Nobel winner Allison did research at UC Berkeley.
Nobel Prize laureate James Allison did the bulk of his award-winning immunotherapy research out of a modest lab at UC Berkeley in the 1990s, working with a team of scrappy post-docs who were bucking conventional wisdom around the role of the immune system in fighting cancer.
Their work, his team members now recall, was propelled by the thrill of discovery and an almost naive enthusiasm. More than 20 years later, they now have the world’s most prestigious stamp of approval.
The Nobel in physiology or medicine was granted to Allison, along with Japanese immunologist Tasuku Honjo, Monday morning. The two scientists developed separate techniques for turning on the
immune system to attack tumors that were unresponsive to other cancer-killing therapies. Allison worked at UC Berkeley from 1985 until 2004, and is now at the University of Texas MD Anderson Cancer Center.
“This is very nice full circle for the work that we did back then,” said Matthew Krummel, a UCSF pathologist who, as a graduate and postdoctoral student, worked closely with Allison at UC Berkeley in the ’90s. “We knew it was a big deal, we knew we were really making progress in areas where no one would have expected. We knew this was not a pedestrian finding, but something fundamentally earth-changing.
“It’s nice to have this acknowledgment,” he said.
Allison’s research led to the first commercially available immunotherapy in the world, a drug called Yervoy that is primarily used to fight skin cancer that has spread to other parts of the body. The drug, approved by the FDA in 2011, costs more than $100,000 for a round of treatment and does not work for all patients, but it nonetheless was hailed as a remarkable addition to the arsenal of tools — including chemotherapy, surgery and radiation therapy — used to fight cancer.
Immune cells have molecular receptors — essentially on-off switches — that stop them from taking action. These receptors, which scientists have come to call immune checkpoints, are key to maintaining a healthy immune response: It would be problematic for immune cells to be overactive and attack a person’s own body.
But the checkpoints can prevent the immune cells from doing their jobs and going after tumors. The work by Allison and Honjo is in developing checkpoint inhibitors — molecules that essentially turn key immune cells back on, for a period of time, to fight an aggressive cancer.
Checkpoint inhibitors now are used to treat multiple cancers, in addition to melanoma.
“There was actually a ton of skepticism in the 1990s that you could ever do this with the immune system,” said David Raulet, director of UC Berkeley’s Immunotherapeutics and Vaccine Research Initiative. “So this was really a sea change. It spurred a transformation of the cancer therapy field. We’re very proud of (Allison’s) accomplishments because they created a whole new type of cancer therapy.”
Scientists who worked with Allison at UC Berkeley recalled an energized, highly motivated lab environment, where young researchers were encouraged to let curiosity drive their work.
Around the world, many of the top scientists in immunology had decided that the immune system was too complex to be easily harnessed as a tool to fight cancer. Allison’s team wasn’t necessarily trying to buck that line of thinking — they were just eagerly exploring the basic mechanics of immunity, said Russell Vance, director of the Cancer Research Laboratory at UC Berkeley who worked briefly in Allison’s lab as a graduate student in molecular and cell biology.
“It was an exciting time in the lab,” Vance said. “It felt like we were revealing the fundamental mechanisms about how the immune system works. Like we were finally understanding its basic nuts and bolts. Those kinds of discoveries, once they’re discovered, they’re discovered forever. It feels momentous.”
Vance said he woke up at 2:30 Monday morning to watch the Nobel announcements online — sitting in the quiet in his house, while his family slept. He let out a yelp of joy when the names were revealed.
Krummel said Allison had a “laissez-faire” attitude toward the scientists in his lab. He would largely leave his people alone to follow their own path, then dive in to help drive their work forward when he saw intriguing results.
“He’s a perfect scientific opportunist, and I mean that in all the right ways. He’s cognizant of that value of what you’re doing,” Krummel said.
The work was done out of UC Berkeley’s Life Science Addition facility, built in 1988, just a few years after Allison came to the campus. His team worked mostly in a fourth-floor lab, but they spent a lot of time on the seventh floor, too, where the laboratory mice were housed and the scientists had “the best view on campus,” Krummel said.
UC Berkeley at the time wasn’t considered the type of institution that produced medical marvels — leaps in basic science, yes, but without a medical school or hospital on site, the scientists couldn’t put their discoveries into play in human subjects. In fact, that was what eventually forced Allison to leave. When his work in immunotherapy had progressed beyond the lab, he moved to Memorial Sloan Kettering in New York to help oversee human clinical trials.
In a press conference Monday morning, Allison said it was gratifying to see such a profound payoff for his long years of work — not just in the Nobel, but in the countless patients whose lives have been prolonged by his discovery.
In truth, though, curing cancer was never what inspired his work, he added.
“What really motivates us as scientists is the desire to know something that nobody else knows,” Allison said. “Hopefully, it’s something important.”