Joshua Lederberg Biography (1925-)


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 mayreproduce 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 newrepertoire for scientists to study the genetic basis of life.

Continuing with his work in bacteria, Lederberg also discovered the phenomenaof genetic conjugation and transduction--or the transfer of either the entire complement of chromosomes or chromosome fragments, respectively--from cellto 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, on May 23, 1925. His father, ZwiHirsch Lederberg, was a rabbi; his mother, Esther Goldenbaum, had emigratedfrom Palestine two years before Lederberg was born. Lederberg's parents movedto New York City, eventually settling in the Washington Heights district. Lederberg attended the city's public schools, where, as he wrote in the book The Excitement and Fascination of Science: Reflections of Eminent Scientists, he was a precocious youth whose inquiring mind was nurtured by "a cadre of devoted and sympathetic teachers." At Stuyvesant High School (which specialized in science education), Lederberg first encountered other youths who could compete with him intellectually. Through a program known as the AmericanInstitute Science Laboratory, Lederberg was given the opportunity to conductoriginal research in a laboratory after school hours and on weekends. Here he pursued his interest in biology, working in cytochemistry, or the chemistryof cells. A voracious reader, Lederberg was influenced early on by science-oriented writers such as Bernard Jaffe, Paul de Kruif, and H. G. Wells. For aBar Mitzvah present he received Meyer Bodansky's Introduction to Physiological Chemistry, and on his sixteenth birthday, E. B. Wilson's The Cell in Development and Heredity.

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 his living at home and commuting to school, madeit 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. Lederberg's workin zoology was fostered by H. Burr Steinbach, who helped Lederberg get spacein a histology lab to pursue his own research. This early undergraduate research included an interest in the cytophysiology of mitosis in plants and theuses of genetic analysis in cell biology. In 1942, Lederberg met Francis Ryan, whose work in the biochemical genetics of Neurospora was Lederberg'sfirst opportunity to see significant scientific research as it occurred. Lederberg graduated with a B.A. with honors in 1944 at the age of nineteen.

At the age of seventeen, Lederberg had 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 WarII. While an undergraduate he also was assigned duty at the U.S. Naval Hospital at St. Albans in Long Island. He began his medical courses at the ColumbiaCollege of Physicians and Surgeons in 1944, but left after two years to study under Edward L. Tatum in the microbiology department at Yale University.

In spring of 1945 Ryan had suggested that Lederberg ask Tatum--who had made substantial contributions to biochemical genetics--if Lederberg could work inTatum's lab at Yale. Lederberg was interested in natural recombination; and Tatum, working with George W. Beadle, had done pioneering investigations proving that the DNA (deoxyribonucleic acid) of Neurospora (a genusof fungi) played a fundamental role in many of the chemical reactions in Neurospora cells. While Lederberg helped Tatum continue his studies of Neurospora, the two 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 ColdSpring Harbor Symposium of 1946, Lederberg and Tatum were graciously grantedadditional time to talk about their E. Coli research in addition to the Neurospora studies. The scientists' announcement that they had discovered sexual or genetic recombination in the bacterium was met with keen interest by an audience that included the leading molecular biologists and geneticists in the world. The prevailing theory among biologists of the time was that bacteria reproduced asexually by cells essentially splitting, creating twocells with a complete set of chromosomes (threadlike structures in the cellnucleus 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.

In The Excitement and Fascination of Science, Lederberg recalled the intense scrutiny this discovery came under at the Cold Spring Harbor Symposium. André Lwoff suggested that perhaps what they had found was across-feeding of nutrients between the cells. But in general at that meetingand a second one the following year, Lederberg found the giants of genetics,such as Jacques Monod, Salvador E. Luria, and Lwoff, to be supportive of and interested in his research. Lederberg also received requests for E. coli cultures by others who wanted to investigate his findings.

Lederberg's interest in basic research began to draw him further and furtheraway from pursuing a medical career. In 1947 while at Yale he received an offer from the University of Wisconsin to become an assistant professor of genetics with a focus on the new field of microbial genetics. Although only two years away from receiving his M.D. degree, Lederberg viewed his return to medical school in The Excitement and Fascination of Science as a "grave (ifnot total) interruption of research at its most exciting stage." His prospective appointment at Wisconsin was met with some skepticism concerning his youth (he was only twenty-two) and his yet-to-be fully-accepted research. More troubling personally were references to his character and his Jewish heritage.But the strong support of senior colleagues at Wisconsin and Yale prevailed.Lederberg accepted the position at Wisconsin (receiving his Ph.D. degree from Yale in 1948) and spent a fruitful and satisfying decade there. He never regretted abandoning his medical training, although he noted his later honorarymedical degrees from Tufts University and the University of Turin as being among his most valued.

Lederberg continued to make groundbreaking discoveries at Wisconsin and firmly established himself as one of the most promising young intellects in the burgeoning field of genetics. By perfecting a method to isolate mutant bacteriaspecies 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 a 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 daycontrolling them, they also posed a clear threat in terms of creating harmfulbiochemical 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. Lederbergshared the prize with Beadle and Tatum. Lederberg's work in genetics eventually proved to be one of the foundations of gene mapping, which eventually ledto efforts to genetically treat disease and identify those at risk of developing certain diseases.

A brilliant laboratory scientist and technician, Lederberg was also concernedwith 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 inthe World Tomorrow," Lederberg acknowledged concerns of the public, and evensome scientists, over the newfound ability to tamper with the genetic code of life. But he was more concerned with the many ethical questions that wouldarise over the inevitable successes the advancing fields of microbiology andgenetics were ushering in. 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.

Although Lederberg had a profound faith in science, he was not so confident of scientists' ability to rationally communicate the ramifications of their work. In Man and His Future, he lamented the "archaic clumsiness of ourbasic mechanisms of communication. Man's dilemma," he said, "is the discrepancy between the size of his population and the complexity of his institutions,on one hand, and his individual feebleness, measured as a data input rate ofno more than fifty bits per second."

Lederberg was also interested in the study of biochemical life outside of earth and coined the term exobiology to refer to such studies. Along withphysicist Dean B. Cowie, he expressed concern in Science over the possible contamination of biological life on other planets from microbes carriedby 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 thebacteria'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 theAlexander Hamilton Medal of Columbia University. After divorcing his first wife, Lederberg married Marguerite Stein Kirsch in 1968, with whom he had two children, a daughter and a son.

While Lederberg recognized the intense competition that sometimes arises among modern-era scientists, he described his own personal scientific dealings ascongenial. "The shared interests of scientists in the pursuit of a universaltruth," said Lederberg in The Excitement and Fascination of Science,"remain among the rare bonds that can transcend bitter personal, national, ethnic, and sectarian rivalries."

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