Jim Allison's easy laugh matches his gravel-worn South Texas accent.


He likes to party, which is unexpected in one of the world’s top research scientists.


A University of Texas alumnus, he also plays a mean harmonica, including at least twice with Willie Nelson, the first time during talent night at a California club called the Stingeree — we’ll get to that story in a bit — and another time onstage at the Austin City Limits Music Festival.


And, oh, yeah, he won a Nobel Prize in 2018.


Along the way, he has saved hundreds of thousands of lives through tumor immunotherapy for some of the deadliest cancers, a treatment that the medical community had for decades practically laughed off the stage.


He also is the thoroughly fascinating subject of a 90-minute documentary, "Jim Allison: Breakthrough," which played South by Southwest in 2019 and airs on PBS’ "Independent Lens" on April 27. After that, it will be available to stream at pbs.org. It is also available from other streaming services.


One learns much about the iconoclastic scientist from the crisply made film written and directed by Bill Haney. Allison added to those insights in a recent laughter-filled phone call.


Advanced biology


Here’s an example: Allison held his own when he challenged the head science teacher as a student at Alice High School. The teacher refused to allow evolution to be taught at that school.


"That was a pretty big one for a small-town school," Allison says, "clashing with a teacher over an issue most people didn’t understand. I caught a lot of crap for that. I was the bad boy of the whole school. I’d walk by and hear: ‘There goes that one.’ The adults back then used paddles with holes in them to whack you whenever they wanted. I got a lot of that. I stood my ground, though, and still took advanced physics from him. He was a fantastic teacher with a blindside."


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Years later, another of his former teachers from Alice was serving in the state legislature when a hearing was held to consider adding creationism to the public school curriculum. She called Allison, who was living in Austin and working at the M.D. Anderson Science Park in Smithville, to testify.


"They’re bringing in three busloads of people to support ‘creation science,’ whatever the hell that is," Allison remembers. "I wasn’t going to argue it point by point. It’s mostly just garbage. They obviously didn’t know what science is. This is junk you can’t use to do things. So not science."


A counselor at what’s now Dubose Intermediate School in Alice, Stan Brooks, had steered Allison, a lonely kid whose father was a physician and whose mother died of lymphoma when he was 11, to a summer science program at UT. When he arrived on campus as a full-time student in the 1960s, he pursued any lab job he could find.


Only one job was left — dishwasher in a lab. Which led to explosive results, as G. Barrie Kitto, director of UT’s Center for Biotechnology, gleefully relates in the film.


"I had forgotten about that explosion," Allison says. "The job paid just a dollar and a quarter an hour, but I’d do anything to be near a lab. I was washing test tubes, and one graduate student insisted on numbering every one with a magic marker, when he could have just marked the first and the last ones in a rack."


So Allison doused the tubes with acetone, a flammable cleaner, and stepped back — as one did in those days — to light a cigarette.


"Yeah, I stupidly blew up the room."


Still, the other research assistants liked the eccentric Allison so much, they begged for him to keep the job. He earned his Ph.D. in biological science in 1973 at UT while working under Kitto.


It was at UT that Allison first heard, during a lecture by immunology professor Bill Mandy, theories about T cells, lymphocytes produced or processed by the thymus that attack intruder cells in the body.


"I was always interested in immunology," Allison says. "I didn’t know much about T cells. But I thought: Hey, these things are cool. Mandy didn’t think they were real. I thought: This is what I am going to work on. T cells go all around the body to protect you."


Many who have become acquainted with Allison’s life story draw the conclusion that the scientist studied immunological treatments for cancer because so many of his close relatives died from the disease.


He has survived three bouts with the cancer himself, the last one with the help of his own discoveries.


"I’ve thought about it a lot," Allison says. "It’s not like I woke up every day wondering how to cure cancer. I woke up every morning wondering how to understand T cells and how their interaction with tumors works."


Allison said that one thing he learned from extensive lab work at UT was perseverance. Another key to his success has been his stubborn distrust of easy answers and of herd mentality when it comes to scientific consensus.


"You’ll read about the results of experiments in a paper, and plenty of people just accept it," Allison says. "There are two kinds of experiments. One where someone says, ‘This is the answer, and I’m going to do the experiment to prove it, and that will agree with my idea.’ … Usually, it’s just sloppy science. The cooler thing is the killer experiment that can only come out one way, no matter your expectations. That’s the most powerful kind."


Enter CTLA-4


After T cells were identified, Allison and other scientists were baffled about why they didn’t always turn on invaders such as cancer tumors, and why they sometimes attacked healthy cells, as happens with autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and lupus.


Allison first singled out the part of the T cell — a receptor — that identifies or misidentifies the nature of the cell to be attacked. If that receptor could be blocked by, say, very specific antibodies, then the T cell could do its miraculous work on a tumor.


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During the 1990s, Allison demonstrated that the antibody blockade of the T-cell inhibitory molecule CTLA-4 could lead to enhanced anti-tumor immune responses and tumor rejection. Once Allison had published the positive results of tests on mice — a key anecdote in the film involves failing to check in on injected mice over the Christmas break and returning to find that their tumors had disappeared — it took at least a decade of Herculean effort, by him and others who backed his science, to get a CTLA-4 treatment through human trials and then to being manufactured by a pharmaceutical company.


Among the roadblocks were pharma companies that could not see the potential profits in this treatment, lawyers who were intimidated by one company’s early patent — "But they got the biology backward!" Allison says — regulators who could not see the point of immunotherapy and, especially annoying, human trials that used timetables set up for chemotherapy, which can work faster, though less completely, than T cell treatments, and with a good deal more harm to the patient.


"I once went to the head of the National Cancer Institute and said: ‘What are you guys doing?’" Allison remembers. "‘What are your goals? I have published this. It’s not going anywhere, because of the preconceived biases of pharmaceutical companies. We’ve done it. It’s all there. It’s all there.’ It was annoying as hell. It pissed me off. For nonscientific reasons, they were not going forward."


Advocates at a small biotech firm — along with one especially persistent guide through labyrinths of regulation — finally got it moving.


"It still took years," Allison says. "But that was record time."



One of the most memorable parts of the documentary follows a patient — a young and healthy mother of two — who was diagnosed with metastatic melanoma. Her specialist at Memorial Sloan Kettering Cancer Center in New York landed her in the human trials for CTLA-4 treatment. She became the first person essentially cured by Allison’s discovery, and they were able to meet.


Also clear from the movie, Allison always worked and played hard. He married his college sweetheart, Malinda Bell, in 1969, and they have one son, Robert Allison, who became an architect. Bell and Allison separated and later divorced. In the movie, Bell talks about their abiding respect and friendship, and also about his obsession with T cells, which left her outside his primary passion. In 2014, Jim married his friend and scientific collaborator Dr. Padmanee Sharma, who shares his professional interests.


"There were many, many more hours of film, and some things were left out," Allison says about the documentary. "Some things are embarrassing, but it’s a pretty accurate portrayal of the personal trials that I went through. In 2018, Bill wrapped the shooting: ‘We’re done!’ Then the next week, they announced the Nobel Prize. Oops."


He was jointly awarded the Nobel Prize in Physiology or Medicine along with Tasuku Honjo for their discovery of cancer therapy by the inhibition of negative immune regulation.


By this time, Allison was mostly associated with the M.D. Anderson Cancer Center in Houston.


"After all the partying and stuff associated with the Nobel Prize, Sharma and I have started our own labs, one more mechanistic, the other more critical," he says. "We are now focusing on immunotherapy combinations.


"You know, when we started, the medium life expectancy for melanoma was seven months. When my uncle got the diagnosis, he said: ‘Well, that’s it. I’m just going to have fun.’ And that was probably not a bad decision at time."


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Now, with one injection, especially if other inhibitors are added to the CTLA-4 treatment, longterm survivability for some of the worst cancers is above 50 percent.


"Why can’t that be 100 percent?" Allison says. "And we are looking at other cancers. Prostate cancer is a personal interest. … We keep asking: Is this combination better? We know what a good response is like. Not all kinds of cancers respond, so what we need to do is look at what we can add."


Immunotherapy, once a joke in the medical profession, is now often the first line of defense against tumors. The usually obstreperous chemo treatments follow if it fails.


The offbeat course


Allison’s idiosyncratic personality shines throughout the documentary.


In 1980s and ’90s, when the researcher was a professor at the University of California, Berkeley — a haven for eccentrics — some there felt Allison had crossed a line. His eccentricity was just too Texan for what many educators consider the top public university in the country.


Back to Willie Nelson: Allison was in Austin when the music scene broke loose in the late 1960s and early ’70s with the 13th Floor Elevators, Stevie Ray Vaughan, Jerry Jeff Walker and, of course, Nelson. He first heard Nelson play from the back of a flatbed truck at a car dealership on South Lamar Boulevard.


"Willie’s songs were part of the soundtrack I grew up with, along with the Beatles," Allison recalls. He was doing postdoctoral work at the Scripps Clinic and Research Foundation in San Diego when he crashed a party and introduced himself to Nelson.


"He was gracious," Allison says. "I told him that I saw him a lot in Austin. He said: ‘I’ve got tomorrow night off, and I’d like to play some music. Do you know of a place?’ I said: ‘Well, there’s talent night at the Stingeree.’"


That nightclub, closed in 2014, was where Allison and other "Texpats" regularly partied and played music. Nelson brought along a couple of his band members and asked whether he could join in. Somebody had the mental wherewithal to take over the rotary pay phone on the wall and to call all their friends to rush down and witness the event.


"I try to have fun. People have told me I have too much fun," Allison admits, before quoting the leader of a seminal country rock band that rose up in the late 1960s and was closely associated with the Armadillo World Headquarters. "As Commander Cody would say: ‘There are a lot of things I haven’t done, but I’ve never had too much fun.’"