Witness to a Pandemic: Bruce D. Walker

In 1981, Bruce Walker was a recent medical school graduate and a resident at Massachusetts General Hospital in Boston, eager to start a career seeing patients after years of lab research. “I thought I was in a place where everybody knew everything about every disease,” he says. Then, a 19-year-old man was transferred from a chronic care hospital, where he had been undergoing treatment for tuberculosis. He was losing mental capacity and was having trouble speaking, which Walker and others assumed meant the condition had spread to his brain. “But as we did the further workup, we realized that he had both pneumonia and cancer in his lungs,” Walker remembers. “He had a second cancer in his brain, and he had another viral infection in his colon. He soon died, and the senior doctor said, ‘Well, you’ll probably never see another case like it.’ And a few weeks later, a case exactly like it came into the emergency room.” Walker had been a practicing physician in the earliest days of the AIDS epidemic, before the virus even had a name. But, the virus ultimately defined his career. More than 40 years later, Walker is a world-renowned infectious disease expert and the director of the Ragon Institute, a collaboration between MIT, Harvard Medical School, and Massachusetts General Hospital that’s centered on innovative immunology research. A Patient-Driven Focus In the 1980s, as AIDS and HIV became a worldwide public health emergency and a source of horrible stigma for infected persons, Walker became determined to figure out how the body fights back and uncover why it seemed to consistently lose the battle. His lab specializes in studying a type of white blood cell called cytotoxic T cells, which kill virus-infected cells. “They travel through the body, and if they find a viral peptide on the surface of a cell, then they can recognize and kill it,” Walker says, noting that much of his research has been driven by his encounters with patients. As Walker saw more patients with HIV, he also encountered a bit of a phenomenon. Some of his patients turned out to be what are now called elite controllers: individuals whose immune systems naturally control HIV infection at undetectable levels without antiretroviral therapy. In 1994, he met a man who had been HIV-positive for more than 15 years, yet exhibited no symptoms of the disease. Together, Walker and his team determined that about 1 in 300 people infected with HIV fit this profile. A Breakthrough: Applying Network Theory Walker’s lab had a breakthrough when they looked at the structure of HIV using a sociological concept called network theory – the idea that messages spread through a network of people thanks mostly to a small number of essential message-spreaders called nodes, and without those, the network falls apart. The “nodes” in HIV cells are its amino acids, and Walker says the immune systems of elite controllers essentially target those and prevent the spread. “These patients’ cytotoxic T cells target parts of the virus that are critical to its structure, and this immune pressure causes HIV to mutate to escape the attack,” he explains. “This change can cause the virus’s amino acids to fall apart.” Now, Walker and his lab are working towards developing a vaccine based on this unique immune response: one that can mimic the same attack in people who aren’t elite controllers. Walker became an HHMI Investigator in 2002, when the enormous scientific mobilization to fight AIDS had made a huge impact in the developed world. Infection rates were going down and antiretroviral therapies were changing the nature of AIDS treatment, but these changes were not felt equally around the globe. Walker took advantage of the intellectual freedom allowed by HHMI to travel to South Africa, where he later helped to open the pathbreaking Kwazulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) at the University of KwaZulu-Natal. After seeing the immense accomplishments in the HIV and AIDS field over the last 43 years, Walker says, “There are places in the world where this epidemic is still raging, and I think people don’t fully understand that. A lot of people think that this is a problem that’s been solved and it’s unfortunately still a problem that needs scientific focus and advancement to ultimately conquer.”