Adapted from the book The Breakthrough: Immunotherapy and the Race to Cure Cancer, by Charles Graeber.

Chance favors the prepared mind. —Louis Pasteur

James Allison looks like a cross between Jerry Garcia and Ben Franklin, and he’s a bit of both, an iconoclastic scientist and musician known for good times and great achievements. He also doesn’t always answer his phone, especially when the call arrives at 5 am, from an unfamiliar number.

So when the Nobel Prize committee tried to reach Allison a few weeks ago to inform him he’d been awarded the 2018 Nobel Prize in medicine, Allison ignored the call. Finally, at 5:30 am, Allison’s son dialed in on a familiar number to deliver the news. The calls have not stopped since.

Allison’s breakthrough was the discovery of a sort of secret handshake that cancer uses to evade the immune system, and a means to block that handshake—what the Nobel committee hailed as “a landmark in our fight against cancer,” which has “revolutionized cancer treatment, fundamentally changing the way we view how cancer can be managed.” (Allison’s co-recipient was Tasuku Honjo of Kyoto University.) Advances in cancer typically come in 50-year increments; the science that Allison and Honjo helped advance, cancer immunotherapy, has made a generational leap seemingly overnight.

Adapted from The Breakthrough: Immunotherapy and the Race to Cure Cancer, by Charles Graeber. Buy on Amazon. Twelve Publishing

Until very recently we’ve had three main methods for treating cancer. We’ve had surgery for at least 3,000 years. We added radiation therapy in 1896. Then in 1946, chemical warfare research led to the use of a mustard gas derivative to kill cancer cells. Those poisons were the foundation for chemotherapy.

These “cut, burn, and poison” techniques are currently estimated to be able to cure cancer in about half of the people who develop the disease. And that’s remarkable, a true medical accomplishment. But that leaves the other half of cancer patients. Last year, in the United States alone, that translated to nearly 600,000 people who died of the disease.

The fight was never fair. We’ve been pitting simple drugs against creative, mutating versions of our own cells, trying to kill the bad ones while sparing the good ones, and making ourselves sick in the process. And we’ve been doing that for a very long time.

But now we have added a new and very different approach—one that doesn’t act directly on cancer, but rather acts on the immune system. And that’s the breakthrough.

The immune system has evolved over 500 million years into a personalized and highly effective natural defense against disease. It is a complex biology with a seemingly simple mission: to find and destroy anything that’s not supposed to be in our bodies.

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Hundreds of millions of immune cells circulate throughout the body, searching out and destroying invaders that make us sick and body cells that have become infected, have mutated, or have become defective—cells like cancer.

Which raises the question: Why doesn’t the immune system fight cancer already, the way it fights even the common cold?

For more than 100 years, medical researchers puzzled over that question. Most concluded that the immune system and cancer simply had nothing to say to each other. The argument was that since cancer is a normal body cell gone rogue, it is too much a part of us to ever trigger an immune response. Cancer immunotherapy was condemned as a quaint if simplistic idea based on high hopes and bad science. But despite the mounting mockery of the larger scientific community and dwindling research funds, a handful of immunotherapy researchers continued to believe—and continued searching, decade after decade, for the missing piece of the cancer immunity puzzle, a factor that prevented the immune system from recognizing and attacking cancer cells.

The stakes could not have been higher. If such a missing piece could be found, it would radically reshape our scientific understanding of both ourselves and disease and possibly revolutionize medicine on a scale not seen since the invention of vaccines. It might allow us to finally unleash our immune system, enabling it to recognize and attack cancer the way it does other diseases. It might even pave a new road to the cure. For the tens of millions more diagnosed with cancer each year, the race to find the missing piece of the cancer-immunity puzzle was literally a matter of life and death.