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Biotechnology at 25 : The Founders

Stanley Cohen's and Herbert Boyer's basic science discovery of recombinant DNA technology in 1973 sparked a revolution in biology and spurred development of the biotechnology industry. The invention’s far-reaching implications for the interconnected worlds of science, commerce, and society are suggested in what follows.

The science
The idea for the gene cloning technique first arose in November 1972 at a scientific meeting on plasmids in Honolulu. (Plasmids are circles of DNA found in bacteria. They carry several genes, including ones for antibiotic resistance.) Cohen, who had been studying plasmids, was intrigued by Boyer's presentation on bacterial enzymes which cut DNA at specific sites in the DNA molecule. On a late evening excursion to a delicatessen in Waikiki, the two scientists talked about a collaboration combining their areas of scientific expertise.
By early 1973, they were launched on a series of experiments resulting in a method to select and replicate specific foreign genes in bacteria. Their purpose was strictly scientific; thoughts of commercial application came later.

Cohen, Boyer, and colleagues at Stanford and UC San Francisco wrote three landmark papers in 1973 and 1974 which demonstrated the method’s use in cloning the DNA of both lower and higher organisms, such as Xenopus, the African horned frog.
In 1975, Cohen wrote an article for Scientific American explaining the DNA cloning technique. He emphasized its usefulness to basic science and also its commercial promise for synthesizing antibiotics, hormones, and enzymes.
The controversy
An international controversy arose due to fears raised in the minds of both scientists and the public about potential hazards arising from recombinant DNA research, which some saw as "tinkering" with life while others saw vast potential for "improving" life. The debate was carried in the scientific press and lay media from the mid 1970s into the early 1980s, and continues in slightly different form today. This Time magazine cover, "Tinkering with Life," and the DNA molecule with the head of a fanged snake are two of the ominous images generated during the years of the DNA controversy. Note the scientists "tinkering" with the DNA helix.
Scientists, rather than government, were first to act to try to contain the controversy. In 1974, Stanford biochemist Paul Berg drafted a letter calling for a temporary moratorium on two kinds of recombinant DNA research until guidelines designed to control any possible biohazard could be formulated. The ten other signatories included Boyer, Cohen, and James D. Watson.
Asilomar conference and recombinant DNA guidelines
Berg was also the prime organizer of the Conference on Recombinant DNA Molecules held at Asilomar in Pacific Grove, California in February 1975. The goal of the conference was to estimate the risk of biohazard and to formulate guidelines for recombinant DNA research. This is the letter which Berg sent to Cohen, inviting him to attend the Asilomar conference.
Cohen's scribbled preliminary notes on the talk he was to give at Asilomar. The program was so concentrated that formal presentations were held after dinner on three consecutive evenings.
Paul Berg was one of many scientists who commented on drafts of the recombinant DNA guidelines, which the National Institutes of Health issued in final form in June 1976. The guidelines have been repeatedly amended with the result that they are currently less stringent than when originally formulated.
The first DNA cloning patent and the growing commercialization of biology
A front page New York Times article on the gene cloning method highlighted its possible practical applications in biomedicine and agriculture. The article sparked Stanford's interest in patenting and licensing the method, activities which in the 1970s were far less common in academic biology than they are currently.

In December 1980, the U.S. Patent and Trademark Office issued the first of three basic patents on gene cloning to Stanford and the University of California. The 1980 patent was the first significant patent to be awarded in the new biotechnology. In 1996, the American Chemical Society awarded plaques with a reproduction of the patent to Cohen and Boyer.
Niels Reimers, manager of Stanford's Office of Technology Licensing, had a large role in orchestrating the patenting and licensing of the cloning technology invented by Cohen and Boyer. In a Bancroft oral history, Reimers remarked on the method's importance for the biotechnology industry. Its importance was not initially apparent to some of the companies he approached to license the technology: "Because a great excitement developed regarding this area [of recombinant DNA], I maintained from the beginning that this work of Cohen and Boyer would underlie the whole field of biotechnology. And I repeated it over and over. When I first went licensing, a lot of the companies, the business people, didn't really understand the technology."
The first wave of biotechnology companies founded in the late 1970s and early 1980s gave rise to tensions over the propriety of patenting and commercial activities in academic biology. This 1981 journal cover depicts the perceived conflict of interest: The university scientist caught in a DNA helix is tugged by a corporate representative on the left and by a university colleague on the right. The mailing label is addressed to William J. Rutter who, as a UC San Francisco professor and Chiron executive, was himself subject to these tensions precisely at this time.
These news articles describe the 'gold mine' which some patents now represent to research universities in the Bay Area and beyond. In contrast to 25 years ago, virtually all American research universities today have on-campus programs for licensing employee inventions. Furthermore, it is the rare faculty member in biomolecular science who does not now have a relationship of some kind with industry.
The biotechnology industry
The Bay Area is home to more biotech companies than any other region of the world. The exhibit focus on three firms – Genentech, Inc., Chiron Corporation, and Tularik, Inc.– is due to their strong link to the University of California, and because Bancroft has collected oral histories with their founders.
Genentech, Inc.
Genentech, incorporated in April 1976 by Herbert Boyer and venture capitalist Robert Swanson, was the first company founded on the basis of recombinant DNA technology. This Genentech annual report pictures the statue memorializing Boyer's and Swanson's initial meeting. The company name, Boyer's invention, is a contraction of Genetic Engineering Technology.
This Time magazine cover of Boyer was published shortly after Genentech went public in 1980. The stock at its initial public offering underwent the most dramatic escalation in value in Wall Street history, a sign of investors' fevered interest in biotechnology at the time.
This article in the journal Nature describes Genentech's dramatic Initial Public Offering. The fact that a science journal saw fit to cover what was largely business news suggests the high-level attention which commercial biotechnology attracted in the early 1980s.
Chiron Corporation
In 1977, a team of UC San Francisco scientists, including William J. Rutter, cloned the rat gene for insulin after an intense race with competing laboratories described in Stephen Hall's book, The Invisible Frontier (1987). The UC San Francisco press release and Time magazine article (June 6, 1977) describe the achievement.

Left to right: William Rutter, Raymond Pictet, John Chirgwin, Axel Ullrich, Ed Tischer, John Shine and Howard Goodman .

In 1981, Dr. Rutter and his former students, Edward E. Penhoet of UCB and Pablo Valenzuela of UCSF founded Chiron in Emeryville, California. From the left: Penhoet, Rutter, and Valenzuela. (Photo by David Powers, 1984)
These are the company's first business plans, one in Rutter's handwriting for "Biotechnology, Inc.," and a second typed version for "Chiron Corporation." Penhoet's son suggested naming the company after Chiron the centaur of Greek mythology known for his medical skill. A centaur is a mythological creature, half man and half horse, and hence an appropriate name and symbol for a company founded on recombinant DNA technology.
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A major commercial target of the new company was a vaccine for hepatitis B, a project supported by the pharmaceutical company Merck. A news release and silver platter commemorate approval by the Food & Drug Administration in 1986 of the Chiron-Merck hepatitis B vaccine. It was the first recombinant vaccine to receive FDA approval.
In 1991, Chiron bought Cetus, its next door neighbor and sometime competitor. A memo to Chiron employees announces the merger as "the most important business event in our ten-year history..." A news release describes Chiron's purchase of Cetus and the sale of Cetus' polymerase chain reaction (PCR) to the pharmaceutical company Hoffmann-LaRoche for $300 million plus royalties. PCR is now used worldwide as a powerful tool for amplifying DNA.

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