Dr Harvey Millar, biochemist

Biochemist

Dr Harvey Millar received a PhD in the Division of Biochemistry and Molecular Biology at the Australian National University. His doctoral research looked at the regulation of electron transport pathways in plant mitochondria, during both normal plant growth and during symbiotic nitrogen fixation with the aid of rhizobium bacteria.

He worked at the University of Oxford investigating plant mitochondrial function. It was here that he was introduced to proteomics (the study of all the proteins expressed at the same time by an organism) as a tool for identifying genes associated with particular physiological phenomena. At the University of Western Australia he is developing proteomics of plants and plant mitochondria in an attempt to better understand plant respiration and how it responds to stress conditions such as chilling, salinity and oxidative damage.


Interviewed by Ms Marian Heard in 2001.

Contents


Family environment

Harvey, where did you grow up?

I was born in Canberra, and I grew up on the edge of the suburbs there – just down the road from a nature reserve. I've got an older brother, who used to beat me fairly effectively in cricket, and a younger sister. (I could probably beat her in cricket fairly effectively.) We went to school quite close to home, within five minutes' walk, right from primary school through to the end of college at 18.

I enjoyed the outdoors, and I spent a lot of time in our large back garden with my Dad, who was an avid gardener. Also, I was very interested in making and mending and breaking things – pulling apart toasters and clocks and that sort of thing.

Did your parents, with their professional backgrounds, influence your childhood?

Yes. My father is a research computer scientist at the Australian National University; my mother was a maths teacher and has now moved into business teaching. I think they had quite a big influence, largely in terms of thinking that learning and finding things out were important. It was a very good environment for a future scientist to grow up in, being pushed along and enthused about finding out new things.

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School years: the springboard into science beyond books

You became involved in debating at primary school, and stayed with that right throughout your schooling?

I really enjoyed debating. My parents would probably have a different take on my reasons, but I greatly enjoyed the process of argument, even from late primary school when we had a 'parliament' – perhaps because we were in Canberra – and different parties and so on. I was always the one trying to form a coalition to take over the government and that sort of thing, on various classroom issues. I kept doing debating throughout high school into college, and especially enjoyed the opportunity to make arguments, to argue with other people and to explore different opinions.

When did science emerge as one of your wide range of school interests?

Science per se, probably in high school. A number of teachers there supported me strongly in doing science and I was very interested in it. Certainly I enjoyed science and mathematics, and I also had a real interest in history, which probably influenced me to think about natural events and things that have happened. But it probably wasn't until college – years 11 and 12 – that science really started to take off for me.

At college I had a great chemistry teacher called Anna Binning, who was very enthusiastic and very interested in a number of the students there having an opportunity to see what science was like in the real world, outside the classroom. I think her main interest was in biochemistry. I remember her recounting to me a story that while she was at a stop-work meeting for teachers, she saw some clover in the lawn, pulled it out and found little nodules on its roots. Realising that the nodules were involved in the process called nitrogen fixation, which she knew somebody in CSIRO had worked on, she contacted CSIRO and said it would be a great project for us to get involved in. And so I went occasionally for a few days' work in a lab there with a scientist, Alan Gibson. That sparked my enthusiasm for science and a recognition that it wasn't all in books but was very practical. You could find out things that weren't in books – things that were new.

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University science: plant respiration and a mentor's insights

After finishing year 12, you went on to your science degree at the Australian National University. What subjects did you study?

My first year was probably fairly standard: physics, maths, chemistry, some biology. But pretty soon I decided that chemistry and physics were a bit dry for me, the lectures for mathematics were far too early in the morning, and biology was definitely the answer. The biology lecturers were really enthusiastic and enjoyable; the science seemed to be really new – everything was just being published, just being discovered – and that caught my imagination.

You went on to do Honours and a PhD, also at the ANU.

I did, yes, in David Day's laboratory. During my Honours and then a PhD – again linked with CSIRO – I looked at a process within respiration in plants. To describe that a little bit: we tend to understand respiration in terms of our own breathing as a gas exchange. So we breathe in oxygen, we breathe out carbon dioxide and water. But in fact that process of using the oxygen and producing the CO2 and water is happening in every cell of our bodies. This process of making energy happens in most organisms, and in plants we were looking at how the process is regulated – how the plant actually makes its energy, when it makes it and what it uses it for.

Was your Honours and PhD supervisor important as a mentor during this time?

He was indeed. I met David Day when he lectured me as an undergraduate, in second year. (I really enjoyed his lectures, even though he seemed to think I wasn't very interested in them.) He asked me to work in his lab for a summer project at the end of my second year, and said he would pay me. 'Well, this is great,' I thought, and taking up his offer sparked a lasting friendship.

I learnt a lot from him, especially about how science works. The key thing was that science unpublished is science half-done, because science is really about communication. It is all very well to find something out, but if you don't tell people about it you haven't fulfilled your job as a scientist.

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Oxford studies in mitochondrial proteomics

What did you do after completing your PhD?

I stayed on in Canberra for a few months, finishing various pieces of work at ANU, and then a few opportunities came up for me to go to Europe on a research fellowship. In the end, I went on a Human Frontier Fellowship to work in a plant respiration lab in Oxford.

There we started to use some tools that I hadn't used previously. A key one was an attempt to move away from the usual very reductionist approach of looking at just a couple of the elements of respiration. The challenge I found there was to work at a holistic level in a plant (or any organism, for that matter) – that is, to take these broad approaches but also to understand how things work at a molecular level.

The technique or approach we were using was proteomics, which may sound odd but has a history in the understanding of genomics. For many years people have realised that you can take a gene which is the blueprint for making a particular protein, and sequence the gene – that is, work out exactly everything that is in it, its entire blueprint. More recently, scientists have found that you don't have to work on just one gene from an organism; you can work on all of its genes and thereby sequence its whole genome. The study of that whole genome is called genomics. This is now possible in a number of model systems – plant systems, bacteria, viruses, worms, flies, and now even humans themselves as the human genome has been sequenced.

But people have realised that the blueprint for everything that an organism could possibly do doesn't actually tell you what the organism is doing at a particular time in a particular place. That is where proteomics comes in: it is a study of all the proteins – a study of everything that a plant or animal, whatever it might be, is doing at a particular time. So that's what we were trying to do.

Why is this work important?

First, it is very important that we understand how genomes work, and how organisms actually use their genetic information to cope with the environment they are in. And, second, our particular interest in respiration was to understand how it is that plants provide the energy they need, at exactly the time when they need it.

One critical thing is that the place where respiration actually happens is in the little structures inside the cells called mitochondria. These are what are 'doing' respiration. People have found out recently that these are involved not only in producing energy but in the decision of cells to die. Often a cell makes a strategic decision to die for the good of the whole organism. Mitochondria have been called 'the breath of life and the kiss of death', and understanding how they and their proteome respond to different conditions is quite important in understanding how plants really tick.

Was Oxford different from Australia to work in?

Very different. Some things were the same, but one of the major differences was that it was really out in the world arena. Australia can tend to be a little isolated, although the negative side of that is starting to be overcome with email and other sorts of communication. In Oxford you had major speakers coming through all the time; you were always meeting new people. There is a dynamic movement of scientists in Europe that I certainly didn't experience as much when I was a PhD student in Australia. Also, that university is very old and has a lot of history – which can be a little hard for an Australian, because we tend to be so pragmatic. We don't do things because they've been done for 1000 years; we tend to question. But it's certainly intriguing to see that in operation. I enjoyed it.

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Joining a Perth-based critical mass of researchers

What did you move on to after Oxford?

My wife and I came back to Australia – to Perth, where a critical mass of researchers involved in plant respiration seemed to be turning up. For example, one of the people I had planned to work with in Europe had actually come to Perth as professor of plant sciences, and I knew another researcher who was there working in the area of respiration. And then my old PhD supervisor, David Day, applied for and was offered the chair of biochemistry at the University of Western Australia, so he came over as well. We now have quite a large group – three or four academics and about 20 students – all working in this area, and that's a really enjoyable environment to be in. I'm very glad we came back.

And your work at UWA is also in the field of proteomics?

It is, yes. We're trying to understand, on a larger scale, what is in mitochondria. What are these respiring systems in plants? What can they do? What are their limitations? So we're really trying to expand that work in proteomics. Technical advances in the last few years have made that a lot easier, as have some major equipment grants from the government to buy the machinery we need to identify those proteins.

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Practical applications: harnessing plant energy for better crops

Does your present work have applications that could be used in Australia?

Yes. Our main focus at the moment is to understand, at a basic level, what is going on in the system. But we see the application in terms of understanding how plants cope with stress and respond to it. To think about agriculture from the broader perspective: often you have the problem that some plants don't grow as well in an ideal environment as they could. People are certainly trying to improve that, to make plants better able to cope with ideal environments. But a lot of the problems in agriculture are, in fact, problems with how your crop copes in a bad year, when it is under stress.

We're trying to understand how respiration, the provision of the energy which is vital for plant growth, is actually responding to stress conditions. We're looking at chilling stress, at drought, salinity and things like that, to understand how the plants respond.

We're also quite interested in germination, to understand how plants establish themselves when the seed has just germinated and a lot of energy is needed. One of the key traits that people are looking for in breeding plants is what they call 'early vigour' – the ability to grow really rapidly at the beginning – because with that they can overcome weeds, they can get going early so as not to flower too late in the season and so on.

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Commercialisation: funds versus scientific freedom?

What are your thoughts on the commercialisation of science?

We have found positives and negatives. The positives can be in terms of gaining greater research funding. We've found it difficult to get enough research funding from the federal government for the sort of research we do. We have quite significant funding from them, but there is a cap beyond which it is very difficult to go, and so commercialisation becomes imperative – not only to prove to public agencies that our research truly is going somewhere, but also because we need funds to continue the research. A lot of our research is getting very expensive. In addition, because a lot of the techniques we use and the approaches we are taking are used also by medical scientists, we have to pay a premium on the use of that technology. So yes, we are certainly working towards goals of commercialising our science.

The negative is that if you commercialise things you can lose some of the freedom to follow avenues of research. The scientist tends to be interested in what they are doing and wants to follow on for the sake of the science, to understand what's really going on in the system. Commercial pressures tend to be more toward what will actually make the money. So we have to try to balance that.

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Communication: a vital skill, excitement shared, new paths to tread

What skills do you think are needed in science today?

One really important area of skill is collaboration, the realisation that science has become something that's very difficult to do on your own. The days of being able to sit by yourself and do science have largely (though not completely) gone, and so there is a need to collaborate – immediately where you are, and internationally. To recognise that we are all working together is a vital skill. It's about communication with different cultures, different people.

There is also a vital need to communicate in general, because in science we are publicly funded. We have an obligation to tell the community about our work. That is not only for ethical reasons, so they can consider whether they think what we're doing is reasonable, but also just because they're paying us. However, society doesn't have an obligation to listen. We are competing in an environment where the media is always trying to get people's attention. As scientists we need to be much better at communicating with the public at large, sharing our enthusiasm with them as well as giving them the facts of what we're doing, what we've done.

What are the rewarding or exciting aspects of a career in science?

The thing that drives scientists – certainly it drives me, anyway – is an interest in finding out what is new. I like to think of us as explorers. There is an obvious macro-level of exploration such as climbing mountains or going to the moon, but what we're doing is micro-exploring. That's very rewarding. You're finding out things which are new, which nobody knows, and bringing them back to tell people about them, and even as a little boy I was really thrilled to find out something new and then to be able to go and tell people about it. Now I can do that and get paid for it.

The other key thing is the chance to travel, which you can do in science more readily, maybe, than in many other professions, and the opportunity to meet people from a very diverse range of countries. You can talk to people across cultures about your interest in a particular area of science. The camaraderie, the friendship, which you can build in that way is a great reward.

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Facets of a committed life

What are some of your interests outside research?

My wife and I have a 10-month-old baby, Jessica, who is the focus of our life. (Indeed, my current hobby could probably be said to be nappy-changing.) My family is very important to me, and is one of the key reasons for coming back to Australia. Linda and I love this country and the lifestyle, the environment and the opportunity here. This is a great place to grow up. I enjoyed it, and the opportunity to grow up here made a real difference for me and probably set me on the road I'm on. So I want that for our children as well.

Linda and I are both committed Christians and very actively involved in our church. My science has been influenced by my belief that everything is not here by accident, that there is reason to it all. I think a recognition of a creator God behind what we are doing in science has real impact for how we interpret our science and also the ethics and the considerations that we think about in doing science. Many people seem to think that science is ethically neutral, but I don't agree. I think that as members of the community we all have an obligation to recognise what we are doing and to make a value judgment as to whether it is a good thing for us to be doing.

As to my other hobbies, woodturning is a major interest for me. I've always been very involved in woodwork, influenced by my father and my grandfather, although I don't get much time for it at the moment. Also, my wife is a musician, and I end up being the sound recordist for her at times. I don't have any musical ability but I do have a technical background, so that's what I'm useful for there.

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Looking ahead: promoting and enjoying scientific exploration

You enjoy working where you are at the moment, in the university system. Where do you see yourself in 10 years' time?

Ten years is a long time. I do enjoy being in a university research environment, especially seeing students move from being undergraduates to doing postgraduate studies and then out into the scientific community. That's a very rewarding thing to be doing and to be involved in. And I enjoy the academic freedom to follow the research that we want to do – providing we can find funding to do it. So I suspect I would still be in a university environment.

But the university system is changing rapidly – it will be interesting to see where it is in 10 years' time – and companies are becoming very important in the provision and development of the technologies that we use. I think that in the future, universities and companies will have much greater connection in the way they operate. I suspect I may well have some involvement in both those spheres.

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