When Michael Bevan was growing up in a small coal-mining town in South Wales he wanted to be a doctor so he could “cure diseases, like cancer.” Ultimately, Bevan chose research rather than medicine as a career.
Although Bevan hasn't cured cancer, as was his youthful ambition, his research has shed light on how T cells—key players in the immune response—fight cancerous cells and infection. Recently, his findings have allowed other clinical scientists to develop cancer vaccines that boost a patient's immune response to fight tumors.
As a young man, watching birds and observing other animals and the plant life in the countryside where he grew up gave him an appreciation of biology. Reading Scientific American articles opened him to the possibility that he might someday be able to do research, rather than become a doctor. With his good grades, Bevan became the first person in his family to attend a university.
Fellow zoology students at University College in London and the school's scholarly environment had a big impact on him. “The students were the smartest people I had ever met,” Bevan recalls. “We spent lots of time pub crawling in London. These discussions with guys from different parts of the United Kingdom were all new to me and very exciting. I had never met anyone outside of my South Wales village.”
As part of the intellectual ferment, he became fascinated by antibodies—why are they able to recognize so many different kinds of offending molecules when they fight infection?
So for his Ph.D., at the National Institute for Medical Research in North London, he studied how B cells, a type of immune cell, assemble the two chains of the antibody molecule. “It was my first exposure to actually doing research,” he says. Soon, he learned about experiments two floors below him that would change his life. “They were researching how B cells and T cells cooperate to generate immunity,” Bevan says. “After that, my interest was in how T cells interact with other cells and how that fosters immunity.”
Since all the “brash and successful scientists in England” he knew had gone to the United States for postdoctoral training, Bevan decided he would also go to the then newly built Salk Institute in California for a postdoctoral fellowship. While there, Bevan made several fundamental discoveries about T cells. His findings helped to explain how a type of T cell, called cytotoxic T cell or killer T cell, can distinguish between self-molecules in the body that it should leave alone and the unhealthy foreign molecules it should destroy.
Bevan's research provided insight about how killer T cells recognize molecules called antigens, on the surfaces of cells. His work also revealed that tumor and foreign antigens need to be processed, or primed, by other immune cells, called dendritic cells, before being presented to killer T cells. After the two cells communicate, killer T cells are activated: they divide rapidly and find and destroy infected and cancerous cells.
His most significant finding, however, was showing how T cells mature in the thymus (which is why they are called T cells). In the thymus, immature T cells are exposed to self-molecules on the surface of the thymus cells. Bevan found that only those T cells that recognize self-antigens with a weak affinity are allowed to mature and leave the thymus, in what is called “positive selection.” “These T cells don't kill normal healthy tissue, and are able to respond to a foreign antigen or a tumor very rapidly when they are in the body," Bevan explains.
If the T cells that left the thymus had a strong attraction for self-antigens, they would wind up killing the normal cells in the body. To prevent such autoimmunity, T cells that strongly recognize self-molecules are killed before exiting the thymus, in what other scientists characterized as “negative selection.”
Bevan continues to study how dendritic and other antigen-presenting cells process antigen to present to killer T cells. He also studies killer T cell memory. This is the persistence of a small population of T cells that survive after an immune response that allows the body to respond robustly to a subsequent challenge with the antigen.
Bevan returns to South Wales routinely to visit family and friends and is grateful for his life's trajectory. “There was nothing romantic about the coal mines,” he says. He attributes his success as a researcher to working extremely hard, having good students in his laboratory, luck, and “good taste.” “When I see something new, it smells `good' and I think I am pretty good at picking up on that,” he says. “I also know to stay away from things that `smell' bad.”
