Lederberg, Joshua (1925- )
American geneticist
Joshua Lederberg is a Nobel Prize-winning American geneticist whose pioneering work on genetic recombination in bacteria helped propel the field of molecular genetics into the forefront of biological and medical research. In 1946, Lederberg, working with Edward Lawrie Tatum, showed that bacteria may reproduce sexually, disproving the widely held theory that bacteria were asexual. The two scientists' discovery also substantiated that bacteria possess genetic systems comparable to those of higher organisms, thus providing a new repertoire for scientists to study the genetic basis of life.
Continuing with his work in bacteria, Lederberg also discovered the phenomena of genetic conjugation and transduction, or the transfer of either the entire complement of chromosomes or chromosome fragments, respectively, from cell to cell. In his work on conjugation and transduction, Lederberg became the first scientist to manipulate genetic material, which had far-reaching implications for subsequent efforts in genetic engineering and gene therapy. In addition to his laboratory research, Lederberg lectured widely on the complex relationship between science and society and served as a scientific adviser on biological warfare to the World Health Organization.
Lederberg was born in Montclair, New Jersey. His family moved to New York City where he attended Stuyvesant High School. Through a program known as the American Institute Science Laboratory, Lederberg was given the opportunity to conduct original research in a laboratory after school hours and on weekends. Here he pursued his interest in biology, working in cytochemistry, or the chemistry of cells. Lederberg was influenced early on by science-oriented writers such as Bernard Jaffe, Paul de Kruif, and H. G. Wells.
After graduating from high school in 1941, Lederberg entered Columbia University as a premedical student. He received a tuition scholarship from the Hayden Trust, which, coupled with living at home and commuting to school, made it financially possible for him to attend college. Although his undergraduate studies focused on zoology, Lederberg also received a foundation in humanistic studies under Lionel Trilling, James Gutman, and others. H. Burr Steinbach fostered Lederberg's work in zoology and helped him obtain a space in a histology lab where he could pursue his own research. This early undergraduate research included the cytophysiology of mitosis in plants and the uses of genetic analysis in cell biology. In 1942, Lederberg met Francis Ryan, whose work in the biochemical genetics of Neurospora (a genus of fungi) was Lederberg's first opportunity to see significant scientific research as it occurred. Lederberg graduated with honors in 1944 with a B.A. at the age of nineteen.
At the age of seventeen, Lederberg enlisted in the United States Navy V–12 college training program, which featured a condensed pre-med and medical curriculum to produce medical officers for the armed services during World War II. During his years as an undergraduate, he was also assigned duty to the U.S. Naval Hospital at St. Albans in Long Island. He began his medical courses at Columbia College of Physicians and Surgeons in 1944, but left after two years to study under Edward L. Tatum in the microbiology department at Yale University.
Tatum, with George W. Beadle, had made substantial contributions to biochemical genetics, including investigations proving that the DNA (deoxyribonucleic acid) of Neurospora played a fundamental role in many of the chemical reactions in Neurospora cells. Lederberg was interested in natural selection and helped Tatum continue his studies of Neurospora. Eventually, Lederberg and Tatum proceeded to embark on a more tenuous line of research, studying Escherichia coli (a bacterium that lives in the gastrointestinal tract) for evidence of genetic inheritance. At the international Cold Spring Harbor Symposium of 1946, Lederberg and Tatum presented their research on E. coli in addition to the Neurospora studies. An audience that included the leading molecular biologists and geneticists in the world met the scientists' announcement that they had discovered sexual or genetic recombination in the bacterium with keen interest. The prevailing theory among biologists of the time was that bacteria reproduced asexually by cells essentially splitting, creating two cells with a complete set of chromosomes (threadlike structures in the cell nucleus that carry genetic information). Lederberg and Tatum had found evidence that some strains of E. coli pass on hereditary material cell to cell. They found that a conjugation of two cells produced a cell that subsequently began dividing into offspring cells. These offspring showed that they inherited traits from each of the parent strains. Lederberg received requests for E. coli cultures by others who wanted to investigate his findings.
In 1947, while at Yale, Lederberg received an offer from the University of Wisconsin to become an assistant professor of genetics. Although only two years away from receiving his M.D. degree, Lederberg accepted the position at Wisconsin and received his Ph.D. degree from Yale in 1948. He worked at the University of Wisconsin for a decade after abandoning his medical training, although he noted his later honorary medical degrees from Tufts University and the University of Turin as being among his most valued.
Lederberg continued to make groundbreaking discoveries at Wisconsin that firmly established him as one of the most promising young intellects in the burgeoning field of genetics. By perfecting a method to isolate mutant bacteria species using ultraviolet light, Lederberg was able to prove the long-held theory that genetic mutations occurred spontaneously. He found he could mate two strains of bacteria, one resistant to penicillin and the other to streptomycin, and produce bacteria resistant to both antibiotics. He also found that he could manipulate a virus's virulence.
Working with graduate student Norton Zinder, Lederberg discovered genetic transduction, which involves the transfer only of hereditary fragments of information between cells as opposed to complete chromosomal replication (conjugation). Lederberg went on to breed unique strains of viruses. Although these strains promised to reveal much about the nature of viruses in hopes of one day controlling them, they also posed a clear threat in terms of creating harmful biochemical substances. At the time, the practical aspect of Lederberg's work was hard to evaluate. The Nobel Prize Committee, however recognized the significance of his contributions to genetics and, in 1958, awarded him the Nobel Prize in physiology or medicine for the bacterial and viral research that provided a new line of investigations of viral diseases and cancer. Lederberg shared the prize with Beadle and Tatum. Lederberg's work in genetics eventually proved to be one of the foundations of gene mapping, which eventually led to efforts to genetically treat disease and identify those at risk of developing certain diseases.
Known as brilliant laboratory scientist and technician, Lederberg was also concerned with the role of science in society and the far-reaching effects of scientific discoveries, particularly in genetics. In a Pan American Health Organization/World Health Organization lecture in biomedical sciences called "Health in the World Tomorrow," Lederberg acknowledged concerns of the public, and even some scientists, over the newfound ability to tamper with the genetic code of life. However, he was more concerned with the many ethical questions that would arise over the inevitable success of the technological advances in microbiology and genetics. Lederberg saw the biological revolution as "a philosophical one" that was to bring a "new depth of scientific understanding about the nature of life." He foresaw advancements in the treatment of cancer, organ transplants, and geriatric medicine as presenting a whole new set of ethical and social problems, such as the availability and allocation of expensive health-care resources.
Lederberg was also interested in the study of biochemical life outside of Earth and coined the term exobiology to refer to such studies. Along with physicist Dean B. Cowie, he expressed concern in Science over the possible contamination of biological life on other planets from microbes carried by human spacecraft. He was also a consultant to the U.S. Viking space missions to the planet Mars.
Lederberg's career included an appointment as chairman of the new genetics department at Stanford University in 1958. In 1978 he was appointed president of Rockefeller University. Working with his first wife, Esther Zimmer, a former student of Tatum's whom Lederberg married in 1946, Lederberg investigated the role of bacterial enzymes in sugar metabolism. He also discovered that penicillin's ability to kill bacteria was due to its preventing synthesis of the bacteria's cell walls. Among Lederberg's many honors were the Eli Lilly Award for outstanding work by a scientist under thirty-five years of age and the Alexander Hamilton Medal of Columbia University.
Join eNotes
Over 3,500 study guides, question and answer forums, literature criticism, reference content, and much more!
