Teachers notes

Professor Frank Fenner (1914–2010)

Microbiologist and virologist

Contents

Introduction
Summary of career
Extract from interview and focus questions
Activities
Keywords

You can order the DVD from us for $15 (including GST and postage).

Introduction

Professor Frank Fenner was interviewed in 1992 and 1993 for the Interviews with Australian scientists series. By viewing the interviews in this series, or reading the transcripts and extracts, your students can begin to appreciate Australia's contribution to the growth of scientific knowledge.

The following summary of Fenner's career sets the context for the extract chosen for these teachers notes. The extract covers Fenner's work with myxomatosis, a virus used to control Australian rabbits in the 1950s. Use the focus questions that accompany the extract to promote discussion among your students.

Summary of career

Frank Fenner was born in Ballarat, Victoria in 1914. He read medicine at the University of Adelaide, receiving Bachelor of Medicine and Bachelor of Surgery degrees in 1938 and a Doctor of Medicine in 1942.  He also received a Diploma of Tropical Medicine from the University of Sydney in 1940. Between 1940 and 1946 he served in Egypt and Papua New Guinea as an officer in the Australian Army Medical Corps, where he worked on the malarial parasite.

After the war, he went to the Walter and Eliza Hall Institute of Medical Research in Melbourne, where he studied the virus that causes smallpox in mice. In 1949,on a fellowship at the Rockefeller Institute in New York, USA, he worked on tubercle bacilli. Returning to Australia in 1949, he was appointed Professor of Microbiology at the new John Curtin School of Medical Research at the Australian National University. Here he began studying viruses again, in particular the myxoma virus. He was interested in the balance between virus virulence and host resistance.

Fenner was Director of the John Curtin School from 1967 to 1973. During this time he was also Chairman of the Global Commission for the Certification of Smallpox Eradication. In 1973 Fenner was appointed to set up the new Centre for Resource and Environmental Studies at the Australian National University (ANU). He held the position of Director until 1979.

Fenner has been elected to the fellowship of numerous faculties and academies, including Foundation Fellow of the Australian Academy of Science (1954), Fellow of the Royal Society (1958), and Foreign Associate of the United States National Academy of Sciences (1977).

During his career, Fenner has received many awards. Among these are the Britannica Australia Award for Medicine (1967), the Australia and New Zealand Association for the Advancement of Science Medal (1980), the World Health Organization Medal (1988), the Japan Prize (1988), the Senior Australian Achiever of the Year (1999), the Albert Einstein World Award for Science (2000), and the Prime Minister's Science Prize (2002).

The honours that Fenner has received include Member of the Order of the British Empire for work in malaria control (1945), Companion of the Order of St Michael and St George for medical research (1976), and Companion of the Order of Australia for service to medical science, to public health and to the environment (1989).

In 2003 he was honoured by the naming of the Frank Fenner Building at the ANU. The building is used by the Faculty of Science and the new Medical School. The establishment of a medical school at the ANU is something that he worked toward for a number of years.

Back to top

Extract from interview

Myxomatosis: a second poxvirus

When you came as Professor of Microbiology to the John Curtin School, how did you find a problem worthy of you?

Well, as I mentioned earlier, I had started off by studying the experimental epidemiology of ectromelia – mousepox – a virus of mice which Burnet had shown was closely related to vaccinia virus and therefore to smallpox virus. Then, when I went overseas, I had drifted away to working on mycobacteria – various kinds of tubercle bacilli – because that was what Dubos was working on. In Australia again, having tasted virology and bacteriology, I wanted to get back into virology. We had no buildings in Canberra while the John Curtin School was getting going, so Burnet offered me space in two labs back at the Hall Institute. He suggested that I might like to take over from him and work on influenza virus genetics, but I felt it would be a mistake to follow on something that he was doing. He was too dominant a personality and I had to be independent. So for a while I carried on with work on the mycobacteria, especially  Mycobacterium ulcerans. Then myxomatosis, a virus that had been introduced to control Australian rabbits, broke out.

It hadn’t been very successful initially, had it?

Its introduction has a long history. It started in 1918, it was tried again in 1934, and finally a determined trial was made in 1950 with the setting up of the Wildlife Survey Section in CSIRO. But the initial releases were made through the winter, even though the Australian research workers had shown that it was mosquito-transmitted. It was about to be written off, when in December 1950 – when the weather conditions and mosquito breeding were right – it escaped and was found 10 miles from the nearest trial site. Then it spread all over south-eastern Australia in a matter of about three months. The case mortality rate, we later found, was over 99 per cent in the field – unbelievable.

There were rabbits dying in hundreds of thousands. And you just walked in on that.

Yes, this fell into my lap. Recently, in the Burnet archives at the University of Melbourne, I found Burnet’s diary entries about it. There was no virologist working on myxomatosis, only zoologists. In his diary entries for 31 January and 1 February 1951, Burnet had written that Lionel Bull – Chief of the CSIRO Division of Animal Health, who had done the early work on myxoma virus in 1936-43 before war pressures and so on caused it to be dropped – thought there ought to be some virological work done. On 31 January Burnet wrote that he was thinking of talking to the ecologist Ratcliffe, the head of the CSIRO field section, who was working on myxomatosis. Then on 1 February he wrote that I had approached him to say I wanted to work on myxoma virus. In brackets he had a note that he thought Dame Jean McNamara, a controversial paediatrician who had been needling the CSIRO to get onto myxomatosis again, had something to do with my request. But he was wrong there. I hadn’t been prodded. I just wanted to get into virology and I saw this as an opportunity. And then I was delighted, as I dug into it a bit more, to find that this was a poxvirus – in line with my previous work with ectromelia. So that kept me in pox virology.

The second great poxvirus in your life.

Yes. I had this marvellous opportunity of a great experiment of nature, in which I was able to follow the way in which the virus changed to become less virulent and then some rabbits survived. And those that survived were genetically more resistant, so they could breed resistance. You got this interchange, this balance between virus virulence and host resistance. In parts of Australia which are valuable for agricultural purposes, the rabbit has now ceased to be a pest.

That period of study of myxomatosis and the myxoma virus lasted for quite a while. It covered epidemiology right down to genetics, at a molecular level. You must have played an extraordinary role in that field of research.

We did look at everything. I remember we started off with electron microscope observations of the particle and showed it was a poxvirus. Then I worked on the pathogenesis: the same things I had done with mousepox, I did with myxomatosis. We worked on mosquito transmission, doing what we call wipe-off experiments. That is, we had mosquitoes in little tubes, let them probe through a tumour and then saw how many positives of the different strains of virus would be taken along. That gave us the clue to why there was a selection for less virulent strains, because the very virulent one was very well transmitted but the rabbits died in four days; some intermediate ones were just as well transmitted but the rabbits lived for three weeks with infectious lesions. So there was tremendous selective advantage.

I had a small team – two research assistants, originally, one of whom became my first PhD student. And that became my virological team throughout the 15 years that I was working in the lab on it. But I had collaboration with all the zoologists, all the help that one needed on the zoological/ecological side, from the CSIRO group and also from various others, from electron microscopists to an entomologist, Max Day, who joined the team working on mosquito transmission. He was interested in the transmission of plant viruses by insects, and here was a chance to look at the transmission of an animal virus which wasn’t an ordinary arbovirus. It didn’t multiply in the vector; it was carried mechanically by it. We did a number of experiments and published two or three papers on that.

Looking back, I see that we published a paper on the pathogenesis, on the classification, on the morphology, on the relationship with other viruses of that group, the poxvirus group, on the immunity – passive immunity, active immunity – almost all aspects of all the things you could look at in the lab. But the most significant work was the study of the changes in virulence, which occurred very early and went on progressively, and the concurrent changes in the resistance of rabbits: the fact that when the mortality rate fell from 99 per cent, which it was originally, to 90 per cent, there were enough survivors for selection for genetic resistance to occur. For a number of years we followed both the changes in virulence and the changes in rabbit resistance. They have subsequently been taken up intermittently by other people, with some very interesting results.

The continuing rabbit story

Perhaps we can stay for a while with the myxomatosis story, which has not gone away. You’ve stayed in touch with that.

Yes. The ecological modellers got very interested in it, especially Robert May, a very distinguished Australian in the Department of Zoology at Oxford. Myxomatosis provides about the only example of a long-continued study of changes in virulence and changes in genetic resistance, and there have been about a dozen substantial papers written on the model, comparing it with the results we got in the early days and with subsequent ones. There are some criticisms of these models, as there always are of models, and I think they are valid ones. But it just is very hard to get a disease where you can get this sort of data.

I believe you are to talk this week about the current resurgence of interest in myxomatosis.

Myxomatosis has done a marvellous job in controlling the rabbit pest in Australia. In many areas of the country it has virtually disappeared. But in the dry outback areas, where mosquito activity is minimal and you only get a mosquito plague every few years, the rabbit causes major problems in promoting erosion and destroying habitat for indigenous, native mammals of Australia. Either the land in such areas is not sufficiently valuable for the landowners to put a lot of money into control, or else it is, say, national park. And in some areas the fall in virulence has been sufficient to allow a lot of rabbits to recover. Myxomatosis is not controlling the rabbit in those areas, and I am a member of an advisory committee to CSIRO which is looking at other methods of control.

The people in CSIRO Wildlife and Ecology are suggesting using an immuno-contraceptive approach by putting the relevant genes for zona pellucida into the myxoma virus and allowing it to sterilise those that it doesn’t kill. It still would have to spread effectively in the presence of existing strains of myxoma virus, and that’s going to be the hardest job, harder than molecular biology. But it’s an interesting approach. I’m going to a conference at Geelong this week on another proposal: to see whether the rabbit haemorrhagic disease virus can be used as a supplement. It’s a very lethal virus for rabbits, but not as lethal as myxoma virus was.

And there is New Zealand interest this time.

Yes. There have been several proposals to introduce myxomatosis for rabbit control there. A recent strong one was refused on the grounds that the flea which would have to be introduced at the same time to spread the virus – because there are not sufficient mosquitoes in that particular area on the South Island – might get on the kiwis. As a sop, I suppose, to the landholders who wanted to have the virus introduced, they were told that rabbit haemorrhagic disease virus might be introduced instead. I think that might cause some problems with the animal welfare lobbies there. We’ll see.

An edited transcript of the full interview can be found at http://www.science.org.au/scientists/interviews/f/ff.

Focus questions

  • Why did the initial releases of myxoma virus not lead to a spread of myxomatosis?

  • Fenner studied a number of different aspects of myxoma virus. What are they and what did he discover?

Back to top

Activities

Select activities that are most appropriate for your lesson plan or add your own.  You can also encourage students to identify key issues in the preceding extract and devise their own questions or topics for discussion.

  • Students find out more about myxoma virus and the more recently introduced rabbit haemorrhagic disease virus (also known as rabbit calicivirus). They write a report comparing the two viruses, including mode of transmission and type of genetic material.

  • Using library and internet resources students investigate the history of the introduction of myxoma virus in Australia. They write a report summarising their information. Note: Information is available at The history of myxoma virus in Australia (Nova: Science in the news, Australian Academy of Science).

  • Graphing and interpreting variation in rabbit numbers (Nova: Science in the news, Australian Academy of Science).
    Students graph and interpret the data provided on rabbit numbers.

  • How do we get rid of pests? (Australian Institute of Policy and Science)
    Provides information and classroom activities relating to rabbits in Australia.

  • Viruses and host evolution (Access Excellence, USA)
    Students participate in group discussions and find out more about viruses and their effects on the evolution of rabbit populations.

  • Rabbit calicivirus disease: Magic bullet or Pandora's box? (University at Buffalo, The State University of New York, USA)
    Students read a scenario about a proposed release of rabbit calicivirus disease in New Zealand as a biological control, then discuss provided questions. Teachers' notes are available.

Related publication: The Science of Immunisation: Questions and Answers

Back to top

Keywords

immunity
host
myxomatosis
myxoma virus
resistance
virulence

Back to top