TMC PULSE

t m c » p u l s e | a p r i l 2 0 1 9 8 "Breakthrough" Debuts at South by Southwest Documentary traces decades of immunotherapy research by Nobel laureate James Allison B y C i n d y G e o r g e T he most compelling sequences in the "Breakthrough" documen- tary, which premiered at South by Southwest (SXSW) in Austin, Texas, are the seconds when the face of immunologist James Allison, Ph.D., fills the frame amid superimposed images and film of his loved ones lost to cancer. His mother. His uncles. His brother, Mike Allison, who lost his battle with metastatic prostate can- cer one week before the immunolo- gist's own prostate cancer diagnosis. Allison, 70, was awarded the 2018 Nobel Prize in Physiology or Medicine jointly with Japanese immunologist Tasuku Honjo, M.D., Ph.D., for the discovery of cancer therapies that stimulate the immune system to attack tumor cells. Treatments developed from Allison's work have extended the lives of thousands of people with advanced disease, though certain cancers have responded better to immunotherapy than others. "Breakthrough," directed by Bill Haney, follows Allison's professional and personal journey over several decades. The film's world premiere at SXSW brought Houston innovators to the epicenter of a festival celebrating the ways people push the limits of creativity and progress through film, music and interactive media. This is what a hero looks like The film opens with a shot of down- town Alice, Texas, where Allison was raised by a father he describes as a "country doctor" and his doting mother, who died of lymphoma when he was 11. The soundtrack for that first scene is the scientist playing a melancholy tune on the harmonica. With a pained voice all these decades later, Allison describes how his mother spent a lot of time in bed and how he remembers burns on her neck, which he later learned were the consequence of radiation. Today, Allison is a researcher at The University of Texas MD Anderson Cancer Center who is fight- ing a third personal bout with cancer following a melanoma removal from his nose a few years ago. The film is narrated by Midland-born Woody Harrelson, with music by the legendary Willie Nelson, who hails from a town north of Waco called Abbott, to create a "holy trinity of Texas," Haney said. Subtitled "This is What a Hero Looks Like," the documentary tells a deeply Texan story laced with the Lone Star State's culture, institutions, characters, places and music—namely country and blues. Allison earned his degrees from The University of Texas at Austin and honed his fascination with under- standing how T cells operate in the immune system at an MD Anderson science park in Smithville. The mutual admiration between Willie Nelson and Allison culminates in one of the final scenes of the film as the immunologist stands onstage with the outlaw country artist at Austin City Limits and plays "Roll Me Up and Smoke Me When I Die" on the harmonica. Allison discovered a way to block a protein on T cells that acts as a brake, thus freeing T cells to attack cancer. Specifically, he developed an antibody to block the checkpoint protein CTLA-4. The film's ongoing threads weave through his work hard-play hard drama by revealing Allison's confidence and doggedness. Those traits fueled his determination to unravel the mysteries of T cells and create a new tool to attack cancer, without the consequences associ- ated with chemotherapy, radiation and surgery. The film climaxes with Allison's move from California to New York City to personally keep the research fire stoked. He had champions, such as medical oncologist Rachel Humphrey, M.D., who took the lead in convincing Bristol-Myers Squibb to invest millions into what became ipilimumab, a checkpoint inhibitor Credit: Uncommon Productions It was 15 years-plus of being frustrated. Luckily, there were a lot of people who worked with me and kept the lights on. — JAMES ALLISON, PH.D. Immunologist at MD Anderson Cancer Center Visit breakthrough.movie online for more information about the documentary.

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