At Stanford Medicine symposium, Nobelists stress importance of basic research to drug discovery

Curiosity-driven discoveries in often obscure areas of basic biological science pave the way to unexpected applications in medicine, according to a panel of Nobelists.

“The most important contribution that we in the university can make to the success of the biopharmaceutic industry is through work that is done quite independently of them, and without any of their needs in mind,” said Roger Kornberg, PhD, Stanford Medicine professor of structural biology, who won the Nobel Prize in chemistry in 2006.

The discussion, moderated by Stanford University President Marc Tessier-Lavigne, comprised four Nobel laureates in chemistry, three from Stanford Medicine and one from the University of California, Berkeley. The discussion took place during the seventh annual Stanford Drug Discovery Symposium, held April 24 and 25 at Berg Hall on the Stanford School of Medicine campus.

Berg Hall is named for the late Paul Berg, PhD, a professor of biochemistry whose groundbreaking research helped forge a path for collaborations between academia and the biopharmaceutical industry. Berg was awarded the 1980 Nobel Prize in chemistry for combining DNA from two different organisms. The result, the first recombinant DNA molecule, sparked the field of genetic engineering, which has led to myriad life-saving drugs.

From its inception in 2016, when it drew 250 attendees, the Stanford Drug Discovery Symposium has grown immensely in both reach and roster. This year’s event featured more than 40 high-ranking academic, corporate, foundation and government executives speaking — in some cases via Zoom — before some 400 in-person attendees and a registered livestream audience of more than 6,000.

“The innovations we discuss at this symposium stand to transform human health as we know it, enabling us to better predict, prevent and cure diseases once thought to be incurable,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. “The pace of this innovation — at Stanford Medicine and elsewhere — is only accelerating.”

Yet the constant call for immediate medical applications risks drowning out funding pleas from those pursuing the fundamental science crucial to generating medical applications, the Nobelists argue.

Decades of research behind discoveries

The invention of recombinant DNA set off the biotech revolution, founded that industry, and marked the beginning of partnerships between schools of medicine and biological scientists with industry, said Kornberg, the Mrs. George A. Winzer Professor in Medicine. “The research that led to the discovery of recombinant DNA spanned about 20 to 30 years of study of DNA and enzymes that react with it, and no other idea of any purpose except understanding, except exploration, except the reward of discovery. I think it would have been far less successful had it been done with an eye to the application at the outset.”

Professor of molecular and cellular biology Brian Kobilka, PhD, told the audience about his work with a class of cell-surface molecules, a field that has become exceedingly important: “My research on G-protein-coupled receptors began in the late 1980s, at a time when we knew there were maybe seven or eight members of this family,” said Kobilka, the Hélène Irwin-Fagan Chair in Cardiology. “We now know there are roughly 800.” The research that won Kobilka the 2012 Nobel Prize focused largely on understanding the structural basis for how G-protein-coupled receptors work, which has enabled structure-guided drug discovery and optimization for these proteins, now the largest class of pharmaceutical targets.

Jennifer Doudna, PhD, a professor of chemistry and of cellular and molecular biology at UC Berkeley, joined the Nobelist ranks in 2020. “From the beginning of my career as a biochemist,” Doudna said, “I’ve been interested in how molecules work, and in particular, the roles of RNA molecules in biology. It was through that kind of curiosity-driven science that I got involved.”

In the mid-2000s, Doudna and her colleagues started investigating a bacterial immune system called CRISPR. “I never had any ambition, or any idea that it would lead in the directions it did,” she said. “CRISPR is, in essence, a targeted, programmable way to cut DNA. It is now universally recognized as a powerful tool for genome editing, which not only is invaluable in research but also holds immense potential for medical applications in gene therapy.

“This year, we’re going to see the first approval of a CRISPR drug, for sickle-cell disease —that’s just the beginning.”

Carolyn Bertozzi, PhD, professor of chemistry, was the newest Nobelist of the bunch, earning the honor in 2022. “As a chemist, I’ve always been interested in developing new technologies to build molecules of complexity,” said Bertozzi, the Baker Family Director of Sarafan ChEM-H and the Anne T. and Robert B. Bass Professor in the School of Humanities and Sciences.

Some of those technologies are now used widely to build molecules such as antibody-drug conjugates, Bertozzi said. “My work has also intersected with biopharmaceutical applications through my fundamental studies of glycobiology, a branch of biology that focuses on complex carbohydrates. We’ve discovered pathways and targets that have led us to develop new types of therapeutic candidates.” Some of those therapeutic candidates have spun out into startup companies, she added.

“It’s fascinating,” Tessier-Lavigne told the panelists, “that your work has led to drug-discovery applications but was rooted initially in curiosity: trying to understand biological systems, molecules, cells and receptors. Here we see the importance of fundamental research that seeks simply to understand the body in health and in disease.”