Professor Joshua Lederberg: Molecular biologist who developed the new science of bacterial genetics and won a Nobel Prize at 33

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The Independent Online

Joshua Lederberg, one of the pre-eminent scientists of the 20th century, was only 33 when he was awarded the 1958 Nobel Prize for Physiology or Medicine for work showing that bacteria were capable of genetic recombination. The presentation of the award specifically mentioned conjugation (frequently referred to as "sex in bacteria") and transduction.

Both of these discoveries were fundamental to the development of molecular biology and biotechnology as we know it today. Many of the procedures that investigators now use, and take for granted, derive from those early investigations.

Born in 1925 in Montclair, New Jersey, Joshua was the eldest of the three sons of Zvi Hirsch Lederberg, and his wife Esther, who had emigrated from Palestine as a newly married couple the previous year. In spite of his father's initial disapproval, Joshua became captivated by science at a very early age and devoted his life to scientific inquiry. He attended Stuyvesant High School in New York, which emphasised training in science and technology, and graduated at the age of 15.

In 1941 he matriculated at Columbia University, obtaining a BA with honours in Zoology in 1944. While at Columbia he worked in the laboratory of Francis J. Ryan, who became an important mentor. In 1946, with Ryan's encouragement, Joshua Lederberg went to the laboratory of Edward L. Tatum at Yale University, specifically to try to demonstrate genetic recombination in bacteria. Tatum had recently moved to Yale from Stanford University in California, bringing with him mutants of a strain of bacteria, Escherichia coli K-12, which proved crucial to the experiments Lederberg wished to perform. It was with these mutants that genetic exchange in bacteria was first demonstrated.

Good luck contributed substantially to the success of this enterprise. Only about 5 per cent of the various strains of E.coli are capable of mating; fortunately K-12 was one them. It was also fortunate that Tatum had moved from far-off California to Connecticut, or the collaboration might not have been possible. A further advantage was the fact that Tatum had already isolated double mutants of K-12, making it possible to do the critical experiments in less time than would have otherwise been required. The results were first published that same year ("Gene recombination in Escherichia coli" in Nature, 1946).

The collaboration with Tatum led to a PhD from Yale in 1947, followed swiftly by a move to the University of Wisconsin in Madison where Lederberg had been offered a faculty appointment. The years at Madison (1947-59) were highly productive. Together with his wife, Esther Zimmer, whom he married in 1947, his students and his colleagues, Lederberg developed the new science of bacterial genetics. Information about genetic recombination was extended, new bacterial mutants were isolated, new combinations of mutants produced, and new phenomena described.

The genetic exchange he had first observed, known as conjugation, depended on contact between bacteria. It did not occur if the bacteria were not mixed together. In Madison a new type of genetic exchange was discovered which Lederberg called "transduction". Transduction was first observed in derivatives of Salmonella, and subsequently in E.coli. Transduction depends not on contact between bacteria but on bacterial viruses that incorporate fragments of the bacterial chromosome and transfer them to other bacteria in which the fragments become functional.

As the genetics of E.coli became more clearly understood, and more experimentally tractable, this bacterium became an increasingly popular laboratory organism, not only for genetic investigations but also for biochemical studies that provided the foundation for the area of scientific inquiry known as molecular biology.

It was for these achievements that Lederberg was awarded the Nobel Prize in 1958, sharing it with George W. Beadle and Edward L. Tatum. His contributions to science and society, however, had only begun.

In 1957 he became concerned about the biological implications of space exploration. Sending objects to the moon, for example, might contaminate it and make it impossible to answer fundamental questions about the origin of life, while returning objects might bring back organisms that could cause catastrophic epidemics on earth. To address these concerns, he became a founding member of the Space Science Board and advised the National Aeronautics and Space Administration (Nasa) on the importance of "exobiology", a term he coined for the study of life beyond earth and its atmosphere.

In 1959 Lederberg moved to Stanford University where he organised the Department of Genetics in the School of Medicine. Here he continued investigations into bacterial genetics as well as exobiology, and, being a true polymath, extended the reach of his interests into computer science and its applications to medicine and chemistry. A few examples of these activities are: the establishment of the Instrumentation Research Laboratory which employed engineers to devise instruments that could detect life on other planets; the development of a national computer network (SUMEX-AIM) to host biomedical research projects; and the collaboration to develop Dendral, a program designed to apply "artificial intelligence" to problems in chemistry and medicine.

One aspect of these activities was that they brought together experts in fields that might otherwise never have interacted with each other: chemists with computer scientists, engineers with geneticists, for example. The outcomes were often unforeseen and synergistic. While at Stanford, in 1966, Joshua and Esther divorced, and two years later he married Marguerite Kirsch.

Lederberg left Stanford in 1978 and returned to New York City as President of Rockefeller University. He reinvigorated the university both intellectually and physically. He appointed talented investigators, emphasising research on biomedical problems, and was the catalyst for the construction of new buildings to provide housing and laboratory space for investigators.

He also continued to serve on various national and international advisory committees, addressing various concerns including emerging infections, internet access, and educating the public about science. In 1989 he was awarded the US National Medal of Science by President George Bush.

Lederberg "retired" in 1990, becoming President Emeritus of Rockefeller, but continued his research activities as Raymond and Beverly Sackler Foundation Scholar and Professor Emeritus of Molecular Genetics and Informatics. In 2006 he received the Presidential Medal of Freedom from President George W. Bush. In addition to many other honours and degrees, Lederberg was a member of the US National Academy of Science and a Foreign Member of the Royal Society.

Ann Ganesan

Joshua Lederberg, molecular biologist: born Montclair, New Jersey 23 May 1925; Assistant Professor of Genetics, Wisconsin University 1947-50, Associate Professor 1950-54, Professor 1954-59; Nobel Prize for Physiology or Medicine (jointly) 1958; Professor and Executive Head, Department of Genetics, School of Medicine, Stanford University 1959-78; President, Rockefeller University 1978-90 (Emeritus), University Professor 1990-95 (Emeritus), Sackler Scholar 1995-2008; married 1947 Esther Zimmer (marriage dissolved 1966), 1968 Marguerite Kirsch (one daughter, one stepson); died New York 2 February 2008.