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Vivid portraits of patients, scientists, and physicians reveal the promise of immunotherapy

The Breakthrough: Immunotherapy and the Race to Cure Cancer

Charles Graeber
Twelve
2018
320 pp.
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Every cancer is a living, ever evolving, mutated derivation of a body’s own cells. This makes fighting a cancer like fighting the mythological many-headed hydra. Cut off one head, and two may grow in its place.

In The Breakthrough, journalist Charles Graeber tells the story of how we may finally slay the beast. The “breakthrough” referenced in the title is not a single drug or treatment but a series of revelations regarding how the body’s immune system regulates itself and how cancer can hijack it to avoid our defenses. This, Graeber argues, is cancer’s “penicillin moment,” opening the door to a radically new therapeutic approach.

Graeber is remarkably skilled at explaining complex immunological phenomena and captures the convoluted dynamics of scientific discovery. He centers each part of the narrative on a character or two, whom he brings to vivid and sympathetic life, highlighting not just their work or their disease but also their humanity, their personality, and the emotional challenges they face.

Nowhere are these strands woven together as powerfully as in the first chapter. To illustrate the game-changing nature of cancer immunotherapy, Graeber introduces “Patient 101006 JDS,” a finance guy turned music industry executive named Jeff Schwartz. Diagnosed with stage 4 kidney cancer in February 2014 and fading fast, on 20 December, Schwartz secured the last spot in a clinical trial of a new immunotherapy candidate.

The physician overseeing the trial, Dan Chen, recalls wrestling with the decision of whether to admit Schwartz—whose advanced disease and poor performance status made him a less-than-ideal candidate—into a trial that could launch or doom the nascent hopes of cancer immunotherapy. “My initial reaction upon seeing him …was, ‘Are you kidding me?’” However, Schwartz was ultimately admitted to the study and responded beautifully to the treatment. “Right away, I just came back to life,” Schwartz would tell Graeber.

Later, Graeber steps back to examine the historical origins of the concept that the immune system could be unleashed to combat cancer. This story is centered on a series of finely drawn characters, including Elizabeth “Bessie” Dashiell, a childhood companion of John D. Rockefeller Jr., whose untimely death would inspire her surgeon, William Coley, portrayed by Graeber as a cross between Indiana Jones and Sherlock Holmes, to chase down every lead—from scientific clues in the laboratory to sociological data in the tenements of Manhattan’s lower east side—ultimately earning him the moniker the “Father of Immunotherapy.” Far from a dry accounting of historical events, look for the themes of chance observation, persistence, and fantastical luck that find resonance throughout the rest of the story.

Graeber intersperses portraits of the scientists seeking to uncover the immune system’s inner workings throughout the book, alongside accessible explanations of their discoveries. Along the way, we meet many luminaries of the field, including a certain recent Nobel recipient who is colorfully introduced as “a hard living harmonica-playing Texan who … looks like something between Jerry Garcia and Ben Franklin.”

Graeber also crafts beautifully evocative phrases that illuminate the workings of the body and the harsh reality of disease, describing, for example, “tumors leapfrogging each other like kids grabbing a bat handle for dibs.” My favorite analogy was one in which he likened the kidney’s filtering glomeruli to “a demolition worker clearing out asbestos from a condemned building” to explain the particular vulnerability of the kidney to aggressive malignancy.

The book’s final chapter takes readers back to the characters we met at the start of the book but adds little to the scientific or clinical story. I recommend saving chapter 6 to read as your final chapter. It too revisits some of the story’s early characters while offering a frank discussion of the limitations of immunotherapy, the latter of which is much needed in the current era of scientific and medical hype.

Readers who come to this book with some knowledge of the immune system’s workings will find a very satisfying read, with entertaining and largely accurate overviews of the workings of the immune system, an exciting fly-over of the scientific journey that’s brought us to our current understanding, and important reminders of the humanity of every player in this saga. Scientists and clinicians who work in cancer or immune-related disorders may wish to gift this to partners, children, parents, and friends who’ve never quite grasped what it is they work on. But this book really shines as a resource for laypeople who seek a better understanding of the immune system, of cancer, and of the research process.

About the author

The reviewer is a physician and molecular biologist who consults on health systems and data for technology and health care organizations. Chevy Chase, MD 20815, USA.