Professor David de Kretser, reproductive biologist and endocrinologist

Professor David de Kretser. Interview sponsored by The University of Melbourne.

David de Kretser was born in Sri Lanka on the 27th of April 1939. He immigrated to Australia with his parents and brother in 1949. de Kretser was educated at Camberwell Grammar School and completed his university studies at the University of Melbourne (M.B.,B.S., 1962) and Monash University (M.D., 1969). de Kretser’s M.D. research was focused on the structure and function of the human testis. He began working as a demonstrator, then a lecturer, in Monash’s department of anatomy in 1965, before moving to Seattle, USA as a senior fellow of endocrinology at the University of Washington (1969-71). On his return to Australia de Kretser again worked in Monash’s department of anatomy as a senior lecturer (1971-75), reader (1976-78) and professor and chairman (1978-91). In 1991 he became the director for the Institute of Reproduction and Development, Monash University. de Kretser has published over 430 papers on male infertility, endocrinology and andrology and founded the educational information program, Andrology Australia. In 2006 he took up the appointment of Governor of Victoria.

Teachers' notes to accompany this transcript.
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Interviewed by Sir Gustav Nossal in 2008.

Contents


From Sri Lanka to Melbourne

This meeting is taking place in Victoria’s magnificent Government House, for the very simple reason that my interviewee just happens to be Governor of the State of Victoria. How wonderful, David, that you could spare the time to come and be interviewed.

I’m delighted to be able to do it.

I suppose we should begin at the beginning. Would you tell us a little bit about your early life?

I was born in Sri Lanka and lived there for the first nine years of my life, and migrated here in 1949 with my family. Basically, my father had decided that once independence occurred in Sri Lanka, in 1948, things would go downhill – the language would change from English to Singhalese and there was a possibility of racial strife. People thought he was crazy, but he was proven right and consequently he left behind not only his law practice but also his mother, who had had a stroke and was paralysed. So it was quite a decision for him to bring us all over here.

How many of you came over?

It was just my mother and my father, and my brother and myself: a family of four.

Where did you establish yourselves in Melbourne?

We stayed initially in a boarding house in St Kilda, having been met on Station Pier by a very distant friend of a grand-uncle of my father’s, a wee Irish lady called Lily Turner. But about two weeks after we got to Australia I caught pneumonia, and that galvanised her into action. She insisted that we would come to live with her in her Hawthorn house – which we did for a period of three months.

I’m wondering whether being a migrant had any influence on your early life in Australia.

Perhaps it did. I recognise now, in retrospect, what a major decision my father had to make, and that to some extent it must have been simply to give my brother and myself a better chance, a better education, and I think that might have influenced me to keep my nose to the grindstone. But, really, that wasn’t too difficult for me. I quite enjoyed schooling and academic life.

Tell us about your school life. Were there any individual teachers who might have had a particular influence on you?

I enrolled at Deepdene state school for fifth grade and sixth grade, and then went on to Camberwell Grammar. I must say that I look fondly on the year-and-a-half that I spent in the state school. It was a very interesting experience trying to assimilate as a migrant and to get used to a different culture and different games – although I had played cricket a lot in Sri Lanka and continued to do that here. A Ms Corbett was our sixth grade teacher. She was a tough lady but she gave us an important fundamental education in mathematics and English. I think that was extraordinarily helpful.

Camberwell Grammar was a very small school at the time when I went there. Those being postwar years, the quality of the teachers varied quite a lot. Some were fantastic. In particular, in form 1, where boys came together from different places, there was a man called Stan Brown who was a wonderful enthusiast. My nickname, by the way, was ‘Blondie’ because I had black hair and somewhat darker skin! (For me that was an introduction to typical Australian humour.) So I had a unique opportunity to get to know kids from a vast different array of backgrounds.

Some teachers later on in secondary school were perhaps not as good. For example, the lass who was my chemistry teacher in years 11 and 12 equivalent was an enthusiastic person but not a very good teacher. But the thing that that did, actually, was to teach me how to self-learn. That was an extraordinarily valuable lesson for me, especially for going on to university.

Also there was an interesting challenge, because I found that I quite liked biology but Camberwell Grammar didn’t teach biology. So in year 11 one of the teachers, a Viennese-educated linguistics and science teacher, actually tutored me after hours in biology for the Leaving. And then, in the HSC or matriculation year, because Camberwell Grammar still didn’t teach biology, I went down to Camberwell Girls Grammar – and the girls came up and did physics and chemistry with us. It was one way that small schools at that stage dealt with the real issue of the lack of skilled teachers.

It is amazing that as recently as one generation ago biology was thought of as a girl’s subject and the real ‘tough’ subjects were physics and chem. How things have changed.

Absolutely. And we had a wonderful teacher, Joe Perjes, who had migrated here at the time of the Hungarian Revolution and taught maths and physics at Camberwell Grammar for about 40 years. He was a marvellously enthusiastic guy – again he was not all that conversant with English, but his heart was in it. We had a lot of fun, and he taught us a lot.

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Medical studies

I get the general impression that you might have been pretty good at physics, chem, maths and biology. When did you get the first inkling that perhaps you might want to do medicine?

It is interesting that probably, at year 11, I was thinking more about engineering – aeronautical engineering. But maybe the course in biology convinced me that medicine could be a good thing to do. Although I had a distant uncle who was a doctor, I didn’t really have any role models; it just seemed the right thing to do.

That was a good few years ago. Was it as tough to get into med as it is for the youngsters today?

[laugh] Well, when I started at Melbourne University that was the first year of a new quota system. Interestingly, in the year previously 200 or 300 people had started first year but a whole lot of them failed. And because there were no regulations they actually got automatic entry. So out of an entry of 200, only 120 new people started. It was competitive.

I imagine you would have been a pretty good student.

I was okay. I did okay in the HSC or matriculation year, but I certainly wasn’t Dux of Camberwell Grammar. Nevertheless, I finished reasonably well.

What can you tell us about your university years and the medical course?

Oh, I really enjoyed the medical course. To me it was a great introduction into the basic sciences, as medicine was in those days: you did three years of basic sciences before heading into the clinical area. And you had some formidable people there. Pansy Wright I can still remember to this day as being in the first lecture. He had the habit of stopping in the middle of his lecture, and he pointed directly at me with his very big long pointer and asked his first question, ‘What’s the derivation of the word “journal”?’ That came totally out of left field, in an early physiology lecture. It was quite striking! (Fortunately, having done some French, I was able to give him that derivation.)

Excellent. Having done medicine in Sydney, I know Pansy’s teaching only by reputation. It is said that he was a great teacher for those who wanted to learn and wanted to do a bit more, and not a very good teacher for those who were expecting to be spoonfed.

Absolutely. The notes you got from his lectures didn’t make a lot of sense until you actually sat down and thought about the topic, and went away and looked at the text and so on. But he was a great teacher. And I can still remember Jack Legge, a biochemistry lecturer there, coming in and shouting out in the lecture, ‘They’ve done it! They’ve actually identified how DNA works!’ It was an exciting time.

Does anyone stand out as a teacher in your clinical years?

In my clinical years I benefited from a range of people. I trained at Prince Henry’s Hospital, which was one of the smaller clinical schools, and that was fantastic. There was, for some reason, an intention to move away from the Royal Melbourne Hospital, and some of the brightest students in our year went down to Prince Henry’s, with a cohort of around 25 to 30 students. That was a great group of people to work with and, because this was a new teaching hospital, the tutors and the clinicians were extraordinarily keen to do well and nurtured us. We used to have lots of extra tutorials and things like that from some of the senior medical staff. They were extremely helpful.

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Moving into endocrinology, not surgery

You got through med and then, presumably, like most of us you did your residency training?

Yes. I was going to be a surgeon, so I did two years of residency at Prince Henry’s. In my second year I did surgical rotations, and then I headed out, as people did in those days, to teach anatomy for a year and to improve my basic science knowledge even further, before coming back as a demonstrator and then taking up surgery to continue towards a qualification in that.

So what happened? Why aren’t you Victoria’s top neurosurgeon or, say, top orthopod?

Well, Monash University, where I did my demonstratorship, was a new university and Graeme Schofield, who was the Professor of Anatomy at that time, was a very persuasive person. He said, ‘Look, if you have enjoyed the year, how about staying on? I’ll give you a lectureship. You can do a degree by thesis and then go back and finish your surgical training.’

Actually, I enjoyed the year at the university – it was some respite from the 80 hours of first and second year. Also, at that stage we had our first child, after getting married pretty much straight after graduation, and there was the opportunity just to enjoy family life a little bit more. So I stayed on and, basically, started looking for a project.

That was where fate again intervened, in that I happened to meet Pincus Taft. He was an endocrinologist who was about to start treating men who had infertility with pituitary hormones which had been recently purified – actually, from human pituitary glands. He wanted to get somebody involved in helping him look at the research side of this trial, and because I had quite liked endocrinology in my physiological and also in medical training, I thought that would be a good idea for me. The idea was that we would treat these men with gonadotrophins and then look at their testes under the electron microscope, which was a new tool.

Schofield was very good at electron microscopy, wasn’t he?

Yes, he was. He was a good biologist and certainly had a department that was quite well equipped for that. So that was really where it all started off and where my surgical career went off the rails. [laugh]

Would you consider both Graeme and Pincus as early mentors in that regard?

Oh yes. Graeme was my notional supervisor for an MD thesis, which really didn’t need supervision. But Pincus was the person who actually taught me endocrinology. Beyond that, he taught me how to communicate with people in complex areas by using simple terminology – just for pleasure I used to sit with him in the infertility clinic at the Royal Women’s Hospital, which was where we recruited the men for these studies, and he would be managing their infertility. He was a great communicator.

Another fabled character from those early Monash days was Joe Bornstein. Did you have a lot to do with him?

Not a vast amount. Joe had taught me in biochemistry as well and, you know, I can remember in a viva [examination] for honours in biochemistry, where Joe was one of the examiners and asked some pretty curly questions – as he could, in a very quiet way. He was a great person in biochemistry at Monash.

I must say one of my best mates from those days, the redoubtable Hugh Dudley, would probably have persuaded me to become a surgeon. But by the time you got into full swing you’d signed off on surgery.

Yes. I found the project very, very interesting. At that stage I met Bryan Hudson and also Henry Burger, who had just come back from a period at NIH [National Institutes of Health] and he and I had started to work through the issues of what controlled testicular function, in addition to using electron microscopy, which was a wonderful tool to look at how a round cell became converted into a sperm with a tail and its sperm head – you know, areas of biology that still remain fascinating. Probably one of the most complex events in terms of cell biology is the reorganisation of that cell, and that still fascinates me. I don’t think we have all the answers yet.

But the project also got me into endocrinology at the grassroots level, where we were talking about using hormones from the pituitary. Nobody yet knew how they worked, and the general view was that we needed to find some sensors or receptors. We did some very fundamental work using labelled gonadotrophins and produced some of the first evidence that there were in fact specific receptors in the testis for the gonadotrophins.

That’s interesting because I associate the receptorology at Prince Henry’s Institute [for Medical Research] mainly with [John] Funder. Am I right or wrong?

Oh, no. The gonadotrophins actually preceded Funder. He was more interested in steroid hormone receptors. But it was an interesting time at Prince Henry’s Institute. It was very new, with people like Hugh Niall, Kevin Catt and Henry Burger, as well as Jack Martin at St Vincent’s Institute. I did some interesting work with Jack and also with Kevin and Henry on labelling parathyroid hormone and labelling gonadotrophins, showing that they bound by autoradiography to very specific cell types.

So maybe you were the first to introduce autoradiography as a tool in finding those receptors on specific cells?

Certainly. Yes, absolutely. That was work which I carried on partly when I went to the United States after completing my MD thesis.

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Fruitful experience overseas

Having done your MD on these endocrinology and receptor related things, you zoomed off to the United States. What did you do there? Where did you go?

I went to Seattle, to the University of Washington. To work there was a fascinating journey for me, because I went to my first international meeting, an endocrine meeting in Mexico City.

I have mentioned Bryan Hudson, who was Professor of Medicine at Monash and a very good friend of Graeme Schofield’s. He was a mentor of mine and took it upon himself to guide me towards a mentor in the US. There were two people in Seattle with whom I could have worked, Carl Heller and Al Paulsen. They had worked together but had fallen out – but I didn’t know any of this history at all.

In Mexico City I met up with Al Paulsen, as had been agreed, because Bryan had suggested that he would be the most appropriate person. But Carl Heller found out that I was there and looking for a job, and he said, ‘Oh, why don’t you come and have dinner with me?’ Well, after Mexico I was to go up to Seattle to actually look at the labs and all that, and so I said, ‘I’ll come along and have a look at what you have to offer.’ It was arranged, then, that in Seattle I would meet Al Paulsen at the hotel for breakfast, after having dinner with Carl Heller the night before.

Now, I didn’t know the geography of Seattle. And Carl Heller lived on an island. Well, I caught the ferry over and had dinner with him. When the time came to get the last ferry back I said, ‘I need to be going to catch this ferry.’ He refused to drive me to the ferry, because he knew I was meeting with Al Paulsen the next morning for breakfast. [laugh]

You were being rather dishonestly wooed?

I was being kidnapped, you could almost say. Fortunately his wife was a much more reasonable person and agreed to drive me to the ferry, which I managed to catch, and I got to my breakfast meeting with Al Paulsen. And I went to work with Paulsen.

I wonder whether your experience has been somewhat similar to mine, namely, that on the whole Aussie postdocs do remarkably well when they go to the United States.

Oh yes. I think the Americans got some very good people.

To what do you attribute that?

I don’t know – perhaps just the quality of the medical education we had here, with a very strong fundamental emphasis on basic sciences. I guess to some extent it was a watershed time: previous to that era most people would have gone to the UK for their training, whereas Henry Burger went to NIH and then to the Middlesex Hospital. Bryan, having worked [on steroids] with Eik-Nes at Salt Lake City, had experience working in the United States and was particularly keen for me to go there. I was very fortunate, in that I managed to get a USPHS [US Public Health Service] Fogarty Fellowship so they paid for my time. And Monash was quite helpful, giving me leave of absence which included some study leave that had accrued for the three years I had been a lecturer. That, combined with the fellowship, made life in America reasonably okay in terms of the salary – rather important because by now we had three kids to look after as well.

Not the easiest thing on any kind of academic pay. But, obviously, you did well in the States. You had a good successful postdoc, plenty of papers, international experience.

Oh, we had a great time. Paulsen was a leader in his field of male reproductive medicine. I hadn’t done the formal medical training here, and I was still learning clinical endocrinology – and still very much general clinical endocrinology. So he enabled me to do that, to attend wards and clinics and so on. But at the same time he allowed me time to do research.

I was there for two years, during which I got a reasonably good training in clinical endocrinology as a whole, but obviously with a major focus in the male. Actually, that was the time when radioimmunoassays for the gonadotrophins started to be developed. That enabled a huge opportunity to explore the interrelationships between the pituitary and the testis, and the pituitary and the ovary, with regard to feedback relationships – starting me on a pathway which has been quite fundamental to my subsequent career.

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A medicine-anatomy appointment, back in Melbourne

When you came back to Australia you then went to Prince Henry’s, did you?

Actually, Schofield and Hudson put their heads together and offered me a joint appointment. I had 70 per cent in medicine at Prince Henry’s Hospital, which was the Monash Hospital at that stage and was where the Department of Medicine was, and 30 per cent in Anatomy. So I maintained my basic science and my structural biology, which to me again has been one of the characteristics of my career, in trying to relate structure-function relationships.

A great combination, it seems to me.

Yes. It took me in several different directions, including following up my continuing interest in sperm production, just as a basic phenomenon and also in the compartmentalisation of the testis and how the components communicated. It was well known that testosterone was essential for sperm production, but what wasn’t known was that if you damaged the tubules you actually altered how the Leydig cells would function. So there was cross-talk in both directions. We produced some fascinating animal models which enabled us to explore that and to show that you could actually cause damage to small areas of the testis, and where that happened the Leydig cells enlarged and their function became different.

These feedback loops are the complete hallmark of the endocrine system, aren’t they – these quite complicated and, in some cases, geographically discrete feedback loops, e.g. in the islets of Langerhans.

Oh, absolutely. And some of the work took us into the paracrinology, the cell-to-cell communication, which actually was fundamental in that cross-talk between the tubule and the Leydig cells outside. But it also provided me with an opportunity to follow through on the fact that when we could measure FSH [follicle-stimulating hormone] we showed that there were some men where testosterone levels were normal but FSH was high. We could build then a case for the hormone Inhibin, which had been predicted in 1932 to be there, and we could set off on the long journey which started when I came back in 1972 and which ultimately, in 1984, resulted in our being able to purify the protein for the first time.

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Significant FSH suppressants

David, the Inhibin accomplishment has been a major one for you and your colleagues. Would you take us over that story in a bit more detail, for lay people to get some appreciation of the hurdles you faced?

Well, in 1932 it had been postulated that, in addition to a steroid hormone which was ultimately purified as testosterone, the testis made something which was not a steroid but which actually suppressed the function of the pituitary. In those days they couldn’t measure gonadotrophin secretion. They were looking at castration cells in the pituitary. That was the bioassay that they used – a very laborious bioassay.

But with the advent of radioimmunoassays we were able to measure the hormones and look at what damage to the testis would do to feedback in terms of FSH secretion. And so we put together a collection of animal model data which said, really, that there had to be something other than testosterone controlling FSH secretion. That was critical in providing the fundamental base which set us off, trying to find Inhibin.

You know, it was a team effort. It involved Henry Burger; it involved Bryan Hudson for a while, until Bryan went to the Florey and left Prince Henry’s. And to some extent we then had a little bit of Australian competition between the Florey group, which had Hugh Niall there, and Henry and myself, and Frank Morgan, who was at St Vincent’s. There was also some competition from other places, which we didn’t actually know much about – it was kept very quiet. So it was a fascinating journey.

But one of the biggest issues was to work out a bioassay such that you could screen large numbers of fractions off columns, which was essential in the purification. Really, it was a graduate student working with us who developed pituitary cells in culture and was able then to measure FSH secretion and show that there were extracts in the testis, initially, which actually suppressed FSH secretion by those pituitary cells.

In the end, though, we purified Inhibin from follicular fluid in the ovary. We used to go down to the abattoirs and collect ovaries, bring them back and suck the fluid out from each follicle. We would put that together, and once you got a litre or so of it you had your starting material.

Does that suggest there’s not much species specificity to Inhibin?

There isn’t, we’ve subsequently found out, in that Inhibin turned out to be a dimer of an alpha and a beta subunit. In fact, there are two Inhibins: the alpha subunits are the same and the beta subunits are different. But it is all related. The beta subunit is conserved 100 per cent in its protein structure from the mouse to the human, and the only variation is one amino acid in the sheep. So it’s a highly conserved molecule.

And where do you actually place it in the grand physiological scheme of things? What’s the role of this blessed inhibitor?

Well, it’s part of the TGF-beta [transforming growth factor-beta] family of proteins to which both the alpha and beta subunits belong. And, interestingly, if you have an alpha and a beta you produce Inhibin, which suppresses FSH. If two betas join together you form activins, which stimulate FSH. The amount of alpha subunit turned out to be critical in driving it towards Inhibin or else in activin being formed. Further, since there is beta-A and beta-B, there are three types of activins that you can get: beta-A squared, if you like, beta-B squared or beta-A–beta-B. That has taken us on a huge journey, in addition to the stimulation of FSH. So the activins would stimulate FSH, whereas the inhibins would suppress it.

Also out of that follicular fluid that we started off with we found another protein that suppressed FSH, which we called FSH suppressing protein but which is now called follistatin. But, interestingly, we didn’t know what the issues were until the Japanese were studying an activin binding protein in the ovary and it actually turned out to be follistatin.

Basically, the reason follistatin suppresses FSH is that it binds activin so powerfully – it’s better than any antibody – that that activin is neutralised in terms of its action, and FSH suppressed. That again shows very clearly that these molecules don’t also act as endocrine feedback regulators but are actually local, because activin is produced in the pituitary and follistatin is also produced in the pituitary, by the folliculo-stellate cells. They bind locally and control FSH secretion.

A fascinating story, and one where I can readily see that there is still a lot to be unravelled.

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Institute-based versus university-based research

I am anxious to explore with you some general issues relating to your research and to research generally. First, from your experience would you say a little bit about institute-based research versus university department-based research? My bias is to think that too many medical scientists in Australia have scurried to the protection of an institute, abstracting themselves from the university teaching enterprise.

That’s a very interesting topic, because the whole way universities were funded made me think quite hard about how to manage a research group. After being on joint appointment I went out and became the Professor of Anatomy, when Graeme Schofield became the Dean. That was a hard decision, but I insisted that I needed to continue my clinical work, because to me that was my ‘human laboratory’ and patients gave me wonderful directions and ideas in working things through.

I was in the Department of Anatomy at a time when Ministers of Education were removing money from universities, putting it into research grants and saying, ‘Go out there and compete.’ And, basically, the infrastructure within a university was disappearing. When I started as the Professor of Anatomy there were something like 12 research assistants available for research. When I went out to form the Monash Institute of Reproduction and Development there was one research assistant. If you didn’t get grants it meant that you actually weren’t able to continue your research. So the idea that you would go into a department and have technicians provided to you disappeared over that period of time. Therefore, you had to compete in a different way.

To me, the idea of forming an institute was really to bring together a critical mass to enable better competition. Medical research is now so multifaceted that you need teams of people, and we had that specific issue in mind in coming together with Alan Trounson’s group to form and build the institute.

But we decided we would keep this institute within the university. The reason is my personal view that Australia is actually too small to sequester the talented people who are in the institutes today – including your magnificent institute WEHI [the Walter and Eliza Hall Institute]. We need to get these people interfacing with the students, not destroying their research career with a vast amount of administration and teaching but getting them to come in and give lectures that turn-on the young people and really stimulate them. They certainly have the capacity to do that. I’m still trying to get that message through a bit more.

To some extent, the infrastructure in universities has been run down to a level where you really need to start to have support from the States – not for all university research but for where you have a concentration of very good people coming together. And you can define it on the basis of the number of fellows that are there on soft funding. I see also a real possibility for the showcase bits in universities to get some State Government infrastructure.

We were very lucky, to enabled that to happen. When we were building the space where we first started the institute, I met with the State Minister for Health and she was able to say, ‘I like what you’re trying to do. I’ll organise for you to get $100,000 from the infrastructure fund.’ And that has built up over a period of time and was absolutely essential in enabling the institute to get under way.

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Maximising the benefits of institute-based research

I understand completely how, faced with a running-down university infrastructure, people would wish to join up with institutes. But explain to me how we are going to change the culture. I feel that in a place like the Walter and Eliza Hall Institute people are over-privileged. They are, to a certain extent, spoonfed with large grants and those brains don’t have any impact on the incredible talents going through the medical school and the various science departments. What can we do to begin to redress that and have more of the institutes behave like your institute?

Well, I think it has started already with the UROP program [Undergraduate Research Opportunities Program], where talented university students during their science careers spend time in relationship to some of the institutes – that’s how it started off, with one of the CRCs – where they come in and do some work during the year. So it’s not just a holiday job; you actually become part of the team. That’s now been extended to some university departments, and certainly to the Monash Institute of Medical Research. That is extraordinarily valuable, and I think it’s tending to build the relationship better.

The universities are partly to blame for the situation you describe, in that – rightly or wrongly – the senior lecturers and lecturers look upon the graduate student pool as ‘theirs’. They are dead scared that, if you have people coming in from WEHI or the Florey and giving stimulating lectures, their best students are actually going to go out and work in those other places. To me, those students need to work in the best place if we’re supposed to continue excellence in this country. There needs to be a bit more of a mix, the barriers need to go down on both sides.

More give and take, yes. You mentioned that when you formed your institute at Monash you wondered about yet one more institute. Are there too many medical research institutes in Australia? Is it time for some rationalisation or, at least, for more co-location?

Certainly more co-location. I perceive opportunities for fusion and amalgamation, and this has got to happen. I think the State Government could drive it quite well, in terms of putting some constraints on infrastructure support. I believe there are opportunities for that to happen and some money would help it along.

It has certainly been wonderful to see the governments of Victoria and Queensland, particularly, getting behind medical research. That seems a new phenomenon in the last 10 to 15 years.

Oh sure, no question about it. Those two State governments have led the way in terms of support of medical research, and it’s been fantastic.

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The need to promote clinical research

Another subject I’d like to pick up is clinical research. You mentioned getting on-the-job training in clinical endocrinology in Seattle. Having experienced clinical research both within a classical university department and within a medical research institute, how would you relate the two?

It’s an issue of partly career pathways, partly exposure of young clinicians to research. I think the reason it was very successful at Prince Henry’s was that Prince Henry’s Institute was in the hospital, Henry Burger was the Head of endocrinology, the registrars went through the institute, and basically we recruited a huge number of people. They did their two years of endocrine training and then there was the third year option where you could do a project or you could start a PhD, and Henry and the people – John Funder, Don Cameron and myself – were there. We were able to convince some fantastic people to, say, do a PhD. And that model was extraordinarily valuable.

I think the biggest problem is that many of the hospitals now don’t actually have full-time medical specialists. That’s a tragedy, because they were the people who drove it. At Prince Henry’s it was heavily in that direction: you had cardiologists like Andy [Andris] Saltups and other clinicians who recruited young people to do that. But that model is not flourishing now.

Could the Royal colleges be more helpful, do you think?

Yes. I feel they’re reasonable in terms of supporting young people to do research and providing them with opportunities, and the College, in terms of the structure of its fellowship degrees, does enable this clinical year to take place. So I think they’re doing their bit. The need really is to get across the idea of the university-based teaching hospital, which actually employs specialist practitioners as Heads of the Unit and gives them professorial appointments.

Now, part of the problem there is that although a specialist can earn lucrative salaries and income, especially in the surgical side of things – but it’s not quite so dramatic in the medical side – and if you are an interventional cardiologist you can earn an awful lot of money, that is not so if you’re just in a staff specialist position. It’s a difficult issue.

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Family and ‘extracurricular’ interests

Let’s explore a few personal matters. How did you meet your lovely wife Jan? Do you have any kids? Do you have any grandkids? Tell us all about that.

I first met my wife when I happened to go with another girl to the school that my wife was at, MLC. (She was involved in some sporting activities.) She trained as an occupational therapist and so our pathways continued to cross at various times. We used to meet quite regularly outside the Department of Anatomy while she waited to get into the building, and we would chat – and progressively we started going out. It’s now nearly 46 years since we married in 1962.

We have four sons: one who is a GP and two chemical engineers, one who did his PhD at University of Melbourne and is a Senior Research Fellow there in chemical engineering, and one who is a lawyer. And we have four grandchildren and one on the way.

I’d be interested to hear about your main ‘extracurricular’ interests beyond this wonderful world of medical research.

I’m interested in sport, and I used to play a lot of it. After I left school I played cricket at the Sub-District level, but medicine and academic life got in the way of that. I used to play regularly for a team called the Melbourne Cricket Club Competition, the Club 11, which meant you had a good game of cricket and afterwards enjoyed a beer and a glass of wine. And you had people like Alan Connolly, fast bowler from Victoria and Australia, bowling at you, which was quite scary.

After I gave that away, I played a lot of squash for a number of years, because it gave me a concerted period of exercise and no matter what the weather was like or what time of the day it was, you could get some good exercise. But then my partner’s body started to fall apart. So I gave that up about six years ago, and play tennis quite regularly now.

Also, we have done a lot of walking in recent times – Milford Track, Cradle Mountain, the Blue Mountains – and are continually doing more of that, trying to get around all the good walks before we get too old to do it.

So sport and outdoor activities play a big part in your life. When did you take up climate change issues?

Really, Gus, that came in because of this job. I can actually remember when it hit me. I was sitting in the car driving in from Monash, as I often did, for meetings in the city. And I happened to be listening to Radio National, where some layperson was talking very eruditely about climate change. As I listened, I wondered where he got all this information, and at the end the announcer indicated that a lot of this information had come from a report by the Lowy Institute in New South Wales, written by a couple of people, Alan Dupont and Graeme Pearman. So I downloaded that and started reading. It’s absolutely a passion now.

I just try, as Governor, to get across the message that it isn’t just about trying to removing CO2 and addressing global warming. By simply taking the facts about population, and the ill-health from pollution, and trying to get people to see that none of the things we do in modifying our lifestyle for climate change would actually be harmful in any way whatsoever. It would be extremely beneficial.

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A very scientific State Governor

Did you have any inkling that you might be invited to become Governor of Victoria?

No, not at all. I had a message from my secretary that I had an appointment to see Steve Bracks, the Premier, and I thought I was going to talk about medical research funding and things like that. So I was a bit surprised when I found that it had very kindly been organised for me to park outside the Treasury buildings. And I didn’t have to go through security but was taken through a side door. I thought, ‘This is a bit strange.’ Anyway, the Premier offered me the job. He said I was looking shocked, and I said, ‘Well, what the hell do you think I should have done?’ [laugh]

Had you had much to do with Steve Bracks before?

When we changed from the Monash Institute of Reproduction and Development and called it the Monash Institute of Medical Research we had a relaunch of the name, and he came out and assisted in that event. And I’d met him a few times before that. But apart from that, no.

It was an inspired idea on his part. I already thought John Landy had been a very good appointment, with his strong agricultural interests married with the sport. It goes one step further, doesn’t it, to have a professional scientist in a role of that sort. Of course, Oliphant was Governor of South Australia for a while, wasn’t he?

Yes, he was. And Marie Bashir [Governor of New South Wales] is a psychiatrist.

She has done fabulously.

Absolutely. My colleagues certainly have been very pleased with the appointment. And I find that having my scientific background enables me to talk quite knowledgeably about climate change and so on.

Another passion is the area of men’s health, for which we formed the organisation called Andrology Australia – of which I am no longer the Director but the Patron. I talk freely about this at receptions and wherever I can, to try and get men to be a bit more proactive in terms of their health. That came purely by accident, through my taking the point of view that if an institute really needed support from the public then it had to give back something to society.

We had a session at the Sofitel Hotel on prostate cancer as an educational exercise on the day that the government’s report about PSA screening came down saying there should be no prostate screening. Well, I had 400 guys in the audience who were pretty irate about that. They said, ‘Why can women have cervical cancer screening, why can they have mammography, yet we can’t have this?’

Now, they didn’t really fully understand the nuances of PSA tests, but it led me to talk to [Federal Minister for Health] Michael Wooldridge. I said, ‘Michael, you just can’t leave these people there. You’ve got to educate them,’ but his answer was, ‘I don’t want to do something purely about the prostate.’ Being somebody who grabs every opportunity, I said, ‘How about an initiative in male reproductive health?’ He replied, ‘Go away and write something’ – which I did. I had to ask him, ‘When do you need it?’ so he said, ‘Oh, next Wednesday.’ And this was Friday! That was a busy weekend. But then it took about a year to be put into “departmental speak”. We finally got a million dollars a year and we set up Andrology Australia and it’s still going. The website gets a million hits a month now.

An excellent initiative. Is it too early to ask whether you have some reflections on the governorship, and on your role and Jan’s role therein?

Well, two-and-a-half years into the job, it’s been a very interesting exercise. You get a great insight into how society works. You meet such wonderful people – many volunteers who are doing fantastic activities which would totally cease if they stopped volunteering. And, obviously, it involves my wife a fair bit. On the positive side, I used to have difficulty finding time to go to the ballet or to the opera, and now it’s sort of part of my job description. [laugh] So I get to do those things.

But I get a little bit frustrated at having moved out of active science, because some of the research that came out of that feedback and those molecules that we purified has taken us into inflammation and tissue repair, which has been a very, very interesting journey with real possibilities for commercial development.

Would you offer any comments about scientists engaging more in public life? It is still somewhat unusual, isn’t it?

Yes and no. I think it comes back to the issue of: how do you educate people about science? We really need to do that. We don’t have enough people going into science and maths education in primary and in secondary school, and into university. This is where I keep trying to tell the young scientist, ‘Look, talk about it passionately. Talk about it in words that your parents can understand, that your friends can understand.’ That’s the way in which we build a strong case and put pressure on government to realise that they have to keep on funding people.

And I think we should be promoting recognition of these people. I’ve just come from the Olympic athletes’ parade. I’d love to be able to see a parade for our best scientists. The Tall Poppy Campaign is one way of developing it, but we don’t get anything like the publicity we need.

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Achievements and potential in endocrinology

This might be an opportune time for you to say a wee bit more about how endocrinology shades into immunology/inflammation, tissue repair, et cetera.

It’s partly by setting up experiments and looking at the results critically. As an endocrinologist you want to know where something comes from. If you think it comes from the ovary or the testis, you remove it and see what happens. In the case of activin, instead of the levels of follistatin falling they actually went up. And it’s part of that acute phase response. But we had the controls that enabled us to do that, because in the sham-castrated animals the levels went up. That set us on a journey to ask, ‘Why is this happening? What is the reason?’ and to go on to say now, ‘Well, activin is really a major cytokine in the inflammatory cascade and follistatin blocks it. And if you block it you alter the whole cytokine cascade.’

More importantly, I can give you probably 10 examples of where follistatin will block fibrosis from things like burns, from inflammatory bowel disease, hepatic fibrosis, and now will even interface with some other proteins – follistatin not only blocks activin but actually blocks myostatin, and myostatin is involved in muscle inflammation and fibrosis. There is some fascinating data just emerging.

So sketch out for me a possible commercialisation scenario?

Basically, I think there’s enough experimental data in animals, and really the next step is to make this under GMP [Good Manufacturing Practice] conditions, do the toxicology and get into a phase 1 study – and, if we want to do something in a simple way, that could be topical therapy for burns. Activin is hugely expressed in keloids, and when the surgeon removes the burn scar he creates another inflammatory response, and you simply get a reoccurrence of the whole system.

David, looking back on a remarkable and hugely productive life, what are you most proud of?

Oh gee, that’s a tough question. You know, it’s been an interesting scientific career. I feel I’ve been extraordinarily privileged, in that I enjoy what I do. I think about all of the people who go to work and don’t enjoy it. And to me, even this job as Governor is really a privilege. It just gives you a wonderful insight into society. I wish I’d had that insight before, and I wish I had known about how you influence government, perhaps, as much as I do now – and the difference between influencing a Minister and influencing his Department – and about trying to work through the maze that is our society.

Obviously a good case for another incarnation. Finally, are there things that you might have done differently?

Sometimes I think that if I’d not done the administrative professor bit but stayed in a research institute – because I was in Prince Henry’s Institute and funded by the NH&MRC as a fellow – maybe I could have pushed the boundaries of research much harder.

But being in touch with students, being in touch with patients has been a great privilege. To me that mix has been really great. So much of medical research today, for instance in genetics, depends on good clinicians recording information. The set-up we had with our genetic repository of DNA samples for men with infertility is now turning out to be a goldmine in terms of new genes that are involved in those sorts of problems.

Thank you so very much for giving up your time for the Academy of Science and for the young people of Australia. I’ve enjoyed this interview tremendously. It’s been a real privilege.

My pleasure.

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© 2017 Australian Academy of Science

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