Sir Frank Macfarlane Burnet

Sir Frank Macfarlane Burnet - one of Australia’s greatest scientists

Sir Frank Macfarlane Burnet, Nobel Laureate and third director of the Walter and Eliza Hall Institute, has been described as “one of the world’s greatest scientists”. He began his research career as a microbiologist, transitioning from bacteriology to virology, and then moving into immunology. Burnet made significant contributions in all these fields, publishing scientific papers over a period of 59 years.

Sir Frank Macfarlane BurnetBurnet’s immense contributions to immunology are highlighted by his receipt of the 1960 Nobel Prize in Physiology or Medicine, with Sir Peter Medawar, for “the discovery of immunological tolerance”. In addition to this, Burnet put forward the ‘clonal selection theory’ of adaptive immunology, which explains how the mammalian immune system can develop immunity to myriad infectious agents. The clonal selection theory is the cornerstone of modern immunology.

Burnet also made many pivotal discoveries regarding important diseases of his era including typhoid, influenza, Q-fever, and polio, and was a pioneer of the study of autoimmune conditions, in which the immune system attacks the body’s own tissues, causing disease.

Fifty years after Burnet’s clonal selection theory was published, Professor Phil Hodgkin of the institute’s Immunology division wrote:

“[Burnet] is remembered as an intuitive thinker and a great example of an eclectic statesman scientist… However, Australians remember Sir Mac for another important reason. While science is ultimately shared and free of boundaries, Burnet seems to have realized early in his career that he could play a role in the development of medical research in the young country of Australia.

He chose to work in Melbourne, breaking the pattern of the day for the brightest Australians to work in Britain. As a result, medical researchers collected around him and his fertile imagination and ideas seeded new directions to explore and gave confidence to ensuing generations of Australian scientists.”

(Immunology and Cell Biology (2008) 86, 15; doi:10.1038/sj.icb.7100145)

Burnet, the microbiologist

Burnet’s medical research career began in 1923 at the Walter and Eliza Hall Institute. As a medical graduate from the University of Melbourne, he took up a training post in pathology at the institute, which at the time operated the pathology laboratories for the Melbourne Hospital (now The Royal Melbourne Hospital).

Burnet initially investigated typhoid fever (caused by Salmonella bacteria), which at the time in Australia was still a significant cause of illness and death. In 1925, Burnet travelled to the Lister Institute in the United Kingdom to further his training in bacteriology. He was awarded a PhD from the University of London in 1928 for his studies of bacteriophages, viruses that infect bacteria.

Burnet and KellawayIn 1928 Burnet returned to the Walter and Eliza Hall Institute, and soon led laboratory investigations into the cause of the ‘Bundaberg Disaster’, in which twelve children died after being injected with diphtheria vaccine. The royal commission, headed by institute director Sir Charles Kellaway, determined that contamination of a vaccine vial with Staphylococcus aureus bacteria had caused the deaths. From this work, Burnet developed an interest in researching staphylococcal toxins, in addition to bacteriophages.

By 1931 the Great Depression was hitting Australia hard. Funding to the Walter and Eliza Institute was substantially impacted, and Burnet took a two-year leave of absence to take a position funded by the Rockefeller Foundation at the National Institute for Medical Research, London. This period was especially productive for Burnet: the National Institute for Medical Research was the world’s leading virus research centre, and Burnet later recalled the excitement surrounding Sir Patrick Laidlaw’s isolation of the influenza virus. Burnet’s own research improved experimental systems for growing viruses in hen’s eggs. Modern methods for growing virus for flu vaccines are still based on Burnet’s work.

Burnet returned to the Walter and Eliza Hall Institute in 1934 to take the position of assistant director and lead the institute’s virology department, supported by grants from the Australian Government and the Rockefeller Foundation. His research in the period before World War II focused on diseases of significance to the Australian community, including discovering the causative agents of Q-fever and psittacosis (‘parrot fever’), and studying herpes simplex virus epidemiology and immunity to polio.

At the outbreak of World War II, Burnet decided to focus the institute’s research efforts on producing an influenza vaccine, to counter the potential for a repeat of the devastating influenza pandemic in the aftermath of World War I. Burnet also expanded the institute’s research effort into tropical infections including scrub typhus, a disease that was prevalent in Australian troops in North Queensland and New Guinea.Burnet at the University of Wisconsin

In 1944 Burnet became the third director of the institute, succeeding Sir Charles Kellaway who had been invited to head the research laboratories of the Wellcome Foundation in London. Burnet continued to investigate influenza, ultimately publishing more than 100 papers on this virus. His achievements included developing assays for the isolation, culture and detection of influenza virus, and he was the first to describe the recombination of influenza strains (which is now recognized as an important source of new influenza strains).

Burnet’s research interests frequently reflected the current disease concerns for the Australian community. In the 1950s he demonstrated that the Murray Valley Encephalitis virus was responsible for an outbreak of human encephalitis in the Mildura area. At the time many had blamed the disease on the myxomatosis virus, which had just been released to control rabbits. Burnet, Professor Frank Fenner and Sir Ian Clunies-Ross famously allayed public fears by inoculating themselves with myxomatosis virus to prove its safety to humans.

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The swing to immunology

Burnet’s research into bacteria and viruses had frequently included studies addressing the development of immunity to diseases. He is now most famous for his contributions to immunology.

Burnet, Dr K Nakamura and Professor Don MetcalfSince the 1930s, Burnet had speculated about the ability of animals to distinguish ‘self’ from ‘non-self’, meaning that an immune response is only mounted against ‘non-self’ molecules (antigens), while ‘self’ molecules are ignored by the immune system. This was elaborated on in his 1941 publication The Production of Antibodies, and in the second edition of the same work, co-authored with Professor Frank Fenner in 1949. In this work it was predicted that a foreign (‘non-self’) cell introduced into an embryonic animal would be accepted as ‘self’ by the developing immune system. Sir Peter Medawar and colleagues were able to demonstrate this ‘acquired immunological tolerance’ experimentally and, for their contributions to this field Medawar and Burnet, were jointly awarded the 1960 Nobel Prize for Physiology or Medicine. 

Burnet also developed the idea that antibody production and specificity had a cellular basis, and in 1957 he published a paper in the Australian Journal of Science on the “clonal selection theory of antibody production”, which he expanded on in his 1959 book The Clonal Selection Theory of Acquired Immunity. In these, Burnet proposed that antibody-producing cells (now called B lymphocytes) randomly develop a specificity to a particular molecule (antigen) during their development. When a foreign antigen enters the body, it encounters cells with varying antibody specificities, and only those cells which react with the foreign antigen will become activated to secrete antibody and, importantly, will proliferate, giving rise to offspring that are also able to respond to the same foreign antigen.

The Immune System - Fighting Infection by Clonal Selection (Etsuko Uno & Drew Berry, 2007)

By the mid-1950s, Burnet had decided that immunology research was an area of huge importance, and in 1957 he rapidly shifted the institute’s focus to immunology. Sir Gustav Nossal, who arrived at the institute in 1957 and succeeded Burnet as director, later recalled,

“I had come to work under the world’s greatest virologist, Sir Macfarlane Burnet… but to my dismay, Burnet was phasing out virus work, turning the institute almost entirely towards immunology. Little did I realise that he had climbed onto a huge wave that was just about to break, propelling us younger workers into a glorious future.”

Burnet’s decision soon placed the institute at the forefront of global immunology research, with almost 50 per cent of the world immunology literature coming from the institute in the next decade.

In the 1960s Burnet, still active at the laboratory bench, focussed his research on the immunology of autoimmune disease, developing experimental systems to test his hypothesis that ‘self-reactive’ immune cells are deleted during their development, and a failure of this process can result in autoimmune disease. Burnet and Dr Margaret Holmes showed that immune cells are responsible for initiating autoimmune conditions, and that there are genetic predispositions to autoimmunity.

Burnet retired from the directorship of the institute in 1965 and was succeeded by his protégé, Sir Gustav Nossal. Burnet took up a position at The University of Melbourne, where he continued to write about immunology, particularly autoimmunity and immune surveillance of cancer. He made many contributions to public policy in this period, and served as president of the Australian Academy of Science from 1965 to 1969.  Burnet continued to publish scientific papers and books until 1983, two years before his death from cancer.

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Awards and honours

Sir Frank Macfarlane Burnet’s scientific genius has been recognised by many international and Australian awards, most notably the 1960 Nobel Prize for Physiology or Medicine, shared with Sir Peter Medawar.

1960 Nobel DiplomaBurnet’s scientific awards, in addition to the Nobel Prize, included the Royal Society’s Royal Medal (1947), Croonian Lectureship (1950) and the Copley Medal (1959), the 1953 Albert Lasker Award for Basic Medical Research, and the 1967 Royal Institute of Public Health & Hygiene Medal.

In 1951, Burnet was appointed Knight Bachelor of the British Empire, the Order of Merit in 1958, Knight Commander of the Order of the British Empire in 1969, and Knight of the Order of Australia in 1978. He also received the Elizabeth II Coronation Medal in 1953, the Elizabeth II Jubilee Medal in 1977, and a Gold and Silver Star from the Japanese Order of the Rising Sun in 1961.

In 1960, shortly after receiving his Nobel Prize, Burnet became the first recipient of the honorary Australian of the Year award. When learning of this award, Burnet said “it does indicate that the community thinks that science is important, which pleases me.”

Burnet has also been commemorated on Australian stamps in 1975, 1995, 1997 and 2012. From 1998 to 1999, in celebration of the centenary of his birth, Burnet received the most Melburnian of honours: a Melbourne tram was adorned with an image and information about him, alongside those of another Australian Nobel Laureate, Sir Howard Florey.

Burnet’s legacy has been honoured through the naming of Melbourne’s Macfarlane Burnet Institute for Medical Research and Public Health in 1986. In 1971 the Australian Academy of Science established the Macfarlane Burnet Medal, awarded to outstanding Australian scientists. In 1987 the Walter and Eliza Hall Institute established the Burnet Prize, awarded annually, through a bequest of Burnet, to an outstanding early-career scientist at the institute.

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External links

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