Laboratory Animal Science Vol 49, No 5 Copyright 1999 October 1999 by the American Association for Laboratory Animal Science Meeting Report Macfarlane Burnet Centenary Symposium on Immunology and Virology 3–5 August, 1999, Melbourne, Australia Abigail L. Smith This meeting was one of several events in Australia to cel- edict from WEHI that urged its scientists to work on flu or ebrate the centenary of the birth of Sir Frank Macfarlane leave the institute, he began an illustrious career as an in- Burnet, fondly known as Sir Mac by his friends and col- fluenza specialist. He elucidated the nature of receptor-de- leagues. The meeting was held in Melbourne during the stroying enzyme, began to characterize the nature of week prior to the XIth International Congress of Virology in reasssortment, predicted that influenza would have a seg- Sydney. Another centenary symposium, “Q fever - An Aus- mented genome, and pioneered the use of embryonated eggs tralian discovery of worldwide importance,” will be held as substrates for vaccine production. Ada then spoke about later in the year in Brisbane, and the July 1999 issue of Mi- the major diseases in the contemporary world (HIV, malaria, crobiology Australia, the journal of the Australian Society chlamydia) and the approaches that are being used to de- for Microbiology, was published in Burnet’s honor. Sir Mac velop vaccines. In these latter initiatives, he stressed the util- won the Nobel Prize in physiology and medicine in 1960 for ity of animal models. his hypothesis of immunologic tolerance, a phenomenon that Michael Alpers (Director, Papua New Guinea [PNG] In- was experimentally validated by Peter Medawar, with whom stitute of Medical Research, Goroka) began his talk by say- he shared the Prize. Ironically, Burnet is best known for his ing that Burnet had a “love-hate relationship” with kuru. work on clonal selection. Carleton Gajdusek, the acknowledged authority on kuru Burnet received his medical degree from Melbourne Uni- and himself a Nobel laureate, was a postdoctoral fellow in versity in 1922 and was director of the Walter and Eliza Hall the Burnet laboratory. Alpers talked about PNG-based stud- Institute (WEHI) in Melbourne from 1943–1965. Despite his ies of kuru and malaria, the former stressing epidemiology many contributions to the disciplines of microbiology (Q fe- and the latter stressing vaccine development with the goal ver) and virology (lysogeny in bacteriophage; Australian X of protection against severe, lethal malaria, not infection disease, now known as Murray Valley encephalitis), Burnet prevention. When transumption was recognized in the 1950s transformed the WEHI into an institute that stressed im- as the primary and perhaps only mode of transmission of munology. The Macfarlane Burnet Institute was established kuru, the practice was banned. This year is predicted to be one year after his retirement as director. the first with no cases of kuru, a disease with a 40 year incu- Having gained international recognition, Burnet was in- bation period. vited to deliver the Dunham Lectures at Harvard University Sir Gustav Nossal (Emeritus Professor, The University of in 1944. He was later offered a chair at Harvard but declined Melbourne) introduced Frank Fenner (Emeritus Professor, and was fiercely dedicated to Australian science. Sir Mac The John Curtin School, Canberra), well known to the labo- was knighted in 1951, was the founding president of the ratory animal medicine community for his pioneering work Australian Society for Immunology in 1959, and was named with ectromelia virus. Nossal told the audience that Profes- Australian of the Year in 1961. Speakers at the symposium sor Fenner, whose career has spanned 55 years, was Sir included colleagues and protégés of the honored scientist. All Mac’s favorite protégé. Fenner then spoke of his Burnet “con- speakers and topics are listed; however, space limitations nection” — he joined Burnet at WEHI in early 1946, remain- prevent detailed accounts of all presentations. ing until 1952 when he joined the faculty at the “nascent” Gordon Ada (Emeritus Professor, The John Curtin School, John Curtin School. Fenner then noted that the symposium Canberra) recalled that Burnet was about half way through honored Australia’s “greatest biologist,” a scientist who his medical studies when the influenza pandemic hit never put his name on a publication without having made a Melbourne. Burnet had a mild case, but was struck by the real contribution to the work reported. Fenner summarized enormous impact of the epidemic. In 1943, as a result of an the history of attempts to control rabbits, introduced to Aus- tralia in 1859 for sport hunting and, ultimately, very suc- Department of Pathology, Loyola University Medical Center, Brookfield Zoo, cessful pests. In 1888, a 25,000 pound prize was offered for Chicago Zoological Society, Chicago, Illinois control of the rabbit population. Even Louis Pasteur com- 471 Vol 49, No 5 Laboratory Animal Science October 1999 peted, but no one was awarded the prize. A colleague of (MV), the first virus shown to have immunosuppressive ca- Burnet’s suggested myxoma virus as a possible “temporary pabilities. The host cell receptor for LCMV and other control” agent; however, there was resistance to the proposal arenaviruses has been identified as ␣-dystroglycan, a because it was not known at that time whether the virus in- heavily glycosylated protein expressed on the basal side of fected humans. After many false starts, largely due to the cells. Clone 13, an immunosuppressive variant of LCMV, tar- fact that mechanical transmission by insects was not appre- gets interdigitating dendritic cells based on in situ hybrid- ciated, the potential of biological control was recognized. The ization studies; however, expression of very little detailed history of that effort was recounted and the devel- ␣-dystroglycan is sufficient to initiate infection. The clone 13 opment of host-determined genetic resistance noted. The virus-receptor interaction is high affinity: expression of 100- conclusion: myxoma did control, but not eradicate, rabbits. fold more ␣-dystroglycan is required for infection by the Jacques Miller (Emeritus Professor, WEHI, Melbourne) Armstrong strain of LCMV. Limited numbers of changes in talked about “biological curiosities.” Prior to 1961, the role of amino acid sequence have been shown to affect the affinity the thymus in immunity was not appreciated — thymec- of binding of LCMV strains and variants. Immunosuppres- tomy of adult mice had no effect and thymus cells were inca- sive consequences may be related to the same amino acid pable of transferring immunity. Miller showed the effect of sequences. Oldstone emphasized that there has not been, thymectomy immediately after birth in 1961 and demon- until now, a good small animal model of MV infection, de- strated in 1962 that there were two types of lymphocytes. In spite the fact that Von Pirquet documented the immunosup- 1972, Sir Mac called Miller’s subjects, mice that had been pressive capacity of this virus in 1890. The World Health thymectomized and sublethally irradiated, “biological mon- Organization has targeted MV for eradication by the year strosities.” But the ultimate importance of the thymus was 2015. The virus currently kills 1 million people per year and shown by Zinkernagel in 1978: MHC restriction is imposed infects 40 million people per year. Immunosuppression, aver- intrathymically. aging 2 to 3 months in duration, can result from infection. Peter Doherty (Professor and Chair of Immunology, St. The CD46 molecule is the host cell receptor for MV, and mice Jude Children’s Research Hospital, Memphis) quoted Bur- transgenic for CD46 may be infected by MV intracerebrally, net: “Science to me is the finest sport in the world.” Noting intravenously, or intraperitoneally. Virus recovery may be that Sir Mac led WEHI out of virology and into immunology, accomplished by co-cultivation. Additionally, MV infection of Doherty quipped “We all make mistakes.” He then discussed CD46 transgenic mice results in suppressed antibody re- his own current studies with the type 2 herpesvirus of voles, sponses to sheep erythrocytes, depressed primary cytolytic MHV-68, an agent taxonomically related to herpesvirus responses to vaccination and secondary responses to LCMV, saimiri, human herpesvirus-8, and Epstein Barr virus and enhanced susceptibility to Listeria monocytogenes after (EBV). The virus is lytic for epithelium, with primary repli- the sixth day of MV infection. Newborn CD46-transgenic cation occurring in respiratory epithelium, and remains la- mice infected with MV die, whereas adult transgenic mice tent in B cells and macrophages. Co-cultivation is necessary are immunosuppressed for an as yet undefined interval and for recovery of the agent from those cell types. As is the case die only if their immune systems are suppressed by a sec- for EBV, MHV-68 infection results in an increased number of ondary mechanism. This small animal model shows promise CD8+ T cells in peripheral blood. The facts that class II in facilitating our understanding of MV biology. knock-out mice die from MHV-68 infection and that anti- Colin Masters (Professor, Department of Pathology, Uni- body has been shown to be important in reactivation imply versity of Melbourne) spoke of “Mad Cows to Demented that all components of the immune system are necessary to People” in place of Stanley Prusiner. He discussed the simi- clear this virus, a potential animal model of EBV infection. larities and differences among Huntington’s disease, Doherty, while serious in dealing with the science, quipped “I Parkinsons’ disease, Alzheimer’s disease, and Creutzfeld- think of myself as part of the living fossil record;” as always, Jacob disease. Creutzfeld-Jacob disease occurs sporadically he had words of encouragement for young scientists in the in 10% of cases and is familial in 90% of cases. Despite the audience, noting that there is still plenty of work to be done. lack of evidence for blood-borne transmission of so-called Rolf Zinkernagel (Professor and Chair of Experimental “new variant” Creutzfeld-Jacob disease, the U.S.