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PETER C. DOHERTY-Immunology-15 October 1940
The immunologist Peter C. Doherty was born in the Australian state of Queensland and raised there in Ox- ley, a working-class suburb of Brisbane. A dislike of his childhood surroundings led the young Doherty to concentrate on the one sure way of escaping from Oxley- getting an education. He chose to attend the Universi- ty of Queensland, where, despite his admission in the Weekend Independent that his “best subjects were literature and writing,” he pursued a career in veterinary science. He received his bachelor’s degree in 1962 and his master’s degree in 1966. Doherty then travelled to the United Kingdom, where, in 1970, he received his Ph.D. in animal pathology from the University of Edinburgh.
By 1971 Doherty had completed a term as a veterinary officer at Brisbane’s Animal Research Institute (1963-1967) and worked as scientific officer at Edin- burgh’s Moredun Research Institute’s department of experimental pathology (1967-1971). In 1972 he received a research fellowship in the microbiology department of the John Curtin School of Medical Research, part of the Australian National University, in Canberra. At the Curtin School Doherty, along with fellow researcher ROLF M. ZINKERNAGEL, probed the inner workings of the human immune system and made a discovery that would one day provide new insight into immune response against a variety of diseases, including cancer and HIV, the virus that causes AIDS.
Prior to the work of Doherty and Zinkernagel, relatively little was known about the signalling and recognition mechanisms of the cellular immune system. It was understood that T lymphocytes, or T cells, were the part of the cellular immune system responsible for recognizing cells infected with various viruses and destroying them. Plaguing immunologists was the question of exactly how these T cells were able to detect and attack only infected cells while leaving healthy cells completely untouched. “There were a number of different people who had been snuffling around this problem, but they couldn’t reach a conclusion,” Philip- pa Marrack, an immunologist at the National Jewish Center for Immunology and Respiratory Medicine, told the New York Times. She further explained that many of these previous attempts had been hindered by extremely complicated experimentation systems that yielded information that was nearly impossible to interpret.
Doherty and Zinkernagel, who collaborated not out of a strong desire to work with one another, but rather because of a shortage of space at the John Curtin School of Medical Research, decided to conduct experiments on the immune system reactions of mice ex- posed to the virus that can cause meningitis. After injecting mice with the virus, the pair mixed samples of both the virus-infected cells and T cells from the mice in a test-tube. The results led to a very surprising discovery: the T cells would recognize and kill the infected cells only if they were from the same strain of mice. Infected cells from different strains of mice would simply be ignored. Doherty and Zinkernagel deduced that the T cells would attack an infected cell only after it recognized two key factors: a set of certain molecules known as the major histocompatibility anti- gens that indicate that the cell is, indeed, part of the self, and not foreign matter; and a fragment of the virus itself, indicating that the cell is infected.
This discovery immediately solved a mystery that had puzzled immunologists for years. The major histocompatibility antigens, which had actually been dis- covered by scientists studying transplantation biology, differ in each individual and quickly label transplant- ed organs as foreign, thus provoking the immune system to attack and reject them. But why, since transplants do not occur in nature, did these major histocompatibility antigens exist? The hypothesis presented by Doherty and Zinkernagel provided a much- needed answer to this question. The major histocompatibility antigens exist because they are an integral part of the body’s two-step process in recognizing infected cells. Suddenly, from the pair of scientists whom Dr. Ronald Schwartz, chief of the Laboratory of cellular and molecular immunology at National Institute of Allergy and Infectious Dis- eases, described in an interview with the New York Times as having appeared “out of left field,” came an answer to one of immunology’s fundamental questions. “Then they took over leadership in the field,” Schwartz added.
The implications of the pair’s discovery are extremely broad. Already, their work has been vital in helping to avoid rejection in organ transplants. Further, Doherty and Zinkernagel have provided a strong foundation upon which scientists may be able to expand the knowledge and, one day, treat such diseases as rheumatoid arthritis and non-insulin-dependent diabetes, illnesses in which the body loses the ability to differentiate between self and nonself and the immune system attacks the body’s own tissues. As T cells are one of the body’s foremost defences against HIV, there is much hope that the work of Doherty and Zinkernagel may lead to better treatments for AIDS. Additionally, their work is being applied to the development of new vaccines for a variety of illnesses. “Already it has led to successful vaccines for animals, and if one has such a vaccine for animals, then it must not be far away be- fore you can do the same with humans,” said Sten Gril- Iner, chairman of the Nobel medicine committee.
After the conclusion of the pair’s work at the John Curtin School of Medical Research, Doherty, the man who had once harbored aspirations of becoming a “country vet,” now found that he was one of the world’s premier immunologists. “It’s not really what I expected to do with my life, but that’s just the way turns out,” he said in a 1996 interview with Reuters.
In 1975 he left Australia to become an associate professor and later a professor at Philadelphia’s Wistar Institute, where he remained until 1982. He then returned to Australia to head the experimental pathology department in the very place where he had con- ducted his research with Zinkernagel, the John Curtin School of Medical Research. In 1988 Doherty accepted a position as chairman of the Department of Immunology at St. Jude Children’s Research Hospital in Mem- phis, Tennessee. Four years later he became an adjunct professor in both the pathology and paediatrics departments of the University of Tennessee’s College of Medicine.
In 1996, more than 20 years after shedding new light on the responses of the body’s immune system, Peter C. Doherty was awarded the Nobel Prize. He shared his award, along with the $1.12 million prize, with the codiscoverer of the body’s two-pronged recognition of infected cells, Rolf Zinkernagel. The academy praised the pair for work that has “fundamentally changed our understanding of the development and normal function of the immune system.” Fellow immunologists were very pleased with the announcement. “Most of us in the field felt this was an award that was coming, and it was only a question of when they would get it,” said Dr. Philip Greenberg, an immunologist and cancer specialist at the University of Washington School of Medicine. “It’s all very exciting and gratifying,” Doherty said upon receiving the news of his award. “It’s very satisfying to have had some responsibility for triggering an enormous area of research.”
Doherty has been the recipient of numerous other awards, including the Paul Ehrlich Prize (1983), the Gairdner Foundation International Award (1986), and the Albert Lasker Medical Research Award (1995). Also, Doherty has been a fellow of the Australian Academy of Science (1983) and the Royal Society of London (1987).
SELECTED WORKS: Restriction of In Vitro T Cell- Mediated Cytotoxicity in Lymphocytic Choriomeningitis Within a Syngenic and Semi allogeneic System (with R. M. Zinkernagel), Nature 248, 1974; Im- munological Surveillance Against Altered Self Components by Sensitized T Lymphocytes in Lymphocytic Choriomeningitis (with R. M. Zinkernagel), Nature 251, 1974; A Biological Role for the Major Histocompatibility Antigens (with R. M. Zinkernagel), Lancet, 1975; MHC Restricted Cytotoxic T Cells: Studies on the Biological Role of Polymorphic Major Transplantation Antigens Determining T Cell Restriction Specificity (with R. M. Zinkernagel), Advances in Immunology, 1979.
