(1925-) Joshua Lederberg, American microbiologist, winner of the Nobel Prize in Physiology or Medicine in 1958, played a major role in the creation and development of bacterial genetics.
Joshua Lederberg, who was born in Montclair, New Jersey, USA, carried out the first experiments demonstrating the existence of genetic recombination in bacteria, similar to that occurring during sexual reproduction in higher organisms. In 1946, while he was still a student at Columbia University, the twenty-one-year-old Lederberg carried out these experiments in collaboration with Edward Tatum during a 6-week stay at Yale. Some years previously, with George Beadle, Tatum had obtained different mutants of the mould Neurospora crassa that were affected in their metabolic pathways and unable to grow on minimal media. He then extended the same approach to the bacterium Escherichia coli. These metabolic mutants were the essential tool used by Joshua Lederberg to demonstrate the existence of a genetic exchange process in E. coli: recombination between the different mutants could be easily observed by using appropriate culture media.
Lederberg subsequently described his discovery as ‘postmature’, in the sense that there was delayed recognition of this mechanism: the absence of any form of genetic recombination or sexual reproduction in bacteria appeared more and more to be a puzzling exception in the living world in the 1940s. The mechanism of genetic recombination in bacteria was further characterized in the following years by Lederberg, William Hayes, Elie Wollman and François Jacob. The amplitude of genetic exchange is limited, and in hindsight Lederberg's success can be considered to be the result of chance choices in the design of the experimental system.
In 1950, in collaboration with Norton Zinder, Lederberg described a second mechanism of genetic exchange between bacteria - transduction. Transduction is the process by which bacterial viruses (called bacteriophages) carry bacterial genes, which are tightly associated with their genomes, from one bacterium to another. Both phenomena discovered by Lederberg - bacterial mating (called conjugation) and phage transduction - were essential tools for the development of bacterial genetics and therefore of molecular biology: they led to Lederberg being awarded the 1958 Nobel Prize in Physiology or Medicine.
Lederberg's third major contribution to molecular biology provided a molecular interpretation of the clonal theory of antibody production proposed by the Australian immunologist Sir Frank MacFarlane Burnet. Lederberg confirmed that each antibody-producing cell synthesizes one unique form of antibody. He suggested that each different antibody corresponds to a specific gene sequence. As the genome is not large enough to harbour as many genes as there are different forms of antibodies, he hypothesized that these different genic forms result from a process of somatic mutation. This was confirmed experimentally some years later.
Lederberg was Professor at the University of Wisconsin, and then at Stanford University School of Medicine before going back to Rockefeller University in 1978. In addition to his research endeavours in bacterial genetics and microbiology, he is also known as the editor of the four-volume Encyclopedia of Microbiology. Lederberg also had many responsibilities in science policy: in particular, he was President of Rockefeller University.
Lederberg's most remarkable trait is probably his capacity to anticipate future developments in science, as well as emerging problems at the intersection between science, medicine and social interests. He foresaw the development of genetic engineering technology, and participated in its first steps. As early as 1960, he encouraged the development of exobiological studies, a proposal that was only accomplished 30 years later with the rise of astrobiology.
His main concerns at the end of his career were public health, biomedical science and developing countries, the problems of toxicology and environment, and the future of infectious diseases considered from an evolutionary point of view with the threat of new diseases. In many cases, such as the problem of bioterrorism, his analyses preceded the social concerns. This prospective work was supported by his deep interest in the past developments of science, a historical scope extending far beyond his own scientific contribution.
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