Bruce D. Walker, M.D.
Bruce Walker, M.D., is an HHMI investigator at Harvard Medical School and director of the Partners AIDS Research Center at Massachusetts General Hospital in Boston.
Guided by Patients
By Karen Hopkin
Bruce Walker was interested in science from the start. Both his parents were academics—his mother had a bachelor’s degree in psychology and his father was a geology professor. In fact, Boulder, Colorado—where Walker grew up—is such a scholarly town, he says, “I thought it was standard that everybody had one or two parents with Ph.D.’s.”
But even though Walker accompanied his father on field trips to collect samples during his grade-school years, he says, “I never imagined that I was going to be doing research as a career.” Quite the contrary. As an undergraduate at the University of Colorado in Boulder, Walker says, “I became convinced I would never do research.”
He was working on a senior research project that would allow him to graduate with honors in chemistry. “It was some sort of chromatography, analyzing different compounds. I really don’t remember much more than that,” Walker says. “I just remember feeling like I didn’t really connect with the project. It seemed extremely esoteric to me, and I realized that there were probably two people in the world who cared about the outcome of the experiments I was doing. Unfortunately, I was not one of them.”
So Walker went to medical school at Case Western Reserve University in Cleveland, intent on becoming a physician. “I was convinced I wanted to be a family doctor and work in an academically connected clinic, seeing patients and teaching patient care to medical students,” he says. And Walker continued to shy away from research, even after he arrived at Massachusetts General Hospital for his internship and residency.
Then Walker saw his first AIDS patient. It was the spring of 1981, and the disease now known as AIDS had not yet been described. The patient was a young man in his 20s who had been transferred to Massachusetts General from a hospital that cared for patients with TB. “It was clear that he was terribly ill,” says Walker. “He had a constellation of diseases that none of us had ever seen occur simultaneously,” including tuberculous meningitis, Kaposi’s sarcoma, and pneumocystis pneumonia. “It was unsettling to turn to the senior physicians for help and have them say they’d never seen anything like it before,” says Walker. “It became doubly worrisome when those of us who were working at different hospitals in Boston talked to each other and learned we were all seeing similar cases—young people coming in with an apparent complete collapse of their immune systems, and we could not save them.”
That June, the first report of what would later be dubbed acquired immune deficiency syndrome—AIDS—was put out by the Centers for Disease Control. “That was when attention started to be drawn to the fact that this was an entirely new and highly lethal syndrome. Young, previously healthy people were showing up in emergency rooms desperately ill, and the reason was not at all clear.”
It became more clear in 1984, when Robert Gallo and Luc Montagnier determined that HIV was the cause of AIDS. Gallo described the discovery at Massachusetts General just as his landmark paper in the journal Science was published. “It was just so unbelievably exciting to hear how medical research had taken us from a completely perplexing new syndrome to the identification of a new virus, the development of a diagnostic test that allowed us to determine the extent of disease, and even to the hope that we could someday discover new treatments,” says Walker. “That’s when I decided I had to try to link clinical medicine to research as a career path.”
Moving back and forth from bedside to bench, Walker began to study why the immune system caves in to HIV and how the virus gets the upper hand. His early experiments, he says, “were quite eye-opening.” Walker and his colleagues took blood from AIDS patients and set out to measure the ability of circulating white blood cells to attack virus-infected cells. “People in the field at the time would have said that you just can’t do that,” says Walker. Because AIDS is a disease that cripples the immune system, he says, “the thought that you would find responses so robust that you could detect them in fresh blood seemed preposterous.”
Preposterous as it appeared, that’s exactly what happened. “We found an astonishing level of immune cell activity—to the point that many people just didn’t believe the data,” says Walker. Indeed, he and his colleagues didn’t quite believe them either. “We were concerned that the results were some kind of artifact or screwup in the assay,” he says. “But when the studies were repeated, we obtained the same results.” The results, showing a robust cellular immune response to HIV in infected persons, were published in 1987. Since then, Walker has continued to try to better understand those initial observations. He has recently found that although killer cells from patients can recognize and attack infected cells in a test tube, the virus has ways to prevent them from doing so in the body.
With those first research results, Walker was hooked. “The process of creating knowledge that had never before existed was thrilling and opened up new questions that seemed extremely relevant to patient care,” he says. “This was at a time when essentially all AIDS patients died. As providers all we could do was hold a patient’s hand and tell him, ‘We’re really sorry, but there’s nothing else we can do.’ So it was really exhilarating to think that we were starting down a path that might have relevance for developing vaccines and treatments that could make a difference.”
For the past two decades, Walker has continued down that path, exploring, among other things, why some people with HIV get sick and others seem to be able to hold the virus in check. He has discovered that treating patients at the very earliest stages of infection can help them keep the virus under control, at least transiently, although the virus usually goes on to get the upper hand. And he has also expanded his reach overseas, securing the funding to construct what he describes as a “spectacular state-of-the-art research facility right in the middle of the worst part of the AIDS epidemic in South Africa” and helping get antiretroviral therapy to the people there who need it.
“On the one hand, the magnitude of the problem there is just absolutely enormous,” says Walker. “And yet, it’s very gratifying to get involved and see the progress we’re making. We’ve definitely made a difference in individual people’s lives.”
All in all, grins Walker, “a very far cry from the chromatography experiments I’d been doing as chemistry major.”
© 2013 Howard Hughes Medical Institute. A philanthropy serving society through biomedical research and science education.