Burnet’s Early Scientific Career
Burnet was born in the small country town of Traralgon, Victoria. Having spent three months there as a resident medical officer, I can vouch for the fact that Traralgon is a dull place. However, Burnet had a happy and uneventful childhood, and in later life he retained his affection for the bush. He went on to study medicine at Melbourne University, where he graduated in 1922 with high honours. During his year as resident at the Royal Melbourne Hospital, he aspired to become a clinical neurologist, but his mentors felt that his talents lay elsewhere, and steered him towards laboratory research. (Rolf Zinkernagel also aspired to become a neurologist, and it is fortunate that fate also took him in a different direction). Burnet became registrar in pathology, and thus gained entry to the Walter and Eliza Hall Institute, with which he remained associated for the next forty years until he retired as Director in 1965.
His first bench work began with diagnostic bacteriology and serology. Even at this early stage he was an acute observer. Starting with practical problems, he used opportunities generated by any unexpected results to expand his intellectual horizons and to seek generalisations. This pattern, repeated over a lifetime, ultimately created the foundations for our current understanding of the immune system.
Burnet's first significant observation came during his time as pathology registrar in 1925, with the finding of patches of bacteriophage lysis on a bacteriological culture plate. The concept of bacteriophages was relatively new. D'Herelle's book, The Bacteriophage; Its Role in Immunity, had been published only three years earlier.
He continued his work on bacteriophages in the Lister Institute in London. By the age of 27 he had become an expert on the subject, and was invited to write a chapter for the Medical Research Council's eight-volume System of Bacteriology. His interest in bacteriophages already went far beyond their medical importance. By the time he had submitted his PhD thesis in 1927, he had formed the belief that the bacteriophage "is a living bug but lives at the expense of bacteria". He saw that phage represented the "raw material of evolution" and might uncover more fundamental truths, including that of life itself (1, 2).
In 1928 he returned to the Hall Institute in Melbourne and was appointed Assistant Director to Charles Kellaway. One of his first tasks was to investigate the "Bundaberg disaster", in which 12 children died as a result of staphylococcal contamination of diphtheria vaccines. This led to his discovery of the alpha toxin of Staphylococcus aureus, but Burnet felt that this toxin was unlikely to be the culprit. The toxin that actually caused the illness was probably staphylococcal enterotoxin that causes what is now known as toxic shock syndrome.
In 1929 Burnet and Margot McKie suggested that bacteriophage could exist as a stable non-infectious "anlage" which multiplies in step with the bacterial host, a concept that was many years ahead of its time. He was thus one of the pioneers in the study of lysogeny, the process by which certain bacteriophages integrate their DNA into the chromosome of the bacterial host and replicate in a hidden fashion, only to emerge at a later stage, either randomly and unpredictably or by certain stimuli such as ultraviolet light, as shown by Lwoff in 1949 (3). In order to appreciate Burnet's vision, we must remember that D'Herelle denied the phenomenon of lysogeny, and even Delbrück initially refused to believe in it, feeling that the experiments by Burnet and others were worthless (3). The importance of bacteriophage in genetics was recognised by the award of Nobel Prizes to Jacob, Lwoff and Monod in 1965 and to Delbrück, Hershey and Luria in 1969.
In 1932-3 Burnet took leave of absence from WEHI to hold a fellowship at the National Institute for Medical Research in Hampstead, London, where he witnessed what can now be seen as a "golden age" of virology, including the isolation of the influenza virus and its transmission to ferrets. A major contribution at this time was his demonstration that canary pox virus (and by implication, other viruses) could be quantitated by making serial dilutions and counting pocks on the chorioallantoic membrane of embryonated eggs. This work became particularly important in his later studies on influenza.
Director of the Walter and Eliza Hall Institute
He returned to the Hall Institute in 1934. Upon the departure of Kellaway to become Director of the Wellcome Foundation in 1943, Burnet became Director, a post which he held until his retirement in 1965. These years saw a stream of discoveries concerning infectious diseases, notably psittacosis, scrub typhus, Murray Valley encephalitis, myxomatosis, poliomyelitis, and Q fever, the causative organism of which was named Coxiella burneti in his honour.
During this time Burnet had a particularly strong interest in influenza virus. The world-wide influenza pandemic of 1918-1919 killed more people than were killed in the whole of the first world war, and he was conscious of the possibility that a similar pandemic might occur again. He devised novel methods for the growth and study of influenza virus in embryonated eggs, although the development of an effective influenza vaccine proved elusive.
His interest in receptors for flu virus led, via an extraordinary combination of brilliance and intuition, to his discovery of a "receptor-destroying enzyme" (neuraminidase) secreted by Vibrio cholerae. This work led on to Alfred Gottschalk's discovery of glycoproteins and the neuraminidase substrate, sialic acid.
The golden age of virology continued at the Hall Institute under Burnet's direction. It included the work of Alick Isaacs on what was later called "interferon", as well as important contributions by Gordon Ada, who discovered the segmented RNA nature of the influenza genome, and the work of John Cairns, Stephen Fazekas de St. Groth, Eric French, Gray Anderson and Frank Fenner.