Recombinant DNA Notebook

In a series of experiments between 1972 and 1974 Stanley Cohen, Herbert Boyer, and their colleagues, at Stanford University and the University of California, San Francisco, developed techniques that formed the basis of recombinant DNA technology and helped spur the birth of the biotechnology industry.

This notebook was used by Stanley Cohen in his lab at Stanford University from January of 1972 through 1978 in his study of plasmids—a specific form of DNA found in some organisms, especially of bacteria. It chronicles his research on creating recombinant plasmids, starting with his efforts to break plasmids through mechanical shearing and following through his ground-breaking experiments employing restriction enzymes with Herbert Boyer.

While not technically a lab notebook—one containing a log of daily experiments—the notebook contains extra information on experiments, many sketches and maps of recombinant plasmids, and outlines for papers to be published (including on p. 51 the “Outline for Recombination Paper” that would become the paper “Construction of Biologically Functional Bacterial Plasmids In Vitro” published in the Proceedings of the National Academy of the Sciences in 1973.)

Scientists knew since 1959 that bacteria contain extra loops of DNA called “plasmids” in addition to their chromosome. In nature, bacteria can swap these plasmids with one another, quickly transferring beneficial genes like those that code for antibiotic resistance. By the early 1970s, investigators had isolated several plasmids as well as special enzymes known as “restriction endonucleases” that worked like scissors to cut open the loops of plasmids. Boyer had expertise with restriction endonucleases, and Cohen studied plasmids. After meeting at a conference in 1972, the two decided to combine their research efforts. Following preliminary experiments in 1973, the Cohen-Boyer team was able to cut open a plasmid loop, insert a gene from different bacteria and close the plasmid. This created a recombinant DNA molecule—a plasmid containing recombined DNA from two different sources.

Next, they inserted the plasmid into bacteria and demonstrated that the bacteria could use the new genes. They had created the first genetically modified organisms. A year later, the team used this technique to insert a gene from a frog into bacteria, proving that it was possible to transfer genes between two very different organisms. The technology for creating these “molecular chimeras” was patented on December 2, 1980 (U.S. Patent 4,237,224.)

The concept that genes from one organism could be inserted into another and still work was the foundation for the biotechnology industry, which emerged a few years later. Biotech companies use recombinant DNA to insert genes coding for useful products into bacteria and other organisms, turning them into tiny factories for making things from medicine to industrial chemicals. The earliest application of this technology was in the pharmaceutical industry. Learn more about this by searching for “Recombinant Pharmaceuticals” in our collection.

Source: Accession File

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