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Celebrating
100 Years
Nobel Laureates of AAI
Rolf Martin Zinkernagel, M.D., Ph.D.
Rolf M. Zinkernagel, M.D., Ph.D., AAI ’76,
University of Zurich, was awarded the 1996 Nobel Prize for Physiology or Medicine jointly with
Peter C. Doherty (AAI ’76) for “their discoveries
concerning the specificity of the cell mediated
immune defense.”1
system to distinguish self from non-self.2 The
strongest T cell responses were elicited by targets that were not completely foreign but were
instead recognized as “altered self,” consisting
of a self-MHC protein attached to a non-self
antigen.
Scientific Accomplishments
This discovery fundamentally altered our
understanding of how the immune system operates and has opened the way to advances in the
areas of transplantation, vaccine development,
and treatment of autoimmune and infectious
diseases.
While examining immune reactions in mice infected with lymphocytic choriomeningitis virus
(LCMV) from 1973 to 1974, Zinkernagel and
Doherty found that virus-killing T lymphocytes
taken from one mouse and injected into another
could destroy infected cells only if the two mice
belonged to the same strain. They discovered
that T cells have to identify two kinds of molecules on the cell surface before they can actually
recognize infected cells. One type of molecule
is the viral antigen, and the other is a molecule
from the major histocompatibility complex
(MHC), a set of genes (and proteins) unique to
each individual.
As early as the 1940s, researchers had noted
variances in MHC proteins in cases where organ
transplants were rejected, but the basis for the
central role MHC played in determining the success of a transplant was not understood. Zinkernagel and Doherty uncovered the biological
function of MHC proteins when they observed
that these proteins served as a surveillance
In subsequent work, Zinkernagel built upon
his research with Doherty in his own laboratory.
In the late 1970s, he elucidated the role of MHC
in the thymus gland in selecting white blood
cells for survival and maturation.3 More recently, he turned his attention to the co-evolution of
viruses and their host immune systems.4
“The whole field was in a mess” before
Zinkernagel and Doherty’s groundbreaking research of 1974, recalled Philippa Marrack (AAI
’74, president 2000–01) of the National Jewish
Center for Immunology and Respiratory Medicine in Denver (now National Jewish Health).
“We were very confused about what T cells were
up to. It wasn’t until they made the observation
that the T cell somehow has to recognize the two
[signals] at the same time that the whole thing
made sense.”5
Celebrating
100 Years
Zinkernagel and Doherty had “changed
everything, really,” commented Philip D. Greenberg (AAI ’82) of the University of Washington
School of Medicine. Upon hearing that they had
been awarded the Nobel, Greenberg said, “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.”6
Biography
Zinkernagel was born in Riehen, Switzerland,
on January 6, 1944. After earning his M.D. from
the University of Basel in 1970, he received a
two-year postdoctoral fellowship in the Department of Biochemistry at the University of Lausanne. He began his training in immunology at
Lausanne and learned first-hand the “frustrations of experimental lab work” while attempting to measure the radioactivity of cells infected
by bacteria. In 1972, after taking a World Health
Organization course on immunology taught by
visiting professor Robert V. Blanden (AAI ’77)
at Lausanne, Zinkernagel applied for a second
postdoctoral fellowship at the John Curtin
School of Medical Research at Australian
National University in Canberra, Australia,
where he planned to study cell-mediated
immunity to Listeria and Salmonella under
Blanden. When Zinkernagel arrived in Canberra
in January 1973, however, the only laboratory
with available space was that occupied by
another postdoctoral fellow—Peter Doherty.
Shortly thereafter, Zinkernagel and Doherty
began collaborating on the study of the immune
response to LCMV, for which they were awarded
the Nobel Prize.7
Although Zinkernagel had not originally
intended to pursue another degree when he
moved to Australia, shortly after he began collaborating with Doherty, he entered the graduate immunology program at Australian National
University, earning his Ph.D. in 1975. Recruited
by Frank Dixon (AAI ’50, president 1971–72),
Zinkernagel accepted a position as an associate
member of the Scripps Clinical Research Institute in La Jolla, California, in 1976. He also began teaching in the Department of Pathology at
the University of California, San Diego. Shortly
after being promoted to the rank of full member
at Scripps in 1979, he returned to Switzerland to
join the faculty of the Department of Pathology
at the University of Zurich as associate professor. Promoted to full professor in 1988, Zinkernagel was appointed founding co-director of the
university’s Institute of Experimental Biology in
1992. He retired from both positions in 2008.8
Awards and Honors
Zinkernagel is a foreign member of the
National Academy of Sciences (1996), the
American Academy of Arts and Sciences (1998),
and the American Philosophical Society (2001).
He is also a member of Academia Europea
(1989) and a foreign fellow of Leopoldina—The
German Academy of Sciences (1994), the Australian Academy of Sciences (1996), the Royal
Society (1998), and the Royal Academy of Medicine of Belgium (1998).
In addition to the Nobel Prize, he has been
awarded the Paul Ehrlich Prize (1983), the
Gairdner Foundation International Award
(1986), the William B. Coley Award for
Distinguished Research in Basic and Tumor
Immunology (1987), the Christoforo Colombo
Award (1992), and the Albert Lasker Basic
Medical Research Award (1995). In 1999,
he was named an Honorary Companion of
the Order of Australia, the nation’s highest
civilian honor.9
AAI Service
After joining AAI in 1976, Zinkernagel
served as an associate editor for The Journal
of Immunology (1978–80). He was named an
AAI Distinguished Lecturer in 2000.
Celebrating
100 Years
1 “The Nobel Prize in Physiology or Medicine 1996—Summary.” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1996/.
2 “The Nobel Prize in Physiology or Medicine 1996—Speed Read.” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1996/speedread.html.
3 R. M. Zinkernagel, “Thymus and Lymphohemopoietic Cells: Their Role in T Cell Maturation in Selection of T Cells’ H-2Restriction-Specificity and in H-2 Linked Ir Gene Control,” Immunological Reviews 42 (1978): 224–70.
4 “Rolf M. Zinkernagel—Autobiography,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1996/
zinkernagel.html; M. F. Bachman and R. M. Zinkernagel, “The Influence of Virus Structure on Antibody Responses and Virus
Serotype Formation,” Immunology Today 17, no. 12 (1996): 553–58.
5 Philippa Marrack quoted in John Travis, “Nobel Prize Honors Insight into Immunity,” Science News 150, no. 15 (1996): 229.
6 Terence Monmaney, “Nobel Awarded for Research on Immune System,” Los Angeles Times, 8 October 1996.
7 “Rolf M. Zinkernagel—Autobiography,” Nobelprize.org.
8 Ibid.; “Rolf M. Zinkernagel—Curriculum Vitae,” Institut für Klinische Pathologie, UniversitätsSpital Zürich,
http://www.klinische-pathologie.usz.ch/UeberUns/Kontakte/Documents/RZI_CV_E_2010.pdf.
9 “Rolf M. Zinkernagel—Curriculum Vitae,” Institut für Klinische Pathologie, UniversitätsSpital Zürich.
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