Pushing the Frontiers
Jim grew up in the small town of Alice, Texas, less than two hours by car from the Mexican border. The 1957 Sputnik launch fueled his interest in science. Thanks to Sputnik, the University of Texas offered summer programs in science for high school students.
Jim started college as a pre-med major at age sixteen. Between listening to the music of Willie Nelson and sneaking down to Mexico with his buddies to hang out in bars, he sometimes went to classes. At first, he thought he might follow in the footsteps of his father, a country doctor who treated patients in the Hispanic part of town where they lived. Eventually, he gravitated towards science. Jim once told me why he didn’t go into medicine: “MDs fill their heads with facts they’ve memorized and then draw on those facts in treating patients. They’re always supposed to be right. What I love about science is that it isn’t about memorizing and trying to be right; in science, you’re supposed to be wrong, which makes it a lot more fun.”
When he was still in college, a biology professor mentioned a new discovery called T cells, which attack foreign substances in the body. Not much was known about these cells, and Jim liked the challenge of figuring them out. After years of hard work, he became the first to explain their structure. Several more years in his lab led to the development of checkpoint inhibitors, one of the most exciting breakthroughs in cancer treatment in the past quarter century. This work earned him the 2018 Nobel Prize.
| Jim explained to [Mike] that there are three reasons people develop cancers: • The patient’s immune system is weakened by age, lifestyle factors, and comorbidities. In the majority of cancers, this causes inflammation, which has become a central focus of cancer research. • The cancer sometimes disguises itself so it can compromise the body’s defenses. Building on Allison’s insight, Dr. Carl June at the University of Pennsylvania later conceived the concept of cellular therapies in which a patient’s own immune cells, rather than a donor’s, are engineered to destroy cancer. The idea is to energize the immune system by removing T cells from the patient, “teaching” those cells how to recognize the disguised cancer cells, and then returning them to the body in “attack mode.” Deploying these chimeric antigen receptors (CAR T cells), Dr. June improved treatments for acute lymphoblastic leukemia, the most common cancer in children. Then, in 2022, the FDA approved Johnson & Johnson’s CAR T-cell treatment for another blood cancer, multiple myeloma. In J&J studies, 83% of patients who received CAR T-cell therapy experienced complete remission and had no detectable cancer cells. PCF has funded Dr. June’s work for many years. • The cancer turns off the immune system. Allison’s greatest triumph may be the development of checkpoint inhibitors that turn the immune system back on by suppressing what had turned it off. In other words, Jim figured out how to block the ‘off’ switch. |
At PCF’s 1997 retreat, long before he was well known, Jim said something that changed Mike Milken’s entire perspective and mobilized him to focus on immunology. In fact, it was an idea that changed the world. “Your immune system,” said Jim, “is smarter than any of us. Disease occurs when it fails.”
Listening to Jim, Mike Milken decided to fund ongoing research at his Berkeley lab. Helped by PCF’s initial grant and other funding, Jim was able to demonstrate the market potential of his “immune system off-switch blocker.” After further development, Berkeley received initial payments of more than $87 million from Bristol Myers Squibb for Allison’s antibody. These funds were plowed back into further research.
In 2011, the Food and Drug Administration approved Yervoy®, which had been developed from Allison’s work, after clinical trials showed that it dramatically extended survival times for many patients with advanced melanoma. And because today’s precision medicine can identify the specific subtype of a tumor anywhere in the body, Yervoy® and similar immunology drugs, such as Keytruda® and Opdivo®, are now being used against several other types of cancer. Millions of people around the world have benefited from the spin-offs of Jim Allison’s breakthrough discoveries.
Excerpt adapted from Faster Cures: Accelerating the Future of Health