Celebrating
100 Years
Nobel Laureates of AAI
Sir Frank Macfarlane Burnet, M.D., Ph.D.
(1899–1985)
F. Macfarlane Burnet, M.D., Ph.D., AAI
’61, shared the 1960 Nobel Prize in Physiology
or Medicine with Peter Medawar (AAI ’73) for
their “discovery of acquired immunological tolerance.”1 Burnet hypothesized that the concept
of “self” was actively defined by the immune system during embryogenesis, a theory for which
Medawar provided experimental proof.
Scientific Accomplishments
Although virology was his primary research
focus in the 1930s and 1940s, Burnet wrote his
first book on immunology, a review of the literature on antibody production coupled with
his own original insights, in 1941.2 In a second
edition of that work, published in 1949,3 Burnet
proposed the theory of “immunological tolerance.” In it, he asserted that if a foreign substance were to be introduced into an embryo
before the maturation of the immune system,
the antigen would be accepted as self, and no
antibody would be produced upon later exposure to the antigen. Medawar successfully demonstrated Burnet’s hypothesis in his laboratory
at University College, London, by inoculating
cells in utero from one mouse strain to another
and showing that the adult mice were rendered
tolerant to skin grafts from the original cell
donor. Their work extended the understanding
of immunology by defining the concept of selfnonself discrimination, and their demonstration
of the basis for acquired immunological tolerance held far-reaching implications for autoimmunity and transplantation.
Burnet’s interest in the theory of antibody
production continued to grow in the 1950s. He
was particularly intrigued by Niels Jerne’s (AAI
’73) 1955 article on natural selection theory,4 in
which Jerne argued that antigen-specific antibodies are present before antigen is introduced.
Building upon Jerne’s theory, Burnet proposed
the clonal selection theory of antibody production in a 1957 article5 that he later expanded into
a book.6
In Burnet’s clonal selection theory, each
lymphocyte is unique in that it has receptors
specific for one particular antigen. When the
antigen binds with the receptor, the lymphocyte
is stimulated to divide, giving rise to a clone
of lymphocytes producing antibodies to the
antigen. Burnet regarded the clonal selection
theory as his greatest scientific contribution.
The theory became a key principle in adaptive
immunity and prompted research into the development and function of lymphocytes, leading
to the discovery of the generation of antibody
diversity, the demonstration of how the antibody and T cell repertoires are developed, and
the elucidation of the role of lymphocyte cell
subsets, among others.
Celebrating
100 Years
“If one had to nominate ‘keywords’ to describe Burnet’s greatness as a biological scientist, they might include—originality, creativity,
biological intuition, high intelligence, discipline, persistence, excellent memory, capacity
for lateral thinking, ability to write rapidly and
clearly, and self-confidence,” recalled distinguished virologist Frank Fenner, whom Burnet
had recruited to join the faculty at the Walter
and Eliza Hall Institute in Melbourne after the
Second World War.
Biography
Born on September 3, 1899, in Traralgon, Victoria, Australia, Burnet attended the University
of Melbourne where he earned an M.B. B.S. in
1922 and an M.D. in 1924. He spent one year as
a resident pathologist at the Melbourne Hospital, working in the laboratories of the Walter
and Eliza Hall Institute. Burnet then went to
the Lister Institute of Preventive Medicine in
London, where he began studying bacteriophage and earned a Ph.D. from the University
of London in 1928. When he returned to the
Hall Institute later that year as a bacteriologist,7
he continued his research on phages. Over the
next few years, he also produced several studies on staphylococcal toxins, having headed the
bacteriological investigations into the “Bundaberg disaster” of 1928, in which several children
died from injections of diphtheria antitoxin
contaminated with the toxins. Supported by a
grant from the Rockefeller Foundation, Burnet
spent 1932 and 1933 at the National Institute
of Medical Research, London, where he began
studying animal virology and made a significant
contribution to the field by devising a method
for cultivating viruses in chick embryos.8
He returned to Melbourne in 1934 and was
promoted to assistant director at the Hall
Institute. With his new method for cultivating viruses, he shifted his research focus from
phage to viruses, particularly the poliovirus. As
the Second World War commenced in the late
1930s, Burnet, anticipating a pandemic like that
of 1918, began extensive work on the influenza
virus, attempting to develop methods of inoculation that might prevent such an outbreak. In
1944, he was appointed the director of the Hall
Institute, which, under his leadership, became
“a Mecca for overseas scientists who came to
work on influenza virus.”9 Later in his career,
as Burnet began to focus on antibody production, he turned his attention to immunology and
reoriented the Hall Institute accordingly.
Upon stepping down from the directorship
of the Hall Institute in 1965, Burnet was given
an office in the School of Microbiology at the
University of Melbourne, where he devoted his
energy to writing. There he published 13 books
over a 12-year period on topics ranging from the
general study of human biology, to immunology,
to gerontology. He retired in 1978 at the age of
78.10
Burnet died of cancer on August 31, 1985, at
the home of his son in Port Fairy, Australia. He
was 85.11
Awards and Honors
Burnet was a fellow of the Royal Society (1942)
and the Australian Academy of Sciences (1954),
which he served as president from 1965 to 1969.
He was also a foreign member of the National
Academy of Sciences (1954), the American
Academy of Arts and Sciences (1958), and the
American Philosophical Society (1960).
In addition to the Nobel Prize, Burnet’s many
honors include the Royal Medal (1947), the Emil
von Behring Prize (1952), the Albert Lasker
Basic Medical Research Award (1952), the
Copley Medal (1959), and the First International
Congress of Immunology Award (1971). He was
also invited to deliver more than 30 endowed
lectures at distinguished institutions around the
world. He was knighted in 1951 and appointed
to the Order of Merit in 1958.
Celebrating
1
100 Years
“The Nobel Prize in Physiology or Medicine 1960—Summary,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1960/.
2 F. M. Burnet, M. Freeman, A. V. Jackson, and D. Lush, The Production of Antibodies: A Review and Theoretical Discussion,
Monographs from The Walter and Eliza Hall Institute of Research in Pathology and Medicine 1 (Melbourne: Macmillan, 1941).
3 F. M. Burnet and F. Fenner, The Production of Antibodies, 2nd ed. (Melbourne: Macmillan, 1949).
4 N. K. Jerne, “The Natural-Selection Theory of Antibody Formation,” Proceedings of the National Academy of Sciences of the
United States of America 41, no. 11 (1955): 849–57.
5 F. M. Burnet, “A Modification of Jerne’s Theory of Antibody Production Using the Concept of Clonal Selection,” Australian
Journal of Science 20 (1957): 67–69. In this article, he noted that David W. Talmage had proposed a similar idea in D. W.
Talmage, “Allergy and Immunology,” Annual Review of Medicine 8 (1957): 239–56.
6 F. M. Burnet, The Clonal Selection Theory of Acquired Immunity (Nashville: Vanderbilt University Press, 1959).
7 Frank Fenner, “Frank Macfarlane Burnet 1899–1985,” Historical Records of Australian Science 7, no.1 (1987): 39–77,
http://www.science.org.au/fellows/memoirs/burnet.html.
8Ibid.
9Ibid.
10Ibid.
11Ibid.
Photo: Lasker Foundation