In April of 1981, an amendment was debated in the Texas House of Representatives proposing to reintroduce the biblical creation story into science lessons in the state’s schools. One of the speakers opposing this amendment was a young scientist who told the House, “The chief problem with creationism purporting to be a science [is that] it cannot be used to construct explanations, or merely observe fact. It does not give us any help whatsoever in understanding how tumor cells arise, or how they are eliminated by the immune system.”
The speaker was Dr James Allison, and the subject of cancer was deeply personal to him, as it is to many of us. The amendment was defeated, but Allison would go on to far greater victories in his war on the disease.
The first loss to cancer
James Allison was born in 1948, in Alice, Texas, and cancer quickly brought tragedy into his childhood; his mother died of lymphoma when Allison was just 11, with two of his uncles also succumbing to the disease soon after. To make matters worse, James’s father was frequently away on business trips, and James spent most of his formative years living with families of school friends in Alice. Despite these setbacks, he was able to thrive in school, demonstrating a determination that would prove invaluable in later years.
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In April of 1981, an amendment was debated in the Texas House of Representatives proposing to reintroduce the biblical creation story into science lessons in the state’s schools. One of the speakers opposing this amendment was a young scientist who told the House, “The chief problem with creationism purporting to be a science [is that] it cannot be used to construct explanations, or merely observe fact. It does not give us any help whatsoever in understanding how tumor cells arise, or how they are eliminated by the immune system.”
The speaker was Dr James Allison, and the subject of cancer was deeply personal to him, as it is to many of us. The amendment was defeated, but Allison would go on to far greater victories in his war on the disease.
The first loss to cancer
James Allison was born in 1948, in Alice, Texas, and cancer quickly brought tragedy into his childhood; his mother died of lymphoma when Allison was just 11, with two of his uncles also succumbing to the disease soon after. To make matters worse, James’s father was frequently away on business trips, and James spent most of his formative years living with families of school friends in Alice. Despite these setbacks, he was able to thrive in school, demonstrating a determination that would prove invaluable in later years.
The creationism debate of 1981 was not Allison’s first battle with educators. As a high school student, he had refused to participate in science lessons because evolutionary theory was not taught in his school. His teachers did not take it well. “Back in those days you could use boards to paddle students, and I seemed to be getting in trouble all the time, getting a couple of licks just for walking by.”
Despite the beatings, he persevered, choosing to take correspondence courses instead. Allison successfully graduated and enrolled as a medical student at UT Austin.
James Allison signing autographs after the Nobel ceremony in 2018
Having fun with science
At university, James swiftly discovered that the doctor’s life was not for him.
“I did not have the discipline to be a physician, so I chose to be a scientist and have more fun.” In his second year, he took a low-level job in a biochemistry research lab, and although the lab was not at that time researching cancer, he convinced his superiors to allow him to look into asparaginase, which was showing promise in the treatment of childhood leukemias. These studies yielded promising results (and asparaginase is used today in chemotherapy treatments), but by now Allison had turned his attention to T cells, which he considered a far more promising avenue.
T cells are part of the immune system, white blood cells that identify and attack threats, including tumors. As Allison puts it, “Nothing was known about how T cells recognize foreign cells, or what regulated their proliferation and function, or virtually anything else. I was fascinated, and decided to devote my career to solving their secrets.” This was an unusual decision, as immunology was an unfashionable area of research, but once again Allison persevered in the face of opposition.
A colorized scanning electron micrograph of a T lymphocyte
Applying gas, applying brakes
James’s first major discovery came in 1992, identifying CD28, a protein on the surface of the T cell that is a positive costimulator, activating the immune process. In Allison’s words, “CD28 can be compared to the gas pedal in a car, which allows the car to start moving.” But a car with only one pedal is a dangerous thing, and the same is true of the immune system; too much ‘gas’ leads to unwanted consequences, with healthy tissue and cells also being destroyed. Also, CD28 bore similarities to another protein called CTLA-4; there had been recent papers published claiming CTLA-4 was also a positive costimulator, another gas pedal.
Allison was not convinced by this and, over the next two years, his laboratory conducted experiments on this hypothesis. What they discovered shocked the scientific community; CTLA-4 was not a positive costimulator, but a negative one. Not a gas pedal, but a brake! The implications were enormous; by controlling CTLA-4 the immune system could be stimulated to fight cancerous tumors.
Not just a Nobel laureate, but a mean harmonica player!
The True Superhero’s new battle line
James had found his weapon against cancer, but he still had to find permission to use it. The clinical trials process is a long and tortuous one, not to mention hugely expensive, and there was a great deal of skepticism in the pharmaceutical world about immunotherapy as a cancer treatment. Similar miracle drugs had been proposed in recent times and failed spectacularly, and consequently funding for trials was extremely hard to come by.
To make matters worse, the standards for clinical trials of cancer treatments were largely defined by chemotherapy drugs, which acted quickly but with relatively low success rates. Allison’s new drug - which now bore the unwieldy name Ipilimumab, more commonly referred to as Ipi - did not deliver instant results, as it took time for the immune system to activate itself. As a result, early clinical trials of the drug were seen as failures, and there was little interest in funding longer-term trials.
Headstrong as ever, Allison responded to these challenges in an unusual way. He packed up his laboratory, and all of his staff, and moved the entire operation from Berkeley to New York. This allowed him to lobby directly with drug companies for the funding he needed for long-term trials, which finally and conclusively demonstrated the efficacy of his approach.
Victory, at a cost
This success did not come without a toll; his marriage to his wife, Malinda, was severely affected, and they separated before approval for Ipilimumab could be secured. In 2005, Allison also lost his elder brother, Mike, to prostate cancer, and one week after his brother’s death, James was himself diagnosed with prostate cancer. Mercifully, the diagnosis came quickly enough to allow effective treatment.
Ipi was approved by the FDA for the treatment of melanomas in 2011, and has subsequently been used to treat many types of cancer the world over. By 2019, it was estimated that Ipi and successor immuno-oncology drugs have treated nearly 1m patients worldwide. It is not universally effective, and is not suitable for the treatment of all types of cancer, or for all patients, but it represents an enormous leap forward in the fight against the disease. And without James Allison’s superheroic determination and perseverance, this could never have happened.
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