- Person
- Stanley Cohen
- Lived
- b. 1935
- Field
- Genetics
- From
- American
The story
To study how bacteria carry and share genes, Stanley Cohen needed a reliable way to put DNA into living bacterial cells. E. coli, the workhorse of laboratory biology, does not normally take up loose DNA from its surroundings, and for years it was thought to be resistant to this kind of genetic transformation. That limited what researchers could do.
A first opening came in 1970, when Morton Mandel and Akiko Higa showed that E. coli treated with a calcium chloride solution could be made to take up DNA from a bacterial virus. In 1972 Cohen, working with Annie Chang and Leslie Hsu at Stanford, showed that calcium chloride treatment also worked for plasmids, the small circles of DNA that carry antibiotic-resistance genes. Their paper in the Proceedings of the National Academy of Sciences that August described how E. coli took up resistance-plasmid DNA, then copied and passed on the plasmids as the cells divided. Bacteria that had taken up a plasmid carrying an antibiotic-resistance gene could easily be picked out by growing them on that antibiotic.
The method was one half of the puzzle that Cohen and Herbert Boyer solved together. In November 1972, at a meeting on plasmids in Hawaii, Cohen described the procedure while Boyer explained how his enzyme, EcoRI, cut DNA. Over sandwiches that night they planned a collaboration. Boyer's enzyme could cut DNA and Cohen's plasmids and transformation method could carry the result into cells, where it would be copied.
In spring 1973 the combination worked. Recombinant plasmids made with EcoRI were introduced into calcium chloride-treated bacteria, and the cells that survived on an antibiotic carried the new DNA, creating the first gene clones.
Chemical transformation remains a routine step in molecular biology laboratories around the world. In its common form, cells are chilled in calcium chloride with the DNA and then given a brief heat shock, a simple procedure that works especially well for circular plasmids. Newer methods such as electroporation, developed in the late 1980s, have added to the toolkit, but the calcium chloride approach remains in wide use.
Why it matters
Getting DNA into bacteria is a basic step in producing medicines such as insulin and in countless research experiments, and Cohen's method helped make it routine.
About Stanley Cohen
Stanford geneticist who, with Herbert Boyer, invented recombinant DNA cloning in 1973, the technique that launched genetic engineering and the biotechnology industry.
More about Stanley Cohen
- Stanley Cohen co-invented genetic engineeringIn 1973 Stanley Cohen and Herbert Boyer first moved genes between organisms, inventing recombinant DNA, the technique behind human insulin and the biotechnology industry.
- Stanley Cohen helped build biotechnology in TaiwanBeyond his Stanford laboratory, Stanley Cohen helped develop research collaboration with Taiwan's Institute of Molecular Biology and a biotechnology industry in Taiwan.
- Stanley Cohen investigated how bacteria resist antibioticsStanley Cohen's genetic engineering grew out of a medical question: how bacteria share genes that make them resistant to antibiotics.
- Stanley Cohen's plasmid pSC101 carried the first clonesStanley Cohen's plasmid pSC101, cut at a single site by Boyer's enzyme and carrying a tetracycline-resistance gene, became the vehicle for the first DNA cloning experiments in 1973.
- Stanley Cohen built tools to watch genes at workAfter inventing DNA cloning, Stanley Cohen developed techniques that use reporter genes to follow how genes behave in the cells of animals and other complex organisms.
- Stanley Cohen backed a safety pause on gene splicingStanley Cohen signed the 1974 letter calling for a voluntary pause on some recombinant DNA experiments until their risks could be assessed, and took part in the 1975 Asilomar conference.
- Stanley Cohen's patent was licensed to hundreds of firmsThe Cohen–Boyer recombinant DNA patents were licensed non-exclusively, for moderate fees, to 478 companies, spreading gene cloning across the biotechnology industry.
Sources
- Herbert W. Boyer and Stanley N. Cohen Science History Institute
- Stanley Norman Cohen Wikipedia
- Transformation (genetics) Wikipedia
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