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Wyndham Miles NIH Oral History Collection 1962-1973
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Biography

Biographical Note

Joshua Lederberg was born in Montclair, New Jersey, on May 23, 1925, the oldest of three sons of Zvi Lederberg, an orthodox rabbi, and Esther Schulman, a homemaker and descendent of a long line of rabbinical scholars. His parents had emigrated from Palestine the year before. Lederberg's family moved to the Washington Heights area of upper Manhattan when he was six months old. Zvi Lederberg originally envisioned that his son would pursue a religious calling as well. Despite his Old Testament name, however, Joshua felt drawn to science at an early age, stating in a homework assignment at age seven that his career aspiration was to become "like Einstein," to "discover a few theories in science." Father and son later reached agreement that science, like religious study, offered a path towards enlightenment and truth, and was thus a worthy pursuit.

According to his own recollection, Lederberg has been guided throughout his life by "an unswerving interest in science, as the means by which man could strive for an understanding of his origin, setting and purpose, and for power to forestall his natural fate of hunger, disease and death." Meyer Bodansky's Introduction to Physiological Chemistry (1934) was his most prized Bar-Mitzvah present, the Washington Heights branch of the New York Public Library his sanctuary during adolescent years in which, by his own admission, by his own admission, he was lonely for "intellectual sparring partners." There he read hundreds of works in the sciences, mathematics, history, philosophy, and fiction, among them Paul de Kruif's The Microbe Hunters (1926), a book that portrayed the work of early bacteriologists like Pasteur and Koch as a heroic quest for human betterment. As Lederberg remembers, the book "turned my entire generation toward a career in medical research."

Lederberg finally found academic peers at Stuyvesant High School, a public school that specialized in science and technology and was open by competitive entrance examination to talented students (only male at the time) from all parts of New York City. If he had earlier sought to emulate Einstein, at Stuyvesant he completed his reorientation towards biology. He conducted his first experiments at the school, in cytochemistry, the study of the structural relationships and interactions of cellular components.

After graduation from Stuyvesant at age fifteen, he continued his experiments at the American Institute Science Laboratory, an offspring of the 1939 New York World's Fair and a forerunner of the Westinghouse Science Talent Search, which provided selected high school students (including fellow future Nobel laureate Baruch Blumberg) laboratory space and equipment. In facilities located in the shadow of the Empire State Building Lederberg learned to prepare and stain tissue samples by using formaldehyde, dyes, and other chemicals, techniques required to preserve and make visible the details of cell structure for study under the microscope. During these experiments he became interested in the cytochemistry of the nucleolus in plant cells, part of the cell nucleus rich in ribosomal nucleic acid. This was Lederberg's first foray into the study of the nucleic acids.

Lederberg took advantage of a $400 scholarship to enroll as a zoology major at Columbia University in the fall of 1941, where he met his most important mentor, the biochemist Francis J. Ryan. Ryan, a gifted teacher, encouraged Lederberg in his self-described "passion to learn how to bring the power of chemical analysis to the secrets of life," and introduced him to the red bread mold, Neurospora, as an important new experimental system in the emerging field of biochemical genetics. Ryan also instilled discipline in his precocious student, a trait much needed, as Ryan's widow remembered: "You could tell that Joshua was in the lab because you could hear the tinkle of breaking glass. He was so young, bursting with potential over which he had no control. His mind was far ahead of his hands."

Lederberg's career goal was to bring advances in basic science to medical problems such as cancer and neurological malfunction. At the time, an MD was the conventional pedigree for entry into biomedical research. In pursuit of a medical degree, and to discharge his military service obligation at the same time, Lederberg in 1943 enrolled in the United States Navy's V-12 training program, which combined an accelerated premedical and medical curriculum to fulfill the armed services' projected need for medical officers. He performed his military training duties as a hospital corpsman during periodic stints in the clinical pathology laboratory at St. Albans Naval Hospital on Long Island, where he examined stool and blood specimens of servicemen recently returned from the Guadalcanal campaign for the parasites that cause malaria. His first-hand experience with parasites at St. Albans helped shape his later thinking about the life cycle of bacteria.

After receiving his bachelor's degree in zoology in 1944, Lederberg began his medical training at Columbia University's College of Physicians and Surgeons. Although research was not encouraged among first-year medical students, he continued to do experiments under Ryan's supervision. Columbia's zoology department had been "ignited," said Lederberg, by news of Oswald Avery's discovery that deoxyribonucleic acid (DNA) was the genetic material, in Pneumococcus bacteria. Inspired by Avery, Lederberg decided to investigate further the genetics of bacteria, and specifically to challenge the common but unproven assumption that bacteria were "schizomycetes," primitive organisms that reproduced by cell division and thus produced offspring that were genetically indistinguishable from one another.

After initial failures in his experiments Lederberg proposed a collaboration with Edward L. Tatum at Yale University, who had been Ryan's post-doctoral adviser and who was an expert in bacteriology and the genetics of microorganisms. During a year-long leave of absence from medical school in 1946, Lederberg carried out experiments with the intestinal bacterium Escherichia coli which demonstrated that certain strains of bacteria can undergo a sexual stage, that they mate and exchange genes. This discovery, and the methods used to make it, had far-reaching scientific and medical implications. First, Lederberg demonstrated that successive generations of those bacteria that mate were genetically distinct and therefore suitable for genetic analysis. Secondly, he created a new understanding of how bacteria evolve and acquire new properties, including antibiotic resistance.

Buoyed by his success, Lederberg decided to extend his collaboration with Tatum for another year in order to begin mapping the E. coli chromosome, to show the exact locations of its genes. With Tatum's support he submitted his research on genetic recombination in bacteria as his doctoral thesis. He received his PhD degree from Yale in 1947.

Only days before his scheduled return to medical school at Columbia, Lederberg, then barely 22, received an offer of an assistant professorship in genetics at the University of Wisconsin at Madison, Tatum's alma mater. (Lederberg's initial 1947 application to the institution was questioned due to his religious beliefs. University officials were concerned he would have difficulty acclimating to Wisconsin because he was Jewish. For an in-depth account of the controversy surrounding Lederberg's recruitment consult the essay by Susan McDonough located in the appendix.) He accepted, despite misgivings about abandoning medicine, because the appointment offered a unique opportunity to pursue basic genetic research full-time. Over the next twelve years, Lederberg and his wife, Esther Zimmer, a microbiologist herself, together with a handful of postgraduate students, most notably Norton Zinder, published a steady stream of original experimental results from a small laboratory in the genetics department, then part of the university's School of Agriculture. The most important of these was the discovery of viral transduction, the ability of viruses that infect bacteria to transfer snippets of DNA from one infected bacterium to another and insert them into the latter's genome. The use of viruses in manipulating bacterial genomes became the basis of genetic engineering in the 1970s.

Scientific prominence brought with it administrative responsibility. In 1957, Lederberg helped found and became chairman of a new Department of Medical Genetics at the University of Wisconsin, one of the first such departments in the country. Following his early ambition to tie genetics closely to medical research, Lederberg in the fall of 1958 accepted an offer to become the first chairman of the newly-established Department of Genetics at Stanford University's School of Medicine, a medical school more broadly oriented towards research than Wisconsin's. His decision to move to Palo Alto was followed within days by news that he had been awarded a share of the 1958 Nobel Prize in Physiology or Medicine, along with Tatum and George W. Beadle, "for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria."

At Stanford Lederberg continued to lead research in bacterial genetics. He also pursued opportunities his new position provided to relate genetics to the wider context of human health and biology. He helped institute an undergraduate human biology curriculum, and launched investigations into the genetic and neurological basis of mental retardation as director of Stanford's Joseph P. Kennedy Jr. Laboratories for Molecular Medicine.

His fame as a Nobel laureate made it possible for him to broaden his field of scientific interests even further. The launch of the Soviet Sputnik satellite in 1958 prompted him to consider the biological implications and hazards of space exploration. Lederberg gained a place for biologists in the burgeoning U.S. space program when he publicly warned against the dangers of contamination of the moon and of other planets by spacecraft carrying microbes from earth. He explored the possibility of extraterrestrial life as a member of the National Academy of Sciences' Space Science Board from 1958 to 1974, and helped develop instruments to detect potential traces of microbes on Mars as part of the National Aeronautic and Space Administration's 1975 Viking mission to the planet.

Lederberg's role in constructing fully automated laboratory equipment for research in space led him in turn to embark on another new pursuit: expanding the role of computers in scientific research. In collaboration with the chairman of Stanford's computer science department, Edward Feigenbaum, Lederberg in the 1960s developed DENDRAL, a computer program designed to generate hypotheses about the atomic composition of unknown chemical compounds from spectrometric and other laboratory data. It was the first expert system for specialized use in science.

Throughout his scientific career Lederberg sought to bring science to bear on matters of public policy, particularly national security and arms control, as a member of several government advisory committees, such as the Pentagon's Defense Science Board, on which he has served since 1979. He worked to bridge the gap between scientists and the public, most prominently by writing a weekly editorial column on science and society for the Washington Post between 1966 and 1971.

In 1978 Lederberg returned to the city of his youth as President of Rockefeller University on Manhattan's Upper East Side. Over the next twelve years he reinvigorated the free-standing, non-departmental laboratories of which the University is made up by refocusing them on molecular biology research with clear medical applications for heart disease, cancer, neurological illness, and infectious diseases. He became University Professor Emeritus and Raymond and Beverly Sackler Foundation Scholar in 1990, when he resumed his own research into the chemistry and evolution of DNA and into computer modeling of scientific reasoning. He continues to advise government and lecture widely about developments in science as they relate to public policy and public health, in particular about the threat of bioterrorism and of both new and reemerging infectious diseases.

Among other honors, Lederberg was elected a member of the National Academy of Sciences in 1957, Foreign Member of the Royal Society of London in 1979, and a fellow of the American Academy of Arts and Sciences in 1982. He received the U.S. National Medal of Science in 1989, and the Allen Newell Award from the Association for Computing Machinery in 1995. He holds honorary doctoral degrees in medicine from the University of Turin in Italy and from Tufts University, in law from the University of Pennsylvania, and in philosophy from Tel Aviv University. Lederberg has published over 300 scientific and policy-related articles and is the editor of several books, including Papers in Microbial Genetics: Bacteria and Bacterial Viruses (1951), Emerging Infections: Microbial Threats to Health in the United States (1992), and Biological Weapons: Limiting the Threat (1999). His first marriage ended in divorce in 1966. In 1968, he married Marguerite Stein Kirsch, a clinical psychologist, with whom he had two children, David Kirsch and Anne Lederberg. Joshua Lederberg died February 2, 2008 of pneumonia at New York-Presbyterian Hospital at age 82.

BRIEF CHRONOLOGY

1925Joshua Lederberg born May 23 in Montclair, New Jersey, to Zvi Hirsch Lederberg, a rabbi, and Esther Goldenbaum Lederberg, a homemaker
1938-41Attends Stuyvesant High School, a selective science and technology school in Manhattan
1941-44 Undergraduate studies at Columbia University, leading to a BA in zoology. Examines genetics of Neurospora (a common bread mold) with Professor Francis J. Ryan
1943-45Military service in the U.S. Naval Reserve's V-12 program, a compressed premedical and medical curriculum, at St. Albans Naval Hospital, Long Island
1944-46Medical Student at Columbia University College of Physicians and Surgeons and research assistant in Professor Ryan's zoology laboratory
1946-47Research Fellow at Yale University with Professor Edward L. Tatum. Discovers mating and genetic recombination in the bacterium Escherichia coli, making E. coli available as an experimental organism for genetic research. Receives his PhD from Yale with a thesis on his discovery
1947-59Professor of genetics at the University of Wisconsin. Conducts research in the genetics of E. coli and Salmonella as well as on antibody formation. Discovers and names plasmids, particles of DNA in bacterial cells that replicate separately from chromosomal DNA
1951Discovers, with Norton Zinder, the exchange of genetic material in bacteria through viral vectors, a process he calls transduction. Their discovery has important applications in bacterial genetics and biotechnology
1957-59Founder and chairman of the Department of Medical Genetics at the University of Wisconsin
1950-1998Member of various panels of the President's Science Advisory Committee
1957Elected to the National Academy of Sciences
1958Shares Nobel Prize in Physiology or Medicine with Tatum and George W. Beadle "for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria"
1958-77Investigates the possibility of life on other planets and of interplanetary contamination as a member of several National Academy of Sciences and NASA committees on space biology, and as organizer of the Instrumentation Research Laboratory at Stanford
1959-78Founder and chairman of the Department of Genetics, Stanford University School of Medicine. Begins research in the genetics of Bacillus subtilis (1959) and in splicing and recombining DNA (1969)
1961-62Member of President John F. Kennedy's Panel on Mental Retardation
1964Together with computer scientist Edward A. Feigenbaum Lederberg launches DENDRAL, a computer program designed to emulate inductive reasoning in chemistry and medicine through Artificial Intelligence
1966-71Publishes "Science and Man," a weekly column on science, society, and public policy in the Washington Post
1969-72Consultant to the U.S. Arms Control and Disarmament Agency during negotiations for the Biological Weapons Convention in Geneva
1973-78Helps establish SUMEX-AIM, a nationwide time-share computer network hosting biomedical research projects
1976U.S. Viking I and Viking II spacecraft explore Mars with the help of instruments for soil analysis designed by Lederberg and his associates at the Instrumentation Research Laboratory. The spacecraft find no clear signs of life
1978-90President of Rockefeller University in New York City, a graduate university specializing in biomedical research
1979-81Advisor to President Jimmy Carter on cancer research as chairman of the President's Cancer Panel
1979-presentTrustee of the Sackler Medical School, Tel-Aviv University, Israel, the Carnegie Corporation, New York, and other academic, research, and environmental institutions. Member of the U.S. Defense Science Board, which advises the Secretary of Defense on scientific developments affecting the military and national security
1989Awarded the National Medal of Science by President George H. W. Bush
1990-presentProfessor emeritus and Raymond and Beverly Sackler Foundation Scholar at Rockefeller University
1994Heads Defense Department Task Force on Persian Gulf War Health Effects, which concludes that there is insufficient epidemiological evidence for a coherent Gulf War "syndrome"
2005Lederberg continues to conduct laboratory research on bacterial and human genetics, and to advise government and industry on global health policy, biological warfare, and the threat of bioterrorism
2008Joshua Lederberg, age 82, dies February 2 of pneumonia at New York-Presbyterian Hospital

Honorary Degrees

1960Yale University
1967Columbia University
1967University of Wisconsin
1969University of Turin
1970Yeshiva University
1979Jewish Theology Seminary.
1979Mt. Sinai College
1979University of Pennsylvania
1981Rutgers University
1984New York University
1985Tufts University
1991Tel-Aviv University
1998Uniformed Services University of the Health Sciences (USUHS)

Distinctions

1957National Academy of Sciences, U.S.
1958Nobel Prize in Physiology or Medicine (for studies on organization of the genetic material in bacteria)
1961Alexander Hamilton Award, Columbia University
1961 Wilbur Cross Medal, Yale University
1961 Sigma Xi, Procter Medal
1979 Royal Society of London
1980New York Academy of Sciences, Honorary Life member
1981New York Academy of Medicine, Honorary Fellow
1982 American Academy of Arts and Sciences, Fellow
1982American Association for the Advancement of Science, Fellow
1982 American Philosophical Society, Fellow
1983Honorary Member AOA (medical honorary society)
1984Institute of Electrical and Electronics Engineers (IEEE) Centennial award
1988Columbia P and S Distinguished Service Medal
1989US National Medal of Science
1993Academie Universelle des Cultures, Founding Member
1993Commandeur, L'ordre des arts et des lettres (France)
1995Association for Computing Machinery, Allen Newell Award
1996New York Academy of Medicine, John Stearns Award for Lifetime Achievement
1997New York City, Mayor's award in Science and Technology
1997National Foundation Infectious Diseases, Maxwell Finland Award

Military Service

1943-45 US Navy (V-12 and Hospital Corps; Ens. USNR)

Public Service

1950-President's Science Advisory Committee panels
1950-National Institutes of Health (NIH)
1950-National Science Foundation study sections (genetics)
1950-Office of Technology Assessment (OTA)
1958-1977National Academy of Sciences committees on space biology
1960-1977NASA committees; Lunar and Planetary Missions Board
1961-1962President (Kennedy)'s Panel on Mental Retardation
1966-1971(Washington Post Syndicate) "Science and Man," Columnist
1967-1971National Institute of Mental Health, National Mental Health Advisory Council
1970-1973US Arms Control and Disarmament Agency, Consultant
1971-1976;1993- World Health Organization, Advisory Committee for Medical Research
1972-Annual Reviews, Inc. (1976- Chairman, Board of Trustees)
1972-1984Natural Resources Defense Council, Board of Trustees
1975-1981Center for Advanced Study in the Behavioral Sciences, Stanford University., Board of Directors
1978-1980National Academy Sciences, Institute of Medicine, Council
1978-Charles Babbage Institute (Computing History) Minneapolis, Minn., Board of Directors.
1979-1980;1984-1986New York Institute of Humanities, Fellow
1979-1981President's Cancer Panel, Chairman
1979-Cornell Medical College, N.Y., Adjunct Professor of Genetics
1979-Sackler Medical School, Tel-Aviv University., Israel, Trustee
1979-US Defense Science Board.
1980-Chemical Industry Institute for Toxicology: Research Triangle Park, NC., Board of Directors
1981-1987Bulletin of Atomic Scientists, Board Sponsors
1981-United States Navy: Chief of Naval Operations Executive Panel
1983-Camille and Henry Dreyfus Foundation, N.Y., Trustee
1984-1987Clean Sites, Inc., Washington, Trustee
1984-1987Conservation Foundation, Washington, DC, Trustee
1985-1988New York City Partnership, Director
1985-1993Carnegie Corporation, New York City, Trustee
1985-1995Council of Scholars, US Library of Congress
1985-United Nations Industrial Development Organization (UNIDO) - Science Advisory to International Center Genetic Engineering and Biotechnology
1986-Corporation. For National Research Initiatives, Washington, DC, Director
1986-1993Revson Foundation, New York City, Trustee
1987-1988Commission on Integrated Long Range Strategy
1988-1993Carnegie Corporation: Chair, Commission on Science, Technology and Government
1988-1993Center for Strategic and International Studies, Washington, DC, Trustee
1988-1995Member, Chair Technology Assessment Advisory Council, OTA, US Congress
1989-1998Council on Foreign Relations, NY, Director
1990-1994US Secretary of Energy, Advisory Board, Member
1990-1996American Type Culture Collection. Washington, DC, Trustee
1990-Columbia University, Adjunct Professor of Biological Sciences
1991- Stanford University, Consulting Professor of Computer Science
1993-1996Soros Foundation/International Science Foundation - FSU, Advisory Board
1993-1997NIH, Advisory Committee to the Director
1993-1997Risk Assessment and Management Commission
1995-1998Federal Bureau of Investigation, DNA Advisory Board chair
1998-Center for International Security, Stanford, Senior Associate
1998-Weizmann Institute, Rehovoth, Israel, Board of Governors