Renegade Texan scientist Jim Allison devotes his life work to find a cure for cancer after the disease takes the life of his mother.
Born in the sleepy South Texas town of Alice, James Patrick Allison entered the world shadowed by two older brothers – Murphy by eight years and Mike by six. According to them, Jim was a hardheaded boy, a trait that would serve him well in the years ahead.
“Breakthrough” tracks the arduous path Allison must blaze in order to ensure that a truly innovative approach to cancer treatment makes its way into the hands of doctors and patients. The challenges prove formidable, but to his credit, Allison never loses sight of the goal. Despite repeated admonishment that he was wasting his time, Allison remained determined to succeed.
In 2015, the University of Texas at Austin – whose tagline is, “What starts here changes the world” – honored Allison with its distinguished alumni award. Three years later in 2018, Allison received the Nobel Prize in Medicine.
Allison has maintained a long history with cancer over the years. Though his mother was afflicted with the disease for some time, Allison did not learn that she was dying of Lymphoma until very near the end because no one talked about such things. Jim was eleven at the time. His father was heartbroken and became detached. Allison’s life changed after that. As a coping mechanism, he would walk in the woods while learning to play the harmonica. In adulthood, his brother Mike also succumbed to cancer.
Allison graduated from high school at age 16, then went on the University of Texas at Austin, determined to become a biologist. Conflict arose quickly with an instructor over the subject of evolution, which he refused to teach. As such, Allison knew there wouldn’t be any biology taught in the course, so he declined to take it.
While Allison was in college, T cells were discovered, which lie at the center of the human immune system circulating in the blood. Allison describes the event as wondrous and it would dominate his research agenda from then on.
Following the T cell discovery, Allison and one of his professors started taking samples of water from nearby streams to survey them for bacterial asparaginases. These substances tested on mice met with favorable results, and this early research convinced Allison that the immune system plays an important role in response to cancer.
By 1974, Allison was working in San Diego at Scripps Clinic so he could learn more about immunology. In the evenings, Allison would meet up with fellow relocated Texans and sometimes played harmonica with a local band at a club called The Stingaree.
In 1977, MD Anderson opened up a new lab in Smithville near Austin, where Allison transferred. His research on T cell receptor research continued. Many labs at the time were also investigating how T cells worked to support the immune system. Yet the studies often conflicted, leading Allison to question the results and ultimately to pursue different, decidedly unconventional methods. He found that a single molecule, a small part of a T cell called the receptor, recognizes diseased cells in the body. In a seminal discovery, Allison was the first to purify T cell receptors in the lab. His findings led to an offer as full professor at UC-Berkeley. Although Allison was happy at Smithville, he decided to take the job as an opportunity to make a larger impact on the field. At the time, immunology was not considered a real science, but rather more of a pseudoscience.
Allison’s knack for innovation and critical thinking enabled his biggest breakthrough. Though previous studies indicated that CTLA-4, a protein found on T cells, activated an immune response, Allison demonstrated the opposite – that CTLA-4 brakes the immune system. While this made CTLA-4 a useful treatment for autoimmune disorders, Allison went in the other direction. He decided to develop inhibitors that block CTLA-4, thus enabling the immune system to reengage and attack cancer cells.
Early on in the film, we meet Sharon Belvin, who describes her symptoms of what she thought was bronchitis. Progressively over the next couple of months, her condition worsened. One day while walking up a hill, she couldn’t manage to take a deep breath. At age 23, physicians diagnosed her with cancer and offered little chance for survival.
Despite repeated rounds of chemotherapy, Belvin never benefitted. We follow Belvin’s story in and out of Allison’s tortuous path to develop his novel approach. When she finally entered the first clinical trial, her quality of life, at last, began to improve.
Bristol-Meyers Squibb figures prominently in the story, at first because it held crucial patents and maintained a formidable legal apparatus. Eventually, the company reluctantly funded the development of Allison’s drug called Ipilimumab despite previous failures of earlier immune system treatments for cancer.
The new therapy takes time and at first actually causes tumors to grow as Ipilimumab enters them – initially leading the FDA to doubt their efficacy. What researchers learned after the clinical trials – canceled due to poor results – was that the patient’s condition often improved later as the tumors shrunk and disappeared altogether. The surprise results in 2006 encouraged BMS to commit to an expensive, risky and lengthy five-year clinical trial, championed almost as much by project lead Dr. Rachel Humphrey as Allison himself.
Interspersed throughout the film are references to Austin’s social life and the rise of the progressive country movement in the 1960s. Willie Nelson had just moved back from Nashville with plans to retire, though that obviously changed when the Outlaw Country music scene emerged in Austin.
While Allison taught at UC-Berkeley, Willie Nelson’s Red Headed Stranger album went platinum and Columbia Records decided to throw a party for him. Invited backstage to the event, Allison met Nelson, who mentioned he had the next night off. Allison then told the legendary singer-songwriter about amateur night at The Stingaree and Nelson thought it sounded like fun. The next night when he walked into the club, people were aghast and elated, as Nelson played to the crowd for three hours. People called their friends and the bar filled up spilling out into the street. In the last scene as the credits roll for “Breakthrough,” footage from Austin City Limits features a live performance by Willie Nelson, with Jim Allison on stage playing the harmonica.
As the film notes near the end, Ipi and successor Immuno-Oncology drugs have now treated nearly a million patients throughout the world. Jim Allison is one of them, now facing cancer for the third time in his life. Although the drugs don’t work for everyone, for so many, they represent a miracle cure essentially in its earliest stages of iteration – with more breakthroughs likely in the future.
Written, directed and produced by Bill Haney, “Breakthrough” is a compelling, often heart-wrenching production, not only because of the toll cancer has taken on so many, but more importantly for the hope the film proffers. Narrated by Woody Harrelson, this excellent documentary tells an uplifting story that demonstrates how original thinking combined with dogged perseverance can literally change the world.
In Theaters Friday, September 27th
