Joshua Lederberg

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Joshua Lederberg

NARA/UPI; NARA/Stanford U.

[b. Montclair, New Jersey, May 23, 1925]

In 1946 Lederberg and Edward Tatum announced that they had discovered genetic recombination in bacteria. Several years later Lederberg discovered that viruses called bacteriophages could transfer genetic material from one bacterium to another, a phenomenon he called transduction.

The geneticist Joshua Lederberg (born 1925) was a pioneer in the study of bacteria and viruses to determine the chemical and molecular basis of genetics.He shared the 1958 Nobel Prize for physiology or medicine with two associates. His work on genetic recombination propelled the field of molecular genetics to the forefront.

Joshua Lederberg is a Nobel Prize-winning geneticist whose pioneering work on genetic recombination in bacteria helped propel the field of molecular genetics into the forefront of biological and medical research. During the first four decades of the 20th century the study of heredity focused largely on the problem of transmission of genetic elements from parent to offspring. The organisms most commonly studied were higher animals and plants, in particular the small fruit fly Drosophila melanogaster and the domesticated corn Zea mays. In the period just preceding and following World War II, however, geneticists' attention began to shift to investigation of the structure and function of genes themselves. Higher organisms being less suitable for such studies, geneticists turned to much simpler forms such as bacteria and viruses. As a pioneer in this new line of research, Joshua Lederberg's studies on both bacteria and viruses paved the way for the modern-day understanding of the chemical and molecular bases of genetics.

Joshua Lederberg was born on May 23, 1925, in Montclair, New Jersey, the son of Rabbi Zwih H. and Esther (Goldenbaum) Lederberg. After his family moved to New York City he attended Stuyvesant High School, where early on he was introduced to biology. Through a program known as the American Institute Science laboratory, Lederberg was given the opportunity to conduct research in cytochemistry (chemistry of cells) after school hours and on weekends. He was influenced early on by reading the works of science oriented writers such as H.G. Wells, Bernard Jaffe and Paul De Kruif. For his Bar Mitzvah he received a copy of Meyer Bodansky's Introduction to Physiological Chemistry. He enrolled at Columbia University in New York in the premedical curriculum in 1941. He received a tuition scholarship from the Hayden Trust in order to afford the university. Serving as a laboratory assistant to Professor F. J. Ryan of the Zoology Department, Lederberg carried out several experiments on the mutation of the bread mold Neurospora, just then becoming an important organism for the study of biochemical genetics (that is, how genes control biochemical reactions in cells).

After receiving his B.A. with honors in 1944, at the age of 19, Lederberg entered the College of Physicians and Surgeons at Columbia University to pursue a medical career. He had enlisted in the US 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. While an undergraduate, Lederberg was assigned duty at the US Naval Hospital at St. Albans in Long Island. Two years into the medical curriculum however, he took a leave of absence from Columbia to pursue graduate research at Yale in the laboratory of Edward L. Tatum, who had pioneered in the use of Neurospora for the study of biochemical genetics. Although he had intended to work in Tatum's laboratory for only a few months, Lederberg remained at Yale for two years, receiving his Ph.D. in 1946. Working with Tatum, Lederberg studied the newly-discovered phenomenon of sexual reproduction in bacteria, particularly the species Escherichia coli. At Tatum's laboratory in New Haven, Lederberg had met his future wife Esther, who became an important geneticist in her own right, obtaining her Ph.D. from the University of Wisconsin.

In 1948 Lederberg accepted an appointment as assistant professor of genetics at the University of Wisconsin; he was named associate professor in 1950 and full professor in 1954. In 1957 he organized the Department of Medical Genetics and became its first chairman. Two years later, in 1959, Lederberg assumed the chairmanship of the newly formed Department of Genetics at Stanford University Medical School in Palo Alto, California. In 1962 he became director of the university's Kennedy Laboratories for Molecular Medicine. In 1978 he was appointed President of Rockefeller University.

Lederberg was most noted for two major discoveries. First, he showed that sex and regularized genetic exchange occurs in bacteria, just as in higher animals and plants (though by a different cellular mechanism). Second, he demonstrated that genetic exchange can also occur between bacteria through the agency of viruses, which carry portions of genes from one bacterial host cell to another. These two discoveries were pivotal in laying the methodological foundation for the study of the molecular organization and function of genes. He also discovered that penicillin's ability to kill bacteria was due to its preventing synthesis of the bacteria's cell walls.

Up until 1940, biologists generally accepted the apparent fact that bacteria reproduce solely by asexual means - that is, by the fission of one cell into two. Thus, in contrast to sexual reproduction, asexual reproduction produces genetically identical descendants; by definition there is no possibility of genetic exchange and recombination. By the end of his first year at Yale, however, Lederberg was convinced that bacteria have a sex life of sorts involving the process of conjugation, in which two cells of opposite ("male" and "female") mating strains come together and apparently exchange genetic information. In studying this process, Lederberg found that genes are transferred in an orderly fashion from one of the bacterial cells to the other during the conjugation process. Moreover, he found that the exchange was directly related to time, suggesting that the donor cell transferred a single linear chromosome at a uniform rate to the recipient. Lederberg immediately saw that if this were true, it provided a means of mapping the bacterial chromosome. He found that he could disrupt the mating process at regular intervals and then determine, by biochemical analysis, the various physiological deficiencies and new capabilities of recipient cells. Thus, it became possible to study the organization of genetic material in bacteria just as in higher animals and plants.

In 1952, in collaboration with his graduate student Norton D. Zinder, Lederberg discovered a second process of gene exchange between bacteria involving a bacterial virus (bacteriophage) as a carrier agent. Known as transduction, this process occurs when a bacteriophage infects one bacterial cell, reproducing itself inside using the bacteria's cell machinery. During this process the bacterial DNA (deoxyribonucleic acid) is degraded. Occasionally, bacterial DNA fragments become enclosed in a bacteriophage shell in place of the virus's DNA. These "pseudophages" are able to infect another host cell but cannot replicate bacteriophage (since they have no bacteriophage DNA). The fragment of bacterial DNA, however, can become incorporated into the second bacterium's genome and even function in its new host cell.

The significance of Lederberg's discoveries was far-reaching. In general, his methods opened up a whole new procedure for studying the structure and organization of the genetic material in both bacteria and viruses. It suggested - for the distant future - the possibility of engineering genetic exchanges so as to produce bacteria with particular desired genetic makeup. More immediately, it provided methods for studying gene function by making possible the isolation of particular genes, and thus made possible the study of their biochemical effects. It also provided the basis for understanding the mechanism of viral and bacterial disease in animals and plants, since in many cases viral genes become incorporated into host cell DNA, producing long-term, even hereditary, effects. Indeed, much of the subsequent work in the development of molecular biology in the 1950s and 1960s was based on the methods developed by Lederberg and his associates. With George W. Beadle and Edward L. Tatum, Lederberg shared the 1958 Nobel Prize in physiology or medicine for, in the words of the committee, "his discoveries concerning genetic recombination and the organization of the genetic material of bacteria." 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.

In addition to his outstanding contributions as a laboratory scientist and technician Lederberg was also concerned about the role of science in society and the far reaching effects of genetics research. He saw that the biological revolution was a "philosophical one" that was to bring new depth of scientific understanding about the nature of life. He foresaw scientific advancements in the treatment of cancer, organ transplants and geriatric medicine developing into a whole new set of ethical and social problems.

After divorcing his first wife, Lederberg married Marguerite Stein Kirsh in 1968 with whom he had two children, a daughter and son. While Lederberg was made very aware throughout his life of the stiffness of personal competition, he remained firm in his belief that scientific discoveries, no matter how slight, were beneficial to the world. "The shared interests of scientists in the pursuit of a universal truth," Lederberg said in The Excitement and Fascination of Science, "remain among the rare bonds that can transcend bitter personal, national, ethnic, and sectarian rivalries." He was a member of the National Academy of Sciences, the Royal Society, London, and has received eleven honorary degrees. Lederberg still considered chemical and biological weapons to be a matter of the gravest concern in today's society, and provided an extensive scientific consulting service to the United States government, which earned Lederberg the National Medal of Science in 1989. In the summer of 1997, Lederberg was studying the deadly 1918 flu virus, found in preserved tissue, in an attempt to find a vaccine against the disease that killed over 20 million people in Europe alone.

Further Reading

Biographical information on Lederberg may be found in the McGraw-Hill Modern Men of Science (Vol. 1, 1960). A general discussion of the significance of Lederberg's work, in conjunction with that of Beadle and Tatum, is in the New York Times (October 31, 1958). Also available are works by Lederber himself Papers in Microbial Genetics: Bacteria and Bacterial Viruses, University of Wisconsin Press, 1951; Man and his Future, Little, Brown, 1963, pp. 263-273; Health in the World Tomorrow, Third PAHO/WHO lecture on Biomedical sciences, PAHO/WHO Scientific Publications no. 175, 1968, pp. 5-15; The Excitement and Fascination of Science: reflections by Eminent Scientists, Vol. 3, Part 1, Rockefeller University, 1990, pp. 893-915.

Joshua Lederberg
E. Lederberg, G. Stent, S. Brenner, J. Lederberg, 1965
Born	May 23, 1925(1925-05-23) Montclair, New Jersey
Died	February 2, 2008 (aged 82) NewYork-Presbyterian Hospital pneumonia
Nationality	American
Fields	Microbiologist
Alma mater	Stuyvesant High School, Columbia University, Yale University
Known for	Neurospora crassa Bacterial conjugation Dendral Astrobiology Transduction
Notable awards	Nobel Prize in Physiology or Medicine (1959) National Medal of Science (1989) Presidential Medal of Freedom(2006)

Joshua Lederberg (May 23, 1925 – February 2, 2008)^[1] was an American molecular biologist known for his work in genetics, artificial intelligence, and space exploration. He was just 33 years old when he won the 1958 Nobel Prize in Physiology or Medicine for discovering that bacteria can mate and exchange genes.^[2] He shared the prize with Edward L. Tatum and George Beadle who won for their work with genetics.

In addition to his contributions to biology, Lederberg did extensive research in artificial intelligence. This included work in the NASA experimental programs seeking life on Mars and the chemistry expert system Dendral.

Contents 1 Early life and education 2 Bacterial genetics 3 Post Nobel Prize research 4 Personal 5 See also 6 References 7 External links

Early life and education

Lederberg was born in Montclair, New Jersey, to Esther Goldenbaum Schulman Lederberg and Rabbi Zvi Hirsch Lederberg, in 1925, and moved to Washington Heights, Manhattan as an infant.^[3] He had two younger brothers. Lederberg graduated from Stuyvesant High School in New York City at the age of 15 in 1940.^[4] After graduation, he was allowed lab space as part of the American Institute Science Laboratory, a forerunner of the Westinghouse Science Talent Search. He enrolled in Columbia University in 1941, majoring in zoology. Under the mentorship of Francis J. Ryan, he conducted biochemical and genetic studies on the bread mold Neurospora crassa. Intending to receive his MD and fulfill his military service obligations, Lederberg worked as a hospital corpsman during 1943 in the clinical pathology laboratory at St. Albans Naval Hospital, where he examined sailors' blood and stool samples for malaria. He went on to receive his undergraduate degree in 1944.

Bacterial genetics

He began medical studies at Columbia's College of Physicians and Surgeons while continuing to perform experiments. Inspired by Oswald Avery's discovery of the importance of DNA, Lederberg began to investigate his hypothesis that, contrary to prevailing opinion, bacteria did not simply pass down exact copies of genetic information, making all cells in a lineage essentially clones. After making little progress at Columbia, Lederberg wrote to Edward Tatum, Ryan's post-doctoral mentor, proposing a collaboration. In 1946 and 1947, Lederberg took a leave of absence to study under the mentorship of Tatum at Yale University. Lederberg and Tatum showed that the bacterium Escherichia coli entered a sexual phase during which it could share genetic information through bacterial conjugation.^[5] With this discovery and some mapping of the E. coli chromosome, Lederberg was able to receive his Ph. D. from Yale University in 1947.

Instead of returning to Columbia to finish his medical degree, Lederberg chose to accept an offer of an assistant professorship in genetics at the University of Wisconsin–Madison. He married Esther Miriam Zimmer, who went with him to Wisconsin. She received her doctorate there in 1950.

Lederberg and his graduate student Norton Zinder went on to show in 1952 that bacteriophages could transfer genetic information between bacteria in Salmonella^[6]. This process, called transduction, explained how bacteria of different species could gain resistance to the same antibiotic very quickly.

Esther Lederberg published a paper dealing with the discovery of lambda in 1950.^[7] This was followed in 1952 by papers written by Norton Zinder and Joshua Lederberg dealing with bacteriophage lambda.^[8]

During her time in Joshua Lederberg's laboratory, Esther Lederberg also discovered fertility factor F, later publishing with Joshua Lederberg and Luigi Luca Cavalli-Sforza. In 1956, the Society of Illinois Bacteriologists awarded Joshua Lederberg and Esther Lederberg the Pasteur Medal, for "their outstanding contributions to the fields of microbiology and genetics".

In 1957, Joshua Lederberg founded the Department of Medical Genetics at the University of Wisconsin–Madison.

Post Nobel Prize research

Joshua Lederberg (right) receiving The National Medal of Science from George H. W. Bush.

In 1958, Joshua Lederberg received the Nobel Prize and moved to Stanford University where he was the founder and chairman of the Department of Genetics. He collaborated with Frank Macfarlane Burnet to study viral antibodies. With the launching of Sputnik in 1957, Lederberg became concerned about the biological impact of space exploration. In a letter to the National Academies of Sciences, he outlined his concerns that extraterrestrial microbes might gain entry to Earth onboard spacecraft, causing catastrophic diseases. He also argued that, conversely, microbial contamination of manmade satellites and probes may obscure the search for extraterrestrial life. He advised quarantine for returning astronauts and equipment and sterilization of equipment prior to launch. Teaming up with Carl Sagan, his public advocacy for what he termed exobiology helped expand the role of biology in NASA. In the 1960s, he collaborated with Edward Feigenbaum in Stanford's computer science department to develop DENDRAL.

In 1978, he became the president of Rockefeller University, until he stepped down in 1990 and became professor-emeritus of molecular genetics and informatics at Rockefeller University.

Throughout his career, Lederberg was active as a scientific advisor to the U.S. government. Starting in 1950, he has been a member of various panels of the Presidential Science Advisory Committee. In 1979, he became a member of the U.S. Defense Science Board and the chairman of President Jimmy Carter's President's Cancer Panel. In 1989, he received National Medal of Science for his contributions to the scientific world. In 1994, he headed the Department of Defense's Task Force on Persian Gulf War Health Effects, which investigated Gulf War Syndrome.

In 2006, Lederberg was awarded the Presidential Medal of Freedom.

Personal

Lederberg married fellow scientist Esther Miriam Zimmer in 1946; they divorced in 1966. He married psychiatrist Marguerite Stein Kirsch in 1968. He was survived by Marguerite, their daughter, Anne Lederberg, and his stepson, David Kirsch.

See also

• LCF notation

References

1. ^ Joshua Lederberg, Rockefeller University's fifth president, dies at 82
2. ^ Warwick, K. "The Joshua Lederberg Papers: Profiles in Science, National Library of Medicine", Biography,Volume 24, Number 4, Fall 2001, pp. 978-982
3. ^ Broad, William J. "Joshua Lederberg, 82, a Nobel Winner, Dies", The New York Times, February 5, 2008. Accessed April 22, 2008. "Dr. Lederberg was born May 23, 1925, in Montclair, N.J., to Zvi Hirsch Lederberg, a rabbi, and the former Esther Goldenbaum, who had emigrated from what is now Israel two years earlier. His family moved to the Washington Heights section of Manhattan when he was 6 months old."
4. ^ "Joshua Lederberg - The Nobel Prize in Physiology or Medicine 1958 - Biography". 1958. http://nobelprize.org/nobel_prizes/medicine/laureates/1958/lederberg-bio.html. Retrieved 2007-10-31. 
5. ^ Lederberg, Joshua, E. L. Tatum, "Gene recombination in E. coli", Nature 158 p. 558, October 19, 1946.
6. ^ Zinder, Norton D. Joshua Lederberg: "Genetic Exchange in Salmonella", Journal of Bacteriology 64(5), November 1952, pp. 679-699
7. ^ Lederberg, E. M., 1950, "Lysogenicity in Escherichia coli strain K-12", Microbial Genetics Bulletin, 1, pp. 5-9, Jan. 1950, Univ. of Wisconsin [Evelyn Maisel Witkin, Editor], Ohio State University, ISSN: 0026-2579, call No. 33-M-4, OCLC: 04079516, Accession Number: AEH8282UW
8. ^ From the series "Perspectives: Anecdotal, Historical and Critical Commentaries on Genetics", edited by James F. Crow and William F. Dove: "Replica Plating and Indirect Selection of Bacterial Mutants: Isolation of Preadaptive Mutants in Bacteria by Sib Selection", Genetics 121, pp 395-399, March, 1989

External links

• National Library of Medicine - The Joshua Lederberg Papers
• Nobel biography
• In Memoriam: Joshua Lederberg (1925-2008)

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