ill, and I don't think he's able to go tomorrow, and he wants you to come and see him." So I got a Jeep and a driver and we went in to the British Embassy. The British Embassy was surrounded by a big wall and the gates were guarded by big, enormous, square bearded, six foot six Sikhs. They presented arms as we came in. We drove up to the entrance, which was quite palatial, and there was a big, wide, red carpet down these wide steps. There was a Butler, in white tie and tails, at the top of the steps, and he greeted usc I asked for Professor Florey and he led us down the corridor to, what had been Churchill's room, and there was Florey looking very pale and apprehensive. He had a fever and he said, "You know, I'm really worried, it may just be the flu or some acute infection, but it might be that it's one of these North African diseases that I may have contracted down there just before I left to come on this trip with you." He said, "If I'm going to really be sick a long time I certainly don't want to be here at the Embassy and cause the difficulties that they would have having a sick man here." He further said, "But, I really would rather not go to the British hospital here."

Page  259259 Dr. 0.: That's rather interesting—-- Dr. H.: Well, he's an Australian originally for one thing. Anyhow, this was my cue and I said, "Well, Howard, let me take you out to our hospital. We've got all these doctors and specialists out there and they're twiddling their thumbs. We've brought about four times as many people here as we needed. After they cleaned out the flies and the mosquitoes, there's no business, and they're getting bored." Florey looked up and said, "Would you? If you do "I'll say it was all your fault and I did it under your orders." I said, "That's all right with me." So, I went back to camp in the Jeep, and went to Col. Ostrander. He was still in his chief surgeon role, and I told him the situation. He said, "Well, if you'll give me a piece of paper—a "from, to, subject" piece of paper, so I'll have something to show people if there's any kickback on this, I'll authorize it." So I sat down at the typewriter--! think it's the last time I've been at a typewriter--and punched out "from, to, subject"--treatment of Professor Florey who was ill, etc. He said, "Well, that's all I want. Go get the ambulance and one of the medical officers and go get him." The ambulance was a converted Ford, The assistant, the second in rank in the Medical Department came along and two GI's, with a stretcher. We went clanging into Tehran. The Camp Amirabad was some five miles out of town. It is now where the airport is. They call it Amirabad Airport. As we clanged up to the gates, the Sikhs presented arms and we went around to the

Page  260260 Embassy. I led the way with the medical officer behind me and the two GI's with the stretcher behind me and up the steps and up to the turn in the hall--the 'chap in full dress was still there. Oh, I should have said that the ambassador was out to dinner. Dr. 0.: Oh, when you were first there? Dr. H.: Yes, and still was. Since I knew where Florey's room was, we didn't ask any questions, we just marched there, unrolled the stretcher, we rolled Florey on it and picked up the stretcher and off we went to Camp Amirabad in less than two, three minutes. I was too anxious to get back in that Jeep to see whether the "majordomo" was bug-eyed at that point, and "clanged" our way out and back, put Florey to bed in the best quarters, and the boys started to work on him. He was sick and he was unable to leave with me and Shimkin the next day, but it was just an acute infection and he followed me a week later. I'll come to that later. I presume nobody has ever had such a thorough going over, because all the specialists took a crack at Howard. Dr. 0.: He was probably worn out by the time he was through. Dr. H.: Well, that's a happy ending, except that the next day there was a delegation from the Embassy, the head of medicine at the British hospital, who was an Indian, that came out to the hospital and wanted to know what goes on. Florey said that he was under my orders and I had ordered him to come out there so we could take care of him. As far as I know, that was the end of it.

Page  261261 Shimkin and I went on, again a C-47, though it bore Russian marks now and I presume we'd given it to them. It was an American-built C-47, and that made you relax because that's the "Jeep of the air;" that's the one plane that's ever been invented that can do no wrong. But it was a little different take-off than ours. In the first place there were no seat belts, they'd never been there. There was no way of flying blind in overcast weather. Dr. 0.: No radar? Dr. H.: No, no radar. I don't know that they even had radio communication. They had to see the ground to fly. The second thing was that as soon as anybody got on the plane, he lit up a cigarette whether he was smoking or not, before.' You can quit smoking after you take off if you want to! Third thing was that the pilot and co-pilot were not aboard. When everybody was in, then they came in, dressed to high heaven with medals and big epaulets, and strutted to their seats and turned on one motor and they turned on another motor and they revved them up and off we went--none of this warming up stuff for them! Dr. 0.: Thank God it was a C-47. Dr. H.: Well, we hopped over those mountains between Tehran and the foot of the Caspian Sea and landed at Baku, where they stopped for everybody to go through customs. I didn't have to because of diplomatic privileges with our special passport, and documents saying

Page  262262 that these packages were sealed officially. I stood at the edge of the brick customs building. The place reeked of oil. It looked like Long Beach, California with all its oil derricks. It started to rain; a nice, gentle rain but enough to keep you from going out in it. So, I stood under the overhang looking out at the rain and I was conscious there was a young chap--oh, twenty, twenty-five feet away--also standing there looking out at the rain. I looked him over and saw that he was obviously a Russian soldier, a GI. Not knowing any Russian I thought he might know some German. It was my only language except English. I sort of pointed to the rain and smiled and said in very bad German that it's raining. He grinned and nodded his head and then said, "You English?" I said, "No, American." "Ah, American.1 I." He did this mostly in very halting English, hunting for the word and he used gestures--"I, Chi-ca-go, five," and he was holding up his fingers, "five years, auto--auto mechanic." I was very interested, I said, "I Chicago, eight years." Well, that seemed to be sort of the end of the conversation, but then he managed to tell me in broken English that he was going back to the front; he'd been home on a furlough and that he had missed his plane and had to wait for the next one. When he got that across to me, his face broke into a happy smile and he said, "Today we half-way Berlin.'" Now this was an important statement for me to get from a Russian GI going back to the Leningrad front, because, though I wasn't assigned any military intelligence

Page  263263 duties, I'd nevertheless been asked by a high ranking officer to see if there were any indications of whether or not the Russian Army was going to stop at the Polish border when they got there. So, it came from the "horse's mouth" as it were, that the objective was Berlin. I marked off that job as having been accomplished. Am I going too far afield? Dr. 0.: No, I don't think so. This is a little social history and everything else mixed in. It's just fine. Dr. H.: Well, that's all that happened at Baku. We took off from Baku after a stop of a couple of hours for Astrakhan, which is at the mouth of the Volga and the head of the Caspian Sea. It is the old capital of southern Russia. It has its Kremlin, has its walls and is a fine old town. It had practically no adult males left except very old men, and under high school age boys and women. They hadn't been expecting us. Their last customers at the inn, which had been in the same family for generations, had been Anthony Eden when he'd also broken his trip at Astrakhan. It wasn't the regular stop. If you couldn't get to Moscow from Tehran while it was still light, you had to break it here. So they opened up the inn. It was cold as all blazes. I slept all night on a hard bench with all my arctic clothing on--my two layers of fur-lined stuff, fur-lined pants, boots with three layers of socks inside--!"ve never been so cold. They stirred up a little food and some vodka and some black bread and the old woman who was

Page  264264 left there stayed in the doorway while five or six of us gathered in one of the bedrooms. One of the members of this group was a man named Alex Wirth, a well-known journalist and authority on Russia. He's written many books. He was traveling with a British young lady who's name I don't remember. Also on our plane that day and in the room with us where we ate this meal, was Herbert Salisbury, a very young fellow who was making his first trip to Russia, but was destined to spend many years there and become an authority on Russia. He's still on the staff of the New York Times. Well, Alex Wirth spoke excellent Russian and Mike Shimkin, who was with me, spoke adequate Russian, and this old woman who, with her granddaughters, was running this old inn, stood at the doorway and first talked to us about what a charmer Anthony Eden had been and how handsome he was. Then Alex Wirth and Mike, alternately, started quizzing her about conditions in Astrakan. The thing I remember so vividly in their translation, is when, suddenly she got sort of livid and replied very loudly and said: "Those northerners have ruined the South!" Dr. 0.: Referring to northern Russia? Dr. H.: Yes. "This had been a great place, but the people of Moscow had neglected it, they had taken all the men...." What I'm referring to is the similarity of things that were occurring in their country with what had occurred in ours.

Page  265265 The next morning we took off for Moscow, but the pilot detoured so we could see Stalingrad from the air and he swept low over it. We all tried to see one intact building, and there wasn't a single identifiable intact building left in Stalingrad on the 14th of January, 1944. We arrived in Moscow about 2 o'clock and we were met by the first secretary of the Embassy and taken directly to the Hotel National, and given a very large and comfortable suite. It included a living-dining room with a very large desk—everything is very large in Russia, even the inkwell was extra size—very high ceilings, and a comfortable bedroom with two beds and a bathroom with a bathtub. We were told by this first secretary that they didn't have hot water in the hotel at all, but they did in their quarters in the Embassy building--not where the Ambassador lived but where the offices and the apartments for the Embassy staff were located. This was right next door to the Hotel National. He said, "Why don't you come home with me or come over as soon as you unpack and have a nice hot shower?"--which we took advantage of, had dinner with him and it was all a very pleasant occasion. The next morning I got up automatically, turned on the hot water faucet and shaved with hot water and didn't think about it. I didn't get in the bathtub because it was "cakedly" dirty. I took a sponge bath. I thought, since we had our own dining room table we might as well have breakfast in our room--being such VIPs--so I instructed Shimkin to order breakfast. He went to the telephone and had a long conversation and ordered it. Well, that was when we first got out of bed.

Page  266266 When I was through shaving, getting dressed, I said, "You'd better check on that." So he went again. Then I got all dressed, ready for my tea--I knew I was going to get hot tea in a glass, not coffee,--! said, "I've got to have the hot tea, so check again." Well, he checked again--! waited probably five or ten minutes and gave up and went down to the dining room and had breadfast and thought to myself, this isn't going to happen again, I'll tell you that. The next day we were taken by the councilor of the Embassy to Ambassador Harriman. We went to Spasso House, which was occupied by Ambassador Harriman and his daughter, who was his hostess. I had a very fine time with him. I liked him right away and he liked me. He hadn't been in Moscow very long, you know, at that time--a few months, maybe only weeks. He knew Bush. Bush had written him and I had all my official documents and he said to me, "Well, I've learned one thing already that these people are very unpredictable and we'll inform them officially you're here and we may hear from them and you may not. You may stay here a month and not hear from them, but we'll see." In the evening we were taken to the opera, actually the Bolshoi Ballet, where I saw the marvelous Ulanova, the premier danseuse of the Bolshoi Ballet. I've never seen anything to equal her since. In a day or so, we were invited to a cocktail party at the British Embassy, and when they had any such party, all the diplomatic corps

Page  267267 of all the nations which were represented there. There weren't many Embassy wives allowed in Moscow at that time. I'm not too sure there were any. Usually the British and American press representatives, of which there were only a few, and the British and American staff were present which made up a sizeable number in all. At this particular party, Russians were not invited, but there were others where they were. At any rate, in the middle of this party, a very nice looking, Embassy-dressed man came over and introduced himself and said he was the Minister from Columbia, I believe it was, who had a message for me from all those members of the other ministries which had their quarters in the Hotel National The other countries didn't have buildings of their own like we did. They had rooms in two hotels, the Metropole or the Hotel National. But there was a bunch of them in the Hotel National and he said he was representing all those ministries in the Hotel National and he wished to welcome us to Moscow and hoped that we would stay a very long time. I said, "Well, we're pleased to be here and it's not our intention to stay longer than a month, however." "Well," he said, "even that will be a great pleasure, because we haven't had any hot water in the hotel for months, since the siege of Moscow was raised but the day you came they have supplied us with hot water, so we hope you will stay a long time." So this pepped me up very much--me and Mike. We thought this is the best evidence that we're really on an important mission. From that moment on, the

Page  268268 first thing I'd do in the morning would be to turn on the hot water faucet to see if it was still hot, and it was! It was hot continuously from then until the morning before we left, a month later, on which it was cold! I remarked on this to Professor Parin, the head of the Russian Medical Research Unit with whom I had become quite well acquainted. He laughed very hard because he said, "Oh, you didn't have anything to do with that." He said, "We had called in a meeting of the Supreme Soviet and they arrived the day you arrived and they left yesterday!" Dr. 0.: That took a little wind out of your sails, didn't it? Dr. H.: Yes, well, I think it's amusing. I love things like that. Well, let's get on with the job. The day after I arrived, the first secretary said that the Vice-Commissar for Medical Education and Medical Research was prepared to see me at my convenience. A date at 5 o'clock in the afternoon was set up. He accompanied Shimkin and me to this quite simple and austere building and quite simple and austere office, where this man of middle age with sandy hair and a sandy moustache was sitting in what I came to recognize as the position of the Commissar. That is, very straight, looking straight ahead with a stony face with thumbs on the edge of the desk and hands below. He had his interpreter there. He formally shook hands with me, and motioned me to the chair beside his desk, and then said in Russian through his interpreter "We hope you've

Page  269269 had a pleasant trip and I said, "Yes, we were relatively comfortable, though it had been slower than we'd expected or hoped it would be." Shimkin translated this into Russian and there were a few more exchange of pleasantries like that. Then, from his interpreter's mouth came the question, "Well, what would you like to do while you're here?" Having spent over 6 weeks getting there, being tired, having had these negotiations go on between their Foreign Office and our State Department for several months on exactly what we were going to do when we were there, my blood pressure blew offI As soon as I heard this question asked, I just leaned over to this fellow, Parin, and said, "Look, we're here to be just a couple of scientists that want to talk with your scientists about medical research, as scientists'" Upon which—he didn't wait for Mike to translate that into Russian—he broke into a grin, relaxed his position of Commissar and said in quite good English, "Well, that's what we want too." Upon which, he and I carried on a very pleasant conversation in English, without involving our interpreters. Dr. 0.: This was Parin? Dr. H.: This was V. Parin. It turned out, you see, he was, in peacetime, a professor of physiology. He came from a long line of academic medical people, and he'd sort of been drafted for this administrative job. Actually, he still taught physiology at the medical school in the morning and, at 12 o'clock, came to this office

Page  270270 and worked through, as he said, usually until 12 o'clock at night. It was one of his administrative jobs. He was, in a sense, A. N. Richards' opposite and he arranged things for us to the best of his ability. Everything we asked to do, we were able to do, though, with our ten subjects we were kept busy every day without anything extra. Florey and Sanders came a week after we got there and stayed a week longer than we did. We visited all the hospitals where there was any research going on and all the research institutes. They'd solved the problem of blood preservation, very simply at the time, because they would build in to the plan for any new offensive, the statistical number of casualties expected and from that, calculate the number of units of blood they would probably need at a certain place at a certain time. It was a straight front, you see, and they could do this so that part of the logistics was getting so many donors in from such and such a factory. They used a very good blood preservation solution. Of course, the important thing was to refrigerate it, to keep it at a low temperature, but they also used a citrate dextrose solution. They did not have an excess of citric acid so they didn't use the ACD formula that we use, but I think this is of minor importance, as a matter of fact. Dr. 0.: I was interested too--they collected it in 250 ml. units rather than 500 ml. units.

Page  271271 Dr. H.: Yes, I don't know why they did that, but I remember we remarked on that at the time too. We were quite surprised when Parin said one day, "Now, I suppose you would like to see our institute where we're making penicillin." At that time, we didn't know they'd ever heard the word. He said they'd been making it, though not in as much quantity of course as we were, and they had treated some 200 odd cases with it. One questions, in retrospect, whether their penicillin preparations were strong enough to have been therapeutically effective. Dr. 0.: Yes, I noticed that in your write-up. It seemed rather surprising. Also, they felt they had a different strain of penicillium. Dr. H.: They were quite cooperative. They gave us samples of their strains of penicillin and these we brought back with us. We sent them to Peoria where they make a business of identifying strains of penicillium. One of their strains was a rather poor penicillin producer and the other was very good--by our standards. Their penicillium turned out to be a mixture of two strains of Penicillium notatum. The other thing that happened that I can't believe, in retrospect, was that at our request they let us set up a parallel study of cases. I believe they were osteomyelitis cases, but I can't remember for sure. Half of their cases would be treated with the American or the British penicillin, which we'd

Page  272272 brought with us, and the other part with their penicillin. This didn't get set up until we were just about to leave and Florey and Sanders were to follow it up. Florey never got to see the cases after the first few days. We don't know how it came out. But the fact that they let the comparison get started at all, was to me amazing. I don't think we'd have done that in our country. Well, there were so many interesting things that happened during that month, it's hard to know where to stop. Perhaps one more small anecdote which becomes sort of important, again, in retrospect. We were entertained by an official luncheon at the Russian Academy of Science and the host at that official luncheon was Orbelli, who was the Vice-president of the Academy and head of the Division of Biology and Medicine at the Academy. Orbelli was the successor to and student of Pavlov, and his successor at the Pavlov Institute in Leningrad. He was also head of the medical school for the army and, as we would say here, "wore a number of hats." I was on his right at this luncheon. He spoke very good English. I said, "Well, you must find it difficult to discharge all your various duties. I don't see how you can do it." He said, "Well, not only is it difficult but on top of that they've just given me a new assignment. Our Institute for Aviation Medicine has not done anything for years, it's in very poor shape, and so they have decided that I must take this over and build it into a great Institute for Aviation Medicine."

Page  273273 This is my link to the fact that they probably had their eye on space research even at that early state. [Side II, Reel 7, recorded February 7, 1968] Dr. H.: Reminiscing about this trip, I'm reminded of the fact that we found so many young people in training, both in the medical school and in research institutes, in the midst and at the height of this terrible conflict and in the face of their very large casualties which were still being incurred on the whole front. As an example of how large they were, I'm reminded that Professor Yudin, a colonel in uniform, came to the party that Ambassador Harriman and I gave (he paid for it) at Spasso House for the British community, the American community, and all the Russian scientists who we felt had made our trip a success. In being transferred from the Kiev front, which they had just taken, to the Leningrad front which was still under siege, he had stopped by his office and found the invitation to the party and got to Spasso House in the middle of the party—dirty, unkempt, but the most vivacious fellow you ever saw. He was a very good surgeon, trained at the Mayo clinic, known for his description of the use of cadaver blood, but this was a very small incident in his life. He was a great GI surgeon. Our people who wanted the latest information from the front, of course, gathered around him, particularly our journalist friends, before the Russians who were at the party

Page  274274 really realized he was there. I got into the edge of this group around Yudin just in time to hear him say, "Why, our casualties have been so tremendous that I've been practicing my specialty," which means gastro-intestinal surgery. In the face of this, they were still ordering young people to continue their education or to become specialists in various phases of science. They were just as much drafted for this as were the men who were drafted to fight the Germans. I've often felt that, whereas this is the way things are done and no questions asked in a totalitarian state nobody asked whether he was happy or not; in a democracy we can't do those things. We're trying to achieve that same thing with our exemptions from draft for the students who are intellectually qualified, but in time of war, it's putting it the wrong way. They ought to be ordered to be there; it should not be their choice. But this is not the way decisions can be made in a democracy. This is one of the reasons why I pray to God that the United States and Russia will never have to go to war. I had to get that off my chestj As I said, it's on record, we saw and talked with over a hundred Russian scientists during this month, from the 14th of January, 1944 to the llth of February, 1944. We had as free exchange of information as scientists can have with the other scientists. However, it was not a comfortable experience. This was my third trip to Russia and each time I've been very uncomfortable but for different reasons.

Page  275275 Dr. 0.: In what sense was it uncomfortable? Physical comfort or do you mean ----- Dr. H. : Well, it was physically uncomfortable, though not tremendously so. It was as comfortable as they could make it under those conditions. But it was winter--the siege of Moscow had only been broken about a few months, heating of buildings was not restored. When we visited Parnas, the great Polish biochemist whose life they had saved and to whom they had given an institute-there was no heat in his institute. So we stood around a Bunsen burner with the ring stand over it and a brick on the ring stand, to keep our hands warm enough. But the thing that of course bothers you most when you're in Russia is that you had the feeling that you were constantly being observed. We were trailed when we walked on the street. Indeed, if I happened to go out alone even to go down the street a few blocks, there was always a woman in GI uniform with a gun walking about ten paces behind me. We heard many stories that were proven, both about Spasso House and various apartments where people lived of tape recordings of what was said. Shimkin and I never discussed anything about our trip or anything unless we went out in the square where we could see on all sides of us We felt we were under surveillance, and I could have kissed that American flag that we passed as we went into the American quarters in Tehran on our way back.

Page  276276 Our trip back was fairly uneventful. I have just been to Tehran and back (November, 1968) and covered about the same amount of mileage as we covered in this other trip,--because coming back we had to cross Africa to Dakar and then to Fortaleza in South America and up to Puerto Rico and Charleston and finally Washington, We covered 30,000 miles with 32 descents. I mark the comfort of my trips in the air by how few descents you have to make, takeoffs I don't mind, descents I still do. Even with a #1 priority, it took us from the 24th of November to the 28th of December—over a month--to get to Tehran. Flying time now, on jets, to get from New York to Tehran will only take you about 14 hours, allowing for a stop in London. I think, on balance, one has to consider this particular mission having been about as successful as it could have been at that time and under the circumstances. As we left Moscow, they loaded us down with so much material, including, as I say, their different strains of penicillin, manuscripts they wanted published, as well as reports, that we had to turn in our pouch which had been issued to us in Washington--a standard size pouch--for a big mail pouch and thereby hangs another anecdote. I think to this day the State Department thinks that I owe them $13.50 for that pouch which I left with Ambassador Harriman. They didn't give me credit for the one I brought back.' I kept getting bills for it for years, but I haven't had one for some time. They never acknowledged that I had made a trade. I hadn't properly disposed of Government property.'

Page  277277 Dr. 0. : There you go again.1 Dr. H.: There I go again. I've got to put this on, I'm sorry, it's way out of place. But this reminds me about my experience on entering the Public Health Service in November 1917 and having violated regulations by buying the two Calomel cells without authorization. In 1921 when I was trying to get things all cleared up so I could be honorably discharged from the Public Health Service and go to the Rockefeller Institute, I thought everything was in fine order until I got a letter from, what was now my friend and protector, William C. Beuchler, saying, "What in the world did you ever do with those cells? They're on the nonexpendable list." I wrote him, "Be yourself, they were glass and they were long since broken." He called me up at that point and said, "Don't ever put anything like that in writing about a nonexpendable item! For God's sake, use your imagination. Break up a couple of test-tubes if necessary, and label them unusable Calomel cells and send them to me and I'll give you an honorable discharge!!" Well, these are true stories; I'm not making them up. Dr. 0.: It's quite interesting in reading over the material you have in your file relating to the Russian trip and immediately thereafter, that, when you first came back you certainly were enthusiastic about setting up more direct liaison between the scientists in Russia and this country, with the assignment to our Embassy of

Page  278278 somebody with the language and technical ability to converse with the Russian scientific community. I think you probably had a fair amount of support from some other people. I don't really know what finally came of this. I am aware, certainly, that it wasn't too awfully long after your trip, within a period of two years, certainly, that our relationship with Russia started to get a little "sticky." I also noticed that there was a Hugh Cabot Fund in 1946, proposed to construct for Russia a mycologic institute which apparently never came to pass. Dr. H.: No, I had nothing really to do with that, though I went to some of the meetings when it was discussed. Dr. 0.: You were approached about being on the committee. Dr. H.: Well, we did feel that it was desirable to create a post of science attache in our Embassy in Moscow. We even felt he should be of professorial stature; a man who had made outstanding contributions to medical research. Preferably one who spoke Russian or who was willing to learn Russian because it made a big difference. We did arrange for an exchange of twenty medical journals between our countries. Theirs were in Russian and ours were in English. At that time their journals always carried a table of contents in English, which they gave up after a certain time. We also talked

Page  279279 about exchange of men in training. We were so hopeful that this would come about that I even persuaded Bernard Davis, now the Professor of Bacteriology at Harvard, to learn Russian, because he wanted to go and be a postdoctoral fellow there. But this never came off. We thought, at the time we left, that there would be another mission just like ours so we prepared and briefed Owen Wangensteen, Jim Gamble--- Dr. 0.: I noticed correspondence from Dr. Wangensteen. Dr. H.: ---Oh, he came to Washington several times and was all ready to go, but we never could get a mission set up again. Dr. 0: Was this because of the political climate of the times? Dr. H.: I presume so. When I first came back, I was told by Bush that President Roosevelt wanted to see me and get an account of what was going on. This never came off. A couple of times it was set up and then Admiral Mclntire said he just wasn't well enough, he had so much to do. Mclntire did ask me to come over and see him and I briefed him as completely as I'm briefing you,more so as a matter of fact. We had an afternoon together and I understand that this was to be transmitted to President Roosevelt. Whether it was or not, I don't know. At one stage, Bush, when I was seeing him over at his office, said, "Oh, by the way, all of the plans for you to see Roosevelt are off." He didn't elaborate on that. Now, whether this

Page  280280 L. _ was due to deteriorating relations even as early as that, I don't know. I did also speak very frankly and fully at a special dinner set up by George Merck at the Metropolitan Club shortly after I returned, which Bush and Conant and several generals attended. I can't remember who all was there but they all "pumped" me for a long time. That's about the end of this story as far as I'm concerned. Except one little extra thing. We abstracted our official report in a form that we thought would be relatively accurate in what it said, though, because of the time we didn't put in anything that was particularly unfavorable to the Russian situation. When this was published in Science in two installments, I got quite a little fan mail. The fan mail was only of two extreme kinds; either "This is terrific and you've obviously done a great thing.'" and the other half came from people who said, "My God, you've been much too favorable to the Russians.'" There were none which described it as we saw it, which was, it's a mixture of good and bad. Their science was not nearly as good as ours, but considering the conditions under which it was being done at that moment, it was a very good effort. Not all the Russians we met were pleasant. I remember one of the Commissars whom I went to see in company with our Red Cross representative who was trying to do something for him. This fellow was greedy and rude and simply wanted to dictate to the Red Cross regarding what they would take and what they wouldn't take.

Page  281281 It infuriated me I But the scientists weren't that way, nor was Parin. He was officially invited to the United States while we were there; Harriman cabled to Washington, got permission to officially invite him to come over within a month or so of our trip. But he did not do so then. He sent a message that he couldn't be spared at that time. After the war, he was invited by Surgeon General Parran of the Public Health Service, and did come. He visited laboratories and hospitals and even pharmaceutical houses from one coast to the other. I saw him in Boston on his return to the East. He left us in Boston after we had had a dinner for him there, as a matter of fact, at the Harvard Club, and went to New York, and that was the end of my contact with Parin until I learned, through reading an article in the Saturday Evening Post, by a fellow who had been ambassador there. He'd been Eisenhower's Chief of Staff—what was that name? Dr. 0.: Oh, Bedell Smith——— Dr. H.: Smith. Bedell Smith. Well, just incidental to describing some of his experiences, he mentioned that V. Parin had been put under arrest and brought back to Russia and accused of having divulged Russian secrets on cancer research in his speech at the NIH and was sentenced to a term in Siberia' Dr. 0.: This was after this trip when you saw him in Boston?

Page  282282 Dr. H.: Yes. He didn't get out of Siberia until Khrushchev got into power. He's in very good grace now. I haven't ever seen him since, but he's been in this country several times. He gave me this book. This is his signature "To Professor Hastings," and he wrote, "In memory of your visit to Moscow, with best wishes" the 24th--what I'm looking for though is a picture of him. (Pause, while looking for picture.) Dr. 0.: Is this it? Dr. H.: Oh, maybe that's it. Yes, the Commissariat of Public Health. This is Miterev, the Commissar of Public Health. This is Parin and this is the guy I've just been referring to, Kolesnikov. Dr. 0.: I noticed in your papers, a letter from Dr. Shimkin. Apparently in 1949, he had been approached about some job for which he needed security clearance and it apparently had been denied him on the basis of his many involvements with Russians who had come to this country though actually he would be on government assignment when showing them around. Did you at any time after this trip have any clearance problems--say during the McCarthy era? I know you made a comment in passing about the McCarthy era as far as his going after some of the Harvard Professors. Dr. H.: No. I expected to be called but I never was. There was never any question, in the security business, until a year or so

Page  283283 before I left Harvard. I think I told you this story about getting clearance for the Quartermaster Research and Development Board. I'd never had Army investigation before because when you're a Presidential appointee, as I was to CMR-OSRD, nobody asks. I didn't start having to get clearance until after the war when I started with the AEG. I had Q clearances. Well, about 1955, the Army started from scratch and turned up this trip to Russia, so they sent a security man around that sat with a microphone and took testimony and quizzed me about my contact with Russia. As far as I know, I cleared up everything except one question he asked me that I'm still puzzled about. That was, what happened when we lived briefly at some address in Chicago. He wouldn't give me any clue as to what might have happened. That had nothing to do with Russia, it might have had something to do with some Communist inclined people that we knew in Chicago in the early thirties. Of course we knew some there; you can't help it, if you run around the world at all. Dr. 0.: Oh, I vaguely remember now, when I was here in December I found a letter amongst your early papers in Chicago. You had bailed somebody out of jail. Dr. H.: Really]I Dr. 0. : Yes. I remember showing this to you and you had forgotten all about it. I can't remember what the situation was now, whether

Page  284284 it was a civil disturbance or what, I don't know. Dr. H.: It didn't make enough of an impression so I could remember it. Dr. 0.: It was either somebody that worked in your laboratory or the son of one of your technicians, something like that. Dr. H.: Well, that sparks me to do the Mishkis thing a little bit--I want it on record. When I was at the University of Chicago, I had as a graduate student, a Russian-born chap named Mishkis--B. Mishkis--I never knew what the B was for. Dr. 0.: Benjamin, I believe. At least that was the English name he would use in his correspondence. Dr. H.: He also worked as the storeroom man. His wife worked for my colleague, Lillian Eichelberger, as a technician, only known to me as Mrs. Mishkis, but a most dexterous technician. They had a son and Mishkis successfully worked on a thesis and received a Ph.D. degree in about 1931, maybe '32. Now Mishkis regarded himself as a good Communist, even though he and his wife had left Russia via Siberia, Vladivostok, during the Kerensky regime. He had never lived under the Communist regime but his ambition was to go back and be a scientist in Russia. Dr. 0.: So in other words, when you say a good Communist, he was very nationalistic, I mean very anxious to get back to his country and participate in the new developing Russia.

Page  285285 Dr. H.: Yes, he bragged about it around the lab, which made it a little difficult when I had a White Russian there also as a postdoctoral student at the time. The two of them would go to great pains, if they had to be in the same laboratory, not to be at the same bench at the same moment. Mishkis was all right, but he wasn't terribly bright. He was awful loud when he got excited. I used to have to make him "pipe down." But I certainly liked his wife and I didn't dislike Mishkis and helped him get his degree. In the summer of 1932, there was the International Physiological Congress in Rome, and at the banquet, I happened to sit next to a Russian who could speak enough German—and at that time I was close enough to my Berlin experience so I could speak enough German--and so we conversed in German. His name was Palladin. Now, there was a great botanical scientist—an internationally great botanical scientist—named Palladin, and this was his son. The son was a man about my age, I think. In the course of the conversation, he said that they had just built a new research institute in Kiev—the first one in Kiev—and that he was in charge of the Biochemical Department and that he wished he could get a well trained biochemist, did I know of any. Well, this was made for my situation, and I rose to the occasion and told him all about Mishkis and how he wanted to come back to Russia and though he wasn't the most brilliant biochemist in

Page  286286 the world, nevertheless, I regarded him as competent and well trained in the tools of the trade as we knew them at that time. Well, we did have a lot of champagne at that dinner, and I really never expected to hear from him again. But the next morning he turned up and wanted more complete details. Eventually, an invitation came to Mishkis and I think it was in 1932 or 33 that he went over and became first assistant to Palladin at the biochemical institute in Kiev. Knowing that he was going to be paid in rubles and that they weren't good for use outside the USSR, I subscribed to the Journal of Biological Chemistry for him and had it sent to him and he always responded promptly with news of the year and so forth, and what he was working on. In 1935, I went to the International Physiological Congress which started in Leningrad and ended in Moscow, and the Mishkis's met me and they took me all around Leningrad. We visited parks and rode on street cars and busses and even went into some private homes. It was Mrs. Mishkis1 home; she came from Leningrad and so she had lots of friends. It was great fun to see that side of Russia-inside Russia, as it were. The day before I left, Mishkis asked if he could see me privately and I said, "Why, sure." Of course, I guess he was just as suspicious as I am when in Russia, so he wanted to know who was on either side of my room in the hotel before he talked, and when he did talk he only talked in a very low voice.

Page  287287 Dr. 0.: This was in 1935? Dr. H. : It was 1935. He asked if there was any way for me to get him back to the United States. He said things were not going well; he said, "The problem is very simple, my chief, Palladin, is jealous of me, because you taught me how to use Warburgs, Van Slykes, and potentiometers, measure pH's and all these things, which he can't do. So everybody is coming to me to learn these things, and," he says, "it's very uncomfortable." So I said, "Gee, Mishkis, I don't know how I can arrange it." I made some inquiries when I got back, but it wasn't possible and feasible to do anything about it. Well, afterwards--! think it was 1937, maybe 1938--I didn't get an acknowledgement of the receipt of the JBC and I simply didn't subscribe to it anymore. That's the last I heard about Mishkis; that was the end. But when we were in Moscow in '44, I ran into Palladin at one of these meetings they'd set up, because they had gathered all the scientists of Leningrad, Kiev; in Moscow, if they had survived at all. So I said, "Oh, Professor Palladin, it's so nice to see you. You know, I haven't heard from Mishkis now for several years. I wonder if you know what happened to him?" He said, "Oh, I simply don't know, I couldn't tell you. After he'd been with me a few years he took another job and I haven't heard from him since." Now, Palladin was a little bit of a fellow with

Page  288288 a very thin, sallow face and a little goatee and a little moustache and looked like a small duck. That's the end of my Mishkis story until the summer of 1947 when I received a letter from Mrs. Mishkis. It was dated June 8, with an address in Russia. Among other things it said that they had lost Mishkis1 diploma--Ph.D. diploma—from the University of Chicago, during the war, as well as everything else that they had owned. They wondered if I could get a copy of this because it would be of great help. Then she said, "I might change my home address, therefore I will ask you to write to my brother and he will forward it to us no matter where we are going to be." She gave the address of her brother, a lawyer, who lived in Des Moines. Before I could take action on this, I got a letter from Lillian Eichelberger saying she had also had a letter from Mrs. Mishkis and had already gotten a copy of Mishkis1 diploma and had already forwarded it to the brother, Mr. Frumkin, in Des Moines. She had received a letter from this brother which described what had happened to the Mishkis's from the time they came back to Russia. This included the fact that Mishkis had been arrested in 1938 on charges that were never made known, placed in prison, and sent to Siberia. Mrs. Mishkis remained in Kiev working double shift to keep her son, James, at the university where he had a bright future in physics, and sending whatever scanty rations she could spare to her husband to keep him alive. When the Germans invaded Russia in '41, one of her brothers put his wife and daughter

Page  289289 in the charge of Mrs. Mishkis. He went to the front and was never heard from again. When the Germans advanced to Kiev, Mrs. Mishkis took her brother's family to the northern Caucasus and had to leave behind everything they had except what they could carry in their bare hands. They were evacuated finally to Miass, behind the Ural mountains, and there Mrs. Mishkis1 sister-in-law died. At the same time, their son was reported lost on the Moscow front. Recently Mrs. Mishkis wrote that Dr. Mishkis was released from exile and planning to remain in Siberia and they're going to be reunited after about ten years' This is the kind of sad story that apparently can still happen in Russia. Dr. 0.: This afternoon, we thought we'd start our discussion with a vignette in a sense, I suppose, of Professor Edwin Cohn of Harvard, a colleague and associate of Dr. Hastings of really more years than just your Harvard years, I believe. Is that not correct? Dr. H.: Yes, to relate either the scientific or social, and personal aspects of my life with Edwin Cohn from 1918 until his death in 1953, it would not be fair to omit some of the incidents that occurred during that span of years. Edwin and I met, first, in the spring of 1918 when he came to the laboratory, known as the Harriman Laboratory, in back of the Roosevelt Hospital, which was across the street from Columbia's old P S building on 59th Street in New York City. He came in the uniform of a 2nd Lt. in the Sanitary Corps, having just been

Page  290290 1 inducted into the service following the receipt of his Ph.D. from the University of Chicago. His assignment, at that time, was to study the proteins of bread and grains that go into making bread. I had, hitherto, used this laboratory as my own because it was the only place where I had access to a potentiometer and hydrogen electrode facilities. This was necessary for the carrying out of my studies on acid-base balance in exercise and fatigue that I was carrying on in the physiological laboratories of Columbia Medical School across the street. Cohn's experiments required his use of this hydrogen electrode apparatus and so we proceeded to share this facility. It was set up in a small—about 6x6--darkroom, because, in those days, you felt you had to have a darkroom in order to see the light spot on the galvanometer scale. I had been using a Kipp generator to generate my hydrogen from zinc and acid, but this was not fancy enough for Edwin. He knew how to make a hydrogen generator with two nickel electrodes and a bell jar and strong sodium hydroxide, hydrolizing the water with electric current, thus separating the hydrogen and the oxygen. So he converted my source of hydrogen into the electrolytically generated hydrogen. The so-called virtue of this particular way of generating hydrogen is, as the inside of the bell jar is filled with hydrogen and rose, it broke the current between the nickel electrode that was inside the bell jar and the surface of the solution which it had pushed away. We oftentimes had measurements to make at the same time, which

Page  291291 brought us into the room at the same time. One morning we were both in there and I was adjusting the potentiometer to the zero point and he had pressed down the key to start the electric current to generate the hydrogen. Without turning around, I started to say, "Edwin, did you wash out---," but that's as far as I got, because at that moment there was a terrific explosion.' Strong sodium hydroxide sprayed over both of us. We staggered out of this little darkroom into the hall; at least I was wondering if I was dead or not I We took our clothes off almost as fast as they fell off and took showers. Nothing happened to me or Edwin except that he got a slight drop of strong alkali on his eye, fortunately not in the center so it healed all right with no after effects. In a sense, it was sort of a beginning of a very close association! Dr. 0.: I didn't know whether you were going to say very close or very explosive relationship! Dr. H.: My wife remembers now, better than I do, his ambition and insensitiveness to other people at times. It caused me a good bit of trouble in the remaining time he was there until the end of the war. At that time he undertook electrophoresis studies of plant proteins, which laid the basis for much of the work that he subsequently did. Oftentimes, he undertook experiments which made it impossible for me to carry out my measurements and this caused some irritation on my part. But on the whole, Edwin and I got along very well during this first period of association.

Page  292292 After the war, he had a National Research Council Fellowship and worked under S. P. L. S^renson at the Carlsberg Laboratory in Copenhagen, and this, I'm sure, set the stage for the subsequent distinguished career that he had in the study of the physical chemistry of amino acids and proteins. On his return to the United States, Professor Henderson chose him to run a department of physical chemistry at the Harvard Medical School which was set up in 1920, with Professor Henderson as head and Cohn as his responsible laboratory investigator. This Department of Physical Chemistry, which went through a progression of names, was Cohn's laboratory home from then until he died age 61, in 1953. He was three years older than I was. From that first acquaintanceship and laboratory association in 1918 and '19, I would only see Edwin at scientific meetings or occasionally socially, because he used to come to Chicago, where his mother lived, from time to time while I was at the University of Chicago. We always had good times together. He was very well-to-do and his wife was even more so. When we happened to meet as we did in Rome at the Physiological Congress, we were their guests on many very nice occasions. In those early days, since I was interested in the physical chemistry of hemoglobin, we had many problems in common because he was, on occasion, interested in certain properties of hemoglobin as well as other proteins.

Page  293293 As an aside, I might say that he occupied part of the fourth floor of the so-called Building C-l of the Harvard Medical School; C-l being otherwise occupied by three floors of the Department of Physiology. In 1928, when I was offered the first opportunity to go to Harvard as a Professor of Biophysical Chemistry, which is the title he ended up with late in his life, I was given the opportunity to occupy all but three laboratories which Cohn then occupied on the fourth floor of this building, including the large corner office and the other facilities which were not his at that time. When I didn't take this job, he did take over the entire fourth floor because he had been approached by Professor George Minot to see whether or not he could use his knowledge of proteins to make a concentrated liver extract that would be more palatable in the treatment of pernicious anemia than the large amount of liver that pernicious anemia patients had to eat per day. He undertook to do this. But Cohn always used each opportunity to improve his situation; he said he would only do it if it would not interfere in any way with either his facilities, his budget, or his personnel that were engaged in basic research on proteins and amino acids. It was because of this that he then received the rest of the space on the fourth floor, and his basic research went on, independently, of the studies that were being carried out by quite different people making a concentrated extract of the pernicious anemia factor.

Page  294294 Dr. 0.: Was this characteristic of Dr. Cohn? Was he not that interested in clinical research or was he very jealous of his time for his basic research? [End of Reel 7, Side II] [Side I, of Reel 8] Dr. 0.: I was about to ask at the end of the other reel, was this attitude of Dr. Cohn's, which he showed when approached about preparing a concentrated liver extract, characteristic of him? Was he always very determined to continue in basic research and was he not overly interested in clinical research or research with direct clinical applications? Dr. H.: Yes, he was adamant about this. He felt that he should never get involved in anything that was of practical importance for medicine, that his job was to do the basic research on proteins and amino acids that needed to be done before anything else was done and he certainly was not going to give up any of that research for what he considered a very inferior type of activity—such as preparing a liver extract for therapeutic use. It was successful; the Cohn fraction is well-known, maybe it's still used for all I know though I doubt it. In those days I think they thought the active principle that cured pernicious anemia was probably a protein or at least a polypeptide. At any rate, he did profit by this because his department became a whole floor, and even though they

Page  295295 stopped activities on pernicious anemia extract long before I went there in 1935, they never moved out of any of their quarters. As a result, in that period from 1920 until 1940, which was when they did undertake some practical activities which I'll describe later, they contributed greatly to the characterization of the physical chemical properties of amino acids, peptides, and proteins, including the purification of proteins so that they had purely chemical substances to work with. I recorded in the biographical memoirs of the American Philosophical Society the main scientific contributions that Cohn made, so I won't repeat them here. Dr. 0.: Was that in 1953? Dr. H. : 1953. The Proceedings of the American Philosophical Society, page 336. But I think it's only fair to try and put some flesh and blood on this rather two dimensional description of Cohn and his work. He was a well built, healthy, vigorous person who, unfortunately, was subject to allergy which took the form of giant urticaria which would come out in great bumps whenever he got emotionally upset. I'm sure that he highly approved of my appointment to the Hamilton Kuhn Professorship and the head of the Department of Biological Chemistry at the medical school. It is seen in his letters and in the reception that he gave me and my wife when we came to Boston to consider this job. He was very helpful and

Page  296296 very enthusiastic and I think we probably both looked forward to a very fine collaboration with our two separate activities. Dr. 0.: Yes, you were separate administratively as well? Dr. H. : We were completely separate—separate physically, separate administratively, separate by name and separate objectively—and there was nothing that went on in our department that was competitive with his. He had no teaching responsibilities. The only trouble with his position was that his department had no stability; it depended on five-year grants from the Rockefeller Foundation. This, more than anything else, was what made life difficult for him and for me--not immediately, but later. Dr. 0.: He received no hard money from Harvard. Dr. H.: Probably a salary, I don't know what his budget was, and he may have had a little more than that, but he certainly couldn't have run his department if it hadn't been for these five-year grants, which had come first to Henderson then to him. You see, from 1920 to 1935, Henderson was still the head of this department and Cohn was an Associate Professor under Henderson. When I came, they promoted him to a full Professor and made him head of the Department of Physical Chemistry at the Harvard Medical School--that was his title. I was Hamilton Kuhn Professor and head of the Department of Biological Chemistry. Even though my budget wasn't very large, nevertheless, it meant that my department

Page  297297 had perpetuity and his didn't. My first apprehension about what the relations might be, came rather early in the fall of '35 after I had arrived at Harvard, when Edwin came across--he had to come through the Library that connected the Physiology Department to mine—to my office and stormed in shaking a check in his hand and saying, "I won't be a second-class professor," and he said, "What are we going to do about this, this check is the same as I got when I was an associate professor?" And the tears began to roll down his cheeks and he began to blow up with giant urticaria. Well, you can imagine that I was pretty upset, because, of course, I had had nothing to do with it whatsoever. It was a mistake in the Bursar's Office; he was supposed to get a raise in salary to what the minimum full professor got--not as much as I got. But as he said, "It isn't the money, it's the principle of the thing.'" Well, that was that, and it was corrected, of course. That was followed a little later by his request—since I had a good bit of unoccupied space on my first floor—if he could put Jesse Greenstein there to make some of the sulfhydryl peptides. He said he didn't have room for Jesse and besides mercaptans were so stinky. I agreed, but with the proviso—which of course I should have put in writing, but didn't,--that as soon as we needed the laboratory that Jesse Greenstein would return to the fourth floor of C-l. Well, a

Page  298298 year later we did need this space and Edwin, I^m afraid, rather conveniently forgot our arrangement and I had to appeal to higher authorities in order to get the room back. Well, I'll only add one more pre-war experience with Edwin. You see at Chicago, I had had a Research Professorship akin to Edwin's at Harvard. Now, I had teaching to do, as well as research, Sometimes I thought of myself as having been a Mary at Chicago and a Martha at Harvard. Edwin proposed, several times, uniting our departments but one of the things I was dead set against was ever getting tied up administratively with Edwin, I'm not his match--! was afraid of it. It was all right as long as we were absolutely separate. I'd built my department by loyalty of my staff to me, whereas many of his people were employees and they, by and large, didn't feel personal loyalty to Edwin. On several occasions I was able to get jobs for the people that he decided he didn't want with them any longer--. I did it several times. Still, he was always very decent to those he liked. I'll have to tie this up for ten years, I suppose, I don't know. Dr. 0.: No, this part, things like this can be very important in an honest evaluation of a man. It certainly can be restricted or closed for a period if you desire.

Page  299299 Dr. H.: I shouldn't have said that, I suppose, but it's true. One time, he made the suggestion that he had access to funds from wealthy Jewish families and that if I would agree to a merger that he would guarantee getting enough money to support both departments. Well, he enlisted the help of Dean Donham of the Business School to persuade me to agree. (Edwin had bought Donham's fine house on Brattle Street when Donham moved into quarters provided by the Business School.) Well, I won't go into the gory details of this except that it was sort of transmitted to me via Dean Sydney Burwell one day, upon which I wrote a letter saying that "if the merger was forced upon me, they could consider it my resignation from Harvard." Dr. 0.: In other words, Cohn did not approach you directly about this proposed merger. Dr. H. : No, it came out of the blue.' I think that if there's any correspondence on this at all, it's so highly classified it's buried somewhere at home; I wrote this letter, but never sent it-I didn't have to. Dr. 0.: Well, I'm wondering, if he were able to get this money to build up the two merged departments, could he not get it for his department alone? This is what seems curious. Dr. H.: I don't know. Dr. 0.: Methinks there's more than meets the eye'

Page  300300 Dr. H.: Yes, yes, well, there always was. I'm sorry to have to say it but I spent a lot of sleepless nights because I was afraid to close my eyes for fear he would be figuring up something else. He didn't have to worry about the teaching and all he had to worry about was whether or not his lab was going all right and how to get his hooks into our department. I was suspicious all the time after some of these things happened. Well, I can't remember whether Burwell took a side on this or not, nor whether Conant actually took a side on it or not. Donham thought it was a great thing; he was a great man at Harvard, a great money-getter. When he got his money for his business school, (it wasn't his turn yet,) it was the Chemistry departments turn and he told President Lowell, "Well, I'll get the money for the Chemistry school and the money for the Business School afterwards if you'll let me go out and get it." And he did; the Converse Laboratory resulted. Well, L.J. Renderson was brought into this merger incident. I admired Henderson very much and he had a great deal to do with my coming to Harvard. So, there were these four people, Donham, Conant, Burwell, and Henderson, with Donham definitely a pro-Cohn man. One day I got a call from Henderson saying would I meet him and go to Donham's house because Donham wanted to have a talk with me that afternoon. I went over and he started berating me for not agreeing to Cohn's proposal. He used this phrase, "You're being a dog in the manger—". You can imagine my reaction; I was 45 or more then--

Page  301301 I didn't take that lying down. I was so furious that I could barely keep my temper, and Renderson, realizing this, said, "Well, Baird, let's go and see if we can't resolve this." We went to Renderson's house, had dinner alone with a bottle of his good wine. He was a great collector of good French wine and he had a high-pitched voice and beautiful, big, bushy whiskers, you know. His opening remark when we took up the subject again was, "Well, Hastings, there's nobody who's sounder in his judgement than Edwin Cohn, except when his own interests are involved.'" And this describes Edwin really very well. He was a man of great culture, great ability and great egotism. Dr. 0. For the clarification now of the record, the Henderson you are referring to now is L. J. Henderson. Dr. H.r I refer to Professor L. J. Henderson, Lawrence Henderson, the great physiologist at Harvard. Well, that's all I ever heard of this merger. The subject was never brought up again after this and I haven't kept any record of it. Then came the war. In 1940, Professor Walter B. Cannon, the Professor of Physiology at Harvard who shared building C with me was Chairman of the National Research Council Committee on Shock. He was famous for his shock work in World War I. One day he came back from Washington and came to see me and said, "You know, we've got to have a better blood substitute," than gum acacia," which was toxic but was all we had in World War I.

Page  302302 It's been suggested that if we can get pure protein preparations out of all the beef blood that goes down the sewers at the abattoirs perhaps this would be a suitable thing." He said, "Whom do you suggest to work on this?" I said, "Well, Edwin Cohn, of course, is the person to undertake that because he's spent his life getting the information to make it possible to do this." Have I read this in here before? Dr. 0.: We really talked only briefly about it in December. Dr. H.: Well, Cohn, quite easily, did identify what should be done and now I remember I've already read that in the record. Dr. 0.: It's in our first section. Dr. H.: When the Committee on Medical Research was formed in 1941, we supported Cohn's work very substantially, well to whatever extent he thought was necessary. As a result, there was available not only concentrated human serum albumin for use in shock, which was what we were immediately after, but subsequently the other plasma protein fractions, the gamma globulins which are rich in antibodies against measles, poliomyelitis, infectious hepatitis, and hema-glutinins for blood-typing, and fibrin preparations of various sorts which could be used in surgery. I don't know whether they have been used very much. These were all developed in Cohn's laboratory and the criteria for preparing them commercially were enforced by Cohn and committees that operated under him (Commission

Page  303303 on Plasma Fractionation and Related Processes). Subsequently, the laboratory expanded to study preservation of red cells, white cells, and platelets. The work of Cohn's laboratory continues (1968) as the "Blood Research Institute." Dr. 0.: Would you say there was any change in Dr. Cohn's philosophy regarding basic research and clinical applied research with this experience of protein fractionation related to the war effort. Dr. H.: I think there was, largely because he would claim this is why we do basic research. The clinical applications were just expansions of his basic research. The fact that it happened to be on a large scale gave him an opportunity to do things that, on a small laboratory scale, he couldn't possibly do. And I think there's something in it. I must read into this record the remark that Professor Parnas made, as I demonstrated the Cohn fractions in Moscow in his presence along with these other Russian blood experts. Parnas was the Polish Professor who was the father of present organic phosphate biochemistry. It was Parnas and Baer who discovered phosphagens, as they were called. These included, what has now become creatine phosphate ATP, etc. Dr. 0.: He was a physiologist. Dr. H.: Chemist, sort of the father of biochemistry and biochemists. He would send his best students over to Cambridge--like Keilin

Page  304304 and Mann--to Hopkins but they'd never come back to Lwow where he was a Professor. The Russians had saved him and his wife. As the Germans were coming in one side of town, the Russians swept down and brought him to Moscow and he lived there until he died of very old age after the war. Anyhow, as I demonstrated the fractions one after the other Parnas, who was a big and handsome man, nodded his head in approval and said, "Ah, there is nothing so practical as sound fundamental workJ" Dr. 0.: Cohn would have loved to have heard that. Dr. H.: Yes, well, he did, I told him that, and I've used it very often since--in speeches. I think that, actually, Cohn never lost sight of his basic goal because he felt that any good basic knowledge you did get would itself beget new knowledge. It would not necessarily itself be of practical value, but given the opportunity and need, it would become so. During these war years, when Cohn's contracts ran into the hundreds of thousands of dollars a year, it was largely my responsibility to oversee them. I was in the position of being Cohn1s--well, I'm trying to avoid saying "boss" because I wasn't, of course. But I had a very large share in the control and what would happen, to the contracts. So I never had any trouble with Edwin during the war years. In his very last year of his life he was, unfortunately unbeknown to other people, a very sick man, and had repeated uncontrollable

Page  305305 flare-ups. Some of his colleagues like John Edsall even transferred to Cambridge. Cohn and Edsall were a very famous team of protein chemists. Everybody knew that Edwin wasn't himself and he died of a cerebral accident very suddenly. His home was a sort of an international salon—cultured people from all walks of life—he had a lovely home in Cambridge and you always found interesting people there in literature, history, politics, etc. In spite of lots of little irritations, I suppose you'd say big irritations sometimes, that he caused me, when Edwin died, I felt a great loss. I missed him, I really mean this! Thank goodness I can't remember all the irritations because they were so numerous that at one stage Jim Conant called me and said, "Look, I've instructed Edwin not to communicate directly with you again but only through me, and I'm giving you the same instructions." I can't remember what year that was. It was after the war, but at some stage it did become a problem to the administrators. He did have quite a good group of fine people working with him and he did have some graduate students—very good ones too—and we had ours, and the two great events in the Department of Physical Chemistry in the Medical School and the Department of Biological Chemistry at the Medical School, was when my Ph.D. students, Renee Zlockover married Howard Dintzis, who was a Ph.D. student at the same time in Cohn's department. That was duplicated some years later. In 1956 my next woman Ph.D. student, Michaela Smits married Tommy

Page  306306 Thompson, who was trained in Cohn's department, but by then Edwin had died. He died in October of 1953. Because I like this too, I think I will read this into this record. Edwin often quoted and indeed headed one of his books from his department with this quotation from Charles Martin, date 1687, "Though man can't fully know what God hath done, yet 'tis his duty still to think thereon." Dr. 0.: That is an excellent portrayal of Dr. Cohn. It really puts some flesh and substance as you say to the name which is so familiar to everybody connected with medicine. Like Hastings and electrolytes and acid-base balance; it's Cohn and proteins and protein fractionation. Dr. H.: Of course he was highly honored for these things. There is a postscript to this description, namely what happened after Dr. Cohn died in 1953. At that time he had a number of titles and a number of responsibilities. He was not only a University professor and Director of the Laboratory of Physical Chemistry related to Medicine and Public Health, but he was also Chairman of the Department of Physical Chemistry which was to go out of existence on his retirement or on his death. He had organized the Protein Foundation which was a corporation to hold patents that were taken out in connection with the plasma fractionation.

Page  307307 He had formed this Foundation after the war as a substitute for the Research Corporation which had previously held his patents. He also was in control of the Board for the control of the products put out by the pharmaceutical houses and the establishment of criteria to be met before their distribution. These were responsibilities which grew up because of the way the program developed in the course of the war, but which in peacetime needed to be returned to the Public Health Service in respect to standards and to the pharmaceutical houses in respect to how they would make their products. They had been held in very tight rein by Cohn throughout the war. After his death there was a problem of what to do with the Protein Foundation, which he had tried very hard to get associated with Harvard. There was a feeling that it was affiliated, though Harvard had steadfastly refused to have any official connection with it even though it was made up of Harvard people and in so far as it had operating laboratories, they were Harvard laboratories. Cohn, though he tried very hard, was never able to get Conant to agree to have any kind of an official connection with Harvard. He died in 1953 and Pusey, Nathan Pusey, was the President of Harvard. Conant had left in '52. Suddenly with Conn's death, here were people like Oncley on a tenured appointment as a professor with no department' The department had disappeared with Cohn's last breath] There were other people not on tenure who were very good on assistant

Page  308308 professor level or other appointments and nobody knew what was to be done with them. Then there was the problem of the Protein Foundation. There was the problem of this Board which has a long and complicated name which had to either be disbanded or at least disassociated from being Harvard's responsibility. Harvard was in big business.' There were all sorts of responsibilities that were not academic responsibilities. Being responsible for setting standards and enforcing standards' It had just developed because it was good to let Edwin do the whole thing since it was important for the military aspects of the war. So it had grown like Topsey and here we were stuck with it.' At Dean Berry's suggestion, I was asked by President Pusey to head a board to make recommendations about what to do with the "Cohn Empire" and the many activities that had to be clarified as the result of his death. We formed a committee with such wise heads as William B. Castle, and Al Coons, a young but able, wise head who was the secretary of the committee. Janeway was involved with the Cohn Empire so we couldn't have him. There were two or three other Harvard people who were not involved directly. In order to insure that this would not be a Harvard star chamber we also had Chester Keefer on from Boston University and Frank Schmitt from MIT. (Francis 0. Schmitt is a Professor of Biology and also a knowledgeable protein man.) There was some talk to the effect that if we did anything to liquidate the Cohn Empire, it would be taken to the public to keep it going. Fortunately, it all ended amicably.

Page  309309 Well, we took testimonies from everybody. All of those people who were in or affiliated with the Cohn responsibilities. I drew up, with Al Coons' writing help—he writes extremely well--a very formal document with recommendations to the effect that this activity should go to the Public Health Service and this should go back to industry and this should happen to the laboratories, the Protein Foundation should be kept administratively separate from Harvard, etc. What was left when all this was done could be amalgamated with the Department of Biological Chemistry. So John Oneley and Douglas Surgenor and Margaret Hunter were simply made members of my department and the laboratories became technically the responsibility of the head of the department though they continued to function quite independently. It was all done with no publicity and there has never been any. Ever since then President Pusey, when I see him, always says, "Well, how is Judge Hastings?" If that were not enough, when I was in Australia in '57, which was only four years later, I received a letter from Charlie Janeway, who had taken over the responsibility of being head of what was left of the Protein Foundation, asking me to be on the Board of Directors of the Protein Foundation. I am not on the Board of Directors any longer, but I am still a Trustee. It has had its name changed now to the Blood Research Institute. It is still trying to get enough outside money to survive. It hobbles along and still does a lot of good research done—mainly through Tullis.

Page  310310 Dr. 0.: Tullis is the man you met on the plane and described this morning. Dr. H.: He is the key man. Oh, I had a wonderful letter from him you should find some place which he wrote when he agreed to leave the New England Deaconess Hospital and join Cohn's group full time. This was the period when things were not "buddy-buddy" between me and Edwin and he had to explain why he was being in a sense "practical but traitorous." I have a lot of interesting letters that you haven't read yet. Dr. 0.: I know this is a problem with not having access to these papers continuously between my visits to La Jolla. [Pause in interview] Dr. H.: This will be a vignette on one of the great biochemists of this century, William Mansfield Clark, who was so well known for his extensive and systematic studies on hydrogen ions and their role in physico-chemical systems and on oxidation-reduction potentials in organic and biological systems. I knew him from about 1921 when I first met him in Washington, but I did not have close association with him until after I had been at the Rockefeller Institute for some time. From that time until he died, I had extensive correspondence with him, saw him several times a year and during the war was very closely associated with him, because

Page  311311 at that time he was Chairman of the Division of Chemistry of the National Research Council. From the time the Committee on Medical Research O.S.R.D. was established, he undertook the study of questions of interest to us: e.g. the sterols of the adrenal gland, particularly what was then known as Compound E of Kendall and is now known as cortisone. He was the first to organize a concerted effort and enlist the cooperation of chemical houses and pharmaceutical houses in supplying compounds that might be potential antimalarial compounds. Thereby hangs another tale, because when this antimalarial program was reorganized on a businesslike way with contracts for the companies, he refused to have anything to do with it. For a time, William Mansfield Clark, whom I loved and revered, and Alfred Newton Richards, whom I loved and revered, would hardly speak to each other. They were on opposite sides of the fence. The one feeling that we must have strict contractual arrangements with these companies; the other, Clark, feeling that he had put his honor on the line with these companies. They freely supplied him with these compounds on his promise that he would not divulge where he got them or what they were used for by the companies. At any rate, it happily was resolved after the war, but I made several visits to Baltimore and spent weekends there trying to get a softening of his position so that he and Richards, who had been fervent friends could have an easy relationship again.

Page  312312 Well, that isn't what I was going to say when I started out, but it shows what really is important in your mind, at least what is left as important in your mind, because it is what floated right to the top and it has not been put on record. None of the biographical memoirs of Clark mention this incident at all. As I say, I became a firm friend and we had a continuous correspondence. His letters were always exciting ones to receive and to read. He was very frank about making comments about my papers. He always praised them if he approved of them and criticized them if he didn't in any respect. Perhaps the measure of our close relations was that on three separate occasions when he received honors, he asked that I make the speech about him! The first was when he received the Nichols Medal from the American Chemical Society, the second was when he received the Remsen Award from Johns Hopkins on his retirement, and the third was in 1957 when he received the Passano Award, which was a $15,000 award set up by Williams and Wilkins. So I would like to read the beginning of my remarks on this latter occasion, June 5, 1957, which was a fancy full dress affair at the Waldorf Astoria with all of the great of chemistry and medicine present who could get there. "Ladies and gentlemen. At last I have an assignment which I can undertake with unadulterated pleasure. I have been requested to make a speech of appraisal of tonight's laureate and his work. Now this is not the first time that this has happened to me. The

Page  313313 first time I did it was on the occasion of Dr. Clark1s receiving the Nichols Medal from the American Chemical Society and the audience was composed of chemists. How unnecessary to waste time describing Bill Clark and his work to a group of fellow chemists. The next time I described him was when Bill delivered the Remsen Lecture before an audience of his friends, neighbors and colleagues at Johns Hopkins. How superfluous to attempt to evaluate him to such an audience. But tonight is entirely different. You are here to do honor to a great medical scientist, but you have no idea why he is great. You take it on faith that he belongs here, and I am to tell you why. This is finally the chance I have been waiting for for years. Fortunately I realized what my problem would be in plenty of time and I dropped all other research in order to devote my time to bringing my earlier analytical data on the output of Clark, the heterogeneous man, up to date. My first analysis of Clark-o-cellulose, trade name, Clarkose, was in 1936. The sample weighed 3,852 grams and on analysis proved to be 98 per cent solid science, composed of 69 per cent biochemical phase and 29 per cent bacteriological phase. The remaining 2 per cent were fluid and gaseous impurities such as Presidential addresses and the like. My second analysis was made in 1952. Although the scientific output was maintained in quality and quantity, there was also a sizeable dilution with war time reports resulting from

Page  314314 his Chairmanship of the Division of Chemistry of the National Research Council during World War II. This material proved to be amorphous, defying crystallization. This time I have found no such contamination of the sample. It is genuine unadulterated C. P. Clarkite. It belongs to the apatite minerals, that is the unsatisfied appetite branch. It just goes to show that one must never trust a single or even duplicate analysis if you want to get a truly accurate scientific picture of a medalist. How few there are who have had to be subjected to triplicate analysis of their scientific deeds, at least not by the same scientific investigator. How unlucky can a fellow be?" Dr. 0.: That is delightful. Dr. H.: I then went on and in a more or less serious vein related a large number of his scientific contributions. I then said, "Perhaps I should speak of Bill as a golfer, who in true Clarkian form did the experiment of making a hole in one in duplicate; or as a glass blower extraordinary, who in moments of frustration would go into the lab, close the door and blow some more glass. I guess it must have been a particularly bad day that led him to attempt to blow a tortuous glass apparatus for anaerobic titrations only to find at the end of an hour's labor that though his intricate and delicate job was done, alas, he had securely and inextricably enclosed within the curly cues a stationary part of the glass blowing table. Small wonder that his cry of anguish

Page  315315 brought Eric Ball and all of his staff running to the glass-blowing room in alarm. At all costs I should not reveal his propensity for poetry which is terrible.' I'll show you what I mean. I have several samples which tend to arrive at Christmas time accompanying another of Bill's inventions known as "Gripit," a secret concoction that comes in a lipstick container and that prevents slipping of the hands on baseball bats, fishing rods, and golf clubs. With it comes this example: 'Come thou Gripit, give the touch, To which a grip without a crutch, Transmits the entropy-less swing, To do the graceful, powerful thing.1 Again, one year, to me: 'To give Gripit to fisherman Hastings Is nothing but profligate wastings.' He'll use it for bait, Then imagine too late, That fish can be cooked in its bastings.1 When he became Emeritus Professor of Biochemistry, he signed a letter on serious things with this postscript: 'Emerititis is a dread disease, It bends the back and bows the knees. Profs, who reach three score and more are favorite victims by the score!

Page  316316 to which I have the temerity to add: If more were like our laureate, Then fewer Profs, would get the gate, When time records them 65 Although indeed they're quite alive; To Bill, we colleagues of all science Give thanks for you and your alliance That brought us man's continuum Electron's web where protons hum. My friends, no biochemist known to me today has made greater contributions to .the basic medical and biological sciences than has our laureate this evening. I represent all who have benefited from his friendhsip, his wisdom, and his works. We affectionately salute him and rejoice in the high honor that has come to him. Professor Meritorious, William Mansfield ClarkJ" [End Reel 8 Side l] [Reel 8, Side II] Dr. 0.: He was truly a fine teacher. Dr. H.: Bill Clark died in 1964. All of his friends and students mourned his passing. Dr. 0.: When was Dr. Ball with Dr. Clark? Dr. H,: From 1929 until 1940, he was there 11 years.

Page  317317 Dr. 0.: For some reason I thought it was more recently than that. I had forgotten that he joined your department in 1940. [Pause] Dr. H.: I don't know exactly when I began to get a reputation for being a good person to make speeches at dedications and after dinner speeches, because I am not in any sense a funny man. To do any of these; to speak at any of these events takes a great deal out of me and a great deal of preparation. Just as much as if it were a lasting contribution of some kind. It has amused me a bit to find that I have given commencement addresses at Western Reserve and Woman's Medical College and dedication speeches of medical school buildings at Baylor Medical School in Houston and the San Marcos Medical School in Lima, Peru and the new medical science building at Boston University. Vannevar Bush was on the same program at Boston University and also made a speech. After the program he said, "Why Baird, I didn't know you had that in you!" I regard any praise from Van as high honor. When they dedicated the Biology Building about 11 or 12 years ago at MIT, I made one of the speeches there along with such people as Det Bronk and ten years later at the dedication of their new Biology Science Center at MIT, I again made a dedicatory speech. I'm not very proud of any of these. Even though they take a lot of work to do, they have no lasting value. I suppose the reason they ask me to do these things is because I manage not to make the whole thing too serious.

Page  318318 Well, why did I want to put that on there? I don't know. I guess I was reminded by the fact that I made the three speeches for Bill Clark's three awards and two for Van Slyke and on the 10th Anniversary of the Arthritis and Metabolic Disease Institute I made a speech. It seems like more because I always had to work so hard on them. It is not a very large number after all, is it? [Pause] Dr. 0.: Can you describe Dr. Walter Cannon for me? Dr. H.: Prior to coming to Harvard in 1935, I had met Walter Cannon from time to time at Federation meetings, but since I seldom attended the American Physiological Society meetings because I usually attended the Biochemical Society meetings, he didn't know me at all well. However, I never missed a chance, before I went to Harvard, to attend any scientific session in which it was advertised that either he was going to give a paper or A. J. Carlson, ("Ajax"), was going to give a paper, because the two never agreed on the interpretation and they would pack any meeting that either of them were speaking at because you knew the "fur would fly." Carlson was a big, two fisted, big-hearted, wonderful Swede with a Swedish accent which he used to best advantage. Cannon was every inch a gentleman, but every bit as forceful and highly cultured, though originally a middle westerner—like most of us.1 (Laughter)

Page  319319 Cannon was inspired to physiology as a youth, because he grew up in the same town as Beaumont who was born in Praire du Chien in 1871. Cannon says in his book, The Way of an Investigator, "My interest in that historic town was intensified in later years, when I learned that it contained the site of old Fort Crawford, where in the 1820s, the American army surgeon, William Beaumont, 'the backwoods physiologist1 as Osier called him, made his classical observations on the gastric mucosa." Cannon, at the time I came to Harvard in 1935, was 64 years old and was even then suffering greatly from the skin cancer that had developed some years before. It was due to the exposure he had given his hands in the late '90s shortly after roentgen rays were discovered. The primitive X-ray machine exposed his hands to X-rays. Indeed he told me that since he couldn't sleep at night he wrote the chapters that make up The Way of an Investigator. I think he was quite surprised to come back in the fall of 1935, from a sabbatical leave at the Peking Union Medical College, to find that I was the Hamilton Kuhn Professor of Biological Chemistry. He hadn't known who was going to take it, but he promptly showed me every evidence of friendship and cooperation as long as he was working actively and he stayed on until '42 until he was 70 as head of the department. When he died a very moving tribute in the form of a Memorial Service was held in one of the Harvard amphitheatres

Page  320320 After I had been at Harvard just a few months and had been put on a number of the committees of the University such as the Admissions Committee and others, Dr. Cannon came in one day and said, "My goodness Hastings I am glad to have you here' You know Folin would never accept an appointment to any committee, so for all the years we were here together, I have always had to do double duty. Now I can relax and leave it to you'" He always had a small department and perhaps the most interesting of the members of his department was Alexander Forbes. Together with Halowell Davis, he made the really first significant observations on what are now called the Berger's rhythms of EEGs. They were pioneers in the use of the cathode ray oscillograph recording of nerve activity. Alex was from the fabulous Forbes family. He never took any interest in dress. He was an enthusiastic and graceful skater and flew his own airplane, at one time having two. He sailed his own ships, once back to Norway; undertook for the Navy, in the uniform of a Lt. Commander, a survey of the coast of Labrador which had never been adequately surveyed. As a result he saved a good many American lives. I am sure he must have worried the Annapolis graduates in Washington. He would turn up there--! used to see him at the old Cosmos Club--in a rumpled tunic and unpressed trousers. One thing that I haven't mentioned about the Harvard period was the fact that Ph.D. degrees were given by medical school pre-clinical

Page  321321 science departments. If a person wanted to take a Ph.D. degree in biochemistry, for most of the period that I was there, he had to register in the Graduate School and take it in our department. As head of the Department of Biological Chemistry, I was a member of the Faculty of Arts and Sciences. In so far as we had graduate students in the department, I was responsible to the Dean of the Faculty of Arts and Sciences in Cambridge. It made me a member of the Faculty of Arts and Sciences. The Dean of the medical school had no jurisdiction over the graduate students or the graduate program. Each of the pre-clinical departments, anatomy, physiology, biological chemistry, bacteriology, pharmacology, and pathology and Cohn's department of physical chemistry were departments that were authorized to give training for Masters and Ph.D. degrees. These departments comprised the Division of Medical Sciences. The President appointed one of the professors Chairman of the Division of Medical Sciences. Folin had been the perennial Chairman until he died. Most of the Ph.D.s had been granted in the Department of Biological Chemistry and there hadn't been many of those really. However, they included such people as Sumner, who was the first to crystallize an enzyme, which was a real landmark in American biochemistry. Prior to this, enzymes were not believed to be crystallizable, and many doubted that Sumner had done it. Indeed he had to go to Stockholm and prove to Von Euler in his own laboratory that he could crystallize the enzyme, before it was accepted.

Page  322322 Dr. Oc: Von Eulerfs son or grandson and I were residents together in Clinical Pathology. Dr. H.: Really? Hsien Wu, afterwards head of biochemistry at the Peking Union Medical College took his Ph.D. with Folin. The Folin-Wu system of blood analysis is probably the best known throughout the world, at least until instrumentation came in. It was used in every clinical laboratory. Their methods were the basis for some of the mechanized methods used now. E. A. Doisy, famous head of St. Louis University, who not only unraveled the chemistry of estrogens, but the chemistry of Vitamin K for which he got the Nobel Prize. Sumner also got the Nobel Prize. Subbarow, who worked with Fiske got his Ph.D. in the department. Fiske and Subbarow discovered phosphocreatine which was the beginning of high energy phosphate bond chemistry. It is ironic that their paper announcing the discovery and identification of phosphocreatine came out just a year or so after Meyerhoff and A. V. Hill had received the Nobel Prize for their work on the chemistry and physics of muscular contraction, because as soon as phosphocreatine was discovered, the stated reasons for giving Meyerhoff and Hill the Nobel Prize had disappeared! Dr. 0.: You can't win them all! Dr. H.: Ah, they got the prize in the nick of time. Well, they deserved it for other work so it is all right.

Page  323323 Probably, if Fiske hadn't been so slow to publish and had promptly followed the discovery of phosphocreatine with publication of their discovery of ATP, they might have had a Nobel Prize themselves. To go back to the Division of Medical Sciences, when I went in '35, Conant at that same time appointed Edwin Cohn as the Chairman of the Division of Medical Sciences. Prior to that it was simply a paper organization which never met or had any real rules or anything. Each department accepted or refused candidates, and after they had a good thesis they would examine them and pass them or not. So prior to 1935, it was pretty much an individual department thing. Cohn very successfully organized it into a unit with rules and admission committees, prerequisites; we had meetings with minutes, etc. We maintained some continuity and equality of requirements. It was really a good thing, because some of the departments were a little lax. I guess Cohn must have been Chairman for 15 years or so. After Cohn, Landis was head for two years and then Ball took over and he has been head ever since. Graduate courses were organized specially for graduate students. This was very important. Prior to Ball's taking over and organizing these courses specially designed for graduate students with special laboratories at the medical school, the only way graduate students could take courses for credits was to take them along with the medical students and then do so well they got an honor grade in

Page  324324 competition. You had to make a B or better in order to get graduate credit. [Pause] Dr. 0.: The date is February 9, 1968 in the office of Dr. Hastings in La Jolla. We are going to start the discussion this morning of the events and circumstances leading up to Dr. Easting's departure from Harvard University. Dr. H. : It was by no means a sudden decision. The ground was being laid over a period of years I guess. I expect that it simply awaited an opportunity that I thought fitted my interest and capacity at that particular time that it did come which was toward the end of 1958. It began I would think in retrospect in 1949. The war had been over a couple of years. I had been back as Head of the Department since the end of '45. Things were going quite well. Our research was going extremely well and we had been able to be one of the first in the isotope business supported by contract with the A,E.G. Beginning in '46 I had a number of postdoctoral fellows and a graduate student or so. The perennial problem of keeping the building C-2 adequate for research and teaching was a continuous fight against obsolesence, because very little had been done except to repair plumbing and to change lighting and update the laboratory furniture in an occasional laboratory since the Harvard Medical

Page  325325 School had been dedicated in 1906! The morale of the department was good and I had a fine group of associates such as Ball, McKee, Fritz Lipmann at the Massachusetts General, Lew Engel. As I look at the 1949 departmental picture which we took annually in June, I see a great collection of young men who have made their mark in medicine and in medical science. In 1948, President Conant had, in his customary thorough way, decided that he didn't know enough about the problems of the medical school, except when people from the different hospitals and from the Longwood Quadrangle would bring up subjects at faculty meetings. One of the very large problems that was looming, was whether or not the Massachusetts General Hospital and other hospitals, but the Massachusetts General Hospital particularly, should go into the development of research institutes in the basic sciences as part of their hospitals. This was a desire and an objective which Dr. Walter Bauer, the Professor of Medicine and Dr. E. D. Churchill, the Professor of Surgery at the Massachusetts General Hospital were very anxious to get underway. Indeed, they were anxious to have a drive for money to get them a research institute building that would house biochemists, bacteriologists, etc of distinction. Those of us who were still operating with very restrictive budgets, and what we thought were inadequate teaching staff to do the best job, emphasized that as far as Harvard was concerned, the first thing they must do is to get more money to

Page  326326 support the on-going departments in the basic sciences and this should take precedence over building full-time research institutes at any of the affiliated hospitals. I did not oppose their having good biochemists, as good as they could get, if they needed them in connection with their work. As an example, I helped to get Dr. Lewis Engel, one of the country's leading chemists in the field of steroids to join Professor Joseph Aub at the Massachusetts General Hospital for his cancer research activities. I had helped other hospitals get their chemists. Also, when we had an opening for such a biochemist, if he was willing to do his share of the teaching as if he were actually physically in the department when the medical students came, I would support his appointment to the department in the same way I would support the appointment of somebody who was going to be full-time in the Longwood Quadrangle. However, this did not satisfy my colleagues at the Massachusetts General. They wanted to be assured that they could offer appropriate appointments as Harvard faculty members to anyone engaged in full-time research at the Massachusetts General Hospital. In other words, a Harvard appointment would accompany any appointment they would make. Rightly or wrongly, I had a rule of thumb that I would have no more people whose loyalties were primarily to affiliated hospitals than I had staff who were paid by Harvard University and therefore whose loyalties would be to Harvard University. Whenever I could get an extra assistant professor supported by Harvard, then I was willing to have an extra assistant

Page  327327 professor who was paid by one of the affiliated hospitals. I had the feeling that in this way, Harvard always had a department on which it could count as far as primary loyalties were concerned. Dr. 0.: I gather from what you say that these hospitals did get their laboratories, etc. Dr. H.: They had such units going. The Huntington Hospital had been moved from land adjacent to the Harvard Medical School, i.e. the funds and activities had been moved many years before this under Aub to the Massachusetts General Hospital to the laboratories in the old MGH building. So they were already doing what amounts to full-time research, but they wanted to expand this and get a brand new building. Of course they did; I can't remember when they got their first building, but I was there for the dedication, participating with Linus Pauling as a matter of fact on that occasion, Subsequently I think they have now added two more full-time research laboratories. I don't want to make too much of this. It was incident, if you will, to Conant's deciding he would use his technique of quizzing people, indeed attacking them in a sense, in order to get information quickly. So he created what we who participated used to call the "Committee of 8." Every week for a whole afternoon each week for about 8 weeks, eight of us plus Dean Burwell went to Massachusetts Hall where Conant had his office and sat at a long table with Conant at one end and Burwell at the other end. More or less, I think through

Page  328328 accident, perhaps just because it was natural to sit down that way, I sat on Conant's right and next to me on the same side of the table were Howard Mueller, then head of Bacteriology; Eugene Landis, who was head of Physiology; and George Wislocki, who was head of Anatomy. Opposite me on the other side of the table was Walter Bauer, and next to him was Pete Churchill, and next to him was George Thorn, and then Charlie Janeway, the head of Pediatrics at the Children's Hospital. Dr. 0.: Clinical side on one side and the basic sciences on the other. Dr. H.: Then Conant would bait us on what were the needs of Harvard Medical School in planning for the future. It crystallized in the end, with our making a big chart of the different disciplines in the medical sciences and putting in the slots that would be needed 10 years hence and checking off those that we had and drawing up a budget if you will of how much more money we would need for this, regardless of where these people were physically to be--i.e. at a hospital or at the Longwood Quadrangle. It was really a hammer and tongs affair before we got it worked out, because Conant is known for using the tough questioning technique and sometimes differing with whomever he was quizzing for the sake of making him defend what he said. This was his technique as a teacher of chemistry. He did this very effectively and I am sure it saved

Page  329329 him a lot of time. It was certainly effective in bringing out the differences in point of view between Walter Bauer and me. Since we were on either side of Conant, he heard us loud and clear when we differed with each other. Parenthetically, I am reminded that when this was all over, the next year and Burwell was retiring, he (Conant) had me over to his house for lunch one day. We had a pleasant time talking and reminiscing about the war. During the war we had often had dinner together at the Cosmos Club in Washington. We would sit alone and both being in the same war business, we could talk freely, except about the Manhattan District, which I didn't know about and he never divulged what they were up to. At any rate, it was while Conant and a succession of faculty committees were hunting a successor for Burwell that Conant invited me over for lunch one day. We just talked about my experiments and our past war experiences and then as we walked across the yard toward his office--! was heading for the subway to go back to the medical school--, he said what was obviously his objective for that noon lunch, "Oh, by the way Baird, I think I should tell you that there is talk that I ought to make you Dean on Burwell's retirement, but I will tell you quite forthrightly that there are two fellows that I would never make the Dean. One is you and the other is Walter BauerJ" (Laughter)

Page  330330 Dr. 0.: He had been exposed to you bothJ Dr. H.: We didn't have what it took . . . Dr. 0.: You weren't diplomatic in expressing your differences. Dr. H.: I'm afraid not. So he lost a couple of good Deans by having that Committee meeting.' (Laughter) Walter sure could raise his voice; of course I'm told I can tool Dr. 0.: You defended the rights of your department; I'm sure there is no question of that' Dr. H.: What I am leading up to though, is the fact that in '49 Burwell did retire. There was a good bit of feeling, particularly by professors who had been Colonels in the war that Burwell wasn't a vigorous enough Dean. He hadn't improved the finances of the medical school; he wasn't much of a money getter, so there were a lot of rumblings that we ought to have another Dean. He had been Dean from '35 to '49, 14 years; that's six years longer than I regard as the normal half-life of a Dean.' He sincerely literally wanted to go back to medicine and laboratory research in the field of pulmonary vascular disease, which he had never completely abandoned. He had taken the Deanship originally on the understanding that he could be a part-time Dean. He was of course much more than a half-time Dean, but he always did at least one month of service at the Brigham and he did keep his

Page  331331 laboratory going and kept turning out papers. As far as Burwell was concerned, he was delighted with the chance to retire. We had a search committee for a successor on which I served with other faculty. We easily agreed early that Chester Keefer would make an ideal Dean and he was asked. Conant tried very hard to persuade Chester to be Dean, but after a good bit of consideration Chester decided that he preferred the Evans Memorial at Boston University. It was something he could handle better than stepping into the kind of mess which Harvard Medical School appeared to be in at that time. We were engaged in a struggle between the needs of the basic science departments at the Longwood Quadrangle and the great pressures that were being brought to bear by the clinical people and the affiliated hospitals to enlarge their resources and facilities. You see each of these big affiliated hospitals; the MGH, the Boston City Hospital, the Peter Bent Brigham, and the Beth Israel each had a complete Department of Medicine and Department of Surgery and there was even a Department of Pediatrics at the Massachusetts General. Yet we only had one Department of Biochemistry, Physiology, etc. Any other medical school would have been delighted to have any one of those four clinical departmentsi Anyhow Chester declined and then Churchill was asked and he declined; Landis was asked and he declined; even Francis 0. Schmitt of the Massachusetts Institute of Technology, the head of Biology was asked and he declined. Then Conant suddenly

Page  332332 called a meeting of the Search Committee and said, "I have just come back from a meeting of the Board of Scientific Directors of the Rockefeller Institute and Tom Rivers who I sat next to at dinner told me that we were foolish if we did not get George Berry, who was the Assistant Dean at Rochester at that time. "I want you fellows to find out all about George Berry." I wrote to Wallace Fenn, the head of Physiology at Rochester, and he gave him a very high recommendation. He said he ran a vigorous shop and thought he would be a good money getter and had been a distinguished bacteriologist at the Rockefeller Institute and at Rochester. I never met Berry until he came to Harvard. So in 1949, Burwell retired and Berry became Dean and we really got along very well. He didn't make any big changes that involved the basic sciences and he understood the problems very well and stood up as an ally. He was very effective in understanding that though the affiliated hospitals should have what ever basic scientists they needed for their work; nevertheless that my position was a sound one, that we ought to keep 51 per cent of the stock in the basic sciences in the department at Harvard. I must say he was generous in helping me add to my staff which in a sense thereby helped the hospitals too. He never opposed my stand of keeping it at least an equal arrangement with the hospitals and the full-time school. However, I missed Burwell. I had had a very easy relationship with Burwell and Berry soon got involved in the big enterprizes

Page  333333 that were needed at the medical school. I mean it eventually grew into his having great plans for new buildings and restoration and rejuvenation of the present buildings, which incidentally when finally done, cost more than it would have for a new building. When they gutted and rebuilt the interior of Building B it took just as much money as a new building would have. He was very vigorous in setting up machinery for getting bigger bequests and more frequent bequests and he added an awful lot of senior professorial appointments. He raised faculty salaries considerably. Because this took up all of his energies and time the business of day to day problems in running the department that required Dean's office decisions were increasingly turned over to Henry Meadow, who was the Assistant Dean. Henry was a perfectly wonderful fellow. He would sit and listen to you; George wouldn't listen. You would go to George's office with a problem and before you could get your problem out, he would say, "Now before you begin Baird, I have something 1 want to ask you about." Then your time would be up and you would have no time to discuss your own problem. George would say, "Well go see Henry about it." So Henry Meadow became the man that we Professors in the basic sciences dealt with very happily. He always took the position that he wanted to be helpful and would listen and try to understand your problem. I think that Henry Meadow being there with George Berry is what made Berry's period as Dean a highly successful one. Everyone looks upon it as a

Page  334334 very good one. But I missed Burwell. We had gone there at the same time; we were about the same age. He was a scholar. We were very good friends, both his wife and my wife and Sidney and I, so I missed him. His retirement was the beginning, I am sure, of the preparing the ground for my eventual retirement in '58. Then I had the invitation from Oxford; actually it was the second invitation, as I couldn't go on the first one. I had the invitation and the nomination originating from Sir Rudolph Peters, then Professor Peters as he wasn't knighted yet, in 1951 to spend as much of the year as I could as a Visiting Professor. It would be subsidized by a Fulbright Professorship. Although, I count my years at Chicago, I had been a Professor since 1926 and had never taken advantage of a sabbatical. I was on an 11 month, so called four quarter system at Chicago and I had taken a leave of absence to go to China during that period but it was not a very extended one. Also it was not paid for by Chicago. After coming to Harvard, I never had had a sabbatical, though I am sure that the University felt that because they spared me 3 days a week without docking my pay for five and a half years, that they had done about all they ought to do for me. To tell you the truth I had never asked for one. I didn't think they owed me anything. So I didn't know whether I would do it this time, but Eric Ball said, "Well, I'll tell you; I've been here now way past the time I

Page  335335 am eligible for a sabbatical, so if you don't take yours, I am going to take mine." He did take a sabbatical the year after I did. So I did take it and accepted this invitation and went to Oxford in 1952 and spent 6 months there. When I got back, in fact the day I got back, the telephone rang in my office and my secretary said that President Conant is on the line. He said, "Baird, I wanted you to hear it from me before you hear it from anybody else that I am retiring and am leaving as President as of March 1st. I'm going to be High Commissioner to Germany." Well this was quite a blow to me I realized afterwards, because I had known him so long. We had been in Berlin together in 1925 and had been good friends ever since. We had probably seen less of each other since I was on the faculty as he was meticulous in not mixing things. Perhaps I should mention this because it will not be in any other papers that you have. [End Reel 8, Side 2] Dr. 0.: This is the beginning of Reel 9, Side 1 on February 9, 1968 Dr. H.: I was about to relate another anecdote about Conant. The incident that I am about to relate occurred in about 1939 or '40 It was the year before our cyclotron became available and we entered upon the Carbon 11 work. As a result of a conversation with him one

Page  336336 day on the work we were doing, he said he wished that he could get into the laboratory again once in awhile, but he didn't want to work in the chemistry laboratories in Cambridge. Indeed he was meticulous about leaning over backwards and not really doing as much for the chemistry department as he did other departments--or so the chemists thought. Dr. 0.: You mean because of his background as a chemist. Dr. H.: Oh yes, he was one of the country's leading chemists and had won all of the chemistry medals, etc. before he became President. I said, "Why don't you come over and work in my lab once in awhile?" He agreed that this would be a good idea and subsequently on several occasions during that year he would call on a Saturday morning and say, "Have you got anything going on in the lab this afternoon?" When I said yes, he inquired, "Can I be of any use?" I said, "Come on over; I'll have a sandwich for lunch for us in my office and everybody else will be gone so we can work in the lab." You know, he did come over and we sat and had a sandwich and a cup of coffee in the office. I would have locked the door of the lab to the hallway and locked the door to my secretary's office, because I had a connecting door between my office and my lab. He would take off his coat and light up a big cigar and say, "Now what is it you want me to do?" Sometimes there were some titrations to do; sometimes there were some weighings to do. Whether any of the department members ever knew he did this, I don't know. At any rate

Page  337337 they never acknowledged it went on. I think he thoroughly enjoyed it. Dr. 0.: I am sure it was a great change of pace. Dr. H.: I insert this as an illustration of the kind of relation I had with Conant, so that when he told me he was leaving I thought, "Well there goes another tie that I have to Harvard." It was a real disappointment. Then I had had this sabbatical and had this glorious time working in the laboratory full-time while I was in Oxford. Whereas I hadn't been able to in my Harvard lab. I suppose actually I felt I couldn't compete with the fine young men who were out there in the lab doing work in that period. They were people like Knox, Ball, Folch - Pi, and Engel. At any rate I hadn't spent working time in the lab for years until I went to Oxford; I managed to get over my "buck fever" there, because I didn't have to keep up with the boys. So I came back with the realization that I did still love to do lab work and still could. I think I have probably said it before, but at the risk of redundancy I will say it again. Having spent the first 18 years of my scientific life in the laboratory and everything I had learned had been learned through doing the experiments, through my fingers! It was just like going home again to be in the laboratory at Oxford.

Page  338338 So that added the fact that I wanted to be in the laboratory, but I wasn't able to be in my own lab when I came back anymore than I had been before. My lab was full of able young people and activity on the problems of intermediary metabolism in liver. I see here that Renold appears in the picture of 1952 which must have been his first year with me. He and the other postdoctoral fellows were turning out so much data and so successfully that it was no place for me to get in! At any rate I didn't. But the desire was there, to be in the lab again; it was kindled. So that is another thing that contributed toward my desire to retire as head of the department. It was only one year after I had been with Peters at Oxford that he jumped the gun and retired before he had to, at Oxford, and went into a full-time research job after being head of the Department at Oxford for about 35 years. He went back to Cambridge, his old home and had a full-time research job which he could keep until he was 70 at Babraham, that is, the agricultural research station just outside of Cambridge. When other opportunities were offered, I looked at them pretty carefully. One was the informal invitation by Jim Shannon to become Scientific Director of the Heart Institute. Another was from Tom Parran, who had then retired as the Surgeon-General of the Public Health Service and had gone to Pittsburgh as the Dean

Page  339339 of the School of Public Health and promptly started to invigorate the University of Pittsburgh, both medical school and School of Public Health. He invited me to come as Professor of Biochemistry V and be in charge of graduate education in the medical sciences there. They didn't spell out the job carefully enough to suit me--otherwise I might have taken it because Mrs. Hastings was quite excited about it. And then in 1956 Dr. John Bugher, whom I had known by his having succeeded Shields Warren as the Director of Biology and Medicine for the Atomic Energy Commission, had moved to the Rockefeller Foundation. I believe as an Associate Director, He, I'm sure, was responsible for my being invited to take a position with the Rockefeller Foundation as an Associate Director for Medical Education and Public Health. This was essentially the Foundation's worldwide Fellowship program. As it was described to me they were particularly anxious to establish fellowship programs in the South American countries and India. I took this very seriously. Dr. 0.: Even though it would be a position totally removed from the laboratory. Dr. H. : Yes! I didn't really think I was as bad a potential administrator as Conant had decided I might be! (Laughter) This had grown on me not because I had always run my own unit since I was 30 years old in Chicago and Harvard, but I think it

Page  340340 had gone to my head when I was in Washington and in this position of making decisions, I thought I was pretty good. Dr. 0.: You also had a great interest in what was good and what was bad in medical education which would make this job attractive. Dr. H.: Yes. Of course the other thing that made it appealing was this; this was still the period in which I was in the business of stirring up fellowships; stirring up means of training more medical scientists at all levels. People knew this and that is why this offer was made. I was prominent at that time for my campaigning. Each time I made an after dinner speech I managed to bring this need in. So it wasn't really unnatural that they might ask me to do it, nor unnatural that I would consider it seriously. I considered it seriously enough to go down and have talks with Dean Rusk who was then the Director and Warren Weaver. Alan Gregg wasn't there. I believe he was on leave of absence for that year and was to retire at the end of that year. He was actually in residence at the Big Sur, California. I took time to see how it would be to live in New York again. Even though they were going to pay me a slightly larger salary than I was getting at that time. I think my salary was $18,000 and they offered me $19,000. I knew that we couldn't live in New York City in anywheres near the standard of living we were

Page  341341 accustomed to in Boston and Brookline, so we would have to live in the suburbs as we had toward the end of our original living in New York. So I even went to Grand Central Station and pretended that I was getting off a commuting train again and walking to West 49th Street and timing it. This didn't help my enthusiasm, because the people I passed on the street were pretty crummy looking and everybody was hurrying and hustling and bustling. So I went home to Boston that Saturday and went down to Westport Point, where we always spent our summers. I would go down weekends and Mrs. Hastings would go down in June and stay until September. I got in my little rowboat with the 3 horsepower motor on it and went out in the tidal waters, where I sometimes fished for striped bass on the surface and sometimes for tautog on the bottorn--that's called a black fish in New York--and this time I was fishing for tautog. I was sitting there in my little rowboat with nobody else around and the water rushing by with the tide, waiting for a big old tautog to take my crab and I can see it as vividly now as I did at the moment I An arm came up out of the water a little ways off from my boat and shook the fist at me and I heard the voice say, "You fool Baird.1 Here you spend all your life learning to be a teacher and a scientist and now you think that you could make good as an administrator. You're an amateur as an administrator and always will be.1" With that I reeled in my line and came back and declined the position with thanks.

Page  342342 One other comment I want to make about this particular position is this. Between the time I had made the trip to New York at the invitation of Dean Rusk and the Rockefeller Foundation and this incident at Westport Point and my actually declining, there had been at the end of May a medical school Class Day exercise, at which they hopefully try to have amusing and informative speeches for the returning alumni of the medical school. They had persuaded Alan Gregg to come and give one of the superb talks. I was also on the program. As we were sitting together before the session began, I said, "Oh, Alan, I'm sorry you weren't in New York last week because I went down to look over that position that the Foundation is offering me; I'm sure you know all about it." He looked at me! He said, "What position?" I said, "Associate Director." He said, "Well, Baird we mustn't talk about this here. As soon as this is over let me come up to your office and tell me all about it." Immediately after the meeting we went to my office and I told him all about it. He said, "This is most surprising. I hadn't heard about it. I must think about this. I will write you a letter." On June 3, 1956 he did write me a letter, long hand on Century Association stationary that cannot be considered a letter either advising me to take the position or advising me to decline it, though it contributed to my declination. He made several statements in this letter that indicated his extreme unhappiness, a personal unhappiness, with the direction that the Rockefeller Foundation had been going ever since the appointment of Max Mason as President

Page  [i] ALBERT BAIRD HASTINGS VOLUME II National Library of Medicine Bethesda, Maryland 1969

Page  343343 in 1929. I think I will leave it at that. [Completion of interview of February 9, 1968] [End of Reel 9, Side 1, (only a third on Side 1 recorded)] [Side I, Reel 10] Dr. 0.: The date is May 1, 1968 and we are in the office of Dr. Albert Baird Hastings at the Scripps Institute of Oceanography in La Jolla, California. This is Dr. Olch of the National Library of Medicine. This is Side I, Reel 10 and the first of this third interview session. Dr. Hastings in our last session we were talking about your impending departure from Harvard, and the last thing I believe we talked about was your offer from the Rockefeller Foundation which you elected not to accept. I thought we might pick up at that point. Dr. H.: Yes, that was in 1956. I must correct your assumption though, your opening remark. I had no desire to leave Harvard; I had a desire to leave the position as head of the Department of Biological Chemistry and get back into the laboratory where I found I still could be effective and enjoyed personal laboratory work which I no longer could do at Harvard because of the administrative responsibilities. When I broached this possibility

Page  344344 both to Dean Berry and to President Pusey, they refused to appoint another head of the Department prior to my retirement which would be obligatory in three years, or at least when I was 66. Of course, they were correct in refusing this because if they were to replace me with somebody that was in the department such as Professor Ball, they would probably be stuck with him as head after I did retire whether they wanted him or not. They could hardly afford to go out while I was still there and on active duty and receiving a full professors salary to add another full professor as head of the department. So it was obvious that if I was to stay at Harvard, I must stay on as head of the department. I must say also for the record that I would have stayed until I was obliged to retire even if it was until I was 70 unless they had permitted me to retire ahead of the retiring age when I actually did leave in 1958. I could not have brought myself to resign my professorship at age 63. However the forces were at work that made me wish that I could get back into research work and part of the reason or one of the reasons that contributed to this was the fact that Dean Berry had decided to undertake a very drastic revision in the curriculum. When it became obvious that the responsibility for the kind of instruction in biochemistry that would be given to the first year medical students--which I felt we were doing very well--was no

Page  345345 longer to be my responsibility as head of the Department of Biological Chemistry, even the fun of teaching had disappeared from my job and I was in the position of being eliminated from personal research fun and personal teaching responsibility. All I had left was the administrative responsibility which amounted to doing the business that permitted the rest of this wonderful Department of mine to have fun. If it hadn't been for the Postdoctoral Fellows who had been a part of my life continuously since the end of World War II, I think I would have had no fun at all. The Tuesday seminars with these Postdoctoral Fellows from noon until late in the afternoon, when we studied books on advanced biochemical matters together and had discussions of their relation to medicine, kept my life from being very sterile indeed in those last few years. At any rate in 1957, the year after I declined the Rockefeller Foundation job, I made two exciting trips with Mrs. Hastings, one to Peru, another to Australia. In April, we went to Lima, Peru as the guests .of the University of San Marcos, the oldest university in this hemisphere. I gave the address for the dedication of the new medical science building of the medical school. A building that had been built with funds partly from the Kellogg Foundation and partly from the Rockefeller Foundation. We were in Lima for two weeks and were given the V.I.P. treatment. The Dean of the school was Dr. Alberto Hurtado. He had worked

Page  346346 in this country at several places and I had known him for many years. He was well known for his high altitude physiology work. He had worked some at the Rockefeller Hospital and some at the Fatigue Laboratory. The Professor of Biochemistry was Alberto Barron. He was the younger brother of E.S.G. Barron, who was my first assistant in my latter years at the University of Chicago. Indeed, Alberto Barron had spent a year on a postdoctoral fellowship with me at Harvard prior to this time. I did no research during these two weeks obviously, but I did give several lectures to the staff and medical students and on the occasion of the dedication as I said. As extracurricular activity they took Mrs. Hastings and me to Cuzco and from there to Machu Picchu which is one of the very great wonders of the world. Since I was there over a Sunday, it was arranged that a wealthy Ecuadorean who represented Ciba and had a fine boat took me fishing. In the summer I was invited to be Visiting Professor in the Department of Biochemistry of the John Curtin School for Medical Research at the Australian National University in Canberra, Australia. This institution was established by Sir Howard Florey. The head of the Department of Biochemistry at the Australian National University was Professor Hugh Ennor. He was a big strapping, two-fisted, redhaired, red complexioned Australian. Hugh Ennor had worked at Oxford in 1952 when I was there and indeed was there in 1956 and had visited us a couple of times in Boston. We were great friends

Page  347347 It was he who had arranged the invitation. He had by now become the Dean of the John Curtin School for Medical Research. Incidentally this School for Medical Research did not give M. D. degrees; it only gave Ph.D. degrees. It had just been finished in 1956 and I was their first Visiting Professor in Biochemistry. It was quite an amazing institution, built more or less according to Ennor's desires. It is true that Florey, who was originally an Australian, had suggested the formation of such a school to Prime Minister Curtin. The thought was that once they had built it, Florey would come as the Dean, but he never did. This school had a Department of Chemistry under Adrian Albert--it really was organic chemistry. It had a Department of Microbiology, a Department of Experimental Pathology, a Department of Physiology under Eccles, and the year after I was there a Department of Biophysical Chemistry under Ogston, whom they had attracted from Oxford We had quite an exciting time during these months between July and November. The Australians are a hearty and vigorous and unselfish people who play hard and work hard. Margaret and I came back with the feeling that if we were 20 years younger, we would migrate there. There is a great future in Australia for young people who want to work hard. They can make a living so easily that they only work about half the time and go to the races the other half or exercise. We went to Sidney and Melbourne and Adelaide in addition to Canberra and I lectured several times in

Page  348348 each place. I feel that Australia has a great future with a land mass about that of the United States and a population about that of New York City. All that is really needed is to have packaged ways of delivering water to the center of the continent. Since we have come back, oil has been discovered and many mineral deposits. They are diverting the watershed of some of their rivers into the interior so I predict a great future. Now Canberra itself was an exciting place to live in because it is laid out for a big city of 250 or 300,000, but there are only about 50,000 people there. It is a planned city. The man who got the prize for laying it out was a Chicagoan, I think in the 1920's. World War II delayed things but they are still following this city plan. It is very beautiful. The population was one third university people, academic people, one third government people as it is the seat of government--the embassies are all there--, and one third business people. This means that with the small population you met people from all three areas of activity at almost any social function. We had a chance to get acquainted with Menzies and his wife and many of the people in his cabinet and many of the Ambassadors as well as the academic people. All together it was a very exciting four months. Again the best part of it was the fact that I worked in the laboratory. I undertook a problem which I really had not done anything on for several years at Harvard. To tell you the truth,

Page  349349 I combined some of the last work that I was doing with Barren at Chicago before I left there in 1935 and a continuation of the thesis work that Elmer Stotz did first in 1936. This seemed a good opportunity to undertake that. As an aside, I might record that the reason this popped into my head was shortly after arriving there I got notice that Barren had suddenly died in Chicago—he inherited my job there—and I was asked to write a memorial about him for Science. In familiarizing myself again with his printed work before writing this memorial, a research idea occurred to me. I decided to look into the effect of deliberately changing the oxidation-reduction potential of hemolyzed cells on the conversion of the hemoglobin to methemo-globin. It doesn't seem like a very earth shaking thing to do but it involves the effect of the oxidation-reduction potential of the environment on enzymatic reactions, in this case an oxidation from ferrous iron to ferric iron in hemoglobin. It had not been done by Stotz or Barren. They had skated around the edge of this. It came out so interestingly that I was able to get a formula, an equation which related this rate of oxidation to the potential at which the medium was stabilized by dyes of different oxidation potentials. In the fall of 1957 we returned to Boston and I took up life again where I had left off at Harvard. As far as I can remember, there was nothing of any great excitement that came off in 1958.

Page  350350 I see here on my Curriculum Vitae that I must have gotten back early enough in November of 1957 to deliver the first John P. Peters Memorial Lecture. Peters was Professor of Medicine at Yale, and I regarded this as a high honor to be selected by Yale and Peters' colleagues to deliver this. The academic year '57-'58 was the first year of applying the integrated curriculum to the medical students. I participated up to the extent that the curriculum committee permitted me to, but my favorite course with a course had been "integrated." This was the study of the transport of oxygen and C0« and the study of blood as a physico-chemical system and the demonstration with the students themselves as subjects and analysts of the nine possible kinds of acid-base conditions that man can have--one normal and eight abnormal--this had been abolished. This was the teaching program that I had worked up with the Department of Physiology as an integrated section of our two courses and had been highly successful. I am sure that my nose was very much out of joint over this action. I could not properly evaluate how the integrated course was really going because I felt they were missing so much! (Laughter) However, I am sure the students were excited about this new curriculum, if only because it was new and something different. They put all they could into it and so did the staff. It is a good thing to have to teach things differently from time to time because

Page  351351 you have to work hard to do it and you can't just rely on the fact that you have done it before. On the whole, it was probably a good thing to have done for the long pull. Earlier in that year (1958) I was asked by Dr. Keeney, Director of the Scripps Clinic and Research Foundation, to come out and consult with him. Actually he wrote a letter to me first asking for some suggestions for staff and stating that they were contemplating a research building. I expect that I have already put in the record that in 1956, Mrs. Hastings and I had come out and stayed with the Revelles in La Jolla around Christmas time for a week because I was giving a lecture on January 2 on the peaceful uses of atomic energy in Los Angeles. Dr. 0.: I don't believe you had mentioned that. Was this your first exposure to the Scripps Clinic? Dr. H.: No, I had been there before from time to time when it was called the Scripps Metabolic Clinic and when Eaton McKay was there. But it was the first time since Dr. Keeney had taken over as Director. I believe he became Director around 1955. I should describe a bit about the Scripps Clinic. In 1924 Ellen Browning Scripps, a very wealthy maiden lady who had been born in England and lived near La Jolla, gave money to start the Scripps Metabolic Clinic. This fabulous woman, who

Page  352352 had no children to whom to leave her money and who we are told in La Jolla was the brains back of her brother who was the successful publisher of the Scripps-Howard newspapers, had built La Jolla. She had built the Presbyterian Church, the Bishop School for girls, the Scripps Hospital, started the Scripps Institute of Oceanography all prior to the Scripps Metabolic Clinic. La Jolla is today, what it is because of Ellen Browning Scripps. Dr. James Sherrill, who was an authority on diabetes and had worked with Dr. Woodyatt of Chicago, had come out here just at the time insulin had been discovered. He became acquainted with Ellen Scripps and at his suggestion she undertook to support a metabolic clinic to be built next to the hospital, the Scripps Memorial Hospital. At first she gave it very small funds every two or three years to keep it going and then it had a big part in the residual estate so it got some endowment. He added Dr. Thomas Lambert to help him and Dr. Francis Smith who was a cardiologist from Washington University. I guess there were some others who have either died or left, but they ran this small diagnostic clinic for the diagnosis and treatment of diabetes and its complications. Also on this staff was Dr. Eaton McKay. He had worked with Van Slyke at the Rockefeller Institute in 1927 and '28, and then had come to the Clinic. He was brilliant and much more interested in biochemical research than he was in clinical medicine.

Page  353353 It is getting ahead of my story a bit, but in a few years he had a chap associated with him named Arne Wick. Eaton McKay and Arne Wick, in the basement of the Clinic because they had no laboratories as such, worked out the correct reactions by which fatty acids are metabolized. They did this in the pre-isotope days. They slugged it through by distillations. When I went there, I inherited a room full of distillation glassware.1 This was a prodigious effort of great biochemical importance. McKay and Wick proved that you had beta oxidation which cuts off the two carbon units that is the basis of the metabolism, and synthesis is beta oxidation and condensation. You have two carbon units and two more carbon units combine, you make it four. Then you reduce that and then two more add to four and make it six. This was a contribution of the first order. It could be made now with the use of isotopes very much more simply, but in those days it was a great effort. I always like to emphasize this, because it was the one thing that put the Clinic on the scientific map. The unfortunate thing was that Dr. Sherrill had not much respect for laboratory research and because McKay wouldn't do his share of clinical work, they didn't get along. McKay used to fight with Sherrill so that McKay used to stay in the basement and he wouldn't come up and Sherrill wouldn't go down. Two years before Dr. Keeney came, around 1953, McKay handed in his resignation one too many times and they accepted it. Everytime McKay wanted something and

Page  354354 Sherrill wouldn't give it to him, he would hand in his resignation to the Board of Trustees. Since his wife was a Scripps they wouldn't accept it, but as I say he handed it in one too many times. Poor Eaton McKay has been batting around ever since. It is one of those tragedies. Dr. 0.: Is he still doing laboratory work? Dr. H.: No, he is practicing medicine. Last time I heard he was in a town near Los Angeles, I believe Anaheim. He tried being the Director of Research at Squibb or Parke-Davis but that didn't work out. At any rate he had left some years before I even thought of going to Scripps and Wick stayed on until 1958 as a biochemist. Wick then decided he wanted to go into academic work, having had enough of full time research. He had a chance to become a professor at San Diego State, so in 1958 he left the Clinic. During 1958, Dr. Keeney, who had become the Director and whom I had met in 1956 at the Clinic when I visited it to see who was still there that I had known from earlier visits. Dr. Keeney is an allergist, originally trained at Johns Hopkins. He had a contract with the CMR, OSRD during the war on athlete's foot, an important problem as a matter of fact' (Laughter) He had contracted tuberculosis and had come to La Jolla some years

Page  355355 before and then recovered from his tuberculosis. I believe that he worked in Eaton McKay's lab as an assistant shortly after he came to La Jolla the first time. When he came out the second time he set up a practice in allergy and was very successful. When Dr. Sherrill died, the Board of Trustees asked Dr. Keeney to make recommendations for a successor to Dr. Sherrill. The upshot of this was that the Board asked Dr. Keeney to be the Director Dr. 0.: Was there an element of wanting somebody local from La Jolla to be the Director in this decision? Dr. H.: I don't think the Board of Trustees had any idea whether he ought to be local or otherwise. It was a very unsophisticated Board of Trustees I can assure you. It probably was a "rubber stamp" to Sherrill. I suppose I ought to say that Keeney inherited a very good diagnostic clinic, but it really was hardly more than a group practice clinic, where the doctors were on a full time salary, It was not an "Institution." Dr. 0.: Did they have hospital beds at that time? Dr. H.: They had 50 beds but no planned research laboratories. They had converted some rooms in the basement for laboratories. Physically it was a small building put up next to the Scripps Hospital and had an underground passage so you could use facilities such as X-ray in the hospital. If they had surgery to be done, it was done at the hospital.

Page  356356 Dr. 0.: Administratively the Clinic and the Hospital have always been separate? Dr. H.: Absolutely separate. There is no overlapping of their Boards of Trustees or funds. The hospital of course had no full time doctors. The Clinic was staffed entirely by full time doctors. When they needed something in the way of consulting service, they simply called in a surgeon or opthalmologist or whatevery they needed and paid him. The significant thing was that it did not function as an institution under Sherrill. The different doctors came in and saw their patients as if they were private patients and put on their hats at the end of the day and went home and didn't see each otherI The letter of gift from Ellen Browning Scripps in effect said that this institution, the Scripps Metabolic Clinic is to diagnose disease, is to do clinical investigation, is to train doctors and is to serve the community. Keeney realized that it had not lived up to these statements, except the first one, and he proceeded to use me as a consultant as to what direction it ought to go. He told me that the first thing he did was to introduce the idea of serving free lunches to the staff and almost requiring them to eat together. This was an important change that started it on the road to being an "institution" instead of an association of half a dozen different clinicians. It was a very important contribution to the growth of the Clinic as an institution and

Page  357357 and they do it to this day. Of course the Comptroller is now complaining how very expensive it is to do this, but they still do it. At one stage during this summer of 1958, Dr. Keeney had written me a letter asking for names of biochemists and I made some recommendations. One of the fellows I had recommended was Gene Knox. He (Keeney) had wanted to replace McKay and Wick. After I had signed my name, I scribbled a little footnote meaning it to be facetious, "I suppose I ought to wait until I retire before I am eligible" or something to that effect. When he got this letter he called me on the phone and said, "look, if you are at all serious about that, come on out and let's talk about it." Anyhow I went out and I still didn't think about it very seriously. He had plans for a 7 story research building, and I made some suggestions verbally like these suggestions here (referring to a letter written in 1958 to Dr. Keeney) (8/4/58). Dr. 0.: This letter was written before you had any serious ideas of going to La Jolla? Dr. H.: Oh yes, the only thing that had happened was that he took me down to the plane after this trip and, as we went through the gate, we were talking about the plans for this building and he said, "You know Walter Bauer has written me that he wants to come out when he retires from Harvard." I said, "Now Ed, don't

Page  358358 forget that when you get that building to save me a place for when I retire too."' He said, "Well, why don't you retire now?" Then I went through the gate. Well, it was a prop plane so it took 8 hours to get back. By the time I got off the plane in Boston, I had really decided that I would try and do it. I thought there was every reason to do it and very few against it. I even worked out the reasons why I thought that they ought to let me retire. As I said earlier I wouldn't resign. I had two arguments. One was that Harvard rules had changed from the time I had been appointed so that instead of it saying a "permanent officer," which a faculty position with tenure is, may request retirement anytime after he is 65 and must retire in the academic year in which he is 66, it had been changed when Conant had retired as President to become the High Commissioner to Germany to read, a permanent officer of the university may request retirement anytime after 60. It was done so Conant could retire instead of resign. The other argument I had to back this up was, that I had gone to Harvard in 1935 at age 40 and I had taught 25 classes of medical students, of 125 each, and 25 and 40 was 65 and the fact that I had done this in 23 years meant that I had done my academic job. I had simply worked harder and accomplished my job in a shorter period. Of course they laughed over this. They did let me retire when

Page  359359 they found I was insistent on getting back into the lab and this was an opportunity to do so. They made me a specific offer which was I thought a pretty generous one--it wasn't as generous as they later made to some other people (laughter)--but it was alright; it was very nice. They paid me my Harvard salary, they paid for our moving, they fixed up a laboratory for me in the basement by modifying some animal quarters and putting in laboratory benches and air conditioning. It was very roomy and entirely adequate. Indeed it was, in many respects, functionally the best laboratory that I ever had in my life for what I wanted to do. It put them to a good bit of expense and they appropriated $10,000 for me to equip it and said they would guarantee $3,000 a year for expenses and would provide the salary for a technician and a secretary. As goes with all memberships in the staff at the Clinic they pay all your dues for memberships in scientific societies and your subscriptions to scientific journals—and free lunchJ For all of these extra things I agreed that I would not expect them to keep up my retirement allowance,! would do that myself, my T.I.A.A. Annuity. Dr. 0.: Could I ask you Dr. Hastings a rather candid question? Did you have any hesitation or any thoughts at that time about joining the Scripps Clinic in light of its somewhat weak clinical

Page  360360 side. I gather there were definite plans to build up the basic sciences, but did you have any assurances at that time that an effort would be made to develop the clinical service which would build on the basic science department? Dr. H.: To tell you the truth I never explored it at all. The thing that gave me the desire to do it was a sudden feeling that it would be like starting again at the Hospital of the Rockefeller Institute. Now this was partly its size. When I think of it, I think of that group of men sitting up there on the steps (referring to a picture of the staff of the Rockefeller Hospital hanging on his bulletin board), though these weren't the same men, I didn't know them, I didn't know their competence one way or the other. I knew that Keeney thought of this as a research institution, I was not told how much endowment they had, which, I believe, is only about $3,000,000 so it isn't very much. I did know that they were solvent and put away a lot of money each year. Actually when I got here and for the years I was chief consultant to Dr. Keeney, I did know their finances. They used to lay away, even after I came, about $80,000 a year in the bank. I didn't realize that it was not financially wealthy, that it could never be like the Rockefeller Institute with a big endowment. It was a pay clinic. I don't know that I even knew that when I first came. I knew of McKay's reputation and that was about all. I didn't know the reputation of the clinical people.

Page  361361 As I say, when I got off the plane in Boston I decided to explore this further. There were negotiations and telephone calls and then it came through in writing and it seemed very generous to me. I hadnft had $3,000 a year that I could spend on my research since World War II from Harvard. It was only when I got to spending it that I realized what a short way $3,000 goes! I made up my mind in September to go and there was great scurrying around in Boston then. I must have my portrait painted, there must be parties, I must make a speech at the last Faculty meeting, the Department had to give me the chair you are sitting in. The most amazing thing about it was the disbelief of everybody. It was just unbelievable to Eric Ball, to Dean Berry, to Frank Rackemann at the Medical Exchange Club when I announced it. With a long face Rackemann said, "Why Baird! How could you? After you had once gotten to Boston!" (Laughter) A typical Bostonian. This probably amused me more than anything else, the disbelief, because I did it very casually as the most natural thing to do. It wasn't something I was hell-bent on doing,, I wasn't being forced into it. It just clicked! Margaret had some misgivings and if she weren't such a wonderful person she would have said no. She didn't want to leave Boston. [End Side I, Reel 10]

Page  362362 [Side II, Reel 10J When they sent me a copy of the picture which appeared on the front of Modern Medicine (July 1960), Margaret said that it should have borne the caption, "How do the feathers taste?" because I've got the smuggest expression--as though I have just eaten the canary! This is the way I felt about it. I was having the best of two possible worlds! I was a Professor Emeritus of Harvard, age 63, and I was an active paid member of the Clinic to do nothing except work in the lab, on what I wanted to work on with my own hands. I was in an environment where I could take up work again because I had no local scientific competition in my research. Maybe I haven't made it clear; the reason I couldn't work in the lab at Harvard after World War II was that I had gotten behind. I had all these bright young fellows going full blast and all I could do in the lab was go out and say, "Have you got anything I can do today?" They would say, "Well you can weigh up some planchets for us." I would do that, sure, but that is not working in the lab. I didn't have a room of my own with nobody working in it but me, and time. So the feathers tasted good! At any rate having decided to go, I declined going on a leave of absence and I declined staying out the next year until June, because there is no fun in being a lame duck. When I announced it in September, Margaret and I left Boston on December 31, 1958, and I appeared on January 1 at the Scripps Clinic and Research

Page  363363 Foundation and made sure that there were witnesses that I appeared there because I also had resolved not to have the trouble that so many people have of having to pay taxes to two different states when they leave in the middle of the year. I never had any kickback on the fact that I finished in Massachusetts at the end of the year and started in California on the first of the year. At any rate I took up life here, and a very good life it has been. I have never personally regretted having made this move at all. Indeed, it was also probably the best possible thing I could have done for the Department of Biological Chemistry at Harvard. The reason is that we needed so much in the way of repairs and renovation and budget for equipment. George Berry had a schedule on when he was going to do this and when he was going to do that. We had monthly meetings of preclinical science heads which I had started without George Berry, but when he heard that we were meeting without him, he invited himself in and proceeded to name them the Preclinical Council and use them. Of course I am not a politician, but I do play politics.' (Laughter) I got tired of our department and Landis with his department of physiology and the other basic medical science heads trying to get something done and approved at the Faculty meetings. If you went in there cold by yourself, your colleagues couldn't even support what it was you wanted because they were ignorant of

Page  364364 your needs. We had 6 to 7 times as many clinicians on the faculty so I conceived this idea that once a month the 6 of us, who were preclinical heads, would have lunch together in each others department. Whoever was host would present the problems of his department and what he had in mind for the future. So we 6 fellows were appraised of what was going to come in the future and we had been doing that for about a year before George Wislocki of Anatomy died. As I said, George Berry joined it. He continued to use it this same way; don't misunderstand me, but he proceeded to take over our planning business and to schedule things so that as soon as it got on the Deans level, it was perfectly obvious that George Wislocki's Department of Anatomy was going to have to be revamped first and after that the Bacteriology Department would come next, then Baird would be retiring in five years, and then Landis. Quite properly, he scheduled these things. In the interim we couldn't get anything^ We needed repairs terribly and space. So when I retired George Berry had to change his schedule because in order to recruit a professor he had to offer him something, and it had to be a hell of a lot more than I was living with. So they did. They got Gene Kennedy to come as my successor. At the same time the surgeons were removed from the top floor and this was turned over to Eric Ball and Manfred Karnovsky. Dean Berry built animal quarters and transferred the surgeons so it gave Biochemistry the

Page  365365 whole of building C-2. He redid my whole floor and the entire first floor and the top floor which he hadn't counted on having to do for a good five years. Now they are about back on schedule for the big student lab which they have divided into two floors. The enormous tall ceilings were a waste of space. It cost them a pretty penny to do this of course. Furthermore they had to add another professor as well as my replacement to get Gene Kennedy to come. I think I will read this into the record though I may scratch it out when I see it in print. It has entertained me no end that in 1935 after a great deal of hunting around, Harvard went to the University of Chicago and the Department of Medicine and selected a person for the head of biochemistry who had never taught an undergraduate medical student, and he was age 40. In 1960 again Harvard went to the University of Chicago, and this time picked out a biochemist who was also 40 years old and who had been in the Department of Surgery for six years and biochemistry for only 4 years. Dr. 0.: I didn't realize that Dr. Kennedy had been in the Department of Surgery. Dr. H. : Well, I exaggerated a little bit. He had been there with Charlie Huggins in the Ben May Laboratory for cancer research from 1950 to 1956. I once offered him an Assistant Professorship in our

Page  366366 Department on Birgit Vennesland's suggestion, but he decided to stay with Huggins. He is a prince of a fellow. I certainly feel highly honored to be succeeded by a man like Gene Kennedy. Dr. 0.: It is nice when one can say that because it is not unusual in this day and age that one's successor is not the individual that you would like to see get it. Dr. H.: Well, they almost didn't get him. I better keep this a complete and honest record. Obviously, I wanted Eric Ball to succeed me. Indeed, this was part of my package of winding up at Harvard. Eric was highly distinguished, a member of the National Academy of Sciences, had run the Department and proven his ability as the head. That was another reason that I felt secure that I was not leaving the Department in the lurch in any way. It was perfectly obvious that when I left, Eric could take over as head--which he so much deserved. The Department wouldn't suffer in the slightest. Dr. 0.: Was he interested in the position as head of the department? Dr. H.: I think he would have taken it, yes. They made him Acting Head for a year and set up an Ad Hoc Committee. The Ad Hoc Committee argued, as such Committees do--I've been on too many of them—and I am perfectly sure that sometime in that first year they made the list of the eligible people and they came to Eric

Page  367367 and they probably said well of course Eric is fine and there is no reason why he shouldn't do it, but of course we have Eric! This is an opportunity to get another person as good as Eric. It would be impossible to get somebody as good as Eric if we offered him the headship, you see. I'm perfectly sure this happened because I have been on too many committees where it did happen! And this of course is the kiss of death. Then, they did not get around to deciding whom they did want in that first year and Eric told me that he knew it was not going to be him and he was darned if he was going to be the Acting Head again, so he went to England for several months and they made Manfred Karnovsky Acting Head. During that year they got Kennedy as Hamilton Kuhn Professor. But this is not the end of this story. I had left 4 or 5 full Professors and 4 or 5 Associate Professors all with tenure. They went on having weekly Departmental meetings after I left and they decided that the time of the Department head, in perpetuity, was over! They felt that a big department like ours should operate like the Department of Chemistry and Biology with a rotating chairmanship. They got themselves so convinced that this ought to be so, that they brought forth a memorandum to the Dean to this effect. When Kennedy was being "rushed" for the job, they asked to have a session with him. I of course wasn't there, but I have heard that it was quite a session with part of my

Page  368368 fellows who were still there like Lew Engel, being very gentlemanly and very nice and part of them being rather adamant that for them to accept Kennedy, he would have to agree to a rotation. This was the bad part of it. He took a long time making up his mind as to whether or not he wanted to do it. Apparently Bernie Davis got into the act some way or another and hard feelings developed between Bernie Davis and the Department that haven't been healed to this day. Dr. 0.: Bernie Davis the microbiologist? Dr. H.: Yes, he is a rather tough fellow. I guess he has just given up the headship of the Department of Microbiology because he was a little too much of a martinet. I don't think I was a martinet, but I liked the feeling of authority as well as the responsibility. I certainly came out of World War II feeling that unless you have authority, you can't justify taking on responsibility. Whereas I know I would have lived very happily as a Professor with Eric as head, because virtually we ran the department as a settee of two and I didn't do anything without consulting him. I believe firmly in continuity of some years as being necessary for a chairman or head or whatever you call him, so he has enough opportunity to build the department, to pick out young men and have them develop and to strengthen weak areas and this sort of thing. If you are only there for a period of 3 years,

Page  369369 you don't do this. It takes more than 5--somewhere between 5 and 10 is the optimum time. I stayed too long; that's quite true. It got harder and harder and yet essentially it was the same problems recurring--so it wasn't fun anymore. It was a great deal of fun the first two or three times around, building the department. Dr. 0.: Have you established a half life for a head of a department as you have for a Dean? Dr. H.: I haven't really thought about it, but in my case I think 10 years would be it. I think, if after the war, I had come back as a professor and not reassumed the headship it would have been better for me and the department. They don't have department heads any more, they are chairman. But I was officially, and in the catalog, Head of the Department and of course this is because even when I went to Harvard Medical School we were one professor departments. You were the Head! You were the Professor! You were the Gehreimrat! You were the boss! Everybody else was your assistant in a sense. However, I didn't work in that way, even though I was Head. The boys would laugh sometimes at my claim that I was "Democratic." They said, "Yes, Baird is very democratic, as long as he gets his way." I did introduce two things that Folin had never done. One was the weekly departmental seminar and two, was to introduce

Page  370370 a staff meeting each Monday noon until the end. I am happy to say these still go on under my two successors. Dr. 0.: I should ask for the end of that story. Did Dr. Kennedy agree to come to Harvard under a rotating chairmanship? Dr. H.: Yes, and he has now rotated to his successor, a man by the name of Elkan Blout, a physical chemist who took over the quarters that Cohn used to have. He was formerly an official at Polaroid. He was a colleague of Land. Everybody is very happy with him. He is a quiet, very sensible person that everybody likes I think they admired Kennedy, but he is a little standoffish, a little forbidding. The few times I was there while he was presiding over the staff meeting, I thought he told them the decisions he had made rather than let them share in them, which I did. I would always take things up and worry them around. Oh, the first meeting I had with the Department was so strange, because Folin and his colleagues had never met together in any way, shape or form, and when I, as Professor, asked them all to come in for lunch in my office, they didn't know what to think. Incidentally, my office had not been Folin1s office, but his lab. I was very wise to use the room that had been his laboratory rather than the room that had been his office. I had them convert his laboratory into my office and his office into my laboratory. This was for psychological reasons.

Page  371371 Well, I have gotten clear back at Harvard, haven't I? You will find my final remarks at the Faculty meeting in the files and you might be interested in reading them, because I'm a very friendly and emotional kind of a guy and I had a very hard time getting through it as a matter of fact when the time came, because by then I was the senior professor. George Wislocki of Anatomy had died. Howard Mueller of Bacteriology had died. I was the senior professor at the Harvard Medical School. I outranked the Dean in years and tenure. The atmosphere in this big Faculty Room with all the old portraits of the old faculty looking down on me--01iver Wendell Holmes and so on. It was quite an experience. I came to La Jolla all by myself. I didn't bring any staff, and I didn't really know what I was going to work on. I was going back in the lab. I even had to import Francis Nesbett for a month. Ed Keeney said he would pay her way and her salary for a month, if she would come out and teach me how to do liver glycogens. You see, there is another point that I haven't explained. Here I was, still publishing papers, on liver metabolism and I got more and more upset over the fact that I hadn't done any of the liver glycogens myself. Dr. 0.: Because you were not at the bench.

Page  372372 Dr. H.: I wasn't participating] I would try to take my name off the paper and the boys would say, "No, no, after all it was your idea, you put us on to this problem when we came and we have just been extending it." Of course I would take part in the writing, but seldom did the first draft. This began to prey on my mind. Fran Nesbett who had been with me for 14 years had left to go down with Del Ames at the Massachusetts General prior to my leaving. She was getting stale and fed up as a technician in the same place. A very bright girl with a Masters degree. She came out to La Jolla and taught me how to do liver glycogens. We had published about 20 papers in which somebody had to do liver glycogens and my name was on them but I had never done a liver glycogen myself.1 She also did many other things to help me set up my lab at the Scripps Clinic. I had managed to find a technician. She was a woman of 50, who had brought up a family of 4 children and had originally had an M. D. from the Peking Union Medical College and was married to one of the Professors of Physical Chemistry here at UCSD. She was a Chinese by the name of Mrs. Jane Bien. She had forgotten all of her biochemistry. Fran taught us both how to do liver glycogens. After all I could do Van Slykes and pH's because I had been doing them in the lab at Harvard with students and I could do other things about the lab such as weighing and slicing rat livers. We were in business pretty soon.

Page  373373 When we had gotten the first successful experiment done, I ran up and down my lab and the corridors in the basement of the Clinic dancing and yelling, "I feel clean again!" (Laughter) I really did. It was a wonderful feeling, having been sort of a fake researcher. People thought I was a researcher and I could talk research, but it isn't the same thing. Then, by Gosh, we ran into this exciting business that we worked on, but I won't put it on the record tonight. The only reason it wasn't done 20 years before is because I wasn't in the lab doing my own liver glycogens'I Let that be a lesson to everybody who listens to this! Dr. 0.: For the record, you are of course referring to your work on the effect of CC^ concentration on metabolism irrespective of pH. Dr. H. : Yes. It was something that had to happen under your eyes. It should have happened when Jack Buchanan was doing his thesis. I was just repeating his experiments when this happened. I saw all the same data that he did and I was repeating it and getting the same data, but I was getting them myself.' Not looking at what he brought into me from the lab. Dr. 0.: I wonder how many department heads would make this admission now. I don't think many.

Page  374374 Dr. H.: Most of them don't have the opportunity. I am in a rare position of having had a chance to go back to the lab, really; in the spirit and the feeling of fear and trepidation that I had when I went from getting my Ph.D. to being Van Slyke's assistant. It was exactly the same feeling] It was my same neural pathway being trod all over again the same way' (End of the first day of interviewing) Dr. 0.: The date is May 2, 1968 and we are again in the office of Dr. Baird Hastings at the Scripps Institute of Oceanography. This morning we are going to discuss the laboratory work done by Dr. Hastings and his colleagues at the Scripps Clinic and Research Foundation. Dr. H.: I would like to talk about the work that I did initially with my own hands and later with the able assistance of a number of young colleagues after coming to the Scripps Clinic and Research Foundation in La Jolla, my seventh laboratory. I should like to introduce this by reminding myself that ever since 1940, the work of my laboratory at Harvard had centered around the general problem of "factors affecting alternate metabolic pathways," meaning by factors, ions, hormones, substrates, and the like. When I last participated actively in laboratory work and to any extent with my own hands, Dr. Buchanan, who was taking his Ph.D. and I, had done some experiments on the effect of pH changes on

Page  375375 the conversion of glucose to glycogen by liver in vitro. [ #174, 175] It was during that series of experiments that we made the discovery which I believe I have already recorded that when one incubates liver slices in a medium made up entirely of potassium and magnesium cations, instead of the usual medium which is primarily made up of sodium cations, we were able for the first time to have a net synthesis of glycogen from glucose by liver slices in vitro. So in undertaking my first experiment at the Scripps Clinic and Research Foundation, I decided to repeat and extend the experiments which Buchanan and I had been doing almost 20 years before. There was good reason for doing this because we had actually done only three such experiments and since they didn't agree perfectly, the question of what pH changes within the physiological range of pH 7 to pH 7.7 did to the rate of the synthesis of glycogen from glucose still was not clear. Having learned how to determine glycogens, we set about doing this. When I say we, I mean Mrs. Bien and myself. Though she was inexperienced in quantitative biochemical analyses, she was adept at learning such techniques. Our first experiments were utter failures. Indeed, whenever we incubated our liver slices with glucose in a high potassium medium, we ended up with zero glycogen instead of more glycogen than we started with. I was much disturbed by this because I couldn't repeat the basic experiment from which we had already published a paper.1 I tried to think of what might be the matter.

Page  376376 In reviewing in my mind what could interfere with incubation of cells and tissues when I had encountered it in the past, one night as I was lying awake worrying about it, I suddenly remembered that Barron and I in Chicago had once had a terrible time getting rid of trace metals from distilled water and finally resorted to distilling from quartz vessels, triply distilled water before we could get the water metal free. So the next morning I said to Dr. Henry Nakada, who occupied an adjoining laboratory and had been at the Clinic for some time, "Henry, how good is this distilled water that comes out of our faucets?' (I should have explained that in setting up my laboratory the Clinic had provided me with a distilled water faucet for each of my sinks, which had pleased me very much. It was a luxury to which I was not accustomed. In making up our several solutions from which we made our incubation medium, that is isotonic solutions of sodium chloride, sodium bicarbonate, potassium chloride, magnesium, etc. Mrs. Bien and I had weighed out the correct amount of each salt and then very carefully, in volumetric flasks, made them up to volume from the distilled water in the faucets.) Well, as I said, I asked Nakada how good the distilled water was. He said, "Oh, I never use it. It's full of copper and iron and all sorts of crap." I asked him what he did for distilled water and he said that he bought it in carboys.

Page  377377 So Mrs. Bien and I threw out all of our carefully made solutions and bought carboys of distilled water and made up new solutions and from that moment on we were in business. We undertook to study the effect of pH on the conversion of glucose to glycogen. Of course you can change the pH between 7 and 7.7 in a variety of ways. You can use what the body does, a bicarbonate solution saturated with an appropriate concentration of carbon dioxide in air or oxygen, which is the method of choice. But you can also make phosphate buffers by combining secondary and primary phosphate in appropriate concentrations and you can also use a buffer that had come into use in biochemical laboratories since I was actively in the lab, called Tris buffer. I have forgotten its correct chemical name. So I decided as our first set of experiments, to study the variation of the pH by using the carbonic acid buffer, another series with the phosphate buffer and another series with Tris. When we did this experiment and compared them, we obtained good increases in liver glycogen in the bicarbonate-carbonic acid buffer, but we obtained zero glycogen in the Tris buffer and in the phosphate buffer. By changing the pH from 7 to 7.7 as Buchanan and I had done using the bicarbonate buffer, we found there was a progressive increase in glycogen from practically no increase in liver glycogen at pH 7, a good increase at pH 7.4 which is the normal pH of blood, and a greater increase at the pH of 7.7. In other words confirming Buchanan's work. But I was not prepared to find

Page  378378 that in the other buffer systems which were with respect to ions and substrate exactly the same as in the bicarbonate buffered experiments, no synthesis of glycogen. This directed my attention to the fact that the only difference in these experiments with the different buffers was that the one where we succeeded in synthesizing glycogen, we had bicarbonate ions and dissolved CCL. So in the next experiment, we compared the glycogen that we got in a bicarbonate-CO buffer system with a Tris buffered system containing bicarbonate and CC>2 as well. In this experiment we got some glycogen, but not as much as we did when the Tris was not present. To complete this one point, perhaps I should say that when this was repeated many times, we found that actually the Tris ion is an inhibitor of glycogen synthesis. Since this demonstrated that CC^ was required for the synthesis of glycogen from glucose, even though there is no chemical step involved in converting glucose to glycogen that requires carbon dioxide, I remembered that in the '40's we had shown that CO present in an incubation medium or in an animal present as bicarbonate ion and CO^ molecules turns up in liver glycogen. Now this had been traced to the fact that some of the precursors of liver glycogen such as pyruvate do have the ability to combine with C0£ and convert it to oxaloacetic acid, a four carbon acid, and thereby provide a means whereby CC^ could get into the gly-colytic cycle and hence to glucose-6-phosphate and on to glycogen.

Page  379379 So, I said, we must see what happens when we have CCL present in our medium both with glucose and with pyruvate. If CCL was metabolically important, then perhaps the concentration of CCL would be important. This was an idea that had never occurred to me before. The opportunity to test this had been there for 20 years but I attribute our failure to do so to the fact that I was not personally in the laboratory, getting the data myself, and looking at the data that I got. At any rate we set up experiments in which we could keep the pH constant and vary the carbon dioxide concentration between roughly 10 millimolar and 40 millimolar in the medium. These are well within physiological limits, at least limits that are encountered regularly in any hospital or clinic. From the first such experiment on we found that there was more glycogen formed from glucose in the 40 millimolar CC^ concentration medium at pH 7.4 than there was in the 10 millimolar C0« concentration at the same pH. When we got enough data to plot our results with some sense of security, and compared the effect of varying C02 concentration at constant pH with the effect of varying pH at both constant bicarbonate concentrations or constant C0£ tensions, the change in the rate of glycogen synthesis due to changing the CC^ concentration was just as great as was the effect of changing the pH at constant bicarbonate or constant C02 tension. This was a brand new idea.

Page  380380 Now to back up just a little bit; though we were trying to do such experiments in the spring and the summer of my first year back in the laboratory at the Clinic, our results were quite variable. In the fall of '59, I had the good fortune of having Dr. Eugene Dowdle join me for a year. He was a clinician from the medical school at the University of Capetown in Capetown, South Africa who had spent a year as a postdoctoral fellow at Columbia University with Dr. John Taggart and Dr. Schacter. At Columbia Dr. Dowdle had been working on the transport of iron and calcium through the gastrointestinal tract. Early, when I went to La Jolla, I wrote to some of my friends telling them I would welcome a good postdoctoral fellow if they knew of any. Dr. Robert Loeb wrote back and suggested that perhaps Dr. Dowdle would like to come out and spend a year with me, because his fellowship was over there. Dr. Keeney agreed to pay for a postdoctoral fellow. I interviewed Dr. Dowdle in May in New York and found him a most able and attractive chap and got him all excited over coming and working on how hens make shells on their eggs. We worked out a series of experiments. This was a problem in the calcium field I had always been interested in, but never worked on. He was quite excited about this and agreed to come. When he arrived, he found that he had a lot more to do than just work on that problem. He had to tool Hastings up for laboratory work again'

Page  381381 I remember his first day when he came to the laboratory and said he wanted to make up a standard solution of hydrochloric acid and asked where was my constant boiling hydrochloric acid? I should have explained that Dowdle had been trained before he went to medical school as an analytical chemist and he had worked in the gold field laboratories in South Africa. Well, he was rather horrified that I didn't have any constant boiling hydrochloric acid and I was pretty ashamed myself.1 This was the first laboratory that didn't base everything I had in the way of standards on some constant boiling hydrochloric acid. That was the way I was brought up originally at Michigan and with Van Slyke and carried it on to Chicago and then to Harvard, but I hadn't taken the time to do that and the people I found at the Clinic, the chemists, were in the habit of buying the standard solutions of various kinds which horrified me but I hadn't done anything about it. I came back after lunch on this first day of Dowdle's arrival and there he was having scrounged enough apparatus to distill his hydrochloric acid and make his constant boiling hydrochloric acid. This is the kind of fellow he was. Having a standard HCL in line, he then watched me and Mrs. Bien do some of our experiments and he decided that we were not randomizing our slices properly, and so he fixed up a system whereby we could properly take random samples of liver slices. He even printed some standard

Page  382382 protocols so we could do exactly the same experiment twice. He really tooled us up. He was awfully bright and from the time he came, our results, when positive, were repeatable and we were able to make them stick. Indeed our results on repeated experiments and in duplicate on any one experiment on liver slices were better than anything we had ever been able to do at Harvard with the boys, even though they were awfully good boys. It was amazing how reproducible our results turned out to be. We quickly established that there was a CC>2 concentration effect at constant pH on the conversion of glucose to glycogen. Having established that, then, my mind was so fixed on the idea that it was related in some way or other to the carboxylation of pyruvate, we switched to pyruvate as substrate. I suppose I thought that more of the glucose went down the glycolytic cycle to pyruvate than would go to glycogen anyhow. If it got to pyruvate, it would pick up some C02 and then some would come back up the glycolytic cycle. So we left out glucose as substrate and put in pyruvate and repeated the experiment and proved very conclusively that the C02 concentration effect on the glycogen synthesis was not due to carboxylation of pyruvate. We got zero CO- concentration effect. Well that is where we stood at the middle of the next year (1960), when I was able to take on a senior associate through having had a grant approved by the National Institutes of Health.

Page  383383 You see, I think I recorded yesterday that I was allowed $3,000 for expenses and by March of '59 I had spent it all and realized that this wouldn't be enough. Fortunately the Clinic let me go on spending with no questions asked, but I knew this couldn't last. Indeed, when I raised the question to the then Comptroller, "What am I going to do now that I have spent this money that Dr. Keeney and the Trustees set aside for me?" He said, "Oh, my orders are to OK anything you want." This was generous indeed, but I didn't want to abuse it. [End of Side II, Reel

Page  384 [Reel 11, Side I May 2, 1968] Dr. H.: It was obvious that I was going to need more funds if I was going to carry on experiments seriously. Though I rather regretted having to ask for a grant, because there was a great feeling of independence through not having to live off of a grant in the laboratory, nevertheless I realized that it was going to be necessaryc I filled out the application for an NIH grant. I had never done this before, but I had for many years read many of them as a member of one Council or another. Dr. 0.: While at Harvard you did not have any NIH grants? Did not some of your postdoctoral fellows have NIH grants? Dr. H.: Yes, and they had NIH fellowships, but we had no NIH grants in my own laboratory. At Harvard I had a portion of a rather large contract made with the Atomic Energy Commission which served the research activities of Joseph Aub, Shields Warren, and Arthur Solomon and me. It was one large grant0 I used only about 10 or $12,000 a year from this contract to support my own research after World War II at Harvard. When I added up what I thought I would need to pay the salary for a man who was trained and had postdoctoral training and in order to buy certain equipment which I still needed, I applied for a 3 year grant, 1st year to be $25,000 and two successive years at $20,000, which when the overhead was taken off would have netted me $18,000. Even then, this was a very small grant for those days because they usually averaged $40 to $50,000. I felt that this was enough to take

Page  385385 care of my needs and actually I would have preferred to have applied for a two year grant, but I had also had the experience of seeing from the Council's side oftentimes, if money was tight or if they didn't think it was much of a problem, they would say, "Well give it to him for a year." And I wanted two years to see if I was really serious about wanting to work in the lab again. I certainly had no thought of working till 70. Well, to be on the safe side, I requested a 3 year grant. Having looked up the composition of the Study Section for Biochemistry and Physiological Chemistry, I felt that there were enough of either my old students or old colleagues, or present friends who were on there that they wouldn't have the heart to cut a three year grant down to one year. Well, you know, it came through in due time after the June Council meeting, and the notice read that it had been approved for 7 years. That was the maximum for which they could make grants at that time. I confess that I was so touched that I had to swallow hard, because it was the nicest compliment that has ever been paid me. There is no question about it. Anyhow, it meant that until I was 70, indeed, until for several months after I was 70, I didn't have to really worry about this grant. As time went on and expenses got greater and the Clinic decided that they couldn't afford to pay even for one technician any longer the NIH gave me a supplement to keep my technician going. With this in hand I promptly got in touch with my source for good people which was Prof. Edward Doisy of St. Louis. I had had a

Page  386386 succession of his graduates and PhcD.'s in my department at Harvard, all of whom were stars. He suggested Ted Mahowald. He was then in his second postdoctoral year at Wisconsin with Lardy and I interviewed him at the Federation meetings and he agreed to come for a very small salary, I must say. I think it was $5,500 to start with and he was getting only about $6,500 when he left. He was with me 2 years and overlapped Dowdle a little bit. He took up the tooling up of Hastings, where Dowdle left off. He had had much experience with radioactive isotopes and modern techniques which even Dowdle hadn't had. He guided me in what we ought to buy for the laboratoryc We had a very well equipped laboratory for the sort of things I wanted to do at the time he left. Unfortunately Prof, du Vigneaud of Cornell paid me a visit in the summer of Ted's second year. Ted was a big strapping six foot two or three 220 or 230 pound fellow but very dexterous and quick in his movementsc Du Vigneaud took such a shine to Mahowald when he met him that he went back and wrote him a letter offering him twice as much money as I could pay him and an Assistant Professorship. I advised Mahowald to take it because there was no future for him at the Clinic, no long term future. I would have been glad to have him stay 5 years, but I wouldn't have wanted him longer than this. This was much too good an opportunity to pass upc Shortly after Mahowald came, Darrell Fanestil, who was first in his class at Kansas and had come presumably to work with Dr. Dimond as a postdoctoral fellow in cardiovascular disease. Dr. Dimond wanted him to get biochemical training and arranged to have him with us for half

Page  387387 the time. Once I got my hooks into him and found that he was just like a dog going after a bone when it came to biochemistry -- he was absolutely terrific and it ended up with Dimond having his services only one half day a week for the first year. The next year we got him a full time Public Health Service Fellowship so that he was with me two years. He is one of the smartest young men in medicine that I know. I expect him to be one of our great Professors someday. He has great ability to not only learn techniques, but to understand problems, and to advance them. He is the quickest reader and most retentive man I have ever seen and is very systematic. For a half an hour each day after lunch he would go to the library and remember what he read. He is a real comer and is now back at Kansas as an Assistant Professor. I doubt if he stays there. In addition Albert Renold sent me one of the boys that had been with him, Bernard Leboeuf. Bernard was from the University of Montreal and had spent a year or so in Renoldfs laboratories. So there were the 4 of us working on problems. Fanestil and Mahowald joined with me in the study of the factors effecting liver glyoogen and Bernard elected to go on with studies of the fat pad and factors effecting the metabolism of the fat pad. Our laboratory was quite capable of handling two separate problems, but it wouldn't have been satisfactory for more than that, considering the different kinds of operations. We of course had to share a good bit of the apparatus. From the time Mahowald came, the books of data rolled forth you see (turning to his shelf where the 41 looseleaf binders of research work

Page  388388 done at Scripps were located). He was a most systematic fellow. We recorded each experiment starting with a protocol and then collected the data sheets of those people participating in any one experiment and then these were summarized. The summarys of the experiments were collected and indexed so that it is not difficult for me to refer back and collect the data on any of the experiments we had done. We continued that after Mahowald left in '62. First we had to repeat the experiments that Dowdle and I had done because Mahowald didn't believe that there could be a CC>2 concentration effect. It didn't fit in with anything he had learned before, so we piled up some more evidence to convince him. It took several of us to do any one of these experiments. I would do the pH's and C02's because we would control the pH and C02 of our solutions from the beginning to the end of the incubation. This was essential if we were going to say that the incubation was carried out at a constant pH. It had required devising a technique whereby we could do this because if we used the customary small size vessels and the customary amount of tissue and medium, the pH would drop. You can't use a closed system. If you stopper them and incubate them for 90 minutes, the CC^ piles up and the pH drops. So we had to devise a means of using what we called the open system where we circulated the CC^ in oxygen gas over the vessels while they shook. All of these problems were licked. Large vessels were also devised so that we could add our substrate at the proper time. Then when we had to retain the C C^, we worked out a different gas-fluid relationship in the vessel so we could stopper

Page  389389 it and retain all the C1402 in the vessel. Mahowald was terrific in meeting each of these challenges as they came. One person had to do the phesphates in each experiment and one person had to do the glycogens, and the glucoses or whatever substrate we were using. It would take about 2 days to finish one experiment though we would get the incubation done in one half day. Having devised the technique that we found was satisfactory, we stuck to that for the rest of my time at the Clinic, so the results are comparable. Now having radioactive isotopes available and counters and having gotten my license so that I was allowed to use isotopes, we were able to use radioactive glucose, radioactive pyruvate, radioactive fructose and radioactive glycerol as substrates. Perhaps the most beautiful experiments that we did were one series in which we had radioactive glucose in one set of vessels, radioactive pyruvate in another, and then trwo more sets, one of which had non-radioactive glucose plus radioactive pyruvate and in the other set we had radioactive glucose and non-radioactive pyruvate. When these results were all completed and calculated it proves just so beautifully that the "C02 effect" was on the glucose to glycogen pathway and it had zero effect on the pyruvate to glycogen pathway. Then we found that the "CC^ effect" was there on the fructose to glycogen and on the glycerol to glycogen pathway, and this began to make it look as if it was at the phosphory-lation of a sugar or sugar like substance such as glycerol. At that point we then carried out experiments to see whether it was at the phosphorylation step. I won't go into the details of this, but it

Page  390390 is a trick that Renold and I had worked out at Harvard, combining two sets of flasks, one of which had glucose and radioactive fructose and the other had radioactive glucose and non-radioactive fructose. The reason for the fructose was in order that you could follow how much of it disappeared and how much of it went to glucose. The problem with glucose as substrate alone was that as the only substrate present its first reaction was to be converted to glucose -6- phosphate. But since we were working with liver which contains glucose-6-phosphatase, it splits a certain amount of the glucose-6-phosphate back to glucose and inorganic phosphate. You have no way then by determining the glucose in the solution, how much glucose has really been taken up because it is also coming back all the time. Whereas from fructose, it is converted to glucose-6-phosphate and if you get some radioactive glucose out of the solution that you have incubated radioactive fructose in, this then will also tell you how much glucose-6-phosphate has split and you can convert that back to the amount of glucose that has come out from glucose-6-phosphatase, you see. Having studied the phosphorylation of glucose by this method, we found sure enough that there was a CC^ concentration effect on the phosphorylation step of glucose. While this set of experiments were going on, Dr. William Longmore joined me on a postdoctoral fellowship, so that for a while there were four fellows in the laboratory together. He had just finished his Ph.D. on phospholipids, and he suggested that we combine glycerol and glucose in the same manner that we had been

Page  391391 doing with fructose and glucose and this turned out to be an even better method for determining glucose phosphorylation. It's more accurate. It confirmed the fact that increasing the CC^ concentration, at constant pH, increases the rate of phosphorylation of glucose. So we felt we were getting close. Now how could C02 effect the rate of phosphorylation of glucose to glucose-6-phosphate? C02 doesn't appear in the chemical reaction in any way. One thing that seemed a possibility to me was that the activity of hexokinase might be effected by virtue of the fact that C0« in solution would combine with the enzyme at one of the points where there was an uncharged amino group. When you have C02 and an uncharged amino group, you have the possibility of making a carbamate, NHCOOH, that would be carbamic acid and, since its pK is low, at physiological pH's, it would be there as a negatively charged carbamate ion. When you have CQ~ available and an uncharged amino group, whether it's just as amino acid or it's an uncharged amino group hanging out from a protein, you have the makings of a negatively charged group from a charged group. This conceivably could change the activity of an enzyme or its affinity for a substrate. This was not a new idea with me. It was a thought that I had discussed many times in Copenhagen with Linderstr^m-Lang. Indeed we even thought of ammonia in body fluids and C02 in body fluids as being substances which could add or be substracted, depending on the tension of the ammonia or CC>2 in solution. That would be, as we said, a fine adjustment of enzyme activity. Now I know of no specific example in which

Page  392392 this has been proven, except that wonderful enzyme model, hemoglobin. We know that hemoglobin makes carbamate in the presence of CO ; this is one of the ways C0« is carried in the blood. We also know that oxygen dissociation curves at the same pH are different whether you have carbon dioxide present or not. So if you visualize the hemoglobin molecule as the enzyme, and the heme part, as the specific part which combines with the substrate, (which in this case is oxygen), we have in this case concrete evidence that there is a COo concentration effect on this model enzyme system. Well, hunt as we did with one enzyme after another all the way from hexokinase up to glycogen, we never were able to demonstrate a C0« concentration effect on the activity of an individual enzyme. That doesn't mean it isn't there. Then Fanestil, in reading, wondered whether or not the ATP was there in sufficient quantity, since ATP has to react with the glucose in the presence of the enzyme to make glucose-6-phosphate. So Mahowald, Fanestil, and Longmore undertook to determine the glucose-6-phosphate concentration at different CCL concentrations and the ATP concentrations, This was too much for our laboratory to prove conclusively. I was looking over the data for this recently and it would look as if there is a CO^ effect on the concentration of glucose-6-phosphate that is there at the end of the incubation, but it's not good enough data so that I would want to publish it. The ATP data were not good enough for us to calculate the turnover. Then Fanestil turned to another approach and that was, whether the ATPase activity of mitochondria is

Page  393393 effected by CC^ concentration There he struck pay dirt, because there is a very large effect of CC^ concentration at constant pH on the ATPase activity of liver mitochondria. This was subsequently confirmed by Longmore and me on the liver after Fanestil left and we also examined the mitochondria of kidney cortex and kidney medulla, we had found a big difference in the C02 effect on carbohydrate metabolism in kidney cortex slices and kidney medulla. However we found no essential difference in the ATPase activity of the mitochondria of the kidney cortex and the kidney medulla, though there was a good C02 effect on both of them. When Longmore was ill, Betty Baker and I undertook the study of ATPase activity of brain mitochondria and again we found a C02 effect. So there is an effect, but of course ATPase activity doesnft mean a single enzymeo All it means is that between ATP and inorganic phosphate, which involves a number of steps, the rate is greater in the presence of C02 than in its absence„ In a word, ATP turns over more rapidly in a high C02 concentration than in a low C02 medium. Well, I am going to stop at this point because this is as far as we were able to explain the CO^ effect on the conversion of glucose, fructose, and glycerol to glycogen. We pinpointed at least one place where this was effective, but we have not proven the chemical reason for it, in chemical termsc Dr. 0.: Are any of these gentlemen still working on this problem? Dr0 H.: Yes. Longmore is. He has gone to St. Louis University.

Page  394394 Fanestil is also but from a different angle. I want to pick this up when I come back and describe the very dramatic effect of 002 concentration on lipid metabolism which was undertaken by Longmore and me because Longmore was capable of handling lipids. This was after the other fellows had left. [ Luncheon break ] Dr. H.: Before I continue further with our subsequent experiments on the C02 effect per se on metabolism in liver, I should like to record the reasons the results we had obtained on the C02 effect on carbohydrate metabolism were so exciting to me and as I believe, of great physiological and clinical importance. When I was at Chicago and Dr. Nathan Shock was taking his Ph.D. with me, he determined the acid-base pathways that the arterial blood takes in returning to normal values after displacement. One of the striking conclusions which resulted from his observations on normal men was this. After a person has been subjected to a severe metabolic acidosis, the arterial blood had a low pH and a low bicarbonate and a low C02 tension. If the person is allowed to return to the normal state without any interference, the path taken on an acid-base chart by the arterial blood of this normal person is not along a constant pH line; it is not along a constant CO^ tension line, but it is along a line which lies between these two parameters. On the average, this line is twice as close to a constant C02 tension line as it is to a constant pH line. We interpret this as meaning, other things being

Page  395395 equal, that the body is twice as interested in trying to keep the C02 tension constant as it is the pH per se. This fact was established through about 30 experiments in Chicago, by many more that I did in Peking and by goodness knows how many that I did by confirming it each year with four different sections of Harvard medical students for 25 classes. But this fact that the body wants to keep the C0? tension constant equally or even more than it wants to keep the pH constant, has made no impact on the teaching of biochemistry or physiology! Students are invariably taught that the body wants to keep the pH constant, period. And indeed, people often go so far as to say that they will adjust the C02 tension to whatever is necessary to keep the pH constant! This just isn't in keeping with the actual facts. But the reason it is done, I presume, is because it is so easy to accept that the body wants to keep the pH constant because each enzyme in the body has a pH optimum, and if you change the pH of its environment you will change its activity,, But until we made these observations on the change of CC>2 concentration at constant pH, which means a change in bicarbonate and a change in CO^ tension proportionately to keep the pH constant, there was no confirming chemical evidence in biochemistry that would make it plausible that the body wanted to keep the CO^ tension of its arterial blood constant. Now the possibility of finding a rational biochemical reason for this interest of the body in CC^ tension as well as pH had been gnawing at me for 30 years. So as soon as we had really established the fact that there was a metabolic role for C02 per se in carbohydrate metabolism in liver, I immediately felt

Page  396396 that here at least was one reason for the importance of CO per se. Now it would have been very nice to have been able to carry this right on to the actual chemical role that the CC^ molecule plays in the phosphorylation step of carbohydrates, but even without that, I have had a great feeling of satisfaction over having at least pointed out one way in which C02 has an influence independent of pH on reactions which must go on continuously and are required for the normal metabolism of the liver. Then as I intimated before lunch, with the arrival of Dr. Longmore who had experience in handling fats and fat metabolism, we undertook to see whether there was a measurable CC^ concentration effect on fatty acid synthesis by liver. As substrate we used carbon 14 labeled acetate, then we isolated the triglycerides and the phespholipids and eventually the cholesterol, after incubation of liver slices with the same technique and in the same medium that we used for our carbohydrate studies. We varied the CC^ within the same limits, i.e., physiological limits of 10 to 40 millimolar. We also carried on studies independently in which we varied the pH from 7.1 to 7.7. Well, from our first experiments on, we found there was a very large effect of CO concentration, easily demonstrable, on the rate of synthesis 2 of long chain fatty acids, both those which ended up as triglycerides and those which ended up as the fatty acids of phospholipids. Indeed between 10 and 40 millimolar C0£ concentration the change in rate of long chain fatty acid synthesis went up between 4 and 5 fold, whereas it had fcero effect on the rate of cholesterol synthesis. I should

Page  397397 say parenthetically that we got very good in vitro synthesis of triglycerides, phospholipids, and cholesterol. Now this, of course, can be chemically explained, though it couldn't have been anticipated, that within these physiological limits CO concentration would be limiting. It is well worked out that the first step in the synthesis of fatty acids from acetate is first the formation of acetyl CoA then a carbon dioxide molecule is added, and it becomes malonyl CoA, and another molecule of acetyl CoA and at that step the CC^ that went on is kicked off. Dr. 0.: CoA is the abbreviation for Coenzyme A is it not? Dr. H.: That's right. After reduction of the carbonyl group, there is another condensation and that is the way the chains are lengthened out from two carbons to fatty acids of 14, 16, 18 on to 20 carbons. On the other hand, the steps for converting acetate to cholesterol do not involve that addition of carbon dioxide and its being kicked out. So the very fact that we got no C09 concentration effect on the cholesterol synthesis whereas we got these very large C0« effects on the fatty acid synthesis makes it almost certain that this step in which carbon dioxide is added to the acetyl CoA is limiting; the more C02, the faster that step goes and the less the C0«, the slower it goes. Within these physiological conditions, the C02 concentration can vary the rate of fatty acid synthesis by a tremendous amount. I made a rough calculation when we got some of these results, and it would indicate that if COo did have this same effect in vivo that we have

Page  398398 demonstrated in vitro, it would mean that the rate of fatty acid synthesis in the liver would vary by as much as 1570 just going from arterial to venous blood, just from the amount of C02 it picks up from the tissues. So this is not a small matter at all. Again, whether or not this has something to do with the body keeping the COo tension as nearly constant as it can, I have no idea. It may be only one of many reasons and there may be many others that we have not explored. These, we have explored. At any rate if one takes the map of the acid-base pathways as I plot them, one can put on or superimpose on such a map, vectors from the normal area which indicate greater or less rate of carbohydrate synthesis and greater or less fatty acid synthesis. I should have said before I made that last statement that as distinguished from the carbohydrate effect, within the physiological limits, pH changes have no demonstrable effect on fatty acid synthesis, whereas there is this enormous CC^ effect. Well, this is in a sense my legacy to physiology. When I started scientific work seriously at the Rockefeller Institute what constituted the criteria for specifying the acid-base balance was not established. Then came the gradual working out of what we called the normal and abnormal acid-base areas; this was Van Slyke's goal at that time. But we were unable to establish acid-base pathways because there were no micro-methods that permitted us to do 50 at that time. When Shock and I developed the 0.1 cc acid-base method we had the tools to establish the acid-base pathways. Finally, in the 1960's we have

Page  399399 found a rational biochemical connection between the interests of the body in its CO tension as well as in its pH. There is one other aspect of the work which we carried on at the Scripps Clinic that has deep roots too. Though it was at Columbia and then at the Rockefeller Institute that I became interested in the blood as a physico-chemical system and the distribution of ions between serum and cells, it wasn't until Chicago days that I studied this in tissues other than the blood and developed in my mind the feeling that the body could be treated as a heterogeneous system made up of a few very distinct phases, or if you will, solutions separated by membranes, at least the soft tissues were. The striking thing was that cells are living in a sea water which is primarily a sodium chloride, sodium bicarbonate solution. However, enzymes and organelles are surrounded and in an environment with high potassium and magnesium concentrations. This of course is what led us to belatedly develop a medium in which the intracellular enzymes of the liver could function normally,, Now when we were doing our experiments on lipid metabolism in the liver at the Scripps Clinic, we were incubating our tissues in the high potassium, magnesium medium just as we had in the carbohydrate studies„ When we compared our results with the amount of fatty acid synethesis from acetate that had been published by Brady and Gurin who were the first ones to do such experiments, we found that our fatty acid synthesis was much greater than they had obtained. They had incubated their liver slices in a Ringer!s solution, a sodium chloride, bicarbonate solution. So before reporting our work, I decided with Longmore,

Page  400400 I that we should have a comparison between experiments done exactly their way and our way, so if we were asked why we didn't do it in Ringer's solution we could tell them. To our amazement, we found that the incubation of the liver slices in the high potassium medium gave results which were several fold greater at the same pH and the same COo concentration than they were in the classical Ringer1s solution, though our results in Ringer's were confirmatory of those of Brady and Gurin. It was interesting to note that Brady and Gurin did not report any phospholipid long chain fatty acids. There is a good reason for this I guess because we were barely able to detect any synthesis of phospholipid fatty acids in Ringer's solution, whereas we had equally good synthesis of phospholipid fatty acid as we had long triglyceride fatty acids in the high potassium solutions. There was no such effect of the potassium versus sodium ions on the cholesterol synthesis. So again here is an example of the importance, in studying intermediary metabolism, of insuring that you are maintaining an ionic environment that is reasonably close to the normal ionic environment of your enzyme, enzymes, or group of enzymes or organelles. I am convinced that the literature is full of very accurately obtained data that have no physiological relevance whatsoever, because there has been either too little attention to the ionic environment or too little or no attention to the manner in which the pH was preserved! Buffering with phosphates or Tris is simply creating a pathological ionic environmentI It is very hard for me to take an interest anymore in reading data on the constants of enzymes because

Page  401401 the conditions under which they establish these data just don't have physiological relevance I It's good chemistry yes, like any other good chemistry is, but unless it has physiological relevance, quite frankly I just am not interested in it! Dr. 0.: Again, hopefully others are taking up the call are they not? Longmore and others. Dr. H.: Oh yes. Some of the boys who have been around me have, but I see no evidence that it has made any great effect. I am delighted that belatedly I am invited to a conference on C02 in Haverford, Pennsylvania in August prior to the Physiological Congress, to be run by Roughton, Edsall, and Forster and some others. It will be a two day conference and I have been asked to preside over one of the sessions on the metabolic role of C0£ and bicarbonate ion. I am going!! [Laughter] Dr. 0.: I am sure you have had the opportunity to express your views on the matter of the using the proper ionic environment in your publications and at meetings, etc. Have you found that people just aren't ready to accept this? Dr. H.: Of course the kind of experiments that we have been doing are not regarded as biochemistry. This is physiology. It's the sort of thing we have had to publish in the American Journal of Physiology. With difficulty we got two papers into the Journal of Biological Chemistry. One was on the CO effect on glycerol metabolism and one

Page  402402 was on the ATPase activity as influenced by CO^. But it has had no influence whatsoever on the biochemical people. It has I am sure had an influence on the physiologists though and on the physiologically minded cliniciansc [End of Side I, Reel II] [Side II, reel 11, May 2, 1968] Dr. H.: I think I should for completeness sake add the fact that in addition to those who were postdoctoral fellows and Mahowald who was an associate at the Clinic and Longmore who succeeded him as an associate, there were also for periods of a matter of months as visiting investigators and colleagues, Professor Coxon from the Department of Physiology at Oxford; Professor H0N. Christensen, Head of Biochemistry at Michigan for two occasions, out of which one paper was published; Professor M0E0 Krahl, a second cousin of mine from the * University of Chicago; Professor E. G. Ball, who spent his sabbatical with me, a couple of medical students through the summer whose names I haven't immediately in my mind; Klaus Schwarz from the NIH spent some months; Dr. Teng from Taiwan; and an Atomic Energy Fellow, Dr. H.H. Liem who was an Indonesian from Jakarta. Most of the years that I was there, I was also supervising the thesis of Dr. Michael E. Q. Pilson, who was taking his Ph.D. in Marine Biology at the Scripps Institute of Oceanography and elected to make biochemical and physiological studies on the abalone blood fluid and of the muscle as well as some metabolic studies. He took his Ph.D. in 1963 and is now at the University of Rhode Island Marine Station. ••WIF'

Page  403403 I continued to have a good number of extracurricular activities while I was at the Clinic« When I came out in January 1959, I resigned from practically everything, thinking I was going to the far corner of the earth, but before the year was out I had been invited to come back on such things as the Visiting Committee to the Brookhaven National Laboratory, etcc I think by the end of the year I was finding it was really just as easy to get from San Diego to Washington and New York or Boston, as it had been to get from Boston to New York or Washington by train and a lot more comfortable. I was on the Arthritis Council when I cameout to La Jolla and my term was up in 1960 and then I was on the Heart Council until 1964. All of the medals and citations and sort of honors other than honorary degrees that I have had in my life, I received after I left Harvard which amuses mec Dr0 0.: Don!t they often wait till someone is emeritus before they start the chain of awards and so on? Dr* He: Yes, but I wasn't retired; I was working! I got this Banting Medal from the American Diabetic Association for the work I was doing! The current work I was doing! I was active! I got the Research Medal from the American College of Physicians because of the research I was doing myself! I guess they knew the difference between having your name on papers and doing the work that the papers represent! I donft know; Ifm just joking a bit. Now I have been honored 3 times by Michigan; once with an honorary degree in 1940, then my students

Page  404404 put on the 70th birthday symposium in 1965, and then last year for the sesquicentennial of Michigan they gave me the Sesquicentennial Award. This Physiological Department Medal and Citation from Columbia last fall wouldn't have happened if I hadn't been working as a physiologist, I think -- I hope! Well they are all hollow honors unless you are turning out people and turning out ideas that give birth to other ideas. The nicest thing that could happen in my life would be to have some folks come along and do some work along these lines of the metabolic effect of CC^. But just don't ignore it! Either prove it or disprove it!I Dr. 0.: Pick up the ball and carry it. Dr. H.: Pick up the ball and carry it! I would like to have been the one to find the enzyme which isn't hemoglobin that makes a car-bamino group and changes its activity. I'm sure its there!J It has to be!! But we didn't do the right experiment with the right enzyme. Well, all good things seem to come to an end sooner or later. And my happy life at the Scripps Clinic did partly because I had worked diligently to turn Keeney's ambition at the Scripps Clinic into a reality and change it from an association of clinicians and three biochemists called members into an organization, a professional one, with some rules about appointment and some rules about tenure and things like that. I was instrumental among other things of having them adopt the Harvard scheme of normally retiring members at 65 and

Page  405405 then inviting you to be on a year at a time, if mutually agreeable, until you are 70 and then obligatory retirement. If I hand't done that, I could have, if necessary, leaned on the fact that when I asked Dr. Keeney before I accepted the job what sort of tenure would I have, "Oh, he said, "Baird, you111 just stay on as long as you want to." But having gotten the rules on the books, when 70 came, I couldnft very well kick! {Laughter] They were very nice and let me stay on until the end of my grant in September '66 though I was 70 on November 20, 1965. My Laboratory of Metabolic Research, as I had named it, disappeared administratively and was amalgamated with the Division of Gastroenterology and I went right on doing what I had done before. The NIH very generously supplied my salary for those extra 10 months which existed between November 20 and the following September 1 when my grant was over. So I actively stopped my work at the Scripps Clinic and Research Foundation and left them on September 1, 1966. Dr0 00: Prior to your coming to the Scripps Clinic were there any other training programs in the sense of postdoctoral fellows such as you had in the basic sciences? Did either of the biochemists who were there have postdoctoral fellows? Dr« H.: No. Dr. Grant Bartlett had an Army Contract for the preservation of blood. His field was the organic phosphates of red cells and he is very good. Nakada was carrying on with carbohydrate metabolism at the enzyme level, a subject which he had started when Dr. Wick was still there. He came from Temple where he got his Ph.D. and was an

Page  406406 assistant to Wick. He was a good organic chemist. Neither Nakada or Bartlett had postdoctoral fellows. The only fellows who were at the Clinic when I came were four young men who had finished their internships and were taking what amounted to a residency. The Clinic grew very rapidly after I came -- it didn't have anything to do with me, except that I hoped that I helped them with some of their problems and didn't interfere, at least, with their getting funds. I think I might as well not make any bones about it. I'm sure that Keeney seized on the opportunity to get me to come, because I would be "seed money," and he certainly treated me extremely well. I never had any complaint from the treatment that I had at the Clinic. I used to be pained over the treatment of some of my good friends at the Clinic because of the way they were treated. But as far as I'm personally concerned, I have nothing but happy memories; they leaned over backwards to treat me nicely. Dr. 0.: One thing I would like to get on the record. Having read through the minutes of the staff meeting and division head meetings and some of your material which is gathered which deals with your strong efforts throughout your stay at the Scripps Clinic to build up the clinical services along academic lines to be complimentary to the basic sciences, I think this is something we should get on the record. I gather it was your understanding, when you came out, that this was the direction that the Clinic was hoping to take and that as time went on, for a variety of reasons, this never really came to pass at least to the degree that you and several others had hoped. r

Page  407407 Dr. H. : This is quite true. When I cam I visualized it as primarily a clinical investigation institution, not realizing at the time I came that except for Dr. Vander Laan, who was already here, there wasn't a single member of the clinical staff who you could say was a pro at clinical investigation. I thought that if we could have a small nucleus of good preclinical investigators, providing basic information and providing a congenial group of what you might call scientific consultants to the clinicians, that this might even stimulate them to carry on clinical investigations in their several areas, whether it was cardiology, or hematology, or gastroenterology. Endocrinology under Vander Laan was the only one that was actually going wellc I have always myself gotten such stimulation out of working with the clinicians. I am eternally grateful for the opportunity I had first at the Rockefeller Institute and then for the 8 of the 9 years I was at Chicago in the Department of Medicine. I have had so many ideas for research growing out of going to rounds and hearing clinical problems presented. I think it is a great opportunity that too few biochemists of the present generation take advantage of. It is intellectually stimulating. Well this is the way I visualized the place would develop as a group, medical research institution. When the time came to grow, Dr. Keeney had made contact with Dr. Frank Dixon of Pittsburg who wanted to get out of the responsibility of his teaching department and so the same year that Salk was trying to decide whether or not to come out here and develop a research institute, Dixon was out here trying to see

Page  408408 whether he could get Keeney to give him the facilities that he wanted. And he wanted a lot! So the second year I was here, the Scripps Clinic had purchased the nurses home to the north side of the Clinic, a three story building and had given Dimond, who had come in Cardiology, a floor, and had given half of a floor to Vander Laan. Then the opportunity to get half the funds to build half the research building became possible. The Trustees dug into their capital for something over half a million. They got about $400,000 out of the NIH because the NIH would not match funds for the amphitheatre or the library. They got a four story building, the first three storys of which were put at Dixon's disposal and that left the top floor undeveloped. At that point I had a big decision to make because it wouldn't be undeveloped very long after Dixon arrived, and I wanted Keeney to agree that it should be biochemistry. However, I really had no desire to go back in the business of developing a big department of biochemistry again. I might better have stayed at Harvard. So I persuaded Keeney to set up an Ad Hoc Committee and hunt for a suitable young biochemist. I did it in the regular way we would have done it at Harvard and made a good search. It boiled down to 3 people which Keeney tried one after the other. Through very good fortune the third one to be approached, Dr. Frank Hunnekens, who was a professor of biochemistry at the University of Washington was delighted to accept the job. He is a highly reputable and well trained man who has developed a good department and my only criticism is that he and his group don't take any part in attending the clinical rounds and so forth. He has work going on with the hematologists, but the young

Page  409409 people in his department do not go to rounds and hear the clinicians talk about clinical problems. I failed utterly in amalgamating the basic scientists that they have at the Scripps Clinic and the clinicians They are as separate as two separate institutions! Unfortunately, they are on opposite sides of an alley and are only connected by that "bridge of sighs". It is so symbolic of the separate activities and spirit -- I go regularly to rounds after my Friday seminar there. I still enjoy them very much. I think the young basic scientists are missing so much. I tried to get Keeney to insist on it, like he insisted on their eating together. You may have run into a letter that I wrote to my clinic colleagues in biochemistry suggesting that they attend rounds, and this even offended some of them, when I posted it. I thought they would take it in the spirit in which it was meant, but no, it was interfering with their right to do what they wanted to do and hear what they wanted to hear. I just feel sorry for them. My boys, even Ted Mahowald, who had never been near a clinician before --just ate it up and so did Bill Longmore. Both of them collaborated with the clinicians. Monroe wrote papers with them. I am perfectly sure that biochemists will get better jobs in the end if they know h0w to get along with clinicians, because I have seen it happen. It made Hal Christensen get the jobs he has had, first at Tufts then at Michigan; it helped Marott Sinex get his job at Boston University; it helped Elmer Stotz get his job at Rochester. So that was one of my failures. I couldn't bring the Dixon, and the Hunnekens, and then

Page  410410 the Spizizen groups together with the clinical groups. They might have even catalyzed the clinicians that were there, if they had done this and asked questions of the cases that were presented to them, even if they were dumb questions. I've got to read one thing in here and take up some more tape for no good reason. The first year I was at the clinic and all we had was our one building, we had rounds on the patio on the roof. It was really supposed to be a place where patients could sun themselves. Dr. 0.: Are you referring to that central court? Dr. H.: No. Clear up on top of the building in an enclosure. We would have rounds on Wednesday at one o'clock. They would present cases and I would help work them up once in a while with Keeney. Well the year Dowdle was here -- I should preface this by saying he had defective speech; you didn't notice it much when you were working with him, but it was quite a stammer and he would have a hard time getting the first word out. One time they had presented a case and it had baffled everybody. I was sitting next to Dowdle. It was in the dark as they had been showing slides. As they discussed this case, one after another, I was conscious of Dowdle, who was a very wiry fellow, getting further and further toward the edge of his chair, and saw his mouth moving a bit but it was impossible for him to get a word out in time before someone else in the audience had asked another question or made a comment. Finally the other people had run out of words and

Page  411411 there was enough time, so to Dowdle's amazement and mine too you suddenly heard, 'Veil if you didn't all have holes in your head, you'd know this was a case of so-and-so", which he had seen many times in Capetown. Keeney had just completed his final pronouncement on the diagnosis! Dr. 00: That must have stopped the show! Dr. H.: Yesc For Dowdle, it was one frustration too much. Drc 0.: We donft have to go in to great detail because it is spelled out very clearly in the Minutes of the Staff Meetings, but it is interesting to note that the Scripps Clinic was obviously going through some "growing pains" through the period you were associated with the groupc The problem of "town and gown"; the slight, but definite problems they were having with some members of the San Diego County Medical Society; the problems with residency certification; the question of how they would relate to the medical school. With your perspective from all your years at Harvard, I wonder how you reacted to some of this even though you were not intimately involved because it did not directly concern your area of responsibility at the Clinic« Dr., H.: Well the administrative problems as they appeared to me seemed to be pretty minor and old hat, but to Dr. Keeney and the other men who had not encountered them before, they seemed potentially catastrophic. When it came to threatened discipline by the Ethics

Page  412412 Committee of the San Diego County Medical Society, I couldn't myself take it seriously, but Ed Keeney was scared to death. They called him up on the carpet over such a silly thing. He had appointed a psychiatrist, Dr. Ziegler from Hopkins and Dr. Keeney had written up a very nice but not flamboyant press notice which was published. He was promptly called on the carpet for advertising. I suppose they had been laying for him because the Clinic had "shot the moon" in announcing me. They had run columns in a number of papers. But they couldn't touch me with a ten foot pole. Dr. 0.: You were not in competition with the private physician. Dr. H,: No. But the Clinic was advertising; the Clinic was taking money out of their pockets. Furthermore, there is in town another clinic headed by a man who was at the Scripps Clinic with Sherrill who just hates Keeney's guts. Dr. 0.: Is it modeled after the Scripps Clinic? Dr. H.: No. No. He thinks he is much superior to the Scripps Clinic Arne Wick is a consultant to him and Arne keeps wanting him to meet me, but he wouldn't meet me as long as I was at the Clinic! He hates the Clinic and everything the Clinic stands for. He has a lot of influential friends around La Jolla who feel he is the greatest clinician. Dr. 0.: Just like so many other communities. Dr. H.: Yes. But by in large except for the Board of Trustees which

Page  413413 I never thought had been given a chance to learn what the Clinic was all about, - I thought for some time that my annual report which I introduced -- they had never had annual reports before -- would be presented to the Board of Trustees. But no member of the Board of Trustees had ever seen those reports. They now see the printed report which Keeney started 3 years ago, making up his own report for the whole thing. I helped him write the first one that they published. Prior to that the Board of Trustees really did not know what was going on at the Clinic except what Keeney told them. Another thing that I wanted Ed to do very early, because I felt he needed it badly, was to have an outside Board of Scientific Advisors. I had it when I ran the Lasker Foundation, I created this for the Children's Hospital Research Foundation, and we always had our visiting committees at Harvard at the medical school. It is a very important thing both as a help when you need help, to be sort of aware of what goes on and why you need help, but also as sort of a referee. Outside minds are good to have to appraise your own institution. Ed was very resistant to this and I saw this tremendous tension building up, because Dixon is a very ambitious man. Dr. 0.: Yes. He is an Empire builder. Dr. H.: Yes, an Empire builder and I saw that he was going to step t all over what clinical investigation there was going on. He would say such things as "We would be better off if we didn't have any clinicians here!" He would say this to me when we would get together.

Page  414414 I felt that if it really came to a showdown, without an outside group, it might really be very bad news for the Clinic. I finally did something that I don't believe that I ever did before. I finally did an end run around Ed because he wouldn't move. I was by then well enough acquainted with Frank Kockritz, a lawyer, who was a member of the Board. I asked him to go to lunch with me one day, and I laid all these cards on the table. It was immediately after that that the Board recommended to Ed that he have such a >. Scientific Advisory Committee and they fortunately set it up so that this group answered to the Board and not to Ed. It was just in the nick of time; it actually was just a little late. The top blew off of things between Keeney and Dimond and Vander Laan, in fact I think everyone of the clinical members signed a petition except Marlow and Lambert that was easily interpretable as critical of Ed Keeney. This was a report to the Board of Trustees which these fellows signed. Ed won that round, though the group was egged on by four powerful members of the Board of Trustees, but not powerful enough and it wasn't a majority. Of course I wasn't at the Board meeting but apparently it was a knock down drag out fight and there were some of the hard boiled business men there like Fred Rohr, since dead, who believed this was insurrection and that you don't do anything in such a case but fire whoever is involved. Dr. 0.: Is this when the tenure business came up?

Page  415415 Dr. H.: No this was after, I don't know if you even have any information about this incident in the records you have seen. Dr. 0.: No. There is no mention of this in the papers that I have seen. Dr. H.: I may have buried it entirely. Perhaps it is just as well. It did result in the President of the Board of Trustees calling all of the Members together who had tenure saying that he was representing the Board and the Board had taken the action that if there was anyone who didn't want to live at the Clinic under the rules and regulations of the Board and under the officers as the Board had appointed, he could resign forthwith, and he got up and left the room. Ziegler did resign as soon as he could and so did Bill Shafer and Torrance. Vander Laan would have also, but he didn't find a suitable place to go, so he has been spanked at every opportunity ever since - until recently. Dr. 0.: That is miserable. Such things should be buried and forgotten and people should concentrate on building instead of throwing salt in old wounds. Dr. H.: Well, his work is going so well and he is doing good work. I don't know how he stood it, but he somehow has managed to weather it. Apparently, he is beginning to be accepted for what he is again. He runs the best training group for young clinicians there. Dr. 0.: One of the things I was quite interested in, was your involvement as Chairman of the Committee that Dr. Keeney had brought together

Page  416416 to decide or rather offer suggestions on what future course the Clinic should follow. I followed this fairly carefully through the material you have gathered and was interested to find that there was a fair amount of disagreement among the members of this committee. Dr. H.: Except me. These were all full time clinicians on this committee. There was a great deal of division of opinion there. For instance, Vander Laan felt strongly that in order that the different specialties have suitable material for teaching as well as research, because Vander Laan has always felt that we must do teaching, that they therefore needed a department of general medicine. Well Keeney was adamant against this, and so was Farr, who was Keeneyfs representative on the Committee. Keeney and Farr were the Department of Allergy, He opposed this strenuously, so there had to be a division of opinion there. Then Monroe and Dimond both felt the loss of the hospital next door so keenly and not having a surgeon handy in case of a problem after cardiac catheterization, or endoscopy, that they were strong for having a department of surgery. It was obvious we couldn't do anything in the way of using the hospital as a source of clinical material or for clinical purposes for five years as it was part of the conditions under which the Scripps Hospital was sold to the Clinic However, they felt that this should be planned for. Again, Keeney didn't want surgery represented.

Page  417417 One of the basic problems which I understand has now been resolved was that Dr. Keeney not only wanted to consider himself the administrative head of the Scripps Clinic, but as the leading clinician. He was good in his specialty yes, but not as an overall internist. Bill wanted to get somebody like Chester Keefer or Bill Castle or somebody like that and I egged him on in this respect, because I felt that this would do the same thing for this institution that getting Van Slyke to go to Brookhaven had done for Brookhaven. I believe firmly that it is a good way to catalyze things. Dr. 0.: It would have done the same thing to the clinical side that you had done to the basic science side. Dr. H.: Yes, that is what I thought. But Ed didn't want to take second place in the Clinic as a clinician. But now he has been sort of kicked upstairs in a sense and made the President of the Clinic and he is on the Board of Trustees. They have added a very good clinician, an unusually good dermatologist, Dr. Stoughton, from Western Reserve. They have replaced Dimond with a very good young man from Yale. So maybe they are at long last on the road to what I had hoped they would do. Dr. 0.: I think it is important that we have had this discussion of the Scripps Clinic because I donft know of any place where you can find much information about the Scripps Clinic. Dr. H.: Well it has made a good name for itself. Annual reports

Page  418418 don't tell you what goes on and what makes an organization tick. [ Pause ] This is an interlude. I am looking at the program folder of the symposium which was given on October 23 and 24, 1965 at Ann Arbor in honor of my 70th birthday which actually was to come on November 20. About 250 of my old students or colleagues turned up for this occasion. It was a well planned symposium in which the speakers and their topics were selected because of the timeliness and the excellence of their research and not because they ever had anything to do with me, although they all had in one way or another. One of the papers was by Professor John R. Pappenheimer, Professor of Physiology of the Harvard Medical School. His paper was "Cerebral Bicarbonate Transport in the Control of Breathing" and he opened his address by stating that when he first came to Harvard in Dr. Landis's department, Dr. Landis assigned him to me as the representative of the Physiology Department to work with me on the two week integrated course on the physiology and biochemistry of respiration. He said that in the course of his working with me during the year, I had had occasion to refer to the fact that ever since the work that we had done on calcium ions in cerebrospinal fluid and in blood plasma at Chicago, I had realized that the cerebrospinal fluid is the extracellular fluid of the brain cells. Upon which he said, he was sure that I was wrong. He said that recently at long last he had gotten around to the point of proving that I was wrong. Then he

Page  419419 went on to describe some very beautiful experiments with a very ingeniously devised way of sampling from the cerebrospinal fluid of goats and of changing the ions in the cerebrospinal fluid of goats. As his work progressed he found that they could alter the respiration by changing the CC^ of the cerebrospinal fluid, but not necessarily of the plasma. So as his final slide he put on a picture of himself, looking quizzical, sitting in front of a Van Slyke manometric apparatus, feeding a Hastings-Singer nomogram to a goat! He ended by saying that he did all this work only to find out that it was unnecessary, that I had been right after all. Birgit Vennesland, when it came her turn to give her address on some work that she had done partly at the University of Chicago and partly at the Max Planck Institute for Biology where Warburg was the Director, talked about the effects of CC^ on the Hill reaction which is another way of saying that C02 influences metabolism, particularly in plants. She ended her speech with a slide depicting a page from the Biochemische Zeitschrift for 1925. This one page made history in the life of Warburg and in the life of the Biochemische Zeitschrift, because it is the only known occasion when Otto Warburg acknowledge that he had been wrong and thanked me for having pointed out the error of his ways. I think I have mentioned this before, but Birgit brought down the house with this. Altogether it was a very warm occasion to see all of these old friends.

Page  420420 Shortly before I had the opportunity to do the same sort of thing for Van Slyke on the occasion of his 80th birthday. Oh, I would like to talk about the Alpha Helix sometime. i But, to go back to the hard cold chronological facts, my 8 years at the Scripps Clinic and Research Foundation I regard as scientifically the most profitable from a personal standpoint that I ever had. It was really rejuvenating to have had this experience at this time of my life. I was content at Harvard but I was getting stale. Stale because I was having no fun out of administration. I was not having the painful joy of being responsible for the teaching and I was not even having fun in the lab. I was becoming more and more regarded as the "old professor", whether I was the old wise professor or not is questionable! At any rate, coming out into a whole new environment with a new set of problems and not bringing any of the old ones with me was rejuvenating. It was customary for people to say, "But Baird, you look ten years younger!" And I felt it, I felt it! Indeed I did not have pains in my neck and very soon I didn't have any more pains in my knees, though to X-rays they are just as moth eaten as ever. So finally following my 70th birthday and the termination of my grant, and my decision to send my scientific books to Shiraz, Iran to be used to form a small medical science library at Pahlavi University, I began to wonder what I should do next. People who knew that I was going to stop active work at the Clinic in the laboratory made various proposals. The Oklahoma Medical Research r

Page  421421 Foundation gave me an open invitation to come and to write my own ticket. The University of Michigan Department of Medicine wanted me to come and spend at least half of my year there teaching medical students. [End Side II, Reel 11] [Side I, Reel 12] Dr. 0.: This Reel 12, Side I, May 2, 1968. Dr. H.: I also had a standing invitation to come and join Van Slyke at the Brookhaven National Laboratory anytime I wanted to. But, due to the fact that Mrs. Hastings, the year after we returned from Taipei where she had contracted amoebic dysentery, developed a muscular disorder which bears the name polymyalgia rheumatica, and is controlled only by cortisone, it did not seem practical for me to seriously consider any of these opportunities which involved a move from La Jolla unless it became absolutely necessary. I must confess that I was very apprehensive as of September 1966 about whether or not we would be able to make both ends meet on my teachers insurance annuity retirement allowance which up to that time we had not tapped. It was to be our only source of income except whatever social security would bring. I don't think it is important or even proper to go into personal things, but since I had been earning some money ever since I was seven years old, and since I had had a steady monthly check come in and expected it to come in from November 1917 when I started with the Public Health Service, I had never been without an income. So it did worry me pretty much

Page  422422 and I was apprehensive. Mrs. Hastings persuaded me that by certain sensible economies we ought to try it and we could break even. We came out even last year. Well, what was I going to do after September 1? Dr. Keeney had said one day in his office, 'Veil Baird we'll find a place for you somewhere." This was not a way to encourage Baird to find a place at the Scripps Clinic. This was appropos of the fact that he said that he didn't think that I could stay in the office which I had been in, because he had other plans for it. I should also have said that this is what precipitated my trying to find another place for my books, not only myself but my books and journals. Even though Dr. Monroe said he was getting more space on his floor and he would fix up an office for me there and if I wanted to share a lab, I didn't want to do it too much, particularly after Dr. Scholander had been saving some space in his laboratory at the S.I.O. At the time that this was happening, Scholander had gone off to the Great Barrier Reef and was inaccessible, so I couldn't ask if he still had that space at S.I.O. for me. However, I did have an appointment as a Research Associate in Marine Biology, with no money involved. It did give me certain kinds of status. Meantime, Betty Baker, since I was closing up the lab, had decided to find a place here at the University. Dr. 0.: Betty Baker was your secretary? Dr. H.: No she was my senior technician. She was very good. She had come from here originally and had been with me for five years.

Page  423423 She ran a fine lab. Every scientist must have a woman in his life if he is going to run a good lab. She couldn't have been better. She had come up here and gotten herself a job and then proceeded to tell Dr. Livingston, when she met him, that I didn't know what I was going to do. The next thing I knew, Bob Livingston was down in my office asking me to come up and join them here and be a Professor in Residence. Bob then went off to the summer neuroscience conference in Aspen, Colorado and the next thing I knew, Dr. Joe Stokes (then Dean) called me one day and said, "Look, Bob Livingston sent over this recommendation for you as Professor in Residence, but Bob doesn't realize that it takes just as much trouble to get you to be a Professor in Residence without remuneration as it does if we were to pay you a full salary because it has to go through all the University committees at Berkeley and the Regents and it would take months and months. Besides I am told that they can't take somebody who is already emeritus and hasn't been on the California faculty." I told him that I didn't care what I was called, I wasn't going to get any money anyhow and I had been a professor and was a Research Associate in Marine Biology now and that was good enough for me if I could have a place to park myself and the books I had left and my files. Stokes said that was easy to accomplish with a stroke of the pen of the Chancellor. So, although it wasn't quite that easy because it turned out that I had to be removed as Research Associate in Marine Biology and reappointed Research Associate in the Department of Neurosciences, both without remuneration. "Without

Page  424424 remuneration" is part of the title that comes with the appointment. It amused me no end to find that they got a column and a half out of this change of title which hadnft cost them a cent! (Laughter) I kidded the Chancellor about it when I next saw him. I said that he got more mileage for less expenditure than I had ever seen in my life. Dr. 0.: You receive no income from the University of California? Dr. H.: I get paid by the days I work on the NLM contract for the NSP (Neurosciences Program) , but my appointment carries no university remuneration. I get this as a consultant to NSP. That's why you see all these inked crosses on my calendar. When I am here and giving full time work to the University I make a record of it. Every little bit helps. I get paid $25 for each seminar at the Clinic so I do that once a week. I'll do anything for a buck! Well, almost anything. Well, I don't travel on my own money I can tell you that. If anybody wants me badly enough, to transport me then I will go, but I can't afford to travel on my own. Dr. 0. : It really is a sad commentary on the values of our society, that someone who has devoted his life to teaching and the areas of i research that you have isnt provided with more security after your retirement. Dr. H.: Well, if it works out, it is alright. I put all of my resources into insurance and by waiting so long to tap my annuity,

Page  425425 it would be alright if I were getting a dollar out for every dollar I put in. But I am getting quarters out and so my income is just about half of what it was prior to 1956, in dollars, let alone with the inflation. I don't want to change our standard of living or have Mrs. Hastings move until she wants to. I think we ought to move into an apartment, but she doesnft want to. This means we have to hire a yard man and a house man once a week. As long as we can do it, that is the way that we will do it. When we can't, we'll do something else. But I think everything has worked out very well for us. I have no regrets whatsoever. I have had a tremendous experience and I look forward to tomorrow. Dr. 0.: Well this is the impression I have had of you since the first day I met you. Dr. H.: You know I am right in the center, even if I don't have any power or responsibility; I am in the center of this medical school here. I am just so excited about it; not in the way the boys involved are, but I am so excited about watching what is going to go on. I have a basis for comparison. As a student I saw Columbia, old P. and S. in those days when basic sciences really didn't count. It was notorious that when the students in the third year went to their first physical examination course, the professor would say, 'Veil now, get out your stethescope, now you are going to learn medicine. You have been wasting your time up to now." Dr. 0.: Some still feel that way as you well know.

Page  426426 Dr. H.: Yes, of course. Then there was this sort of ivory tower existance for 5 years at the Rockefeller Institute. It was the best of all possible years! Van Slyke had all the responsibilities and I had all the fun! I had responsibility within certain limits of planning experiments and executing them, with him serving as sort of an extra pair of hands in the experiments. Then at the age of 30 I had the chance to run my own show at the University of Chicago and to see what I could do, and thank God, that turned out to be in the Department of Medicine after a year and not in the Department of Biochemistry. I found I was useful to the Professors of Surgery and Medicine. I helped Charlie Huggins grow; I helped Phil Miller grow; Lowell Coggeshall grow as well as Dallas Phemister, who really was not much of a researcher. Lester Dragsted was good; he was very good. I was very young when this was happening and with resources of $50,000 a year hard money from the Lasker Foundation what could be better? You canft come by that kind of money even now! At 40, came all the fun of having Harvard for quarter of a century, a short quarter of a century. Then 8 years again to go back and see what I had learned! Now I have had to tack on another phase to my sheet of life phases. The question you know was when I pasted one on, where should I cut it? Dr. 0.: It should be open ended! Dr. H.: Well, I carried it out to 1975. I feel that if I am still extant and can't paste another strip on, then there shouldn't be

Page  427427 anymore pasted on! Well that will be my 80th birthday if I make it. [Pause] This will be about what I will call my biochemist's Odyssey, or a Tale of Two Islands. By two islands, I mean Israel and Taiwan, defining an island as a piece of land which you as an inhabitant can only leave by sea or by air. All together to make this Odyssey, I covered 47,000 miles which is almost twice around the earth, but I never got all the way around even once. I had to do it this way because, since I was traveling from La Jolla to Israel for the National Heart Institute of the Public Health Service and from La Jolla to Taipei for the United States Navy, it was not possible within the length of time that I had available to arrange for a single ticket around the world that would take me to Israel, to Taipei and finally back to La Jolla. On August 29, 1962, I left La Jolla for Israel but my first stop was Athens, this being my first opportunity to fulfill a date at the Parthenon which I had with a shade. It was the shade of Mr. Forsythe, my ancient history teacher at Shortridge High School, who said to me in 1910, "And when I meet you at the Parthenon 50 years hence, and ask you what was the Age of Pericles, you are to remember it was 480 to 430 B.C.!" So I laid over 24 hours in Athens and had my date with Mr. Forsythe and there he was. I was thrilled at having this opportunity to relive my youthful thrill over Greek history, Greek

Page  428428 culture, and the Greek language. I went on after this stopover, to Tel Aviv and rendezvoused with six other American scientists, and we seven, met with seven Israeli opposite numbers. We fourteen men spent two weeks together, visiting all the medical research institutions and hospitals engaged in cardiovascular or related basic research in Israel. We would hold seminars and discussions after these sessions at the laboratories and ended up by preparing a report for the United States Public Health Service with recommendations for joint participation on cardiovascular problems. To finish off my itinerary, I then returned directly, as fast as planes could take me, from Tel Aviv to La Jolla, arriving on September 15, left my dirty shirts and picked up some clean shirts and my wife and took off on the 17th for Taipei, Taiwan, where we arrived on September 22. I'll come back to what I did there, but we stayed until November 6, or rather we were there 6 weeks and returned directly from Taiwan to La Jolla arriving in La Jolla on November 6 and I took off on the 7th for Washington for a meeting of the National Heart Council in order to report on the trip to Israel. Hence this amounts to 47,000 miles without circling the earth. Of course we were easily able to cover Israel from its southern to its northern tip. It is so narrow that we were never out of range of the Jordanian guns. The work that was going on there was very good.

Page  429429 There really seemed to be little reason to set up teams of American medical scientists to study heart disease in the different types of Jews. I have forgotten the names of all the groups. The Yemenites, for countless generations, had lived on the same diet and had the same habitsc They had never been westernized. It is an opportunity which the Israeli scientists are taking advantage of. They are studying the incidence of different kinds of heart disease and stroke. A good deal of very excellent basic science was going on and I was delighted to see the Weizmann Institute, which seemed to me to be as good as the Rockefeller Institute, the Max Planck Institute or the National Institutes of Health. It is well equipped and well staffed My next assignment which had been of long standing was to spend six weeks at Taipei, working with Dr. Robert Phillips on the treatment of cholera. This was at the Naval Research Unit 2, known as NAMRU 2. Dr. Phillips, who was formerly at Harvard with Cannon and at the Rockefeller Institute with Van Slyke and had been in the Navy since World War II, was in charge and had been the Director for 8 yearso This is the Phillips who with Van Slyke during the war had devised the simple, ingenious and really very accurate method of determining specific gravity of blood or plasma with copper sulfate solutions of different strengths. It is a very simple and scientifically sound method.

Page  430430 Phillips, using the principles that had been my bread and butter throughout my life -- which is, if you can get the mass and electrolyte concentration of the several fluid phases of the body corrected to normal values and if there is an acid-base abnormality, get it corrected to normal values, then you give your cells the very best opportunity to heal themselves. Until you have done this, you don't give your cells the proper chance, which is the principle of the Phillips1 treatment of cholera. He had proven to his satisfaction that if you can get to a cholera patient within 8 or 12 hours of the time of the onset of an acute attack, you can save him if you will keep the fluids up, and monitor the water and electrolyte needs. He had devised very simple means of monitoring. Of course, if it is in the field, you start giving straight isotonic sodium chloride; you don't worry about the acid-base balance, you first try to get the mass of the extracellular fluid built up so the blood can flow. As soon as you can you get a specific gravity of his plasma to monitor his need for fluids. He is placed on a canvas cot with a hole in it and a can underneath, where you can monitor how much fluid is coming out per hour. This amount of salt and water loss is replaced by mouth or vein in an equal quantity per hour, and as soon as you can get a C0£ determination and preferably a pH with it, you can start monitoring the acid-base balance. Then you start bicarbonate administration according to need. There is also a loss of about 10 milliequivalents of potassium per liter which is added to the repair fluids. With this therapeutic routine

Page  431431 he always saved them 100% of the time under these conditions. Well, I had been invited to participate in this work and it was a good year to be out there because they had had a small epidemic of cholera in Taiwan, not in Taipei itself but in one of the southern cities. I worked for six weeks doing research and gave a number of lectures, both teaching and research lectures at NAMRU 2 and at the University. Dr. 0.: Are you looking for the name of the University? Well there are two medical schools. There is the National Taiwan University Medical School which is staffed by Taiwanese and there is the NDMC, National Defense Medical College, which is supported by the Peking Union Medical College. It is the PUMC of Nationalist China. The PUMC now exists as the NDMC in Taipei. Some of the old staff that were there when I was in Peking in the 30's were still there. A parasitologist, a pathologist, and a physiologist were all still there. The rest were all younger faculty people, [Pause] Dr. 0.: The date is May 4, 1968 and we are again in the Office of Dr. Baird Hastings at the Scripps Institute of Oceanography in La Jolla, California. Dr. Hastings i£ first going to continue with his discussion of his work with NAMRU 2 on Taiwan, in 1962. Dre H.: I had two scientific activities in addition to my lecturing

Page  432432 while I was there. One was to survey and plot the data that Dr. Phillips and his colleagues had obtained previously in their studies on the treatment of cholera in the Phillipines and in Bangkok. It was the most beautiful data on the changes that occur with time in the treatment of cholera with respect to the acid-base balance of the arterial blood that I have yet seen. When I plotted the pH and CO^ and calculated C02 tensions of the successive samples of blood before treatment was begun and in the course of treatment, it was dramatically shown that the cholera patient before treatment was suffering from a severe metabolic acidosis and superimposed upon this, due to the extreme loss of fluids and contraction of the extracellular fluids and circulation of blood, a severe respiratory acidosis,, With the rapid restoration of the extracellular fluid volume by intravenous isotonic sodium chloride, the respiratory acidosis, that is, the retention of CC^ and high C02 tension in the blood promptly disappeared, although the metabolic acidosis was intensified. Then with the treatment of the metabolic acidosis by adding sodium bicarbonate and potassium to the intravenous fluids, the metabolic acidosis was corrected and in a matter of 24 hours the acid-base balance was restored to normal. What was exciting to me about this, was that in spite of the severe metabolic acidosis, the low pH, the low bicarbonate, and the low CC^ tension, the pathway taken by the blood in its return to normal was the same pathway that Shock and I had found when we artifically created a metabolic acidosis in normal human beings. The pathway was closer to a constant C02

Page  433433 tension than it was a constant pH thus emphasizing the metabolic importance of CC^ tension. In the laboratory I worked with one of the laboratory assistants on trying to produce cholera experimentally in animals. So far this has not been successfully accomplished. For some reason the cholera vibrio does not produce the disease even when it is injected in large amounts in the gastrointestinal tract of animals. The actual experiments that we did was to study the change in the contents of a closed loop of the small intestine of rabbits, in which the circulation was maintained intact. In other words the loop was simply tied off but remained in the animal. We would inject a solution of known bicarbonate concentration into the loop and then take small amounts out from time to time and analyze it. For this we used the micro Van Slyke manometric apparatus and measured the pH as well as the C02« We did this in loops of intestine in normal animals and in loops in which we had previously injected a rich cream of cholera vibrio 24 hours before. Though we found no effect as a result of having introduced the cholera organisms, I at least was surprised to find that no matter what concentration of bicarbonate we used in this solution which we introduced into the loop, that is whether it was isotonic sodium chloride, or a solution that had a concentration of 150 millimolar bicarbonate, with time, we always ended up with a solution whose concentration of becarbonate was about 100 millimoles per liter. I should have also said at the beginning that this was a loop of the ileum.

Page  434434 The laboratory at NAMRU 2 was very well equipped and very well staffed Phillips had as associate an excellent biochemist, who had been a professor at Northwestern, named Quentin Blackwell. His wife, who was a M.D. from Thailand, a beautiful woman, was also well trained in biochemistry. One of the things that pleased me about this visit to Taipei was to find that a most careful and complete comparison had been made between the micro pH method, known as the Hastings-Sendroy colorimetric method for the pH of blood plasma, published in the early 20's and the most modern electrometric glass electrode method. The two methods agreed to within a hundredth of a pH the limit of accuracy of each method. We were royally entertained while we were there and met many of the important Chinese and foreign representatives from the Embassies. It was rather reminiscent of the experience we had had in Canberra, Australia some years before. One thing should be recorded. At a dinner given us at their Academy of Science, I sat next to the President of the Academy and when I inquired why it was that they did not offer Ph.D. training but only training for Masters Degrees, he said, "Until we can be assured that the training that we offer for the Ph.D. degree is as good if not better than that one would obtain in the United States, we shall not offer the degree." Dr. 0.: I find this very interesting. I don't imagine all of the Asian institutions adhere to such standards.

Page  435435 Dr0 H.: No. By and large I've seen such programs develop abroad and I have never heard this idea expressed before, nor has it been followed out elsewhere as far as I know. As I previously recorded, we returned directly to La Jolla and I took off immediately for Washington where we discussed our trip to Israel for the National Heart Institute and prepared recommendations for the further activation of research in Israel on cardiovascular disease. [ Pause ] Now I would like to talk a little bit about the problem and importance of communication between interfaces of adjacent activities if we are talking about science; between one institution and another institution if we are talking about education; or the relations between people engaged in different activities. I shall illustrate this from my own experiences. Which comes first, the hen or the egg in this respect, I don't know. It may be that it was simply the accident that in my first efforts in research as an undergraduate at Michigan, I was directed by my Professor, Dr. Floyd Bartell, to the study of the exchange of water and ions across collodion membranes. I think I have already described what I did, but this was my first exposure to what happens between two phases which are separated by a restraint (the membrane) which doesn't let them mix easily and completely and rapidly. Since then I seem to have always been studying some aspect or other of this same simple

Page  436436 problem. In later years I undertook the study of the blood which is a two phase system in which the contents of the erythrocytes are separated by a membrane from its environmental fluid, the blood plasma, and later the relations that exist between the blood plasma and the extracellular fluid, separated by the capillary membrane, and later still the differences in the composition and behavior of the intracellular fluids of the cells of the several tissues and their extracellular fluid. Even now, in my new life, I find myself mostly concerned with the cerebrospinal fluid and the cells of the brain, the neurones and the glial cells. As I hear my colleagues talk about the origin of life here at the Scripps Institute of Oceanography, searching for ways in which large molecules were formed from the small molecules that may have been accidentally synthesized either by solar energy or electrical phenomena, I ventured the guess the other day that perhaps one would find templates in the inorganic matter of the earth before the organic matter became organized, that would provide a proper surface for the formation of, let us say, an a polypeptide alpha helix. This isn't as far fetched as one might imagine, perhaps because it has been pretty well accepted now that the reverse phenomena occurs in the calcification of bone. We know that we have body fluids that are supersaturated with respect to hydroxy-apatite, the solid phase of bone. But we also know that hydroxy apatite will not spontaneously form from such solutions, although we can expose the plasma or other solutions, which are similarly supersaturated, to solid hydroxy apatite and bring about precipitation and equilibrium.

Page  437437 However this would not be a suitable thing to happen in the body because it wouldn't allow for proper and organized growth. It now appears from the work of Dr. Glimcher, growing out of work which Francis Schmitt had done on collagen, that the native collagen fiber, when first synthesized, has a crystal structure mimicking that of hydroxy apatite. Our thought at the present time about the initiation of calcification is that the native collagen fiber with an hydroxy apatite dimension and conformation is first formed. This rather promptly brings about a local precipitation from the supersaturated solution of hydroxy apatite on to this native collagen, which then grows to about three crystals, three hydroxyapatite molecules in depth. But its further growth is inhibited by the fact that the surface becomes coated with other ions. [End of Side I, Reel 12] [Side II, Reel 12, not recorded ] Dr. 0.: This is Side 1 of Reel 13, recorded May 4, 1968. Dr. H.: Well, I was just talking about how the calcification of bone seems to occur. After the precipitation of the molecules of hydroxy apatite -- about 3 molecules thick -- on the collagen fiber which has the same dimensions and crystal structure as a crystal of hydroxy apatite, this hydroxy apatite exposed to the surrounding solution takes up carbonate ions, citrate ions and sodium ions which are there in large amounts. This surface is now no longer a surface which will permit the

Page  438438 preciptiation of further hydroxy apatite. The hydroxy apatite crystal does not grow as it would if it were just in an inorganic solution without these other ions present in the solution. In order to get more calcification, you must spin out more native collagen fiber to make another unit. This gives us another example of surfaces which determine what's going to happen. In speculating on this, I have ventured the thought that if collagen can be a template for hydroxy apatite, then hydroxy apatite conceivably could be a template for a protein spiral such as collagen. This is not something that is proven experimentally, but the marine biologist who was venturing theories about the origin of protein fibers said it might be something worth looking at. I suppose that since all of my scientific thinking time was related in some way to what happens across membranes, this may have had some influence subconciously on my efforts to build bridges, membranes or connections -- what you will -- between different areas at the University when I saw that they were unnecessarily separate„ An example would be the fact that while I was at Chicago, I did biochemistry both in the Department of Medicine and in the Department of Physiology. Through becoming acquainted with Professor Thurston, the Professor of Psychology, who introduced many testing methods to psychology and was himself originally an engineer, we made a deal to train a person both in psychology and in physiology0 This person turned out to be Nathan Shock, whose Ph.D. actually was in psychology though his thesis was done entirely with me in physiology. As you know I had an appointment in Physiology as well as in Medicine. The important thing at Chicago probably was trying

Page  439439 to keep biochemical science well represented in the thinking and activities of the Departments of Medicine and Surgery and Pediatrics. At Harvard I had too much to do to start with in the Biological Chemistry Department at the medical school to carry on this bridge building business at first, but later I spent a great deal of effort trying to build bridges between the Harvard Medical School which was on Longwood Avenue in Boston and Harvard College in Cambridge. Certainly at the time I went there these functioned as two separate institutions. The faculty at the Harvard Medical School regarded themselves as quite independent of the activities at Cambridge. It had done this almost from its inception, though there is a story told about President Eliot after he had been elected President and attended the first faculty meeting of the medical school. When the Dean of the Harvard Medical School came to the meeting he found the chair at the head of the table which bore a plaque saying "President's Chair" occupied by President Eliot. He was taken aback and apparently according to the story was obviously surprised that the chair was not emptyc He is reputed to have said, "Well, Mr. President it's a surprise to see you here at the head of our table." Upon which Mr. Eliot is reputed to have said, "Well, Mr. Dean, you have a new President!" I think this has continued from that time on. Certainly Conant always attended the faculty meetings and presided, but it hadn't had much influence on the way that people felt about it, iee., the independent status of the medical school. They felt decisions of the medical school were to be made in the interest of the medical school, whereas I felt from the beginning that decisions made there at the meeting should

Page  440440 always be considered in terms of the interest of the University. Perhaps I succeeded in part, but I don't know. I tried. There were small ways in which I went about this. For instance, each Department head created his own stationery and had printed whatever he wanted as the heading. Since there was no official Harvard stationery, I designed our stationery to read in biggest type at the top HARVARD UNIVERSITY and in small type on the next line, Medical School and in smaller type under that, Department of Biological Chemistry. I was chided a bit about this, because people who saw it and paid any attention to it said, "But Baird, we always call this the Harvard Medical Schooll" I said, "Well this emphasizes what I feel about it. This is the Harvard University Medical School." Dr. 0.: Did you also find yourself a bridge between the basic scientists at the medical school and the clinicians? We haven't really talked to this point. I would suspect from what I have learned about you that this would not be surprising if this were the case. Dr. 0.: Yes, I certainly did try my darndest to keep a close intellectual, scientific, administrative and social relation to the clinical departments. Indeed I feel as much at home among the academic clinicians as I do among the physiologists or biochemists. Perhaps even more so. I have always been very proud of the fact that I was elected to the Association of American Physicians. As long as I was on the east coast and at Chicago I would never miss a meeting of the Association in Atlantic City in the spring. I enjoyed them and I always got a great deal of stimulation out of the papers.

Page  441441 I didn't limit it to the clinicans. I was struck by the fact that there were no PhcD. candidates in the Division of Medical Sciences, of which our Department was a part, who had done their undergraduate work at Harvard, who had been chemistry majors and then went on to take their Ph.D.'s at Harvard,, So I made it a point to get well acquainted with the professors or Organic Chemistry and Physical Chemistry at Harvard. It didn't have much influence on the chemists who came, but some did and it did make it very much easier and for better relations in our being able to send our people over there for special training in organic chemistry and physical chemistry when that seemed to be desirable. We had a bridge with M.I.T. Francis 0. Schmitt came to M. I.T. in 1941, as Head of the Department of Biology. He is a biologist who concentrated on the physical side of biology, molecular biology. Since M.I.T. had no biochemistry we made an "informal" arrangement, that being the most successful and easy way to do things in Boston, whereby when his students needed to have a course in biochemistry they could come and take our course and they would accept our grade and give them credit. When we wanted our people to get experience in X-ray analysis and electron microscopy and physical methods which we didn't have available, at Harvard, they could take courses over there. M. I.T. had once, many years ago, when Eliot was President almost amalgamated, but there was a hitch at the last moment and it hadn't occurred. Instead of going through a lot of formalities

Page  442442 which would have taken a lot of time, Professor Francis Schmitt and Baird Hastings made their own arrangements which worked and were never questioned by anybody, which is the best way perhaps. I suppose this business of building bridges has been the basis for my attempt to get people to sit down together, particularly if they have had differences of opinion. This was true with respect to Richards and Clark, which I have already recorded. I'm not sure I recorded the instance in which Subbaow had been working on the antipernicious anemia factor about which many rumors had arisen. It happened right after I came to Harvard. Since at that time there were several units in different hospitals all interested in pernicious anemia, I decided the best thing to do was to get them all in my office and have Subbarow tell them exactly what he had accomplished and where he was» I wonft elaborate on this, except that it solved that problem at that time. When I developed our course of biochemistry, I built a bridge between our department and Physiology. This collaboration, first with Drc Cannon and then with Dr. Landis improved both our courses immensely. It was complementation - not integration!1 I think that building bridges is very important, but it must be between two phases, physical or social, each of which has something to give. Though non identical phases, each will profit by an exchange with the other. Integration is taking out all the membranes and homogenizing all of them and getting a "gemisch." When you do that

Page  443443 you don1t have a biological system! Whether you do it with liver or whether you do it in an institution! or a medical school! I find I am making a speech I used to make when George Berry wanted integration of the curriculum! [Laughter] I think I have had a great deal of fun and what success I have had by working at the interface myself between chemistry and biology, and physiology and medicine„ I used to say that as long as biochemistry was an interface between chemistry and biology, it was a viable portion of science,, But the minute it became a homogeneous unit without being that interface, then it was no longer a viable biological science and indeed was dead! It was natural I suppose then when I came out to the Scripps Clinic and Research Foundation to have as my goal for the institution that it should have appropriate interfaces. It should have two phases at least, basic science and clinical investigation, but that they should have an active exchange and a close relation between the two phases. If I have any regrets in my life, it is that the basic science phase, once started there, overwhelmed the clinical phase and instead of having a semipermeable membrane between the two, itfs been more like an iron curtain in which there has been much too little interchange of ideas. Perhaps the thrill that I have had and the rejuvenation again for the second time--a head lifting instead of a head shrinking—in moving from the Clinic to the University, and particularly by occupying space at the Scripps Institute of Oceanography, has been to find here very active interchange

Page  444444 between the laboratories and people of such diverse interests and technology. Dr. 0.: You refer now to the oceanographers or the folks in the neurosciences? Dr. H.: I mean the oceanographers. Whether it's physical oceanography and the study of the currents and sea floor, or the biology of the ocean, itfs a whole new world. In a sense, at long last, I am studying the sea around us, rather than the sea within us. [Pause] This will be an account of my life with Pete Scholander. His actual name is Per Fredrik Scholander, born in Sweden and educated in Norway. He has an M.D. and a Ph.D. in Botany from the University of Oslo. He was an instructor in anatomy at Oslo for 2 years and then a research fellow in comparative physiology. In 1939 when he was 34 years old, he came to this country and worked with Lawrence Irving, who was Professor of Physiology at Swarthmore College. It was during this period that I met him first„ He is by all odds the broadest based biologist in interest and competence that I have encounteredc But these interests are in a body which is inherently skeptical of all previously accepted concepts. On top of this he is ingenious in devising techniques, new techniques and amazingly resourceful in assembling equipment necessary to pursue his problems.

Page  445445 "The world is his onion." As he goes through the activities inherent in every day living, almost every thing he notices, suggests a problem to him. He has worked on plants and animals, one might says all over the world. While working with Irving, he became interested in why seals can dive and stay under water so long. He and Irving attached EKG's to seals and recorded the electrocardiograms while they dived. I am told that during this period he kept a seal in his bath tub to the horror of his landlady. During World War II he was a Captain in the Air Force and was Chief Physiologist Test Officer, Air Force Base Egland Field, 1943-45 and then at Wright Field at Dayton. He came out of the service as a Major and received the Legion of Merit. The story goes that when he was sent to the Arctic research laboratory during the war to investigage adaptation to cold in the interests of the Air Force, after a few hours there he presented himself to the commanding Colonel and said, "Sir, I must go to Panama." The Colonel was aghast and said, "But you just got here! What for?" Scholander said, "I must get the parameters I" Shortly after he was at a small research laboratory in the center of Panama Canal getting his parameters for adaptation to heat and cold. He did do some ingenious work in the Arctic at that time. Following the war, he had a brief period with the Office of Naval Research from 1947 to 49, but was pretty restive under the restrictions of military life, and so I arranged for him to have a fellowship paid for by the Milton Fund at Harvard. I was able to support

Page  446446 Scholander from the Milton Fund because I could swear that the work he would do was not in any way a substitute for work which would be undertaken otherwise by Harvard funds, or would his research activities be otherwise paid for by Harvard funds. The Milton Fund was a large and very desirable fund, but it had been so tied up by the lawyers in the deed of gift that it was practically impossible to get the legal department to authorize its use. Scholander was in the Department for 2 years and was a catalyst with everybody, but most irregular in his working habits. When he was in a working phase, he would work day and night, and then he would disappear for several days. It was then that I learned how to get the most out of Pete Scholander, but always expect the least in terms of regular activities that you could count on. He had devised a crude apparatus while in the Arctic to measure metabolism of small sea organisms, i.e., measure their oxygen consumption. Out of this grew the idea that he could adapt this method and refine it so that it would take the place of the Warburg apparatus for measuring oxygen consumption of tissues. It was basically a six cent medicine vial, a glass vial, which was attached through a stopper to a small manometer. The manometer carried an air tight plunger so that you could always bring the manometer level back to the same mark. Basically this was a constant pressure apparatus in which you measured the change in volume, because you would read on a millimeter scale how much the plunger had to be

Page  447447 changed in its position in the manometer in order to bring the reading on the arm back to the same point so it was a constant pressure. He read the change in volume by means of the height of the plunger whose diameter was known. Well, arrangements were made to have six of these running at a time, 6 or 7 in a thermostat with shaking. It gave results quite as accurate for oxygen consumption as those one would get for a similar amount of tissue in a standard Warburg apparatus. Basically it was much, much less expensivec However, when it was put on a commercial basis with all the fanciness and profits, it was never marketed for less than a Warburg apparatus. We had 3 in the department and graduate students who became used to it, preferred it to the Warburg. It had many points about it that made it more flexible and since one of the things that one wanted to do at that time was to use radioactive isotopically labeled substrates, you wanted to take successive samples of alkali which had absorbed the carbon dioxide which you can't do in the Warburg apparatus whereas in this Scholander apparatus one can. That is just one example of this. So that is what he produced the first year. Meantime, during that year he had questioned the work that had been published from the Carlsberg laboratory of Copenhagen on the oxygen consumption when a single cell divides. Nobody had an apparatus at that time that would permit you to measure the oxygen consumption of a single cell and so the Carlsberg laboratory had based their conclusions on the simultaneous division, or what was hoped to be

Page  448448 the simultaneous division, of 100 cells with the apparatus that Linderstr m-Lang had devised. For them to say that this was the same as the consumption of a single cell was enough for Scholander to say, "I bet it isn't!" His ambition was to devise an apparatus for measuring the oxygen consumption of a single cell. This was what he did the second year he was in our department. He succeeded in devising what came to be known as the "bubbleometer". He used the principle of the Cartesian Diver. He had a little bubble of air on a tiny plastic float and a single cell starfish egg, or something of that size. He couldn't get his apparatus down to a point where he could use a leucocyte. However, he was able to follow respiration of his cell with this very ingenious method, having the cell actually part of the Cartesian Diver which would use up the oxygen in the bubble and then it would sink. He had an arrangement whereby he could put on negative pressure (and read it through a cathetometer) until he brought the Diver back to the mark. I have forgotten the accuracy of this method but it was something in the order of a millionth of a cubic millimeter of gas. Using this both at Woods Hole and at Friday Harbor in Washington subsequently, he found that sometimes there is an increase in oxygen consumption but usually there is not. The apparatus itself I think is still in use in certain laboratories at Woods Hole. He then went back to Oslo because the Norwegian government had built him a research laboratory and made him director. By then they

Page  449449 should have known that they should never make Pete a director. He was very restive under this responsibility and when Dr. Roger Revelle learned in 1957 that he wished he were not in this administrative position, he wrote to me while I was in Australia on whether or not I would advise him to try to get Scholander to come to the Scripps Institute of Oceanography. I wrote back that he couldn't find a better man, one that would be more stimulating and productive but under no circumstances should he ever expect him to carry out any administrative activities as it would make both Pete and him unhappy. He got Scholander to come here to the Scripps Institute of Oceanography in 1958, the year before I came. Though they did not have these buildings we are in as yet, he had some very small quarters and promptly got to work. He had one room and another small room that had to serve all the purposes of an office and a laboratory. When I first saw him after I arrived in '59 and said, "Well Pete how are you getting along?" He said, "Oh, terrible! My lab is full of secretaries and alligators I" When I saw it I found that this was true! He had a bathtub in the center of the lab that was full of an alligator who was so big his tail hung out! And a secretary and people milling around at the lab benches. He said, "I wish I could work on a problem to find out about myoglobin. What do you think myoglobin is there for?" I said, "Why ask me? You and Larry Irving worked on it for a long time." "Yes", he said, "but the textbooks and everybody writes that it is just there to store oxygen. It can't be! It has got to have another function.

Page  450450 All the blood goes through the muscle; there is plenty of oxygen, plenty of oxygen!! You don't need myoglobin to store it. But I'm going to need room to work on it." I said, "Well there is nobody but me and Mrs. Bien in this nice big lab with three big bays. Come on down to the Clinic and set up shop." Which he didc That was in the spring of '59. He said, "Now Baird, give me some myoglobin!" I said, "Well Gee, I don't know how to make it. I never have, though I suppose I could learn." He then said, "Veil then give me some hemoglobin!" So we got some blood, hemolyzed it and cleaned it up and made our hemoglobin solution. He had an idea in the back of his head which he then converted into having the glassware made so that he could measure, with accuracy, the rate at which oxygen diffuses from a gas phase through a fine sinter-glass filter with a big area, with and without a layer of hemoglobin on it, to the other side. He first proved that he could duplicate the physical constants for the diffusion of gases this way, before he undertook to see what effect hemoglobin and eventually myoglobin would have on the rate of diffusion,, I am sure in the back of his head he had a hunch that myoglobin would influence the rate at which oxygen went from one spot to another in the muscle. Otherwise he wouldn't have undertaken to measure this. He immediately found that if you have active hemoglobin, that is hemoglobin that can reversibly bind oxygen, that you increase, at physiological pH's, the rate at which oxygen is transported through this very thin membrane

Page  451451 8 to 12 fold1. It was very easily demonstrated that this was not an artifact, because all you had to do was to convert the hemoglobin to methemoglobin and it stopped coldc I named this the "Scholander Effect." He did this in less than 2 months I would think. In that same spring, he took off and spent several weeks in Labrador with one of the boys from Boston to study why fish who are in supercooled water don't freeze whereas other fish would. This is a problem he is still interested in up in the Arctic this year. He finished writing up the results that he had gotten in Australia the year before on the adaptation of aborigines to cold, because they are practically naked and it gets very cold there at night. He made some observations en route on the Japanese pearl divers, on the bradycardia of diving, and he also was off on the joint Danish and American expedition to 1 R 1 / Greenland to date the glacial ice of Greenland by Oxygen C ratios. He started while he was in the lab in '59 telling me that the ships here at S.IcOe weren't really suitable for field laboratory work. They were fine for collection, but they werenft adapted for field biological work and there should be a ship specially designed as a sea-going laboratoryc This was the beginning in 1959. He kept nagging me about this. He always referred to me as Mr. Moneybags. He said, "You sit on all the money in this country. Give me some money so I can have a boat." Eventually, through Pete's nagging about it and his increasing reputation; he was elected to the National

Page  452452 Academy of Sciences and the American Philosophical Society -- the National Science Foundation did undertake to provide him with a sea going laboratory, which was built and came off the ways 3 years ago. It is now on its third expedition. This is the R/V Alpha Helixc We had many arguments about the name. We wanted to name it the Revelle, but the University did not permit us to do this because they were planning to name the first college, Revelle College. So it was Pete's choice to name it the Alpha Helix, which I think he did, not so much because he had any idea at all of what alpha helix is in chemistry, but because he had the picture of the medical Caduceus in his mind as his idea of what an alpha helix would be and its visualization as the mermaid of Copenhagen Harbor stretched out with he twisted fins extended. This ended in a very handsome bronze figurehead which adorns the bow of the Alpha Helix, made by a gifted young sculptor, Ed Schumpert. Of course even with this ship coming into being, Pete was not resting on his oars at all. He, at the same time, succeeded in having a 3 story building attached to a large circular tank of sea water built at the Scripps Institute of Oceanography. The building was to be called the PRL, the Physiological Research Laboratory, and the tank was to provide a means of studying large sea mammals, porpoises, small whales, and large fish such as sharks and rays. As matters worked out, these were both going to be completed at about the same time, the same year, and Scholander meantime had not been able to

Page  453453 get the University to provide funds to increase the size of his laboratory and staff. I worried about this a good bit, because I saw a great deal of Pete while I was at the Clinic. I said to Drc Revelle, who was then the Director, "You are going to soon have one Scholander and he is going to have a sea-going laboratory and a land-based laboratory and what are you going to do then? You know you just can't count on Pete to administer either of these things." I said, "The least I would do is to have a group of people who know Pete and know how to get the most out of him and also know how to protect him from himself and would be senior enough that could be a help to you in administering these things." He said, "All right, set up such a committee," which I did. I was the Chairman of this committee for the first two years0 It is now functioning actually for the National Science Foundation which is supporting Scholander*s activities and the Alpha Helix more or less in lieu of a Study Section for the National Science Foundation. [End of Reel 13, Side l] Dr. 0.: Reel 13, Side II Drc H.: The National Science Foundation having decided that the Alpha Helix was to be a national facility informed Revelle that they would like to have him set up a National Advisory Committee. Revelle was able to say that he had done this. When he hung up the phone he called me and said, "Stick National in front of the name!" This

Page  454454 committee is still functioning with Dr. Bullock as the Chairman. It makes the decisions on the advice of Pete and other people involved as to where the expeditions of the Alpha Helix will go and if there are too many applicants, who will get priority, which protects the University and protects Pete from having to make such decisions. The coming into being of the Alpha Helix was not without its amusing points. First at the laying of the keel, I was asked by Pete to come up and preside at a little ceremony at the Tacoma Boatyard„ There I found that they don't lay keels anymore; they weld parts of the hull on the land and then a crane comes and picks it up and puts it in a cradle. Later when it came time for the christening, Pete insisted that I preside again. I said I would go to it but I wouldn't preside. I got up there the afternoon of the evening it was to be christened only to find that Pete hadn't paid any attention to me and had gone ahead and had a program printed, with me as the Master of Ceremonies. I had about an hour to try and devise some remarks in advance of the ceremony. There were to be about 8 speakers, including the builders and various functionaries from herec At 5:00 Pete said "I want to take you down to the boat before everybody comes at 6:00." So we went down to the boatyard from the motel and as we went through the gate of the shipyard, there was a great crash, bang, booml from the inside of the shed. We ran for the

Page  455455 edge of the water, just in time to see the Alpha Helix, having launched herself, sailing with even keel across to the other side! Fortunately nobody was in the shed, thank goodness, because these big 4' by 4's went flying in all directions. The men had been sent off to get a bite to eat to be back by 6:00 PM. The designer, as we ran to the water's edge, emerged from someplace, looking white as a sheet -- his name was Glosten -- and he said, "Oh, a catastrophe, a catastrophe!" He was running for a phone. But his wife, Mrs. Glosten had more presence of mind than any of us. She ran to the edge of the water and seeing a little tug that had been pushing log rafts around, yelled, "Get a line aboard her!" So he steamed out after her and before our lovely Alpha Helix and her 60,000 dollar propeller buried herself in the mud on the other side, he slowed her down, and stopped her and took her in tow and brought her back. At 6:00 we had the ceremony. After I got back here, I wrote up the incident, entitled "She Couldn't Wait"! She is quite a gal. Dr. 0.: A lady with a mind of her own. Dr. H.: A lady with a mind of her own. They were late delivering her to San Diego by about a month. (That was two years ago last fall.) So she couldn't take a one month shake down cruise to see if everything worked all right. But Scholander wouldn't change his plans to start

Page  456456 on time for the Great Barrier Reef, so her shakedown cruise was to take off across the Pacific for Australia where she had a phenemonal expedition. The way it works out roughly is this: she is on station between 8 and 9 months of the year. This is divided into 3 programs and there is a different scientist in charge of each program. Dr. 0.: I see, they fly in new scientific groups each time. Dr. H.: Yes they rotate the scientists. But, if possible, the big and important scientific apparatus is put aboard before she takes off. They have been able to fly in things subsequent people have needed. They had scores of research projects worked out on the Great Barrier Reef. Last year she went up the Amazon a thousand miles and produced this volume of abstracts of work done 115 abstracts in all. The Alpha Helix is really a well equipped laboratory and can do very sophisticated isotope work. It has a shop, a combination study, seminar room and library., It has a wet lab and a dry lab. It has a couple of small motor driven boats so they can fan out from the ship to collect specimens. One of the things that Scholander has used on all 3 expeditions is a shore camp. At the Great Barrier Reef, they set up the shore camp in tents and provided electricity

Page  457457 by an umbilical cable from the ship and they did the same thing up the Amazon. In the present expedition to the Bering Sea they have been unable to do that because they set up the shore camp in a small village of 250 people on the shore of the Bering Sea but they were unable to reach the camp with the Alpha Helix because of the ice. Dr. 0.: What is Dr. Scholander's formal title here at the Institution of Oceanography? Dr. He: He is Professor of Physiology and Director of the Physiological Research Laboratory. He has two functions. One an academic function and one administrative. [Pause] Dr. H.: I would like to record a few remarks about Dr. Roger Revelle, because I regard him as one of the important men in American education. I encountered him in person in 1956 though I had corresponded with him previously while I was at the University of Chicago. When he was taking his Ph.D. at the Scripps Institute of Oceanography, he was working on factors that effect the precipitation and solution of calcium carbonate in the ocean. Having encountered the paper on factors effecting calcium carbonate solubility and solution which I had published with Murray and Sendroy in the Journal of Biological Chemistry, he adapted the

Page  458458 studies that we had done at 38 C° under mammalian blood conditions, to similar studies in sea water. Coming back from the trip that I made in 1955 for the National Academy of Science to Hiroshima, I found Roger Revelle and his wife on the plane. We had plenty of time on this old prop plane, a Stratocruiser, and we spent our time sitting in the lower deck, usually alone. During that trip, they invited me to bring Mrs. Hastings out to La Jolla for the week between Christmas and New Years which I have already recordedc From that time until the present time, I have seen a great deal of Revelle both officially and socially. He was the Director of the Scripps Institution of Oceanography from 1951 until 1964. He is the person who developed the Scripps Institute of Oceanography into its international position at the present time. It was under his directorship that this small institution which was hitherto affiliated with UCLA for administrative purposes, was expanded to a full fledged university campus of the University of California. It was under Roger that this started. He never had the opportunity, in spite of being the one who drove this through, to be the first Chancellor of this University. This is very sad I think and it saddened him. Certain of the Regents felt that he had been much too active in the period during which they were "witch hunting." He had taken a very active part on the professor's side against the "Professors' Oath." The result of this was that a number of the very influential Regents would not listen

Page  459459 to his becoming the first Chancellor. He stayed on as the Director of the SIO, even though Dr. Herbert York was appointed the first Chancellor of the University. Under Kennedy, he took a leave of absence and was a Science Advisor, or some such title to Udall in the Department of the Interior. He then came back to the University and had a title as Vice-President for Government Relations, attached to Berkeleyc I guess he was still Director of SIO in that period after he came back. One day, at the clinic, I got a telephone call from Dr. John Snyder, who had now become Dean of the School of Public Health at Harvard, saying that President Pusey had asked him to get in touch with me because they were thinking of offering Dr. Revelle an appointment to head a center for population studies. I didn't think there was much of a chance of getting himc They asked me if I would discreetly find out whether or not there would be any chance at all of his seriously considering the position. It was to be a big job; 4 or 5 full professorships had to be filled. Though it would be technically in the School of Public Health under Dean Snyder, nevertheless it was quite an independent responsibility. He had been very active in all sorts of foreign activities in India and Pakistan particularly on population problems, sort of his extracurricular activities. In the years we were both here together in La Jolla, the travel people who served both of us said it was a tie as to which one of us

Page  460460 gave them the more business! Well, fortunately, Roger had a good friend here, Dr. Carl Eckart, one of our great physicists at the University and long a member of the National Academy. Unhappily for himself, he had been the Director, just before Roger became Director. Carl didn't like being the Director -- but he was Roger's best friend in town. Dr. 0.: This is the Director of the SIO you are speaking of? Dr. H.: Yes. So I got hold of Carl Eckart and he said, "You know it would be a God-send if something like that were offered to Roger." With that information in hand Roger was offered the job, he moved to Harvard but kept his house here on the ocean. Ellen Revelle his wife is a niece of Ellen Browning Scripps. Dr. 0.: Oh, well I'm sure he wants to keep his ties with La Jolla. Dr. H.: His exact title is Head of the Center for Population Studies, Harvard University — here it is listed in Who's Who in America. There is another thing that I would like to put in the record about Roger. He is the one who dreamed up this idea of having a cluster of colleges that comprise U.C.S.D. He drew it out for me one night at our house after dinner -- on a paper napkin no less! It was he who had the concept which he then transmitted to David Bonner, of building the medical school into the University as an integral part

Page  461461 of the University and not have standard departments in the basic sciences. This is usually called Bonner's idea, but it originated with Roger. He may have gotten the idea from somebody else, but it was his idea for this campus. What makes this medical school unique among those that I have had any contact with, is that they are building the medical school at the same time that they are building,the University. All other medical schools have been engrafted on to an existing University,, This has been one of the things of course that has made medical education less a university enterprise and more a trade school enterprise! It has influenced medical education throughout the country. If they can just stick to it here, they have a unique opportunity to do something quite differentc Dr. 0.: So they plan to incorporate general university courses into the medical school curriculum? Dr. H.: Yes. In various areas. Not only the social sciences, but history and langauge. These, as it is working out, will be mostly in the form of electives and as we get closer to the opening of the school there is more and more tendency to create a curriculum that is going to be more orthodox than originally planned. They are panicking a little bit as they fear that the students will not be able to pass their National Boards, if they don't teach them the orthodox things,, The ACM.A« is still having its heavy hand on how this is coming about. It is too bad that more of the medical faculty

Page  462462 that will actually be doing the teaching, and particularly the clinical men, haven't been on the job a year or so before we admit students so they could partake of this desire and ambition and the atmosphere and the opportunity. They are going to come in cold and then start teaching in the Fall, and they can only do it in terms of what they have known before. It may not achieve Roger's ambition, but I do want it on the record for the history of medicine that this was his concept, his idea, and if it doesn't come off, it shouldn't be laid at his door. If it hadn't been for those Regents, and he had been made Chancellor throughout this period, it might have been an entirely different story. Don't you think we ought to get some food in us before I get grouchy? [LUNCH BREAK] Dr. 00: The date is May 6, 1968 and we are again in the office of Dr. Hastings at the Scripps Institute of Oceanographyc We will start our discussions today with some remarks about Mrs. Margaret Hastings, the wife of Dr. A. Baird Hastings. Dr. H.: It certainly would be a serious omission from this oral biography if I were not to record the important role that my wife for 50 years has played at all stages in my life since 1917« Dr. H.: She is a second cousin who was brought up by her uncle

Page  463463 and aunt in Evanston, Illinois, her mother having died when she was about seven years old. After her mother's death, her father, Mr. Herbert Johnson, Margaret, and her brother, Herbert, Jr. lived with her father's brother and his wife, named Robert Johnson, close to Northwestern University in Evanston. This wonderful uncle and aunt of Margaret's had much to do with creating the desire to reach for high standards in education and behavior, even though they were not themselves attached to the University. Living only a block from the University, however, and mixing daily with Northwestern faculty, Margaret's environs were permeated with the academic atmosphere, I met her first in 1915 and was first attracted to her, I think largely, because she played the piano so well. In 1916 she came to the University of Michigan for our "J hop" and I fell in love with her. On my way to Officers Training Camp on May 15, 1917, having one day en route to Fort Logan H» Roots in Arkansas, I proposed to her and, thank God, was accepted by her and her father. We carried on, during that period at the Officers Training Camp, a daily correspondence. This is the way we became acquainted with each other really. She in retrospect has been constantly amused by the fact that my early letters at the camp were written with my right hand, were quite formal and legible, in excellent more or less stilted college English. As our acquaintance with each other through correspondence progressed through that summer, I

Page  464464 found myself writing to her in my more relaxed and usual fashion with my left hand in which the sentences carried more emotion and were more like me, though somewhat less legible. (Though left-handed, I write with both hands«,) We were married on May 31, 1918 and took up housekeeping in New York. I think it is only fair to say that we had seen very little of each other in person, because even in this year between the time I proposed and we were married, we only saw each other through correspondence except for rare occasions. Margaret was a sophomore at Northwestern when I proposed to her so she did not complete her work for her Bachelor's Degree, but she has continued up to this time to educate herself. I know no women and few men who are better educated than she is. She has a systematic mind. She is dexterous. Indeed, I often tell her that she should have been the scientist in the family. She played the piano very well and had had a recital before we got married, and my only regret is that she has been unable to keep up her activities in music in later years. The reason she is important for this biography is that because of her and her standards, I kept to the path of working for my Ph.D. even though it involved a great deal of financial hardship on her part, because our son was born in May, the year after we were married. When decisions had to be made as to whether I would go into industry to earn more money, there was never a question on

Page  465465 her part as to what I should do, providing it was what I wanted to do. As the years of our companionship went on, there were many other times when decisions needed to be made as to whether I would or would not take a position, and she was always able to sort out the pros and cons, though she always left the final decision up to me saying, "Whatever will make you happiest, is what I would most want to do." She has this same effect on other people. People are quite accustomed to come to her with their problems. As I became administratively responsible for a large department, she helped me tremendously with her relations both with my staff and their wives and with the students. Indeed, it was Margaret who suggested at Harvard that we give tea parties on Sunday for the first year medical studentsc To this day when we encounter some of these men who are now getting along in years and successful in medicine, they go out of their way to tell Margaret that this experience of being invited to our house on a Sunday afternoon for tea was the only friendly thing that they encountered in their first year at Boston. Her own interests are in the arts, in which she has shown the ability to teach herself almost any kind of artistic activity that she sets her mind to, including needlework of the most beautiful sort and silk screening, enameling on copper, and even to cane chairs. Though she has had no scientific training, I wouldn't think of delivering a lecture which I had prepared without

Page  466466 first trying it out on Margaret, because she has intuitively the capacity to put her finger on either the inappropriate or incorrect points. I am sure they have all been improved from this criticism on her part. Since coming to La Jolla, she found an immediate outlet for her interest in music through having been made chairman of the women's committee of the local symphony society and after two years of such service has been a member of their Boardc A more wonderful helpmate and partner throughout the years can't be imagined by me. Indeed, my happy start of being able to go directly from my PhcD., to being Van Slyke's first assistant at the Rockefeller Institute is said by Van Slyke to have been the result of his having met Margaret at a University of Michigan Alumni Dance at the Astor Hotel in New York and finding that she danced so wellll [Laughter] [Pause] Since the problem of aging, or gerontology, as it is now called, entered my life long before I appreciated its practical importance, in other words when I was 32, and has been in and out of my life until the present time, I would like to make a few remarks about "the aging I have known"! My first contact with the fact that it was an important medical problem was at Chicago at the time that I undertook to engage in

Page  467467 research on what were called the "degenerative diseases" for the Lasker Foundation. It seemed to me that one of the first things that should be done before undertaking the study of diseases of older individuals or animals was to have a description of what normal aging was. At that time there were really no careful and complete data on even the change in oxygen consumption of animals with age. We set up a program of having a colony of mice in which we would follow the oxygen consumption of the whole animal and then sample tissues of different animals of known ages and determine their oxygen consumption. This of course was in the period 1928 to 1935 and before one had the advantage of air conditioned rooms and such things as we take for granted today. The result of this was that in the second year of our mouse colony experiment, there was a sudden and severe heat wave and we lost a great many of our animals which we had followed since birth. But even so, we got a good start on this change in metabolism of animals with age from birth toward old age and by now this of course is all very well documented. We also were in the business of studying the electroytes of tissues and had become aware of the fact that the extracellular phase of the tissues should include not only the extracellular fluid that is there, but the extracellular solids which are primarily collagen and elastinc I won't go through the activities other than the ones I have just referred to that were strictly restricted to aging at Chicago, except to record that it was there that Nathan Shock got his Ph.D. He is the present Director of the N.ICHC Gerontological Research Center.

Page  468468 I was still very interested in aging when I moved from Chicago to Harvard in 1935. I was a member of the Club for Research on Aging in which most of the members were much older people such as Professor A. J. Carlson. At Harvard when Dr. Oliver Lowry joined me, I asked him to continue the chemical study of the tissues with respect to aging and he did this for the first two or three years that he was with me there. This resulted in documenting the changes in the solids, particularly collagen, of tissue such as skeletal muscle, heart, kidney, liver, and brain. This was done on rats up to 3 years of age. He found that there was a gradual increase in the extracellular phase, mainly the solids of the connective tissue with age. Though amusingly enough, in extreme old age, I presume because circulatory changes have taken place, the tissues tended to become water logged, Even the extracellular solids of these very old animals, which were the equivalent of 90 to 100 years old if they had been men, became water loggedc Drc 0.: This was without any clinical signs of accumulation of fluid. Dr. H.: That's right. Yes. In connection with this work was a very important opportunity to make similar studies on tissues of Clyve McCay rats. These were animals that he had grown on half rations and were half as big

Page  469469 as their litter mates who had been able to eat as much as they wished. This was to me a very dramatic effect of undernutrition if you will, or at least restricted growth. The animals as soon,as they were weaned, were put on half rations which had been determined in previous experiments, throughout the rest of their lifec Plenty of mixed vitamins and other nutrients were provided other than calories. I remember so well the day that these animals came with their litter mates for us to analyze and Lowry and I took two litter mates out and put them on the laboratory bench. The 3 year old rat which had eaten ad libitum was large and was very arthritic, he dragged his hind feet. He had a scaly tail. His hair was coarsec He had gnarled teeth and he was mean! His litter mate was half his size but scampered away like a 3 month old rat, his hair was smooth and whitec His teeth were good. His tail was good. It was a dramatic difference. When these animals were sacrificed and their tissues analyzed, electrolyte wise and collagen wise, their muscle was equivalent to that of a 6 month old rat! equivalent to his size! The under-fed animals lived much longer than their well-fed litter mates. So I have always been interested in the role of connective tissue in aging. Though it seems to have been supplanted these days with other theories, I have the feeling that other things being equal, perhaps aging is not far different from the slow, inexorable invasion by connective tissue which, with time, has the ultimate

Page  470470 effect of making it more difficult for oxygen and the nutrients to get from the nearest capillary to the viable cell that it is supposed to serve and making it more difficult for the waste products to find their way back to the blood for their excretion. Itfs sort of like having a house where you don't take care of the lawn well enough and the brambles grow up and the sidewalk from the street into your house becomes much more difficult for the grocery man to get in and the garbage man to get out. There are some other things that Lowry and I did too on the hearts of young and older dogs along with Herman Blumgart at Harvard that confirmed these rat studies«, But that is about all I have done experimentally, in the aging field. Administratively I have been mixed up with it for years because Dr. Parran, when he was Surgeon General, called a conference to advise him on whether or not to undertake a study of aging program at the National Institutes of Health and invited me to be present,, The upshot of this conference was that there should be such a program and the question was who should be recruited to head it. My suggestion was Nathan Shock, who by then had had 8 years experience studying 50 boys and 50 girls through puberty as a physiologist. He was selected to undertake the study of aging for N.I.H. He has been very active research wise, and also administratively in developing the field of research in gerontology ever since. He is the head of this

Page  471471 unit on gerontology now in Baltimore where they are about to dedicate a fine new facility for research in aging on animals and other organisms and on aged human beings. Dr. 00: I believe that is located on the grounds of the Baltimore City Hospitalo Dr. H.: That's right. I may go there for the dedication. A rather interesting thing has developed it seems to me in this field. It has been very difficult for Shock to keep and interest good people to work in this subject. I have sent him a good many. There seems to be no future in aging; it doesn't excite these good young men! Not the way research on the other end of the life scale, pediatrics, doesc I'm now on the training grant committee of the Aging Program of the N.I.C.H«D. [End Tape 13, Side II] Dr. 0.: This is Tape 14, Side I, date May 6, 1968. A question I would like to ask regarding gerontology, I have the feeling that one of the problems has been that some people seem to use gerontology as a gimmick. They approach many problems that have been approached many times before, but seem to put the word "gerontology" or "geriatric" in the title of the paper and try to pass it off as something new. Am I correct in this impression? Dr. H.: Well there is some truth in what you say, Peter, because

Page  472472 young people, as I was when I was in my 30's don't regard the period of deceleration as a particularly exciting activity. I didn't undertake the study of aging at Chicago because I was fascinated by it; it seemed the logical thing to do since I had accepted the responsibility of undertaking research on degenerative diseases in the Department of Medicine as a biochemist. I'm not too sure, as a matter of fact, that Shock undertook this job originally because he was interested in aging, but it seemed to him to give him the opportunity to carry on research for a part of the life span in which he was interested in growth and metabolic changes with time, in humans and other organisms« For those who think of this in this way, it can be very exciting, particularly if they are not limited in their outlook. One might compare the period from 60 to 100 years of man with the first decade of life. I think personally there is great excitement in it if you think of it that way, because now the first few years of the life of a baby or a child are very well documented and people take the plateau of the middle years more or less for granted and anything unusual that happens there is disease --but I am sure it is not that simple, there are these small unnoticed things which each individual adapts to as they go on slowly--but there is a stage of deceleration of adaptation, or acceleration of the catabolic processes, if you will. The slowing up of the ability to adapto These are the exciting things to study because things are changing rapidly here again0 It is when you get these rapid

Page  473473 changes that people get most excited when you are studying physiological and chemical things. So I think there is plenty of excitement possible, but just the fact that you are tying your interest to a field which is going to end in death; too many people in it think they are studying pre-death! Dr. 0«: I believe this is what I am driving atc When I was in training in surgery I happened to be in an institution which had a very high incidence of truly elderly patients on the surgical service. Paper after paper would be published on cholecystectomy in such and such an age group. This to them was geriatrics or gerontology. Merely doing the same old thing, studying it and marveling at the fact that people in a certain age group did so well. Dr. H.: I think it is a great mistake to look on research in. aging as a means of lengthening the life span. What I think ought to be done is the study of how to make the present life span a happier and more efficient one. While I was in Shiraz recently, Will Forbes, who is there as the Professor of Physiology, showed me a paper he had just written. This paper pointed out that whereas 20 years ago, the United States stood third among the nations of the world in life expectancy, in spite of all the money we have put into medical research today, now we stand around 20th, way down the list.

Page  474474 Any number of countries which you wouldn't expect are higher than the United States, countries that were formerly lower. The conclusion being that in spite of all of our efforts and probably more money devoted to medical research than all the other countries put together, healthwise we haven't really improved our standing among the nations of the world. It had nothing to do with the life expectancy itself which still seems to stand at three score years and ten and I am going to settle for that; it's fine! I have been living on velvet ever since I have been 401 Oh, this is part of this discussion and part of that on Margaret. I want to insert a story. As Margaret and I were getting acquainted during the year before we were married, I informed her that after our marriage I was going to continue to work to the limit of my ability and intensity and fully expected to die at age 400 My father had died at age 40. I was an idealist. I worked morning, noon, and night. I had no bad habits including smoking, drinking or any other of these pleasant things! (Laughter) She nevertheless accepted me on this basis, but ever since I have reached 40 and have survived to 72, she has kidded me from time to time about the fact that I didn't live up to my promise! Of course I reply that this is because I wanted to be sure she picked the right man after me and I haven't found him yet! (Laughter) But seriously, though I don't believe much in psychology, I think

Page  475475 in this instance there has been a psychological advantage through having made this statement to Margaret, because ever since I was 40, I have been relaxed. I feel I am living on velvet and I have been living on it so long now, some 32 years, that I take it for granted! I'm not bucking for a Nobel Prize and bigger and better things; I take life sort of as it comes. I still put all of my energies into it, but I feel anything that happens nowadays is that much velvet. I got way off gerontology,, I'll go back to one more thing which again will be perhaps facetious, or half facetious, but only half facetious. Being now on the training committee for aging and participating 3 times a year in meetings of fellow biological scientists, a few M.D.'s, sociologists, psychologists, I hear a great deal of discussion of what are the basic problems in aging, particularly aging in man. I went to a conference in Massachusetts over a weekend last year and there were several very learned papers by what I would call young men and women between 35 and 45, who were very serious about their recommendations on what to do for the person over 70. Well, I stood it as long as I could because I was not on the scheduled program to deliver a paper, but when I had a chance I said that when I was their age I would have made similar remarks and drawn similar conclusions, but having now reached the age for which they were prescribing, I wanted to tell them that from where I stood the most important thing to provide for aging was to insure that at a certain date you didn't completely change your life and your work suddenly on a_ day I This should

Page  476476 be a gradual thing. A child going to school is prepared for it in some way when he goes from grade school to high school and from high school to college. These things are more or less gradual, but a man who has had a salary, who has had an office and most of all a secretary as I had since he was 30 years old up to August 31, 1966 and on September 1, 1966 didn't have any of these things. I said as far as I was concerned the most important of these was the secretary! If I had simply been sort of weaned from my secretary over the previous 3 years, by having her 3 days a week, then 2 days a week, then 1 day a week, and finally no days a week, perhaps it wouldn't have been quite so traumatic! (Laughter) This may seem very unimportant to you, but it was so very important! Fortunately, I had the opportunity to move from one office at S.C.R.Fo* to another office at U.C.S.D. so that was taken care of in a sense. I had things to do which were important for me, but the first few weeks without a secretary was impossible! I wasn't in the habit of even paying my own bills. I found myself putting the checks in the wrong envelopes. I didn't have carbon copies of what I was doing. I couldn't find things in the files. You can say I was spoiled, like my wife does, but you know a man spends more waking hours with his secretary than he does with his wife actually, and I had the good fortune of having secretaries in Chicago, Harvard, and at the Scripps Clinic, who were with me many years and got so they could handle ordinary correspondence almost without my

Page  477477 dictating or writing it out. This is an important item which you never hear discussed. Dr. 0.: I think this is very true. This aspect you don't hear discussed. It is a good case in point. It is one of several things that happens when one is suddenly retired on i day. In many instances they don't have — as you have had--a continuing involvement in many things which has kept you busy. For you it was more a physical relocation, but to literally have an active career suddenly stop on a day and find yourself expected to twiddle your thumbs is really very unrealistic and a traumatic affair. Dr. H. : Well, it probably is what keeps our life expectancy low! The lower you put the retirement age, the more vulnerable the person becomes to inactivity, or the wrong activity, or no activity. The human organism wasn't brought up to be that kind of an animal. Dr. 0.: I must admit this isn't something that I have given a great deal of thought--again a case in point, a person of my age. If in the academic and business community there could be a means of having "emeritus professors and executives" who no longer have the administrative responsibility but have a place where they can continue their own work, they can contribute to the business with their background and knowledge, have secretarial

Page  478478 assistance and yet they do move aside and let the young man coming up the ladder get into these positions. But we should utilize these people. Dr. H.: Along that line I met a man at our next door neighbor1s recently who is about my age and had been President of an engineering company. He is now retired and has made himself available to our government for training people at the managerial level in foreign countries. He specializes in Brazil. He is about to leave on another trip to Brazil. He isn't making any money out of it but he gets his expenses and it keeps him busy. Yes, I think jobs for the aged are just as important as jobs for the teenagers. Dr. Oo: Before we wrap this up on gerontology; what are your feelings about the area of biochemistry as applied to the process of aging? Are the problems being attacked these days? Is there a shortage of interested biochemists in this field? Dr. H.: There is a shortage of involvement of good physiologists and good biochemists in this field. I can't blame them too much, because there is so much excitement at the cellular and subcellular level for biochemists and physiologists too, particularly in the nervous system. If we could only get a certain number of the very good ones to think of it as part of the necessary description of life; that it is just as necessary to adequately describe the

Page  478a478a physiological and biochemical changes with time at all levels from the molecular on up to the organ system and whole animal. As a continuum from birth to death with no one fraction of this being of less interest than the other; that the whole thing was the unit they were trying to contribute to, then I think we would have the right kind of people working in the field. I don't think it is any more important than any other; I think it is just as important and could be just as fruitful. Even to the geneticist! They don't do anything about why aging takes certain forms--Just for an example, why the collagen may pile up more in the coronary arteries than it does in the cerebral arteries. This may go back to genes I Up to the present time I know of nobody who has turned his attention to such a question. Well, that is all I have to offer on gerontology„ All I can say, is what I have said before. When I was in my 30's and earning my living studying aging I wasn't very much interested in it as a scientific project. Now that I am in my 70's I am very interested in it as a scientific project. [Pause] Dr. 0.: I believe you wanted to discuss Phase IV of your career now. Dr. H.: Yes. Phase I was full time research up through my Chicago days. Phase II was my Harvard days. Phase III was my

Page  479479 years in full time research again at the Scripps Clinic and Research Foundation. Phase IV is my current life at the University of California, San Diego, the Department of Neurosciences, and physically situated at the Scripps Institute of Oceanography. On September 1, 1966 I moved to my office in the Scripps Institute of Oceanography which is situated in that part of Sverdrup Hall on the 3rd floor, in space temporarily allocated to Dr. Livingston and his Department of Neurosciences. I might say that though this office is small—what is it, about 12' by 12'? --it is a beautiful situation. I look out on the coast of the Pacific Ocean, down toward the center of La Jolla. Since my office at the Scripps Clinic only looked out on an area way, and I kept the blinds drawn and was cooled by air conditioning, this is the first time since I have been in La Jolla that I have been able to really enjoy this beautiful climate. In my position as Research Associate, I have no assigned teaching duties; I have no laboratory at my disposal. Through Dr. Livingston^ kindness I have access to a part time secretary, at the present time the secretary of Dr. Robert Galambos. I feel more or less at home because Dr. Keeney allowed me to borrow the office furniture that I had lived with at the Clinic. The numerous filing cabinets are my personal property as are my Harvard chairs. Most of my library is in Shiraz and I will talk about that in more detail later and the wall space is not expansive enough for me to

Page  480480 hang all of my students1 and former associates1 pictures as I have previously been in the habit of doing, though I have just a few up and one hook where I rotate my favorites depending upon my mood or expected visitor. To be in the Department of Neurosciences is a strange experience for me because of all the tissues in the body that I have not studied, the nervous system leads all the rest. Dr. Livingston, the head of the department, continually refers to me as his neurochemist and I continually deny the rolec However I have been reading assiduously trying to find out what other people have learned about the chemistry of the nervous system. As a result I find myself in a complete state of confusion. There must be things about the chemistry of the nervous system that are unique beyond the fact that the axones are surrounded by myelin, a carefully concocted composition of phospholipids, cholesterol, proteins, and mucopolysaccharides, lipoproteins and proteolipids. As far as the energy transformations that go on in the protoplasm and its organelles are concerned, there seems to be nothing specially unique about them unless it is of a quantitative nature. Ever since I found that anatomically the brain has about an equal weight of glial tissue and neuronal tissue and perhaps 10 times as many glial cells as neurones, and since nobody as yet knows the chemical composition of neurones separated from glia,

Page  481481 or glia separated from neurones, it is not possible to make much biochemical sense out of the numerous and accurate chemical analyses of brain, whether it's been divided into gray matter or white matter. One is left with what chemical analyses have been done on the contents of the squid axone, and these alas leave much to be desired. You cannot even balance the equivalents of cations and the equivalents of anions with the present data available. It is off by 100 milliequivalents. So with my point of view of an approach to the biochemistry of tissue, I can't get a start at it! (Laughter) I'm stuck! I have the further disability I find, in that never having worked with my own hands at getting data on nerve tissue, I have no capacity to remember what I read! It has made me realize that what I do seem to know about biochemistry and physiology, is what I have worked on. My capacity to remember things is intimately related to my having done something with my hands in connection with that work. At any rate that is my present status with respect to neurochemistry. I had the assignment last summer, for which I have been reimbursed for the time I put on it, of assisting Dr. Charles Spooner in writing one of the big and early sections of the neuroscience study plan which involved all the chemistry and the morphology of the nervous system. Dr. 0.: Is the conception of this Department of Neuroscience, purely in the area of basic science related to the nervous system?

Page  482482 Will it include clinical neurology, neurosurgery, neuropharmacology, etc.? Dr. Hc: No, it includes the responsibility for clinical neurology but not neurosurgery, not psychiatry and not psychology as I understand it. Things like neuropharmacology are included. Dr. Livingston was appointed here several years ago. I think he was perhaps the first appointment by Dr. Stokes as a matter of fact. He was until last year the only Department Head that had been appointed for the medical school, because the Department of Surgery head, Orloff, was appointed last year and Braunwald, the Head of Medicine, this year and there are to be no other departments as such except neurosciences. Dr. 0.: Only the three? Dr. H.: Well, I'm not sure about psychiatry. Oh, and maybe Pediatrics. They expect to use the staffs of the Department of Biology and the Department of Chemistry for much of the preclinical teaching. For the rest, the Department of Medicine and Surgery are supposed to supply added members as required for preclinical departments. Dr. 0.: Liebow is out here in Pathology too. Dr. H.: Pathology. I forgot that, yes.

Page  483483 Well this has been a very exciting experience really. Reminiscent in many ways of our first few years when we established a full time medical school at the University of Chicago in 1926 where the problems of "town and gown" were even more severe than they are herec The question of establishing a teaching hospital was opposed in Chicago and was opposed here. Even to the relation of the organization of the school. Just at the time the University of Chicago established its full time medical school on the Chicago campus, while it was still running a part time medical school, Rush Medical College in connection with the Presbyterian Hospital on the west side, they had had a reorganization of the University into four divisions. These were, the Physical Sciences, the Biological Sciences, the Social Sciences, and the Humanities, each headed by a Vice-President. In connection with this organization, in connection with the establishment of the full time medical school, on the south side,--that means the University proper--they added to the ordinary departments of the Division of Biological Sciences - such as Physiology, Biochemistry, Botany, Zoology, Cytology, Anatomy, Microbiology, - they added a Department of Medicine, a Department of Surgery, and a Department of Pediatrics. At the time the medical school was founded on the south side, administratively in the University, each of these Heads of Department got one vote. The organization of the medical school was not as an ordinary medical school, though they realized

Page  484484 that for purposes of meeting legal requirements they would have to also have an association of these departments which they could point to as "the medical school unit." They appointed an Associate Dean--at this time the Head of these Divisions was not called a Vice-President, he was called a Dean of Biological Sciences or whatever—and then the Associate Dean was in charge of the group of sciences that made up the curriculum for the purpose of giving degrees«, But administratively in the University, Phemister (surgery) got one vote, McLean (medicine) got one vote. The Head of Pediatrics got one vote just like the Zoology Professor. This is the way it was when we started I So it is very much like the way they are trying to start here. Since then it has changed in Chicago. The University of Chicago Medical School exists as a separate administrative unit, and just what they call the Dean there, I donft know. Up to the time I left 8 years later, the medical school didn't exist as a separate unit. I had forgotten about this situation completely and yet here it is again—this is !68 and that was !26; that is 40 years later, that they are trying to do it again! It will be very interesting. It will be very interesting. Except here they are trying to do it with even less administrative division of labor, because at Chicago they at least had Departments of Biochemistry and Departments of Physiology, etc., which they are not going to have here.

Page  485485 Dr. 0.: They will incorporate the medical school classes in these courses in the undergraduate school? Dr. H.: They have made appointments in the Department of Biology and in the Department of Chemistry with an eye to these people being both interested in medical school teaching and in the preclinical sciences, but whether they have made enough such appointments, I don't really know. Well it will be very exciting. There is nothing that keeps you alerted like having the kind of problems that arise when you are trying to build a new institution, Maybe the reason I did so many extracurricular things at Harvard was because after all I didn't have to build from the ground up. I built, but it was easy to build; I didn't have to fight for each point very hard, you see. I knew what I wanted to do and you could either afford it or you couldn'tc So at Chicago, and again at the Scripps Clinic and now here even if I am not in the same decision-making position, I have the same fun of worrying about it. I feel that if Bob Livingston is about to take an action that I don't think he should, I try to keep him from doing it as if I were in a decision-making position. You don't teach an old dog new tricks very easily! Of course it is enriched by the fact that I am physically right here in the middle of the Scripps Institution of Oceanography and all its biological and physical scientists and oceanographers. Andy Benson, who is

Page  486486 Associate Director of SIO and one of the best biochemists of any kind that I know of, though he calls himself a plant biochemist, is my neighbor. I usually ride to work with him and he usually brings me home during which we get a great deal of science discussed and sometimes administrative actions taken. I ought to comment at some point that it would be a very interesting study to analyze how much it has meant to me, or not meant to me by my never having learned to drive an automobile, in an age where there is hardly anybody who can say this anymore. I decided at Harvard that I saw a great deal more of my colleagues because I would start walking to work and would always be picked up usually by a different colleague. One of the extravagances of this world is that we have all this cubic footage of space, empty space, which is carried around by a great deal of horsepower but only single individuals occupy it. It is not the way evolution would plan it. That doesn't mean that I wouldn't like to drive my own car down to the fishing pier since taxis are getting so expensive! Somehow I have never failed to do what I have wanted to do because I didn't drive an automobile. This is a luxury which very few people can afford!I [Laughter] Dr. 0.: Let me ask you about your role here in the Department of Neurosciences. You serve as a consultant for both the science side of things and I gather the administrative side of things as

Page  487487 well. I gather Dr. Livingston calls upon your vast administrative background as well as your scientific background. Dr. H.: You make this sound very important, but I do, sure! But not in any formal wayc He consults me with many things, or about many things in relation to recruitment and in relation with some of the other administrative people. It's hard to tell at this moment how having a Department of Neurosciences as perhaps the only specified categorical department in the sense that the NIH uses it will work out. Of course there is also Pathology, -I keep forgetting Pathologyc They are the only two they are contemplating. Medicine covers a multitude of things and so does surgery«, Livingston has an amazing capacity for visualizing broad pictures of the neurosciences and their integration and he is an extremely good writer and can indeed dictate into a machine with adjectives and adverbs and have it come out very good English. He has many irons in the fire and is a bundle of energy. He has been successful in recruiting Dr. Theodore Bullock, who is one of our very distinguished Professors of Zoology and Comparative Neurophysiology and Dr. Robert Galambos, who very young in life, teamed with Donald Griffin to discover the sonar system of bats and is quite distinguished in his field of acoustic neurophysiology. He is immediately from Yale, but he was at the Walter Reed Institute of

Page  488488 Research for many years. Both Bullock and Galambos are members of the National Academy. He has made some other junior appointments, but his attempt so far in neurochemistry and neuropharma-cology and the basic science side of neuropathology for which he is responsible -- the clinical neuropathology is Liebow's responsibility -- have been very difficult to get through. I won't say that he won't get them through, but ever since the University of California has had its financial difficulties, it is so difficult to get any faculty appointments. So many difficulties are put in the way that some of these young people can't wait. So I don't know what our future will be here. I am most appreciative of the opportunity that I have to continue to feel useful, and I wish I knew more neurochemistry and a little more about the nervous system so that I could be more useful. Meantime living with the oceanographers and the marine biologists, my life is very rich. When I am not worrying about Livingston's problems, I am worrying about Benson's or Scholander's or somebody else in the SIO, and next week I am supposed to lecture to the Marine Biology Class. Dr. 0.: You still give a number of lectures do you not? Dr. H.: Yes, I keep one foot in the door of the Scripps Clinic by going there every Friday to give an hour and a half seminar. I lecture there for the young clinicians who are in training in the Division of Gastroenterology. Also, I have an official connection at Sd.O.; I am on the program committees of one of the graduate students for his thesis at S.I.O. Each student here has such a committee that makes sure he gets on a good problem and works on it and gets it done. I haven't served on such a committee before so I am not sure how far its responsibilities go, but maybe it is the nucleus of his examination committee when he completes his thesis. This is a growing university as you know. It is going to have a 25,000 student body, eventually made up of a cluster of ten colleges with about 2,500 students each. Roger Revelle, even at the time he was here, and it is just as true now, was extremely proud of the fact that the percentage of faculty members who were members of the National Academy of Sciences was the largest in the country, of course partly because they attracted such people as Harold Urey, and the Mayers. They are doing pretty well on people who have Nobel Prizes too. We also have Martin Kamen, the man who discovered Carbon 14, who is a physical chemist whom I have known for a long long time. I met him first at Berkeley in 1939. He has a very interesting arrangement. He is also the Director of a French Biochemical Research Institute. He spends 6 months a year in Paris and 6 months a year here, dividing it in four 3 month periods. He is the man who with Ruben discovered Carbon 14

Page  489489 I lecture there for the young clinicians who are in training in the Division of Gastroenterology. Also, I have an official connection at S0I.O.; I am on the program committees of one of the graduate students for his thesis at S.I.O. Each student here has such a committee that makes sure he gets on a good problem and works on it and gets it done. I haven't served on such a committee before so I am not sure how far its responsibilities go, but maybe it is the nucleus of his examination committee when he completes his thesis. This is a growing university as you know. It is going to have a 25,000 student body, eventually made up of a cluster of ten colleges with about 2,500 students each. Roger Revelle, even at the time he was here, and it is just as true now, was extremely proud of the fact that the percentage of faculty members who were members of the National Academy of Sciences was the largest in the country, of course partly because they attracted such people as Harold Urey, and the Mayers. They are doing pretty well on people who have Nobel Prizes too. We also have Martin Kamen, the man who discovered Carbon 14, who is a physical chemist whom I have known for a long long time. I met him first at Berkeley in 1939. He has a very interesting arrangement. He is also the Director of a French Biochemical Research Institute. He spends 6 months a year in Paris and 6 months a year here, dividing it in four 3 month periods. He is the man who with Ruben discovered Carbon 14,

Page  490490 Ruben is now dead -- but it is a shame that with all that Carbon 14 has meant to research all over the world, he has never received the Nobel Prize for this discovery. It is just as important certainly as Urey's discovery of Deuterium, maybe more so. Drc 0.: There are many instances I am sure of people who don't get it when many people think they should. Dr. H.: I don't think I have any more to say about the University at the moment. I can tell you more next year after we have seen our first medical student, I am sure that when the first medical student comes to the campus and our first lectures have to be given, everything will come down to earth. Dr. 0.: And you will feel even more like you are at home again. Dr. H.: Yea! [ End of Tape 14, Side I] Dr. 0.: This is Side II, Tape 14, recorded on May 6, 1968. The discussion on the first portion of this tape is Dr. Hastings' description of his two contrasting visits to Iran. Dr. H.: I think I have already said that one of the problems in retiring from the Scripps Clinic and Research Foundation was the fact that I had accumulated quite a sizeable scientific library. Journals, textbooks, and monographs devoted to the subjects of

Page  491491 biochemistry, physiology, medicine and an assortment of other books and monographs in the fields of physics, chemistry and the history of medicine. Since there was no room in our home for these books and journals and there would be no room for them in my quarters at the University, I expressed my concern about this at luncheon one day at the Scripps Clinic in the summer of 1966. Dr. Josef Hatefi, who is a biochemist who works in the field of electron transport and is a Member of the Scripps Clinic and Research Foundation was at the table when I made these remarks. He followed me into my office and asked what I would think of making a present of my library to Pahlavi University, Shiraz, Iran. It seems that Dr. Hatefi had, the year before, and for a year and a half before that, been the Provost of this new University in Iran. This is a university which is being especially developed by the Shah. Pahlavi, parenthetically is the family name of the present Shah. Dr. Hatefi had been on leave of absence from the Clinic at the personal request of the Shah to help it get started. I should also say that Dr. Hatefi had his undergraduate and graduate work in this country and had been an Associate Professor at the University of Washington before he came to the Clinic. Well, Dr. Hatefi had decided after a year and a half of being an administrator, since he was under 40, that this should not be his ultimate career so he returned to the Clinic in order that he could continue his career as a biochemist. However, he was still intensely interested in the future of this University. He said that if I would do this,

Page  492492 it would be on the condition that the University would keep the books together as a separate library unit. I talked this over with Mrs. Hastings in the evening and she thought it was a splendid idea and I felt it probably would do more good than giving them to Harvard or the University here or any other existing Library which had duplicates of practically everything I had. So we agreed to make such an arrangement. In due time the Chancellor of Pahlavi University, his Excellency Assadollah Alam wrote a letter thanking us for the offer and stating that it would be set up as a separate library unit as we hoped and inviting me to be Visiting Professor at Pahlavi University at a time convenient to us. We selected the fall of 1967. After attending the 200th Anniversary Celebration of Columbia University in New York, we proceeded to Shiraz by way of Copenhagen and Cambridge, England. We spent a month in Shiraz. I gave lectures to the undergraduate medical students and two scientific lectures to the students and staff« We returned to La Jolla in the middle of December 1967. We were treated extremely well and our quarters were as nice as could be had in Shiraz and were very comfortable. We were given an especially fine party shortly before we left as a birthday party for both Mrs. Hastings and myself in one of the old palaces of one of the fine and wealthy families of Iran. It had been their home but it had been given to the University for social

Page  493493 affairs. In the course of the month, we were able to visit also Persepolis, the great capital of the Persian Empire under Darius and Xerxes, whose descendents ruled over the better part of the civilized countries that were then known for about 500 years. A most impressive ruins, that I had not realized previously had existed prior to the development of Greek culture. On the way home we visited the Isfahan, called by many the most beautiful city in the world, and by the inhabitants of Isfahan, "half the world" -- that is they considered it half the world, not the most beautiful city in half the world! [Laughter] It was very impressive What gave me such a pleasant surprise was to find the tremendous difference in Iran and in Iranians between Iran as it exists today and Iran as I saw it in January 1944 when I spent 3 weeks there on my way to Russia. At that time I was shocked by the poverty, widespread poverty, and widespread disease that existed on all sides. All the wealth of Iran was concentrated in a few families. The tremendous oil resources of Iran were entirely under the control of Britain. Having been in China, in Peking in 1930, I had thought that poverty and indeed disease probably was greater there than any place else. But having been in Iran in 1944, I felt that China as of 1930 had a much higher standard of living than the Iranians. Whole villages in large number were owned by only a few families. These people lived almost in slavery.

Page  494494 This had all been abolished in these intervening 20 odd years, and it was due to the present Shah and the wisdom of his advisors I am sure. Though only in his 40's, at the present time, 10 or 15 years ago he had resolved to improve the economic status and education of the people of Iran. He has made every effort to this end. Important in this has been the taking over of the oil resources and its administration by a consortium of England, the United States, France, and Iran, where I think something like 60% of the profit comes to Iran and 40% goes to the other participants which seems to give plenty to everybody concerned and the Iranian government has plowed most of this back into improving the status of Iranians«, They have widespread electricity, roads; they are getting more railroads. They have encouraged factories to develop and most important of all and, closest to the Shah's heart, is getting rid of the illiteracy, which I suppose must have been over 90% twenty years ago. I was told in December when I was there that now no child of school age is illiterate. This is because they utilize those children who have graduated from school to spend a certain amount of time teaching. He is making great strides so that the whole complexion of the country has changed. It is true that it is not a democracy. It depends upon having the Shah as interested in doing this as he is and in the kind of people he has around him giving him advice. I am sure that there is a lot of Court politics, but

Page  495495 they are making sufficient progress so that the Shah decided he would now have an official coronationc He had never been crowned. He is reputed to have said that he wouldn't be crowned until he could be proud to be Shah-an-Shah, which means King of Kings of a people that he wouldn't be ashamed of. This magnificent coronation which was the occasion for a great deal of national celebration in all the towns and cities of Iran occurred just the week before we arrived. They had had a competition on which city would have the finest electrical decorations. I suppose it is natural that Abadan, which was the largest city close to the oil wells got the first prize and I believe I was told that Tehran, the capital, got the 3rd prize, but even so it was a very dramatic electrical display. We were hardly prepared for it because we arrived just before 5:00 o'clock in the morning, having been due at 3:00 from the London airport, and it was dark. We got in the Embassy car and started down the big divided boulevard from the airport to the center of the city and the hotel and as we started down this great boulevard, suddenly the lights were all turned on! They had been turned off at midnight. I said that they didn't have to go to all this trouble! There was no other car on the road and every 20 feet there was this great display, you see. We proceeded the next day from Tehran to Shiraz and I took up my duties as a Visiting Professor there. At the end of the first

Page  496496 week, they informed us that they were to open our library which they had labeled the "Hastings Library" and the Shah was coming for the opening. I might just insert a word about what this library looked like because they couldn't have set it up better to serve the purpose that I hoped it would serve. It was a reference collection for students and faculty in the basic medical sciences and located within the neighborhood of these basic medical sciences so they could drop in and browse or look things up easily. I had found it so very helpful to have had such a library at Harvard. We had a departmental library between physiology and biochemistry, known as the Bowditch Library. It was easily accessible to the students and faculty of our department and those of physiology and was used a great deal. Whereas if they had had to go out to another building, to the top floor, they wouldn't have used it nearly as much. You must have your books accessible! Not all the old ones, but the current ones. And this is what I had hoped this library would be, and they had set it up in just this way. I must give credit to Dr. Amir Fakouhi, who is the head of pharmacology and a young man of 30 educated at the University of Oregon and a friend of Dr. Hatefi, who had been responsible for setting it up in this way. It was on the first floor of the medical school, just inside the main entrance and was adjacent to the Departments of Physiology and Pharmacology. Immediately on the floor above

Page  497497 and easily accessible to it were the Departments of Biochemistry and Microbiology, and on the floor below, the Department of Pathology. Help and mahogany are both cheap there so it was paneled in mahogany. The shelves are mahogany. They had bound all of my unbound journals and that meant all except the Chemical Abstracts which went back to 1919 and the Journal of Biological Chemistry. Those I had already bound privately, but the other journals were unbound and they told me they could bind them for $1.50 a volume whereas it costs us $5.00 or $6.00 a volume or per book here. They had bound them in rather gaily different colors, pink, purple, blue, yellow. So it made a very gay appearance. They were not quite in order so I spent my spare time for the next few days getting them ordered. They also had prepared a little name plate or book plate to be inserted in each volume. You can read that into the record if you want to. It is rather more ornate than I would have myself thought of. Drc 0.: It states,"A Baird and Margaret J. Hastings Library. This library presented September 1966 by Professor A. Baird Hastings, Ph.D., Sc.D. and his wife Margaret J. Hastings to the students and faculty of Pahlavi University for scholarship and research." I think it is very interesting that this is not just the A. Baird Hastings Library.

Page  498498 Dr. H.: Yes, this was one of the conditions I made of their accepting it. There is no question about it, my Margaret paid for these books just as much as I did by the many ways in which she made my salary go further than it would have otherwise. Furthermore everything we own, we own in common, so I wouldn't think of giving our books away anymore than I would our house. Indeed I told Fakouhi one night when we were talking about this, I said, "Of course this is a very small gift as such things go." It probably didn't have a monetary value of more than $10,000. It was about 3,000 volumes when they got them, which is only a small nucleus for a library really, but except for our house and our house furnishings and our automobile, this is all we ownl I don't even own any stocks! So it represented percentage wise from the Hastings family, a very substantial part of our belongings. I didn't discover till after I said that I would send it, that a gift like this abroad cannot be deducted from your income tax. I was able to deduct the value of the books that I left at Harvard, which I did. So this was an outright loss of capitalc But it came out so well, that Margaret and I have no regrets. I am sure it is doing more for Iran and the students of Pahlavi University than anything else I could have arranged to do with these books. For instance they now have bound copies of Chemical Abstracts from 1919 to 1965. That is the only such set

Page  499499 there is in all of Iran! Iran is a land mass about the size of continental Europe minus the Scandinavian Penninsula. One little footnote to this. On the stopover in Tehran on the way back, I was asked by the Science Attache to come to the American Embassy though we were only going to be there one day, and Margaret was ill in the hotel. However the Ambassador wanted to meet me. I went over and expected to have ten or at most 15 minutes with him and he kept me over half an hour. He could hardly believe that somebody had made this sort of a gift with no strings tied to it! Why did I do it? What did I expect? He was a very experienced person in the Middle East. He had spent much of his life there. He was a fellow Hoosier from Fort Wayne. When he found that I was perfectly sincere and didn't have any axe to grind, he was then more interested than ever. Finally when he did usher me out and had his arm around my shoulder, he said, "Well Professor, if there just would be more people who would do things like that, maybe we wouldn't have this ugly American image quite so widespread." I think this was a very interesting thing to experience from a man like that. Well, the Shah did come to the opening. Though security insured that there would be nobody in the room with us except Dr. Ghalambor and Dr. Fakouhi. He chatted a few minutes with me and then turned to Margaret, upon which his rather stern face broke into a most engaging smile -- he is a very handsome man -- and

Page  499a499a he was very charming with Mrs. Hastings. I wish him well. He has a tough, tough job. I am so glad that I got to see Iran again, because I had had a very uncomfortable and not complimentary opinion of the country before. Dr. 0.: Did you have the opportunity to express your feelings of delight at the changes on your second trip to anyone in the Government? Dr. H.: I had no such opportunity. No. I guess I had better put that differently. Presumably I could have discussed this with the Dean, Dean Ghavami, who is a member of one of those big wealthy families and who is also Professor of Medicine, a very fine well educated man. I did have a chance to talk with him at length on one occasion. At other times other people were present. But I did not bring up this question of the formerly very low standard of living. It was so low, I was afraid they might not want to be reminded of it. That really is how low it was. You see to feel that there were people that were as badly off as the coolies of China, which was my previous feeling about the Iranians in 1944 is something I wouldn't want to remind them of. I didn't on this occasion anyhow. I was just as glad that that part of our report on our Russian trip had never been published. That is, the report of Shimkin and me. You have to be awfully careful with people. I think I was accepted just for myself, and I didn't have to live down a

Page  500500 prior statement. I never even have discussed it with Joe Hatefi to tell you the truth. Maybe someday I will. [Pause] Dr. 0.: The date is May 7, 1968 in the office of Dr. Hastings at the Scripps Institute of Oceanography. Our discussion this morning will start with a consideration of the so called "Long Report," whose formal title is "A Study of the Medical Research Activities of the Department of Health, Education, and Welfare." Dr. Hastings was a member of this study group and we will proceed from there. I will ask you a number of questions after you have gotten into it. Dr. H.: In January, 1955, Dr. Chester S. Reefer, who was at that time Assistant to the Secretary of the Department of Health, Education, and Welfare, Mrs. Oveta Gulp Hobby, asked me one day whether I would be a member of, and hopefully chairman of, a committee to review and evaluate the activities of the Department of Health, Education, and Welfare in the Health Sciences. He said that Mrs. Hobby had requested the National Science Foundation to appoint such a committee and carry out the review and evaluation on recommendation by Dr. Keefer who was her advisor on medical affairs. Perhaps it would be worthwhile to quote a couple of points in Mrs. Hobby's letter to Dr. Waterman of the National Science Foundation, dated January 14, 1955.

Page  501501 She said in part, "the Public Health Service programs, both intramural and extramural have grown rapidly since the war. The amount available for research and development in the health, medical, and related fields will reach the approximate level of 66 million dollars this fiscal year." Further on she said, "in view of the importance of this program and the increasing demands upon this Department for aid to medical research, I feel that it should be subjected to critical review, particularly with regard to its scope and the distribution of support among the various special areas of medical research." Then finally she said, "Realizing that the National Science Foundation has as one of its responsibilities the evaluation of scientific research programs undertaken by Federal agencies of the Federal Government, I wish to request that the Foundation undertake a review and evaluation of the medical research programs of the Department of Health, Education, and Welfare,," In due time such a committee was appointed by the National Science Foundation, I declined the Chairmanship largely because I found that I was obliged to make an extended trip abroad that would interfere with my initiating the meetings as early as Mrs. Hobby and Dr. Keefer felt that they should be initiated. Indeed, the committee which was appointed in the early summer of !55 started its meetings in August and we were given the deadline of December 1 to complete our report.

Page  502502 Dr. C.N.H. Long, Professor of Physiology at Yale was the Chairman and the other members were Dr. Edward Doisy of St. Louis University, Nobel Laureate; Dr. Ernest Goodpasture, Emeritus Professor of Pathology at Vanderbilt; Dr. Charles Huggins, Professor of Surgery, University of Chicago; Dr. Colin MacLeod then Professor of Microbiology, New York University; Dr. C. Phillip Miller, Professor of Medicine, University of Chicago and microbiologist; Dr. Wendell Stanley, Professor of Biochemistry, University of California at Berkely and Nobel Laureate, and myself. The committee met very frequently, about every other week. Dr. 0.: Every two weeks during the months of September, October and Novembero Dr. H.: That's it. The committee undertook to devote two months primarily to fact finding and most of the last month to preparation of the report. Altogether, 68 individuals were interviewed and numerous printed reports were consulted. Most of the effort was devoted to the activities of the National Institutes of Health, both their intramural and extramural programs. However, the Children's Bureau, the Office of Vocational Rehabilitation, the Food and Drug Administration, and the Bureau of State Services were also reviewed and recommendations were made with respect to these

Page  503503 other activities, these other Bureaus of the Public Health Service. But it was to the extramural and intramural research activities of the National Institutes of Health that we directed our primary attention. It was the consensus of the committee that the intramural program of the National Institutes of Health, which at that time consisted of 7 Institutes, was well staffed and that the research programs were important and being carried out at about the optimum rate. Dr. 0.: Along these lines, did the committee restrict itself to the basic science research programs intramurally or did they also consider the clinical investigations conducted in the Clinical Center which had been open for 2 years by this time? Dr. H.: It took into account the clinical research activities in respect to all of the Institutes. Indeed, I think it should be said that the clinical research activities were the primary activities to be examined and there was never any thought that the National Institutes of Health intramural program should simply be engaged in research for research sake. However this doesn't mean that we didn't all feel that progress in basic research must go on in relation to all of the Institutes, in spite of the fact that they were given categorical names. In other words in the Heart Institute there should be biochemists working on problems of biochemistry at the most basic level that they could conceive.

Page  504504 Dr. 0.: I think why I was driving at -- my impression is that --I arrived first at NIH around this period, mid year '56 and I have the impression that there were those that felt that some of the intramural Division Chiefs who at that point in time were in some instances long term Public Health Service officers, were perhaps not the most qualified men for certain rather key posts. In fact there were some at NIH at that time who felt rather strongly about this, and I wonder if the committee sensed this at all. Were there instances where the committee questioned the caliber of some of the intramural staff? I may be making a mountain out of a mole hill, but it is an impression I have hadc Dr. H.: As everybody knows, there were 2 Directors for each Institute at that time. The administrative director who is always a Commissioned Officer, a career man and who really held the pocket book but who also did the defending at the Congressional Hearings, and though I can't be sure of all of them, some of them such as the Cancer, Heart, and Arthritis Institute also had a Scientific Director. On two occasions I had been offered such a position. Once in the Cancer Institute and later in the Heart Institute«, Dr. 0.: Well perhaps the people I am thinking of were not at that high a level. Dr. H.: Now that you remind me, I do remember that there was

Page  505505 concern about their ability to staff the Clinical Center with adequately distinguished chiefs of the various clinical departments. For instance, they had no distinguished surgeon at that time. Dr. 0.: Well these are the people I am thinking of. These are the people I had contact with. Dr. H.: I remember that Huggins was much concerned about this and felt they never would get anybody, because they couldn't offer enough to compete with an academic surgeon who always gets much more money, even in full time medicine than the preclinical people. So at that particular period there was some question whether or not the clinical investigation would ever reach the state of ability and distinction that they could in the nonclinical activities. Do you have any other questions? Dr. 0.: No, this answers my question. Dr. H.: Reading some of the conclusions and recommendations at this point in time which is 13 years later; the recommendation that there be no major expansion in the intramural program in medical research and no increase in the number of categorical institutes at the National Institutes of Health seems a little ridiculous because neither of these recommendations has been followed. Dr. 0.: In general the committee was not overly in favor of a categorical approach to research were they?

Page  506506 Dr. H.: No! We deplored the fact that there had been any categorical names attached to these Institutes for fear it would hamper the productive acquisition of knowledge along whatever would be the best lines that a particularly well qualified person could develop. However, we accepted the fact that they were so named and hoped that there wouldn't be anymore! We even went so far, I see, as to say that we recommended that Fellowships be awarded on a non-categorical basis. We also recommended that a board of medical scientists fron non-Government institutions be appointed that would answer to the Surgeon General. Dr. 0.: This I find interesting. What was the reaction of the administration of NIH, people like Dr. Shannon, to this suggestion? Dr. H.: To anticipate this, I am sure that the administration of NIH did not look upon these recommendations favorably at all at that time. I'm still on the intramural section. On the whole we were not particularly critical of the activities intramurally at the NIH, except that all of us being old scientific pros feared bigness. Dr. 0.: In the sense of bigness leading to mediocrity? Dr. H.: That's right. Each of us in our own experiences had done our best work in relatively small units and all of us having been involved in the crash research and development programs of the

Page  507507 war, had realized the dangers of such undertakings. In the course of crash programs with too many people, too much rush, one smothers the growth of ideas in the hurry to get things out with the immediate objective in mind. You know what you are trying to get, so you hurry to get it. This is not researchl But our greatest concern was with the extramural program, which even at that time had a level of a 90 million dollar budget since the letter of January from Mrs. Hobby which mentioned 66 million. We felt that it was essential to slow down this growth of the extramural program until enough able scientists could be developed. The important thing was the development of the new post-war generation of able medical scientists to make up for the 5 year war-time deficit, when no such scientists were trained and we were still feeling this very keenly in 1955. We also felt that the direction that the National Science Foundation was going and the way it had been set up with its extramural program, though not supported financially as well as the NIH, nevertheless provided a better model for administration of such an extramural program than did the administrative set up of the NIH. [End of Tape 14, Side II ] Dr. 0.: This is Tape 15, Side I, date May 7, 1968. A continuation of the discussion of the "Long Report."

Page  508508 Dr. H.: The Director of the National Institutes of Health was and is the chief administrative officer for both the intramural and extramural programs. Our committee felt that this was undesirable, that it was an adequate responsibility for any one man to be Director for the intramural Institutes, particularly if their ambition was to provide the best medical research in the health sciences equal to or superior to that of the Rockefeller Institute. You wouldnft think of having had Dr. Simon Flexner, when he was Director of the Rockefeller Institute, also the President of the Rockefeller Foundation and responsible for both the intramural and extramural activities of the Rockefeller Institute and Foundation. That would be a comparable situation. So we recommended that the Director of the intramural research activities of the National Institutes of Health be responsible for only these activities and not for the extramural program. Then we recommended that the extramural activities be separately established as a new agency of the Department of HEW for the purpose of administering support of medical research and training in universities and research institutions. We even went so far as to suggest that it have the title of Office of Medical Research and Training. Then, as with the National Science Foundation, we recommended that its chief administrative body be a council responsible to the Secretary of DHEW and that it be made up of representatives of the several medical sciences, of education and public affairs. We recommended that this council have the administrative authority for making long term institutional grants,

Page  509509 for grants in both categorical and non-categorical areas, for fellowships and traineeships, and grants for construction of research and teaching facilities. Under this then there would be an organization, a Director and an administrative organization for administering these extramural funds. These were the main points in our recommendations and we arrived at them after a great deal of debate. They were not easily accepted by all committee members, because some of the members felt that everything was going so well, that we shouldn't tamper with it! In the beginning I was inclined to feel that way, because I had seen it grow from its beginnings in the CMR -- I'm talking about the large extramural program now -- and I had admired so much the manner in which Dr. Dyer and Dr. C.J. Van Slyke had gone about mobilizing the best scientific brains and experience in the country as study sections, so that these scientists who applied for grants from the beginning and up to the present time, had the assurance that the merit of their proposal was being evaluated by their peers. There was no feeling on the part of our committee that this plan shouldn't be continued. Dr. 0.: I gather this plan has been approved by all such committees who have studied this area of study section review. The Woolridge Committee of 1965 included. Dr. H.: All except the present Congressional committees, who say,

Page  510510 I presume because they are in the habit of such things, that there is bound to be "log rolling", and when you get so many scientists who also have grants, how can they be dispassionate? This of course disturbs me terribly because I have never seen it done!! Dr. 0.: This is what I wanted to ask you very candidly. I have often wondered myself when I see the composition of these Study Sections who evaluate these grants and based on my experience in surgery; I see many of these committees made up of scientific colleagues of long standing, all of whom at one time or another have had grants, or currently probably have grants, and you can see where somebody could suggest that this must go on to some extent. I know steps have been taken whereby if a gentleman on a Study Section has submitted a grant, or somebody in his Department has submitted a grant request to that Study Section he leaves the room while it is under consideration. It is inevitable that somebody would suspect a "you scratch my back, and I'll scratch yours" situation. Dr. H.: I suppose it is human nature to be suspicious of these things, but all I can say is that I have never seen it happen!! I was on the Councils, as I have said before - the Cancer, Heart, Arthritis and General Advisory Council. Occasionally, there were people on these Councils who also had grants, and I've seen the Council vote against one of the members of its own Council. I could cite chapter and verse, but maybe I had better not. The Training Grant

Page  511511 Committee that I happen to be on now has voted to shut down the program of one of its members. If somebody can give me chapter and verse where log-rolling has happened, then I will believe that it has happened I But until I hear of such an instance I shall continue to think it is the cleanest administration-wise that I know ofc Heavens, why should these fellows do log-rolling?! They are mostly Professors; they are men with a high scientific reputation. They wouldnft anymore do that then they would change the data in their notebook to make it fit! They're not that kind of men! I wish you were Mr. Fountain sitting here!! [Laughter] Dr. 0.: Well this is why I am digging into the "nitty gritty". I really wanted to see your reaction. I am delighted to get this on the record. I must admit that my very limited contact sitting in on Study Sections, I have seen just what you have described„ I saw a gentleman who was about to join the Study Section, who was there at this meeting to be oriented, which apparently is the system for this particular study section. He left the room as he had a request for a very large training grant to develop a new program at his institution. Everybody on the committee were friends and colleagues in his particular field and they proceeded to tear the thing to pieces. So I agree with you. I have yet to see evidence of any "hanky-panky" at all.

Page  512512 Dr. H.: When I was on the Heart Council, I argued against Fred Stare, formerly in my Department and still my good friend and head of Nutrition, having a departmental primate facility. I thought it wouldn't be good for our NIH Primate Program or for him or Harvard to have this. I was out of the room when they voted, but they called me back because I was no longer at Harvard and they are allowed to call you back to get facts. Maybe this could be interpreted as "anti log-rolling", I donft know! But I certainly have never done any log-rolling and I just don't know of anybody who has taken personal advantage of the situation. Well, we made our deadline with this "Long Report". The only trouble with it was that just before December 1, sometime in November, Mrsc Hobby had resigned as Secretary of DREW and with it, Dr. Reefer, who had been her appointee. Folsom became the Secretary and Coggeshall took Reefer's place. Since the Report was made to the Secretary, our committee couldn't do anything about it, about publication of the Report* It's existence was not announced until the following February 27th, when Secretary Folsom announced its existence and the New York Times for February 28, 1956 carried three half columns which very briefly described it. In the course of this article which was on the second page, because of some other big news at the time -- I can't remember, I wish I had saved the whole paper. -- Folsom reported that he thanked the committee for its report and said that its recommendations would be studied intensively,, On the question of setting up a new agency, he was reported as being non-committal on the proposed new agency and that's the last that's been heard of itc

Page  513513 Dr« 0.: I imagine there was general support from the scientific community for the recommendations that you folks made in reference to the extramural program at NIHC Dr. H.: We will never know, because they have never seen it. This report has never been published or distributed. Dr. 0.: You mean it has only come on in this mimeographed form? Dr. H.: That's right. As far as I know it was never even distributed within the Public Health Service. This is the form in which we handed it in. It was reproduced in other mimeographed forms, how many copies I don't knowc I have given away my last mimeographed copy. I only have these 2 leftc By and large the scientific community and I'm afraid Congress and the scientists at NIH, if they have ever heard of it, have never seen the report. Drc 0.: What do you think the major factors were that "killed" it? Do you think it was chiefly because of the change in administration? Dr. H.: I think the change in administration prevented it from getting a hearing, because, after all, Folsom came in without any intimate background of what it was all about and I'm sure that the administration of NIH opposed it» I think I would have opposed it had I been the administration of NIH. Probably, I don't know. But it didn't get a chance«, There was no chance with Folsom. He never called any of the committee in to talk about it. There was no way

Page  514514 to answer any criticism if it did occur„ If Dr. Shannon had said that it wasn't practical, there was no chance to reply. Dr. 0.: As a postscript to your comments on the Long Report, we have this report known as the Woolridge Report, named after Dean Eo Woolridge, whose formal title is "Biomedical Science and its Administration: A Study of the National Institutes of Health". This was published in February 1965. Here again, one of the major recommendations pertaining to the extramural program is a committee or a council, very similar to what you and your colleagues recommended, again being recommended! Now this one obviously has seen the light of day, but this is now 1968 and I don't see that any action has been taken on such a movee Dr., H.: I think I should amend my statement about distribution, because I know that Bayne-Jones had a copy for his report. I think that Berry had a copy before they brought out their report, so perhaps it has carried down, who knows. Dr. 0.: I have been negligent in not having gotten out a copy of the Bayne-Jones Report and this Berry Report and followed this recommendation through., It would be interesting to see if it persists. [Pause] Dr. H.: There is one part of the administrative organization of the NIH which I feel has been instrumental in its success in addition to the establishment of the Study Sections. And that is this. When

Page  515515 Congress passed the law authorizing each of the categorical institutes, it established a Council for that Institute which was appointed by and answered to the Surgeon-General. These Councils receive the requests for grants for research and training and fellowships from the Study Sections, or in the case of Training Grants the Training Grant Committee. They receive all of them. Those that are recommended for approval. Those that are recommended for disapproval, and those that are deferred for further information. The study sections have also given a priority number to each of these recommended for approval. The Councils, made up of 12 members, 8 of whom are scientists, and 4 of those 8 are specialists in the categorical field of the Institute, and 4 are men or women of affairs. They review each of these grant requests. Fortunately they don't have to, in all instances, review the entire request as they do in the Study Section. They have a summary sheet which states in some detail the objective, the manner in which the research will be conducted, and an evaluation of the merits and demerits of the request as written and approved by the Study Section, and of course the budget. Now these Councils must approve these grants if they are going to be paid by the Surgeon-General. He cannot pay any grant, whether it has been approved or disapproved by the Study Section unless the Council has approved it. He can veto; he has the power of veto, which as far as I know is only used for administrative reasons. But he could for scientific reasons if he wished,, In effect this means that the Councils, not the Surgeon-General, have been the administrators of the grant

Page  516516 programs. They have the power to decline grants. If they have additional information or decide they want to get other information from the Study Section, they have the right to do this. And it has happened in my experience at least once, or perhaps twice in the course of a meeting. The meetings go on three times a year, a two or three day meeting. This is a big job and if by any chance somebody on the Council wants more information on the complete grant, then it is always there and available for their study. I, for one, always read every one of the Study Section reports and very often got out and studied the whole grant request,, I am not sure all of my colleagues on the Councils were always this conscientious as I was about this, but I am very proud of the fact that I would take days to do this ahead of the meetings, - as soon as these big thick books arrived„ You see with 17,000 active grants, it means that on the average about 1,000 pink sheets had to be evaluated per meetingo I would evaluate each one of these pink sheets for four different things. One, the man; the place it was being done; the problem; and the budget,, I got so that I could do this very fast fortunately, and I would give either an "OK", a "?", or an "NG" on each of these four items on the basis of reading each of these pink sheets. This I did religiously for those the Study Section had declined too! Dr« 0.: Were a significant number of "declined" grant applications approved by the Council? Were there on the other hand many that were approved by the Study Section, declined by the Council?

Page  517517 Dr. H.: There were very few that were declined by the Council unless they had a very low priority., I used to convert these numbers in my mind to sort of A, B, C, D, and E; E would be failing, D would be some division of opinion,. If the Study Section had a divided vote, this was always recorded and you would question the Executive Secretary of the Study Section as to what went onc What was the divided vote about? Nowadays with money in short supply, they can't pay even those that are approved with a very respectable priority, even a B. It is very different from those days when we had more money than we had good projects. Dr. 0.: Dr. Hastings, would you give me your reactions to the recent reorganization of the Public Health Service. With your background and long association with NIH and its development, and having been involved in the study of NIH in the Long Committee Report, do you have any feelings one way or another as far as the new position in which the National Institutes of Health now stands. Dr. Hc: I am not completely familiar with the final organization of the Public Health Service, but I read last week the Director of the NIH shall be responsible directly to the Secretary of Health, Education, and Welfare,, What I mean is that Shannon is now directly responsible to Lee and the Surgeon-General is in some sort of "box" on the side. I asked at the recent meeting of our Training Grant Committee, one

Page  518518 of the Administrators, what the role of the Surgeon-General would be and he said that everybody was asking the same question. I must say that I am at a loss to know what this will gain in terms of the administration of the intramural and extramural programs of the NIH. I am not at all sure that I know why it was done. It may be that it will make it easier for administrative actions to be taken. It will perhaps remove one step between approval or disapproval by the Secretary of actions that Shannon and his administrators want to get going. Instead of having to go through the Office of the Surgeon-General and then to the Office of the Secretary. Dr. 0.: There of course is the added factor that also under the administration of Dr. Shannon and his staff are the National Library of Medicine and the Bureau of Health Manpower which has been added to the "Institutes" of the National Institutes of Health. Drc H.: Oh, I didn't understand that the National Library of Medicine is now under Dr. Shannon. Dr. 0.: Yes, Dr. Cummings now answers to Dr. Shannon rather than going directly to the Surgeon-General. Dr0 H.: Well previously he answered directly to the Surgeon-General just like Dr« Shannon did, didn't he? Dr. 0.: Yes. Drc H.: Well, well. Well you can see that I don't have any special

Page  519519 feelings about this because I don't quite understand why it was done this way. I guess Shannon is going to stay on for at least a year. They tried very hard to find a suitable successor, but I guess they couldn't agree on onec Shannon certainly carried a big load and has done it remarkably welie I have from time to time differed with Shannon on some of his actions. Time for another anecdote? Dr. 0.: Absolutely. Dr. H.: While I was on the Heart Council, Shannon would try to come to open the meeting and give a very brief account of things that were in the works either in Congress or in his Office. I remember well on one occasion when Ralph Knutti was the Director of the Heart Institute, and he had placed the agenda for our meeting in front of Shannon and Shannon was scanning this and making off the cuff comments on some of the things we were going to discuss --unfortunately I can't remember what this particular matter was --but he came to an item and said, "Well there is no use in your spending any time on this item, because I would administratively disapprove of it I" Upon which I broke in from the end of the table and said, "Jim!", I pointed my finger at him, "Jim! You can't say things like that. You know perfectly well that you don't have any control over what this Council does, administratively or any other way!!" [Laughter]

Page  520520 Dr. 0.: That must have brought the house down! Dr. H.: It was terrible. There was dead silence. I used to always carry a copy of the law creating the Institutes in my folder, and almost every meeting I had occasion to read from the law that it was the Councils which had the administrative authority,, It is true they are called Advisory Councils and when they set up the NICHD, what I call the "cradle to the grave" Institute, somebody changed this in the law forming this new institute. This was actually after I had pointed out in the guidelines that they were getting up, that the Councils had administrative power and not just advisory. The NICHD Council is very specifically not given the power of the other councils. It is strictly advisory. They actually made this change in setting up the new institute. I am going to quote from what is known as the "Heart Act", Public Law 655 of the 80th Congress. This Act is similar to the other Acts which established the other categorical institutes, except the last one which was the NICHD. In Section 412, Part B it states, "In carrying out the purposes in respect to heart disease, the Surgeon-General shall make grants in aid to universities, hospitals, laboratories, and other public or private agencies and institutions and to individuals for such research projects relating to heart diseases as are recommended by the Council." This is what I mean by giving the power of making grants to the Council.

Page  521521 This is to be compared with Public Law 87-838, enacted by the 87th Congress in 1962 in which in Section 443A it states, "The Surgeon-General is authorized with the approval of the Secretary to establish an Advisory Council to advise, consult with, and make recommendations to the Surgeon-General on matters relating to the activities of the Institute." Nothing further is stated in that to the effect that the Surgeon-General shall only approve those grants which have been previously approved by the Council0 Dr. 0.: Was there a concerted effort by the PHS to make this change? Had there been any instances of strong differences of opinion with some of the Councils that led to their altering this in the creation of the new Institute? Dr. H.: No it arose as I remember rather insidiously if you will. Not through any clash. It arose because as the program got so much bigger, there developed an increasing number of instances in which for some reason, after the grants were approved by the Council, there would need to be an adjustment of the money involved. Drc 0.: Because there were more approvals than money available? Dr. H.: Not at that time. It would be over very small items that for some reason had to be adjusted up or adjusted down. Now the Surgeon-General and Shannon and his office had the power

Page  522522 to adjust down, but they could not adjust up. So the first request that came to us as Council members was to authorize them to make adjustments -- I believe in the range of 107o plus or minus of the budget we had approved. Because this law was so specific you see, that they couldn't spend an extra dollar on a particular grant that we had not approved! That seemed reasonable, so we did itc We granted that authority0 Now maybe that was the first mistake; that perhaps is when I should have said no! But it didn't seem proper at that point to say no. It is just what I would have wanted at that point to cut down the paper work and speed up the business. It was that request that was then followed with a request to really approve things without going through the Council. It was over something of that nature that I began to disapprove of such suggestions and won my point to the extent that in the guidelines for the Council, when they came out finally, the Councils were advisory to the Surgeon-General except when otherwise provided by law. Drc 0.: So to this day the Heart Council still has this authorityc Dr. H.: As far as I know all of the Councils except the NICHD Council have this authority. I wish I had the original Cancer Act because the story of these laws is roughly this: -- the Cancer Act which went through in 1937, I believe, to establish the Cancer Institute, gave very broad

Page  523523 powers to the Public Health Service to carry on research and trainingo As you know this Act was introduced by all the Senators. Even at the risk of repeating what I have already said earlier, the year before the OSRD and the Committee on Medical Research went out of business, Dyer and Parran arranged to have passed an empowering act for conducting medical research on a broad scale and available to the Public Health Service if and when the Committee of Medical Research ceased operation. Dyer told me that what was done was essentially to take the Cancer Act and cross out Cancer and put in "medical". The problem as I have been told by some of the administrative people of the Public Health Service has been to sensibly cut back the provisions that are embodied in these Actsc They are so broad they can't legally carry them all outc They need to be reinterpreted you seec That's why I am sure that Shannon and Ernest Alien with the best of intentions have been trying to interpret the law so that they can go on doing as good a job as they have been doingc Fortunately they haven't had too many Baird Hastings looking over their shoulders 1 tLaughter ] They have been able to run it pretty much the way they have thought best,, It isn't that I wanted the Councils to have power so much as I wanted them with that power to be of most help to their administration. It is the best defense that they have with the Fountain Committee and so forth. He should get after every Council memberI

Page  524524 They are the boys who have done this; it hasn't been the Surgeon-General. It hasn't been Jim! If bad things have been done, it is the membership of the Councils that have done it! They are the ones that Congress themselves have said are legally responsible! Only, I don't think the Senators have read the law! [Laughter] Dr. 0.: I am delighted we have covered this on tape as it sheds a lot of light on an area many people are not aware of. Dr. H.: Medicine has been very different because of the postwar extramural programs of N.I.H. Certainly in this post war period because of the people who have been involved! Starting with Dyer, and Van Slyke, Shannon, and Sebrell and those of us who have served on these Councils and the Study Sections of course. But the Study Sections are advisory. They don't have any power. They have the responsibility for making the scientific decisions, but they don't have any power with this responsibility. The Councils, the make up of the Councils, deserve great credit for this development of medical research and medical training in the last 25 years. Dr. 0.: This may be an inadequacy on my part, but I always have been aware of the Study Sections and what they were doing and I have known that there were "Councils" for the Heart Institute, Cancer Institute, etc., but I wonder if many people share my former

Page  525525 ignorance of the role of these Councils. Perhaps so. Dr. H.: I think many of the Study Section members may not know thiSc They think that they are making the decision. If they know there are Councils at all, they think of them as "rubber stamps". On occasion when we have thrown something out that they have approved, they have shouted to high heaven and the Director always warns the Council at the beginning if you make any changes, be sure to document them very completelyc That never deterred me, but maybe it did some people. I wish I had the make up of the Heart Council when I was on it. I can't remember who the members were on my 4 Councils. [End Tape 15, Side I] Dr. 0.: This is Tape 15, Side II, date May 7, 1968. Dr. Hastings is going to relate a series of vignettes or characterizations of some of the individuals with whom he has been associated during his career. Dr. H.: William Herbert Sweet, Professor of Neurosurgery at the Massachusetts General Hospital, Harvard Medical School. I first encountered Bill Sweet in December 1943, when I was introduced to him by Joe Ferrebee in the OSRD office in London. He was in a blue gray uniform without any distinguishing insignia and looked like a relatively insignificant person,, However his soft, well

Page  526526 modulated voice and his choice of the English language immediately indicated that he was probably something special. At the time, as I learned later, he was the only neurosurgeon who was practicing neurosurgery in the whole city of Birmingham, England. He had volunteered for this activity before we got in the war and they needed him so badly that he had stayed as a civilian neurosurgeon. He had been educated at the University of Washington and taken his M.D. at Harvard in 1936, though he had entered Harvard in 1931. He had interrupted his medical training to be a Rhodes Scholar in Oxford under Sherrington from 1932 till 1934. He had had his neurosurgical training at the University of Chicago and at the Harvard Medical School. Though I enjoyed talking to him during this brief period in England when I first met him, it wasn't until after the war that he entered my life very intimately. He did not return to the United States until 1945, and as I say, served as a neurosurgeon in Birmingham from 1941 to 1945. When he left, the city of Birmingham had a very large celebration and the Lord Mayor presented him with an emblazoned citation of appreciation from the city of Birmingham., He was also decorated with His Majesty's Medal for Service in the Cause of Freedom. Before he came back, the house next door to ours on Chestnut Place in Brookline had come on the market due to the death of Dr. Reginald Fitz's sister, the previous occupant. By chance, Bill Sweet's wife, Mary, heard of its availability and looked at it. They had two small children whom he had left in the United States during the war. She had written her husband after she looked at it describing

Page  527527 it and asked whether she should buy it. Incidentally in her letter she said that it was next door to the Baird Hastings' house. Upon which he cabled back, "By all means". He later said that this was all he needed to know. So from 1945 until we left for La Jolla, he was by all odds my closest friend in many ways. Our next door neighbors until we sold our house in 1950, but even after we moved to another house closer to the medical school he ordinarily would pick me up in the mornings at 7:30 because all neurosurgeons like to get started operating by 8:00! Bill and I became and are fast friends. I admire this man as much as anyone I know in medicine. He is first and foremost an expert neurosurgeon . Should I need neurosurgery, I would go to him at once. He is a basic scientist of the first order in addition to this. When, after the war, and shortly after he returned, we undertook the use of radioactive isotopes in biological and medical problems in the Harvard Medical School, Bill immediately wanted to capitalize on the use of isotopes for the better localization of brain tumors. A slightly younger budding neurosurgeon named Bert Silverstone obtained a postdoctoral fellowship and undertook with Bill in Art Solomon's laboratory to develop a pencil type probe for insertion into the brain following the injection of radioactive phosphorous, the idea being that phosphate permeates

Page  528528 all normal tissue and cancer tissue with about equal ease, but not the normal brain substance. The blood brain barrier delays this. So if the tip of this probe which was a microcounter for on radioactive isotopes, counted a high concentration of PJ^ then it would immediately make itself known. This worked. A young man from Wisconsin, an ingenious man named Robinson, Charlie Robinson, had come to work in Solomon's lab and he worked with Sweet and Silverstone in developing such probe counters, making them more and more micro so they would do less and less damage to normal brain tissue. As soon as Bill got interested in this field, he studied physics and nuclear physics as if his life depended upon it. Night after night I would see his light on in his study from my bedroom when I was going to bed. He would study his physics during this period as avidly as if he were getting his Ph.D. It was no time at all until he was as good as anybody who had been brought up as a physicist. He amazed me with his memory and his excellent training in chemistry. I remember one night I had to miss an exciting lecture by Professor du Vigneaud at M.I.T. Bill attended and when he came back he sat in my house and with pencil and paper reproduced this lecture and the formulas 1 This was du Vigneaud's announcement of the synthesis of penicillin. It was a lecture I wanted to go to very much as it was what I had wanted our Committee on Medical Research to dol It was considerably after the war when it was done for the first time and it was by no means near a commercial

Page  529529 production. It isn't today as far as chemical synthesis is concerned. Bill did a much better job than I could have done, if I had heard the lecture. As Bill learned more and more about nuclear physics, he became interested in the possibility of capitalizing on the cross section capture of the radioactive isotopes in different materials. This is when he conceived the idea that if they could find a non radioactive atom, which they could inject and would concentrate in tumor tissue, relative to normal brain tissue, perhaps then by irradiating the brain, hopefully without removing the skull cap, they could convert this atom if it had a high cross section capture into a radioactive atom which would destroy the tumor cells. He hunted through the atoms of various kinds that might be subjected to this procedure and discovered that boron had a high cross section capture figure. By starting with Boron^ they could convert this to a radioactive boron atom which on decay would release a high amount of energy. The problem then became will borate ions concentrate in tumor tissue relative to normal brain tissue. They found that indeed it did« He didn't know how to go further with this problem so I sent him to Brookhaven National Laboratory to consult with Van Slyke about it. At that time Lee Farr was head of Medicine at Brookhaven and Bill came back delighted with the arrangements for collaboration. He would supply the patients; indeed he drove them down himself in his own car from Boston and they would inject the Boron . They had an adapter port put on the reactor at the Brook-

Page  530530 haven National Laboratory and they irradiated the heads of these patients. The port was on top of the reactor. It was a valiant effort. Of course the only patients selected for this were very advanced and inoperable brain tumors. The idea was an excellent one and was pursued by Bill and Lee Farr. Later Lee Farr undertook studies on his own after Bill more or less gave it up as an impractical means of treating brain tumors. They proved that they killed the tumor this way, but the complications first of destroying the skin which could not be avoided led them to irradiate the brain with a skin flap turned back. However, they never were able to avoid the secondary complications of the skin burns, though it was sufficiently promising that the Department of Medicine at Brookhaven National Laboratory got approval to have their own reactor especially designed for such studies. Though Bill pursued this as actively and as effectively as I think was reasonable, he didn't put all of his eggs in one basket. He also studied problems of cerebrospinal fluid, and of ways to combat the edema which occurs during a brain operation. His operations would take 8 or 9 hours sometimes. He associated with himself a good organic chemist during this period so that they could synthesize different kinds of boron containing compounds. He complexed the boron compounds with others, such as sugars, to try to get a higher concentration of boron in the tumor tissue. He is an all around biological scientist and has a high capacity

Page  531531 for learning new things even in physics and chemistry. He is quite unusualc For quite a while at Harvard, his fellow brain surgeons at the different hospitals would say to me, "How can Bill be a good brain surgeon, when he is such a good scientist?! No brain surgeon can be that good I" They had the feeling that unless you were 100% brain surgeon you couldn't be a competent brain surgeon. Dr. 0.: He sounds like the type of personality that one does not generally associate with a neurosurgeon if you think of the Walter Dandys and the Harvey Cushings. Dr. H.: He is very slight and wiry. He is by no means a push over though„ He is a person with strong convictions of what is right and what is wrong and what standards should be maintained. He is a wonderful companion. As he became more and more involved in the peaceful aspects of atomic energy, it was natural that he should be chosen by the Atomic Energy Commission to go to the first Atoms for Peace Conference in Geneva. I was fortunate in also being chosen - so we traveled together. I was also pleased when President Pusey at the suggestion of Dr. Berry made him one of the Trustees of the Brookhaven National Laboratory 10 or 12 years ago. He is so valuable that they have kept him on because he has continued to be very active in their affairs. He had a great deal to do after the Associated Universities, Inc.

Page  532532 took on the responsibility in addition to the Brookhaven National Laboratory, of the very large radiotelescope affair in West Virginia. Apparently this turned out to be a very difficult thing for the Associated Universities, Inc. to do. I understand that Bill played a very big role in getting it underway. His appointment as a full Professor was much delayed so during this period he was an Associate Professor. There were many universities, including that in Birmingham, England, who wanted to have him come and take charge of the neurosurgery, but he has a great devotion to Harvard and decided to wait out Jim White's retirement at which time they advanced Bill to full Professorc People are still after him. They offered him the moon at the University of California, San Francisco the year before last. After looking it over carefully and thinking of all the implications, he decided to stay where he was. I should say that he also added to his research staff, Dr. Adelbert Ames, a Harvard medical graduate who had spent about 3 postdoctoral years in our department. Though Del had excellent opportunities to go elsewhere, particularly the Rockefeller Institute, his heart belonged to Boston and when Bill offered him an opportunity to come down with his group he went there and is now, I would say, a leading investigator in the study of how ions can effect nerve activity,, I suppose because his father was very famous as an ophthalmologist in Northhampton, Del decided to start with the retina. His first

Page  533533 objective was to remove a rabbit's retina and determine a solution in which it would be viable. This worked out while he was in our department and which we published together. Subsequently he was able to attain his objective, that is, with the retina in vitro to expose it to light flashes and get electrical discharges into the optic nerve which I think was a very great achievement. I am glad to say he is now studying cerebrospinal fluid from different regions of the brain and is also concerned with what are the electrolytes of glial cells and neurones, a problem which has me stumped in my present capacity at U.C0S.DCJ He has with him Frances Nesbett, who was with me for some 14 years and the two of them make a great team. Dr. 0.: They are working right in Dr. Sweet's laboratory? Dr. H.: Yesc He has several things going for him there0 For a short period, Fernandez Moran was there with Sweet. Dre Sweet has never gotten over the fact that Harvard didn't see as he did, the great advantage in having Fernandez Moran at Harvard, so he went to the University of Chicago where he has been for some years and where he has done the most phenomonal experiments with electron microscopy0 The morphology at the molecular level, of synapses has really been tremendously advanced by Fernandez Moran. Well, Bill Sweet is one of the memories of Harvard that I cherish. One other thing about him. Not many people do things as thoroughly

Page  534534 as Bill does. He was invited to Japan to attend a neurosurgical meeting and to give some lectures. He wrote out his lectures and had a Japanese in the laboratory translate his lectures into Japanese. He then had this chap tape them and then he learned them from the tape, and he delivered his lectures in Japan in Japanese. This made such an impression on the Japanese medical scientists that he has been back several times since that first time and of course has to do it every time -- he has a bear by the tail! Of course he can only accept those invitations for which he has time to go through this routine. He went on a lecture tour in Germany after the Atoms for Peace conference in '56. He drove a car through Germany with his son and delivered his lectures in German, though this is perhaps not so astonishing. I admire him though because I have never done anything like this. He is an American Medical scientist of the first order and has been honored with an Honorary degree from Oxford. He is a member of the Gushing Society of course. [Pause] Drc Hc: Joseph C. Aub. I had met Joe Aub only occasionally prior to my going to Boston, but for the first few years we were there, Margaret and I saw a great deal of Joe and his family. Joe Aub as a young man had worked at Cornell with Du Bois and the basal

Page  535535 metabolism standards are still recognized as the Du Bois-Aub standards. He then came to Harvard as an instructor in the Physiology Department under Dr. Cannon. He advanced to Assistant Professor from 1919 to 1924. He then became an Assistant Professor in the Department of Medicine and in 1928, after I declined the Professorship at the Cancer Research Unit at Harvard, Joe Aub took the position. He was an Associate Professor from '28 to !43, after which he became a full Professor until he retired,, He was the Physician in Chief of the Collis P. Huntington Memorial Hospital from !28 to '43, after which they moved that hospital, or rather, transferred the funds to the Massachusetts General Hospital and labeled that portion of the hospital of which Aub was the Director as the Collis P0 Huntington Memorial Laboratory. He served as Chairman of the Department of Medicine at Harvard for many years. He was perhaps the most beloved of all the people in the clinical sciences. Everybody was devoted to Joseph C. Aub. I donft know of any special work that Joe did that was very outstanding though. When Fuller Albright and Walter Bauer were young, they, working with Aub, did some of their pioneer work on parathyroid activity. Joe was always very interested in endocrine problems and endocrine research. He took a very broad view, a biologists view of cancer, and encouraged basic research in his cancer research laboratory. The outstanding work that Paul Zamecnik had done and is known for, was really because Joe had stimulated

Page  536536 him to do this. It was this work which led to the realization that the ribosomes are the seat of, or the site of protein synthesis. He was President of the Ella Sachs Plotz Foundation, following Dr. Cannon's death, until it was incorporated into Harvard funds. The Ella Sachs Plotz Foundation was one of the more interesting and productive of the small foundations. It was founded by the Sachs family in honor of Ella Sachs, wife of Drc Harry Plotz, who died quite young. Her brothers created this small medical research foundation to which they contributed $10,000 a yearc It was managed by a local committee. When I joined it, Dre Cannon presided and Dr. Aub and Dr. Wislocki were members. Later Drc Janeway was also a membero Dr. Paul Sachs who established the Fogg Museum was a member and one of the business brothers would always come up from New York for the annual meeting. It was done in those early days with great simplicity. All one had to do was write a letter. The amount you could ask for was anything up to $500. Many of the requests came for $200, most of them from abroad. The number of reprints which emanated from this small foundation was the greatest scientific productivity that I have ever known. It was tremendous to think that with $500 a man could have an assistant for a year, or for $200 buy a piece of apparatus without which he couldn't do any of his work. Joe was supposed to write the history of this foundation. I hope he does, because it is a very dramatic thing to think that only $200,000 spread over all those years served many

Page  537537 scientists in good stead. Joe took a great interest in this Foundation and even fought very hard to preserve its independence when the Sachs family decided they were getting old and didnft want this responsibility any longerc They gave it to Harvard to be used as the Dean saw fit. This hurt Joe's feelings very much, because he knew that once it had been given to the Dean, that would be the end of the Ella Sachs Plotz Foundation. He is getting so hard of hearing that it is very hard to communicate with him when I see him. He is one of the men at Harvard that I am very very fond of and admire very much. [Pause] Dr. 0.: The date is May 9, 1968 in the office of Dr. Hastings at the Scripps Institute of Oceanography. This morning we will continue with a number of vignettes about individuals with whom Dr. Hastings was associated. Dr. H.: I would like to make a few personal comments about some of my colleagues, first some of those at Harvard. I might start with Dr. William B. Castle. At the time I went to Harvard, the Thorndike Laboratory was located at the Boston City Hospital and was, I believe, the successor to the Francis P. Peabody Research Unit there. It was headed by Dr. George Minot with whom was associated Dr. Castle, Dr. Chester Reefer, and Dr. Soma Weiss. This was a powerful quartet of the

Page  538538 Harvard faculty in the Department of Medicine in the 1930's. They were all Associate Professors except Dr. Minot, who was a full Professor. They were very different in their interests and yet all very able in their respective fields. They made such a distinguished and effective group of teachers that the Harvard medical students in their 3rd year, when they were allowed to choose where they would take their clinical work, or at least express preferences, and had the opportunity to go to the Peter Bent Brigham, the Massachusetts General, the Beth Israel or the Boston City Hospital -- would choose the Boston City Hospital as their first choice about 80% of the time. Minot had received the Nobel Prize in 1934 along with Whipple and Murphy for their discovery of the efficacy of liver extract in controling pernicious anemia. Minot was still engaged in the search for the identification of the factor or factors found in liver which counteracted pernicious anemia. Castle was also interested in anemia, but he had approached the problem in an entirely different way, namely to see what it was in the gastric secretion which would control pernicious anemia. By experiments on himself, which involved allowing protein -- I believe it was a beefsteak --to be digested in his own stomach, or partially digested, and then by regurgitating it and feeding it to pernicious anemia patients had produced a rise in the reticulocyte count and a remission of the anemia. He named this the intrinsic factor. This rather

Page  539539 unusual but quite effective way of therapy in anemia has resulted in continued research on the isolation and identification of this substance up to the present time. Bill Castle was a true biologist in the field of human biology. He was not chemically trained or chemically oriented. Indeed, in later years he was a bit resistant in having a professional biochemist work intimately with the research group at the Thorndike, because he felt that there was so much to be learned by thoughtful observation and simple experimentation. But there aren't many Bill Castles in the world. A wonderful teacher and a most modest man. His father who lived to be 90 or more had been one of the country's great biologists, and his brother is a Harvard Professor of Biology in Cambridge. Bill was a great human being and the students all worshipped him. He used to run around in the oldest Ford open car he could find. When the old one gave out, he would get the next oldest available I Dr. A. N« Richards admired Bill very much and when we started our Committee on Medical Research activities in Washington, he felt that Bill would be of great service to us. He persuaded Bill to spend a few days each week with us in Washington, but after a month of commuting such as I was doing, he gave up and wouldn't come back. He said the life was much too strenuous for him. To tell you the truth --at least he says, he couldn't keep up with our martini diet after work!! [Laughter]

Page  540540 Let me go on with the others of this quartet. It was a very famous quartet, as long as it lasted. Minot of course was of the Boston Minots. I think one of his ancestors, perhaps grandfather, had been Professor of Anatomy at Harvard. At any rate he was a typical Bostoner. Very quiet, a little bit on the bumbling side when he talked, was forever jotting little notes to himself on a piece of paper from a pad that he always carried with him and stuffing them in his pockets. I am told that his first action in the morning when he would come to work would be that he would stop at his secretary's desk and unload his pockets. It was her responsibility to sort them out and make sense out of them. I met him first in 1928 when I went to consider the job as Professor of Biophysical Chemistry in the Cancer Research unit. At that time he was a member of the Board responsible for the administration of this cancer unit along with L. J. Henderson and Hans Zinsser. It was Minot, who shortly after I came there in 1935 and wanted to assemble all the people working on pernicious anemia at Harvard in my office to let them all find out what Subbarow was doing and the Dean had offered to assemble such a group -- it was Minot who said to Dean Burwell who was his good friend, "Oh you must never do that! No Dean ever gives instructions to a Professorl" The dramatic story of how Minot developed diabetes of a very severe type in the early '20's and how the discovery of insulin at just

Page  541541 that time saved the life of Minot so that in later years he could discover an effective remedy for pernicious anemia, has been told by Frank Rackemann in a most engaging and sentimental volume called The Inquisitive Physician. A third member of this quartet was Soma Weiss, who died I believe in 1942. Hungarian born, gay, married to the daughter of Paul Sachs. A most exciting teacher, one who had gotten his start in medicine in clinical investigation through working with Herrman Blumgart at the Beth Israel, [ End Side II, Tape 15 ]

Page  542542 [Reel 16, Side I] (May 9, 1968) Dr. H.: Well, I was about to recall that, as a very young man, Soma Weiss worked with Herrman Blumgart at the Beth Israel Hospital on circulation problems. They were one of the very earliest to use radioactive isotopes to study physiological processes. They scraped the residue from outdated X-ray tubes where a radioactive decay product called Radium G could be found. By using a recording device over an artery in the arm and then injecting this Radium G, they were able to measure circulation time. I heard them report this in New York. Well, Soma had joined Minot at the Thorndyke Laboratory and he was the cardiovascular man of the team, though he had many other interests such as vitamin B deficiency. He was an effervescent personality who transmitted his excitement to the medical students and they were devoted to him. Mrs. Hastings is fond of remembering that until his early and untimely death, we would go with him and his wife, Elizabeth Sachs Weiss, to the Copley Plaza Hotel on Monday nights because hardly anybody went on Monday nights and since the four of us loved to waltz. When the music was on we would waltz and when it wasn't Soma and I would talk science. Dr. 0.: That's quite a combination1. Dr. H.: The fourth member of this quartet was Chester Keefer, Now, Chester had been a close friend of mine since the first year at Chicago where McLean had put him in charge of everything that happened in connection with opening of the Billings Hospital. His title at that time was only that of Chief Resident, but he was so able after his training

Page  543543 at Hopkins--experienced--that he established the traditions of the Billings Hospital and there were many indeed in opening a teaching hospital. After two years he went to the Peking Union Medical College as an Associate Professor where he stayed for a number of years, returning to Harvard to work at the Boston City Hospital. Dr. 0.: Were most of the medical staff of the Peking Union Medical College from Chicago and Harvard? Dr. H.: No- Dr. 0.: Did they come from throughout the country or was there sort of a nucleus of schools that supplied the staff--and the Rockefeller Institute, of course. I've just been impressed by the number of people throughout your career who have spent time at the PUMC. Dr. H.: This is just because I happen to know them, I guess. I suppose that one might say that most of them had come from Hopkins or Harvard, or the Hospital of the Rockefeller Institute that were Americans, but of course there were Dutch, there were Canadians, there were Scotch, English. It was an international representation, at least at the time I got there in the '30s. To go back to Keefer, he was in Peking for two years and then he came to the Harvard Medical School where he was at the City Hospital from 1930 to 1940--ten years—upon which he became the Wade Professor of Medicine at the Boston University Medical School and Director of the Evans Memorial, which was a small clinical investigation unit, very reminiscent

Page  544544 of the hospital of the Rockefeller Institute. His field was infectious diseases and microbiology. Though he was not a flamboyant teacher, he was so clear, had such a wonderful memory and was exact in his lectures, that he, too, was very popular with the students. Indeed, it is told of him that a student could ask a question about some aspect of a disease that he had just discussed or may not have discussed recently, and Chester would say, "Well, on page so and so in such a journal in an article by so and so, you'll find the answer to your question," and he would go and find this would be true. Having related that, "I'm reminded of an incident which happened a few years after World War II when both Chester and I were back in Boston and I had been called by a person unknown to me previously who was vice-president of a pharmaceutical house asking about somebody whom I did not know that they were considering as a Scientific Director. And knowing that Chester had had intimate contact with a number of pharmaceutical houses while he was the "penicillin czar" during the war days, I thought I might get a lead on who this man was and how reliable he was. So I called Chester on the phone and he rattled off the age, the education, the previous positions of this man, and I said, "Well, Chester, I expected you to maybe tell me something about him, and I know your reputation for having this kind of a memory, but I don't see how you did it this time." "Oh," he said, "it just so happened that I have a card here in front of me that was in the top drawer of my desk, when you called; I was reading from that1." (Laughter)

Page  545545 Keefer would very much have liked to have succeeded Henry Christian at the Brigham. I think perhaps since this is a medical history this item is also recordable. Of course I would have been very glad, too, though I was not on the ad hoc committee that chose Christian's successor. However, I did what I could, both at the faculty meetings and at the committee of professors meetings and outside to further this. Well, I should introduce the fact that when Henry Christian retired, Soma Weiss succeeded him immediately--was the immediate successor—and then Soma died a couple of years later, in 1942. And it was that, who was to be Soma Weiss1 successor that I am speaking about. But Chester thought of it as Henry Christian's Chair because Soma was not really at the Brigham long enough to be identified as his successor. Well, Henry Christian wanted Chester to be his successor, too, because Henry Christian was still alive. However, there were clinical people at the other teaching hospitals who were not as excited and well-impressed with Chester as some of the rest of us were so there was a good bit of discussion. He had a lot of support, mind you, but to get such a professorship you needed to have unanimous, enthusiastic support. And the only thing that the people who had their own candidates or ideas about who ought to succeed—because it wasn't so much that they were against Chester, as that they had their own man they wanted to get in--but the only thing they could bring up against Chester was that he had published too much I It is true. He had a very long bibliography and it's because he saw to it that when he gave lectures they got published. He had in this field of infectious diseases—written up all their experiences, so instead of having, say an

Page  546546 average of four publications a year, he had tenl So the statement was made at the professors meeting, "Well, no man can publish that much and be a good scientist!" Anyhow, he didn't get this position at the Brigham and so he took the position as Professor of Medicine at Boston University and built up that Department of Medicine by surrounding himself with four very brilliant young men, Wilkins and Ingelfinger and Joseph Ross, and I've forgotten who the fourth one was. Since they were well supported by the endowment of the Evans Memorial, he had a very choice clinical investigation group, and with Weiss1 death, with Minot's death, with his leaving the Thorndike, I would say that for a number of years until the Brigham and the General got going well again, the Evans Memorial had the best clinical investigation and department of medicine in Boston. I think Ifve already recorded that during the war he was the medical director for the Committee on Medical Research and magnificently managed the several programs with such subdivision chiefs as Joseph Wearn and Det Bronk and Jim Shannon. After the war, he took up his position at the Evans Memorial again. Though he was brought back to Washington when streptomycin appeared. He was put in charge of the clinical documentation of this, the second of the antibiotics. Mrs. Hobby was made Secretary of DHEW, he became her advisor in medical affairs, Assistant to the Secretary I guess his title was. I always referred to him when I used to introduce him as "Public M.D. No. I1." Dr. 0.: You must have a picture of Dr0 Keefer around somewhere; it's one of the few men that I haven't seen a picture of»

Page  547547 Dr. H.: I don't have a good picture of Chester. I belabored him many times for one. He's in the CMR group picture; it's the only one that I've got. Well, this great quartet being the ones most admired by the medical students, they obviously were the ones who were the most prominently affectionately maligned at the annual Aesculapian Club play. One classic one was a musical show and one of the songs had a refrain that went, "I'm Minot, I'm Castle, I'm Keefer, I'm mel:--the me being Soma Weiss and the student who portrayed this had all the mannerisms and even to the looks of Soma; his name was Landsteiner, the son of Karl Landsteiner. I've forgotten his first name, but he's now a very successful obstetrician in Providence, Rhode Island. Just mentioning Landsteiner, reminds me that I knew Karl Landsteiner very well. He came to the Rockefeller Institute while I was there and was then well along in years and had already done the blood-typing work--I've forgotten where he came from--Vienna or some such place--for which he eventually got the Nobel Prize after he came to the Rockefeller Institute. He was one of the sweetest persons I have ever known; a big man with big brown eyes and a bushy mustache. He was a perennial student; he was learning Russian; he studied physical chemistry at night. It was while I was at the Institute that he used to ask me about physical chemistry. He was going through a textbook studying it hard and he came to a section on the independent solubility of different solid phases — that is if they don't have a common ion, if they're two different substances

Page  548548 they will dissolve to the same extent that they would if they were there alone. Well, this immediately struck him as something that he would like to study, and since his experience had been with blood and blood-typing, to some extent with hemoglobin, he wondered whether hemoglobins from different species would have independent solubilities, or whether having hemoglobin of one species there would interfere with the hemoglobin of another species. He interested Michael Heidelberger, who was then crystallizing horse hemoglobin for us, in preparing crystalline hemoglobin from animals of different species0 I should say that Landsteiner had been able to show that you do get specific antibodies. It's a weak antigen, but it is specific, the hemoglobin from the individual species. So Michael undertook to prepare these hemoglobins and as they found this was true, then Michael got more and more interested in preparing hemoglobins for Landsteiner than horse hemoglobin for me and my gang in Van Slyke's department. We had a little problem with that for awhile there, which in retrospect seems a little silly, but I had to bear down0 This was the year that Van Slyke was in China, and I was in charge of getting results. Just to go back to these experiments of Landsteiner and Heidelberger, they quite logically reached the point where they wondered whether the hemoglobin of a donkey and the hemoglobin of a horse would be independently soluble—have independent and different solubilities. So they tried it and they were. The hemoglobin of a donkey was different from that of a horse and when they were mixed together they still had their individual

Page  549549 solubilities. So, of course, the next experiment was to take the hemoglobin of a mule, and there, their independent solubilities broke down. The hemoglobin of a mule influenced the solubility of the hemoglobin of a donkey and that of the horse,, Well, that's the end of that story. Oh, one more little Landsteiner thing. After I came to Harvard in '35, I used to see Landsteiner annually because Zinsser, who was a great admirer of Landsteiner, would always invite him up once a year to give a lecture to the students, and he would always come over and see me. His son was then an undergraduate at Harvard and he would say to me, "Oh, my son is a no good; he is a playboy; he will never get into medical school; he does not study; he makes bad grades1.11 But in due time, young Landsteiner did get his undergraduate degree and was accepted as a Harvard medical student. Indeed he was a member in 1938 of my most famous class. At least it was famous to me because it seemed to be loaded with the sons of my friends' It was about three years after I came to Harvard, and I looked over the list of freshmen and I'm rather fond of telling that, were I to call the role in that class, I would have had to say, "Bloor, Clowes, Peters, Landsteiner, Van Slyke, Zinsser!"—all sons of famous fathers whom I knew well. Dr. 0.: For heaven's sake, they were all in the same class? Dr. H.: All in the same class! Well, Landsteiner did better in biochemistry than any of these other famous sons; Van Slyke and Bloorand Clowes were chemists. He graduated from college with honors; and he

Page  550550 was one of the more successful members of his class. Each year, as long as his father lived he came to Boston even while his son was in medical school, and say, "Oh, my playboy son; he will never amount to anything I" After his father died, young Landsteiner, after he'd gone into practice in Providence, brought his father's book on immunology up to date, and I had the pleasure of enthusiastically endorsing its publication by the Harvard University Press. Dr. H.: A short word about James Gamble. Jim Gamble was trained in pediatrics I think at Hopkins. At least he was one of the famous group trained by the first biochemical pediatrician-—— Dr. 0.: Dr. Rowland? Dr. H.: Rowland, yes. Jim was one of the young men who worked in the early days with Rowland at Hopkins. When he came to Harvard—I think it was with Blackfan who was another one of Rowland's group—he undertook to study the salt and water relations, particularly in children, which is such a very important problem in early life. He also became a student of L. J. Henderson, so that—though his own chemical training was meager and mathematical training poor—he was able to translate the data of the composition of body fluids and of the acid-base balance and its control into visual quantitative diagrams that were comprehensible by students and physicians. These came to be known as II Gamble-grams" and eventually Jim collected them into a small monograph

Page  551551 which he called "The Chemical Anatomy, Physiology and Pathology of Extracellular Fluid." It is nothing except an assortment or a collection of the diagrams and extended legends. Being of the Cincinnati Gamble family, Jim never had to take any salary from Harvard. Indeed he put his own money into supporting his laboratory and building a library for the Children's Hospital. Dr. 0.: Well, that book was in the hands of every medical student at Hopkins in my day. Dr. H.: He published it himself, privately for years and years. I finally got him to let the Harvard Press take it over, but he didn't want it published in any way that would be costly to the student. So that it never was put in a hard binder. Dr. 0.: It had the impression that he died at a relatively early age, did he not? No, he was either in his late 60s or early 70s when he died. He was a member of the Medical Exchange Club and everybody was devoted to Jim Gamble« He didn't take much part in the teaching because to give a lecture, for Jim, would take him weeks to prepare. Dr. 0.: He was a bedside teacher rather than a lecturer. Dr. H.: No, and he never took any active part in the clinical work, he was entirely involved in the laboratory work. At least in the time that I was there he never did any bedside teaching. He would use

Page  552552 patients in some of his lectures on pediatrics. He wrote the most beautiful English„ His Lane lectures, which he took a year to write, he wrote and rewrote and are models for other people. Another person whom I might mention briefly because of my friendship with him, was J. Howard Means. He was the Professor of Medicine at the Massachusetts General Hospital, Dr. 0.: It's a large array of titles to remember, as I remember the Harvard catalog. Dr. H«: Yes, they all have names [named Chairs ] , you see. I've forgotten what the one is at the General. Means was primarily interested, scientifically, in the thyroid gland and hyper and hypothyroidism. At least that's what he made his name in. As the senior Professor of Medicine at Massachusetts General Hospital, he of course had a great deal to do with the way the Department of Medicine was staffed and the way it was taught during all of my sojourn at Harvard. He was another born and bred New Englander with the typical Boston accent, and lived on Beacon Hill. I think that Howard Means, as he preferred being called, made his biggest contribution in surrounding himself at the Massachusetts General with a most distinguished group of colleagues—Walter Bauer, Fuller Albright, and people like that. He was very active. He was President of the Association of American Physicians and wrote the history of the first 75 years of the Association. It was published in 1961. After his retirement from the

Page  553553 Massachusetts General, which was obligatory at age 64 or 5, I guess, he became student physician at MIT--student and faculty physician— where he said he enjoyed the practice of medicine. He was a great bedside teacher. Dr. 0.: This is my impression from what I have heard. Drc H.: He loved the practice of medicine, as does Keefer to this dayc Chester Keefer has repeatedly said he wanted to be known as a physician; that was his ambition. Well, to go back to Means. He wrote extremely well and easily, and after he retired from his "private practice" at MIT, as he used to call it, he devoted himself entirely to writing and turned out a number of books, most of which I was able to get him to give to the Harvard Press for publication. Some of them were historical and some of them were on economics and philosophic problems connected with medicine. He was one of the very strong opponents to the AMA establishment. He was an active member of the famous 300 physicians who opposed the stranglehold that the AMA had on American medicine. One of the other ringleaders in this was John P. Peters--Jack Peters of Yale,, Means was also almost a professional painter. He worked mostly with watercolors, and was always delighted when his pictures would be included in the annual art exhibit at the Century Association in New York* Century Club itfs usually called. I think one of his proudest moments was when somebody bought one of these and this really made him

Page  554554 a pro. He would always paint a special painting for Christmas and his Christmas cards are collector's items. John Enders is another close colleague and distinguished Harvard professor. He's about my age. I met him soon after coming to Harvard through Dr. Zinsser. John Enders had majored in English and was headed for English as a profession. I seem to remember that he was even taking a Masters degree in English when he met Zinsser. Zinsser was so attracted to him and Zinsser made such an impression on Enders that he switched his field and eventually in 1930—which would have made him 33 years old--took a Ph.D0 at Harvard in immunology and bacteriology. He has been at Harvard ever since. I see here in American Men of Science that Zinsser had made him an assistant in the department in 1929, and he rose successively from instructor, assistant professor to associate professor in the Department of Bacteriology. When Zinsser died, then Mueller became head—Howard Mueller the discoverer of methionine among other things. Enders didn't enjoy the teaching activities that Mueller expected him to do, so they parted with mutual consent. When Sidney Farber organized a research unit at the Children's Hospital, Enders moved to this research group where he operates independently. Dr. H«: He was still an associate professor. Incidentally, he remained an associate professor until 1956 which was two years after he had received the Nobel Prize with Robbins and Weller for their dramatic work in the in vitro cultivation of the polio virus. This was his work, though he had Fred Robbins and Tom Weller with him as young assistants.

Page  555555 I am told that he would not consider the prize alonee He's that kind of man, a most modest man. Dr. 0.: This is not too uncommon at Harvard, is it? I mean a man of tremendous value and reputation may only be an associate professor and the competition is so great for professorships at that institution that you just may have to wait for a couple of years after your Nobel Prize„ Dr. H.: Yes, and it is not really quite respectable to take yourself out of the mainstream of teaching activities. Being a full-time research professor is not really regarded by the people who are carrying the ball and who are the ones who have to vote the professorships in the last analysis. Dr. 0.: Well, this was undoubtedly a factor too. Dr. H.: Though his work was perfectly respectable, nevertheless it wasn't outstanding above other people who could only do their work part time, until he did the polio business. Until it was done, well, you hardly knew it was going on. Dr. 0.: Did he have graduate students working with him? Dr. H.: No, I don't think so. He had postdoctoral fellows like Weller and Robbins. He's a member of the Medical Exchange Club. I think he was made a member about the same time I wasa as a matter of fact. He always looks as if he didn't have any money, but he was terrifically wealthy—inherited it.

Page  556556 Dr. H.: John Punnett Peters, known always as Jack Peters, was a friend of mine from the time I went to the Rockefeller Institute with Van Slyke. He had been at the hospital of the Rockefeller Institute up to the previous year, that is until June 1921, when he went to Yale along with William C. Stadie, who had also been at the Rockefeller Institute with Van Slyke„ Dr0 0.: Had Dr. Blake already gone to Yale? Dr. H.: Dr. Blake was the Professor of Medicine and acquired these two well-trained biochemically minded clinicians. Stadie continued to stay more or less as a biochemist in the Department of Medicine, and indeed many times had to be summoned from the library, where he was studying physical chemistry and thermodynamics, in order to do his clinical work. Jack Peters, however, was a most conscientious and wonderful clinician,, He applied his chemistry to his clinical activities at all times, and today this country has many men who are professors of medicine or engaged in clinical investigation who value their training under Peters above all their other experience. He was a hard taskmaster. To get training under Peters, meant that you had to learn to be a good biochemist as well as an expert and conscientious physician. Jack was, by all odds, the hardest worker I have ever known. He wrote a fine, clear hand and he kept all of his records in hand. He would work every night--often until three o'clock in the morning. We became fast friends. Shortly after going to Yale, Williams and Wilkins approached him to write a book on quantitative clinical chemistry, and Jack,

Page  557557 quite wisely, felt that this wouldn't be possible for him to do alone so he persuaded Donald Van Slyke to join him in this endeavor. Ten years later, the first edition of "Quantitative Clinical Chemistry" in two volumes--volume 1, Interpretations; volume 2, Methods—appeared, There has never been a second edition of this book, although ten years after the first edition, Dre Peters brought out, with some help from Professor Hugh Long, a second edition of part of Interpretations, but this suffered greatly from Van Slyke's not having had any responsibility for it and it was not of the same quality or standard of the first edition. Dr« Ooi Was there any reason why Van Slyke wasn't involved? Dr. Ho: Oh no, no, they were trying to bring out a second edition and all of us would pitch in and try and help revise. Even McLean approached Van with the idea that, just in order to get this new edition done, he and I and anybody else that Van wanted would be glad to take over the responsibility of whipping the chapters into final shape so that they didn't get bogged down being continuously revised by Peters and Van Slyke. They would ship the chapters off to each other, but by the time it got back there*d be more to do or other things to add and they never could get a chapter finished. It was bad enough in the first edition; this is why it was so delayed. But the second edition never got off the ground because Peters would not agree to our having--McLean and I--having the final word on the chapters. He was a purist.

Page  558558 But Jack Peters was a man of great conscience, too. He was the son of a minister, a bit of a martinet—at least so far as his departmental unit was concerned—and he had no hesitation in voicing his criticism of and to other people whom he thought were holding the wrong ideas whether it was politics or religion, science or medicine. Indeed, it was notorious that in any discussion of any subject he would open his sentence with, "Yes, but--——I" [Side II, Reel 16] (May 9, 1968) Dr. H.: It was impossible to have a discussion on any subject with Jack in which he could not find some fault. This was his way of life. He and his wife, Charlotte, who also served as John Fulton's librarian, customarily would make a trip to Boston once or twice a year and stay over a long weekend with us, arriving Friday night and leaving late Sunday. Jack would bring a large briefcase packed full of data and partially completed manuscripts, and from the time he arrived until the time he left—except for our periods of eating—he would discuss these data or this manuscript with me and if I agreed with everything, he would disagree with my agreement1. He was always trying to find exceptions to the application of the Donnan equilibrium between serum and cells, I would try to impress on him that if there was such an exception, it would violate the second law of thermodynamics and since water never ran uphill it couldn't possibly be. But he would find clinical cases in his clinical experiences, where it was perfectly true, our theoretical formulation did not fit the facts, and since he

Page  559559 was a meticulous and very critical analyst and all his people were, you had to believe his facts. Well, this did lead to the discovery that just taking into account the hemoglobin and the cations was not enough to account for the existing distribution of chloride and bicarbonate. There were changes in the organic phosphates which were not diffusible through the red cell membrane and they had an influence on the distribution of diffusible ionsc This does not mean a violation of the second law of thermodynamics, however, nor that the Donnan equilibrium does not apply. Well, this is just an example of the sort of discussion that we would have. Sunday afternoon, late, he and Charlotte would pack up and get in their car at our Brookline home and Jack would say, "Oh my, Baird, I feel so refreshed; this has been the most restful weekend I've had for months!" As soon as they got off I would go and flop onto the bed because I was absolutely exhausted by this weekends experience! (Laughter) He was a terrific tennis player; he was very slim, very wiry. Dr. 0.: Yes, from the picture he looked—white flannel pants and white shoes--he looked quite athletic. Dr. H.: Oh, you've got that; that's a nice picture. You want to preserve that. Another instance, at the height of the rebellion of the famous "300" distinguished clinicians who had formed this committee to oppose the

Page  560560 AMA establishment; it seems they had recruited Elliott Cutler (Prof, of Surgery) as a signer of this proclamation and the AMA had started a backfire committee and he had also signed the AMA's statement Well, since Soma Weiss had been in charge of recruiting the Harvard people and Jack was the Secretary of this rebellious group. Jack promptly came up and stayed at our house. I arranged for Soma to come over the next morning, Sunday morning, and for Elliott to come over. He lived in Brookline. Though Elliott had signed both statements, when Soma explained what he had done, Cutler said, "Oh well, I'll resign from the AMA's." He did officially resign from the other one. But this wouldn't satisfy Jack so after our breakfast we turned the dining room over to Jack Peters and Elliott Cutler and Soma Weiss, but I stayed in my adjoining study with the door not completely shut so I could hear what went on--or I did hear what went on--because I knew it was going to be amusing. And Elliott, in his blustery way said, "Well, there's nothing to worry about," he said, "I didn't mean to sign that other. I didn't know what that was all about. I just signed without thinking, and now I've resigned from it so I don't know what all the shouting is about." And Jack would say, "Yes, but you did sign!" He wouldn't let him off the hook. So pretty soon Elliott got so darned mad at Jack, he said, "Well, I'll resign from yours and I'll sign up with the other!" (Laughter) And then in the Spanish Civil War, Dr, Cannon who always took the sides of liberal affairs, and Jack were in the thick of forming a committee to help the Spanish Loyalists or Republicans.

Page  561561 They did this in good faith, I think perhaps before there was known to be any Russian Communist help. But at any rate, there was an American committee to help the Spanish Loyalists. Cannon was the chairman and Jack was the secretary and they continued to do everything in their power to helpc Dr. 0.: I imagine Henry Sigerist was involved in that. Dr. H.: Oh yes. At one stage, there was a report that they were suffering from pellagra and that they needed nicotinic acid. So they took up a collection to buy a kilogram of nicotinic acid to send to the Spanish Loyalists and people and they collected a dollar from me. Unfortunately, the New York Times published a list of all those who contributed and to this day, it's in my dossier as having been mixed up with the Spanish Loyalist Party0 I've had to live this down every time I was investigated. Dr. 0.: With all your government clearances. Dr. H.: Yeah. And the, of course, during the McCarthy period the Public Health Service decided that they'd have to get clearances of their consultants. Jack wasn't cleared for being on even an advisory committee, a study section of the Public Health Service. Dr. 0.: On the basis of this Spanish Loyalist support? Dr. H.: On the basis of this one thing, the Spanish Loyalist activities Well, Cannon hadn't been cleared during World War II for this. He had

Page  562562 to resign as Chairman of the Committee on Shock of the National Research Council because he couldn't get clearance. This was pretty ridiculous, of course. But, then this happened of course during the McCarthy era and Jack is so damned stubborn, you see, he wouldn't take this. So he requested a hearing and of course took lawyers and that sort of thing, so funds were taken to help his defense of this, and he won. He was exonerated, but it was quite late in his life, shortly before he died. This hurt him very much because he had been a volunteer in World War I with the American Ambulance Service. He was a captain or something all through World War I in the Medical Corps. There is no questioning his loyalty in any sense of the word. It's such a good example of what a terrible thing "witch-hunting" can be Dr. 0.: Well, this is very interesting, I hadn8t realized he was caught in that web. [Pause] Dr. H.: A few remarks on Hsien Wu might be in order. Or Wu Hsien, as he would be called in China. He was the first, and for many years, the only Chinese to be made head of a department at the Peking Union Medical College. Dr. 0.: This was after his training in this country? Dr. H.: This was after his training in this country. He came from an important Chinese family of the old school in Fukien province and

Page  563563 he was given a classical Chinese education. This was followed by going to Tsing Hu University in Peking. Following this Western education, he came to MIT and earned an engineering degree—I believe in chemical engineering. Incidentally, it was while a student at MIT that his fellow students dubbed him "Tommy," and his highest compliment to me, when I was with him in Peking in 1930, was to ask me if I wouldn't call him "Tommy" because he felt the years at MIT with the weekends climbing mountains in New Hampshire and so forth, were the happiest years of his lifec His period at MIT was followed by graduate study in the Department of Biological Chemistry at the Harvard Medical School under Professor Folin. It was as part of his thesis that he, with Folin, worked out a system of what was then called a system of blood analysis. This was the combination of many other studies made previously by Folin but adapting them to ones being able to make all of the analyses one might need for clinical evaluation on the same sample of blood. This involved working out a proper filtrate--it turned out to be a tungstic acid filtrate on whole blood or plasma—and then adapting the methods that would be applied to this filtrate for the determination of blood sugar, creatine, nonprotein nitrogen, urea, uric acid, and the various other things that one could do at this time, except for CCLs and pHs which had to be done directly. Well, this was known as the Folin-Wu blood sugar method which was adopted practically all over the world. These were all adapted to determination by the use of the Duboscq colorimeter which Folin introduced to this country.

Page  564564 Dr. 0.: It seems to me we used it in biochemistry in Dr. Clark1s course. Dr. H.: Yes, I'm sure you did, because until spectrophotometers or photometric colorimeters became available, that was the main method that one had for quantitative determination of body fluid constituents. Dr. 0.: Is this the one with the graduated scale and two prisms that we used to determine creatinine? Dr. H.: Yes, that's right. Oh, I should have mentioned creatine and creatinine in connection with the Folin-Wu filtrate. Dr. H.: Well, as soon as Wu got his degree, he was by all odds the best Western-trained Chinese biochemist. Indeed, by any standards he was top-notch. He was made head of the Department of Biochemistry for the Peking Union Medical College as soon as it was founded. And he was there as head of the department until the Japanese took over in World War II, during which he was able to escape and came to this country. But his family couldn't follow him until after the war though they managed to get out of Peking. His wife was the daughter of a very wealthy Shanghai silk exporter. Dr. H.: He had five children and they came to this country. He spent some years after the war as an Acting Head of the Department of Biochemistry at the University of Alabama and then having retired from that, they settled in Boston. He lived close to us, and we saw a great

Page  565565 deal of them. He used to come to the department frequently. He died in 1959 after I came out here. Dr. 0.: He was still living in Boston? Dr. H.: Yes. His wife, who was trained in nutritional biochemistry at Wellesley, is working now for the United Nations, whatever the children1s bureau is called there, on nutritional matters. One of his sons is in Pennsylvania and the other, I believe, at MIT, probably professors by now. I don't know what's become of the daughters. In China, at least in my day there, the sons alone got names; the daughters were no. 1 daughter, no. 2 daughter, no. 3 daughter« They of course had names; they had Christian names but not Chinese names. He was a mixture, a great mixture of East and West. He walked like a Chinese grandee with his toes pointed out, and we once climbed the Kleine Scheidegg in Grindelwald. With his pointed shoes and his toes turned out, I never saw how he got up there. Dr. 0.: It's not quite the way you normally climb a mountain! Dr. H.: The year we were in Peking was the first time I suppose in centuries that the Forbidden City was open to the public. As he and I went through the throne room one day—he always carried a cane and wore a fine sable hat, and it was in the middle of winter so he needed that fur hat, I had a fur cap too--he made a gesture to the attendant there, to take down the rope that was across the throne. He had an authoritative way you know. So the attendant took down the rope and

Page  566566 he climbed up on there and as he sat there you could just see it going through his mind, "By gosh, I could be the Emperor of this nation!" He had a combination of Chinese and English that he used around the Laboratory which his technician and secretary could understand, but nobody else. Because his English was perfect but being from south China, he never spoke Mandarin perfectly—he had a southern accent and strange inflections. One day we were out "Tunghsihing", as we said. That's a made-up word, "Hsih" means "thing" in Chinese. Wu had never stopped himself, but I wanted to get some curios and so forth, so that he took me--I think the first time probably reluctantly--after we finished an experiment, about 4 o'clock one afternoon. From then on he'd say, "Well, let's get started early so we can get through and go "Tunghsihing". He'd discovered it was great fun to prowl around and bargain for things which had been below him to do previously. He wouldn't have done this with Chinese colleagues. But in my presence it was perfectly all right to do it, and he just loved it. He became an avid shopper. He'd bring all sorts of stuff home. He even got me to go to auctions with him and he'd buy so many things, that Daisy, his wife and business manager for the family, would make him take them back the next day. The auctioneers didn't want to or didn't have to, nevertheless, they were scared of Daisy, so they took them back. Well, one day we were shopping around--by then I'd learned a little of what we call "kitchen Chinese". While I was bargaining for something with the proprietor, he said to me, "What nationality is he?" pointing to Wu who was prowling around in another part of the shop; he couldn't understand his Chinese!

Page  567567 Well, Wu was internationally known because of his association with Folin, I suppose, and it was sort of amusing to visit foreign laboratories with him in 1932. I remember particularly going to Abderhalden's laboratory—he was well along in years. Abderhalden was so surprised to find that Wu was one person, he'd always thought Folin-Wu was one person. Because his name was Wu and because he'd been associated with Folin and my name was Hastings and had been associated with Van Slyke, we found a warm welcome wherever we went. (Pause) Dr. H.: Dr. Rufus Cole, the Director of the Hospital of the Rockefeller Institute, lived well into his nineties, was a person who left his mark on American medicine not because of his personal scientific contributions, but because of his selection and training of men. He was an Osier student from Hopkins and had been selected by Dr. Flexner and Dr. Welch to head the Hospital of the Rockefeller Institute when it was inaugurated in 1910. He carefully made the proviso before he accepted this responsibility of being Director of the Hospital, that for any one year he would have complete responsibility as its administrative head. In other words, Flexner couldn't do anything within any one year that was contrary to what Dr. Cole wanted to do, although the hospital was an integral part of the Institute and Dr. Flexner was the head of both parts. But this made it possible for Dr. Cole to set the tone, the standards, and the way that he wanted to develop the Hospital of the Rockefeller Institute, without interference from a higher authority. I think they had altogether the capacity for 50 beds in the hospital,

Page  568568 but I don't believe they ever had more than ten or twenty patients in at any one time, and they concentrated on just a few diseases. Dr. Cole's interest was pneumonia and Dr. Alfred Conn's interest was cardiovascular disease; Dr. Swift's interest was rheumatic fever and Dr. Van Slyke's interest was first diabetes and then nephritis. Dr. Cole selected two young men to work with him, A. R. Dochez and Oswald T. Avery. They are the ones who developed the typing of pneumococcus; they're the ones that developed the type specific anti-pneumococcus serum. Dochez kept a connection with the Rockefeller Institute even after he went to Columbia and, indeed, kept a horse there--Dochez's horse. It was this horse that permitted him to prove that scarlet fever is due to streptococcus and to develop an effective anti-streptococcus vaccine, though the Dick's get credit for this. Avery stayed on until he retired from the Institute. He made the study of the pneumococcus his one and only activity, his one and only interest; he studied it in all its ways; he lived and breathed it morning, noon and night. He is responsible for bringing Heidelberger into the study of the capsule of the smooth pneumococcus and finding out its chemical composition. He was responsible for studying the other kinds of proteins and phenomena which, though he wasn't much of a chemist himself, he knew the kind of phenomena that needed to be explained and resulted in his discovery of—along with MacLeod and McCarty--the transforming factor which of course has turned out to be DNA. Everybody pays homage to this work as the beginning of all modern genetics at the molecular level.

Page  569569 Dr. Cole picked the senior people and picked the junior people that came to the hospital, even the assistant residents. They were M.D.s. He paid as much attention to his impression of their personality and character as anything else. He set high standards for their behavior and their attitude toward medicine. He brought the teachings of Osier to the Hospital of the Rockefeller Institute. He was an avid student of the history of medicine and took his turn at the journal club which we would hold monthly. Everybody was expected to attend; we'd all stay for dinner in the hospital dining room. We then would adjourn to the study and take turns reporting on papers. He would always report something on the history of medicine. These young men have all become professors of medicine hither and yon and I regard them as the most important product of the Hospital of the Rockefeller Institute—the men, the people. I regard one of the secrets of this was that the Hospital of the Rockefeller Institute was never more than a small group! It was a large family, but it was still a family! And Rufus Cole was the father. He kept track of what you were doing. He showed an interest in what you were doing whether he understood it or not. He also loved to paint, and right up to his last year in his nineties he painted his own Christmas card and then had it reproduced. Dr. 0.: Do you have samples of Means1 and Cole's Christmas card? Dr. H.: Golly, I always mean to keep them. I have some stored away somewhere.

Page  570570 Dr. 0.: I think it would be very interesting to preserve a collection of these as art work done by some of the medical figures. [Pause] Dr« H.: Sir Rudolph A. Peters was Professor of Biochemistry at Oxford from about 1923 to about 1954—at least over 30 years. He was the first Professor of the Department of Biochemistry at Oxford. Prior to his coming, it was simply a part of the Department of Physiology. The Biochemistry Department at Cambridge preceded it some years under F. Gowland Hopkins. Peters as a young man had taken his M.D. and his D. Phil., as they call it at Cambridge, had engaged in research with Barcroft and with Hopkins. He was the first one to make accurate measurements of the iron and oxygen capacity of hemoglobin. He is a person who was well trained in medicine and in chemistry and in mathematics. I've already recorded some of his main scientific activities, but perhaps it's worth noting some of his personal characteristics. He's very blonde and thin-skinned—I mean literally—and he used to have a sandy mustache which is now white, and he's a bundle of energy, always working wherever he goes. He is a fairly competent violinist and loves to play, so he takes his violin wherever he goes. Dr. 0. : Did he and Linderstr^m-Lang ever get together? Dr. H.: This, I don't know, but I know that whenever he goes on the continent there are a number of people that he plays with—particularly

Page  571571 in Italy and in Germany, I'm not sure about Scandinavia. Whenever I was in England, both before, during, and after the war, I always enjoyed spending as much time as I could with Rudolph Peters. Rather soon after he went to Oxford, he took up the study of intermediary metabolism and its relation to certain vitamin deficiencies, particularly vitamin B-, , and made the discovery that in vitamin B^, or thiamine deficiency, the pyruvic acid in the blood accumulates. This led him to study the effect of the absence of thiamine from the system on specific chemical reactions that were required. That led to the discovery of the fact that thiamine must be converted to thiamine phosphate, the coenzyme for decarboxylations of all kinds. You can carry the metabolism of glucose down as far as pyruvate, but if there is no thiamine phosphate present—even though the enzyme decarboxylase is there—it cannot act and therefore the pyruvate accumulates. Due to this interference with metabolism, the animals, in his case pigeons, develop an abnormal metabolism in their central nervous system which leads to a most striking opisthotonos, head retraction on the part of the pigeons, and eventual death. From his further studies of metabolism one might say that this was the first step towards the discovery of the Krebs tricarboxylic cycle, and has always seemed to me to have been worthy of sharing the Nobel Prize with Krebs. I made an effort to see that this came about but Krebs actually received the Nobel Prize in company with Lipmann, who had been mostly responsible for the discovery of acetyl CoA, which was the first decarboxylation product of pyruvate.

Page  572572 Dr. 0.: Fritz Lipmann? Dr. H.: Yes, Fritz Lipmann. At any rate, Peters, in the course of years, made many important contributions to intermediary metabolism, to providing the real chemical basis for either the deficiency of special substances like vitamins or the effect of adding special competing substances like fluoroacetate. This approach to biochemistry led him to refer to all such things as biochemical lesions. I would say that his entire scientific life, since going to Oxford, has centered around the study of biochemical lesions, which is another way of describing the chemical basis for specific abnormalities which really accounts, chemically and specifically, for the pathological things which take place. Since I've already recorded his work on British anti-lewisite and on fluoroacetate, I guess I'll let it go at that. I'm sorry that I'm not prepared to expand on this, on the man himself, in more detail at the present time because I feel he's one of my very good and intimate friends. He's coming to La Jolla at the end of this month to be with us. (Pause) One of the great memorable things that happened to me at the Rockefeller Institute was to become closely acquainted with Jacques Loeb. He was one of the great biologists of the latter part of the nineteenth century and the first part of the twentieth century. He was in his

Page  573573 sixties when I went to the Rockefeller Institute, and died in 1924 before he retired. He was very vigorous and intellectually as active as he'd ever been. After having spent so much of his life as strictly a biologist, it amazed me to find that he went into a pure chemical problem about age 60. He undertook to study whether or not proteins were individual chemicals and subject to the laws of chemistry or not, because up to that time, they were regarded as colloids with undefinable specific characteristics. Nobody had had any crystalline protein except perhaps those who worked on hemoglobin, and molecular weights of proteins were not yet something which one accepted. I suppose the very name deterred you from trying to think of them as individuals, because since life was the beginning and since I suppose protein had its origins in the beginning of life, I suppose that the very name must have had vital implications. At any rate, Jacques Loeb and his then assistant, about my age, John Northrop, were subjecting the simplest protein that we knew at that time, gelatin, to simple reactions. They found that the proteins combined in a way with such ions as copper, in a reproducible and chemically reasonable way that one might expect if proteins were subject to the same sort of reactions as other not so large molecules« Their most important tool was to change the pH which would change in a predictable way the amount of copper the protein would combine with. They would even set this up in test tubes so you could see it with your eyes, and they extended this to silver and other combinations between gelatin and salts. They were able to show that after a certain pH they combined with anions

Page  574574 instead of cations so that there must be a crossover point. Mind you, this was before you had even electrophoresis methods to study such things; all this came easily afterwards. But at this time proteins were not accepted as respectable chemical individuals. I remember one night that the Society for Experimental Biology and Medicine had its monthly meeting at the Rockefeller Institute. It was their habit to meet at different institutions. I think Van Slyke and I were on the program with a fifteen minute paper, and Loeb reported some of his and Northrop's more recent experiments. At the end of Loeb's paper, a biochemist named Harris, who had gone into the business of making purified casein, etc., commercially, got up and said,'I'd like for Dr. Loeb to describe how pure his proteins were that he was using in these experiments." Harris was, I think, wanting to do a little advertising for his company. Oh, Loeb also used casein and I think it was the casein from milk that Harris also was marketing. Well, Jacques Loeb hadn't the foggiest idea how he had prepared the casein, but he made the mistake of trying to mumble something about how it was prepared, but Northrop had done all that--Northrop or Kunitz--and he never paid any attention to its purity, I'm sure. Well, after failing to satisfy Harris, who said something rather disparaging then about his inability to tell how pure his casein was, which you know, sort of had the affect on the audience of throwing doubt on the work. I got up to leave a little early to catch my train, so I went to the coat room to get my coat and hat. I was in the rear of this coat room, picking

Page  575575 it out when Harris came along also after me and he was in the front of the coat room and Loeb had followed him out, and this old gentleman--this firey old gentleman said, "Young man, if I'd known what you were after I would have thrashed you within an inch of your life!" (Laughter) Oh, Jacques Loeb had his prejudices. He couldn't stand the colloid chemists of the day; Wolfgang Ostwald, son of the great Wilhelm Ostwald, was a colloid chemist, and the mere mention of his name at luncheon would be enough for Loeb to say, "Oh, that fellow! Oh, no, never mention him to me, it spoils my digestion!" There was another one at the University of Cincinnati, Martin Fisher. He was professor of physiology and, in many ways, was very smart, but he was a Wolfgang Ostwald follower and being in this country he kept running afoul of Jacques Loeb. So we were always counseled never to mention Martin Fisher's name, otherwise Loeb would get up and leave the table. Well you know, the people who were originally part of the German tradition of science, had violent likes and dislikes. Dr. 0.: This was not uncommon then? Dr. H.: Oh no, I mean it is true to this day in chemical laboratories. If you're a young man working in somebody's lab you must never be caught talking with a young man from a rival laboratory. One of my friends was working in Ruzicka's lab in Zurich. There are two great steroid chemists there, Reichstein is the other one, and he's just as famous. When my friend came back I said, "Did you see much of Reichstein?"

Page  576576 He said, "Oh, no, I soon found that if I was in Ruzicka's lab, I must never go visit the other lab and vice versa!" This is today in Switzerland. Dr. 0.: I can understand this in industrial chemistry or something where everybody's worried about losing their secrets, but in academic life it seems rather absurd. Dr. H.: Well, I suppose they're supported by industry. Well, I don't know the basis for this; all I know is that this is fact. And this was true at the Rockefeller Institute. Haven't I already told about Rous and so forth in the Institute proper? Dr. 0.: Well you mentioned that Carrel and Murphy did not get along. Dr. H.: However, Dr. Cole's principle in the hospital was "everybody works with open doors" so that it was great fun to exchange your successes and your failures with your colleagues. This was just as opposite as it could be from the way things were in the Institute proper.

Page  577577 (Tape 17, Side I) (May 9, 1969) Dr. H.: I might add in connection with Dr. Jacques Loeb, that while I was at the Rockefeller Institute I became acquainted with his son, Robert Loeb, who was even then becoming interested in electrolyte problems in relation to disease and I had an opportunity while we were working with a calcium problem to talk with him frequently about his first interest and first attempt to study the state of calcium in blood plasma. It was in this connection that he showed, for the first time, that if one acidifies blood plasma and then dialyzes it, one can dialyze out most of the calcium, whereas if you do it at normal pHs, the calcium refuses to dialyze out. This was a very early forerunner of the now-recognized fact that the calcium ions and plasma proteins are in equilibrium as a calcium-protein salt with a definite ionization constant. Bob Loeb is, as he's known, about my age--—- Dr. 0.: He is the author of a very fine textbook which I used. Dr. H.: Yes, and became a Professor of Medicine at Columbia University until he retired and is now one of the elder statesmen of American medicine, much in demand in committees, various activities in Government in medical health problems. Dr. 0.: Leo Loeb was Jacques brother, is that not correct? Dr. H.: That's right. He was an endocrinologist in St. Louis.

Page  578578 Dr. 0.: At Washington University. Quite a medical family. (Pause) Dr. H.: Rene Dubos came to be the assistant of Dr. Avery--"the Fess" as we called him--in 1925, the year before I left the Rockefeller Institute. I became acquainted with him that year. Since he wanted to study the metabolism of pneumococcus I gave him the Warburg machine which Dr. Flexner had given me. Dr. H.: Since I had only used it one year—though I wanted to take it to Chicago with me, and wrote back from Chicago to Dr. Avery, "could I have it," he said that Dr. Dubos was actively using it. Dubos had joined Avery at the Hospital of the Rockefeller Institute to engage in the type of research that he had already started while working with Dr. Waksman at Rutgers. IBm not sure how long Dubos had been in this country. He was French, had a French accent which he still has. Waksman was a distinguished student of soil bacteria and, I think I'm correct in saying that he had devised this so-called "flower pot" method of developing bacteria which could create defenses against other bacteria. As I understand it, you took a bunch of dirt from a New Jersey bog and you fed it bacteria that you'd grown in the laboratory and then youfd see whether or not you could culture strains that were resistant to something in the flower pot. They call it a "flower pot" technique, but whether they actually used flower pots or not I don't know. But you see Dubos did develop, in this work with Avery, gramicidin and tyrothricin. These were early antibiotics. But they were so toxic

Page  579579 that they could only be used and I guess are used still as local applications. These preceded penicillin and the present antibiotics. They were pre-war developments. Even prior to that, however, during the first year or so that Dubos was with Avery, he undertook to study the pneumococcus and its properties, and defining not only the pH limits of its growth, but its oxidation reduction potential limits as William Mansfield Clark might have done. It was during this period that I first became acquainted with Dubos. I saw him from time to time after I left the Institute, but our real intimacy occurred during the two years that he was at Harvard as a professor. I think he was called a Professor of Comparative Pathology and Parasitology. It was an endowed professorship, full professorship, but not a head of a department. Dubos came to Harvard from the Rockefeller Institute in high hopes that the academic life would be much richer than his circumscribed life at the Rockefeller Institute where he had no students and where there was very little discussion between one colleague and another. Dubos is an intellectual who likes to discuss the arts and humanities. Dr0 0.: He's an extrovert. Dr. H.: Yes, and a philosopher of science. Well, unfortunately, these two years occurred in the middle of the war when those of us who hadn't gone off to the wars were doing double duty in some way or other.

Page  580580 Indeed, he soon found that as a Professor of Parasitology, he, to his surprise, was expected to give the course himself to the medical students and the students of the School of Public Health. He had no idea he was going to have a big teaching load. The combination, the absence of his colleagues—and even when they were there too busy to sit down and be leisurely--plus a teaching load which made it almost impossible to get his research going, made him vulnerable to Herbert Gasser's offering him a job back at the Institute at the end of two years, which he took. We were all terribly sorry to have him leave and I have the feeling that if he'd stayed another year it might have all worked out the way he had anticipated. But, as Dochez and I used to say sometimes during the war years and particularly in connection with Dubos when this happened, "Well, it takes three years to get the Rockefeller Institute out of your system, and if you don't stay away three years, you'll never give the other place a chance," because this was my experience and this was his experienceI Any time within the first two years, I was ready to go right back to the Institute; I couldn't stand the unprotected life that you had to lead out in the cold, cold world, and fight for everything. Since then, Rene and I run into each other as regularly as we can at the Philosophical Society, lectures, or some place. I find him one of the wisest and most stimulating men intellectually in the sciences today. I am very pleased with the fact that I was able to get a book

Page  581581 out of him, The Microbial Cell, as a publication of the Harvard Press in a monograph series. Dr. 0.: You really were a go-getter for that outfit. It sounds like you used to--the second you heard one of these people was writing a book you'd get in the mails or on the phone. Dr. H.: Well, I played both ends against the middle as I think I told you. As chairman of the Dunham lectureship committee and a syndic of the Press, it gave me a kind of an "in" particularly when I was chairman of the monograph series, too--Monographs of Medicine and Public Health. It simplifies one's life if one is pooh-bah enough. Dr. 0.: Pooh-bah? Dr. H.: Pooh-bah. Didn't you ever go to the Mikado? Dr. 0.: Yes, but not for many years. Dr. H.: Pooh-bah? I guess he wasn't Lord High Executioner, but Pooh-Bah was sort of like I guess Churchill must have been during the war when he took the different ministries unto himself. You can run things so much easier if you simply have a whole bunch of hats, and keep them on one hat rack--within limits. I'm getting silly, as you see. You mustn't let Marty Cummings see how I'm wasting his time and cut me off with a shilling. Dr. 0.: I can assure you he won't think that.

Page  582582 Dr. H.: I want to add something to Rene Dubos because I just happened to open this volume of letters that I received on my fiftieth birthday, to the one sent me by Rene Dubos. He wrote it in the form of a quotation from an ancient philosopher, but the quotation is strictly Rene's invention. Though I won't quote this whole page, it starts, "A young soldier returned from the wars, came to the learned man, a philosopher in the East, asking the formula for wisdom and happiness," and then for three paragraphs, Rene goes on in a rather amusing way makes reference to some of my activities — this being the year 1945--so that my Washington activities were over, November of !45, or about to be. "Reveal to us, dear and respected master, the secrets which were unveiled to you by the goddess of power in the deep and mysterious temples of OSRD; tell us of the DDTs, penicillin, seasickness powders and antishark ingredients which doubtless gave you smiling mastery over the furies haunting the rest of the mortals." And then further, in terms of the master, "Learn to know and control your gaseous phases and the tensions of your inner fluids; discover and maintain the subtle equilibria between your intra and extracellular atmospheres; the salts of your body kept skillfully in their place and yet properly blended, will assure the diversity and harmony of life; then watching without despair the eternal folly of men, you will be amused by their various antics and will even enjoy participating in them." That last line I think describes Rene's secret of living; I think he does just that.

Page  583583 Since there may be no other record in American archives about Professor Vladimer Lebedenko* I'd like to spend a moment on this fine man. During my active war years, particularly after having made the trip to Russia in January '44, I had frequent meetings with Dr. Lebedenko. He was the representative of Russia for the Red Cross and for their Ministry of Medical Education and Medical Research. He was, if you will, V. Parin's opposite in the USA and he was also, as I say, the official representative of the Russian Red Cross and Red Crescent. In normal times he was a neurosurgeon, and I'm told a very good one. When I returned and had, through our State Department, made arrangements so that we could keep up an exchange of information, he arranged for me to transmit things directly through our State Department to our Embassy in Moscow. There were two medical officers--we had no science attache--but there was an Army medical officer and a Navy medical officer in the Embassy there and they kept up the contacts I had made, particularly Commander Lang from the Navy who had gone with me to most of our meetings with the Russian scientists. Dr. 0.: Yes, he was on that film we saw this morning. Dr. H.: Yes. Well, so the opposite of that was that things could be transmitted to us to the Russian Embassy in Washington and then Lebedenko was to contact me. I was officially designated as the contact with their Embassy on Medical Affairs. This was all officially done, as one had to do even in those days. He didn't speak much English, though he was studying it, to begin with, but before the war was over in a year

Page  584584 or so, he was able to get along with me without his interpreter. But to begin with, he had to talk through an interpreter. I remember the first time when I had asked to have a conference with him, he joined me at the old Cosmos Club without his interpreter. He wanted to try out his English. By then we were feeling relaxed enough so he didn't mind making mistakes in front of me. I kept promising I'd take him fishing at Westport Point when the war was over, but we never got to do it because just as soon as the war was over he went back. Dr. 0.: He was recalled to Russia. Dr. H.: He was recalled to Russia and died shortly after of a coronary occlusion. But he loved the United States. He loved to hunt and fish so he told me--a very lovely fellow. I was quite touched by his telegram which he sent on this occasion of November 20, 1945, because it was very shortly before he returned to Russia and I never saw him again. Among other things he said, "When you look back and sum up what you've accomplished in half a century of living, I find particular pleasure in doing this because you were one of the first representatives of American medicine to visit the Soviet Union during the war, and because you found a common language and established warm, friendly and active mutual relations with the scientists of the U.S.S.R." I was very pleased and am pleased to value this statement from Professor Lebedenko. He didn't have an easy time. At one stage, our National Research Council Committee in charge of getting better rodenticides, decided that since

Page  585585 the Russians had the reputation of having done a great deal of good research on rodenticides, that one of the things they should get was a bibliography of the best and recent work of Russian scientists. By then my channels were well-known and so I was officially asked to get this from Russia. I immediately got ahold of Lebedenko and officially transmitted the request to him. He was delighted to be of use. He frequently said, "How can we be of help to you," and he said, "Yes, I'll get that right off by pouch." A couple of weeks went by and I ran in to him and I said, "What about that bibliography?" He said, "Well, I haven't heard anything about that yet. I didn't hear in a week, I cabled and I hadn't heard from that." So another couple of weeks went by and so I called him up on the phone. Indeed I decided I wouldn't risk his misunderstanding or anything, and I asked if I could come over, so that actually it was the first and only time I went over into the Russian Embassy. Dr. 0.: It's the same one I think they have now on 16th St. I don't think it has moved since then. Dr. H.: Well, I don't really remember where it was that I went to, but I know that I went to his office and said, "What about this? You said you'd get this bibliography and that you'd be glad to do it." He said, "Professor Hastings, I've done everything I know how to do to get this information. I'm so embarrassed. But you know, the truth is, they not only don't answer me on this, they don't answer me on anything'." He was so pained. Well, I believe him because it's unbelievable to an

Page  586586 American as to the mixture of iron autocracy and inefficiency; itfs a blend of these two things. I must record this illustration. When I was in Moscow in '44 and visiting Prof. Parnas one Sunday evening, after dinner in their Metropole Hotel room, he said, "I have something to show you." He brought out a scroll like a Harvard honorary doctorate diploma on very fine paper. Well, I couldn't read any of it except "V. Parnas" at one spot, but I could also see scribbled at the bottom, "V. Molotov." and I said, "What else does it say?" He said, "It says that Academician V. Parnas is entitled to the use of an automobile and driver to take him from his residence to his laboratory and home. Signed V. Molotov." I said, "How in the world does this come about?" This was after I'd visited him in his Institute which was hell-and-gone out on the outskirts It was one of the institutes that had been hit by the Germans but it hand't been repaired yet. Parnas said to me: "Well, as I told you, my wife and I are extremely grateful to the Russians for having saved our lives and I must say, I shouldn't complain because they made me a member of the Academy. They treat me as an academician and insofar as they could have provided me with laboratory facilities even though they are not very good yet." But he said, "You know, at my age," and I think I've described him as a tall, well up in years 65 or 70 you know, and heavy set man, he said, "at my age and my size, I really find that I spend almost all my energy getting from the hotel to the laboratory and from their home, because there are so few busses running and even when you can get on one, you have to hang on the outside." He said, "I take

Page  587587 a couple of hours in the morning and a couple of hours in the afternoon to get back and forth. One of my colleagues noticed that it was really sapping my strength and he said, 'Well why don't you get them to bring you by car?1" Parnas said, "Oh, no, no, I wouldn't know how to go about it anyhow, I wouldn't know who to ask, 'oh he said that's very simple, all you do is write a letter to Molotov and you take it to the gate of the Kremlin where there is always a man on sentry duty to receive requests from Soviet citizens.'" "Well," he said, "I thought that's very strange so I didn't do it for awhile, but it got more and more difficult particularly as the winter came on here, and I thought well, there's nothing to lose." So he said, "I did, two weeks ago take such a letter over and deposited it there at this gate with the sentry and yesterday I get this." Signed by the Foreign Minister, Molotov. Dr. 0.: I think so. He's the one responsible for signing cards I Dr. H.: It is inconceivable to us to have such a thing happen, and still it was in the midst of a war. I think that one little story told me more about Russia. Well, they didn't think it was funny. Dr. 0.: Parnas didn't think it was amusing? Dr. H.: No. Parnas thought it was very strange; he couldn't understand it. But Russians didn't think that this business was strange at all. No, it was all right. It's almost as if rugged individualism could co-exist in a totalitarian state.

Page  588588 Dr. H.: Well, you don't get any feeling of Communism over there you get a feeling of a ----- Dr. 0.: Police state? Dr. H.: Police state. A dictatorship. It may have changed a great deal, but certainly under Stalin it was a dictatorship. There were so few people that even were in the Communist Party, and that was the only party there was. What Stalin said went as far as these few people who were allowed to call themselves Communists, and then everybody else was obliged to have no thoughts otherwise, in what they did, whatever that went on--whatever was needed to be done. So the average person, I guess, just divested himself of all thought about changing things. The thing to do was to live within the framework that you were allowed to live in and if you happened to be a scientist you were lucky, because science had priorities with respect to food and lodging. If you were an Academician you even got a pass that permitted you to be out after dark. The members of the Bolshoi ballet and the members of the Academy could be out after dark. They all carried their passes, though. Well, all my thoughts seem to lead me back to Russia, that's a bad business, isn't it? (Pause) Dr. H.: Charles B. Huggins, who is the professor--! presume now of cancer research of some kind or other—at the University of Chicago,

Page  589589 but originally came there as a junior staff member of Phemister's department of surgery as a urological surgeon. He came in a very poorly paid position because Phemister had spent most of his money on three full professors. Dr. 0.: Of general surgery? Dr. H.: Well, one was Dragsted and one was Van Alien and one was Curtis in different specialties. But then he realized he'd have to cover urology and Coller had recommended this young man Huggins. But when he came, Phemister said, "Now if I give you this job you've got to do research." Dr. H.: So Charlie told me that he needed a job so badly that he said, "Oh, yes I'll do research" but really in his heart he thought anybody that did research was a little "screwball"--at least that was the way he always felt about it when he was at the Brigham. So he took on this job and the job carried with it, not only an office, but a very nice laboratory. Our school at Chicago was brand new, the laboratory was big and he had access to animals and a diener. After a month or so, Phemister called on him in his office one day and said, "What research have you got going?" and Charlie said, "Well, I've just been thinking about it." "Well," he said, "young man you'd better get at it." Because though Phemister had not done research prior to taking on this full time job, he had spent a year before he came to Chicago when he knew he was coming to this full time job with Anrep in London

Page  590590 and had come back imbued with the idea that everybody must do research. Dr. 0.: Phemister might be worth a few words too, he was a bit of a character. Dr. H.: Yes. Well, it's a good idea, maybe I'll do that. Dr. 0.: You don't see much about him, except the idolatry of his train