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NHMRC

A conversation with Professor Caroline McMillen

Professor McMillen is Pro Vice Chancellor and Vice President Research and Innovation at the University of South Australia. She is also the Director of the Research Laboratory for the Early Origins of Adult Health and heads a research group of about 15 staff and students. Her research focus is pregnancy and foetal development and the role that the nutritional environment, before conception and during the early stages of gestation, plays determining cardiovascular and metabolic health in later life.

In this conversation, Professor McMillan describes her passion for research and supporting the bright young minds who will be the next generation of scientists and medical researchers.

Voice-over: Welcome to the National Health and Medical Research Council podcast series, a conversation with some of the great minds and leaders in Australian medical research. The NHMRC is Australia's leading funding body for health and medical research. We provide the government, health professionals and the community with expert and independent advice on a range of issues that directly affect the health and wellbeing of Australians.

Interviewer: Professor Caroline McMillen is currently the Pro Vice Chancellor and Vice President Research and Innovation at the University of South Australia and she's also the director of the research laboratory for the early origins of adult health. Her research focuses around the area of pregnancy and foetal development and her laboratory are looking at the mechanisms that are underlying this early programming of adult disease, the focus on the impact of poor environment during the early stages of gestation, and the role of the period before conception in determining such factors and determining cardiovascular and metabolic health in adult life.

Caroline, thanks very much for joining us today on this NHMRC podcast. And we're here at the University of South Australia, in the chancellery. We're going to have a talk about some of the things that you're doing in the area of pregnancy and foetal development. Your laboratory has been working on this and the mechanisms underlying the early programming of adult disease, which sounds very ominous, and particularly with the focus on the impact of poor environment, both during gestation and, uniquely enough, the period before conception. So I just wondered if we could step back and you could just tell us a little bit more about what the research focus of your group is.

Prof McMillen: Certainly. It's become clear during the past five or 10 years, from work in a large range of populations in different countries across the globe, that one's environment before birth has everything to do with one's health after birth. Interestingly, babies who are born small have been found in later life, as adults, to be more at risk of high blood pressure, heart disease, and the sort of obesity that gathers fat around the waist. And that, of course, carries a greater risk for those individuals of developing diabetes. And those population studies have shown an association, therefore, between having a poor environment before birth and having an increased risk of the emergence of these adult diseases, but the mechanisms have not been clear, because it's a long time between one's period as a foetus in the womb and then adult life some 50 or 60 years later.

Interviewer: That's in the human, but maybe just tacking for a second, do animal models show similar things?

Prof McMillen: Well, that's been the impetus for those observations for a large number of studies using animal models, where one can tackle the relationship experimentally, and in models that take a little less time to move from before birth to, if you will, adult life. So there's been a very major set of experimental studies using a range of animal models - sometimes the rat, the mouse, but also sometimes using large animal models of pregnancy. Large animal models ‑ by which I mean the sheep is a particular model of pregnancy ‑ are very helpful in studying human pregnancy, because like the human pregnancy they have a long gestation period, the foetus undergoes some of the same developmental stages in the womb as does the human foetus, and is born at a similar stage, in some senses, and a dissimilar stage in other senses, of development. The sheep foetus we can access and we can have a readout, if you will, from the foetus about its behavioural state, about its developmental stages, its hormonal, its nutrient environment, so we can understand the impact of poor nutritional support for the foetus on how the foetus adapts to that whilst it's in the womb.

Interviewer: Now, I said in the introduction that intriguingly also there's a period before conception which can influence this. I find that absolutely fascinating.

Prof McMillen: It is absolutely fascinating. I think what the current ‑ and the current observations support that ‑ which is that the nutritional environment of the embryo has everything to do with how that embryo develops as a foetus and then develops again into adult life. And I think the thinking about our environment as we develop is that as we go through key developmental stages, whether as a little embryo or as a growing foetus, we sample our environment and we adapt to that environment. And in doing so, we are making predictions about what life is going to be like after birth, so we build our physiology and anticipation of the same environment continuing after birth. But what can happen in human pregnancy is a poor nutritional environment before pregnancy may occur, the embryo and foetus may adapt to that, but when the foetus is born it then comes into a life of plenty, and it is the mismatch between the environment before birth and the nutritional environment after birth that appears to cause the damage.

Interviewer: Now this potentially has some implications for IVF?

Prof McMillen: It has major implications for IVF, because when we talk about nutritional environment of the embryo we could be talking about the nutritional environment of a mother and the embryo in vivo, but we could also be talking about the nutritional environment of the embryo in the culture dish, ex vivo, and there has been for some time a great deal of interest in assisted reproductive technologies in how to create, if you will, a replica of mother's home environment for that embryo in the culture dish. And it's become clear, particularly through studies using experimental animal models, that changing the nutrients in a media in which an embryo may be cultured may have some long lasting consequences for that embryo, some subtle and sometimes some less subtle consequences.

Interviewer: Now coming back to some of the specific research projects that you've currently got going in the laboratory, I know you're working on, as you say, cardiovascular issues, development and metabolic issues, and neuroendocrine issues.

Prof McMillen: Indeed, neuroendocrine issues.

Interviewer: Why don't we take those in turn and you tell us a little about each of those particular projects.

Prof McMillen: Well, one of the first sets of observations relating a poor environment before birth to ill health after birth was the relationship between being born small and having an increased risk of high blood pressure. That observation has stood up over many, many replicates of population studies. What we're exploring is that when the foetus is exposed to an environment where, for instance, the placenta fails to function properly ‑ and that can occur and in fact is the predominant cause of being born small in the Western world ‑

Interviewer: Is there a condition ‑ is there a name for that condition?

Prof McMillen: We would call it placental insufficiency, meaning the placenta fails to work properly for reasons that are really poorly understood. Another reason for being born small is maternal smoking. And in the developing world it can be a poor maternal diet. In all of those instances, the foetus is faced with a problem ‑ it wants to grow and it wants to grow to its maximum, its genetic potential, but it's not getting sufficient nutrients across or oxygen across the placenta to enable it to achieve that. So it has to make some kinds of adaptations if it's to survive. It has to put the brakes on growth, so it conserves its energy. As it puts the brakes on growth, it doesn't do that symmetrically. What it does is it diminishes blood flow to the limbs, so you get a small, thin baby with small, thin limbs. But what it really does is divert its precious oxygen resources and its nutrient resources to protect the blood flow to the brain and the heart, because they're the organs that the foetus reckons it needs for life. So we spare the growth of the brain and the heart. Now those adaptations are made through harnessing control systems that diminish blood flow in key body areas and allow blood flow to flow in the other critical systems, and it is thought, and some of our work has shown, that the systems used to diminish blood flow in that instance include the sympathetic nervous system. Now that's the system we use in adult life ‑ the fight or flight. It constricts our blood flow and gets us energised and ready to, as it were, move quickly.

Now if the sympathetic nervous system is recruited in this situation before birth, we are finding evidence that the small baby relies to a far greater extent on its sympathetic nervous system for its maintenance of its normal blood pressure, its normal cardiovascular function, than a normally grown foetus. And our hypothesis is that this hyperactivation of the sympathetic nervous system, if it persists into adult life as we grow, then we can have a contribution of that towards causing our vessels to, as it were, narrow in adult life and therefore be a contribution towards high blood pressure. We've found a number of neuroendocrine systems, those systems that the foetus is very clever in using, to, as it were, optimise its chances of survival in times of adversity, and as it recruits those systems, so in later life is there almost a memory of that, there's often a hard wiring of this in later life to contribute to the persistence of high blood pressure.

Interviewer: This sounds like epigenetics at work. I'm going to ask you to explain what epigenetics is.

Prof McMillen: Okay. In the example I've just been describing we think that this is, if you will, an adaptation of the foetus to its environment, which is operating through, in probably the human and the sheep foetus, physiological systems that have been set up. But there is a very powerful interaction between one's environment and development and one's gene expression patterns, and this is epigenetics. Now epigenetics is recognising that, for instance, we have very similar patterns of ‑ we have a very similar complement of genes between different individuals, but of course we don't all look alike and we're all quite different. And some of those differences are because the environment in which we are developed interact with our DNA and with the wrapping of the DNA, the histone proteins that form, as it were, part of our chromosomal makeup, and there's a chemical interaction between our environment and our DNA which alters and modifies, through methylation or acetylation, the probability that some of our genes will be expressed. And importantly this can be heritable ‑ a cell in which this change has occurred can pass that change on, that chemical modification, into the daughter cell and their daughter cells. And this is quite a powerful way, if in our early embryonic life we have our environment altering the expression patterns of our genes, particularly those controlling growth, then what subsequently occurs is passed on to all of the cells and we carry, as it were, a memory of our early environment in our cells. We've modified our gene responses, again in anticipation that we're going to need to have that change to deal with an adverse environment after birth.

Interviewer: But those changes can't be carried on to the next generation ‑ or was that still a question.

Prof McMillen: There is some very interesting work that suggests that there can be a transmission of some of this, if you will, nutritional memory across generations, into generational transmission. One interesting example I'll give you of intergenerational health, as it were, is one where we know there may be a very important consequence for us as a species, but where the mechanism is not clear whether it is or it is not an epigenetic mechanism. We know that mothers who are heavy have heavy babies, because they pass a lot of nutrients through to the baby. And we know that heavy babies, even after they've come out of that nutrient rich environment, grow up to be heavy adults, heavy mothers going into the next pregnancy. And those heavy mothers have heavy babies. And this intergenerational cycle of obesity is beginning to be of real concern, particularly in Western countries. And this is a concern because the biology is coming into the next generation because it is expressing itself, the obesity, in the next generation is expressing itself as the individual moves into their reproductive prime. And there is work currently to understand to what extent this may be contributing to some of the current epidemic of obesity that's being seen.

Interviewer: It would make the control of that very difficult, because you've got this almost insidious imprinting that's going on.

Prof McMillen: It's a very interesting phenomenon, and because in this field, in the early origins of adult health, has focused on those early studies, which were remarkable and came out of major population studies, carried out predominantly in people born in the '30s, '40s and '50s, small baby, high blood pressure, type 2 diabetes and heart disease. But more recently we've seen in the Western world an increase in birth weight, and the consequences of that are becoming clear as having potentially as important an effect on health and in contrast to the low birth weight baby, where high blood pressure and type 2 diabetes may emerge in very late adult life in the fifties and sixties, that's not going to impact on the next generation, because they're after their reproductive prime.

Interviewer: As you were talking I was thinking back to an interview we did last week with John Hopper, and we were talking about twins. I was thinking, have twins been useful in any of this work that you've been doing?

Prof McMillen: Oh, very much. There have been some very interesting twin studies and some clear evidence in those twin studies that the smaller twin can indeed be at greater risk in adult life of high blood pressure and insulin resistance.

Interviewer: But we see twins ‑ even identical twins, we often see subtle differences that we can see in them. And again, this could be well explained through the mechanisms you've just described.

Prof McMillen: And the epigenetic mechanism ‑ without a doubt, and there's been some very good work in Australia on exactly that. From my perspective, the epigenetic mechanism is one of those critical range of mechanisms which could explain the way in which the environment in which we develop is transduced into our physiology after birth and into pathophysiology as we get older.

Interviewer: Now 20 years ago, if you mentioned epigenetics you'd be probably run out of the room?

Prof McMillen: Yes, I know.

Interviewer: It's amazing how these things have changed and the attitudes have changed as the data starts to come in.

Prof McMillen: Well, I think what's become clear is that perhaps we thought understanding the human genome, the sequence of the human genome, would explain all of human ills, and what's become quite clear is that there are relatively few monogenic disorders and, indeed, it becomes quite complex as we try to explain, even based on polygenic basis of disease.

Interviewer: What do you mean by polygenic?

Prof McMillen: Multifactorial ‑ multiple genes contributing to a poor health, whether it's cardiovascular disease. So people have had to look carefully for different explanations, particularly for chronic ill health that emerges in later life. And this is where the population studies provided the first observations, and then compelled us to look earlier in our development for some of the consequences in later life, and then compelled us to look at a range of mechanisms which includes epigenetics, and active foetal responses to its environment, which in themselves carry a subsequent pattern of responses, particularly to poor nutrition or ill health in later life. One of the key axes actually that's been really identified as critical in how we develop and respond and transduce information about our nutritional environment is the stress axis.

Interviewer: And what does that mean?

Prof McMillen: In our development, if we are exposed to an excess of the stress hormone ‑ and in us that's cortisol, a steroid hormone ‑ that exposure can have consequences for our development which are as profound as exposure to very poor nutrition before birth, for instance.

Interviewer: Sorry, are you saying that exposure to cortisol while in the uterus ‑

Prof McMillen: While in the womb, yes, indeed. And that's been very interesting, because again it's the mechanism by which we receive information about our external world. The stress axis, in small animals such as rodents, the rodent, the little rat pup in the womb, can be exposed to high concentrations of maternal stress hormones, corticosterone in the baby rat, and we can be at risk of exposure through maternal stress to high concentrations of the stress hormone in development.

Interviewer: Does this have implications for our lifestyle today? Pregnant mums tend to work often well into pregnancy, they're running around doing stuff, raising a family at the same time ‑

Prof McMillen: Well, maybe different things stress different people. For some people being at work is less stressful than not being at work. For some people they may encounter more stress. So it's one's individual response to one's own environment. There are certainly some studies currently going on to try and understand how you capture, if you will, the array of stressful life events that a pregnant mother might experience before and during pregnancy, how you capture that and determine the biology of what that means for her growing foetus. And I think animal experiments draw our attention to the fact that biology uses the stress axis to send clear signals to us in development that we may have to consider.

For instance, cortisol will act to mature our lungs in utero; it will act to mature development of our cardiovascular system. And these are all good if we're preparing to make the leap, as it were, to being inside the womb to outside the womb. It's preparing us to exit early. But some of the changes that occur with that can cause a change in development of blood vessels, of the kidney, of the heart, and if we carry that into our postnatal life and our adult life, again there is evidence that that can be one of the features that result in poor health after birth. So there's been a great deal of interest in the area of not only how the stress response can act before birth, but there also is good evidence that exposure to stress before birth can alter our own response to stress after birth. So the axis almost programs its own reaction ‑ very interesting.

Interviewer: It's fascinating. Of course, this research is very elegant, and the results that you've been summarising today are really, really, I think many people listening to this will be quite surprised by some of the things you're talking about, because we're not hearing about it that much out there.

Prof McMillen: Yes, it is interesting.

Interviewer: Yet it's so critical to all of the lifestyle issues that we have, the health lifestyle issues that we have at the moment. How are people in your community, doing this sort of research, translating this into health policy, lifestyle issues, better ways of informing the public?

Prof McMillen: I think there's a range of approaches there. Firstly, for instance, in countries such as India there is a clear mismatch between one's nutritional environment before birth ‑ often babies in India are born small, so there's a greater incidence of low birth weight ‑ and there's a rapid transition in that community from the rural to urban lifestyle. And in India there's an epidemic of early insulin resistant diabetes, cardiovascular disease. So interventions on how to ‑‑

Interviewer: Can I just interrupt. Has that always been the case in India, though, or is there something else that ‑

Prof McMillen: Well, this has been very recent, because the transition, perhaps, as the country's economy is booming, from the rural to the urban, in particular an increase in, as it were, life, socio‑economic level and nutritional environments coming ‑ there's been some interesting studies in India where mothers for instance may traditionally not eat an enormous amount during pregnancy because they're giving the food to their family, their growing family. Then their baby is born and the baby gets well fed. And you have this mismatch of poor nutrition before birth, good nutrition after birth. In that context, there's a great deal of focus on how you can ensure that a girl, a young woman, is healthy and well nourished going into pregnancy. So the emphasis currently in the developing world is the health of the daughter, the health of the young growing girl, to ensure that she achieves her own growth potential and is well nourished when she starts her pregnancy. And that would be one of the key messages coming out currently across the world ‑ very interestingly. I went recently to a meeting in Japan. Japan is the only country I think in the Western world where we are seeing an increase in the proportion of babies born small, because women are going into pregnancy in Japan underweight.

Interviewer: Is it because they want to have this very thin Western sort of look?

Prof McMillen: Many different views about why that might be, but it certainly is at odds with the changes in body weight and body mass index in other countries in the Western world. And now Japan has got particular concerns, because you have a high proportion of underweight young women in pregnancy, a high proportion of low birth weight babies, who are now faced, of course, with an increase in nutrient availability, and of course moving in from a different lifestyle, different diet in Japan, more again of the McDonald's influence, if you will, the fast food influence, and again there is a growing incidence of obesity in children in Japan and concerns about the metabolic syndrome, insulin resistance, high blood pressure. So what we have there is a very interesting set of concerns and again building a healthy young woman going into pregnancy, a healthy body image, perhaps, or certainly a healthy diet, has become a real concern. There are remarkable cultural differences in the US. When I'm talking about the issue of obesity it's helpful to understand there's a U‑shaped curve ‑ low birth weight babies are at risk of the central obesity that we call abdominal obesity; high birth weight babies are at risk of, if you will, a full body obesity. There are thought to be two different biological pathways. And in the US, you have, of course, the high incidence of obesity and being overweight, and that's at the other end of the spectrum.

Interviewer: What about Europe? We've often thought of France as being ‑ the French are amazing, the French phenomenon, where they eat all these rich foods ‑

Prof McMillen: With a wonderful eye to quantity, I think, and quality, both.
Interviewer: And remain relatively lean?

Prof McMillen: Yes, indeed. I don't know the figures coming out of France, because I don't know that they're strikingly different. The figures from Japan are strikingly different. The concern in Asia, particularly in China with the one‑child family, is, of course, that the baby is the little Buddha, is beautifully and wonderfully spoilt by four grandparents and two parents. So again there's a growing concern there about an epidemic of childhood obesity, coming again from a difference between the early nutritional environment and the late. So we're seeing across the world these issues emerging, as developing countries move in a transition to a better economy and as developed countries deal with the epidemic of maternal obesity. And throughout the intervention story and how to intervene here, intervention in early growth of girls, supporting women's nutrition, in some cultures that may not be the prime concern.

Interviewer: You paint, I think, a worrying picture?

Prof McMillen: Yes, it is. I think in the environment in which, if we take the obesity epidemic, I think there's been a focus for probably the last 20 or 30 years which implies that adult obesity ‑ childhood and adolescent and adult obesity has all got to do with simply too much energy intake or too little physical activity. Some of the work that's been done in our laboratory by Dr Beverley Mulhauser has shown that if you are exposed to high maternal nutrition you alter the way in which the neurones in the brain respond, which normally control our appetite, respond to signals of high nutrition after birth.
So if we can get a better understanding that people's appetite level, their food preferences, whether they choose carbohydrate or fat or protein, may actually be set at an early stage in their development, then we may be able to use more appropriate methods of intervention, because it is quite clear if we look at the planet that caloric restriction has not worked as a mechanism to make the world thinner. The figures support an ever increasing increase in body mass, despite what must be a huge plethora of weight reduction schemes. So I think we're moving to recognise that obesity is a multifactorial condition in which there may be patterns of brain wiring that we have to live with in life, that actually set some of our responses, both behavioural and appetite responses, to our nutritional environment, and that's very interesting.

Interviewer: And some people will say, 'Well, I can't help it. I'm wired that way.'

Prof McMillen: Yes, but then, for instance, you may be able to say, whilst for instance restricting caloric intake will simply cause a rebound and your brain to find its set point again, you may be able to, for instance, have a high protein diet that sidesteps some of the insulin sensitivity issues, or you may be a better candidate for a different form of diet. There may be more ‑ we're future gazing now ‑ there may be a better opportunity to understand how, given your early life experience, your feeding, for instance, in early infancy; for instance, we all know that small babies are born and the first thing that their grandparents might say is how have they grown, are they putting on weight? And this is not a good outcome for the small baby to grow very rapidly, because it is that very early growth experience that may actually then set up some of these changes in the brain, some of the changes in metabolism. So I think as we learn more we will learn more how to tailor rather better some of the intervention strategies for the small baby, for the large baby, and through childhood.

Interviewer: And I think for the first time you've just explained ‑ the explanation I've just heard is why most diets don't work.

Prof McMillen: Absolutely. I'm really intrigued that we have a very mono‑monocular ‑ set of strategies to deal with what's a very complex issue. So therefore I think that whilst it's a complex pathway from early development to childhood obesity and adult obesity, within understanding that complex pathway may be some of the solutions that we've been missing for some time.

Interviewer: What inspired you to enter into medical research?

Prof McMillen: Well, I came into medical research ‑ I took the scenic route. I started off doing a PhD, having done my first degree, and I did my PhD and I loved it, and I enjoyed finding new things out.

Interviewer: What was that in, as a matter of interest?

Prof McMillen: It was in development ‑ it was how the foetus responds to stress in the womb. And I found that I really enjoyed this area and I enjoyed the fact that we tended to think of the foetus as being simply a passive passenger, but in fact it was an active, developing, thinking, strategic period of our development that was critical for our survival and then for our health. Then I went into medicine and very much enjoyed training in medicine, but I got a call, as you do, late one night ‑ I was working in Edinburgh in the Children's Hospital there ‑ I got a call very late one night and I had been working a long time, it was my PhD supervisor calling from Australia, who said, 'Do you want to come out for a year, Caroline, and just work at Monash for a year?' And it was cold outside. I'd been on duty for about 40 hours, and just at that point a year in Australia seemed a lovely idea. So I said yes and in the morning I said to my colleagues, 'I think I agreed to go to Australia for a year.' And so much later I finished my training there and in Cambridge and then I did indeed go to Monash for a year and I rediscovered that for me, whilst I loved clinical practice, I was less interested in practising the known and much more interested and excited in finding out about the unknown, and understanding how things worked. And I was able to take my medical training into medical education, of course, and I loved all of the undergraduates and postgraduate training and postgraduate research training. And so that's been ‑ people often say, you know, they want to go into medicine. I see a lot of students because they want to work with people. I found that all through my life and research, it's very critical as you build your team, that you work very well with people in your team.

Interviewer: Are you seeing lots of young people wanting to enter into medical research?

Prof McMillen: Look, I think I do, in my role I see a lot of young people do come through my door.

Interviewer: As a researcher or as the Deputy Vice Chancellor Research?

Prof McMillen: This is as a researcher. No, as a researcher I'm consistently impressed by the calibre of the young people, what they're interested in, and they will respond really early in their life something influences their desire to both understand, I think, to help, every young student who would come through the door is interested in making things better for the next generation, and are very interested in how you use science to understand at a deeper level how the body works in order to do so. And the training is very long, but it allows a lot of professional and personal development. So I think the PhD is one of the toughest degrees ‑ it asks of you a lot. It asks you to be creative. It asks you to do something nobody has done before. But I think you come through it with a real sense of achievement and knowing that you have taken yourself to absolutely reach your potential.

Interviewer: And what about aspiring young high school students, later on in their high school term? Do you go and speak to them about what you do?

Prof McMillen: Oh, yes, I do. I'm really committed. I talk to primary schools and high schools.

Interviewer: And do you turn those kids on, do you think?

Prof McMillen: I think actually in my view young people are really bright, intelligent, thinking and if what you're saying is your experience is something close to what they want to do, they will find their way. I don't think you can ‑ for somebody who is sort of glad that somebody else is interested in this, but it's not their interest, they're going to find a different path. But I just find that the high school students and university students are so wired, they're so bright, and they're listening and thinking and processing. And the great thing is they take nothing of what you say for granted ‑ your experience is not their experience. But something about why you're interested in what you're interested in and why you took the path into science and medical research might speak to them about something that they've thought they might be interested in.

Interviewer: Yes, that's what it's about, capturing that imagination, I guess.

Prof McMillen: It just is, and I never cease to be amazed at the quality of the discussions, the questions that students ask. They're very sharp. They're straight into why things happen as they do. They ask brilliantly incisive questions and they demand a really straight, thoughtful response, and I think in teaching undergraduates, which I've done for 20‑odd years, that's what I enjoy a lot. If you go in front of a lecture theatre in front of 150 undergraduates, you will not get away with anything that is not clear. And they will ask of you to clarify and explore and expand.

Interviewer: The NHMRC has obviously played an important role in your career?

Prof McMillen: Absolutely critical.

Interviewer: Tell us about that.

Prof McMillen: As a young scientist, getting my first NHMRC grant was one of the most important events in my working life, because it said that the NHMRC, which is the prestigious national body, was willing to take a chance on me as a young scientist with three years' worth of funding which allowed me to hire a person to help me with my research and to be comfortable I could support my PhD students, and to be very clear that what was required was very high calibre outputs from that work, but that was a very significant achievement, and it is for the young scientists I work with and train, the first NHMRC grant.

And then support ‑ it was a difficult time for the NHMRC, I think, in the 1980s in Australia; there wasn't a large amount of support for the organisation in financial terms and they worked very hard indeed to provide that strong base. I think there's been a better funding base for Australian health medical research since it's become clear, I think, through some of the reviews about the benefits to the health of the nation and it's so ‑ I mean, it's very competitive funding and you would expect it to be so, so 25 per cent, 28 per cent success rate, that's pretty tough to put yourself in every year and go into that competition.

And it's critical to support creative, bright, thinking scientists and medical researchers who then make their career in Australia. They may go away for two or three years. They come back, often with a fellowship to bring them back to Australia and then they set up their labs and they're working on problems of national and international significance. That gives us, in Australia, a seat at the international table from which we bring global knowledge to the local doorstep.
So I think the NHMRC, it's worked enormously hard to ensure that it meets Australia's strategic health priorities and to build the capacity and the capability required for us to respond to health issues, and it's absolutely a critical part of why I'm here in Australia working, in Australia having come from the UK for that one year, I'm still here and I could not be here without that support. I've built and supported a team of 20 students, research assistants, post doctoral fellows, that's employment, that's training the next generation, and they'll train the next generation. That's an important legacy for Australia.

Interviewer: Good comments, and I thank you very much for the story that you've told us today. I think it's been illuminating and I just see it as being challenging going forward.

Prof McMillen: Yes, indeed.

Interviewer: But you've really opened up an interesting door here and I think that's the most important thing.

Prof McMillen: Well, I came into research for the challenge and living as a researcher, you understand the challenge will never go away. You wake up the next day and there is always a new question. And really that's why you enjoy getting up the next day.

Interviewer: Caroline, thank you very much.

Voice-over: This podcast was brought to you by the NHMRC, working to build a healthy Australia. To find out more, go to our website at www.nhmrc.gov.au.