Download Nobel Laureates of AAI

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Nobel Laureates of AAI
Peter Charles Doherty, Ph.D.
Peter C. Doherty, Ph.D., AAI ’76, St. Jude
Children’s Research Hospital and the University of Melbourne, was awarded the 1996 Nobel
Prize in Physiology or Medicine jointly with
Rolf M. Zinkernagel (AAI ’76) for their work
in explaining how the immune system recognizes cells infected by viruses. Their research
is lauded for having laid a foundation for an
understanding of the mechanisms that the
immune system uses to recognize foreign microorganisms and “self.” Their work elucidated
distinctions between antibody-mediated and
cell-mediated immunity and has had profound
implications for organ transplantation, vaccine
development, and the treatment of both infectious and autoimmune diseases.1
Scientific Accomplishments
In a series of experiments in mice infected with
viruses, Doherty and Zinkernagel found that,
while cytotoxic T cells from one mouse strain
targeted and destroyed virus-infected cells in
the same mouse strain, the same T cells did not
kill infected cells from another mouse strain.
They discovered that T cells first have to identify
two kinds of molecules on the cell surface before
they can actually recognize infected cells. One
type of molecule is the virus antigen, and the
other is a molecule from the major histocompatibility complex (MHC), a set of genes (and
proteins) unique to each individual. Differences
in MHC proteins had been noted in cases where
organ transplants were rejected, but the exact
role of the MHC in transplants was not understood until Doherty and Zinkernagel’s discovery that MHC proteins tell the immune system
whether or not the infected cell is from the host
individual. They found that T cells have to recognize both the viral antigen and the animal’s
characteristic MHC protein to kill an infected
cell.2
“Their observations paved the way for the
current understanding of how the immune
system recognizes both microbial invaders and
the body’s own cells,” said Anthony S. Fauci
(AAI ’73), M.D., director of the National Institute of Allergy and Infectious Diseases, upon the
announcement that Doherty and Zinkernagel
would share the Nobel. “They also helped us
understand, more broadly, how the immune
system recognizes a molecule as self or non-self.
This is a richly deserved prize for an extraordinary discovery, one that ranks among the most
important in the field of immunology because
of its influence on subsequent research in infectious diseases, autoimmunity, transplantation
immunology, rheumatology and cancer research.”3
Doherty and Zinkernagel subsequently developed a pair of models to further explain
their findings. One model was based on a single
recognition of altered self, wherein the histo-
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100 Years
compatibility antigen was changed by a virus
infection to make it appear foreign. The second
model was based on dual recognition of both
foreign and self molecules. Researchers later
showed how this dual recognition actually
occurs, with T cell receptors simultaneously
recognizing the viral component or other
antigen bound to an MHC protein and the
MHC protein itself.4 In recent years, Doherty’s
work has focused mainly on the T cell response
to viral infection, with a particular emphasis
on influenza.5
Biography
Doherty was born in Brisbane, Queensland,
Australia, on October 15, 1940. After earning
bachelor’s and master’s degrees in veterinary
science from the University of Queensland,
he received his Ph.D. in pathology from the
University of Edinburgh in 1970. He returned
to Australia to a postdoctoral fellowship followed by an appointment as a research fellow
in the Department of Microbiology at The John
Curtin School of Medical Research (JCSMR) at
the Australian National University in Canberra.
It was there that he and Zinkernagel conducted
their Nobel Prize-winning research. In 1975,
Doherty moved to the United States, where he
was appointed associate professor at the Wistar
Institute in Philadelphia. He later returned to
JCSMR in 1982 as professor and head of the
Department of Experimental Pathology, a position he held until 1988, when he became chair-
man of the Department of Immunology at St.
Jude’s Medical Center in Memphis.6 In 2002, he
was named Laureate Professor in the Department
of Microbiology and Immunology at the University of Melbourne. He currently splits his time between the University of Melbourne and St. Jude’s,
where he is the Michael F. Tamer Chair of Biomedical Research.7 He is also the namesake and
Patron of the Peter Doherty Institute for Infection
and Immunity at the University of Melbourne,
which expects to open a state-of-the-art facility
capable of housing more than 700 researchers
and clinicians in 2014.8
Awards and Honors
Doherty is a fellow of the Australian Academy
of Science (1983) and the Royal Society (1987)
and a member of the National Academy of Sciences (1998) and the Institute of Medicine
(2009).
He has also received many awards, including
the Paul Ehrlich Prize (1983), the Gairdner Foundation International Award (1986), and the Albert
Lasker Basic Medical Research Award (1995).
AAI Service
Doherty served AAI as an associate editor
(1980–82, 1989–91) and as a section editor
(1991–95) of The Journal of Immunology. In
addition, he has been an instructor for the AAI
Advanced Course (1991–95), served on the AAI
Nominating Committee (1995–96), and was selected as an AAI Distinguished Lecturer (1980).
1 “Physiology or Medicine 1996—Press Release,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1996/press.html.
2 R. M. Zinkernagel and P. C. Doherty, “Restriction of In Vitro T Cell-Mediated Cytotoxicity in Lymphocytic Choriomeningitis
within a Syngeneic or Semiallogeneic System,” Nature 248, no. 5450 (1974): 701–2; R. M. Zinkernagel and P. C. Doherty, “Immunological Surveillance against Altered Self Components by Sensitised T Lymphocytes in Lymphocytes Choriomeningitis,” Nature
251, no. 5475 (1974): 547–8; “Physiology or Medicine 1996—Press Release,” Nobelprize.org; “Physiology or Medicine 1996—Speed
Read,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1996/speedread.html.
3 Greg Folkers, “Doherty, Zinkernagel Win Nobel Prize,” NIH News Release, National Institutes of Health, 8 October 1996,
http://www.nih.gov/news/pr/oct96/niaid-08.htm.
4 “Physiology or Medicine 1996—Press Release,” Nobelprize.org.
Celebrating
100 Years
5 “Peter C. Doherty,” St. Jude’s Children’s Research Hospital, http://www.stjude.org/stjude/v/index.jsp?vgnextoid=e5dd10e88ce7
0110VgnVCM1000001e0215acRCRD&vgnextchannel=a0d513c016118010VgnVCM1000000e2015acRCRD.
6 “Peter C. Doherty—Autobiography,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1996/doherty.
html.
7 “Professor Peter Doherty: Full CV,” Department of Microbiology and Immunology, University of Melbourne, http://www.microbiol.unimelb.edu.au/research/immunology/doherty/cv_doherty.html.
8 “About Our Project,” Peter Doherty Institute, University of Melbourne, http://www.doherty.unimelb.edu.au/project.html.
Photo: Lasker Foundation