Above: Jim Allison talks with Ph.D. students in his lab.
Just a few years ago, Jim Allison was considered something of a “snake oil salesman” by other cancer researchers. The ruddy-faced, scraggly-haired scientist from Alice is used to forging his own path. He fought his high school teachers who refused to teach evolution. Later, he became convinced that the body’s immune system could be harnessed to combat cancer, even as colleagues said it would never work.
It turns out Allison was right. Now chair of immunology at the University of Texas MD Anderson Cancer Center in Houston, Allison will be in Sweden Monday to receive the Nobel Prize in Physiology or Medicine, shared with Japanese immunologist Tasuku Honjo. Allison — who plays harmonica in a band of immunologists called The Checkpoints — developed the first immune checkpoint inhibitor drug. His research led to life-saving treatments for patients who had little chance of survival. Now, Allison is focused on broadening the efficacy of immunotherapy.
Q:Can you put your work in the context of how cancer research has changed over time?
A: The whole idea of using the immune system to treat cancer has been around for over 100 years, but nobody ever really got it to work all that well. There was a lot of skepticism. The three pillars of cancer therapy were surgery, radiation and chemotherapy, discovered in that order. Immunology was kind of in the backwaters; only crazy people were doing it.
Our metastatic melanoma data kept looking better and better, so [the drug ipilimumab] was approved by the FDA in 2011. It was a big hallmark. But the skeptics said, “Oh, it’s just a melanoma drug.” Then there were responses in prostate cancer, kidney cancer, and that kind of shut that up. In about 2014, there was enough data where there were 10 years of follow-up from about 5,000 patients, and it showed that 22 percent of the patients were alive 10 years after a single dose. When this work started, if you were diagnosed with metastatic melanoma, your median life expectancy was 11 months, and there was nothing to improve that.
Finally [immunology] has become the fourth pillar of cancer therapy, and this is what really revolutionizes everything. If you get chemo or other target therapies, they’re going to kill a cell with a particular weakness. But without doing something else, they’ll become resistant. The nice thing about immunology is you can add it with those and it’ll play friendly. That opens thousands and thousands of combinations.
Have you heard from some of the immunology skeptics since winning the Nobel?
Oh yeah. Jim Watson, the guy who worked out the structure of DNA.
In 2006, I was invited to give the opening-night lecture at the big Cold Spring Harbor [cancer research conference]. I was the only immunologist there, and I’d been warned that a lot of people there were real skeptics. My friends, joking around, said, “You know, after you finish they’re just going to build a fire and burn you.” But Jim came up to me and said, “Nice talk, you almost convinced me.”
[After the Nobel Prize announcement] I got a very nice note from him that said, “Congratulations, you did it.”
You’ve said that your high school wouldn’t teach evolution. What was it like growing up in Alice?
My dad was a country doctor. He gave me a chemistry set and a microscope and other gizmos. You know, if you don’t play football, you’ve got to do something.
I also was lucky enough to have some good teachers — not in biology. I looked at the syllabus and it had a little bit of biochemistry and the rest was just memorization and animal species, genus, all that stuff. Which is cool, but after a while it’s boring. I said, I’m not going to take that, where is evolution? Trying to teach biology without Darwin is like teaching physics without Newton; you don’t go anywhere. It was pretty ugly for a while. One teacher decided I had betrayed him, because I excelled at all his classes but he thought I was some kind of heathen.
But several other teachers and counselors helped hook me up with programs at the University of Texas at Austin. Every summer I would go from Alice to Austin, and it really opened my eyes. I got hooked.
You testified on evolution at a Texas Legislature committee hearing in 1981—
Ernestine Glossbrenner [then a state representative from Alice] was my eighth-grade algebra teacher. She was pretty liberal, but somehow she got elected. She was on the Education Committee, and Mike Martin — that guy was a lunatic — he introduced a bill to require the teaching of creation science. Ernestine said, “Martin’s going to have three or four busloads of people from his church area in East Texas [to testify], I’ve got to have somebody come.” So I went down.
I said: Use your creation science to show me how bacteria become resistant to antibiotics. Use your creation science to tell me how a tumor escapes the immune system. To try to predict something that has never happened before. What you’re proposing isn’t even science. You can believe whatever you want, but it’s not science, and it has no place in a science curriculum.
The bill died, but the State Board of Education is still fighting over evolution. What do you make of that?
I just think it’s nuts. It’s not scientific reasons they’re giving; they’re always religious reasons. After that bill failed, then it just moved down for a while to the local schools. The rabid anti-evolution folks can mobilize people and scare the crap out of principals and teachers and just bully their way in. I just don’t know why people are so afraid — of knowledge, basically.
Texas has the nation’s highest uninsured rate, and cancer treatment is expensive. Do you see a way for these drugs to be widely available?
There’s no simple answer to that. I think [Bristol-Myers Squibb] gets $130,000 for four doses of ipilimumab. They deserve to make their money back, but that cost has no relationship whatsoever to what it costs to make the drug. Something’s gotta happen. I think the sad truth is that almost any cancer drug, even ones that don’t work very well, are expensive. That’s just somehow hammered into the system.
How did your history with cancer influence your path?
When I was about 10, my mom had lymphoma. I was holding her hand when she died. Two of her brothers died of cancer. So it’s not that it made me say, “I’m gonna go cure cancer,” but I always had that in the back of my head. I had a gut feeling that T cells were going to be a way to treat cancer, but I also knew that unless you know extremely deeply how they work, it’s not going to go anywhere.
Then my brother died about 12 years ago of metastatic prostate cancer; I was also with him when he died. Right after he passed away, I was diagnosed with prostate cancer. It was caught early, so successfully treated. Then, a couple years ago, I had a melanoma removed from my nose. I’m currently getting another round of treatment for localized bladder cancer. So I’m on my third cancer, and hopefully I don’t get a fourth. Luckily, these were all caught very early, so the treatment is just surgery. Except for this one, which is surgery followed by, ironically enough, the crudest immunotherapy that could possibly be.
One of the reasons I guess I’m still here is that I was at a major cancer center. I probably wouldn’t be here if I wasn’t doing this.
Some scientists are hesitant to talk about “curing” cancer. What’s your view?
I’ve faced that a couple times. But we’ve got this data now: 5,000 patients, and one in five of them are alive 10 years after a single treatment, and show no sign of getting it again. Is that a cure? Technically, no.
But I know a patient that got tired of just worrying about it all the time, being told she had a chronic disease that was manageable. Doctors told her, “Don’t have babies.” Finally she just said, “To hell with this, I’m cured, I’m not going to let this thing dominate my life.” So she went ahead and had babies and got on with it. People still need to get checked out, but you’ve gotta give them some hope. I know enough about cancer, and it’s really scary. But now it’s not a death sentence at all.
This interview has been edited for length and clarity.