Cancer Scientist Blues

~ Jim Allison: Breakthrough ~

The backlash against scientific evidence and skepticism about data-driven consensus has reached alarming proportions, the most obvious instances being the anti-vaccination movement and the refusal to accept climate change.

Into this atmosphere comes a wonderful documentary called Breakthrough, focusing on an equally wonderful real-life scientist called Jim Allison.

Allison looks unusually grim in this poster, but the film shows him as an amiable man, and a strongly independent thinker.

Allison is certainly not one of your East or West Coast elites. He grew up in a small town in Texas (where he argued against creationism taught in schools) and studied at the University of Texas in Austin. He plays blues harp in a country music band and got to jam with Willie Nelson in a small dive in the 1980s. He is also an extremely accomplished scientist, having won a fleet of awards topped by the 2018 Nobel Prize in Medicine.

Allison’s interest in cancer was sparked, says the film, by his family history. His mother died young of lymphoma, and his brother battled prostate cancer for years. As a researcher in Texas, he investigated how the T cell — a central part of the immune system — identified ‘foreign’ proteins to attack, and eventually published a breakthrough paper identifying the mechanism.

Allison in the 1990s

This ‘hot’ paper led to an offer of a professorship at Berkeley. At the time, he was reluctant. He and his wife were Texans born and bred, and he had a job he liked without academic pressure, so that he could do his own research in peace. But a colleague told him:

Twenty years from now you’ll be sitting in that same chair thinking ‘I coulda been a contender’.

Allison was convinced. Over the next few years in Berkeley in the 1990s, his lab identified a protein that inhibited the T-cell action. The next step was to block this protein, called CTLA-4, and see if that allowed the T-cells to attack tumor cells.

The documentary does a great job of showing the nuts and bolts of biomedical research. It follows Allison and introduces us to his wife and labmates. We get to see the student and postdocs as well, the ones who are spending days and nights in the lab to elucidate these immune system mechanisms. We feel the dejection of the grad student who spent three years trying to produce an anti-CTLA4 molecule without success. (He was eventually successful). We also feel the thrill of the post-Christmas moment when Allison found that mice with tumors treated with the student’s molecule survived, while the control mice had died. And we see both the competitiveness and collegiality of science: ambitious scientists who are working on alternate hypotheses, projects that get ‘scooped’ by another lab, but also scientists who cheerfully admit that they had been wrong.

There are surprisingly few good films about biomedical scientists. Medical movies often tend towards determined parents finding cures despite the entire medical and scientific establishment (like Lorenzo’s Oil, Extraordinary Measures). Doctors and scientists are often shown as callous or remote ivory-tower individuals (as in Dallas Buyers Club, And the Band Played On). I’m not saying that these films (based on real-life stories) are ‘wrong’; just that the majority of scientists are engaged, hardworking, focused people who don’t usually make it into movies.

Allison in 2018

The film does an excellent job of making the complex biomedical projects accessible, with cool understandable CGI visuals of molecules and pathways interspersed with actual humans describing the science. Regardless of their scientific background, most viewers will be able to follow the plot.

The human face of cancer is not ignored. Along with the scientists and Allison’s family, the film periodically catches up with Sharon Belvin, a young Texan who was diagnosed with stage 4 melanoma in 2004, when just 22 years old. Available treatments failed. She was able to join in the clinical trial of the immunotherapy drug developed from Allison’s research, ipilumibab, and has been cancer-free ever since.

Allison (second from right) playing with the Checkpoints, a band of doctors and scientists who live all over the country and rarely get to practice together

Set over 50 years, the documentary also exhibits the changing face of American science. The early biomedical students in Texas are largely male and white. More women start appearing over the years, and by the end, there are female scientists who played a critical part in getting Allison’s discoveries into a production drug. Among them is Rachel Humphrey at Bristol Myers Squibb, a passionate scientist who convinced the company to invest in the drug. Later in the film appears Padmanee Sharma, an Indo-Guyanese research oncologist who worked with Allison on immunotherapy projects; they eventually married.

Why is it so difficult and time-consuming to take a brilliant scientific discovery and translate it into a treatment that can benefit patients? The film does a good job of explaining the reasons: years of testing in vitro, in vivo, in mice; layers of clinical trials before FDA approval; small-scale trials on a few terminal patients before larger-scale trials; refinement of the drug and its delivery mechanism for patients; many failures at many stages; and last but not least, incentive for a pharmaceutical company to invest its resources in this particular drug.

For all that he is a determined, driven person, Allison is a relatable, empathetic character, and his cause is so obviously beneficial to humanity that every viewer will be rooting for him all the way to the Nobel Prize and beyond.

Highly recommended.

Breakthrough’ Trailer

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