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When I arrived at the Walter and Eliza Hall Institute on 1 February, 1946, almost all the staff there were working on influenza virus, which, remembering the disastrous outbreak of influenza just after the World War I, Burnet had undertaken as his contribution to the war effort. As he had suggested, I undertook studies of various aspects of the epidemiology of infectious ectromelia virus. As I found when I had access to the library there, Burnet’s suggestion that I should work on the experimental epidemiology of this virus stemmed from work carried out with it in England (Greenwood et al., 1936). Selection of this virus was made more attractive because of Burnet’s discovery (Burnet, 1945) that it was an Orthopoxvirus, i.e., it belonged to the same group of viruses as smallpox and vaccinia viruses.
I used the same animal room as the other research workers to carry out experiments, but had a separate room to house infected mice—a wise precaution in view of the disastrous outbreaks of this disease that occurred in laboratory mouse colonies in Europe and the United States. Throughout this work, Bobbie acted as my part-time and unpaid technical assistant. We started by using cylindrical cages that could be attached together according to the number of mice in the cages, as developed by the British team. The first experiments looked at the effect of vaccination with vaccinia virus, the next two on the portal of entry and the sites of elimination of the virus in naturally infected mice.
At the end of the first year, I learned that the University of Melbourne had just introduced the PhD degree (previously, scientists went to the United Kingdom for their PhD). Since as an ex-serviceman I would not have to pay any fees, I applied to the University to be admitted as a PhD student, only to receive the reply that as a Senior Haley Research Fellow of the University of Melbourne I held too senior a post to do a PhD.
During these early experiments we handled all the mice in the cages every day, and made the observation, not easy because of the hair all over the mouse’s body, that those mice which did not die of acute hepatitis usually developed skin lesions all over their body–—a generalized rash. This had never been described before and was of particular interest because it suggested that ectromelia would be a good model for studying the pathogenesis of smallpox and other generalized diseases that produced a rash. We immediately undertook experiments to investigate the pathogenesis of this generalized infection, in particular to find out what happened during the incubation period. We had to use the crude techniques available in those days, namely infecting mice by inoculation of a small dose, in a small volume, in the footpad, and then titrating virus from the internal organs (blood, lymph nodes, spleen and liver) and, when a rash developed, from the lesions and from seemingly uninfected skin. The titrations were supplemented by histological studies, since most ectromelia-infected cells produced very characteristic inclusion bodies. Most of my papers were published in the ‘Adelaide journal’, the Australian Journal of Experimental Biology and Medical Science, but I published the detailed experimental results of the pathogenesis experiments in the British Journal of Experimental Pathology and a paper drawing generalized conclusions in The Lancet. Nearly 50 years later, the latter paper was republished in 1996, as a ‘Classic paper’, in Reviews in Medical Virology. Over the next two years I published five more papers dealing with various aspects of the experimental epidemiology of mousepox, as we now called the disease and the virus, concluding with a long and comprehensive review in the Journal of Immunology (Fenner, 1949). My baptism in virology, the study of ectromelia virus, led to a lifetime’s interest in the poxviruses and ultimately to my involvement in the smallpox eradication campaign of the World Health Organization.
Frank Macfarlane Burnet
My relations with Burnet, who was the most creative and imaginative scientist that I have known, were very cordial. At the time I arrived there in 1946, he and all other staff were working on influenza virus. Burnet kept tight control over their investigations, for in those days of non-existent overseas travel, he thought that he had to compete with large teams in the United States. In contrast, he allowed me complete freedom to do as I wished within my topic, the experimental epidemiology of ectromelia. At that time he worked at the laboratory bench from 9.30 am until 4 pm each week-day, and although we met at the tearoom, he was a reserved man and talked little. However, when I had completed an investigation and written it up I would give the manuscript to Burnet. He would read it that evening, and at 4 pm next day we would meet in his office to discuss its publication, and he would then ask about my current and ongoing work. In contrast to common practice in many laboratories, then and now, Burnet never put his name on a paper involving experimental work unless he had done some of the bench work, and all 11 of the papers on mousepox were published in my own name, or linked with that of my wife.