02 Nov 2020
Issue #31: People and the institutions they build: an Australian story
Setting it Straight - Issue #31
Written by Nobel Laureate Professor Peter Doherty
We’ll get back to our story of cell-mediated immunity (CMI) next week when I discuss the work that Rolf Zinkernagel and I did (1973 to 1975) at the John Curtin School of Medical Research (JCSMR), Canberra, that led to our 1996 Nobel Prize. First, though, I’d like to summarise a little of the underlying history. More detail can be found if you scroll down through the following links.
The Australian National University (ANU) was founded in 1948 as a postgraduate institution to produce PhD graduates for the State Universities and the CSIRO. Constituted as independent Research Schools, the ANU spanned the humanities (Asian languages, anthropology, social sciences) and the hard sciences. Australian Nobel Prize winner (1945, for penicillin), Howard Florey, the head of the Sir William Dunn School of Pathology at Oxford University, played a major part in establishing the JCSMR and though he did not, as hoped, become the first Director, he did serve (1963-8, from the UK) as ANU Chancellor.
Australia’s most powerful medical researcher, Sir Macfarlane Burnet, opposed the idea of the JCSMR from the outset. But, when he switched the focus of Melbourne’s Walter and Eliza Hall Institute (WEHI) from virology to immunology, the appointment of his protégé, Frank Fenner, as the inaugural ANU Professor of Microbiology meant that many of the WEHI virologists could conveniently transfer to Canberra. The resultant virology group was a leading force globally for decades.
By the time I arrived in Canberra at the end of 1971, Fenner had moved on to be the JCSMR Director. His replacement as Microbiology Head was WEHI biochemist, then immunologist, Gordon Ada who, among other achievements, was the first to show that the genetic information of the influenza viruses is, like SARS-CoV-2, passed on as RNA. At the end of the 1960’s, Fenner and Ada recruited a young immunologist RV (Bob) Blanden to pursue a state-of-the-art analysis of T cell-mediated immunity in ectromelia (mouse pox), the model used early on by Frank to disprove the then prevalent (but wrong) idea of rigid viral tropisms.
From Adelaide and trained initially as a dentist, Bob returned from the Trudeau Institute, Saranac Lake, New York, where he had gone with his mentor, the macrophage biologist George Mackaness. An MD, George was one of several young Australians funded to spend time learning research skills at the Sir William Dunn School of Pathology before becoming tenured Fellows at the ANU. Passed over for the JCSMR Chair in Experimental Pathology, which I later held for a while, George left for the University of Adelaide, then to take up the Trudeau Directorship. Mackaness was a real loss to Australia but his trainee, Bob Blanden, blazed as a bright young star. Appointed to a tenure track position after completing his ANU PhD, Bob started to collaborate with JCSMR Professorial Fellow, English MD Cedric Mims, who had long been interested in the pathogenesis of both ectromelia and another virus infection of mice, lymphocytic choriomeningitis (LCM).
My final five years (of nine) as a veterinary researcher were spent as a Senior Scientific Officer (a Civil Servant) at the Moredun Research Institute, Edinburgh. My boss, Dick Barlow (also a talented wood sculptor), was a veterinary neuropathologist who later, as Professor of Pathology at the Royal Veterinary College, London, played a major part in the ‘Mad Cow disease’ story. Apart from conducting our own research, the job was to do neuropathology diagnostics for the field Veterinary Service. The Moredun was famous for its work on scrapie (the original prion disease), and for developing an early vaccine to the tick-borne flavivirus encephalomyelitis, louping-ill, a major cause of economic loss in Scotland.
After a brief dalliance with scrapie (too difficult for a thesis project), I completed a part-time PhD on the pathogenesis of louping-ill meningoencephalitis as an external student at Edinburgh University Medical School. For that research, I collaborated with another young veterinarian, Hugh Reid, who did the virology and antibody measurements (which he also used for a PhD thesis) on our experimental sheep, the type of approaches I’d pursued earlier-on as a staff pathologist at the Animal Research Institute (ARI), Brisbane. In those Edinburgh years, my main scientific society ‘homes’ were the British Neuropathology Society and the Association for Veterinary Teachers and Research Workers which, as described in The Incidental Tourist, held memorably bibulous annual meetings at the Grand Hotel, Scarborough. I also attended the local immunology meetings of the ‘Metchnikoff Club’.
I was being recruited back to Australia as a senior researcher in the CSIRO Division of Animal Health group led by former WEHI virologist Eric French (the discoverer of Murray Valley Encephalitis virus) when, after agreement with Eric, I opted to spend a couple of years learning about CMI at the JCSMR. Gordon Ada organised a postdoctoral appointment for me to work with Cedric but, shortly before we left Edinburgh, Cedric told me that he had accepted the Chair of Microbiology at Guy’s Hospital Medical School, London. We overlapped very briefly in Canberra; I inherited both his technician, Gail Essery, and his much-reduced lab space. The fact that I was both an experienced investigator and a transient led to me being left to my own devices. When Rolf arrived later to work with Bob, space constraints meant that he was moved into my lab.
Rolf, a Basel University MD, is from an academic family. His father was a leading researcher in the Swiss pharmaceutical industry, while his grandfather was a Professor of German Literature. After completing a University of Zurich course on immunity led by Jean Lindemann, the co-discoverer (with Alick Isaacs) of Interferon, Rolf was working on a problem in bacterial immunity at the University of Lausanne. There he was also exposed to the experiments of cancer researchers Jean Charles Cerrottini and KT (Teddy) Brunner who were using an in vitro cytotoxic T lymphocyte assay to investigate alloreactivity, the basis of transplant rejection. After meeting both Bob and Gordon, Rolf arranged funding from the Swiss National Science Foundation and, in January 1973, arrived in Canberra.