“Breakthrough’s” James Allison is having fun and curing cancer
The Nobel laureate talks about his new documentary and the cancer treatment revolution
September 27, 2019 10:00PM (UTC)
Dr. James Allison doesn’t look the part. The diehard Willie Nelson fan has an unruly head of gray hair and plays harmonica with his blues band. He’s been described in the press as a “carousing Texan.” He’s also a Nobel laureate, a man whose unwavering faith in and curiosity about the human immune system led to one of the most revolutionary developments in cancer research in over a century. Oh, and he saved my life.
Eight years ago, after a diagnosis Stage 4 melanoma, I became one of the first human subjects in a combination clinical trial Allison was heading up at Memorial Sloan Kettering Hospital. The trail would take a unique approach, stimulating my T-cells to recognize and destroy my rapidly running amok tumors. Twelve weeks later, I was cancer free.
There have been plenty more encouraging successes like mine over the past several years, thanks to clinical trials and FDA approvals for innovative, immune system-based approaches to cancer. And Dr. Allison is now the subject of a new documentary from director Bill Haney, narrated by Lone Star State native Woody Harrelson and carrying the appropriately simple name, “Breakthrough.” It’s a deep dive into the fascinating science of immunotherapy, and a portrait of an iconoclast who always believed there was another way to treat cancer beyond the traditional — and unreliable — trifecta of chemo, radiation and surgery.
The last time I saw Jim Allison was a year ago, when he was in New York to receive the Dr. Paul Janssen Award for Biomedical Research. There was a lot of buzz in the room that evening that this award might be a prelude to the Nobel. Sure enough, a few weeks later, Allison did indeed find himself standing on a stage with the king of Sweden. “Breakthrough” captures the electricity of that moment, and then goes back and shows you just how much frustration and heartbreak and failure and hustle and tenacity and collaboration led up to it. I spoke to Allison via phone recently about the new era in cancer, and the long journey from Alice to Stockholm.
Bill emailed me about two years ago. I got an introduction from a mutual friend of ours, the cancer biologist Tyler Jacks from MIT. Bill was searching for something, a unifying topic. He thought about cancer drugs, so Tyler suggested me. We started talking way before anything with the prizes. He came to Houston. He spent a lot of time filming, getting to know me and talking in various locations. Filming had actually ended when the announcement about the Nobel was made. Everything else had been shot, but it made a suitable end to the movie, I guess.
This is an intimate exploration of your life, your family, your losses, your marriages. Did you have any hesitation about doing something like this? You are also a man of medicine. People expect, I think, a certain degree of detachment from people in the medical world. This is very personal. This is very raw and unguarded, you holding a beer and playing with Willie Nelson.
One of the things that Bill wanted us to do, and I actually agree with, was to try to have an accurate portrayal of what scientists and what doing science are like. I’m not going to say my way of doing it or my experience is generalizable to everybody, but the point is, you can do science and have fun. [But] you’ve certainly got to be detached in weighing evidence and weighing data when you’re making a diagnosis for a patient. The same is true when doing research. We do believe there’s such things as facts, and you have to get the facts right. Your views don’t matter. It’s, the data, the data.
And then there’s the human side. This movie is about the passion and the personal drive of not just you, but everyone in this story. You were out there in the trenches when very few people believed in the power of immunotherapy. You had to lobby for financial support and for research support. What does it feel like now? Does it feel maybe it could’ve happened faster if we’d had more people who had more faith?
When we were doing the early work, it was all basic science. Nobody could criticize that. We were trying to understand how T-cells work. When you’d get up to the point of saying, “Well, we’re going to do immunotherapy,” that’s when skepticism started coming out from cancer biologists and oncologists.
In time, I tried to flip it around. Instead of saying, “Hey, we’re looking for a cure for cancer,” I said, “Here. Look at this mechanism we’ve discovered. Look what we can do with it.” That flipped it on its head, both in our approach to doing the science and also the approach of trying to get it to people.
I didn’t want to start off saying, “I’m going to show you how we’re going to cure cancer.” I’d expect people immediately to say, “Oh, yeah, right. Here we go again, some more of this immunology junk.” So, “Okay, let me show you something here. This is a really cool thing about how T-cells are regulated. There’s this little bitty place here where we’ve got a system built in to stop a response. If we can figure out how to let that loose, let the immune system rip, the cancer part will take care of itself. Imagine that.”
Can you explain why is it that immunotherapy only seems to work right now on certain cancers, and why it only seems to work right now on certain people? We’re not yet at the point where this is the magic bullet. It was magic for me, but that’s still unusual.
Let’s step back, since we are not doing anything whatsoever to directly engage the cancer but rather manipulate the immune system. In the real world, cancer is not just cancer. It’s many different diseases. Some, like melanoma, have already attracted the attention of the immune system. They’re robustly infiltrated with immune cells but just can’t get the job done. Melanoma and other kinds of cancers, particularly those caused by carcinogens such as tobacco or ultraviolet radiation, have many, many many mutations in the cells. The fact that some of these cancers have so many mutations is what makes them largely resistant to therapy by more conventional means. The immune system really thrives on diversity and heterogeneity. Some of the cancers that have fewer mutations don’t have so many target antigens probably. That’s one reason that they don’t respond quite as well.
Prostate cancer, for example, although we’re getting responses for prostate now. It’s early days. In other tumors like glioblastoma and pancreatic cancer, which are notoriously difficult, there are a lot of individual aspects that would make them difficult targets. They’ve got their own defense mechanisms which help protect them. This is a harder nut to crack, but we’re studying it. Where we’re at now, it’s not just melanoma on the approvals, by the way. It’s melanoma, non-small-cell, small cell lung cancer, kidney cancer, bladder cancer, Hodgkins lymphoma, head and neck cancer, Merkel cell carcinoma. The list goes on and on.
A few years ago, the kind of diagnoses that people like me had, it was just a death sentence. I certainly as a patient didn’t understand immunotherapy, because the common parlance of cancer previously was, “Everybody does chemo, everybody does radiation.” Do you think that that is changing? Do you think that patients are becoming more sophisticated?
I think they are, and also I think we are becoming more sophisticated. Oncologists for example. They’ll call us to get biopsies of tumors and start dissecting them, in terms of how cellular and molecular things are going on and how they change when they hit it with immunotherapy. We are beginning to learn how to go from a 30% to 40% response, like we’re seeing in kidney cancer now. We are learning carefully how to start building on that to get it up. Maybe we can get melanoma close to 100%, Maybe we can get some of the other cancers up higher by studying what’s going on. In the movie, the question was “Will this work?” Now the question is how do we get in to work in more kinds of cancer at higher frequencies.
What we’re doing now is sort of a reverse translation approach. Before, we’d look at what happened to the mouse in the laboratory and then take it to the people. Now we’re looking and seeing what’s going on to the people. We’re going back to the bench with human tissues and seeing what changes, and maybe we can model that in some cases in the animals to see, “Does this work in this situation?” We’re constantly in process from the lab to the clinic, from the clinic back to the lab and to the lab back to the clinic again. We’re trying to accelerate that cycle as fast as we can. It is disappointing that we’re not at 100% for the more kinds of cancer, even 50%. We can be, I think.
There’s something that I learned from [pioneering immunotherapy researcher] Lloyd Old. He always said, “You should learn something from every patient.” So that’s what we’re at now. It’s not just treating patients, looking for clinical signal or not, and moving on. It’s rather, “What happened? What are the molecules that changed? What are the cells that changed? Which ones are good? Which ones are bad? How do we stay on top of this?” It’s an exciting time, and I’m really optimistic about these combinations to improve things.
Saved my life. Saved my life when the outlook was not good. It was very moving to me near the end of the film when you were reading that letter from a woman whose husband was treated. You still take this very personally. I saw it when you were at the Janssen Awards, you were teary and moved. This is still a person to person experience for you.
Absolutely. I’ve gotten to know [early clinical trial success story] Sharon Belvin very well. Just saying, “Wow, here she is, many years later with a family and everything, after she had nothing to look forward to,” that’s what it’s all about.
This is a movie that shows a lot of disappointment and a lot of failure. The story of of medicine is often, “We have these expensive drugs and these protocols and the pharmaceutical industry, they’re the big bads.” What is rarely understood is the amount of failure and the amount of time that goes into a scientific breakthrough like this one. Was that a priority for you in telling the story?
It usually is. What I try to say is, “You can’t just walk in and prove something. How science works is you try to disprove something and if you can’t, maybe it’s right.” You are wrong most of the time and you have to get used to that, but you learn from the mistakes.
The movie does a great job of capturing some of the major frustrating moments along the way. There were many side routes we started to take, and they didn’t work out so we pulled back, regrouped, started again. That’s just the way it works. If you’re really doing cutting edge stuff, you don’t know what the right answers are when you ask the question. Otherwise it’d be easy to show. So you just have to persist. People say, “When did you start this work?” I think the first paper that I published which relevant to this was in 1982.
What is the end goal? When will you rest, Jim Allison?
I don’t know. Right now the goal is to keep building on what we’ve got try to bring it to more people. I guess I’ll rest when I don’t have enough energy to do it, or the brains to keep making contributions.