Lederberg, Joshua

Lederberg, Joshua
May 23, 1925-Feb. 2, 2008
American geneticist


The American geneticist Joshua Lederberg was born in Montclair, New Jersey, to Zwi Hirsch Lederberg, a rabbi, and Esther (Goldenbaum) Lederberg, who had emigrated from Palestine two years earlier. Lederberg received his early education in the New York City public school system, graduating from Stuyvesant High School in 1941. He studied zoology as a premedical student at Columbia University and received his B.A. with honors at the age of nineteen. He went on to medical school at the College of Physicians and Surgeons, Columbia University, but continued to do research with F. J. Ryan of the department of zoology at Columbia.

After two years in medical school, Lederberg went to Yale University during the summer of 1944 as a research assistant in the department of microbiology. Although he had planned to return to medical school that fall, he stayed on at Yale to continue his research and study for a Ph.D. in microbiology under Edward L. Tatum, a microbiologist and biochemist.

At Stanford, Tatum and his colleague George W. Beadle had done pioneering work in the field of biochemical genetics, a subdiscipline of genetics that seeks to determine the biochemical processes involved in the translation of the genotype (a specific set of genetic instructions) of an organism into its phenotype (a specific set of physical traits). The science of genetics began in 1865, when Gregor Mendel, a Dominican monk, published his studies of the laws of inheritance. Mendel postulated that "elements," now called genes, govern the inheritance of physical traits.

At the turn of the century Mendel's work, which had been rejected in his lifetime, became the basis for new research. Scientists found that genes reside on chromosomes, strands of material in the nucleus of the cell. Yet it was not until 1940 that researchers discovered that genes are made of the nucleic acid deoxyribonucleic acid (DNA). From Hermann J. Muller's work in the 1920s, it was known that X rays produce genetic mutations, and thus Tatum and Beadle were able to produce mutations in a fungus in the early 1940s. They proved that genes, or DNA, direct the production of cellular enzymes (proteins necessary for a variety of chemical reactions in the body), and thus control the biochemical processes of the cell.

At the time Lederberg began studying the genetics of bacteria with Tatum, scientists believed that bacteria reproduced asexually, one bacterial cell dividing into two cells. From the work of Tatum and Beadle and from his own research at Columbia, however, Lederberg knew that fungal organisms reproduce sexually by the temporary combination, or conjugation, of two separate fungal organisms to form a third, or daughter, cell. Lederberg suspected that bacteria also reproduced sexually, and to find out whether this was true, he and Tatum investigated the colon bacillus, the rodshaped bacterium Escherichia coli, which resides in the gastrointestinal tract of humans and other animals. They discovered that this bacterium may reproduce sexually by the conjugation of two separate bacterial cells. The bacterial daughter cell that is produced in this way divides, and new generations of cells are produced by successive divisions of its offspring. When Lederberg and Tatum mated two different strains of colon bacillus, they discovered that the offspring cells inherited certain traits from each parent strain, a process they called sexual genetic recombination. Genetic recombination of bacterial cells involves the transfer of a full complement of chromosomes, and their genes, from one cell to the other.

Lederberg left Yale in 1947 to become professor of genetics at the University of Wisconsin, where he continued to investigate genetic recombination of bacteria. The following year he received his Ph.D. in microbiology from Yale. At Wisconsin Lederberg developed the technique of replica plating, a laboratory method that isolates mutations of a bacteria species by using ultraviolet light or other mutant-inducing agents. He proved that genetic mutations occur spontaneously, thus confirming a long-held hypothesis in the field of evolutionary genetics. By using the replica plating technique to mate bacteria that were resistant to penicillin with others that were resistant to streptomycin, he produced bacteria that were resistant to both antibiotics. He also demonstrated that by similar methods clinically weak bacteria could be made virulent, and clinically virulent bacteria could be made weak.

In collaboration with Norton Zinder, a graduate student at the University of Wisconsin, Lederberg discovered the phenomenon of transduction in bacteria. Transduction, the transfer of fragments of chromosomal material from one cell to another, alters the genetic code of the recipient cell. Some scientists believe that viruses may also alter the genetic code of bacteria by a process resembling transduction. Because determination of the order of genes on chromosomes depends on methods related to transduction, Lederberg's work contributed to subsequent research and discoveries in the genetics of bacteria. It also prepared the way for the development of modern recombinant genetics, the study of processes whereby the genetic code of bacterial cells can be manipulated to produce certain biochemical substances.

In 1957 Lederberg was asked to organize the department of genetics at Wisconsin and serve as its chairman. A Fulbright Fellowship enabled him to conduct research at Melbourne University in Australia before assuming his new responsibilities.

Lederberg was awarded the 1958 Nobel Prize for Physiology or Medicine "for his discoveries concerning the genetic recombination and the organization of the genetic material of bacteria." The other half of the prize was divided between Beadle and Tatum for their work on the role of genes in specific chemical events.

The same year he received the Nobel Prize, Lederberg was named the Joseph Grand Professor of Genetics and chairman of the newly created department of genetics at Stanford University, where, in 1962, he was also appointed director of the Joseph P. Kennedy Jr. Laboratories for Molecular Medicine.

During the early years of the American space program, Lederberg speculated on the scientific and medical consequences of space exploration and served as a consultant to the Viking program that sent a spacecraft to Mars. He was also a scientific adviser to the World Health Organization on biological warfare and biological weapons.

In 1978 Lederberg left Stanford to become president of Rockefeller University. In addition to his work on genetics, he has written extensively on the biological sciences and the future of the human species.

In 1946 Lederberg married Esther Zimmer, a former graduate student of Tatum's. After their divorce, he married Marguerite Stein Kirsch in 1968; they have one son and one daughter.

In addition to the Nobel Prize, Lederberg has received the Eli Lilly Award of the Society of American Bacteriologists (1953) and the Alexander Hamilton Medal of Columbia University (1961). He has received honorary degrees from Yale, Columbia, and New York universities and from the University of Turin. He is a member of the National Academy of Sciences, the American Chemical Society, and the Genetics Society of America. He was elected a foreign member of the Royal Society of London in 1979.

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