Stanley Norman Cohen
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Stanley Norman Cohen (born February 17, 1935) is an American
geneticist A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic processes ...
and the Kwoh-Ting Li Professor in the
Stanford University School of Medicine Stanford University School of Medicine is the medical school of Stanford University and is located in Stanford, California. It traces its roots to the Medical Department of the University of the Pacific, founded in San Francisco in 1858. This ...
. Stanley Cohen and
Herbert Boyer Herbert Wayne "Herb" Boyer (born July 10, 1936) is an American biotechnologist, researcher and entrepreneur in biotechnology. Along with Stanley N. Cohen and Paul Berg he discovered a method to coax bacteria into producing foreign proteins, the ...
were the first scientists to transplant genes from one living organism to another, a fundamental discovery for genetical engineering. Thousands of products have been developed on the basis of their work, including
human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...
and
hepatitis B vaccine Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and t ...
. According to immunologist
Hugh McDevitt Hugh O'Neill McDevitt ForMemRS (26 August 1930 – 28 April 2022) was an immunologist and Professor of Microbiology and Immunology at Stanford University School of Medicine. Academic career After receiving his M.D. from Harvard University in 1955 ...
, "Cohen's DNA cloning technology has helped biologists in virtually every field". Without it, "the face of biomedicine and biotechnology would look totally different." Boyer cofounded
Genentech Genentech, Inc., is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within ...
in 1976 based on their work together, but Cohen was a consultant for Cetus Corporation and declined to join.


Early life

Cohen was born in
Perth Amboy, New Jersey Perth Amboy is a city (New Jersey), city in Middlesex County, New Jersey, Middlesex County, New Jersey. Perth Amboy is part of the New York metropolitan area. As of the 2020 United States census, 2020 U.S. census, the city's population was 55,4 ...
. He graduated from
Rutgers University Rutgers University (; RU), officially Rutgers, The State University of New Jersey, is a public land-grant research university consisting of four campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's College, and was ...
with a B.S. in 1956, and received his M.D. from the
University of Pennsylvania The University of Pennsylvania (also known as Penn or UPenn) is a Private university, private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest- ...
School of Medicine in 1960. Cohen then held internships and fellowships at various institutions, including Mount Sinai Hospital in New York City, University Hospital in
Ann Arbor, Michigan Ann Arbor is a city in the U.S. state of Michigan and the county seat of Washtenaw County. The 2020 census recorded its population to be 123,851. It is the principal city of the Ann Arbor Metropolitan Statistical Area, which encompasses all ...
, and
Duke University Hospital Duke University Hospital is a 957-acute care bed academic tertiary care facility located in Durham, North Carolina. Established in 1930, it is the flagship teaching hospital for the Duke University Health System, a network of physicians and hosp ...
in
Durham, North Carolina Durham ( ) is a city in the U.S. state of North Carolina and the county seat of Durham County. Small portions of the city limits extend into Orange County and Wake County. With a population of 283,506 in the 2020 Census, Durham is the 4th- ...
. During a residency at the National Institute for Arthritis and Metabolic Diseases, he decided to combine basic research with a clinical practice. In 1967 he was a postdoctoral researcher at the
Albert Einstein College of Medicine Albert Einstein College of Medicine is a research-intensive medical school located in the Morris Park neighborhood of the Bronx in New York City. Founded in 1953, Einstein operates as an independent degree-granting institution as part of t ...
.


Career

Cohen joined the faculty of
Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is conside ...
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. At Stanford he began to explore the field of
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
l
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
s, seeking to understand how the genes of plasmids could make bacteria resistant to
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s. 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 University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It ...
. The Stanford researchers isolated the plasmids, and sent them to the San Francisco team, who cut them using the
restriction enzyme A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class ...
EcoRI ''Eco''RI (pronounced "eco R one") is a restriction endonuclease enzyme isolated from species ''E. coli.'' It is a restriction enzyme that cleaves DNA double helices into fragments at specific sites, and is also a part of the restriction modifica ...
. The fragments were analyzed and sent back to Stanford, where Cohen's team joined them and introduced them into
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
. Both laboratories then isolated and analyzed the newly created recombinant plasmids. 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. 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 ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are faculta ...
plasmid genes into E. coli demonstrated that genes could be transplanted between species. These discoveries signaled the birth of
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
, and earned Cohen a number of significant awards, beginning with the
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
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." 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). From 1978 to 1986, Cohen served as chair of the Department of Genetics at Stanford. During the 1970s and 1980s, Cohen was an active proponent of the potential benefits of DNA technology. 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. He also attended the Asilomar Conference on Recombinant DNA in 1975, and was reportedly uncomfortable with the process and tone of the meeting. He was vocal in the recombinant DNA controversy as the United States government attempted to develop policies for DNA research. 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. 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." 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. He has continued to study plasmid involvement in
antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
. In particular, he studies mobile genetic elements such as
transposons A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Tran ...
which can "jump" between strains of bacteria. He has developed techniques for studying the behavior of genes in eukaryotic cells using "reporter genes".


Plasmid pSC101

Stanley Cohen and Herbert Boyer made what would be one of the first
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including ...
experiments, in 1973. They demonstrated that the
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
for
frog A frog is any member of a diverse and largely Carnivore, carnivorous group of short-bodied, tailless amphibians composing the order (biology), order Anura (ανοὐρά, literally ''without tail'' in Ancient Greek). The oldest fossil "proto-f ...
ribosomal Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to for ...
RNA could be transferred into bacterial cells and expressed by them. First they developed a chemical cell transformation method for
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
, then they constructed a
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
, which would be the
vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...
, called
pSC101 pSC101 is a DNA plasmid that is used as a cloning vector in genetic cloning experiments. pSC101 was the first cloning vector, used in 1973 by Herbert Boyer and Stanley Norman Cohen. Using this plasmid they have demonstrated that a gene from a f ...
. This plasmid contained a single site for the
restriction enzyme A restriction enzyme, restriction endonuclease, REase, ENase or'' restrictase '' is an enzyme that cleaves DNA into fragments at or near specific recognition sites within molecules known as restriction sites. Restriction enzymes are one class ...
EcoRI ''Eco''RI (pronounced "eco R one") is a restriction endonuclease enzyme isolated from species ''E. coli.'' It is a restriction enzyme that cleaves DNA double helices into fragments at specific sites, and is also a part of the restriction modifica ...
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.


Patents

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". 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. 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.


Awards

* 1979 elected to the
National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nat ...
* 1980
Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Medicine; almost 5 ...
* 1981
Wolf Prize in Medicine The Wolf Prize in Medicine is awarded annually by the Wolf Foundation in Israel. It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The ...
* 1988
National Medal of Science The National Medal of Science is an honor bestowed by the President of the United States to individuals in science and engineering who have made important contributions to the advancement of knowledge in the fields of behavioral and social scienc ...
from President Reagan * 1989
National Medal of Technology The National Medal of Technology and Innovation (formerly the National Medal of Technology) is an honor granted by the President of the United States to American inventors and innovators who have made significant contributions to the development ...
(shared with
Herbert Boyer Herbert Wayne "Herb" Boyer (born July 10, 1936) is an American biotechnologist, researcher and entrepreneur in biotechnology. Along with Stanley N. Cohen and Paul Berg he discovered a method to coax bacteria into producing foreign proteins, the ...
) from President Bush * 1996 Lemelson–MIT Prize * 2001
National Inventors Hall of Fame The National Inventors Hall of Fame (NIHF) is an American not-for-profit organization, founded in 1973, which recognizes individual engineers and inventors who hold a U.S. patent of significant technology. Besides the Hall of Fame, it also oper ...
* 2004
Albany Medical Center Prize The Albany Medical Center Prize in Medicine and Biomedical Research is the United States' second highest value prize in medicine and biomedical research, awarded by the Albany Medical Center. Among prizes for medicine worldwide, the Albany Medical ...
(shared with Herbert Boyer) * 2004
Shaw Prize The Shaw Prize is an annual award presented by the Shaw Prize Foundation. Established in 2002 in Hong Kong, it honours "individuals who are currently active in their respective fields and who have recently achieved distinguished and signifi ...
in Life Science and Medicine (shared with Herbert Boyer) *2006 elected to the
American Philosophical Society The American Philosophical Society (APS), founded in 1743 in Philadelphia, is a scholarly organization that promotes knowledge in the sciences and humanities through research, professional meetings, publications, library resources, and communit ...
* 2009
Double Helix Medal The Double Helix Medal has been awarded annually since 2006 by Cold Spring Harbor Laboratory (CSHL) to individuals who have positively impacted human health by raising awareness and funds for biomedical research. At the inaugural dinner, Muhammad ...
* 2016
Biotechnology Heritage Award The Biotechnology Heritage Award recognizes individuals who have made significant contributions to the development of biotechnology through discovery, innovation, and public understanding. It is presented annually at the Biotechnology Innovation ...
, from the Biotechnology Industry Organization (BIO) and the
Chemical Heritage Foundation The Science History Institute is an institution that preserves and promotes understanding of the history of science. Located in Philadelphia, Pennsylvania, it includes a library, museum, archive, research center and conference center. It was fo ...


References


External links


Oral History with Stanley N. Cohen
Stanford Historical Society Oral History Program, 1995. {{DEFAULTSORT:Cohen, Stanley Norman 1935 births American geneticists Jewish geneticists Physicians from California Jewish American scientists Lemelson–MIT Prize Living people Members of the United States National Academy of Sciences National Medal of Science laureates National Medal of Technology recipients People from Perth Amboy, New Jersey Recipients of the Albert Lasker Award for Basic Medical Research Rutgers University alumni Stanford University School of Medicine faculty Perelman School of Medicine at the University of Pennsylvania alumni Wolf Prize in Medicine laureates Members of the American Philosophical Society 21st-century American Jews Members of the National Academy of Medicine