Peter C. Doherty Biography (1940-)

immunologist, virologist

Peter C. Doherty was born to a piano teacher and a government employee in Brisbane, Australia, on October 15, 1940. A fine student, he earned his bachelor's degree from the University of Queens a year early. He went on to pursue aveterinary (agricultural) career, obtaining his B.V.Sc. from Queensland in 1962, and an M.V.Sc. in 1966.

Later, though, Doherty's career took an unexpected turn. By reading the booksof Sir Frank Macfarlane Burnet, a countryman who had won the 1960 Nobel in medicine for his work on immune tolerance, Doherty became interested the immune system. Doherty went to the University of Edinburgh, Scotland, earning a Ph.D. there in 1970 for his studies of viral infection of sheep brains. In 1972he returned to Australia as a research fellow at the John Curtin School of Medical Research, Australian National University, Canberra--setting the stagefor his seminal discovery.

At the Curtin school, space was at a premium. Doherty had his own laboratoryfor a project studying killer T cells--white blood cells that destroy virus-infected cells in the body by recognizing viral proteins on the cells' surfaces. In the nearby laboratory of Robert Blanden, which was working on a similarproject, space was so short that they needed to export a worker. That worker, Rolf Zinkernagel, moved into Doherty's lab; together the two began studying how killer T cells know which cells to attack.

At the time, immunologists were very interested in a group of genes collectively called the major histocompatibility complex, or MHC. These genes, clustered together in the DNA sequence, encode a series of proteins called the MHC antigens, which determine whether a transplanted organ will be accepted or rejected by a recipient. If the MHC genes of the donor and the recipient match,the organ survives; if they do not, the organ is attacked by the recipient'simmune system and dies.

A number of researchers had guessed that the rejection of MHC-mismatched organs was essentially the same process as the killing of virus-infected cells bykiller T cells. Doherty and Zinkernagel demonstrated that this was true, andthat the MHC antigens were necessary for killer T cells to tell friend fromfoe. When they investigated further, they found something unexpected. Most immunologists had expected that when virus-infected cells and killer cells werepoorly MHC matched, the immune cells' killing response would be strongest, much as in badly matched transplants. But the opposite was true. In order to get proper T-cell killing of the virus-infected cells, Doherty and Zinkernageldiscovered, the cells' MHC regions had to match.

The two had discovered that T cells--indeed, the immune response in general--can only recognize viral proteins when they are displayed in the context of properly matched MHC antigens. The immune system, which had evolved to recognize "self" from "other" did not react most strongly to "other," but to a thirdstate, "altered self." This discovery finally put transplant rejection intobiological context: the body does not purposely reject mismatched organs because they are different, it rejects them because it mistakenly identifies themismatched MHC antigens as "self" antigens that have been altered by interaction with viral proteins. The finding also opened the way to better methods for heading off transplant rejection, for creating vaccines, and for further unraveling the workings of immunity; vulnerability to certain infections; and autoimmune disease, where the body mistakenly attacks its own tissues.

While immunologists recognized that Doherty's and Zinkernagel's 1973-1974 discovery was important, its true significance took time to sink in. The successful collaborators went their separate ways, with Doherty heading for the Wistar Institute in Philadelphia, as an associate professor in 1975. He returnedto the Curtin school in 1982 as professor and head of the Department of Experimental Pathology, leaving once again in 1988 to be chairman of the Department of Immunology at St. Jude Children's Research Hospital, Memphis, Tennessee.At St. Jude's, in addition to heading the hospital's immunology research program, he has maintained his own laboratory work on viruses that cause canceras well as the Epstein-Barr virus, which causes severe infections in the compromized immune systems of AIDS patients.

Along the way, international recognition of Doherty's work grew. In 1983 he was given the Paul Ehrlich Prize in Germany; in 1986, he gained the International Award of the Gairdner Foundation of Canada; and in 1995 he received the Albert Lasker Medical Research Award, often a prelude to a Nobel. Finally, in1996, for his collaborative work with Zinkernagel, the two were awarded the 1996 Nobel Prize in Physiology or Medicine.

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