Professor Ian Frazer was born in 1953 in Glasgow, Scotland, into an academic family. He studied medicine at Edinburgh University and trained as a renal physician and clinical immunologist. He received a BSc(Med) in 1974 and an MB ChB in 1977. In 1974, as part of his studies, Frazer spent three months at the Walter and Eliza Hall Institute of Medical Research in Melbourne. In 1981 Frazer returned to the Walter and Eliza Hall Institute where he continued his clinical training and undertook studies in viral immunology and autoimmunity and became particularly interested in human papilloma viruses (HPV). In 1985 he took up a teaching position with the University of Queensland. When he moved to Brisbane he decided to continue his work with HPV, in particular HPV and cervical cancer. He was awarded a MD from the University of Melbourne in 1988. The work of Frazer with his colleague, the late molecular virologist Dr Jian Zhou, has led to the development of a vaccine which prevents infection with HPV and cervical cancer.
Frazer is currently CEO and Director of Research at the Translational Research Institute (TRI).
Interviewed by Robyn Williams in 2008.
Born in Edinburgh, or born in Glasgow – which is it?
Born in Glasgow, lived there for all of two years, moved to Edinburgh. They couldn't get rid of me fast enough from Glasgow!
There's tremendous tension between Glasgow and Edinburgh, isn't there?
There certainly was when I was a student, yes. But nothing too serious – just crossed knives at dawn! [laugh]
Yours is a professional family, with lots of science in it.
Yes. My father was trained as a doctor, and then ran a diagnostic pathology laboratory for most of his life until he became a professional administrator in his later years. My mother was a more conventional scientist – BSc, PhD. She was interested in zoology but eventually did a PhD in matters relating to the peripheral nerves of patients with diabetes.
Would you say you absorbed a culture of science at home, even at a young age?
Well, my father was (I guess he would forgive me for saying this) more of a technologist. He was interested in getting things to do things; he was into automation in the laboratory, and he certainly would be building things. He had a workshop in the house – still does, in his house up in Noosa – and he constructed things, usually from whatever was left over and lying around the place. Certainly there was a little bit of science taught, but a lot more of it was about how you would practically solve a technical problem.
Did you go ever into the surgery?
On several occasions I went in to the hospital where my father worked, and played round in the labs. I think he was hoping some of the scientific approach would rub off on me. And I suppose it did, although it's hard to identify exactly how and when the desire to be a scientist came out of my education.
Did your mother's work impinge on you at all?
Yes, I got much more practically involved in that. She was doing her PhD while I was at high school, and she used to bring her work home with her – not, fortunately, the nerves, but the electron micrographs of the nerves – and I would sit there and count the diameters of nerves for her, because it was a sort of routine and technical thing to do. But at the same time I was thinking, 'Well, why is this being done? And what are we learning by doing it?'
Going back as far as you can remember, what sort of kid were you?
A curious one, I guess. I liked to take things to bits and put them back together again – or usually not manage to put them back together again. I was curious about the way the world worked. I remember thinking, even when I was five or six years old, that I would be involved in the practicalities of science somehow.
Were you very friendly, or solitary, or what?
Oh, fairly friendly. I lived in a very friendly neighbourhood. When I was at primary school, one of my best friends lived in the house on one side of where I lived and another lived on the other side, and so we were always together and usually well away from our parents, roaming round the neighbourhood doing things we probably oughtn't to have been doing.
For example, we decided to build a tunnel through one of the Braid Hills, and we actually started in a quarry there, knocking rocks out [laugh] and gradually building a tunnel through. We didn't get very far, but it seemed like a great idea at the time. What we did manage to do was drill a hole through the wall between my house and my neighbours' house – they weren't very pleased about that [laugh] but it allowed us to talk to each other without having to go round.
Did you get into trouble at all?
Yes, I regularly got into trouble, I'm sure – hopefully, not serious trouble. But probably my parents were more concerned when I wasn't around than when I was.
At school, did your brains become obvious quite quickly?
Ah, I don't remember particularly thinking of myself as a bright kid when I was in primary school. Indeed, probably it wasn't until I was about 13 or 14 that I started realising that maybe I was a little bit higher up the path than the average. And by that time I'd already got a fairly strong focus on science and maths in my mind.
Physics was what I thought I was going to do when I went to university, and I did eventually enrol in physics, which I saw as a challenge. I had a strong interest in what I suppose nowadays would be called cosmology, how the Universe worked – you can't really answer that but I thought it would be interesting to find out.
I still retain that curiosity, and the interesting thing is that I probably did more outside of my own science than inside my present particular science area. Remember, this was the time when everybody wanted to be an astronaut, and maybe I thought I wanted to be one too. And then I realised that being an astronaut was just like being a car driver – there wasn't anything very exciting about it. But the science behind going out into space, that was interesting. I read a lot of science fiction when I was a kid, and in those days most of the science fiction was about exploring the outer Universe.
You'd have to be in the RAF [Royal Air Force], I suppose, if you were going to be selected as an astronaut, and I suspect you weren't that easy to discipline.
No, I wouldn't have fitted into that model at all. The idea of doing what I was told was never high on my priority list.
What about high school and exams? Many of us think of the Scottish and the British systems, especially, as being very tough in those days. Did you sail through?
I guess I have to be honest and say I did. I mean, everybody else used to work for exams, and I couldn't understand why they bothered. I took on subjects which I deliberately found difficult so that I would have something I could work at, simply because I recognised that if I didn't, I was seen as being a bit different from everybody else. So I studied Russian at high school. But for science and maths I couldn't see where the problems lay. It was kind of intuitive.
And did you ever find that you were outpacing even the teachers?
It's an interesting question. The Scottish syllabus in those days was one where conformism was expected, but I was actually going outside of that in my own stuff that I was doing on the side. I was interested a lot in electronics, and would build things at home to see how they would work – and you rediscover things that other people discovered.
I 'discovered' how to make a shocking-coil, for example, just by playing around with a transformer and seeing what I could do. It's a device which makes a very high voltage but very low current. As kids you used to hang on to the handle of one of these and when the thing was turned on you'd get a zzzz-zzzz zzzz-zzzz zzzz-zzzz and it really felt like you were in serious trouble, but you weren't. I found out that you could produce this by making a transformer in which you missed out one pole and just put something which was magnetically attracted to it as a switch to make the device vibrate at very high frequency. I converted an old TV set into a whole series of these things, which I gave away to friends. I don't think they were very popular with the parents, but they worked very well.
Were there any major upsets for you in your teenage years?
Education-wise, no, not really – except perhaps for when I moved from Edinburgh to Aberdeen, when I was about 11. The two school systems were sufficiently different that I was made to go back a whole year in the education system, so basically I was repeating what I regarded as old ground and found very boring. That I objected to, and I didn't work for a year. I didn't even try to do well in the exams, and that annoyed both my parents and my teachers. But after that I sort of settled in.
The school that I was at was very much a school of mixed ability, and the brighter kids were seen (well, as they are today) as nerdy. I realised that you weren't going to be very popular if all you ever did was work. So I had to actually adopt a plan to be something else besides the educated student, if you like.
I thought the Scottish system was better. It did value scholarship to some extent.
The school that I was at valued scholarship, there is no doubt. It was just that not all of my friends there valued scholarship in the same way as the school did.
The move to Aberdeen was one which I was reluctant to make, because I left behind my Edinburgh friends at what I guess was a critical age. When you're just pre-teen, the friendships that you have are very important to you. And really I went not to Aberdeen but to Aberdeenshire. My parents bought a very nice house about 10 miles out from Aberdeen – which in those days might have been about as far away from the city as the Moon. We were outside of the area that the city buses went to, and that was very important because it meant that I now found socialising more difficult.
Also, at that time I hadn't really taken up any particular sporting interest. I didn't have an outside interest, if you like, beyond going to school.
Even though you didn't necessarily want to be an astronaut, you could have been all sorts of other things in physics. What stopped you?
Oh, pragmatism. Having finished my high school in Aberdeen I came back to Edinburgh and went to university. But I found out what people who graduated in physics ended up doing – teaching physics or even doing something totally unrelated – and I realised that my chances of actually making a career in research in physics were pretty minimal, because the opportunities were scarce. So I decided that while I was really interested in physics, I could be really interested in other things as well. At high school I had become gradually more interested in biology, so that it seemed logical to maybe not do physics.
And therefore to do medicine. When did that loom?
I guess there was a sort of vacuum: 'If I'm not going to do physics, what am I going to do?' That, I think, was the point where my parents took a positive step in influencing me, saying, 'Well, why not do medicine?'
Weren't you put off by all those orifices and fluids and people with unfortunate tendencies wanting attention?
I suppose initially I was, because I wasn't sure what I was letting myself in for. I didn't have any practical experience of what it was like to look after somebody who was sick. But the first three years of the medical course in Edinburgh in those days was very much science, and that bit appealed to me. Fortunately, the people who design medical courses realise they have to rapidly desensitise people who haven't been through the process of being a doctor, to enable them to understand what it's about, and that's why they invented an anatomy course. You very rapidly get desensitised to the whole idea of worrying about people being sick, and dead bodies and such things.
And you coped with your first dissections and so on?
Yes. Again the scientist overtook the person, and I was just interested in how the body worked as a machine, I guess.
Did you not at any stage during that time wonder whether you should become an accountant or a businessman, and a rich person, instead?
Oh no, I always knew I wanted to be a scientist. And even when I went through medicine I thought that at the other end of that I would probably end up in science.
Well, because it was logical and physiological. Renal medicine, with the idea of fluids and fluid balance, was relatively science-based, whereas a lot of medicine in those days was not particularly scientific but rather empiric. Plus the training that I got in Edinburgh was focused round physiology, and the professor of medicine in those days was a renal physiologist. And Lambie, one of the professors of medicine, was a very good mentor when it came to thinking about the science behind medicine.
Medicine had become thoroughly scientific by the late 1960s and early '70s. Before the war, before Florey and so on, it was very much tender loving care and an awful lot of hope – if you discount the public health developments at the turn of the 19th–20th century. Then a revolution in the science took place, and you were caught up in the sweep of the really scientific part of medicine.
Yes. Fortunately, in Edinburgh there was a good school of science behind the medicine, and the physiology (and perhaps most importantly the pathophysiology, the systematic pathology that we were taught) was taught in such a way as to make me realise that if you could understand the science you could understand the medicine.
So what was the sporting interest that came along?
That was snow skiing. It was my first real sporting interest. In fact, I would quite happily have become a ski instructor. I enjoyed working up in the mountains and I enjoyed working with the people there, and indeed I did work for the Cairngorm Chairlift Company for a number of years as a part-time job.
It was through skiing that I met my wife. I was always the organiser, and the Edinburgh University Ski Club certainly needed organising. It had the largest membership of any university club but the vast majority joined to drink, because it had the best pub lunches – on a Friday afternoon, in an Edinburgh pub called the Yellow Carvel. To get the ski club to actually go skiing required some organisation, so I got involved in my second year at university and became what was called the Bus Convenor. In other words, I organised the trips to the ski slopes.
One of the advantages of being the Bus Convenor was that you got a chance to look over the 'talent', so to speak, and it was during one of the trips that I decided that I kind of liked one of the girls that was along on the trip. Unfortunately, she was already spoken for, but her girlfriend and I spent that weekend together, and that was the start of the relationship that led to my selecting my wife.
Always one for compromise!
Well, it was a good compromise. I'm very glad I ended up with her.
As for the work on kidneys: what stopped you from becoming a urologist outright?
By the time I was practising as a clinician, I was keen on the clinical aspects of the work that I was doing. I really enjoyed the business of doctor-patient relationships, much more than I could have ever imagined that I would. I was never the sort of doctor that wanted to tell the patient what to do; I wanted to discuss it with them, to solve problems. But the real problem with renal medicine was then – and still is now to some extent – chronic dialysis.
When I worked in the dialysis unit, which was a necessary part of the job of being renal physician, the first person I was introduced to was the resident psychiatrist. I thought that the psychiatrist was there to help the patients, but I very rapidly worked out that their major job was actually to help the staff. I realised that looking after patients on chronic dialysis was a stressful job, and that it wasn't really something I wanted to do for the rest of my life.
In those days being a patient on chronic dialysis was challenging, there is no doubt. Remember, this was just after the epidemic of hepatitis B went through the dialysis unit, and just at the time that the epidemic of aluminium-induced dialysis dementia went through the unit, so that the patients recognised that there were lots of things happening to them that were not in their control – and weren't much in the doctors' control either. On top of that, most patients on dialysis felt lousy most of the time. It was better than being dead, but it wasn't a great life.
This was before we got some of the technologies that allowed us to control the minor metabolites that created problems for dialysis patients. One of my patients was a walking exoskeleton: his whole skin was calcified because we hadn't got his calcium balance right. Parathyroid disease was very common. And the patients just didn't feel good. Looking after patients who just didn't feel good all the time and trying to persuade them that they really felt good enough to keep going with dialysis was quite a challenge.
Fortunately, towards the end of the time that I was a renal physician, ambulatory peritoneal dialysis was introduced routinely. That made a real difference for the majority of patients. They could actually start enjoying life again.
Had transplants come to be done so much then?
Oh yes, there was a fair transplant program. But, again, then as now there were not enough kidneys. We used to sit once a month in debate on what priority we would give to various people to get transplanted, and you just knew you were talking about people's lives: 25-year-olds who basically were not going to be transplantable for one reason or another, and were sentenced to dialysis for the rest of their life.
At what must have been around that time, I used to talk to Kevin Lafferty at the John Curtin School of Medicine about the transplantation of pig kidneys. And we're still talking about it, of course!
Yes, and we do still rely heavily on cadaver donors. In those days it was thought to be unethical to do living related transplants. We simply weren't even allowed to talk about doing that, and yet now that's the major source of kidneys for the majority of patients who need a transplant.
It was thought to be too risky to expose a relative to the risk involved in being a donor, and it was thought also that the moral compulsion to do something for your relative would preclude a sensible and balanced decision as to whether you should actually give the kidney. We had to get psychiatrists involved on the one or two occasions when we actually did living related donor kidneys because there simply was no other choice for the patient – they couldn't carry on on dialysis, and it was that or die – and all of that really put a lot of strain on the medical staff.
Was it hard to turn away from those kidney patients? Did you feel guilty at all?
Well, I'd always wanted to be an immunologist, and the reason I chose renal medicine (apart from the physiology side of things) was that it had the immunology component – transplantation – built in. I saw that as a way to get into immunology at a time when, at least in Scotland, there were no training programs in clinical immunology. Consequently it wasn't that hard to make the decision to go and train properly in clinical immunology.
So you actually came to Australia to go to the Walter and Eliza Hall Institute, WEHI, where you landed on your feet.
Yes. The Walter and Eliza Hall Institute had a clinical research unit, headed by Professor Ian Mackay, which basically was a training ground for clinical immunologists.
I had previously visited it as an undergraduate. When I was training in immunology, halfway through my medical training, I did an honours year in pathology with an interest in immunology. Every second paper we read came from the Walter and Eliza Hall Institute and you could see that the talent was there, and I really wanted to be part of that. It's a measure of what the institute thought of me, though, that I wasn't thought to be up to going directly there at that time. (They had too many students wanting to come.) Instead, I spent three months working in the Department of Medicine, next door, and during the time that I was working with John Mathews in that department I also visited the institute regularly. That gave me access to the institute and the people there. So I kind of knew what was on offer at the institute, and they got to know me during that time as well.
What was the atmosphere there? Was it relaxed and friendly, or was it very serious and self-important?
It was a very good place to work in. It was small enough that you could get to know everybody. The morning tea was the social scene. Turning up for morning tea was compulsory; Gus (Sir Gustav Nossal) was watching and he would know if you were there or not. But the most important thing was that whatever you wanted to talk about in technology, science, there would be somebody around the place who knew about that or knew somebody who knew about that, so over the morning tea you solved the problems that you wanted to get on and deal with.
I was a newcomer to the game. I had done a little bit of research when I had been an undergraduate, but not very much at the bench. But the old-timers, if you like, took that as a challenge – you know, 'Let's get this guy up to speed' – rather than trying to put me down for not knowing what I was talking about, and I was really very well looked after. The fact that I was a Scot might have helped a little bit too: I might have been seen as a foreigner who didn't speak the language very well and had to be shown how to do things! [laugh] I found it a great environment to work in.
Did you manage to meet Mac Burnet [Sir Macfarlane Burnet]?
Yes, I met Sir Mac. He came up once a week for afternoon tea until he got quite frail at the end of his life. He was always willing to talk about anything with anybody. He had some ideas then that vitamin C was the solution to all the problems of ageing, and couldn't really be easily dissuaded from those ideas, but he was also quite happy to talk about immunology at any time. You could see he was still the great theoretician.
Who else was there?
Jacques Miller, Graham Mitchell, Don Metcalf were there – all people whose papers I had read. And while some of the other people whose papers I read were no longer there, I got introductions to them, for example Gordon Ada. I was always interested in immunology of infectious disease, and while that wasn't the main flavour of the institute in those days, there were plenty of people who had been through the institute who were interested in that and also knew about immunology.
When did the study of genital warts arise?
That came out of the work that was going on in the WEHI. It's a complicated story.
I started working on chronic liver disease. Ian Mackay was interested in autoimmunity, and in this case the variety of liver disease which was driven by the immune system attacking the liver. (Autoimmune chronic active hepatitis is still as much of a mystery now – at least to me – as it was then in 1980.)
After a couple of years I realised that I wasn't going to get anywhere with autoimmune chronic active hepatitis, because we just didn't have the tools available to do the work that I thought ought to be done. Remember, this was just at the beginning of an era when we knew that T cells did what T cells do, and when monoclonal antibodies were a real novelty and you basically had to sell a child into slavery to buy enough to do a few lab tests.
But the interest in autoimmune liver disease lent itself very easily to a move to thinking about chronic active hepatitis caused by hepatitis B virus infection, which I thought would be more easily understood – clearly there was a virus at the bottom of it, and the immune system was doing something and damaging the liver, and hey, there were all these small round cells in the liver which were clearly immunocytes of one sort and another. We started staining with the monoclonal antibodies and looking to see what they were, but boringly they all turned out to be the same as in every other chronic inflammatory thing. There was a mixture of suppressor cells, as we then called them, and helper cells, as we still call them, and cytotoxic T cells, which all seemed to be basically much the same, whatever the disease was. But it got me interested in why some people got hepatitis B virus infection and cleared it, and some people didn't.
That's still some way from the warts, though.
Well, to find out a bit more about why people did or didn't clear hepatitis B virus infection we started studying men who had sex with men, because a lot of them became chronically infected with that virus. Of course, this was at a time when the epidemic of HIV AIDS was starting. We didn't know yet that that was the problem, but I realised very quickly, in about 1982, that among the men in the cohort of men who had chronic hepatitis B virus infection, some clearly had a damaged immune system. And I thought that was interesting: maybe that was why they were getting persisting hepatitis B virus infection. But it was clear that this was an evolving problem. It wasn't something that had been around for a long time; it was quite new.
Then a visitor came from Boston saying, 'Oh, that's interesting. This sort of thing's going on in Boston,' and told us all about it. We realised that the immunological disorder that was being described in Boston and San Francisco was also present in Melbourne, and indeed in about a third of all the patients in my cohort from what was called the Middle Park study, the group of men who had sex with men and who had hepatitis B infection. So that was amongst all the things that we looked at, and we eventually went on and did serology, with Bob Gallo and Sam-gadharan, which showed that those men were not positive for human T-cell lymphotropic virus type I (HTLV-I) (our first attempt at picking the virus). Subsequently, however, we did the HTLV-III test and found out that the men who had the immune problem matched across to the men who had the positive test. So we realised that that was likely the cause.
But also we looked to see what the consequences of being immunosuppressed were for other problems that they might have, and one of the things that leapt out at us was that these men were having a terrible problem getting rid of genital warts.
Had anyone else considered that possibility?
It seems not. I went and looked up the textbooks to see what was known about the immunology of genital wart disease [laugh] and, well, it wasn't a very long story and it all seemed to be pretty much incorrect.
Around that time I met Gabrielle Medley, who was running the Victorian Cytology Service and was very interested a connection between papilloma virus and cervical cancer that had been described just a couple of years previously by Harald zur Hausen, in Germany. He then had put forward the hypothesis that some papilloma viruses might actually be responsible for cervical cancer, and Gabrielle Medley asked me if I would look in the men who had sex with men to see if there was an equivalent papilloma virus disease in men.
So we started looking at the cytology of the cells from the back passage, from the anus, of these men who had sex with men. And lo and behold, we found all these precancer cells there, particularly in the immunosuppressed men. That really got me interested: it said, 'Hang on a tick, now we've got some proof of a hypothesis that Mac Burnet put forward, that the immune system is involved in protecting us against cancer.' He had no evidence to support his hypothesis, because there were no cancers that were clearly more common in people with damaged immune systems than in people with healthy immune systems. But now we had a cancer that appeared to be more common, and we thought that was really interesting.
We were wrong, because the problem was not that the immune system couldn't clear the cancer. Rather, the problem was that the immune system couldn't control the chronic virus infection – which, if we had thought about it, would have been more sensibly the conclusion we'd have reached. But we didn't know enough about the natural history of papilloma virus infection in these days to come to that conclusion, so we got really excited by the idea that we had found a cancer that was more common if your immune system wasn't working. We wrote it up and sent it to the Lancet, which accepted and published it.
Later, when I decided I was going to leave WEHI, I had to make a choice about which of all the different things I was doing I was going to take with me – whether to continue to work on autoimmune liver disease or hepatitis B virus associated liver disease, or to take this newfound interest in how the immune system dealt with HPV [human papilloma virus] infection with warts. I decided the latter looked much more interesting, because there was nothing in the literature [laugh], and the one thing I did learn from Ian Mackay was to get into a field early. He used to say, 'Look, get in while it's still breaking off in chunks,' and that was basically what I decided to do with it. I would take with me the interest in papilloma virus infection.
In 1985 you took that interest in the warts to Brisbane. Why Brisbane?
Ahh, I stayed at the Walter and Eliza Hall Institute for about four and a half years while Ian Mackay was head of the clinical research unit, but when it was clear that he was getting close to retirement I well understood that when he left there would be a clearout and it was better to go before you were pushed, so I started looking round for another job. I looked at jobs in Western Australia, Boston and Cambridge and then in Brisbane, and decided that Brisbane was the best bet.
Was the arrival a shock, or was it easy?
One thing I remember about the move was that we had to come up by train and then actually drive up from Murwillumbah, because the railway stopped at the New South Wales border. I thought, 'That's interesting. I didn't realise Queensland was quite that backward' – that they hadn't heard of railways. But it was just explained to me that the gauge was different.
The thing I most remember, though, was being told that Brisbane would be warm and we wouldn't need any clothing for cold weather. We arrived in July and the house that we were staying in had no heating. It was one of those nice July mornings, the whole house was at 4° centigrade and we had three screaming, freezing kids who had thought they were coming to somewhere nice and warm but it wasn't. So that is my immediate recollection of coming to Brisbane.
Lots of nasty jokes were made about coming to Queensland from Victoria and improving the average intelligence of both states, and about what it meant to go and join the banana-benders. But it was at the end of the era of Joh [former Premier Sir Joh Bjelke-Petersen], and things were beginning to change. It was clear, at least here at the Princess Alexandra Hospital, that there was a strong culture of wanting to get medicine to move forward, however reluctantly, into the second half of the 20th century, and to get a scientific basis to medicine and clinical practice.
What was the job you got?
I was appointed as director of clinical immunology in the hospital, and I had a lectureship in the university at that time as well. I was supposed to be everything for everybody. I was to run a clinical service in the hospital and also a diagnostic pathology laboratory for Queensland pathology services, and to teach medical students medicine…
And save lives, all the same time?
Oh yes, and to do a bit of research at some point: it was, 'By the way, if you don't perform in research you'll be out of a job.' But the job was paid by the hospital, so that although I was strictly an academic – my appointment was to the University of Queensland – I was really working largely for the hospital at that time. It was quite important that I was appointed to the University of Queensland, because I wanted to be seen to be doing academic medicine. Also, however, it had a practical significance. Some comments that I made about the ability of the Queensland government to deliver an AIDS service found themselves on the front page of the Sunday Mail. So I had a phone call from the then health minister saying that I'd be out of my job by Monday. Fortunately, he didn't realise that I was working for the university and wasn't quite so easy to get rid of as that. But I have survived 17 health ministers in Queensland now.
Did you still enjoy seeing patients at that stage?
Very much so, yes. And I was quite keen to set up a new diagnostic and clinical immunology service in the hospital here. Prior to that, an immunologist (Michael Robinson) had come in as a visiting specialist from time to time, but there hadn't really been an organised clinical immunology service, nor was there a diagnostic laboratory doing the clinical immunology work. My primary task right at the very beginning when I came here was to set up a clinical immunology service, to make sure that the hospital was aware that it was there, and then to get the diagnostic lab up to speed so it was doing the work that I thought was appropriate at the time. Previously it had been spread out amongst the other divisions of pathology – which was sort of okay, but wasn't really the state of the art.
What happened to the papilloma virus interest?
Very fortunately, when I came to Brisbane I managed to come with two National Health and Medical Research Council research grants which I had applied for while I was still working at the Walter and Eliza Hall Institute, with a view to the move that was coming up. I don't think it would necessarily have happened so easily nowadays, but it meant I came with enough money to get some research assistance off the ground. Also, the Lions Kidney and Medical Research Foundation, as it then was (funded by the Lions Clubs of Queensland and northern New South Wales), gave me money for a fellowship. I was able to appoint a research fellow pretty much within a month or two of my arriving here, and so to get a research group off the ground fairly rapidly. And while none of them particularly wanted to work on papilloma virus, I suppose I pulled rank. I encouraged them: 'Look, by all means carry on your own interests, but at the same time we're going to work on papilloma virus too.'
You had been looking at the papilloma virus in men. How did you begin looking further at the virus in women?
Well, what I wanted to do initially was just to understand how the immune system 'saw' human papilloma virus infection, because there was nothing useful in the literature at all about that. There were a couple of papers, obviously wrong, which predated the realisation that there were lots of different human papilloma viruses – they were written in an era when it was thought there was only one, causing warts.
There are about 30 of those viruses, aren't there?
Oh, about 200, and then a whole heap more that we just really don't know how to number, because they haven't been sequenced. But when it was thought there were about 30 I decided that what we should do first of all was to build up a set of reagents to actually look at the immune response to papilloma virus. After I'd gone to a few international papilloma virus meetings it was clear that, really, nobody apart from Margaret Stanley, in Cambridge, was working on papilloma virus immunology at that time. So I met up – in the bar, as I was wont to do in those days – with Margaret Stanley at a couple of papilloma virus meetings, and we talked through what was known and what wasn't known, basically working out what would be worth doing.
Then I got hold of some reagents from Lutz Gissman, in Germany, who was working on the mechanisms by which these viruses cause cancer, and started to use those to explore how the immune system might see the virus. We did a lot of work in mice and some in humans. I recruited Dr Robert Tindle from the UK, and he helped make some monoclonal antibodies that were able to react against the viral proteins so we could start to find out what was happening.
Initially we were just collecting the tools that you needed to do the work. My aim eventually was to look at the immune response in patients infected with the virus, to see if we could understand how people got rid of it, but I rapidly came to the conclusion that we really didn't know enough about the natural history of the disease. Nobody knew how long you got the virus for: was it a quick infection that most people got rid of? And how common was it? Nobody knew that either. Indeed, it wasn't until the mid-'90s that we developed the model we now have, that these infections are extraordinarily common – most people get them, most people take a couple of years to get rid of them, without knowing they've had them – and it's only a few people that get persisting infection and get into trouble. In those days we thought the infections were pretty rare; everybody got into trouble. And we didn't realise why the immune system couldn't control the infection.
I decided that we needed to get better reagents for working in humans rather than continuing the mouse work that we had been doing up till then, because the laboratory mouse and rat really don't get papilloma virus infection. They know what's good for them! So that drove me to do a sabbatical in Cambridge, in 1989, because I wanted to learn enough molecular biology that I could start to make reagents by deliberately producing human cells transfected with these viruses. I went to work with Martin Evans, who was working in those days on embryonic stem cells – for which he more recently got the Nobel Prize.
How did you find the environment in Cambridge?
It was quite an eye-opener for me, because here was Martin Evans working in Cambridge (in what was supposed to be the centre of a field of embryonal stem cell research) on the open bench, doing cell culture between two Bunsen burners. Even we were using fume hoods in those days to keep the cells clean. And he was just doing very basic stuff; he was making his own glassware. He quite rightly deserves the Nobel Prize, considering he did all his work on embryonal stem cells in that sort of environment and with virtually no resources.
I wanted to learn specifically how to make cells express these virus proteins, which is why I decided to go and work with Martin Evans. But because Martin was, at least in my mind, unapproachable – I felt that being a guru in the field he wasn't going to be interested in some poor hick coming from Brisbane to do the work – I decided to do the actual work for the sabbatical with Margaret Stanley, whom I'd been working with for several years by that time, at least by proxy. And so I took a place in her lab for six months in 1989. The aim was to make use of the expertise in molecular biology in Martin Evans' lab, which I did, and also in Lionel Crawford's lab, which was next door to Margaret Stanley's in Tennis Court Road, Cambridge.
Lionel probably wasn't too interested in having me around, because I was spending his money and using his bench space, but in Lionel's lab were a number of really good postdocs, people who are still good friends of mine – for example, John Doorbar and Alan Shaw – and who were working on papilloma virus infection. They were basically people who were doing the molecular biology of papilloma virus, so I just spent my time in their lab and was learning from them how to do all this stuff.
I wanted to get two things out of it. First, could I make cells expressing papilloma virus proteins from human cells? We managed to do that, and I was really pleased and brought that technology back to Brisbane. And the second thing I wanted to do was to make a mouse transgenic for papilloma virus proteins, so we could actually start exploring the immunology in the mouse. I failed completely to achieve that, because I didn't realise just how bad these proteins were for cells. They killed the cells very effectively. I couldn't understand why all my controls kept working perfectly but none of the experiments ever did. In retrospect, it's easy to see why, and I just wasn't bright enough at the time.
Aren't failures useful!
They always are – in retrospect. At the time they're merely a reason to curse. But basically I learned the tools of molecular biology over that six months, and how to use those tools to work with mammalian cells. Remember, this was in an era when most molecular biology was still being done in bacteria, and to move into mammalian cell culture at that time was very exciting for me. Also, it was fairly groundbreaking stuff. So that gave me a great head start when we started doing what we were going to do.
The other thing – perhaps the most important thing – that happened in Cambridge was that I met the late Dr Jian Zhou there, because he was also one of the team working in Lionel Crawford's lab. He was a visitor from China who had come as a graduate physician like myself, with an interest in papilloma virus like myself. He was the technologist; he was really good at working with gene cloning and gene expression. So if there was any gene cloning problem that I couldn't do, or indeed that anybody else in Lionel's lab couldn't do, we went always to Jian. And Jian could do it.
Did you click straight away?
I think we did. Jian, like myself, was on sabbatical, and therefore we tended to be in there doing things out of hours: nights, weekends. I had a limited time and I wanted to get a certain number of things done. Whenever I was there in the evening, Jian was there in the evening – and most of the other people were down at the pub. That meant we naturally hit it off, in the sense that we were around and trying to solve similar problems. He was interested in immunology and wanted to learn immunology, which I could help him with, and I wanted to learn molecular biology, which he was very good at. The two of us got on very well, because we were exchanging ideas all the time.
Did you bring him back to Brisbane?
Yes. I really wanted him to come back to Brisbane and work in my lab, and he really wanted to come, but it wasn't that easy. He finished up his time with Lionel Crawford, but he had to get a visa to come to Australia and that wasn't easy for a Chinese national in those days – he was there with his wife, but his son was in China still, with his wife's mother, and it was not easy to get all that fixed up. He was offered a job by CSIRO during the time I was trying to get him to come to work with me in Brisbane, but he really didn't want to go to them because they wanted him to work on something which wasn't of particular interest to him. Fortunately, he stuck it out and waited till I could get him a visa so that he could come and work on what he wanted to work on, papilloma viruses, and he came out about six months after I returned from sabbatical.
When did it occur to you both that a vaccine was possible?
Well, we set out to build reagents to work on the immune response and perhaps also on a vaccine, because even before I went to Cambridge I'd already been working on trying to get a vaccine to treat papilloma virus infection. We wanted to actually build the papilloma virus itself. We knew we couldn't grow it in the lab (other people had tried and failed) and we pretty much thought we knew why – although we were actually wrong about that too. We had the wrong reason. Anyway, it was clear that it wasn't going to work.
So what Jian set out to do, with my encouragement, was to try to make an infectious papilloma virus. And in due course, after about three years, he did that. But as part of that we really wanted to make the shell of the virus. We thought that that would be quite hard, but it turned out to be even harder than we imagined. Jian, however, had the ability to express viral genes using vaccinia virus, and that turned out to be a great asset, because of all the expression systems that we might have tried to do that work, only vaccinia worked. If we'd tried any of the other common expression vectors that people were playing around with at that time, it would have failed – for a whole range of reasons which Jian subsequently went on to discover and map out over the course of the six or eight years that he worked with me, and then in collaboration with me when he went overseas.
Vaccinia virus worked, and we made progress once we'd twigged to the fact that we needed to start expressing the viral gene from a start point different from the one that was self-evident from the sequence of the virus. I can remember actually writing the sequence out on bits of paper! Nowadays you'd get a computer to do it, but in the lab in those days we had an Amstrad which we cursed at because it never worked and we couldn't get it to do anything. So we worked on the sequence manually and decided that maybe the right place to start the gene expression from was the bit downstream of the initial start codon. Then Jian had the idea that if we put in the L2 capsid protein at the same time as the L1 capsid protein, maybe that would lead to better expression of L1 and it might form a virus-like particle. All that turned out to be true and it did, and in about March 1991 we eventually got this picture of the virus-like particle, the 'skin' of the virus.
The really interesting thing was not expressing the L1 protein – I had managed to do that, others had managed to do that, Jian managed to do that, and we all got the same result: we got the protein but it didn't assemble itself. What Jian managed to do with the various tricks that we put together was to get the L1 protein to assemble itself to make the shell of the virus.
Was this shell capable of looking at the 'universal' virus? We have hundreds of them to consider, so how do you narrow it down to get a vaccine that knocks them all off?
Well, we don't get a vaccine from that which knocks them all off. What we got was a vaccine. When we saw the shell, we knew we had the potential to make a vaccine, because I was aware that vaccines, to work, had to mimic the shape – not the protein sequence but the physical shape – of the virus. So as soon as we got something that looked like the virus, we were pretty sure that could be the basis of a vaccine. We didn't know it would work, but what we did know was that if there was going to be a vaccine, that would be how it would be made. (We couldn't make a vaccine by the conventional means, because if you can't grow the virus you can't make an attenuated virus, and neither can you make a killed virus.)
So we started with the tough one, HPV 16, the virus which is most associated with cervical cancer. In retrospect, we could have made life an awful lot easier for ourselves by starting with one of the other types, but because that was the one most associated with the cancer we thought we had better start with it. What we didn't realise was that HPV 16 was not very good at assembling itself. It still isn't. What we also didn't realise was that there was a mistake in the clone of the virus that was being routinely used in the lab for HPV 16. But fortunately Jian had decided in Cambridge that it would be better to start from scratch, rather than using the then circulating clone, to reclone the viral gene. We had to make the shortened version anyway that we wanted, a version that wasn't the whole length of the gene. So, actually, Jian used the technique called polymerase chain reaction to reclone the viral gene.
In those days, doing polymerase chain reaction over 1600 base pairs was, in effect, like climbing Everest – a very big task. People were thinking they were doing pretty well if they were getting 200 base pairs cloned, and he managed to get 1600.
Kary Mullis got the Nobel Prize for inventing that, didn't he?
That's right. It was a very exciting technology. Fortunately, all these technologies came together at the right place at the right time.
It was Jian's ability to get this gene cloned by putting it into the vaccinia virus that eventually led to the potential for making a vaccine. If we'd used another virus type it would have been quicker, but we wouldn't have had the right virus. We really needed HPV 16. That was the tough one. When we got 16, we knew all the others would follow, and indeed they did. We did some of them and other people did others of them, and basically we got a collection of different viruses cloned.
We also switched expression systems, because by the time we finished cloning HPV 16 in 1991 a new expression system had come along – in insect cells – which wasn't around when we started doing the work in 1990. We rapidly went on to express other types using that one, which turned out to be a good move because that was one of the bases of how the vaccine is now made.
That all came together over the course of about a year after Jian came out to the lab in Brisbane. And, as they say, the rest is history, because at that point the technology, the science bit, had been done and it wasn't so much a case of technology as just a few proof of principle experiments to show that these virus-like particles were immunologically interesting and made an immune response which looked like the virus's immune response. We did those very quickly in animals and showed that it worked. Then we handed it on to the companies and said, 'If you're going to have a vaccine this will be where it comes from.'
You've always been tremendously generous to Jian. How do you feel about that episode of the work together and his surprising death?
Well, Jian stayed working in our lab for about three and a half years after he came out to Australia, and then he went off to work with Lutz Gissman, who by that time was in Loyola University, Chicago. I visited him there a couple of times. He quite enjoyed working in Chicago but he didn't like the weather there very much, and also he recognised that he would get more independence if he came back to Australia. So he came back into the institute in 1996, and worked as head of his own research group for about three years.
He had had no particular health problems during that time, although he mentioned to me that from time to time he hadn't been feeling particularly well. But in the start of 1999, when I met up with him in a conference in South Carolina, he didn't look particularly well and he said he was feeling very tired. After the conference he went back to Brisbane, and when I got back to Brisbane a couple of weeks later it was obvious that he really wasn't very well, and he was tired and unable to work.
It was the time of year when you write grant applications, so he went home to do that. Most of us didn't see him from then on but he kept in touch with us by phone and by email. I arranged for him to go and see one of my medical colleagues to get some advice, but I never found out just what the result of that transaction was. (Really, I was only brokering it, if you like.) The next thing I heard, about a month later, he'd gone off to seek medical advice in China and to 'get a bit of a rest', as he put it. Three days later we got a phone call to say he was seriously ill in hospital – and the next day he was dead. So we don't know exactly what happened. He had had a number of minor chronic health problems, as Chinese people often do, some of which may have contributed to his demise, but even his wife Xiao-Yi doesn't know exactly what the cause of death was.
It was all very sudden, and obviously very upsetting for everybody in the institute. Jian had become a very popular scientist. He was generous in everything that he did – in his friendships and in his science – and had formed good working relationships with everybody within the institute, so that he was very much missed. Nobody could believe that that happened.
To return to the vaccine: huge numbers of women are susceptible to the virus and very large numbers die.
Yes. Cervical cancer is caused by a group of the human papilloma viruses. The cancer itself affects about half a million people every year worldwide, and half of them die. The infection is extraordinarily common. You've got one chance in three that you'll get it in your lifetime, if you're sexually active. The vast majority of people have it but never even realise it's there, and then they just get rid of it. But during the time they've got it they're infectious for other people and they pass it on, which is why this is such a successful virus. On average you have it for about two years. You get it, you've got it for two years, you don't know you've got it, you're infectious all the time during those two years, and mostly you just clear it, without ever knowing you've had it. But 2 per cent of people go on to get persisting infection which can then lead to cancer.
Those who are going to receive the vaccine need to receive it when they're quite young, presumably. For people who have got the infection it's too late, is it?
It is. The vaccine can only prevent infection with human papilloma virus. It can't cure you if you've already got it. We recommend that the vaccine is given to 12-year-olds in this country, largely because a significant number of people become sexually active from 14 onwards. And while it's true that you won't get the virus the first day you become sexually active, you don't know when you are going to get it, and once you've got it the vaccine doesn't make any difference. If you're going to get rid of the infection, you'll get rid of it anyway; if you weren't going to get rid of it, the vaccine isn't going to help. So it's really important to get the vaccine before you become sexually active.
Indeed, that's a big challenge worldwide. In Australia we reckon 12 is the right age; if you were in south east Asia, nine would be safer. And persuading people to take this vaccine is partly one of coming to terms with the fact that you're going to be sexually active some time. Parents never like to think their children will be sexually active, although the human race depends on it! That has created some problems in getting acceptance of giving this vaccine to younger people.
How serious has that been? The times of Joh Bjelke-Petersen in Queensland are over, but nonetheless there has been resistance around the world, with suggestions that you're a new person advocating permissiveness. How'd you cope with that?
Well, it surprises me a little that the [United States] Bush administration still promote the idea that celibacy is the best way to prevent sexually transmitted diseases. That is manifestly unsuccessful as a strategy, and just not in tune with the fact that people experiment sexually from a fairly early age. Probably the right comment on the idea of the vaccine promoting promiscuity was the one that was made by a correspondent for the New York Times, who wrote that ever since he had been vaccinated against tetanus, he really felt obliged to jump on every rusty nail he could find, simply to prove the vaccine was working.
I think that there is no connection between immunisation and human sexuality at all, but clearly it is important to get the message out there that this is a vaccine to be given before you're sexually active, and that vaccines and viruses do not discriminate according to your degree of promiscuity. This is such a common virus that you do not need to be in any sense of the word promiscuous to get it. One partner is quite enough to give you the virus.
We've talked mainly about Australia. What has the effect been in other countries?
Australia has led the world, let's be quite honest, in rolling out this vaccine program. We were very fortunate that our government chose early on to adopt a strategy of universal immunisation of young schoolgirls. I think they should be given a big tick for doing that. I think that it would have been – in the Sir Humphrey Appleby expression – a 'courageous decision', but that it was the right one.
How many of Australia's young women are now vaccinated?
A year and a bit into the vaccine program, about 80 per cent of schoolgirls have received at least two of the three shots. Obviously, we'd like to get that up to all three shots, but the coverage has been remarkably good and the vaccine has been taken up very quickly.
Worldwide the vaccine is licensed in over 80 countries now, and in Europe it is being used in programs similar to the one that was started in Australia last year. They're running about a year behind us. In the United States the uptake has been a bit more patchy. Some states have gone for 'mandatory' immunisation of schoolgirls. They don't really mean it is compulsory; what they mean is that it will be compulsory for the government to pay for it, so that it makes sure that everybody gets immunised. Other states have been more reluctant. And outside of what I guess you'd call the developed world, vaccine uptake has been (as you would expect) rather patchy. Some notable countries, including China and Japan, have not yet even licensed the vaccine.
Having found how a vaccine could be made, you would have had to file for a patent, to establish intellectual property, IP. But a slight dispute arose with the University of Rochester over priority and so on. What is the situation now?
Fortunately, that's all resolved now. In the United States, the way that the patent laws work, the American patents get looked at before the ones from overseas. There were in fact a number of patents filed in the United States with priority dates later than our priority date for the filing of the patent that we took out in April of 1991, and those patents were granted in the United States because they were examined first. Then when ours came up a thing called an 'interference' was filed, basically saying, 'Well, we don't really know who invented it first, so we're going to have to take it to court to find out.'
From the point of view of vaccine development that didn't really make any difference at all – the vaccine companies went on with the development program for the vaccine. And the whole thing was resolved in the courts over the period 2005–07. The end outcome, as it happens, was that our patent was granted as dominant in pretty much every jurisdiction in the world, including the United States. There are dependent patents that other people have for particular sequences of particular virus types, but the idea of making virus-like particles and a vaccine for cervical cancer based on those was, I think correctly, assigned to us.
Obviously, you don't want to claim that you did it first if you don't think you did. But I really think we taught people how to do it, because Jian and I went off to a meeting in September 1991 and published a paper in October 1991, on both occasions clearly disclosing what we'd done, how we did it and how other people could do it based on what we'd done. From talking with the people who went on and did it after that, who were involved in the patents – and who happened to be reasonably close friends – I think probably we were the ones that did it first.
What were the companies like to work with in the actual preparation of the vaccine?
Well, initially we worked through CSL with Merck, because we originally 'handed on' the right to use the patents to CSL and then to Merck. A large part of that work in the 1990s was just trying to understand a bit better about how papilloma virus was involved in cervical cancer – not that it caused the disease (we knew that already) but rather who got the infection, how common it was, what happened after you got the infection, how long it took to cause the cancer, all these questions which were really unanswered in 1990 but became clear through the work, mostly funded by the vaccine companies, that was done in the 1990s. CSL themselves didn't do too much, but Merck and subsequently GSK [Glaxo Smith Kline], the other company that has developed the vaccine, did large epidemiological studies so they could understand where a vaccine would fit into the natural history of the disease.
Working with the companies about all of that was really very interesting. Clearly, I was one of many people giving them advice, and quite often they were advising us rather than us them, but it was a way we learned about what the virus was all about.
What about the application for other areas – not simply for other manifestations of the virus, because presumably men might also be affected, but with other vaccines?
The vaccine isn't just a vaccine to prevent cervical cancer. And it can only prevent 70 per cent of cervical cancer as it's currently construed, because it has in it only two virus types that are responsible for about 70 per cent of the cancers. The next-generation vaccine, hopefully, will have more types in it and be able to get up to 95 per cent or maybe even 98 per cent of cervical cancer prevented.
But cervical cancer is only half of the burden of cancers caused by these viruses worldwide. Men and women equally can get cancer of the inside of the throat from these viruses, and also other cancers in the genital region. And it's possible that quite a large part of skin cancer is also caused by these viruses, and a few other cancers as well. There the evidence isn't quite so clear, and it'll take a little bit longer to work it out.
These viruses are bad news generally, and you don't want to have them if you can avoid them. So the vaccine should be able to prevent a whole slew of other diseases apart from cervical cancer. I'll just not live long enough to find the answer to that. You get these infections in your 20s, and most of the other cancers you're getting in the 50s and 60s, and so even if we immunise universally – and we've certainly not achieved that yet – it will be 40 years before we find out if the vaccines have really worked to prevent all these other cancer types.
What about work now? What about the prospects of curing the disease where it can't be prevented in the first place?
Our research work at the moment is focused on two areas. One is working out strategies for delivering the vaccine in the developing world, and the other one remains focused very heavily on developing immunotherapeutics to cure people already infected with the virus. Out there at the moment there are 20 million women who are already infected with the virus. They are the unlucky ones, who are going to go on over the next 20 years to develop cancer. It would be really nice to have something we could give to them in the way of a vaccine to prevent that from happening, because we can't screen for cervical cancer in the developing world in the way that we do through the pap smear program in Australia.
In the lab we are working on immunotherapeutics, and I have to say I am very encouraged that we're getting some much better results now than we were 10 or 15 years ago. In those days I thought it would be easy, and I was wrong – as I usually am in science [laugh] but that's how you learn. And what we've learned is that the real problem is not with the vaccines. We can get the right sort of immune responses with the vaccines, something to kill an infected cell. But, for some reason or other, the immune cells that we induce won't go and do the job in a real person in the way that they will in the lab.
We have learned that in principle that's because the local environment, where the virus is, instructs the immune system to ignore it. This seems to be a universal problem for immunotherapeutics, not just for papilloma virus infection but for other viruses, and also for cancer cells where there are proteins expressed which the immune system could be interested in. Basically, the immune system has a default 'off' position – in other words, it doesn't do anything unless it's specifically instructed to do it. So the vaccines make the right sort of response, but they don't go out and do anything.
So what we've been learning is strategies for overcoming that problem, and at least now in the animal models we can overcome it. We know what we need to do to get past this, and the nice thing is we could actually do it in a patient as well.
Even the men?
Yes, even the men. There are strategies which could be used in real people to do what we're doing in animals. A lot of the time you do something in a mouse and say, 'Well, you could never do that in a human.' But for these things we actually could do it in a human, so we're hoping to go into clinical trials with that next year.
The vaccine works. It has been a success. And you got all these prizes – the Florey Prize, the Eureka Prize, Australian of the Year et cetera. Were you slightly embarrassed by that? How did you cope with it?
Well, 'slightly embarrassed' is somewhat of an understatement. I was grossly embarrassed. I mean, Jian and I did a bit of the process of developing the vaccine, back in 1991. Sure it was an important bit, but if we hadn't done it, someone else would certainly have done it, and we would have got to a vaccine.
It's nice to get the recognition for science. I think it's very important to show the community at large that science contributes to society. I just felt embarrassed that it had to be me that was in the spotlight.
I didn't waste the opportunity. I'll be quite honest: I saw that as a great opportunity to go and promote science to politicians and the general public alike – and to promote some of my own more direct interests, like the building of a new research institute here. I was keen to show Australia that if we really wanted to get the benefit of the science that we were doing, then it was important to be able to translate it into practice here.
And while I'm delighted that we have got a vaccine, it bothers me slightly that it had to go to Merck and GSK in the United States to be made. We could have done that here if we'd had the appropriate facilities, and I think it's a great shame that we have to give our IP away to other people when in fact we could have done the work here.
Has anyone back in Edinburgh noted the fact that you are now famous, indeed the Australian of the Year, and do they send you up?
Yes, you get a bit of a ribbing for that. I managed to make it into the British edition of the Reader's Digest, so fame has arrived at last. But the Perthshire Advertiser I think had the right line about that. When I became Australian of the Year, the headline read, 'Perthshire woman's husband acknowledged in Australia.' That was my wife they were talking about – she was born in Perthshire.
You mentioned your father, living in Noosa. I believe your mother also is still alive. What do they think of young Ian?
Ahh well, when asked about what it was like to have a clever son, my mother's response was the correct one: 'All of my children are clever.' In other words, I'm not any different from the other two – which is fine as far as I'm concerned. Look, they've dined out on this, they became celebrities in their own right in Noosa, for sure, and indeed they are the ones that tell me about all the times I appear on television and where I've been and what they've read, because they scan the literature for me! (I don't have time to do that sort of thing.)
But I do think they are a little bemused by it all. They really enjoyed my becoming Australian of the Year – they got to go to all the best parties without having to get up and give the talks afterwards – but they clearly thought it was really quite something for someone who'd come from Scotland originally and was in their eyes 'just a scientist'.
Professor Ian Frazer, thank you very much indeed.
Thank you. It's been a great pleasure talking with you.
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