5th President of Rockefeller University in office : 1978–1990

• Preceded by Frederick Seitz

• Succeeded by [ Dr. David Baltimore (born 1938) ]

• [...]

• Alma mater

  • Stuyvesant High School

  • Columbia University

  • Yale University

• Known for

  • Neurospora crassa

  • Bacterial conjugation

  • Dendral

  • Astrobiology

  • Transduction

• Awards

  • Nobel Prize in Physiology or Medicine (1958)

  • National Medal of Science(1989)

  • Presidential Medal of Freedom(2006)

• Scientific career

  • • Fields : Microbiologist

    • Thesis : Genetic recombination in Escherichia coli (1947)

    • Doctoral advisor : Edward Tatum

• Doctoral students

  • [Dr. Norton David Zinder (born 1928)]

Joshua Lederberg, ForMemRS^[1] (May 23, 1925 – February 2, 2008)^[2] was an American molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was 33 years old when he won the 1958 Nobel Prize in Physiology or Medicine for discovering that bacteria can mate and exchange genes (bacterial conjugation).^[3] He shared the prize with Edward Tatum and George Beadle, who won for their work with genetics.

In addition to his contributions to biology, Lederberg did extensive research in artificial intelligence. This included work in the NASA experimental programs seeking life on Mars and the chemistry expert systemDendral.

Early life and education

Lederberg was born in Montclair, New Jersey, to a Jewish family, son of Esther Goldenbaum Schulman Lederberg and Rabbi Zvi Hirsch Lederberg, in 1925, and moved to Washington Heights, Manhattan as an infant.^[4] He had two younger brothers. Lederberg graduated from Stuyvesant High School in New York City at the age of 15 in 1941.^[5] After graduation, he was allowed lab space as part of the American Institute Science Laboratory, a forerunner of the Westinghouse Science Talent Search. He enrolled in Columbia University in 1941, majoring in zoology. Under the mentorship of Francis J. Ryan, he conducted biochemical and genetic studies on the bread mold Neurospora crassa. Intending to receive his MD and fulfill his military service obligations, Lederberg worked as a hospital corpsman during 1943 in the clinical pathology laboratory at St. Albans Naval Hospital, where he examined sailors' blood and stool samples for malaria. He went on to receive his undergraduate degree in 1944.

Bacterial genetics

Joshua Lederberg began medical studies at Columbia's College of Physicians and Surgeons while continuing to perform experiments. Inspired by Oswald Avery's discovery of the importance of DNA, Lederberg began to investigate his hypothesis that, contrary to prevailing opinion, bacteria did not simply pass down exact copies of genetic information, making all cells in a lineage essentially clones. After making little progress at Columbia, Lederberg wrote to Edward Tatum, Ryan's post-doctoral mentor, proposing a collaboration. In 1946 and 1947, Lederberg took a leave of absence to study under the mentorship of Tatum at Yale University. Lederberg and Tatum showed that the bacterium Escherichia coli entered a sexual phase during which it could share genetic information through bacterial conjugation.^[6][7] With this discovery and some mapping of the E. coli chromosome, Lederberg was able to receive his Ph.D. from Yale University in 1947.^[8] Joshua married Esther Miriam Zimmer (herself a student of Edward Tatum) on December 13, 1946.

Instead of returning to Columbia to finish his medical degree, Lederberg chose to accept an offer of an assistant professorship in genetics at the University of Wisconsin–Madison. His wife [Dr. Esther Miriam (Zimmer) Lederberg (born 1922)] went with him to Wisconsin. She received her doctorate there in 1950.

Joshua Lederberg and [Dr. Norton David Zinder (born 1928)] showed in 1951 that genetic material could be transferred from one strain of the bacterium Salmonella typhimurium to another using viral material as an intermediary step. This process is called transduction. In 1956, M. Laurance Morse, Esther Lederberg and Joshua Lederberg also discovered specialized transduction.^[10][11] The research in specialized transduction focused upon lambda phage infection of E. coli. Transduction and specialized transduction explained how bacteria of different species could gain resistance to the same antibiotic very quickly.

During her time in Joshua Lederberg's laboratory, [Dr. Esther Miriam (Zimmer) Lederberg (born 1922)] also discovered fertility factor F, later publishing with Joshua Lederberg and Luigi Luca Cavalli-Sforza. In 1956, the Society of Illinois Bacteriologists simultaneously awarded Joshua Lederberg and Esther Lederberg the Pasteur Medal, for "their outstanding contributions to the fields of microbiology and genetics".

In 1957, Joshua Lederberg founded the Department of Medical Genetics at the University of Wisconsin–Madison. He has held visiting professorship in Bacteriology at the University of California, Berkeley in summer 1950^[12] and University of Melbourne (1957). Also in 1957, he was elected to the National Academy of Sciences.^[5]

Sir Gustav Nossal views Lederberg as his mentor, describing him as "lightning fast" and "loving a robust debate."^[13]

Post Nobel Prize research

Lederberg (right) receiving The National Medal of Science from George H. W. Bush.

In 1958, Joshua Lederberg received the Nobel Prize and moved to Stanford University, where he was the founder and chairman of the Department of Genetics. He collaborated with Frank Macfarlane Burnet to study viral antibodies. With the launching of Sputnik in 1957, Lederberg became concerned about the biological impact of space exploration. In a letter to the National Academies of Sciences, he outlined his concerns that extraterrestrial microbes might gain entry to Earth onboard spacecraft, causing catastrophic diseases. He also argued that, conversely, microbial contamination of manmade satellites and probes may obscure the search for extraterrestrial life. He advised quarantine for returning astronauts and equipment and sterilization of equipment prior to launch. Teaming up with [Dr. Carl Edward Sagan (born 1934)], his public advocacy for what he termed exobiology helped expand the role of biology in NASA.^[14]

In the 1960s, he collaborated with Edward Feigenbaum in Stanford's computer science department to develop DENDRAL.

In 1978, he became the president of Rockefeller University, until he stepped down in 1990 and became professor-emeritus of molecular genetics and informatics at Rockefeller University, reflecting his extensive research and publications in these disciplines.^[15][16]

Throughout his career, Lederberg was active as a scientific advisor to the U.S. government. Starting in 1950, he was a member of various panels of the Presidential Science Advisory Committee. In 1979, he became a member of the U.S. Defense Science Board and the chairman of President Jimmy Carter's President's Cancer Panel. In 1989, he received National Medal of Science for his contributions to the scientific world. In 1994, he headed the Department of Defense's Task Force on Persian Gulf War Health Effects, which investigated Gulf War Syndrome.

Awards and accolades

Impact crater Lederberg in Xanthe Terra on Mars

• The Benjamin Franklin Medal for Distinguished Achievement in the Sciences of the American Philosophical Society, 2002.^[17]

• The Presidential Medal of Freedom, 2006.

• In Lederberg's honor, the 87 km diameter large impact crater in Xanthe Terra on the surface of Mars was named in the year 2012.^[18]

Personal

Lederberg married fellow scientist Esther Miriam Zimmer in 1946; they divorced in 1966. He married psychiatrist Marguerite Stein Kirsch in 1968. He was survived by Marguerite, their daughter, Anne Lederberg, and his stepson, David Kirsch. [...]

When Joshua Lederberg (known to friends and colleagues as Josh) died on 2 February 2008, the world lost one of the most extraordinary scientists of the twentieth century. It is difficult to write an adequate memorial for him, or to convey on paper the outpouring of admiration and affection expressed in written and oral presentations by experts in widely diverse fields of inquiry. Even listing his various interests and achievements is a formidable task, and adequately evaluating the importance of his contributions to science and society is almost impossible. As the founding father of bacterial genetics, Lederberg was the first to demonstrate the conjugal transfer of genetic markers in bacteria. Together with his associates, he went on to make many more discoveries that laid the foundations of molecular genetics. For this work he received the 1958 Nobel Prize in Physiology or Medicine, sharing the award with G. W. Beadle and E. L. Tatum. While retaining an interest in bacterial genetics, he went on to explore and make seminal contributions to numerous other disciplines including exobiology (a term he coined), the application of computers and artificial intelligence to chemistry and medicine, and the epistemology of science. He advised US presidents and international organizations on a wide variety of issues, and devoted a prodigious amount of time and effort to the task of informing policy makers and the larger public on important scientific matters. Joshua Lederberg was a man not only of towering intellect but also of impeccable integrity and dedication to human welfare.

The early years

Joshua Lederberg was born 23 May 1925, in Montclair, New Jersey. He was the firstborn of the three sons of Zvi Hirsch Lederberg, an orthodox rabbi, and Esther Lederberg (née Goldenbaum). Before World War I, Esther’s father had fled to the USA from Safed, in what was then Palestine and is now Israel, to escape from the Turks. He became a rabbi in Brooklyn and sent money back to his family in Palestine. His family, however, was unable to join him as a result of the war and its aftermath, and they remained in Palestine.

Esther and Zvi were married in 1924, a marriage arranged by their parents. They opened a clothing store in Haifa but shortly thereafter emigrated to New Jersey, where Zvi became rabbi of the congregation in Montclair. Zvi was well educated, having more of a seminary education than a university or a collegiate one. He had been viewed as a brilliant scholar and in fact had been sent to the USA for studies. Fluent in Hebrew and Arabic, he would have studied English and acquired some Yiddish. He had acquired entry rights to the USA on his study trip to New York City in 1921 (Bohning 1992). Although they initially lived in Montclair, six months after Joshua was born the family moved to Washington Heights in Manhattan where his father took a position in a small orthodox synagogue, Ahavat Israel. Virtually penniless when they arrived in the USA, the rabbi and his wife struggled to make ends meet. According to Lederberg, his mother was a heroic soul in many ways. His father was ill during most of Lederberg’s upbringing and his mother had to work very, very hard to help keep the family together.

Joshua’s younger brother, Seymour, was born on 30 October 1928. According to Josh, ‘His presence introduced me to executive responsibilities, whilst my parents were fully occupied bringing home what must not be called the bacon.’ Seymour recalls, ‘[Josh] treated me as his first student and he [was] my first mentor after my parents.’

As the elder son, Josh was initially expected to become a rabbi like his father; however, while still very young he developed a keen interest in science and this guided his life’s work. In second grade (at the age of seven years) he wrote, ‘What I would like to be. I would like to be a scientist of mathematics like Einstein. I would discover a few theories in science.’ At his request, he received as a Bar Mitzvah present the book Introduction to physiological chemistry by Meyer Bodansky. An extremely precocious child, he found little stimulus for his interests in the New York City public grammar and junior high schools he attended; however, he took refuge in the Washington Heights public library and later in the Cooper Union Library stacks, where he read voraciously (justifying Peter Cooper’s vision). His early education was therefore largely self-directed and eclectic. One of his teachers, Mrs Fanny S. Rippere, later wrote, ‘Early in 1937 I had a most unusual pupil whom I still remember vividly. I can still remember how he prepared a paper on the classification of Protozoa using a graduate text for a reference.’ Lederberg would have been 12 years old at that time.

In 1938 he entered Stuyvesant High School, which emphasizes science, mathematics and technology. Open to male students from all parts of New York City, Stuyvesant had (and still has) a highly selective admissions process based on competitive examinations. There he finally found a supportive environment for his intellectual activities, and with the facilities available at Stuyvesant he was able to begin experiments in cytochemistry. He graduated from Stuyvesant in January 1941, planning to continue his education at Columbia University; however, because of his age he was not allowed to enter Columbia until the autumn. He successfully applied for laboratory privileges at the American Institute Science Laboratory and was able to continue his experiments there until he could matriculate. The American Institute Science Laboratory had been established after the 1939 World’s Fair in New York with support from Thomas J. Watson, the first president of IBM, and it occupied an IBM showroom on Fifth Avenue. Its purpose was to allow high-school students to engage in after-school scientific research. Here Lederberg began to focus on the chemistry of the nucleolus, continuing his investigations until September 1941, when he entered Columbia University at the age of 16 years (figure 1).

Although Lederberg had applied to Cornell, he had not been accepted for a scholarship at Telluride House there, and without financial support he could not afford to go to Cornell. Two factors made it possible for him to attend Columbia, located at the Morningside Heights campus in New York City: he could live at home, and he received a $400 tuition scholarship from the Hayden Trust. His previous autodidactic reading allowed him to take several graduate-level science courses. At Columbia he met an important mentor, Francis J. Ryan. Ryan had received his PhD from the Zoology Department at Columbia in 1941, and then spent a year as a postdoctoral fellow at Stanford University in California. While at Stanford he worked in the laboratory of Edward L. Tatum and George W. Beadle studying growth properties of Neurospora crassa, the ‘red bread mould’. When Ryan returned to Columbia in 1942 as a faculty member in the Department of Zoology, he continued to study Neurospora. Ryan was the first working scientist whom Lederberg had met, and he introduced Lederberg to experimentation in biochemical genetics, taking him on as a protégé and part-time laboratory helper. From Ryan, Lederberg learned how to conduct experiments and record the results in a disciplined and professional way.

While at Columbia, Lederberg joined the Navy V-12 programme. This programme, which ran from 1 July 1943 to 30 June 1946, was designed to provide officer candidates for the US Navy. The navy had expanded enormously as a result of World War II, and the Naval Academy at Annapolis, Maryland, could not meet the resulting increase in demand for officers. At the same time, colleges and universities were suffering a severe attrition in enrolment because of the large number of men who had gone into the military services. In response to this situation, the navy created a programme to support students at various colleges, paying tuition and stipends for those who passed the competitive examinations and enlisted in the V-12 programme. For those like Lederberg who were training to be medical officers, the programme compressed pre-medical training to about 18 months and medical training to 3 years. Lederberg was able to continue his studies at Columbia and his research activities with Ryan, alternating them with periods of duty at the US Naval Hospital, St A lbans, Long Island. There he was primarily assigned to the clinical pathology laboratory, screening samples from US Marines returning from Guadalcanal: stool samples for parasite ova and blood samples for malaria. He later remarked that this experience contributed to his thinking about microbial life cycles.

Figure 1. Joshua Lederberg at the microtome at the American Institute in 1941.

Discovery of genetic exchange in bacteria

In October 1944, having finished his pre-medical studies and having obtained a BA in Zoology from Columbia, Lederberg was reassigned to the Columbia College of Physicians and Surgeons at the Washington Heights campus to begin his medical courses, but he maintained his contacts and activities at the Morningside Heights campus. The seminal work of Avery, MacLeod and McCarty (Avery et al. 1944) was published that year. The paper documented experiments showing that DNA was the active agent that could cause the conversion of one form (rough) of the bacterium Pneumococcus into another form (smooth). These results provoked vigorous discussion because they were the first to show that DNA is the genetic material, and they inspired Lederberg to propose experiments to look for DNA-mediated transformation of Neurospora. As it happened, the mutant chosen to be the recipient in his experiments proved to be too revertible for the purpose, although a study of the reverse mutation phenomenon resulted in Lederberg’s first publication with Ryan (1)*. Lederberg then turned his attention to bacteria, specifically Escherichia coli, and set about obtaining nutritional mutants that would permit him to look for genetic recombination in this organism. Fortunately, at this time he was interested in the possibility of a sexual cycle in bacteria and did not attempt to detect DNA transformation. In contrast with several other kinds of bacteria (for example Pneumococcus, Haemophilis influenzae and Bacillus subtilis), E. coli turned out to be relatively recalcitrant to DNA transformation, and the results would almost certainly have been negative. Lederberg had determined that mutants containing at least two nutritional requirements would be needed to avoid ambiguities of interpretation posed by the reversion of individual mutations; however, obtaining double mutants was a laborious process in the absence of the many techniques now available for isolating such mutants.

In 1945 E. L. Tatum moved from Stanford to Yale, bringing with him nutritional mutants of E. coli that had been isolated in his laboratory. These included double mutants of the E. coli strain K-12. At Ryan’s suggestion, Lederberg asked Tatum whether he might come to Yale and use Tatum’s mutants to perform the experiments he proposed. Tatum not only replied in the affirmative but also helped Lederberg to obtain financial support from the Jane Coffin Childs Fund for Medical Research. Lederberg arrived in New Haven in the spring of 1946, and about six weeks after the first serious crosses had been set up he obtained reproducible, positive results. This amazingly rapid success was due in part to the availability of double mutants and in part to their having been derived from the K-12 strain of E. coli. Only later was it realized that most E. coli strains, including the popular E. coli B , would have given negative results. In addition, the experiments had been designed to allow the selection of rare prototrophic recombinants, which did not require any organic nutrients, from among enormous numbers of the auxotrophic parents, each of which required two or more organic nutrients for growth. This design made it possible to detect the extremely low frequencies of recombination initially observed. Moreover, as Lederberg later remarked, the linkage relationships of the genetic mutations involved were favourable for recombinant formation. Thus, his success in these remarkable early experiments depended on several fortuitous circumstances, including the generosity of both Ryan and Tatum in supporting Lederberg, whom they must have already recognized as a brilliant intellect. The results were presented at very short notice at the 1946 Cold Spring Harbor Symposium, ‘Heredity and Variation in Microorganisms’ (2). Although cautiously worded in light of our current knowledge, the presentation elicited ‘lively discussions’.

* Numbers in this form refer to the bibliography at the end of the text.

In September of 1946, Lederberg was due to return to New York to resume his medical studies but was able to defer his departure from Yale and to obtain another year of support from the Jane Coffin Childs Fund. During this time he extended his analysis of bacterial recombination (3) and prepared a dissertation that led to a PhD from Yale.

In December 1946, Lederberg married Esther M. Zimmer, who had received a Bachelor of Arts degree from Hunter College in New York City, and then a Masters degree from Stanford University for work on Neurospora with Beadle. She and Lederberg first met at his request, on the basis of her work on Neurospora. She later obtained her PhD at the University of Wisconsin working with her new husband, although R. A . Brink was her formal adviser.

Lederberg was once more scheduled to return to his medical courses at the Columbia College of Physicians and Surgeons in the autumn of 1947, but again fate intervened, this time in the form of an offer from the University of Wisconsin in Madison for a position as Assistant Professor in the Genetics Department. The offer was largely due to the efforts of Brink, chair of the Wisconsin faculty search committee, who was encouraged by a letter from Ray D. Owen endorsing Lederberg. Although Lederberg was strongly motivated to finish his medical training, financial constraints made this difficult. The V-12 programme had ended, and he had not been granted the Merck fellowship for which he had applied. After considering his options he accepted the offer from Wisconsin. He spent the summer at the Woods Hole Marine Biological Laboratory completing his PhD dissertation, and then he and Esther headed west for Madison. There was some worry among the Wisconsin faculty about his fitting in at Madison, due in part to the fact that he was a city boy, and the Genetics Department was part of the College of Agriculture with close ties to local farmers, and in part to his ‘race’ and ostensibly ‘aggressive’ personality; however, his tenure was an unqualified success.

The University of Wisconsin - Developments in bacterial genetics

During the years at Wisconsin, Lederberg and his colleagues, including his wife Esther and graduate students Norton Zinder and M. L. Morse, not only extended analyses of the genetic system of E. coli, but documented several new phenomena. One of these is now known as ‘transduction’, a term originally coined by Lederberg (7). It was initially observed in Salmonella typhimurium when Zinder found that the bacteriophage P22 could carry genetic material from a donor bacterial strain on which the phage was grown to a recipient strain. This form of genetic exchange differs from conjugation because the donor and recipient bacteria do not need to be in direct contact, and it differs from what we now call DNA transformation because isolated DNA is not involved.

Another important discovery was the latent, or lysogenic, bacteriophage that E. coli K-12 carries. Esther, who first observed it, called it lambda (9). This phage was shown to integrate into the E. coli chromosome at one specific location near the genes for galactose metabolism. Subsequently, Morse found it to be capable of transducing bacterial genes but only genes located near the site of integration (11, 13). This phenomenon is known as ‘specialized transduction’ to distinguish it from the ‘generalized transduction’ characteristic of P22.

Together with L. L. Cavalli, the Lederbergs described the K-12 infectious fertility factor F (8, 10), later recognized as the first evidence of a plasmid replicon and of a plasmid-specified conjugation system (Ippen-Ihler & Minkley 1986). These discoveries laid the foundations for much of molecular genetics.

Several novel and useful experimental techniques were devised during this period. One of these was the development of the chromogenic substrate o-nitrophenyl-β-d-galactoside (ONPG) for measuring the activity of β-galactosidase (5). Hydrolysis of the substrate by the enzyme produces a yellow product that can be accurately measured by spectrophotometry in alkaline conditions. This substrate facilitated the analysis of the lac operon, a complex and important genetic system in E. coli. The principle behind the technique was subsequently adapted to great effect in other enzymatic assays, including those based on fluorogenic substrates.

Another novel technique was a procedure known as replica plating, in which velveteen was used to transfer an exact copy of the bacterial growth on one plate of solid growth medium to another plate (6). This procedure was used not only to identify and isolate new mutants of E. coli but also to provide qualitative evidence that mutants did not necessarily arise in response to selective conditions, for example the presence of an antibiotic, but existed in bacterial cultures before exposure to selective conditions, and therefore occurred independently of them. Variations of this technique have been adapted to many other applications in molecular genetics.

A different procedure, called sib selection by analogy with animal breeding procedures (Lush 1945), was used to corroborate the conclusion that mutants could arise in the absence of selective conditions and to provide quantitative information about mutant behaviour (12). It was developed in collaboration with L. L. Cavalli-Sforza (ForMemRS 1992) and was effectively a development of the Luria–Delbrück fluctuation test (Luria & Delbrück 1943). A relatively laborious procedure, sib selection involved several series of liquid cultures. In the initial series, each culture was inoculated with approximately 100 bacteria from a single clone. After the cultures had grown, half of each culture was plated on nutrient agar containing the selective agent, for example streptomycin, and the remainder of each culture was stored. The cultures that gave rise to the largest number of mutants were subcultured from the stored remainder. By using an amount of the original culture that was expected to contain one or two mutant cells, a series of subcultures was inoculated. The number of subcultures was chosen to ensure that at least one culture would contain a mutant. This enrichment procedure was repeated until the ratio of mutant to non-mutant cells in a culture had increased from less than 10−8 to approximately 1%. At this point it became feasible to dilute the final culture, plate out samples on nutrient agar without any selective agent, and test individual colonies for resistance to the selective agent to allow the identification of a mutant colony. This colony was subcultured from nutrient agar (without selective agent) and used to inoculate a sequential series of liquid cultures (also without selective agent). After more than 200 bacterial generations the resulting culture was observed to contain only mutant cells, indicating that the mutation was stable. The mutant bacteria had never been in contact with the selective agent, demonstrating unequivocally the existence of a mutant in the original culture and clearly refuting the claims of Sir Cyril Hinshelwood PRS that resistance could be explained by some form of induced chemical feedback rather than by a genetic change.

Studies of the antibiotic penicillin resulted in a practical procedure for isolating nutritional mutants of E. coli and Salmonella (4) as well as a clearer understanding of the biochemical mechanism by which the antibiotic kills bacteria (14). It had previously been shown that penicillin kills only growing cells, not those that are quiescent. In minimal medium, nutritional mutants are unable to grow in the absence of their required nutrient, whereas non-mutant bacteria can grow and be killed by penicillin. Lederberg developed a method using this effect to enrich for nutritional mutants in a culture. He was ready to publish his findings when he learned that Bernard Davis was doing similar work, and he graciously postponed publication so that the two papers could appear simultaneously (4) (Davis 1948).

The University of Wisconsin - Genes and antibodies

In 1957 the Lederbergs spent three months in Australia, where Josh was Fulbright Visiting Professor of Bacteriology at the University of Melbourne and the institute headed by Sir MacFarlane Burnet FRS . Burnet had put forward the clonal selection theory of antibody formation, which proposed that a lymphocyte made only one antibody and was selectively amplified in the presence of the relevant antigen, rather than being ‘instructed’ by the antigen to make the corresponding antibody. Stimulated by these ideas, Lederberg and G. J. V. (later Sir Gustav) Nossal (FRS 1982) collaborated on some elegant experiments demonstrating that individual cells from rats immunized with two different Salmonella antigens made detectable levels of antibodies against either one or the other antigen but not against both (15). Their results provided the first direct evidence to support the clonal selection theory of antibody production as put forward by Burnet and helped to clarify thinking about the mechanisms of antibody production, including the issue of secondary responses and the cellular basis for tolerance (18).

Space science, advisory committees, academic developments and the Nobel Prize

In 1957 Lederberg was elected to the US National Academy of Sciences; he also joined President Eisenhower’s Scientific Advisory Committee. Stimulated by the launch of the Russian Sputnik, the first Earth-orbiting artificial satellite, and by a conversation he had with J. B. S. Haldane FRS in India on his way back from Australia, Lederberg became increasingly interested in the possibility of searching for extraterrestrial life, or ‘exobiology’ (a term he coined (19)). He set out to ensure that fundamental biological science was properly represented in the programmes of space research that were just emerging. He predicted that rapid developments would lead to more space vehicles, some of which would land on the Moon or on other planets. His concerns were twofold: space vehicles landing on alien soil might carry terrestrial organisms that would make it difficult to answer questions about the origin(s) of life, and returning vehicles might contaminate the earth with alien organisms that could cause serious, even catastrophic, epidemics. He began to raise awareness of the need for scientists, especially those with biological training, to participate in the design of experiments to detect signs of extraterrestrial life. He considered the possibility of finding another branch of evolution to be of ‘compelling scientific interest’ in spite of the scepticism of many of his colleagues. He was able to persuade the President of the National Academy of Sciences, Detlev Bronk, to put the issue before the Academy’s council. This led to an official statement of concern in February 1958, and shortly thereafter to the establishment of the Space Science Board at the request of the US National Committee for the International Geophysical Year. Lederberg was a founding member of the board and served on it until it was disbanded in 1974. Recommendations of this board adopted by the National Aeronautics and Space Administration (NASA) resulted in efforts to sterilize spacecraft before they left on missions, and to quarantine returning space vehicles until they could be shown to carry nothing malignant. As described in the National Library of Medicine’s Profiles in science series (http://profiles.nlm.nih.gov/BB):

By publicly promoting exobiology, Lederberg almost single-handedly gained a place for biologists in the burgeoning US space programme, as well as a share of its ample research funds. He pressed upon NASA the need to include biological science in its mission and research designs, and represented the interests of biologists on the agency’s Lunar and Planetary Missions Board between 1960 and 1977. In this role he helped define the scientific objectives for the Mariner Mars missions, launched between 1964 and 1971 to map the planet’s surface and study its atmosphere from close-in orbits.

During this same period, drawn by his interest in medicine and his desire to relate genetics to medical research, Lederberg founded and chaired the Department of Medical Genetics at the University of Wisconsin in 1957, one of the first medical genetics departments in the country.

In the following year, Lederberg received the Nobel Prize in Physiology or Medicine ‘for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria’. He received one-half of the prize, the other half being shared by E. L. Tatum and G. W. Beadle. According to his own recollections (21), the award came at a delicate time because he was preparing to leave the University of Wisconsin for Stanford University. This posed both a diplomatic challenge and a strategic one. On one hand it meant that Wisconsin’s first home-grown Nobel laureate was leaving the university just at the time of his award, and on the other it presented a challenge with regard to organizing the move to Stanford and preparing for the Nobel festivities in a very short period. He was relieved to discover that his Nobel lecture could be postponed for up to six months after the award ceremonies, making it somewhat easier to concentrate on the move. The news of the award also aroused mixed reactions of another sort: while the prestige and the money from the prize might help in setting up his new laboratory at Stanford, the publicity, the ‘fuss and bother’ (16), and the added responsibilities accompanying the award might detract from his scientific activities. Moreover, he felt the prize was antithetical to the way in which science progressed because it singled out a few individuals to credit with a discovery, whereas in fact the discovery was the product of the efforts of many. As he said in his Nobel Banquet speech, ‘Here pride must merge with humility in the same contemplation of the webs of interdependence of each investigator in the global community of scientific research, of each elusive fact in the continuum of human knowledge’ (17). He briefly considered refusing the prize, but decided that would be discourteous to Tatum and Beadle. He and Esther attended the Nobel ceremonies in December, returning to Stockholm in the following May for the presentation of his lecture. In January 1959 they moved from Madison to Stanford.

When Lederberg left Madison for Stanford, James F. Crow (ForMemRS 2001) succeeded him as Chairman of the Department of Medical Genetics. Lederberg later recalled, ‘At Wisconsin I had a wonderful environment. I made so many wonderful friends there. I want to mention Jim Crow in particular.’ Crow was a population geneticist who had been recruited to the Genetics Department partly through Lederberg’s influence. They had originally met at conferences and, in spite of their different interests, had immediately struck up a friendship that lasted for the rest of Lederberg’s life. It was no doubt the association with Crow that made Lederberg appreciate the importance of population genetics in a human context, reflected in his later recruitments to Stanford University of Walter (now Sir Walter) Bodmer (FRS 1974) and Luca Cavalli-Sforza, another of Lederberg’s lifelong friends.

Two attributes that impressed Lederberg’s friends and colleagues were his prodigious memory and the rapidity with which he assimilated and analysed new information. His ability to recall information was equally amazing. Crow has said, ‘I used to file information with Josh. Several times when I told him something that he did not know, he remembered it after I had forgotten. Of course I also relied on him for information other than what I had imparted. I don’t know whether he realized that he played a Google-like role with me.’

Stanford University

Starting in early 1957 Lederberg had been negotiating the possibility of a position as Head of the Genetics Department at the University of California, Berkeley. He had laid down specific requirements, including a position for his wife, Esther, in a way that that would circumvent the State’s nepotism rules. Early in the negotiations he wrote, ‘It seems to me utterly silly that a regulation of this kind—which is designed to forefend real abuses in other contexts to be sure—should frustrate and waste the professional lives of trained and competent women who happen to be married.’ Inexplicably, after long and apparently successful negotiations with the department head and the university administration, his appointment was turned down in March 1958, both by the then President and by the incoming President of the university. Whether this was for financial or other reasons, Berkeley’s loss turned out to be Stanford’s great gain.

Although there had been some not very encouraging discussions with Stanford at the end of 1956 about Lederberg succeeding Tatum there (and rumours about that may have been the basis for the approach from Berkeley), he did not consider Stanford to be an attractive possibility at that time. However, when discussions with Stanford started again just after Berkeley had turned him down in the spring of 1958, the situation had completely changed. The plans for moving the medical school from San Francisco to the Stanford campus near Palo Alto had been completed, and [Dr. Arthur Kornberg (born 1918)] (ForMemRS 1970) and his group had agreed to move from Washington University in St Louis, Missouri, to Stanford to establish a Biochemistry Department in the new Medical Center. Lederberg was encouraged to come, not only by [Dr. Arthur Kornberg (born 1918)]'d decision but also by Henry S. Kaplan, chairman of Stanford’s radiology department. Kaplan, who had recently turned down an excellent offer from Harvard, was instrumental in persuading both [Dr. Arthur Kornberg (born 1918)] and Lederberg to move to Stanford. When Lederberg arrived in January 1959, the new Medical Center was still under construction, but Kaplan arranged for him to occupy temporary quarters in the Hansen Laboratories on the Stanford campus until the Medical Center was ready for occupation.

Lederberg, attracted by the prospect of better laboratory facilities, a supportive environment to develop his ideas about medical genetics, and the calibre of the colleagues he would encounter, was recruited to establish a Genetics Department in the Medical Center. He especially valued the possibility of interacting with [Dr. Arthur Kornberg (born 1918)] because he viewed nucleic acid biochemistry as a necessary complement to molecular genetics. Kornberg, shortly after his arrival at Stanford, received the Nobel Prize in Physiology or Medicine for his work on the mechanisms of the biological synthesis of DNA, sharing the prize with Severo Ochoa (ForMemRS 1965), with whom he had once worked. Having two Nobel laureates on the faculty enhanced the cachet of the Medical Center and contributed to its becoming an attractive destination for promising students and faculty. Over the ensuing years the two Departments, Genetics and Biochemistry, have continued to contribute to the development of the Medical School’s leadership in biomedical research.

Unlike [Dr. Arthur Kornberg (born 1918)], who brought a large and cohesive department with him, Lederberg arrived with a small group of people and only built up his department after coming to Stanford. In developing the Genetics Department, Lederberg was both prescient and eclectic, creating a department of diverse interests and expertise. It included molecular genetics, cellular genetics, clinical genetics, population genetics, exobiology, immunology and neurobiology. Among those he recruited to the department were Leonard A. Herzenberg (developer of the fluorescence-activated cell sorter), Gustav Nossal, Elliot Levinthal, Walter Bodmer, Eric Shooter (FRS 1988) (who, with Lederberg’s stimulus, later initiated the Department of Neurobiology in the Stanford Medical School), A. T. Ganesan, Luca Cavalli-Sforza and Stanley Cohen (who succeeded Lederberg as Head of the Genetics Department).

Lederberg was also instrumental in creating the Joseph P. Kennedy Jr Laboratories for Molecular Medicine, dedicated to the study of mental retardation. These laboratories involved a formal collaboration between the Departments of Genetics, Pediatrics and Obstetrics, with additional input from Biochemistry, Medicine, Neurology and Psychiatry. They were initiated with funds from the Joseph P. Kennedy Jr Foundation, and at the behest of the Kennedy Foundation, Lederberg became its first director. He also served on President Kennedy’s Panel on Mental Retardation (1960–61) and on the National Mental Health Advisory Council of the National Institutes for Mental Health (1967–71).

In addition to his contributions to the Medical School, Lederberg also left a legacy to undergraduate education at Stanford. He has said (Hyde 1996):

One thing I’m particularly proud of is: I am one of the founders of the Human Biology curriculum for undergraduates at Stanford. Together with a number of people, Don Kennedy, David Hamburg, Norman Kretchmer, Sandy Dornbush, we came to the conclusion that undergraduate education didn’t give enough choices. Students interested in science could become premature graduate students in one scientific area and they would be the darlings of the Chemistry Department or the Biology Department, the PreMeds were sort of barely tolerated and these were not the broader scientists we were concerned about. If you took a liberal arts degree, you’d be almost devoid of science. We wanted to have some concept of Liberal Education with a scientific bent. That’s really what the Human Biology curriculum was intended to be and [it] became eventually a resounding success.

After arriving at Stanford, Lederberg retained an interest in bacterial genetics, especially DNA transformation in Bacillus subtilis, and members of his department, particularly A. T. Ganesan and W. F. Bodmer, made significant contributions to the understanding of mechanisms of DNA synthesis and transformation in this organism. However, Lederberg soon began to devote more time to other projects. Thus, in 1960, as a result of his efforts to ensure that fundamental biological science would be properly represented among the national programmes of space research, he and Elliot Levinthal, a physicist and engineer, developed an instrumentation laboratory at Stanford supported by NASA. The main goal of this project was to design instruments that could detect signs of biological activity, past or present, in the soil of Mars. The results contributed to the choice and design of experiments that went to Mars on the Viking Landers in 1975. An important by-product was that the laboratory, led by Levinthal and a team of engineers, provided the fundamental technology and many of the basic ideas for the subsequent development by L. A . Herzenberg of the fluorescence-activated cell sorter (figure 2).

Computing, chemistry, and scientific literature

Partly as a result of being involved with NASA and the development of the US space programme, which ‘brought (him) into intimate conversation with (the technologies) of automation, process control, communications, and computer management’, and partly as a result of being asked to serve on a President’s Scientific Advisory Committee panel on the management of scientific information, Lederberg began to devote more time to developing his computer skills. He has said that his interests in computing were first aroused at the age of 16 years by exposure to a punch-card-based tabulator/calculator in high school. Figure 2. Joshua Lederberg at the John F. Kennedy Space Center on 7 A ugust 1975.

By the early 1960s he had become aware of the power of computing and interested in its potential scientific applications. He therefore decided to master writing computer programs himself by taking a summer course in 1962 in BA LGO L, the dialect of ALGO L that was used by the main Stanford University computing facility at that time. One of us (W.F.B.) had already started using this facility for the analysis of experimental results and census data. Lederberg had hoped that the latter could be used for some aspects of human genetics. Meanwhile, Lederberg decided that his own first computer application would be to the systematic enumeration of all the chemical isomers that were compatible with a given mass spectrum. He had become interested in this problem through his contact with the organic chemist Carl Djerassi (ForMemRS 2010), who had come to Stanford in 1959 and was an accomplished mass spectroscopist. As Lederberg put it, ‘How to represent organic molecular structures in graphs, and then their dissection into sub-graph fragments, as occurs in the mass spectrometer, became my task for 1963–64.’ Of this activity he noted, ‘When it came to cyclic graphs, I had a particularly entertaining time, almost at the level of recreational mathematics’ (24). In fact Lederberg actually laid the foundations for fundamental new developments in graph theory, stimulated by his determination to solve the problem of dealing with cyclical organic compounds. Examples of the graphs he derived can be seen in figure 3.

He took up the challenge of writing his first computer program to enumerate chemical structures by a system he called a ‘dendritic algorithm’, shortened to ‘DENDRAL’. As E. A . Feigenbaum, with whom he later developed this approach, has written, ‘Josh’s DENDRAL programme was quite sophisticated for its time as it dealt with mathematical graphs and their manipulation, rather than the mathematical formulas that ALGOL or FORTRAN were designed for.’ Feigenbaum, an expert in artificial intelligence (AI), had first met Lederberg about the time that the original DENDRAL program was written. He came from Berkeley to an appointment at Stanford in 1965. This set in train an extraordinarily productive collaboration between Lederberg, Feigenbaum and Djerassi and their colleagues. The DENDRAL project led to the development of extremely sophisticated software for inducing correct organic structures from mass spectra. The program made use of the chemical knowledge obtained from the extensive experience of Djerassi and his colleagues, who supplied the expertise in interpreting mass spectrometer data. The goal was to emulate inductive reasoning in chemistry through AI and to develop a practical aid for chemists to facilitate the interpretation of data obtained from mass spectrometry. To a large extent this goal was achieved (22), but more fundamentally the project clarified the limits of AI and its potential for practical application (25). This was one of the first practical uses of AI computing and is the origin of the term ‘expert systems’ and the ideas that underlie it. An outgrowth of these ideas is ‘Lederberg’s principle’, which is that ‘machines will become really smart only when 1) they can directly read the literature and 2) spend some time living in the real world where the survival of the fittest is what will determine who’s out there’ (Hyde 1996).

The DENDRAL project clearly illustrates one of Lederberg’s great talents: the ability to bring together innovative individuals from different areas of specialization and to catalyse synergistic interactions between them. His expressed appreciation of the fraternity and scientific community enjoyed on this project shows another Lederberg trait. As he said, ‘The fraternity that came out of the DENDRAL effort was a high in my life experience, matching the gratifications of scientific excitement and (perhaps belated) recognition.’

Through the DENDRAL collaboration and his contacts with computing at Stanford, Lederberg had become aware of the power of time-shared systems for using computers more effectively in medical science. He therefore managed to obtain support from the National Institutes of Health for implementing what he called a ‘community-access time-shared system’ for the Stanford Medical School, or ACME (Advanced Computer for Medical Research), which was managed by Feigenbaum. This concept, allowing direct online access to what, for their time, were powerful central computing facilities, was far ahead of its time. This was long before the advent of personal laptop computers. It took one of us (W.F.B.) at least 10 years after returning to the UK in 1970 before being able to have access to a facility comparable to ACME. Lederberg later extended these ideas to a nationwide resource for AI research, SUMEX-AIM (Stanford University Medical Experimental Computer—Artificial Intelligence in Medicine) (figure 4).

Lederberg later said about DENDRAL, ‘The project also dramatized the values of electronic communication in project management’, and in 1978 he wrote an amazingly farsighted article entitled ‘Digital communications and the conduct of science: the new literacy’ (23). In this he predicted the huge benefits that would come from easily accessible, widespread electronic communication, using what he called ‘Eugrams’, together with access to central sources of information. All of this we now recognize as emails, openly available databases, and web-based access to an almost unlimited amount of information. However, he also warned:

‘Biology, in particular, will soon suffocate in the sheer bulk of knowledge about DNA and protein structures, and the complex interactions of the causal chains they initiate, unless new epistemological machinery can be invented.’

Another area of computer applications in which Lederberg had a major interest and on which he made a considerable impact was the analysis of scientific literature by citation indexing, pioneered by Eugene Garfield. His first contact with Garfield, through a hand-written note of May 1959, starts, ‘Since you first published your scheme for a “citation index” in Science about 4 years ago, I have been thinking very sincerely about it, and must admit I am completely sold.’ Lederberg had soon realized the value of computers for enabling access to the scientific literature, something we now take for granted but which was simply not appreciated at that time. It was Lederberg’s encouragement that led first to the Genetics Citation Index and then to the general Science Citation Index. Garfield and Lederberg became great friends. It was through that relationship that one of us (W.F.B.) became acquainted with Garfield and arranged to use the early, computerized version of the Index in the early 1980s. It was received once a week as a package of magnetic tape at the Imperial Cancer Research Fund in London. Clearly, Lederberg anticipated the current and coming revolution in online publication. He once commented (personal communication) how odd it was that a Sunday newspaper could produce what amounted to a whole book every week, and yet it still took months to produce just one issue of a scientific journal. How times have changed since then!

Rockefeller University

In 1978 Lederberg left Stanford to become President of Rockefeller University in New York City. He was ‘drawn by the substantial scope, but simple structure and coherent goals’ of the 60 independent laboratories, the strong commitment to biomedical research, and the relatively limited routine clinical burden required of the faculty of that university. He later said (Hyde 1996), ‘the Rockefeller is a place that is just really quite special. And I felt, and quite authentically, that this would be the one job in the country where one could have a position of leadership at a significant academic research institution and still stay close to the scientific content.’ According to his notes for his inaugural address, he came to Rockefeller ‘not to invoke radical changes, but to conserve the most vital traditions of biomedical research to be found anywhere today.’ At the same time, he warned:

In my view, the most cogent risk is the very success of the basic programmes of research, and the social consequences of drastic reductions, in death and illness from our major afflictions, which I have no doubt will be surmounted. No one will cast a vote against ‘living’; but we have certainly not begun to face up to the social problems of the prolongation of life, even those that have already been achieved in this century.

During his tenure he not only conserved but also greatly enhanced the strengths of Rockefeller University, in spite of the fact that he was President during a time of financial difficulty that made it hard to recruit promising young investigators to a city of astronomical housing costs. Not all the senior faculty appreciated his style of leadership, but he was helped by having good relations with key members of the board of the university, including David Rockefeller. During the 12 years of his Presidency he reinvigorated the free-standing, nondepartmental laboratories that make up the university and refocused them on molecular biology research with clear medical applications for heart disease, cancer, neurological illness and infectious diseases. His recruits to the university included Torsten Wiesel (ForMemRS 1982), Tom Kaiser, Jan Breslow and the young Jeffrey Friedman. New buildings included a Scholars Residence and a laboratory building to house joint appointments between the university and a unit of the Howard Hughes Medical Institute that was established during his time as President. He also continued his extensive advisory activities, which meant he was often away from Rockefeller, and this led to complaints that he was away too much. However, whenever he could, he would come to the regular Friday lectures and ask his characteristically penetrating questions after having apparently slept through most of the presentation.

Twelve years after becoming President of Rockefeller University, Lederberg reached the customary retirement age of 65 years. He became University President Emeritus and the Raymond and Beverly Sackler Foundation Scholar in 1990. He had purposely not maintained a laboratory while he was President, but on his retirement he established a laboratory, which he named ‘The Raymond and Beverly Sackler Laboratory for Molecular Genetics and Informatics’, and resumed his own research into the chemistry and evolution of DNA, epistemology, theory formation in molecular genetics, and computer modelling of scientific reasoning. There were many visitors to the laboratory and many publications from 1990 until shortly before he died. David Thaler, who was Lederberg’s close collaborator in the laboratory during this period, has emphasized (personal communication) that although Lederberg did not put his name on most of the research papers, he ‘was intellectually involved in it all’. Lederberg’s own later publications included historical essays on research in which he had been involved and commentaries, for example on security in the USA in the twenty-first century (written with President Clinton), and the health implications of human genome mapping (26). He placed a special emphasis on the risks of emerging infections. His last publication in 2008 was on ‘quorum sensing’ and how bacteria regulate their growth by measuring their population density and limiting their growth when a critical density has been reached (27).

Public policy and advice

In addition to his scientific activities after he retired as President of Rockefeller University, Lederberg engaged in a wide variety of responsibilities related to public policy and to the public understanding of science. For nearly 20 years he continued to advise government and private institutions, and to lecture widely about developments in science as they related to public policy and public health, especially the threat of bioterrorism and infectious diseases, both new and re-emerging. Even while he was at Stanford he had begun to devote his attention to such activities. For example, from 1966 to 1971 he wrote a weekly editorial column for The Washington Post entitled ‘Science and Man’. In it he discussed the social implications of various scientific discoveries and endeavours, ranging from space exploration to the use of chemical contraceptives. He was a founding member of the Institute of Medicine and played an important role in its establishment in 1970. This institute, a sister academy to the National Academy of Sciences, is the principal organ for health policy pronouncements.

One of his major concerns, and his principal extramural commitment over many years, was the perceived threat of malignant microorganisms in the form of emerging infections and bioterrorist weapons. Beginning in 1970, he was a consultant to the Arms Control and Disarmament Agency during the negotiations of the biological weapons disarmament treaty, and a member of the US Defense Science Board. In his remarks at the Conference of the Committee on Disarmament in Geneva in 1970 he clearly foreshadowed the recombinant DNA revolution of the mid 1970s and foresaw the dangers that might arise if this technology were to be applied to the development of serious pathogens for biological warfare. Together with the late Robert Shope and Stanley C. Oaks Jr, Lederberg organized and co-chaired the 1992 Institute of Medicine (IOM) study ‘Emerging Infections: Microbial Threats to Health in the United States’, which in turn led to the formation of the Forum on Global Microbial Threats of which Lederberg was the first chair. He was also active on the Committee on International Security and Arms Control (CISAC) formed by the National Academy of Sciences in 1980 as a permanent committee to bring the resources of the Academy to bear on critical problems of international security and arms control, including biological warfare. According to Alexander Keynan of Hebrew University (personal communication), who was a close friend, Lederberg ‘never believed that the Russians would really destroy their stockpile of biological weapons. He therefore advocated continued US preparedness against biological attack.’

He never joined a political party and he maintained neutrality on political issues, as he felt that to do otherwise would compromise his ability to advise whichever party happened to be in power. He felt that he had a moral duty to advise those in power, especially on issues of national security (he was one of the first to take the biological dimension seriously), and that it was important that decisions be made on the basis of the best possible scientific advice. He was a valued adviser for the intelligence community and was recognized by the military as someone with particular foresight in the area of information technology. In the broader area of defence policy, Lederberg served on the Defense Science Board for more than two decades beginning in 1979. Paul Berg (ForMemRS 1992), who had a key role in the mid 1970s in discussions on the possible hazards of recombinant DNA technology, has emphasized the sensible support that Lederberg gave to the public discussion of this issue. As Berg put it (personal communication), ‘During the period when the safety of recombinant DNA was in the headlines, Josh was a voice of reason and a fountain of advice.’

Lederberg was also very influential in his advice to many private foundations including, for example, the Sackler and the Carnegie foundations. It was Lederberg who persuaded Larry Ellison, the founder of Oracle, who had spent a month in Lederberg’s laboratory at the Rockefeller, to set up a foundation specifically for the study of ageing. He was active in giving advice to the National Academy of Sciences and the New York Academy of Sciences, although he preferred not to chair committees. However, he did produce, with William T. Golden, a major report on science and government, based on a four-year study from 1989 to 1993. In addition to his interest in defence and related topics, he was concerned about environmental issues well before these became as popular as they are now. According to his biographical profile in the National Library of Medicine’s Profiles in science series, ‘Lederberg served on the Board of Trustees of the Natural Resources Defense Council from 1972 to 1984. He resigned his position in disagreement over the Council’s growing emphasis on litigation, rather than lobbying and public education, as its primary strategy for protecting the environment.’ Jesse Ausubel, who was for many years closely associated with Lederberg at the Rockefeller

University, has stated (personal communication) that Lederberg would have liked to introduce more environmental and evolutionary research through his appointments there. He was also very supportive of the life ‘barcoding’ and other related projects that Ausubel and colleagues developed at the Rockefeller University.

For many of Lederberg’s later years he advised the Government of Thailand on developing their scientific infrastructure and became very friendly with the Thai royal family who, as Marguerite Lederberg has remarked (personal communication), ‘took very good care of Josh on his last visit there.’

As outlined in Lederberg’s biographical profile in the National Library of Medicine’s Profiles in science series, he

advised presidents, cabinet members, government agencies, non-profit organizations, and international bodies on science and medical research policy, mental health, emerging infectious diseases, space exploration, national security, and arms control. In his public career, he personified the postwar American liberal, inspired by a belief in the ability of modern government to improve society and ensure peace, and in the responsibility of experts to help guide government action.

Personal life

Following the Lederbergs’ move to Stanford, Josh and Esther no longer worked as closely together as they had in Madison. This was at least partly because of Josh’s change of interests, especially in the direction of exobiology and computing. Eventually, in 1966, he and Esther divorced, and in 1968 he married Marguerite Stein Kirsh, who had been born in Paris, was educated as a physician in the USA, and now serves as Clinical Professor of Psychiatry at the Memorial Sloan Kettering Cancer Center in New York. This was an extraordinarily happy and mutually supportive marriage over a period of nearly 40 years. Marguerite had a young son, David, from her previous marriage, and together Josh and Marguerite had a daughter, Annie. Josh was a devoted father to both and treated David as his own son. He would have liked to adopt him, but David’s father objected to that. Alex Keynan describes (personal communication) how on a visit to Israel, when David was still very young, ‘Josh was able to explain what we were seeing to little David, in a language he could understand.’ Lederberg had a deep interest in his family’s origins, and on one visit to Israel was keen to visit the graves of his ancestors. He was aware of his Jewishness and of being a product of Jewish culture, with which he identified. Although brought up in a religious family, he was not himself religious, but he was very tolerant of other people’s religious beliefs.

In addition to his brother Seymour, who also became a scientist, Josh had a very much younger brother, Dov, who became a Chabad Chassid and an artist. Josh was on friendly terms with his brothers and visited Dov’s art exhibitions in New York. Even people who knew Josh Lederberg quite well, however, were mostly not aware of his personal life because, as Marguerite has said, he was ‘basically a very private person’.