New Cancer Treatments Just Won 2 Scientists a Nobel Prize Heres How They Work
It wasn't the Nobel Committee that reached James Allison first on Monday to inform him that he had won the coveted annual prize in Physiology or Medicine. It was his son who broke the news with a 530 am phone call. Minutes later, a Swedish reporter reached him before the committee could. "I was like, Oh my God, it happened,'" Allison says to TIME. "I'm just in shock, I guess.", Allison, chair of immunology at the University of Texas MD Anderson Cancer Center, was awarded the Nobel for his discovery in 1994 in mice that led to an entirely new class of anti-cancer drugs called checkpoint inhibitors. They're designed to unleash the power of the immune system and have saved tens of thousands of livesincluding that of President Jimmy Carter, who was treated with an experimental version of this type of drug when he was diagnosed with advanced melanoma that had spread to his liver and brain. Dr. Tasuku Honjo, professor of immunology and genomic medicine from Kyoto University in Japan, was also awarded a Nobel in the same category for a his discovery of another checkpoint inhibitor pathway. Allison and Honjo both discovered a key feature of the immune system that prevented it from robustly attacking cancer cells. Because cancers arise from normal cells that have accumulated mutations that propel them to divide abnormally, the immune system is loathe to destroy these cells in the same way that it would easily recognize and destroy bacteria or viruses. Allison found one proteinCLTA-4, which is found on a group of immune cells called T cellsthat prevents those T cells from attacking tumors. A few years earlier, Honjo had discovered a protein, PD-1, that also held back T cells from destroying cancer cells, but in a different way than CTLA-4. Those discoveries led to checkpoint inhibitors, the first class of drugs designed to strip away that protective molecular cloak. The U.S. Food and Drug Administration FDA approved the first checkpoint inhibitor in 2011. Allison credits his discovery to an unbiased curiosity about basic science and the luxury of chasing interesting scientific questions without necessarily knowing whether they will lead to something useful for treating disease. "The way I prefer to do science is to pursue basic science, and every now and then you put your feet up and think, how can I use what I've learned?" he says. "The best science doesn't worry about the implications.", Allison, a Texas native, spent much of his spare time as a child in the family garage, tinkering with the science lab he had built there. He didn't know then that cancer would soon consume his life, in more ways than one. The disease would claim his mother, two uncles and a brother, losses that would play a role in shaping his scientific career. As he trained to become a scientist, he grew obsessed with the one of the immune system's foot soldiers the T cell. Allison was among the first to reveal how T cells do their job of recognizing and eliminating bacteria and viruses by using receptors, or proteins, on their surface to bind to foreign intruders. It wasn't long before he turned to the trickier problem of training these T cells to recognize tumors. Unlike bacteria and viruses, cancers develop from the body's own cells, and T cells weren't designed to destroy their own cousins. Figuring out how to make cancer cells look more like bacteria to the immune system became Allison's goal. While other scientists had been looking for characteristics of cancer cells themselves that would make them more visible to the immune system, Allison focused on immune cells. He found that the immune system has a special way of protecting the body's cells from becoming targets. Like a car's automatic braking system that can sense obstacles ahead and engage the brakes, the immune system has a braking system that prevents it from attacking any of the body's own cells  including tumors. The molecule responsible, CTLA-4, was a revelation for immune scientists. Until Allison's work, experts never thought that the immune system had such a system. They assumed that the way the body's cells were spared from immune destruction was by receptors that signaled them as friend and not foe. "I wanted to take a rational approach to figure out how T cells worked," Allison says. "And I thought maybe disabling the brakes was a simple idea. But until I knew there was a brake, there was no way to come up with this.", Honjo discovered an additional checkpoint molecule, PD-1, and others have revealed even more molecular brakes, launching a pharmaceutical bonanza of new anti-cancer targets. So far, the medications are contributing to remarkable remissions in people with lung and skin cancers, but Allison is hopeful they will soon be applied to more stubborn cancers such as breast, prostate and colon. The key to expanding the reach of checkpoint inhibitors, he says, lies in combining them with existing treatments such as chemotherapy and radiation. New studies are already finding ways to use lower, less frequent doses of these standard therapies to awaken the immune system enough in cancers to then make the checkpoint inhibitors more effective. Now, Allison is excited and humbled by what his curiosity has wrought. He keeps in touch with many of the patients who have benefited from the drugs developed from his discovery, but the first one he met stands out a 22-year-old woman who was diagnosed with late-stage melanoma and was given a 50-50 chance of surviving six months. Treated in New York at Memorial Sloan Kettering Cancer Center in 2004, she was among the first to receive a checkpoint inhibitor that Allison had helped develop and was still testing. After four injections of the drug, her cancer disappeared. Allison happened to be in the building when she received the miraculous news, and when her doctor offered to introduce them, she jumped at the chance. It's an experience that remains with Allison today. "It took many years for me not to cry every time I think about her," says Allison. Today she is still cancer-free, thanks to Allison's discovery.