Stanley Norman Cohen | |
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Born | |
Nationality | American |
Alma mater | Rutgers University, University of Pennsylvania |
Spouse | Joanna Lucy Wolter [1] |
Awards | National Medal of Science, Wolf Prize in Medicine |
Scientific career | |
Fields | Genetics |
Institutions | Stanford University |
Doctoral students | Kelly 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]
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]
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]
External videos | |
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Electron micrograph of a bacterial DNA plasmid, “Medal of Science 50 Videos -- Stanley Cohen”, National Science Foundation | |
“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]
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]
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 developed by Cohen had been withdrawn by the FDA in 1976, for its potentially lethal side effects, having led to the loss of limbs and death in some cases. As reparations, Cohen paid $29.2 million in damages.
Bacterial conjugation is the transfer of genetic material between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells. This takes place through a pilus. It is a parasexual mode of reproduction in bacteria.
Escherichia coli ( ESH-ə-RIK-ee-ə KOH-lye) is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes such as EPEC, and ETEC are pathogenic and can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. Most strains are part of the normal microbiota of the gut and are harmless or even beneficial to humans (although these strains tend to be less studied than the pathogenic ones). For example, some strains of E. coli benefit their hosts by producing vitamin K2 or by preventing the colonization of the intestine by pathogenic bacteria. These mutually beneficial relationships between E. coli and humans are a type of mutualistic biological relationship — where both the humans and the E. coli are benefitting each other. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.
A bacterial artificial chromosome (BAC) is a DNA construct, based on a functional fertility plasmid, used for transforming and cloning in bacteria, usually E. coli. F-plasmids play a crucial role because they contain partition genes that promote the even distribution of plasmids after bacterial cell division. The bacterial artificial chromosome's usual insert size is 150–350 kbp. A similar cloning vector called a PAC has also been produced from the DNA of P1 bacteriophage.
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 Roche. Historically, the company is regarded as the world's first biotechnology company.
Herbert Wayne "Herb" Boyer is an American biotechnologist, researcher and entrepreneur in biotechnology. Along with Stanley N. Cohen and Paul Berg, he discovered recombinant DNA, a method to coax bacteria into producing foreign proteins, which aided in jump-starting the field of genetic engineering.
An expression vector, otherwise known as an expression construct, is usually a plasmid or virus designed for gene expression in cells. The vector is used to introduce a specific gene into a target cell, and can commandeer the cell's mechanism for protein synthesis to produce the protein encoded by the gene. Expression vectors are the basic tools in biotechnology for the production of proteins.
In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to take place, the recipient bacterium must be in a state of competence, which might occur in nature as a time-limited response to environmental conditions such as starvation and cell density, and may also be induced in a laboratory.
Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination that bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome.
Stanley "Stan" Falkow was an American microbiologist and a professor of microbiology at Georgetown University, University of Washington, and Stanford University School of Medicine. Falkow is known as the father of the field of molecular microbial pathogenesis. He formulated molecular Koch's postulates, which have guided the study of the microbial determinants of infectious diseases since the late 1980s. Falkow spent over 50 years uncovering molecular mechanisms of how bacteria cause disease and how to disarm them. Falkow also was one of the first scientists to investigate antimicrobial resistance, and presented his research extensively to scientific, government, and lay audiences explaining the spread of resistance from one organism to another, now known as horizontal gene transfer, and the implications of this phenomenon on our ability to combat infections in the future.
The blue–white screen is a screening technique that allows for the rapid and convenient detection of recombinant bacteria in vector-based molecular cloning experiments. This method of screening is usually performed using a suitable bacterial strain, but other organisms such as yeast may also be used. DNA of transformation is ligated into a vector. The vector is then inserted into a competent host cell viable for transformation, which are then grown in the presence of X-gal. Cells transformed with vectors containing recombinant DNA will produce white colonies; cells transformed with non-recombinant plasmids grow into blue colonies.
Esther Miriam Zimmer Lederberg was an American microbiologist and a pioneer of bacterial genetics. She discovered the bacterial virus lambda phage and the bacterial fertility factor F, devised the first implementation of replica plating, and furthered the understanding of the transfer of genes between bacteria by specialized transduction.
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 frog could be transferred into bacterial cells and then expressed by the bacterial cells. The plasmid is a natural plasmid from Salmonella panama.
Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms. The use of the word cloning refers to the fact that the method involves the replication of one molecule to produce a population of cells with identical DNA molecules. Molecular cloning generally uses DNA sequences from two different organisms: the species that is the source of the DNA to be cloned, and the species that will serve as the living host for replication of the recombinant DNA. Molecular cloning methods are central to many contemporary areas of modern biology and medicine.
Escherichia coli is a Gram-negative gammaproteobacterium commonly found in the lower intestine of warm-blooded organisms (endotherms). The descendants of two isolates, K-12 and B strain, are used routinely in molecular biology as both a tool and a model organism.
The history of genetics can be represented on a timeline of events from the earliest work in the 1850s, to the DNA era starting in the 1940s, and the genomics era beginning in the 1970s.
Genetic engineering is the science of manipulating genetic material of an organism. The concept of genetic engineering was first proposed by Nikolay Timofeev-Ressovsky in 1934. The first artificial genetic modification accomplished using biotechnology was transgenesis, the process of transferring genes from one organism to another, first accomplished by Herbert Boyer and Stanley Cohen in 1973. It was the result of a series of advancements in techniques that allowed the direct modification of the genome. Important advances included the discovery of restriction enzymes and DNA ligases, the ability to design plasmids and technologies like polymerase chain reaction and sequencing. Transformation of the DNA into a host organism was accomplished with the invention of biolistics, Agrobacterium-mediated recombination and microinjection. The first genetically modified animal was a mouse created in 1974 by Rudolf Jaenisch. In 1976 the technology was commercialised, with the advent of genetically modified bacteria that produced somatostatin, followed by insulin in 1978. In 1983 an antibiotic resistant gene was inserted into tobacco, leading to the first genetically engineered plant. Advances followed that allowed scientists to manipulate and add genes to a variety of different organisms and induce a range of different effects. Plants were first commercialized with virus resistant tobacco released in China in 1992. The first genetically modified food was the Flavr Savr tomato marketed in 1994. By 2010, 29 countries had planted commercialized biotech crops. In 2000 a paper published in Science introduced golden rice, the first food developed with increased nutrient value.
Janet E. Mertz is an American biochemist, molecular biologist, and cancer researcher. She is currently the Elizabeth McCoy Professor of Oncology in the McArdle Laboratory for Cancer Research at the University of Wisconsin–Madison. Mertz is best known for disputing Lawrence Summers' 2005 suggestion that women lack the intrinsic aptitude to excel in mathematics at the highest level and for discovering an easy method for joining DNAs from different species. This latter finding initiated the era of genetic engineering whose ramifications form the basis of modern genetics and the biotechnology industry.
Keiichi Itakura is an organic chemist and a Professor in the Department of Molecular and Cellular Biology at the Beckman Research Institute at City of Hope National Medical Center.
Daisy Roulland-Dussoix was a Swiss molecular microbiologist. She was one of the discoverers of restriction enzymes during her doctoral studies. There is controversy over whether she should have received the 1978 Nobel prize in Physiology and Medicine, which was awarded to Hamilton O. Smith, Daniel Nathans, and Werner Arber.
Edward Allen Adelberg (1920–2009) was a founder of microbial genetics and biochemist who spent much of his career at Yale University. He was a member of the National Academy of Sciences and co-author of influential textbooks.
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