One of the greatest transformations in modern medicine arguably began with a corned beef sandwich.
It was the late 1960s, and new Department of Medicine Chair Lloyd Hollingsworth “Holly” Smith Jr., M.D., was set on turning UC San Francisco into a basic science research powerhouse. It was a move bolstered by a rise in National Institutes of Health (NIH) funding for science across the board. He hired biochemist William J. Rutter, Ph.D., to resuscitate the Biochemistry and Biophysics Department.
“Academic leadership depends, in considerable measure, on betting on people,” Smith remembered in a 1998 interview. “Bill had, and still retains, an innate and uncanny ability to judge people.”
Herbert Boyer, Ph.D., was ascending. Smith’s pick for microbiology professor, who had once named his cats Watson and Crick, was peering into medicine’s future. Fresh from his post-doctoral fellowship, Boyer was fascinated with restriction enzymes — ninja-like proteins in bacteria that slice and dice DNA from invading viruses as part of their defenses.
If he could control these microscopic snips, UC Berkeley historian Sally Smith Hughes writes in her book, “Genentech: The Beginnings of Biotech,” he could manipulate “the stuff of life.”
Within six years, Boyer’s lab isolated a restriction enzyme that could slice DNA’s twin strands in a predictable and repeatable way. What’s more, the snipping protein produced a jagged edge, leaving one “sticky” strand dangling longer than the other. He and others suspected that this sticky bit could eventually latch onto another piece of DNA, combining the strands like Velcro strips.
This recombinant DNA, at the heart of scientists’ dream to cut life’s fabric apart and restitch it, wasn’t a novel idea. But, until Boyer, the cutting was tedious. He accomplished it with just one step.
Still, by 1972, no one, not even Boyer, had stitched DNA back together.
Dawn of modern medicine
When Boyer embarked on his quest, medicine was made the way it had been since the dawn of time — from plants, animals, and, ultimately, chemistry. Life-saving insulin, for instance, was still hand-culled from the pancreas of millions of pigs, contributing to deadly global shortages. Gene splicing would mark a whole new era, allowing scientists to genetically engineer targeted and scalable medicines, including antibodies and hormones like insulin. Unbeknownst to Boyer, it would also give rise to a whole new industry and set the stage for not one but two medical revolutions.
In November 1972, Boyer found the missing stitch at a conference in Honolulu. Also attending was Stanford University Professor Stanley Cohen, M.D., who was studying plasmids — tiny, circular pieces of independent DNA found in bacteria that can transfer genetic material to their host organisms. Months earlier, he had, for the first time, removed and replaced sections of plasmid DNA. The only problem was that it shredded the DNA so haphazardly that it made studying what survived difficult.
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After a long day of presentations in a stuffy conference hall, Cohen and Boyer decided to take a stroll with some colleagues. The walk gave Cohen and Boyer a chance to talk about the ongoing experiments in their labs. In a flash, it struck them that they might have between them the makings of a method for joining and cloning DNA molecules.
Pausing at a delicatessen near the beach at Waikiki, the group settled into a booth and ordered sandwiches and beer. Cohen and Boyer grew increasingly “jazzed,” as Boyer later put it, about the potential synergism.
– Sally Smith Hughes, “Genentech: The Beginnings of Biotech”
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Within roughly five years, the pair succeeded in combining Cohen’s plasmids and Boyer’s enzymes to create recombinant DNA technology, genetically engineering bacteria that could produce a foreign protein. The feat turned harmless bacteria into “factories,” capable of pumping out large amounts of proteins, like those needed to make insulin.
The first biotech company
Shortly afterward, up-and-coming venture capitalist Robert Swanson pitched Boyer on co-founding the first biotech company, which they named Genentech, Inc. Boyer and Cohen had produced a new era of medicine, but Genentech created a new model of industry.
“Commercialization of biological discoveries was far from novel at the birth of Genentech: Big Pharma had been doing it for a long time,” recalled former UCSF Chancellor J. Michael Bishop, M.D. “But for a member of the academic community to be so intimately involved, that was a sea change.”
Biotech was born, creating a boom in American jobs. In September 1978, Genentech scientists and others used this technique to produce synthetic insulin, making possible the inexpensive, large-scale production of insulin globally.
Meanwhile, Rutter’s knack for snapping up the best and brightest young scientists helped catapult UCSF’s basic science research into the big leagues, surpassing that of many large private institutions. In 1981, he founded the biotech firm Chiron Corp. with former UCSF biochemistry professor Pablo D. T. Valenzuela, Ph.D, and UC Berkeley professor Edward Penhoet, Ph.D. Under their leadership, Chiron became the first to map the DNA structure of HIV and produce the world’s first recombinant vaccine, which targeted hepatitis B.
Billion-dollar industries
Today, UCSF continues this tradition, creating hundreds of new companies and partnerships that have produced thousands of well-paying jobs and fueled the growth of biotech, pharmaceutical, and related industries in every state across the country.
In 2017, UCSF created Innovation Ventures to support the transition of UCSF innovation out of the laboratory and into the marketplace. By January 2022, there were almost 7,000 biotechnology companies in the U.S. and at least 240 from UCSF faculty alone. UCSF faculty-founded firms had raised almost $12 billion in venture capital and had a combined valuation of almost $170 billion as of 2023.
UCSF faculty registered 171 new scientific inventions in 2024, while nearly 100 were licensed to companies for development. Examples of inventions include:
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An artificial kidney that could transform the quality of life for the more than 800,000 Americans with kidney failure. Invented by bioengineer Shuvo Roy, Ph.D.
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The first artificial intelligence-enabled X-ray program to flag potential collapsed lungs and now used globally. Invented by radiologists John Mongan, M.D, Ph.D, and Andrew Taylor, M.D., Ph.D.
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Bioengineered immune cells that can be programmed to locate diseased cells anywhere in the body and execute a wide range of customizable responses, like targeted drug delivery. Dubbed synNotch cells, this technology was led by biochemist Wendell Lim, Ph.D., and is the first innovation from UCSF’s Living Therapeutics Initiative to enter human clinical trials.
Innovations like these continue to drive America’s global leadership. They are also ushering in yet another new dawn in modern medicine in which scientists can biologically engineer living cells to outwit even the most aggressive cancers.
“We are at an inflection point in the history of life sciences, with new computational tools and biological methods that can accelerate discovery at unprecedented rates,” said UCSF Chancellor Sam Hawgood, MBBS. “Now, more than ever, patients are counting on us to invest in the life-changing therapies that will address the most devastating diseases.”
