Joshua Lederberg

Joshua Lederberg ForMemRS
Lederberg in New Delhi, India
5th President of Rockefeller University
In office 1978–1990
Preceded by	Frederick Seitz
Succeeded by	David Baltimore
Personal details
Born	(1925-05-23)May 23, 1925 Montclair, New Jersey
Died	February 2, 2008(2008-02-02) (aged 82) New York City
Spouse(s)	Esther Miriam Zimmer (1946–1966; divorced) Marguerite Stein Kirsch (1968–2008; 1 child, 1 stepchild)
Alma mater	Stuyvesant High School Columbia University Yale University
Known for	Neurospora crassa Bacterial conjugation Dendral Astrobiology Transduction
Awards	Nobel Prize in Physiology or Medicine (1958) National Medal of Science (1989) Presidential Medal of Freedom (2006)
Scientific career
Fields	Microbiologist
Thesis	Genetic recombination in Escherichia coli (1947)
Doctoral advisor	Edward Tatum
Doctoral students	Norton Zinder

Joshua Lederberg ForMemRS^[1] (May 23, 1925 – February 2, 2008)^[2] was an American molecular biologist known for his work in microbial genetics, artificial intelligence, and the United States space program. He was 33 years old when he won the 1958 Nobel Prize in Physiology or Medicine for discovering that bacteria can mate and exchange genes (bacterial conjugation).^[3] He shared the prize with Edward 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.

Later in his life, he was a proponent of eugenics.^[4]

Early life and education

Lederberg was born in Montclair, New Jersey, to a Jewish family, son of Esther Goldenbaum Schulman Lederberg and Rabbi Zvi Hirsch Lederberg, in 1925, and moved to Washington Heights, Manhattan as an infant.^[5] He had two younger brothers. Lederberg graduated from Stuyvesant High School in New York City at the age of 15 in 1941.^[6] 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

Lederberg alongside his wife, esteemed microbiologist and feminist figure,^[7] Esther Lederberg and their friends Gunther Stent and Sydney Brenner in 1965

Joshua Lederberg 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.^[8][9] With this discovery and some mapping of the E. coli chromosome, Lederberg was able to receive his Ph.D. from Yale University in 1947.^[10] Joshua married Esther Miriam Zimmer (herself a student of Edward Tatum) on December 13, 1946.

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. His wife Esther Lederberg went with him to Wisconsin. She received her doctorate there in 1950.

Joshua Lederberg and Norton Zinder showed in 1951 that genetic material could be transferred from one strain of the bacterium Salmonella typhimurium to another using viral material as an intermediary step.^[11] This process is called transduction. In 1956, M. Laurance Morse, Esther Lederberg and Joshua Lederberg also discovered specialized transduction.^[12][13] The research in specialized transduction focused upon lambda phage infection of E. coli. Transduction and specialized transduction explained how bacteria of different species could gain resistance to the same antibiotic very quickly.

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 simultaneously 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. He has held visiting professorship in Bacteriology at the University of California, Berkeley in summer 1950^[14] and University of Melbourne (1957). Also in 1957, he was elected to the National Academy of Sciences.^[6]

Sir Gustav Nossal views Lederberg as his mentor, describing him as "lightning fast" and "loving a robust debate."^[15]

Post Nobel Prize research

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.^[16]

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.^[17]

Lederberg was elected to the American Academy of Arts and Sciences in 1959 and the American Philosophical Society in 1960.^[18][19]

In the 1960s, he collaborated with Edward Feigenbaum in Stanford's computer science department to develop DENDRAL.^[16]

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, reflecting his extensive research and publications in these disciplines.^[20][21]

Throughout his career, Lederberg was active as a scientific advisor to the U.S. government. Starting in 1950, he was 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.

During a 1986 fact finding mission of the 1979 Soviet Union epidemic of anthrax bacteria that killed 66 people in the city of Sverdlovsk, Russia now named Yakaterinberg,^[22] Lederberg sided with Soviets that the anthrax outbreak was from animal to human transmission stating, “Wild rumors do spread around every epidemic." “The current Soviet account is very likely to be true."^[23] After the fall of the Soviet Union and subsequent US investigations in the early 1990s, a team of scientists confirmed the outbreak was caused by a release of an aerosol of anthrax pathogen from a nearby military facility, the lab leak is one of the deadliest ever documented.^[24][25]

Political and social thought

Eugenics advocacy

He presented at a eugenics conferences alongside fellow Nobel prize winners in Physiology or Medicine, Hermann J. Muller and Francis Crick, as late as 1963^[4] and was equally concerned over the civilizational prospect of dysgenics.^[26]

In his book, Man and his Future, he asked:

Do we not still sinfully waste a treasure of knowledge by ignoring the creative possibilities of genetic improvement . . . to accomplish in one or two generations of eugenic practice what would now take ten or one hundred.^[27]

Euphenics

Euphenics, which literally means "good appearance" or "normal appearing", is the science of making phenotypic improvements to humans after birth, generally to affect a problematic genetic condition. Lederberg coined the term in the 1960s to differentiate this practice from eugenics, which was widely unpopular at the time.^[28][29] He emphasized that the genetic manipulation he described was intended to work on phenotype rather than genotype; he felt it was more feasible to positively change an individual's genetics rather than attempt to change the course of evolution as eugenics proposed.^[30] Theodosius Dobzhansky, an outspoken proponent of euphenics, argued that by improving genetic conditions so that people could live normal, healthy lives, people could lessen the impact of genetic conditions, thus lowering future interest in eugenics or other kinds of genetic manipulation.^[31]

In the 1970s, considerable effort was put towards the developing field of euphenics since it was seen as a positive form of genetic engineering.^[32] One of the first publicized applications of euphenics was the use of vitamins containing folic acid during pregnancy to combat neural-tube deficiencies such as spina bifida in the 1970s.^[33] However, medical science had been using euphenic strategies years before the term itself was coined.^[34] Euphenics is used today in the medical community to more generally refer to methods of affecting a genetic condition in a positive manner through diet, lifestyle or environment, such as the use of insulin to control diabetes or installation of a pacemaker to offset a heart defect.^[35]

Awards and accolades

Impact crater Lederberg in Xanthe Terra on Mars

• The Benjamin Franklin Medal for Distinguished Achievement in the Sciences of the American Philosophical Society, 2002.^[36]
• The Presidential Medal of Freedom, 2006.
• In Lederberg's honor, the 87 km diameter large impact crater in Xanthe Terra on the surface of Mars was named in the year 2012.^[37]

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

• Euthenics

• List of Jewish Nobel laureates
• LCF notation

References

1. Bodmer, W.; Ganesan, A. (2011). "Joshua Lederberg. 23 May 1925 – 2 February 2008". Biographical Memoirs of Fellows of the Royal Society. 57: 229–251. doi:10.1098/rsbm.2010.0024. S2CID 57778869.
2. "News - News". News.
3. Warwick, K. "The Joshua Lederberg Papers: Profiles in Science, National Library of Medicine", Biography, Volume 24, Number 4, Fall 2001, pp. 978-982
4. Lynn, Richard (1997). Dysgenics: Genetic Deterioration in Modern Populations. Praeger Publishers. p. 15. ISBN 9780275949174.
5. Broad, William J. "Joshua Lederberg, 82, a Nobel Winner, Dies", The New York Times, February 5, 2008. Accessed October 29, 2018. "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."
6. "Joshua Lederberg - The Nobel Prize in Physiology or Medicine 1958 - Biography". 1958. Retrieved 2007-10-31.
7. Schindler, Thomas E. "The Lederbergs' Stanford Years, 1959–1976: Growing Apart, the Collaborative Couple Divorce". A Hidden Legacy: The Life and Work of Esther Zimmer Lederberg. Oxford University Press. pp. 117–129. doi:10.1093/oso/9780197531679.003.0014. ISBN 978-0-19-753167-9. Retrieved 25 August 2021.
8. Lederberg, J.; Tatum, E. L. (1946). "Gene Recombination in Escherichia Coli". Nature. 158 (4016): 558. Bibcode:1946Natur.158..558L. doi:10.1038/158558a0. PMID 21001945. S2CID 1826960.
9. Zinder, N. D.; Lederberg, J. (1952). "Genetic Exchange in Salmonella". Journal of Bacteriology. 64 (5): 679–699. doi:10.1128/JB.64.5.679-699.1952. PMC 169409. PMID 12999698.
10. Lederberg, Joshua (1948). Genetic recombination in Escherichia coli (Ph.D.). Yale University. OCLC 702748249 – via ProQuest.
11. Griffiths, Anthony JF; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (28 September 2018). "Transduction". An Introduction to Genetic Analysis. 7th Edition – via www.ncbi.nlm.nih.gov.
12. Morse, M. L.; Lederberg, E. M.; Lederberg, J. (1956). "Transduction in Escherichia Coli K-12". Genetics. 41 (1): 142–156. doi:10.1093/genetics/41.1.142. PMC 1209761. PMID 17247607.
13. Morse, M. L.; Lederberg, E. M.; Lederberg, J. (1956). "Transductional Heterogenotes in Escherichia Coli". Genetics. 41 (5): 758–779. doi:10.1093/genetics/41.5.758. PMC 1209815. PMID 17247661.
14. "University of Wisconsin-Madison Archives Oral History Project (Joshua Lederberg)" (PDF). U.S. National Library of Medicine. Retrieved 5 April 2018.
15. "Sir Gustav Nossal in Forging the Path - A Find My Pathway Interview". Find My Pathway. 30 October 2018.
16. Herzenberg, Leonore; Rindfleisch, Thomas; Herzenberg, Leonard (1 December 2008). "Joshua Lederberg: The Stanford Years (1958–1978)". Annual Review of Genetics. 42 (1): 19–25. doi:10.1146/annurev.genet.072408.095841. ISSN 0066-4197. PMID 18983254. Retrieved 23 February 2023.
17. Scharf, Caleb (January 21, 2016). "How the Cold War Created Astrobiology". Nautilus. Archived from the original on 2016-01-23. Retrieved 2016-01-24.
18. "Joshua Lederberg". American Academy of Arts & Sciences. Retrieved 2022-11-29.
19. "APS Member History". search.amphilsoc.org. Retrieved 2022-11-29.
20. Center for Oral History. "Joshua Lederberg". Science History Institute.
21. Center for Oral History. "Joshua Lederberg". Science History Institute.
22. "AAAS".
23. "Readonly NLM-id ssim: 101584906X18717 - Joshua Lederberg - Profiles in Science Search Results".
24. Troianovski, Anton; Matsnev, Oleg (20 June 2021). "Soviets Once Denied a Deadly Anthrax Lab Leak. U.S. Scientists Backed the Story". The New York Times. Yekaterinburg.
25. "The 1979 Anthrax Leak | Plague War | FRONTLINE | PBS". PBS.
26. Lederberg, Joshua (1963). "Biological future of man." In G. Wolstenholme (ed.), Man and His Future. London: Churchill, p. 264. "Most geneticists [...] are deeply concerned over the status and prospects of the human genotype. Human talents are widely disparate; much of the disparity has a genetic basis. The facts of human reproduction are all gloomy - the stratification of fecundity by economic status, the new environmental insults to our genes, the sheltering by humanitarian medicine of once lethal defects"
27. "Man and his Future", Gordon Wolstenholme (Ed.), J. & A. Churchill Ltd., London, 1963, Back flyleaf.
28. Bud, Robert. The Uses of Life: A History of Biotechnology, Cambridge University Press, 1993, p. 167
29. Khanna, Pragya. Essentials of Genetics, I. K. International Pvt Ltd, 2010, p. 367
30. Lederberg, Joshua. "Molecular Biology, Eugenics and Euphenics", Nature 63(198), p. 428
31. Minkoff, Eli and Baker, Pamela. Biology Today: An Issues Approach, Taylor & Francis, 2000, p. 115
32. Pai, Anna. Foundations of Genetics: A Science for Society, McGraw-Hill, 1974, p. 408
33. Burdyuzha, Vladimir. The Future of the Universe and the Future of our Civilization, World Scientific, 2000, pp. 261−263
34. Guttman, Burton. Genetics: The Code of Life, The Rosen Publishing Group, 2011, p. 101
35. Maxson, Linda and Daugherty, Charles. Genetics: A Human Perspective, W. C. Brown, 1992, p. 391
36. "Benjamin Franklin Medal for Distinguished Achievement in the Sciences Recipients". American Philosophical Society. Retrieved November 26, 2011.
37. "Planetary Names: Crater, craters: Lederberg on Mars". planetarynames.wr.usgs.gov.

External links

• Joshua Lederberg Papers (1904–2008) – National Library of Medicine finding aid
• The Joshua Lederberg Papers – Profiles in Science, National Library of Medicine
• Joshua Lederberg on Nobelprize.org
• In Memoriam: Joshua Lederberg (1925–2008)
• National Academy of Sciences Biographical Memoir
• Center for Oral History. "Joshua Lederberg". Science History Institute.
• Bohning, James J. (9 December 1992). Joshua Lederberg, Transcript of an Interview Conducted by James J. Bohning at Rockefeller University on 25 June, 7 July, and 9 December 1992 (PDF). Philadelphia, PA: Chemical Heritage Foundation.
• Center for Oral History. "Joshua Lederberg". Science History Institute.
• Wolfe, Audra J. (18 August 2000). Joshua Lederberg, Transcript of an Interview Conducted by Audra J. Wolfe at Rockefeller University New York City on 18 August 2000 (PDF). Philadelphia, PA: Chemical Heritage Foundation.