Professor Jonathan Stone, medical scientist

Professor Jonathan Stone

Professor Jonathan Stone was born in 1942 in Auckland, New Zealand and moved to Australia with his parents when he was a baby. He received a Bachelor of Medical Science from the University of Sydney in 1963 and a PhD in 1966. After a year as a visiting lecturer at the Hebrew University of Jerusalem, Stone did post-doctoral research at the Institute of Biomedical Research in Chicago with Sir John Eccles, and then spent a year in Munich at the Max Planck Institute for Psychiatry. Stone returned to Australia in 1970 to take up a position as a research fellow at the John Curtin School of Medical Research. Here he continued his research on the retina. In 1976 Stone moved to the School of Anatomy at the University of New South Wales (UNSW) initially as a senior lecturer, then as an associate professor (1978–85). He became head of the school and took up a Personal Chair in Anatomy in 1985. During his years at the UNSW, Stone's research interests shifted from the study of parallel processing to the development of the brain. His next appointment was as Challis Professor of Anatomy at the University of Sydney (1987–2003). Here he worked on the interaction of neuroglial cells during the stresses of birth, particularly focusing on types of blindness that result from the degeneration of photoreceptor cells. Stone was appointed Director of the Research School of Biological Sciences at the Australian National University (ANU) in 2003. At the ANU his research concerns the stability and degeneration of the central nervous system, including dementia and a group of inherited eye diseases that affect the retina.

Teachers' notes to accompany this transcript.
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Interviewed by Dr Max Blythe in 1996.

Contents


Cradled with warmth, intellect and no nonsense

Perhaps we could start with your family – the cradle of your attitudes and achievements.

I was born in Auckland in 1942, three years after my parents had gone there for my father to take a Chair of Law. (He was very young, in his early 30s.) As a babe in arms I was brought to Sydney, where my father had been appointed to the Challis Chair of International Law and Jurisprudence. My mother tells me we came in one of the old QANTAS flying-boats and landed out on Rose Bay.

As you grew up, the family environment that moulded you was fairly tough.

Yes, it was. My parents were by then immigrants to Australia but their own parents had been immigrants to England from Russia, fleeing the Tsar's armies and their claims on the Jewish population in Lithuania. They were fighting their way up to the middle class, and doing a good job of it. From the slums of Leeds, my father went to Oxford just at the time when it was opening up. Although he recognised that it gave him his start, and on his study wall he kept his college shield – Exeter, I think it was – he had a love/hate relationship with the place. He was never invited back despite all the distinctions he gained, and didn't himself ever want to go back, yet he spoke with great affection of his tutor there, Geoffrey Cheshire – Leonard Cheshire's father. He kept up contact with the elder Cheshire for many, many years.

They were tough people who had come through tough times, a very strongly Jewish family. That was the time when the British mandatory powers in Palestine were being debated, and as a young man, newly arrived in Australia, my father took a very strong stance against our Governor-General. When I read those old papers I can sense the mixture of intellect and anger that was driving him. But that was not part of my life. Being just a babe, I was unconscious of it. Then I found myself in postwar Australia, growing up, going to school.

I think your father was a strong, powerful loner, perhaps not unlike you.

Yes. You never know whether you are imitating somebody or you just are that way yourself, but my instinct has been to follow my mind. I have never had any problem with authority of the institutional sort but I have always had a problem with intellectual authority.

You got into a few conflicts.

Yes, which with a bit more of a smile and a shrug and a tug of the forelock I could have just gotten round, but my instincts weren't there. They are well in place now, with all the learned reflexes, but I do not think I somehow or other inherited them.

I'm sorry I am never going to meet your fascinating father. Tell me about the rest of the family: your mother, brother and sister.

It was a close marriage. My mother, Rebecca – Reca, as we call her – is still alive. She devoted herself to the family and provided the traditional background which my father drew on. My elder brother has for many years been Professor of Religious History at the Hebrew University of Jerusalem, and my sister is a psychiatrist practising in Sydney. They have very stable marriages and happy families, and ours is a very warm sibling relationship.

Mother was strong, as well as Father?

Yes. She came from that generation that had fled and then lived. Luckily my parents found themselves in England and therefore unaffected by the Holocaust, but they were fiercely burnt by it psychologically. That gave a toughness, a no-nonsense attitude. For example, I didn't do much sport at school because it just wasn't encouraged – what mattered was the knowledge, learning, getting qualifications. I have since made up for that in various ways, however.

I became aware of the Holocaust only in the most peripheral way, although of course as a kid you learnt about it. But I realised that within central Europe something of the most awful nature had happened. Out of that I drew a scepticism about the role of culture – Kultur, in the German sense – and I realised the amorality of culture. Like my father, who at core was intellectual, a common lawyer, I came to appreciate the value of the British tradition: a powerful set of mechanisms, quaint and odd and full of idiosyncrasy, which nevertheless had provided England and could provide Australia with a form of government that, for all its imperfections, got rid of that terrible instability that afflicted middle Europe. And I thought about that, trying to understand it at its fundamental levels.

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Knowledge, philosophy and cheerfulness

Did your primary schooling have much influence on you?

No. After the local school, Gordon Public, which I remember with affection, I spent two happy years at one of the selective primary schools which were called 'opportunity schools'. Then I passed into a selective high school, North Sydney Boys. That was a tough environment, not really a caring one – not care-less, though – and I have since learnt through my children's experience how much more caring and attentive schools can be. But it was a fair environment, which I appreciated. I threw myself at the academic windmills there and did well enough. I wanted to have a go at everything, but the area that I really found myself standing out in was English: for some reason the words came and I could be a star at that subject.

I suspect it was through parental pressure that you went into a medical course at Sydney.

Yes. I came out of high school young, only 16, with no clear idea of what I wanted to do. Hell, I thought I was ready for anything. I'm sure my parents would have supported me in doing any of a number of professions, but I wasn't sure which I wanted. They suggested medicine, and in I went.

Going in at 16 couldn't happen now, could it?

No. School has been extended by a year, for a start, and there are increasing attempts to bring people into medicine at an older age. And I was a case in point. I threw myself at the medical course. It was then, even as it is now, a flood of knowledge that people package for you as best they can. It didn't help that those were extraordinary years: after the war, the Australian universities were asked to cope not just with the normal flow of kids coming out of high school but also with the returned servicemen. They were not allowed to put academic restraints on. There were 700 of us in that year, of whom 300 failed, and when we passed on we picked up 300 more that had failed. It went on for a few years like that, during which we were dealt with en masse. I wasn't enjoying it, and when the opportunity came to do a research degree, the Bachelor of Medical Science I quit the medical course and went into research.

You liked writing and I've got a feeling that you were reaching out for quite a bit of philosophical material. Was that linked with your father?

Yes. I got from him, whether through genes or absorption, a need to understand at some fundamental level what was going, without getting into either the scholasticism of a lot of modern philosophy – which I read and just couldn't handle and then came to understand for what I think it was – or the gloom that Boswell referred to in his Life of Johnson. (He commented that he had tried to be a philosopher but cheerfulness kept breaking in.) At some point you walk away from it, because it just drags you into deep and difficult debates, but you realise that the philosophers have tackled very difficult issues that afflict us generation after generation, and I found I could make my way better in science if I understood those issues.

You were already strongly analytical. Did science help to further that?

Yes. Science gave a lot of materials for understanding. For example, I found it fascinating to read about the debate over evolution – not so much the debate itself, which was a confrontation between two systems of knowledge, but the drive in some people within the scientific system to have a clear-cut classification that everybody could understand, while others said, 'Wait a minute. What we need is a classification that can deal with errors, that can be creative.' Heuristic is the word that the philosophers use. As I came to understand that, I could see what was drawing my colleagues in certain directions. I felt I became a fuller scientist for doing that.

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Retinal insights: developing the whole mount

Perhaps you can put me in tune with the environment that Peter Bishop had created for that Bachelor of Medical Science degree.

Peter had the passion in him to establish the study of the brain in Australia. Eccles had a group in Canberra, in the very specialised environment of the Institute of Advanced Studies, but there was almost nothing else. After Peter had been to University College in the late '40s, he set up major labs at the University of Sydney, he started to bring in people and I was one of those lucky enough to go into his lab. Some were extraordinary people, who have gone on to make their mark right throughout Australian neuroscience and overseas. And in Canberra he attracted a lot from overseas who later made their mark in their own countries. I feel privileged to have been one of those people.

Peter was interested then in the cerebral cortex. He had moved on from the study of individual neurones, which he did so well, to studying the system as a whole, going to the highest levels. The first project he gave me was to explore the visual cortex but I couldn't do it. He was so busy that I found myself on my own, and I remember gritting my teeth and saying, 'I'm just going to work till I find my way out of this.' The way out came partly through a collaboration with Bob Rodieck, an American – extremely bright, full of ideas, full of self-confidence – who now has just about retired after a very distinguished career. I was lucky to meet him at that stage. The group included also Bill Levick, who has just retired from a personal Chair at the ANU, and Jack Pettigrew, who now heads a research centre at the University of Queensland.

But also I created something myself, when I got really interested in the structure of the retina. Peter gave me an experimental project on the retina, the starting point of the visual system, and I had an insight into how to look differently at the retina. I drew on old sources to figure out a way of taking the whole retina and laying it flat, instead of cutting it up into pieces. This proved to be an enormously powerful way of surveying it. I presented that at my first scientific meeting, of the Australian Physiological and Pharmacological Society in Melbourne, in 1962. I can remember during the long train ride back from Melbourne after that meeting thinking how to use the technique to explore new features of the retina.

Is the retina easy to peel off? Does it dislodge easily?

Once you get confidence, yes, and now the method is used in hundreds of papers in many, many labs every year. Although its origins are forgotten, I have some pride in having contributed at that point. I must have been about 19 or 20 when I made those first whole mounts. And I'm still looking at them – I spent time on the microscope on one this morning. It's a powerful technique. Of course we have brought in the more molecular techniques in subsequent years and the new forms of microscopy (fluorescent, confocal), but that was a core thing for me.

The use of whole mounts gave me incisive data, new ways of looking at things, and I was ready to go. We came up with a series of studies then which led to an understanding of aspects of the retina on which Peter could draw to strengthen his cortical work. I've always been grateful to him because, once he understood what I was getting at, he gave me freedom and support to go for it.

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From the retina to receptive fields

Peter Bishop had already looked at the cortex – a mosaic of cell areas, interpreting the messages from the retina – looking at the optic nerve and the geniculate nucleus on the way through. Were you actually providing a fresh look at that mosaic?

Yes. I went out to the periphery.

So you were mapping this retinal structure?

That's right. With all my analytical and holistic desire to see the large picture, I found myself getting down to very detailed counting – one, two, three, four, five – but I did get the data on which I could see patterns of specialisation of the retina. Two of Peter's collaborators (Wladimir Kozak and George Vakkur) had started to look at that but hadn't concentrated on it. I picked up from them, getting down to the microscopic level. That enabled us to see how the retina divided its projection into the two halves of the brain and we began to pick up the morphological differences among the ganglion cells, which then became the basis of the parallel processing story.

After that first period in Peter's laboratory, in the '60s, you did a PhD with him.

Yes. Peter was my supervisor. The study had physiological parts which I did with Bob Rodieck, the American collaborator, and it had anatomical parts which were much more my own. We were working at a point in the study of visual pathways at which people had started to look at the receptive fields of the cells. Once it was realised that the cell would not respond to the whole visual field but only to part of it, you could define the part (the 'receptive field'), analyse it, start to model it, and then when you surveyed many you could start to see the differences. That had been begun in America in the late 1930s by Hartline, who got the Nobel Prize for his work. The work had stopped during World War II but this was its renaissance, certainly in Australia. That work culminated in a mathematical model that Bob Rodieck produced, calling it the convolution model. I went a fair way down that stretch with him – he did the mathematics – and that became a paper of reference in the literature from which then we could begin the classification work.

Peter was quite insistent that for my post-doc years I should go overseas, and he arranged for me to work with Jack Eccles, who by then was in Chicago.

Leaving Peter Bishop's unit was not totally without some stresses with colleagues, because you were burning rather a bright light at that stage.

Certainly with Peter it was a friendly leaving and later he welcomed me back to join the department he then headed at the ANU. With my colleagues, I suppose there must have been something in the chemistry of personalities but the substantive issues on which I found myself at tension with them were conceptual. Although I felt I did do my time painting the fine strokes, perhaps I was more willing than some other people to draw broad strokes.

I knew I had so much to learn from those colleagues, because they had skills and enthusiasms and abilities that I didn't have. But science is a matter of choices. I was always drawn to where I thought we were breaking through into new ground. Creative science is always done on the edge of the unknown. You are always stumbling in the dark. You will be clumsy, fall, look silly, but I was never afraid of that. Others were more content to stay in the safe ground which was a bit explored, where they could do much more elegant work. I rejoiced in what I believed was new, despite my clumsiness. They rejoiced in the (very real) elegance of their work. That was the tension.

So you really were ready to go to Eccles in Chicago in 1965?

Oh yes, I was ready to go.

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Working with Jack Eccles

My post-doc years were exciting. Working with Eccles was a terrific experience. I did intracellular recording. Two of my collaborators were Henri Korn, who is now a major figure in French neuroscience, and Nakikira Tsukahara, who was rising in Japanese neuroscience when he died tragically in an airline crash.

Can you give me a portrait of Jack Eccles himself?

He was a gorilla of a man. He was quite big, still full of energy – in his youth, I think, he'd been a great swimmer. He was positive and quick to judge, and if you were on the line that was his at the time, he was there and supportive. But if you differed too much, dug in your heels, he would just walk away from you. He was in his late prime by then: he had achieved great things and had great self-esteem. I was prepared to absorb, and I learnt a great deal from being in that group. Later, I drew a lot from Eccles' philosophical writings – from the fact that this man of empirical commitment believed he had something to learn from philosophy.

And, as you were saying of yourself, he was comfortable with being on the frontier of science, with getting things wrong and stumbling.

Yes, he was. At one conference I remember, when somebody put forward what was then a fairly radical idea – I think it was the proposition that all the climbing fibre inputs to the cerebellum come from the olivary nuclei – only Jack Eccles would speak up and support it. He just wasn't afraid. He was willing to take a strong position, and he had real judgment. Jack Coombs, who had worked with him, remembered this judgment in one of Eccles' great discoveries. While they were working on a quite different issue, recording synaptic potentials in the spinal cord, they kept seeing something unexpected and irrelevant: a synaptic potential inverted on the screen as the neurone became injured. Jack Coombs told me that after that happened two or three times, Eccles said, 'Forget about what we're doing. That's what we're investigating.' Out of seeing that epiphenomenon came his analysis of the mechanism of this inversion, and later his book on the ionic basis of synaptic transmission, which was his key contribution.

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A parallel-processing odyssey: working again with Peter Bishop

When Eccles left Chicago, you went to one of his first-rank people.

I was offered a position in another lab in Buffalo, where Eccles went, but I'd dragged my family round enough. I stayed with Rudolfo Llinas' group and worked with John Freeman, a young American who showed me how brilliance and good hands could take you a long way very fast. I greatly enjoyed that year with John, going into intracellular recording using classical electrical stimulation techniques, which I then took back to Canberra.

Via Munich.

Yes. I had a year in Munich, partly to see Germany but also because I was lucky to get a position there in the Max Planck Institute for Psychiatry. The head of the lab was Otto Creutzfeldt, a very distinguished neuroscientist whose father's name is attached to the Creutzfeldt-Jakob disease. Otto later headed a group in Göttingen, and Bert Sakmann and Erwin Neher, who got the Nobel Prize a few years ago, were his protégés. He too supported me and left me to my own devices while I brought together the techniques I had learnt with Eccles with the work I had done with Bishop.

From Eccles I had learnt to watch for the unexpected in what you see down the microscope or on the oscilloscope screen. And that's what happened in the transition from Germany back to Peter Bishop's group. When I worked in Germany on a very detailed study of conduction velocity of cells with different receptive field types, I saw variations that no-one had described. Hanging out on the end of the traces were cells that didn't fit into the two major types. I put them aside…

And that's where you stumbled across the W-cells?

Yes. Briefly, when you stimulate along the visual pathway – as Bishop had shown 20 years before – you get two groups of fibres turning up at very precise moments on the oscilloscope screen. When I started to work on their receptive field properties, I saw a very occasional scattering of cells which I guessed to be small neurones that others hadn't seen in the past 20 years because of microelectrode technology. I went back in, using the glass electrode technology that I'd learnt with Eccles, and then they started to turn up, one in five. When I did look at the receptive fields they were quite different, and I realised that I was dealing with a class of cells that hadn't been recognised before.

Were these patterns and populations of cells with very precise influences that turn them on or switch them off?

That's right. And that was the excitement that came out of Hartline's work. Buried small in my doctoral thesis had been a chapter in which I gave – when I look back at it – an incomplete description of receptive fields that hadn't ever been seen before. It was very exciting at the time and it got published in Science, but they were not easy to record and I couldn't do more with it. It stayed somewhere in my memory traces, however, and when I reached back to it I found that although it was a bit untidy it looked better with passing years.

I had five fruitful years with Peter's group. He put me in a lab, with tremendous support. I got technical support equipment; I didn't have to write a grant, just go. The first story that we pulled out was this new class of cell in the retina. Having absorbed that, then I turned to how the retina sent information to the brain. The ganglion cells are the output cells of the retina, and in your eye and mine there are a million of them, each has its own private line into the rest of the brain. Among the ganglion cells there are clearly different cells doing different things. The retina is not just a light processor but is specialised, through these different output cells, to pull different things – movement, shape, colour in the primates – out of the visual image and channel them into different parts of the brain. The idea driving me was that when you then traced them in the brain you would find they went to different areas, and this worked.

I mustn't fail to acknowledge the superb work done by the others working in the same area in Canberra. We drove the idea right through to the visual cortex. With colleagues who made tremendous input to it – Peter Hoffmann, Bogdan Dreher – we argued that these ganglion cell classes are reaching the cortex without mixing and are driving some of the variation in the cortex which American workers had interpreted as serial processing. They had seen the same variation but had thought the information was being processed in a hierarchical manner. One of the papers we wrote together was on hierarchical and parallel visual processing. It contained large areas of analysis that I still am pleased to read.

That driving idea of parallel processing was resisted by the Americans. They had done such a lovely constructive job; they broke open so much, and were rightly rewarded with great honours. But on this…

You were not yet 30 and you were pushing against big, established ideas.

Yes, and was stupidly fearless about the matter. But I must say that Peter Bishop understood it: he saw what was happening and his philosophy was that out of the ferment, which he welcomed, would come the hard testing, the discarding of what was wrong, and so he gave us great intellectual freedom. I like to think that he found that a very productive period in his lab. I believe those ideas are now part of the mainstream. My father used to say in his own field, 'There comes a stage, son, where not only don't they remember the details of the battles, they forget that there ever was a battle.' I think we've got to that stage now with the parallel processing concept of visual processing.

I haven't done the cortical work since then, but we have seen evidence that different areas of visual cortex are handling motion information, information about movement, information about colour. Even the recognition of faces – you would be aware of the work of Oliver Sacks – seems to be packaged into parts of the cortex. I didn't believe it would go as far as it has. Quite extraordinary stuff.

You were drawing now on the Eccles time, those five years out of the Bishop world, as a philosophical time when you probably read Popper – an exciting time of transition.

Yes, although I must admit I didn't really tackle the philosophy until, in Peter's group at Canberra, I started carving out new paths. That's when the fire really started and I found myself under a philosophical attack as well as an empirical one. And that's when I went back to it.

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The family man and sportsman

Jonathan, before we move you on from Canberra, could we look at how you took a wife and became a family man.

I met Margaret as a lab technician in Peter Bishop's lab. She was then studying Arts part-time. We rubbed along well enough in the lab but struck up a relationship after a few years of being together there, and ours has been a warm and successful marriage that I've relied on. I've drawn very deeply on her intellect as well as her warmth as a person. We have three daughters, but after we returned to Canberra she enrolled in law, did wonderfully well, got a job when I moved up to Sydney in 1976 and began her own career. She stayed with the New South Wales University Law School for perhaps 15 years, and is now going strong with one of the big law firms in town. That's been a very positive, warm, stable family life.

But not so strongly Jewish as your background. I think you put aside some of the religious pressures.

Yes. The issue of ethnic involvement is such a fascinating one for anyone brought up in that tradition, because obviously there is a religious core to it. And on issues of faith I am a sceptic, an agnostic. There is a ritualistic core to Judaism, and I am not an admirer of ritual. It has both strengthening and divisive aspects to it. But nevertheless it wasn't a sanctuary into which I could escape, nor did I really want to escape. In fact I have close colleagues in Israel and work there from time to time, and I enjoy and am fascinated by the extraordinary history of that place and time and of those people, of whom I am certainly one.

Are you ethnically associated now, rather than religiously?

That's right. Every religion goes through its own evolution. It seems to me that the evolution of Judaism was stunted by its diaspora, by its being spread out – that now, having its own space and patch in the sunlight, it is starting to evolve again. But that's another story. I am part of that, but just a part.

As your career took off, you began to find the odd leisure opportunity. You become a sailor. You haven't been a sportsman before but have just ground away at it all.

Yes. I had played a few games – a bit of squash and so on. But my enthusiasm, to which I didn't come till after I was 40, is racing dinghies. I realised I had grown up in Sydney, with that superb harbour, and had not sailed. I have since learnt to sail them and to enjoy the racing, and I have as many friends in my small harbourside club as I have in the rest of my career. That has been a wonderful side to the sport.

What did you and your family find Canberra like? It must have been a culture shock.

Yes, but we were at the stage, with young kids, where Canberra was ideal – just laid on for young families. You can complain of Canberra even now that it is less culturally rich than great cities, and that is certainly true. Canberra was and is still a middle-class town. If you take it as it is, it is just great. You can grumble but we didn't. We had a wonderful five years there.

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Moving on: balancing teaching with brain research

You mentioned that you moved next to Sydney. To a senior lectureship, wasn't it?

Yes. I applied for and was appointed to a senior lectureship in the School of Anatomy at the University of New South Wales. Despite the scientific ferment in Peter's department, I found the institute life, the life of turning up to work with a small group day after day, quite stunting, I wanted to be interactive. I was looking for lots of faces. I wanted to teach, very actively.

You had been coming to Sydney to teach, hadn't you?

Yes. I had come up year after year to give a few lectures, and always enjoyed doing it. Also, my father loved to teach and he taught me a lot about teaching, just by example. He became a media figure in Australia. I can still remember him giving his last lecture (he was very sick at the time but he was determined to do it) when he must have been 75, saying that it was 50 years from his first class. He taught me that what you need to be a teacher is knowledge and passion and commitment. He said, 'It doesn't matter whether you stand on your left foot or your right foot, or it's a small class or a big class. If you have that knowledge and passion, you will teach.' I accepted that, not just at face value but with some thought in it, and it has enabled me to deal with the educational enthusiasms that sweep over the teaching scene from time to time, trumpeting the value of some technology or a particular way of presenting knowledge to the student. These ideologies come and go. What you need to be a teacher is to have a passion and communicate that passion, and the kids do respond. You can stumble and mumble but they'll still respond if the passion is there – and the knowledge, of course. They won't let you hoodwink them.

In those first nine years how did the research evolve?

During the years at New South Wales I shifted from the parallel processing model to study development. I became more and more interested in the ontogenetic development of the brain and the fascination of how the organ could wire itself together. That included a period of sabbatical at Yale with Pasko Rakic, which was very influential: I found him a very powerful, thoughtful figure. But I got stuck into the teaching and balanced the demands as best I could, and we had good, productive years. I must say, looking back, that not quite such a theme developed from them, although the themes have started to develop in the last three or four years.

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Building up research

In the 1980s you got a personal Chair. When did you go on to become Challis Professor of Anatomy?

That appointment was in 1987. It involved moving from the University of New South Wales to the University of Sydney. The department there needed building up, particularly on the research side. My predecessor – Michael Blunt, who was English by origin but had been in Australia for many years – had been an enthusiast for teaching and had introduced two things which I still cherish. One was a commitment to small-group teaching: if you have to have a structural philosophy that's a pretty damn good one to have. The other was to leave a teacher with a group for a long period so they could establish a relationship. We needed building up in research and also in another area. He had done a very good job on classical, topographical anatomy but anthropology, which was the great science in Sydney Medical School at the turn of the century, had languished. An important collection of Aboriginal remains had been built up, and a long string of very important papers on the anthropology of indigenous Australians had been published from that. Another predecessor, Macintosh, was the last of the great figures in that tradition.

So you became curator of these remains?

Yes. And with help, through a generous benefaction from his widow, we refurbished that museum magnificently. We have brought it back to life. Anthropology is the history of anatomy and it's really exciting when you realise that on a bone that is millions of years old you can see, drawn out on that bone, the same tubercles and tuberosities that are on your own, drawn by the same muscles, but millions of years ago. There has to be a sense of understanding of that history, and I want to communicate that to the students. So you can see that I would resist – and I do, but only in the gentlest of ways – the modern philosophy of teaching medical students related to clinical problems only. They will learn about the clinical problem, but they need to experience that scientific and historical background of anatomy too, although we don't really get time to go into Australian anthropology.

But that legacy also brought its burden. Because of the fierce debate – which we had to have – over ownership/control of these remains, I have had to deal, in as deep and analytical and thoughtful way as I can, with the Aboriginal claim to control all bones of Aboriginal origin, and work through it in a sympathetic way. I have as clear understanding as anyone can have, because I come from a victim group. Not in this continent: it is curious that when I travel to Europe I belong to a victim group; when I come back to Australia I am a member of an oppressor group. Sometimes, I tell you, when the shooting's done it is easier to be a member of the victim group.

I have done everything I can to fit in with the Aboriginal claims and always will. But I must say that the Aboriginals and all indigenous peoples claim – absolutely rightly – to be part of the human family and to deserve recognition. But if that is true, then their history is also my history, because I am part of the same family. So the claim of the most extreme to exclude people like me or white anthropologists from the study of these bones seems to me to be flawed. And I am sure that will come to be accepted. I hope that we can with care and responsiveness work through to that position, but it will take a few years.

Being a head of department was a good and bad experience. You realise how much management is required in an institution like a university. I was trying to live up to the old model, in which a professor took some of his or her time out from scholarship to build up the discipline but then got as quickly as possible back to the lab, but I found the universities in a mood of requiring more and more management. They didn't want professors or associate professors to be getting back to the lab; they wanted people who were happy to stay sitting at the committee table and to deal with the flow of reports that the modern institution needs. I stuck with it perhaps a little longer than I should have, but in 1992 the point came to get out. I got out still full of energy and by then it was time to become trained in molecular work. I took that opportunity and have had a wonderful year since. I am looking forward to the next 10 or 20 years.

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Blindness: the ontogenetic link

Brain development sounds fascinating. Was that a rewarding line to take?

Yes. I have realised in the last few years how rewarding, because in that time it has been going better than I deserve. It wasn't a dry patch, because we published paper after paper and I was interested in it, but I had to get the concepts, the data of development into my mind. I had to understand not just the neurones of the brain, to which Peter Bishop had introduced me, but the neuroglial cells, the supportive cells, because they are the architects, the scaffolds of development. And so I spent several years getting into understanding those glial cells and getting the techniques to study them. Introducing one talk, just off the cuff I said, 'Look, techniques give you power but they're also prisons.' I was thinking of this whole mount preparation, which I'd always studied with stains which showed me neurones. I'd worked at it, I'd walked across it this way, I'd walked across it that way. Now we have techniques that show us the glial cells and they break out of the prison of that old technique, but of course only to admit you to another room of the prison. But nevertheless years and years of fruitful work opened up and we began to understand the conversations that glial cells have with themselves and with neurones, and the roles they play.

Then we began to understand the interaction of neuroglial cells with the stress of birth. That is the concept I am now developing, that as the brain comes on line it goes through a period of stress, which is related to its enormous oxygen demand. It goes through episodes of hypoxia, of lack of oxygen. We became tremendously interested in the role of oxygen levels in control of events – of neurone birth, death, movement. Just to give you a feeling for the fruits that have come off the tree: there exist a series of human blindnesses which result from the death of the photoreceptor cells of the eye. Our contribution there – and we are still in the midst of the excitement of it – has been to pick up that the degeneration sets in in this birth period of stress, and realising that if we can relieve that stress we can rescue the cells and prevent blindness.

So there are categories of blindness that can actually be rescued?

I believe so. We have done it in animal models where the gene defects are probably like the human ones, but we have been lucky to get a transgenic mouse in which the condition has been produced with a human gene. If we can save this one – and we haven't done it yet; that's the gleam in our eyes – then we can go through the difficult and demanding process of transferring it to the human models. We can go to the people who handle the human condition and say we've got something to offer. So that adds a medical component to what has been a very basic scientific thrust.

Was it that kind of work, with its genetic aspects, that took you to Jerusalem? Or did Jerusalem actually show you that avenue?

I went to Jerusalem because in 1992, when as I said it was time to break out of the administrative shackles, a group there published the right molecule: evidence of a gene which turns on in hypoxic conditions and makes blood vessels grow to supply oxygen. I wrote to my colleague there, Eli Keshet – he didn't know me from Adam and I wrote by mistake to his graduate student, whose name was first on the paper, but I got the reply from the right guy – and now Eli and I have a close and warm relationship, and I hope to see him in a few weeks to push it along.

So I found myself in Jerusalem. Margaret and I had accepted a period of months apart for me to do this, but I have family there so there was an element of going home and now I have very warm relationships with that university. I had deliberately spent a year there in 1966–67 (Margaret came with me) just to experience that part of the world, and I found myself in the middle of the Six-Day War. I saw Jerusalem under siege and under fire, and even came under fire myself in that medical school.

They were bright and vivid memories but they were already 25 years old. I didn't go back for those memories; I went back for this molecule. We published papers together of which I am very proud. Of course, Eli's input to them was determinative. What pulled me in was the publication of genes which are hypoxia-induced, and I knew that hypoxia was driving developmental events. He gave me an insight into the molecular changes, and that has been of tremendous importance.

You have brought with you some wonderful, beautifully coloured illustrations.

These are a mixture of technology and ideas. The reds and greens are the dyes that work so well in the fluorescent microscope and therefore in the modern confocal microscope, so the technical excitement for me has been to learn to use this superb new instrument. The red is showing the glial cells in a piece of nervous system, the retina. The green is showing blood vessels. What we are exploring in these images, which you see in these red blobs, is the death of the glial cells so close to the vessels. And where that death occurs actually along the vessel, then the vessel breaks out; in this case out of the retina into the vitreous humour of the eye. That is the very beginning of the damaging proliferative vasculopathies which destroy vision in so many people with severe diabetes and venous occlusive disease. With that additional insight I think we then have ways of rescuing those cells, of healing the retina that has been exposed to hypoxia in the diabetic, and better ways than are now available of dealing with these blinding diseases.

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A wider arena: Alzheimer's disease

You have also been drawn into the great and fascinating sink of Alzheimer's disease –being pulled, perhaps, into a wider arena.

Yes. Alzheimer's disease has such links and then such differences. It has been with us for a long time but it has been identified for 70 or 80 years and has become a basket group of dementias for which we don't understand the cause. Alzheimer's thrust, when you read his original papers, was to distinguish his patient's dementia from a dementia that arose from syphilis, which we don't see any more. He drew attention to two pathologies, the plaques and tangles prominent in the cerebral cortex of the sufferers. Molecular biologists today have done beautiful work on both of those molecules, and on another protein, apolipoprotein E. But I was drawn in first through the Hebrew University connection and through a Jewish businessman, John Hammond, in Sydney, who was very committed to this because of his wife's affliction and who felt his own strength failing. He is in his late 80s now. I had returned from places that made sense to him and he asked would I be a trustee of the Sir Zelman Cowen Universities Fund, a charitable trust which he had established. That drew me into the field, and to understanding it.

A paper in a major meeting in Kyoto last year argued that the best correlates of Alzheimer's disease are not plaques and tangles but brain inflammation. I knew enough of the glial cells of the brain and the cells which might be involved that I could read the data – and it had an element of the loner idea which maybe struck a chord with me. I came back from Kyoto with this idea that I felt had fallen on a mind that was ready for it (but I don't mean that immodestly) and convinced that it was worth exploring. Not that it was true, because science isn't like that, but obviously the other techniques were not offering anything to the patient, the sufferer, and this did. There was evidence from retrospective epidemiological studies that anti-inflammatory drugs could prevent Alzheimer's disease. There was one prospective study which suggested that once it had started you could stabilise it and stop it from progressing. And those drugs are available. They all have side-effects, but it's so much more than is available to the sufferer.

So I persuaded the trustees; we convened a group of scientists to monitor it; and we convened a working party of real Alzheimer's scientists who took it on board. We have funded it and it is about to be launched officially. We aim to report within 12 to 18 months, and I hope we will do enough work to convince our Medical Research Council that there is a case for clinical trials. If so, it's exactly what that Fund wanted: at the earliest possible moment to produce something that could offer some hope.

It must be nice for you to have made the transition from focusing on nerve cells and the structure of the brain to dealing with wider human need.

Yes. But certainly it has a tie-in with the work I am doing now on cell death and survival in development, because we are talking about massive neuronal death. I believe it's quite different. I don't think it is driven, as it is in retinal development, by hypoxia or oxygen radicals. It may be an activated microglial cell rampage that sweeps through the temporal lobes and then the parietal lobes, and destroys the brain of these sufferers. And I think if that is true we can stop it. That would be a tremendous gratification.

We are beginning. We have funded four projects, one of which includes a preliminary clinical trial. That will be carefully done because the drugs have side-effects. One of the valuable contributions of the molecular work is that it has identified a group of people who are really likely to get Alzheimer's disease and to whom you have some justification to say that they really should take on this drug, with all its side-effects, if they get to a certain age. There is a great deal of caution about clinical trials. I am not a clinician but I am of the view that you have to try, otherwise you are never going to break down that caution. I am hoping I will see strong methodological connections that might bring me to work on Alzheimer's but I'm content at the moment to have coordinated that group and I'm looking forward very much to helping write the report.

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And wider still: animal welfare

Jonathan, we've taken you through the central strand of your career – neurophysiologist, neuroanatomist – to some new things at the cutting edge. This wider holistic person has published in a number of other fields as well – concerned about animal welfare, animals in experiments; concerned about population and the future of the world environment, and a number of other issues of public debate.

There were two or three of those debates into which, yes, I was drawn – by circumstance and by inclination too. I was drawn into the one over animals by a rising debate, principally in the United Kingdom but with its eddies coming out here, over vivisection. It was a renewal of an old debate and I wanted to get to the bottom of it. Having done a lot of animal-based research, I wanted to understand the moral challenge and respond to it by changing or not changing what I did. I came to understand the nature of debate, the tricks and also the earnestness of debate. I came to learn a lot about how well-meaning, good-hearted – and I mean that without patronising – societies like the British Union for the Abolition of Vivisection could be raided by fascist societies, as they have been, how anti-vivisectionism could become a cloak for a general anarchism, and how to deal with that, how then to respond in the most creative way. And that was obviously by trying to clear away the terrible edges of that debate and concentrate on the core moral issues with the real and earnest people.

That had its awful moments. The Australian group drew from England in deciding to focus on individuals and for some reason I turned out to be their focus. I decided not to delist my telephone but to just walk out and take the flak. It drew me into public debate and also into earnest writing, and I've tried to do both of those as best I can. I think we have managed, with a lot of input from a lot of people, to take that debate in Australia along very creative lines, where the issues of animal experimentation are handled by institutional ethics committees in which the debate takes place on a weekly or monthly basis, in detail, with animal welfare people brought in. And now there is legislation through all the States. So yes, I played a small role in that: some of my writings went beyond what was in the literature and maybe I made a contribution.

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Population biology

How were you drawn into the population debate?

That was really through my Academy work. In the '80s I was privileged to be asked to be Biological Sciences Secretary for the Australian Academy of Science and had a thoroughly enjoyable and instructive four years seeing science, as academies do, as groups with energy needing to be brought together. I was very encouraged by that fascinating period.

I was asked to represent the Academy at an international meeting of academies which was held in Bologna in '89 with the theme 'Scientific Problems of the Next Century'. Sitting down with a blank page to prepare a presentation, it slowly became clear to me that overpopulation was the great challenge we faced. It has a lot to do with medical history because the reason we are overpopulated is the success of medicine in reducing death rates. When I got into that debate I found it quite fascinating, because I began to disagree with the David Suzukis and the Paul Ehrlichs of this debate – not because they weren't right on so many of the issues but because they constantly took the high moral ground. I felt they didn't deserve the high ground and that taking the high moral ground was destructive.

Despite both Suzuki and Ehrlich being biologists, they have not dealt with the reality that we are overpopulated not out of carelessness or mismanagement, as is their constant refrain, but out of our success in doing something which we all accept is good, and that is keeping children alive. That although birth rates have fallen since the middle of the 1850s, the fall in death rates has been so dramatic that we have massive overpopulation. And if that is true, then the evil of overpopulation that is making a mess in so many ways is deeply entwined with the good of what we do. Until their entwining is realised, they can't be untangled.

I like the start of your lecture. You went back to Dickens: 'It was the best of times, it was the worst of times.'

Yes. It is the human condition that the good and evil of what we do are tightly bound together, and those who would preach usually are thinking of themselves as having the insight or faith to separate the good from the evil – which they have not. You can sense in that a loner's position, that I was not a conservationist nor a populationist nor a growth advocate, but I felt that I had identified the core issue of overpopulation and that it was worth arguing. People do respond to it.

The next step in that path, after the talk in Bologna and the Australian Foundation for Science lecture in 1991 in Adelaide, was to convene a symposium – which again the Academy was generous in taking under its auspices, not as its opinion but by giving it its platform. We were very lucky in that we met in 1994, just as the Australian Government through Barry Jones' committee (the House of Representatives Standing Committee on Long-Term Problems) was convening its inquiry into the population of Australia, and our submission was just in time for that. I think we made an important contribution there. That was a rewarding experience.

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Optimist or pessimist?

You're a great private crusader, but these are tremendously big issues and I don't see them all being untangled in time. Are you an optimist or a pessimist?

It's difficult sometimes to be an optimist. But in that lecture on population control I drew an analogy with the Cold War. Underlying what was happening during the depths of the Cold War – mutually assured destruction (MAD for short), the constant building up of the arsenals – was a constant series of meetings and a series of treaties on the use of the seabed, on nuclear weapons in space; the START I negotiations go back, I think, to the middle 1970s. START II is a bit later. Good was emerging but it was being outpaced by the growth of the armaments. And so I thought it was a striking and unique moment in history when Gorbachev declared that the Soviet Union would not again intervene militarily in Eastern Europe. It was an absolutely key moment, when a very proud revolution announced its limits. I can't remember another revolution that has done that quite so superbly as the Russian Revolution, and the Russians deserve enormous credit for saying, 'This vision has come to its limits.' That opened up so much, leading to the first disarmament since the Romans formed the centurion brigades. It's been an upswing ever since.

So yes, in times when we can't see the solution to a problem such as overpopulation we must work to lay the framework, because somewhere it will come. There is some element of optimism, in that birth rates are falling so universally that the United Nations people are correct to project a levelling of the population. It is at a very high level, but perhaps somehow we can manage through to there and learn not constantly to grow the population. I think we are going to accept the limits to population growth very soon, even within 20 years.

Limits to growth are going to be harder to accept. Governments who accept that their population should stop growing – I think the Australian government is close to doing that – will not be ready to accept that economic growth should stop, because it is the solution to unemployment, to the problems of the needy, of how to bring the needy help without soaking the rich. That second stage, of stopping economic growth, will be much slower. I can see reasons for optimism, but no reason for stopping developing the infrastructures with which we must one day solve these things, in good times or bad.

Your exciting book Parallel Processing in the Visual System, published in 1983, seems to me to exemplify your work. Such a contribution to the literature was overdue.

It was due in its time. It picked up on a theme that for me finished in the early 1980s, of the parallel processing in the visual system and its implications. It has in it two or three chapters which distil what I had come to understand of the heuristic debate that underlay both the creative ferment and the conflicts of that time, and have been reference points for me ever since. I tried to make it very strong empirically, because you become vulnerable as a scientist if you spend too much time with the cheerlessness of the philosophy. You've got to be careful to understand the philosophy but then not to be too entranced by it, but I think that scientists do need to understand the philosophical framework, the philosophical problems within which they are working. As I said before, Eccles and Popper were very influential with me. Popper, in one of his books, wrote that if you want to understand a philosopher you should understand the problems he was dealing with. That has helped me a lot, including when I go into the public debates: why are people taking particular positions, what are they defending, what are they trying to bring forward – a very good reference point that has helped me in these many ventures.

Jonathan, we've covered a rich story, a rich tapestry. It's been fascinating to talk with you. Is there anything behind the story that I have missed?

I've been lucky to be born at a time when I didn't have to die in somebody's army; I've had good health and a clear run. I have debts all over the place: to family, to my present family, to scientific mentors. I have tried to name the important ones but I'm sure I've missed some. I am still thoroughly enjoying it. Perhaps I could end on the message that the excitement is there and I'm looking forward to the next 25 years with the same sort of zest.

Before that's up, though, perhaps I'll come back and talk to you some more.

Sure. I look forward to that. And thanks for having me.

For so many things, thank you very much.

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© 2017 Australian Academy of Science

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