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Stanley Norman Cohen

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For other people named Stanley Cohen, see Stanley Cohen (disambiguation).
Stanley Norman Cohen
Stanley Norman Cohen, 2016
Born (1935-02-17) February 17, 1935 (age 89)
Perth Amboy, New Jersey
NationalityAmerican
Alma materRutgers University, University of Pennsylvania
SpouseJoanna Lucy Wolter[1]
AwardsNational Medal of Science, Wolf Prize in Medicine
Scientific career
FieldsGenetics
InstitutionsStanford University
Doctoral studentsKelly Ten Hagen

Stanley Norman Cohen (born February 17, 1935) is an American geneticist[2] and the Kwoh-Ting Li Professor in the Stanford University School of Medicine.[3] Stanley Cohen and Herbert Boyer were the first scientists to transplant genes from one living organism to another, a fundamental discovery for genetical engineering.[4][5] Thousands of products have been developed on the basis of their work, including human growth hormone and hepatitis B vaccine.[6] According to immunologist Hugh McDevitt, "Cohen's DNA cloning technology has helped biologists in virtually every field".[7] Without it, "the face of biomedicine and biotechnology would look totally different."[7] Boyer cofounded Genentech in 1976 based on their work together, but Cohen was a consultant for Cetus Corporation and declined to join.[8] In 2022, Cohen was found guilty of having committed fraud in misleading investors into a biotechnology company he founded in 2016, and paid $29 million in damages.[9]

Early life

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Cohen was born in Perth Amboy, New Jersey. He graduated from Rutgers University with a B.S. in 1956, and received his M.D. from the University of Pennsylvania School of Medicine in 1960.[3] Cohen then held internships and fellowships at various institutions, including Mount Sinai Hospital in New York City, University Hospital in Ann Arbor, Michigan, and Duke University Hospital in Durham, North Carolina.[10] During a residency at the National Institute for Arthritis and Metabolic Diseases, he decided to combine basic research with a clinical practice.[11] In 1967 he was a postdoctoral researcher at the Albert Einstein College of Medicine.[10]

Career

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Cohen discussing his life and career.

Cohen joined the faculty of Stanford University in 1968. He was appointed as a professor of medicine in 1975, and as a professor of genetics in 1977. In 1993, he became the Kwoh-Ting Li professor of genetics.[10]

At Stanford he began to explore the field of bacterial plasmids, seeking to understand how the genes of plasmids could make bacteria resistant to antibiotics. At a conference on plasmids in 1972, he met Herbert W. Boyer and discovered that their interests and research were complementary. Plasmids were sent back and forth between Stanley Cohen, Annie C. Y. Chang, and others at Stanford, and Herbert Boyer and Robert B. Helling at the University of California, San Francisco. The Stanford researchers isolated the plasmids, and sent them to the San Francisco team, who cut them using the restriction enzyme EcoRI. The fragments were analyzed and sent back to Stanford, where Cohen's team joined them and introduced them into Escherichia coli. Both laboratories then isolated and analyzed the newly created recombinant plasmids.[12]

This collaboration, in particular the 1973 publication of "Construction of biologically functional bacterial plasmids in vitro" by Cohen, Chang, Boyer and Helling, is considered a landmark in the development of methods to combine and transplant genes.[13][14] Not only were different plasmids from E. coli successfully joined and inserted back into E. coli cells, but those cells replicated and carried forward the new genetic information. Subsequent experiments that transferred Staphylococcus plasmid genes into E. coli demonstrated that genes could be transplanted between species.[10][15] These discoveries signaled the birth of genetic engineering, and earned Cohen a number of significant awards, beginning with the Albert Lasker Award for Basic Medical Research in 1980 for "his imaginative and persevering studies of bacterial plasmids, for discovering new opportunities for manipulating and investigating the genetics of cells, and for establishing the biological promise of recombinant DNA methodology."[16]

In 1976, Cohen co-authored a proposal for uniform nomenclature for bacterial plasmids (with Royston C. Clowes, Roy Curtiss III, Naomi Datta, Stanley Falkow and Richard Novick).[17] From 1978 to 1986, Cohen served as chair of the Department of Genetics at Stanford.[18]

During the 1970s and 1980s, Cohen was an active proponent of the potential benefits of DNA technology.[10] He was a signatory of the "Berg letter" in 1974, which called for a voluntary moratorium on some types of research pending an evaluation of risk.[19] He also attended the Asilomar Conference on Recombinant DNA in 1975, and was reportedly uncomfortable with the process and tone of the meeting.[20][21] He was vocal in the recombinant DNA controversy as the United States government attempted to develop policies for DNA research.[2][10] Government efforts resulted in the creation of the Recombinant DNA Advisory Committee and the publication of Recombinant DNA research guidelines in 1976, as well as later reports and recommendations.[22] Cohen supported the Baltimore-Campbell proposal, arguing that recommended containment levels for certain types of research should be lowered on the grounds that little risk was involved, and that the proposal should be "a non-regulating code of standard practice."[23]

Today, Cohen is a professor of genetics and medicine at Stanford, where he works on a variety of scientific problems involving cell growth and development, including mechanisms of plasmid inheritance and evolution.[10] He has continued to study plasmid involvement in antibiotic resistance.[7] In particular, he studies mobile genetic elements such as transposons which can "jump" between strains of bacteria.[24][25][26] He has developed techniques for studying the behavior of genes in eukaryotic cells using "reporter genes".[5][27]

Plasmid pSC101

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Stanley Norman Cohen's genetic engineering laboratory, 1973 - National Museum of American History
External videos
video icon Electron micrograph of a bacterial DNA plasmid, “Medal of Science 50 Videos -- Stanley Cohen”, National Science Foundation
video icon “Mechanism of Recombination, 3D animation with basic narration“, DNA Learning Center

Stanley Cohen and Herbert Boyer made what would be one of the first genetic engineering experiments, in 1973. They demonstrated that the gene for frog ribosomal RNA could be transferred into bacterial cells and expressed by them. First they developed a chemical cell transformation method for Escherichia coli,[28] then they constructed a plasmid, which would be the vector, called pSC101.[29] This plasmid contained a single site for the restriction enzyme EcoRI and a gene for tetracycline resistance. The restriction enzyme EcoRI was used to cut the frog DNA into small segments. Next, the frog DNA fragments were combined with the plasmid, which had also been cleaved with EcoRI. The sticky ends of the DNA segments aligned themselves and were afterwards joined using DNA ligase. The plasmids were then transferred into a strain of E. coli and plated onto a growth medium containing tetracycline. The cells that incorporated the plasmid carrying the tetracycline resistance gene grew and formed a colony of bacteria. Some of these colonies consisted of cells that carried the frog ribosomal RNA gene. The scientists then tested the colonies that formed after growth for the presence of frog ribosomal RNA.[30]

Patents

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Cohen and Boyer were not initially interested in filing patents on their work. In 1974 they agreed to file a joint patent application, administered through Stanford, and benefiting both universities. Three patents were eventually granted for the Boyer-Cohen process, one on the actual process (1980), one on prokaryotic hosts (1984) and one on eukaryotic hosts (1988). Licenses were granted non-exclusively for "a moderate fee".[6]: 166  Four hundred seventy-eight companies took out licenses, making it one of the university's top five revenue earners. Thousands of products have been developed on the basis of the Boyer-Cohen patents.[6]: 162, 166  The Boyer-Cohen patents however were controversial due to its scope as they laid claim to the fundamental technology of gene splicing, and led to many challenges to the validity of the patents in the 1980s. The patents were unusual in that they dominated almost all other patents in the field of molecular biotechnology, and in no other industry have there been patents that had such an all-embracing impact. It also made other universities around the world become aware of the commercial value of the scientific work by their academic staff.[31]

Nuredis fraud case

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In 2018, Cohen was sued by Christopher Alafi for misleading investors in the biotechnology company Nuredis, and hiding details of the FDA disapproval of a drug Cohen had discovered for Huntington's disease.[9][32] Upon losing a long court battle, Cohen was found guilty of "a species of actual fraud and ... deceit", and he admitted to providing wrong testimony in court, although he was not found guilty of intentionally misleading investors. The drug had been approaved and tben withdrawn by the FDA in 1976 for its potentially lethal side effect. As reparations, Cohen paid $29.2 million in damages. In 2024 the court's decision was found to be faulty by the Appeals Court, and was reversed. The damages were ordered entirely refunded to Cohen.

Awards

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References

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  1. ^ a b "Autobiography of Stanley N Cohen". Shaw Prize. Retrieved 5 May 2016.
  2. ^ a b Hughes, Sally Smith (1995). "Stanley N. Cohen SCIENCE, BIOTECHNOLOGY, and RECOMBINANT DNA: A PERSONAL HISTORY (Oral history)" (PDF). Regional Oral History Office, The Bancroft Library, University of California. Berkeley, California.
  3. ^ a b "Stanford School of Medicine Profiles: Stanley N. Cohen, MD". Stanford School of Medicine. Retrieved November 17, 2014.
  4. ^ Yount, Lisa (2003). A to Z of biologists. New York: Facts on File. pp. 47–49. ISBN 978-0816045419. Retrieved 4 May 2016.
  5. ^ a b Cohen, S. N. (16 September 2013). "DNA cloning: A personal view after 40 years". Proceedings of the National Academy of Sciences. 110 (39): 15521–15529. Bibcode:2013PNAS..11015521C. doi:10.1073/pnas.1313397110. PMC 3785787. PMID 24043817.
  6. ^ a b c Granstrand, Ove, ed. (2003). Economics, Law and Intellectual Property Seeking Strategies for Research and Teaching in a Developing Field. Boston, MA: Springer US. pp. 162–166. ISBN 978-1-4757-3750-9. Retrieved 6 May 2016.
  7. ^ a b c Wang, Bruce (10 November 1999). "Cohen: DNA genius on the Farm". The Stanford Daily. Vol. 216, no. 38.
  8. ^ Berlin, Leslie (2017). Troublemakers : Silicon Valley's Coming of Age (1st ed.). New York. p. 199. ISBN 978-1-4516-5150-8. OCLC 1008569018.{{cite book}}: CS1 maint: location missing publisher (link)
  9. ^ a b "Stanford professor pays $29M in fraud case". 2022-12-21. Retrieved 2023-04-16.
  10. ^ a b c d e f g "Cohen, Stanley N. (1935- )". World of Microbiology and Immunology. Encyclopedia.com. 2003.
  11. ^ "Biography 34: Stan Norman Cohen (1935 - )". DNA Learning Center. Cold Spring Harbor Laboratory. Retrieved 6 May 2016.
  12. ^ "Herbert W. Boyer and Stanley N. Cohen". Science History Institute. June 2016. Retrieved 21 March 2018.
  13. ^ Cohen, SN; Chang, AC; Boyer, HW; Helling, RB (November 1973). "Construction of biologically functional bacterial plasmids in vitro". Proceedings of the National Academy of Sciences of the United States of America. 70 (11): 3240–4. Bibcode:1973PNAS...70.3240C. doi:10.1073/pnas.70.11.3240. PMC 427208. PMID 4594039.
  14. ^ Kiermer, Veronique. "Milestone 2 (1967, 1972) Discovery of DNA ligase; Cloning The dawn of recombinant DNA". NATURE Milestones. Retrieved 5 May 2016.
  15. ^ Chang, Annie C. Y.; Cohen, Stanley N. (1974). "Genome Construction Between Bacterial Species In Vitro: Replication and Expression of Staphylococcus Plasmid Genes in Escherichia coli". Proceedings of the National Academy of Sciences of the United States of America. 71 (4): 1030–1034. Bibcode:1974PNAS...71.1030C. doi:10.1073/pnas.71.4.1030. PMC 388155. PMID 4598290.
  16. ^ a b "1980 Albert Lasker Basic Medical Research Award Cloning genes by recombinant DNA technology". Albert And Mary Lasker Foundation. Retrieved 5 May 2016.
  17. ^ Novick, Richard P.; Clowes, R C; Cohen, S N; Curtiss, 3rd, R; Datta, N; Falkow, S (1976). "Uniform Nomenclature for Bacterial Plasmids: A Proposal". Bacteriological Reviews. 40 (1): 168–189. doi:10.1128/MMBR.40.1.168-189.1976. PMC 413948. PMID 1267736.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  18. ^ The international who's who 2004. London: Europa. 2003. p. 340. ISBN 9781857432176. Retrieved 6 May 2016.
  19. ^ Berg, Paul; Baltimore, David; Boyer, Herbert W.; Cohen, Stanley N.; et al. (1974). "Potential Biohazards of Recombinant DNA Molecules" (PDF). Science. 185 (4148): 303. Bibcode:1974Sci...185..303B. doi:10.1126/science.185.4148.303. PMC 388511. PMID 4600381.
  20. ^ Grace, Katja (2015). The Asilomar Conference: A Case Study in Risk Mitigation (PDF). Berkeley, CA: Machine Intelligence Research Institute.
  21. ^ Bourne, Henry R. (2011). Paths to innovation : discovering recombinant DNA, oncogenes, and prions in one medical school, over one decade. San Francisco: University of California Medical Humanities Consortium. ISBN 9780983463924.
  22. ^ Committee on the Independent Review and Assessment of the Activities of the NIH Recombinant DNA Advisory Committee; Board on Health Sciences Policy; Institute of Medicine; Lenzi RN, Altevogt BM, Gostin LO, editors. Oversight and Review of Clinical Gene Transfer Protocols: Assessing the Role of the Recombinant DNA Advisory Committee. Washington (DC): National Academies Press (US); 2014 Mar 27. B, Historical and Policy Timelines for Recombinant DNA Technology.
  23. ^ Office of the Director (1976). Recombinant DNA research : documents relating to "NIH guidelines for research involving recombinant DNA molecules. National Institutes of Health (U.S.). Retrieved 6 May 2016.
  24. ^ Cohen, Stanley N.; Shapiro, James A. (1980). "Transposable Genetic Elements" (PDF). Scientific American. 242 (2): 40–49. Bibcode:1980SciAm.242b..40C. doi:10.1038/scientificamerican0280-40. PMID 6246575. S2CID 6562135. Retrieved 6 May 2016.
  25. ^ Guilfoile, Patrick G.; Alcamo, Edward (2006). Antibiotic-resistant bacteria. New York: Chelsea House. ISBN 978-0791091883.
  26. ^ Koonin, Eugene V.; Krupovic, Mart (January 1, 2015). "A Movable Defense". The Scientist. Retrieved 6 May 2016.
  27. ^ Brenner, D. G.; Lin-Chao, S.; Cohen, S. N. (1 July 1989). "Analysis of mammalian cell genetic regulation in situ by using retrovirus-derived "portable exons" carrying the Escherichia coli lacZ gene". Proceedings of the National Academy of Sciences. 86 (14): 5517–5521. Bibcode:1989PNAS...86.5517B. doi:10.1073/pnas.86.14.5517. PMC 297654. PMID 2501787.
  28. ^ Cohen, S. N.; Chang, A. C.; Hsu, L. (1972). "Nonchromosomal antibiotic resistance in bacteria: Genetic transformation of Escherichia coli by R-factor DNA". Proceedings of the National Academy of Sciences of the United States of America. 69 (8): 2110–2114. Bibcode:1972PNAS...69.2110C. doi:10.1073/pnas.69.8.2110. PMC 426879. PMID 4559594.
  29. ^ Cohen, S.; Chang, A.; Boyer, H.; Helling, R. (1973). "Construction of biologically functional bacterial plasmids in vitro". Proceedings of the National Academy of Sciences of the United States of America. 70 (11): 3240–3244. Bibcode:1973PNAS...70.3240C. doi:10.1073/pnas.70.11.3240. PMC 427208. PMID 4594039.
  30. ^ Thieman, William J.; Palladino, Michael A. (2004). Introduction to biotechnology. San Francisco: Pearson/Benjamin Cummings. p. 55. ISBN 9780805348255.
  31. ^ R.W. Old; S.B. Primrose. Principles of Gene Manipulation (5th ed.). Blackwell Scientific Publishing. pp. 56–57.
  32. ^ "Stanford prof pays investors in defunct biotech Nuredis $29m". pharmaphorum. Retrieved 2023-04-16.
  33. ^ "Stanley N. Cohen". The National Academy of Sciences. Retrieved 5 May 2016.
  34. ^ Gurdon, John (2012). Wolf prize in medicine 1978-2008. Vol. 1. Singapore: World Scientific. ISBN 978-981-4291-73-6.
  35. ^ "Stanley N. Cohen Winner of Wolf Prize in Medicine - 1981". Wolf Foundation. Retrieved 5 May 2016.
  36. ^ "National Medal Winner - Stanley Cohen". The White House. Retrieved 5 May 2016.
  37. ^ "The President's National Medal of Science: Recipient Details, Stanley N. Cohen". National Science Foundation. Retrieved 5 May 2016.
  38. ^ Sanders, Robert (October 18, 1989). "President Bush awards National Medal of Technology to UC San Francisco's Herbert Boyer and Stanford's Stanley Cohen". UCSF News. Retrieved 5 May 2016.
  39. ^ "Herbert Boyer and Stanley Cohen". Lemelson-MIT. Retrieved 5 May 2016.
  40. ^ "Innovators Cohen, Fogarty to enter National Inventors Hall of Fame". Stanford Report. May 16, 2001. Retrieved 4 May 2016.
  41. ^ Adams, Amy (April 28, 2004). "Early genetics discovery wins Cohen the Albany Prize". Stanford Report. Retrieved 5 May 2016.
  42. ^ "An Essay on Prize One in Life Science and Medicine 2004: Stanely N Cohen & Herbert W Boyer". Shaw Prize. Retrieved 5 May 2016.
  43. ^ "APS Member History". search.amphilsoc.org. Retrieved 2021-05-24.
  44. ^ "$2.8 million raised at 2009 Double Helix Medals dinner". Cold Spring Harbor Laboratory. 12 November 2009. Archived from the original on 2 June 2016.
  45. ^ "Biotechnology Heritage Award". Science History Institute. 31 May 2016. Retrieved 22 March 2018.
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