The 2018 Nobel Prize in Physiology or Medicine was awarded jointly to James Allison of MD Anderson Cancer Center at the University of Texas at Houston and Tasuku Honjo of Kyoto University for work that “established an entirely new principle of cancer therapy.” Each independently discovered that our immune system is restrained from attacking tumors by molecules that function as “brakes.” Releasing these brakes (or “brake receptors”) allows our body to powerfully combat cancer.
This remarkable advance has been a long time coming. The idea that our natural defenses could be mobilized against tumors extends back more than a century, to the case of a young woman named Elizabeth Dashiell. In 1890 Dashiell, then seventeen years old, consulted a Manhattan surgeon, William Coley, for a painful swollen hand. After several weeks of conservative measures, Coley operated on her hand and found her bones encased by a sarcoma—a cancer of the connective tissue. He sought to cure the cancer by amputating Dashiell’s arm just below her elbow, but tumors soon appeared in her neck and abdomen. Several months later she died at home, with Coley at her bedside.
Dashiell’s death had a profound emotional impact on the young surgeon. He began to comb through the records of New York Hospital, searching for cases of sarcoma with better outcomes. One success stood out from the expected fatalities: Fred Stein, an immigrant housepainter, had undergone multiple operations for a sarcoma that had been rapidly spreading in his neck. His case was labeled “absolutely hopeless” by his surgeon. Then Stein developed a bacterial infection in the region of the tumor. Antibiotics didn’t exist at the time, but his own white blood cells were able to eradicate the bacteria. As they did, the cancer shrank and ultimately disappeared.
This stunning outcome prompted Coley to search for a way to make the body combat tumors, as Stein’s apparently did. The surgeon initially inoculated cancer patients with what he called “laudable pus,” extracts of bacterial abscesses, and then with bacteria themselves. While Coley documented occasional instances of tumors shrinking, he never arrived at a reproducible way to cure cancer by stimulating a patient’s natural defenses.1
Over the ensuing decades, cancer treatment largely consisted of surgery to excise tumors, radiation to burn them, or chemotherapy to poison them. There were moments, though, when it seemed that Coley’s dream would be realized. Researchers studying the immune system discovered the molecules interferon and interleukin-2; each was initially hailed as a promising treatment based on their dramatic effects in shrinking tumors in rodents. But both failed to have robust and broad benefits when used to treat cancer in humans.
Such frustrating setbacks did not deter James Allison, a young scientist from the small town of Alice, Texas. Counseled by mentors to stay away…
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