Jim Allison: Breakthrough is the astounding, true story of one warm-hearted, stubborn man’s visionary quest to find a cure for cancer.
Today, Jim Allison is a name to be reckoned with throughout the scientific world — a 2018 Nobel Prize winner for discovering the immune system’s role in defeating cancer — but for decades he waged a lonely struggle against the skepticism of the medical establishment and the resistance of Big Pharma.
Jim Allison: Breakthrough takes us into the inspiring and dramatic world of cutting-edge medicine, and into the heart of a true American pioneer, in a film that is both emotionally compelling and deeply entertaining.
Jim Allison Bio
James Allison, winner of the 2018 Nobel Prize in Medicine, was born on August 7, 1948 in a tiny South Texas town called Alice. Named for the daughter of the legendary King Ranch owner, Alice has boasting rights as birthplace of a second Nobel winner, Robert F. Curl, Jr., who took the honor for chemistry in 1996. It is also where Tejano, a unique Tex-Mex musical genre, took root in the mid-1940s. Tejano may have inspired young Jim to take up the harmonica, which he still performs at parties and events, sometimes sharing the stage with fellow Texan Willie Nelson.
Allison’s father, Albert, was a physician and his mother, Constance, a homemaker and “positive influence” who tragically died of lymphoma when he was eleven years old. There were two older brothers, Murphy and Mike. Life was difficult for Jim following his mother’s passing. His father, an officer in the Air Force Reserves, was often away from home, during which time he was fostered by a local family with a son about his own age.
Even as a kid, Allison displayed a yen for science. Encouraged by his parents, he toyed around with a Gilbert chemistry set, setting off little bombs in the woods behind their home. A summer in a NSF-funded science-training program deepened his interest. After graduating from high school at sixteen, he entered the University of Texas, Austin where he would earn a B. S. Degree in microbiology (1969) and a Ph.D in biological science (1973). He was a member of Delta Kappa Epsilon fraternity.
But the fierce passion which kindled his interest in curative science, was unquestionably ignited by the early passing of his mother. His life’s path was set by the time he entered graduate school, when he convinced his PhD advisor to bring cancer study into the lab.
It was a propitious moment. The immune system’s “T-cell” had recently been discovered. A type of white blood cell, the T is a front-line soldier in the battle to keep us healthy, its role assigned by nature to distinguish friend from foe. Though immunology was not even a bona fide science at the time, Allison zeroed in on the immune system’s potential against cancer. (His dissertation proposed a new approach to treating leukemia but decades would pass before a similar drug was patented.)
Soon after graduation, Allison began criss-crossing the country in a quest to unlock the mysteries of the T cell. How do T cells work? How do they identify an invader? Why can they recognize the flu virus, for example, but not cancer? In addition to pure knowledge, he sought institutions open to innovative research - not a simple matter in a profession tending toward caution and rigidity. His first stop was Scripps Clinic & Research Foundation in San Diego (1974-77) where he did post-doctoral work. Married by now to the former Malinda Bell, the couple often joined other Texas ex-patriots at the port city’s Stingaree bar. He fondly remembers one night playing his harmonica until the wee hours
with Willie Nelson and his band. “I didn’t have to buy a beer for a couple of years after that,” he recalls.
In 1977, he back-tracked to Texas - to the newly opened MD Anderson Center in Smithville, where he could both teach and freely experiment. Above all, he sought the ‘Holy Grail’ of immunology research: the means by which a T cell recognizes an invader.
By 1982, he believed he had found it. Boldly, he took himself to a convention in California where ordinary scientists like himself were allowed to present their data on a poster board, for all to see and critique. “That is the T cell receptor,” he declared, pointing to a spot on the board with the confidence of Luther at Wittenberg. His proof created a sensation. By identifying the molecule by which T cells recognize everything - the T cell Antigen Receptor,
or TCR - Jim Allison made history. His subsequent article in the Journal of Immunology shot him to the top of immunologists world-wide, and he no longer toiled in shadows.
After a year at Stanford as a visiting scholar, he continued to the University of California, Berkeley as a professor of immunology and director of the Cancer Research Laboratory (1985-2004), and was concurrently appointed professor at the University of
California, San Francisco from 1997. This was the longest and perhaps most fruitful single period of his career. Selecting his lab staff from the best-and-brightest, he fired them up to go the distance - to break through academic dogma.
Time magazine’s 1980 cover on Interferon had made immunotherapy a hot topic, and though that drug’s potential was never realized, a small group of immunologists were desperate to better understand the immune system’s role in fighting cancer. When a French scientist announced the discovery of CTLA-4 (a new protein on the surface of the T cell). While many colleagues believed that CTLA-4 was another accelerator of the immune system, Allison was unconvinced. He insisted they do “the killer experiment,” ultimately proving that, in fact, CTLA-4 acted as a brake (or inhibitory molecule) on the T rather than an igniter to action. (The University of Chicago’s Jeff Bluestone separately confirmed his findings.)
Only by persistence and years of inconclusive, almost maddening, laboratory experiments, did Allison and his team finally find a way to free the T to do its job. His crucial insight was to find a way to block the protein (CTLA-4) by developing an antibody that allowed the T to identify - and attack - a cancer cell. This represented a new way of using the immune system in cancer treatment because it focused on the immune system and not the cancer.
But this was only the beginning. Now Allison had to convince his colleagues in the medical and pharmaceutical communities to actually manufacture the drug and do the trials. That is why Jim Allison made his next-to-last move - across the continent to New York City - because of its proximity to major companies such as Bristol-Myers Squibb and Pfizer, and to medical institutions such as Memorial Sloan Kettering.
In 2004, Allison re-located to Sloan-Kettering’s Cancer Center as director of its Ludwig Center for Cancer Immunotherapy. Over the years he was also affiliated with Weill Cornell Medicine, Weill Cornell Graduate School and the Howard Hughes Medical Institute. He was establishing immunology departments and continuing research but above all else he oversaw the Ipilimumab trials. Finally, in 2011, “ipi” became the first (immune checkpoint inhibitor) drug approved for late stage melanoma treatment by the U. S. Food & Drug Administration (FDA) - commercially known as “Yervoy.” Ironically, while Allison’s anti-CTLA-4 work shattered its status as a ‘wonder drug,’ it laid a foundation for the development of “ipi” and many other drugs currently in use against cancer.
In 2012, Jim Allison went home to Texas, to the MD Anderson Center at the University of Texas, Houston, as professor and chair of the department of immunology, and executive director of the Immunotherapy Platform. His marriage to Malinda Bell was over but he would find a new partner in scientist Padmanee Sharma, whom he married in 2013. By now he had become one of the most lauded immunologists on the planet. In October of 2018, a telephone call from the Karolinska Institutet, Stockholm said he would share that year’s Nobel Prize in Medicine with Tasuku Honjo of Japan’s Kyoto University, a colleague with whom he had
previously shared the Tang Prize in 2014. Life was good.
2018 Nobel Prize in Medicine (with Tasuku Honjo)
2018 Jessie Stevenson Kovalenko Medal (U.S. National Academy of Sciences)
2017 Sjoberg Prize, Sjoberg Foundation & Royal Swedish Academy of Science (inaugural)
2015 Lasker-Debakey Clinical Medical Research Award
2014 Breakthrough Prize in Life Sciences
2014 Tang Prize for Biopharmaceutical Science (with Tasuku Honjo)
2013 Lloyd J. Old Award in Cancer Immunology, AACR Cancer Research Institute (inaugural)
2011 Lifetime Achievement Award, American Association of Immunologists
Membership in the National Academy of Sciences and the National Academy of Medicine
Jim Allison Timeline
Aug. 7, 1948
James Patrick Allison born in Alice, Texas
June 8, 1960
Mother dies of lymphoma
Graduates from University of Texas, Austin with B.S. in Microbiology
Sept. 6, 1969
Jim and Malinda Bell get married
T-CELL DISCOVERED IN 1959
Jim sees possibilities in “These wondrous cells at the center of the immune system (which) go all over your body to protect you.”
Sees Willie Nelson play in Austin.
Becomes a fan.
Receives Ph.D. in Biological Sciences from University of Texas, Austin
Post-doctorate study at Scripps Research in San Diego
Plays harmonica with Willie Nelson on stage at Stingaree Bar. Gets free drinks for two years afterward.
Joins faculty of University of Texas MD Anderson Center in Smithville, Texas where he is allowed exceptional freedom to experiment.
An early immunotherapy treatment, Interferon promises to be a wonder drug, but falls short of expectations, fueling skepticism of cancer immunology for decades to come.
Inspired by a lecture from Irv Weissman who would become a mentor and friend, Jim has an ‘ah ha’ moment and discovers the Holy Grail of immunology research - T-cell Antigen Receptor (TCR).
Seminal discovery at a conference in California. Jim presents his data on a poster board, points to a spot and declares: “That’s the T-cell receptor.”
Jim is first to discover the TCR: how a T-cell recognizes an invader. Overnight recognition follows
Stanford University to study under Prof. Irv Weissman as visiting scholar. Jim receives a job offer to teach at UC Berkeley; Irv tells him to go for it.
University of California, Berkeley & University of California, San Francisco (concurrently)
Jim hired as Professor of Immunology and Director of Cancer Research Laboratory. Though immunology was not considered a science, Jim and his ‘lab rats’ put it on the map. “His lab was like a pirate ship. We worked like crazy and then partied to unwind. Creativity is important. Can’t...let the mind go linear.”
- Max Krummel
Jim's son, Robert, is born - now an architect in New York City.
CTLA-4, a molecule on the surface of T-Cells, is discovered by French scientists in 1987 - setting off a race to discover its significance. Its role in the activation of the immune system is contentious. Some leaders in the field claim it’s another activating signal, but Jim & his collaborators prove that CTLA-4 acts as a brake, not activator - i.e. stops the T-cell from attacking an invader.
March 22, 1996
Publishes seminal article proving theory. March 22, 1996 article in Science
magazine. Files patent in July 1995.
BREAKTHROUGH IN BOULDER, COLORADO
In Boulder, Colorado, NeXstar Pharmaceuticals licenses anti-CTLA-4 technology from UC Berkeley. Alan Korman introduced.
Fed-up with delays, Jim, Nils Lonberg & Alan Korman make hand-shake deal to prove efficacy of ipilimumab. Take night-and-day wild ride of experimentation. 466 days later, they have it in a patient: a world record.
Nils Lonberg’s company, Medarex sublicenses from NeXstar.
Jim and Medarex collaborate on trials at UC San Francisco.
Critical Phase I results of ipilimumab (‘ipi’) trials published.
GLOBAL RACE ON T-CELL BEGINS BIG PHARMAS COMPETE TO FIND NEW DRUGS FDA WATCHES
New York City
Jim relocates to New York to be near well-funded medical centers and drug companies. 90% of his labmates move with him. “I went to be nuisance - to stay on their backs so they would fund experiments. My research with animals showed potential for humans but Berkeley had no hospital and therefore no patients.”
Works with Memorial Sloan-Kettering, Weill-Cornell Graduate School of Medical Science, Howard Hughes Medical Center (et al). Becomes embroiled in politics of scientific research - “keeps fighting like a bloodhound on a scent.”
Near death, Sharon Belvin’s metastatic melanoma gets four doses of ‘ipi’ and improves
Jim’s brother, Mike, dies from prostate cancer.
Jim also diagnosed but gets early intervention.
Sharon Belvin is cancer-free - meets Jim Allison for first time.
Jim & collaborators convince Bristol- Myers Squibb to do lengthy trials.
Hallelujah! FDA approves ipilimumab, to be called “Yervoy.”
JIM ALLISON, NOW A WORLD-FAMOUS SCIENTIST, GOES BACK HOME TO TEXAS
The University of Texas MD Anderson Cancer Center, Houston Professor and Chair of the Department of Immunology & Executive Director of the Immunotherapy Platform
Jim marries fellow scientist, Padmanee Sharma
Jim Allison receives Lloyd J. Old Award in Cancer Immunology, AACR-Cancer Research Institute (inaugural – first winner)
$3 million Breakthrough Prize in Life Sciences
Tang Prize (shared with Tasuku Honjo of Kyoto University) (inaugural)
Jim Allison receives Lasker-DeBakey Clinical Medical Research Award
Jimmy Carter cured of metastatic melanoma with Keytruda, a second generation drug based upon Jim’s original research.
Wolf Prize in Medicine
Sjoberg Prize from the Sjoberg Foundation and the Royal Swedish Academy of Sciences (inaugural)
Nobel Prize in Medicine (shared with Tasuku Honjo of Kyoto University).
Jessie Stevenson Kovalenko Medal from the U.S. National Academy of Sciences
Plays harmonica with Checkpoints, Checkmates and (sometimes) the great