Lederberg, Joshua (1925-) is an American geneticist and pioneer in the field of bacterial genetics. He received the 1958 Nobel Prize in physiology or medicine for his discoveries concerning the mechanics of genetic recombination and the organization of the genetic material of bacteria. He shared the prize with George Wells Beadle and Edward Lawrie Tatum, who won for their work related to the role of genes in particular chemical events.
Lederberg grew up in the Washington Heights district of Manhattan and attended Stuyvesant High School, which was highly regarded for its outstanding science curriculum. By the time he graduated, at the age of 16, he had already begun immersing himself in the study of cell biology and carried out some of his own independent research.
Intending to become a physician, Lederberg enrolled at Columbia College, taking the premedical track. While there, he met Francis Ryan, whose research into the biochemical genetics of the bread mold Neurospora further inspired Lederberg's interest in cell biology and genetics. In 1944, after receiving his B.A. degree with honors in zoology, he began graduate studies at Columbia University's College of Physicians and Surgeons, while continuing research with Ryan.
In the summer of 1946, after two years in medical school, Lederberg joined Yale University's Department of Microbiology and Botany under a research fellowship from the Jane Coffin Childs Fund for Medical Research. While there, he became increasingly fascinated by the study of bacterial genetics and at the end of the summer abandoned his plan to return to medical school. Instead, he continued on at Yale, working as a lab assistant under Tatum, a microbiologist and biochemist.
Before coming to Yale, Tatum, in collaboration with geneticist Beadle, had pioneered advances in the area of biochemical genetics, which studies the ways in which genetic code stored in cells translates into an organism's specific physical traits. Like Ryan, Tatum was studying Neurospora, and at Yale Lederberg helped him carry on with this research. At the same time, they also began investigations into other related areas.
In those years, the prevailing theory was that bacteria lacked genes and nuclei and that they reproduced asexually, through cell division, in which the cell split in half and the resultant two cells each contained a complete set of chromosomes. To test this theory, Lederberg and Tatum employed the bacteria Escherichia coli, an organism that lives in the human gastrointestinal tract. Their suspicions that bacteria might be capable of sexual reproduction were based on Tatum's earlier findings with Beadle regarding Neurospora and Lederberg's own joint research with Ryan in this area. These studies had shown that two fungal organisms could temporarily combine, or conjugate, to produce a “daughter” cell that combined genetic material from both of the two original organisms.
Applying variations of techniques already developed by Tatum and Beadle, Tatum and Lederberg found that sexual genetic recombination did indeed occur in some strains of the E. coli bacteria. The conjugation of two different strains of bacteria resulted in a genetically recombined cell that thereafter began to divide into new offspring cells whose genetic material was inherited from both parent cells.
This proof that bacterial reproduction echoed the normal fertilization processes of higher organisms was a significant break-through. The rapid growth and simple structure of bacteria, and the fact that bacterial conjugation was a common occurrence, provided much new fertile ground for genetic research, including the possibility of bacterial gene mapping.
Lederberg remained at Yale, working with Tatum until 1947, when he became assistant professor of genetics at the University of Wisconsin. The following year, he received his Ph.D. degree from Yale in microbiology.
Among other work in microbial genetics, he proved the longstanding hypothesis that genetic mutations are spontaneously occurring, and developed a laboratory procedure known as replica plating to isolate mutations in a bacteria species. By this method he successfully mated penicillin-resistant bacteria with streptomycin-resistant bacteria to produce a new strain that was resistant to both antibiotics. This work demonstrated that it was possible to strengthen or weaken the disease-producing powers of bacteria, as Lederberg managed to make an originally weak organism more virulent and vice versa.
One of Lederberg's most significant achievements at Wisconsin was his discovery of the phenomenon he called transduction. Assisted by Norman Zinder, then a graduate student, Lederberg found that bacteriophages, or viruses that infect bacteria, can carry the chromosomal material from the cell of one strain of bacterium to another entirely different strain. This process of transduction is unlike conjugation in that, whereas conjugation transmits the complete chromosomes from one bacteria to another, transduction transfers only fragments of DNA indirectly via the viral infection process.
Transduction begins when a virus infects a bacterium by inserting its genes into the cell. The viral DNA then directs the infected bacterium to produce new viruses, which will include copies of the original viral DNA. Some of the bacterium's own DNA may accidentally be copied and distributed by the next generation of viruses as well. When, in turn, the new viruses then infect another set of bacteria, some of the bacterial DNA will be incorporated into these newly infected cells along with genetic material from the second generation of viruses.
The discovery of transduction signaled the true beginning of recombinant genetics, in which bacterial cells may be manipulated or “engineered” in a laboratory setting through the intentional introduction of selected genes into a cell. Lederberg pioneered this work by breeding and crossbreeding microbes and viruses to create entirely new and unique strains of organisms having little similarity to the original parent cells.
During his 12 years at Wisconsin, Lederberg was promoted, in 1950, to associate professor, to full professor in 1954, at the age of 29, and in 1957, he organized the university's new department of medical genetics, becoming its first chairman. He held that position through 1958 and then moved to Stanford University in February 1959 as professor of genetics and biology. He was responsible for developing Stanford's new genetics department and served as its director from its inception. In 1962, Lederberg additionally took on the role of director of the Joseph P. Kennedy, Jr., Laboratories for Molecular Medicine. He remained at Stanford until 1978 and then served as president of Rockefeller University in New York City until 1990.
By proving that it might be possible to alter the genetic material of any organism, Lederberg's work revealed many potential applications in medical and biological research. Genetic engineering holds great promise for the treatment of numerous diseases, including cancer. With gene mapping comes the possibility of identifying those at risk of developing certain medical conditions and thereby genetically developing corresponding treatments through gene therapy, or the creation of “designer genes.” The advances in microbiology and genetics additionally promise new hope in organ transplants, geriatric medicine, and other areas. But the ability to develop intentionally harmful biological substances is already a realized hazard, one that Lederberg himself has devoted much time to speaking out about.
His concerns about the moral questions involved in recombinant genetics, and the far-reaching effects such technology may have, led him to become a scientific adviser to the World Health Organization and a consultant in international negotiations to control the use of biological weapons. He has also published and lectured extensively about the implications of such bioengineering.
With the advent of the U.S. space program, Lederberg became greatly interested in the field of exobiology, a term he coined to define the study of biochemical life beyond Earth, and acted as consultant to the U.S. Viking space missions to Mars.
Since 1990, Lederberg has been a professor emeritus at Rockefeller University's Laboratory of Molecular Genetics and Informatics, and continues to lecture, research, and serve on several advisory panels.