James Waldo (Jim) Lance was born in Wollongong in 1926. Lance completed his medical degree at the University of Sydney in 1950. He began his clinical work as a resident medical officer at the Royal Prince Alfred Hospital (1950-51). Cutting his residency short, Lance took up a National Health and Medical Research Council (NHMRC) fellowship at the University of Sydney (1952-53) to work towards his Doctor of Medicine (MD, awarded 1955). In 1954 Lance travelled to London, England to train as a neurologist and accepted a position as assistant house physician at the National Hospital in Queen Square. Upon his return to Australia Lance combined teaching and clinical practise with appointments as tutor at St Paul’s College (1956-60), visiting lecturer at the University of Sydney (1956-62), superintendent at the Northcott Neurological Centre (1956-57) and honorary assistant physician at Sydney Hospital (1956-61) and St Luke’s Hospital (1957-61).
In 1960 Lance once again left Australia to follow his passion for research work at the Massachusetts General Hospital in Boston. Lance returned to Australia as the founder of the department of neurology in the newly established medical school at the University of New South Wales (UNSW). He remained at UNSW throughout his professional career starting as senior lecturer (1961-63), then associate professor (1964-74), professor of neurology – personal chair (1975-92) and currently, as emeritus professor. Concurrent with his research, Lance continued his clinical practise at the Prince Henry and Prince of Wales Hospitals where he was chairman of the department of neurology (1961-92) and foundation director of the Institute of Neurological Sciences (INS, 1990-91). Lance continues to see patients as a consultant neurologist at the INS.
Interviewed by Professor David Burke in 2010.
Descended from veterinarians and merchants
Jim, you have had a career which has combined clinical medicine and scientific research and you were responsible for founding the first academic department of neurology in Australia. Can we start at the beginning with you telling us how you came into the world?
I was born in Wollongong, literally in the front bedroom of our house there, dragged into the world with forceps by a local general practitioner. I also spent my early years in Wollongong.
Can you tell us something about your forebears?
On my mother’s side, the first ones were veterinarians and they came to Australia from Edinburgh in about 1840. My grandfather on her side was born in Sydney but had to go to Edinburgh to complete his studies in veterinary science, as there was no school here. In fact, he ended up founding the School of Veterinary Science in Sydney—in about 1909. The main building there, the JD Stewart Building, is named after him.
That is the James Douglas Stewart Building.
Yes, James Douglas. I was named James after him. On my father’s side, they were merchants in the Birmingham area. Walter Lance came to Australia in 1870 and started a store down near Central Railway Station in George Street, which I’m afraid didn’t prosper. So he moved to Wollongong. This was fortunate as there was an enormous boost there in population, firstly with the coal industry and later the steel industry settling at Port Kembla. So that business did flourish. My father took that over from his dad when he died— my dad was only 26 when he did this—and built it up to be a very good local department store. The store was taken over eventually by David Jones when my father retired. So one side were veterinarians and the other side were merchants.
School days and a painful introduction to science
So you grew up in Wollongong?
In a sense. But, in fact, I suffered from asthma very badly as a small child and my parents were advised to send me to Tudor House, which is a small boarding school for boys near Moss Vale. It was and still is an extremely good school. I was there for five years and was miserable for the first year, I might say, at the age of seven. But subsequently I enjoyed it very much, and it certainly cured my asthma.
There was a famous headmaster there?
Mr Medley. He was later Sir John Medley and he became Vice Chancellor of the University of Melbourne and Chairman of the ABC.
Did you suffer under him?
He was a rather formidable person. He didn’t cane me—I was caned later on in my school career—but he had a very formidable presence. He was a very dignified man and he certainly played a part in my formative years. Actually, at Tudor House I suppose I had my first introduction to the sciences, by a chemistry master who took phosphorus out of its protective jar and thought he’d entertain us by showing how it glowed in the dark when he wrote on a board. Indeed, it did glow, very spectacularly, and it exploded. The result landed on my left shin and caused a bad phosphorus burn, the scars of which persist to the present day.
Despite that, you still kindled an interest in science.
Yes. Cotter Harvey, who was a well-known thoracic physician in Sydney, came to Tudor House, which his sons attended, to give a talk on respiratory problems. I asked a question afterwards. I said, ‘Why do people yawn?’ He said, ‘Well, I don’t know that I can give an answer to that.’ This was a revelation to me, because it had never occurred to me that there were questions that proper grown-up people and specialists couldn’t answer. I found out later in my career, of course, that life was studded with such questions.
Was this the sort of thing that was stirring in you at the time, a scientific interest?
I can’t honestly say that it was at that stage. I think it must have been at the end of my time at Tudor House because I sat for a scholarship to Geelong Grammar School. I didn’t get the scholarship but was awarded an exhibition, which I think was a sort of consolation or runner-up prize that involved a gift of £5—or I think five guineas it was in those days. I bought a very nice leather bound set of Shakespeare’s Plays, which one was obliged to as a part of the prize and which I still have. I spent all the rest on things of not so much scientific but medical interest—things like AJ Cronin’s The Citadel, Axel Munthe’s Story Of San Michele, and numerous medical histories.
You have mentioned Geelong Grammar School, but I have always associated you with The King’s School?
Well, this was at the beginning of the war. I went Geelong Grammer School in 1939, when war was declared. By the time that 1941 came, it had become very difficult to travel interstate, so my parents moved me over to dad’s old school, The King’s School in Parramatta. But Geelong Grammar was a marvellous school in those days, and I am sure it still is. It had very broad cultural interests. Some of its masters transferred without any problem to academic appointments. For example, Chauncy Masterman became Professor of Classics at the ANU; and the definitive historian of Australian history at that time, Manning Clark, became an Associate Professor of History at the ANU. So they had a remarkable team of teachers. Unfortunately science was not really a major specialty at that stage, but it had a very broad cultural impact.
I think you have used the term ‘Athens enlightenment’. Tell me about King’s; was there much of a contrast?
Moving to King’s was like going from Athens to Sparta because, during wartime, a lot of the younger masters were serving in the Defence Force. Four of the teachers there actually had taught my father. One of them was a quite outstanding man, a chap called Bartlett, and he really instigated the proper scientific method in teaching physics. About half of the physics course was didactic and one had to learn all the definitions and formulae that were necessary—and I still think this should always form the basis of any sort of scientific career. Then the other half was experimental. We were given the equipment and the tasks to do. We had to nut out the experiment, perform it, record accurately the results, analyse them and then present the experiment in written form to Mr Bartlett, who would give a very conscientious appraisal of it. I think, in retrospect, this played a very important and formative role in my scientific thinking.
Many people tend to associate physics and chemistry at the same time. You focused on physics there. Tell us about chemistry at King’s.
We had a lovely chemistry teacher, but he got a bit confused. At the beginning of every lesson, he’d say, ‘Is this my fourth form chemistry or my fifth form geology?’ and we’d have to enlighten him so that he could go on with the appropriate lesson.
Medical degree at the University of Sydney
With that background, why did you choose medicine?
Since I was twelve I’d always had a great desire to do medicine. I’m not quite sure why. I didn’t have any medical forebears. I did have an uncle by marriage, Justin Markell, who was a cardiologist at St Vincent’s Hospital. But I don’t think that was the real reason—I guess, simply, I was intrigued by health and disease and the whole history of medicine. I suppose lurking in the back of my mind was a vaguely altruistic feeling that it would be quite a good thing to do some good for somebody, if one could.
When did you start medicine?
I started then in 1944. Because the war was still in its final stages in that era, we had a fiveyear shortened course. But we had a lot of formal teaching in anatomy. Physiology was very weak at that time, but the basic sciences were otherwise well taught and we had some very good clinicians teaching us too.
Was there any research component to the undergraduate curriculum that you took in medicine?
No, not really. The other person in our year who was interested in research was Henry Harris. The Professor of Bacteriology, Hugh Ward, very kindly introduced Henry Harris and me to Howard Florey of penicillin fame, when he was visiting Australia, and he gave us advice about what to do for a research career. He recommended that we should go to Melbourne, which had the only really good department of physiology in Australia at that stage, and do the honours course, headed by ‘Pansy’ Wright. Florey suggested we then travel to the UK and do honours again at Oxford and proceed from there. We both flew down to Melbourne and Henry Harris adopted Howard Florey’s advice completely, to the extent that he replaced Florey, when he retired, at the Sir William Dunn School of Pathology and later became Regius Professor of Medicine, was knighted, became a Fellow of the Royal Society and has had a most distinguished scientific career. I wasn’t intrigued by the work going on in Melbourne, so I returned disconsolate. But my feelings—not exactly of despair—were alleviated by meeting Peter Bishop.
But I understand that you did undertake a research project when you were a student.
I inveigled a colleague, Alan Holmes, into doing a funny little bit of clinical research. I had observed that the rate at which the blood platelets settled in pregnant women became higher than it was before and, under normal circumstances, the ESR, as it is called—the erythrocyte sedimentation rate—is always a bit higher in women than in men. I postulated that possibly, if these pregnant women were carrying a female foetus, they would have a higher ESR than those pregnant women carrying a male foetus. So we took blood from all of these ladies during their pregnancy and then correlated the results with the sex of the baby when it was born. Unfortunately, like so many experiments, it was negative; there was no correlation.
But you still published that.
In a university medical journal, yes.
But that was your first scientific publication?
It was, indeed.
You mentioned that you came under the influence of Peter Bishop; can you tell us about that?
Peter was an outstanding man. After serving in the Navy, he’d spent four years with J. Z. Young in London and came to Australia and started one of the first research units, called the Brain Research Unit, at the University of Sydney. I met him and was enchanted by his enthusiasm and I felt that this was for me.
Was this after or before you graduated?
It was after I graduated from the University of Sydney. In fact, I foreshortened my senior year as a resident medical officer at Royal Prince Alfred Hospital in order to start with the Bachelor of Medical Science students that he was taking in at that time; in other words, I did three out of the four terms available in my senior year at the Royal Prince Alfred. The reason I did this was that Peter Bishop had some outstanding people who were joining him to do their Bachelor of Medical Science degree by research. These included Jim McLeod, who has been a very close friend of mine all my life, who became a Professor of Medicine and then of Neurology at Sydney University and has become a Fellow of the Academy; and Bill Levick, who became a Professor of Physiology and, again, an academician. Some very outstanding people were Fellows at that time.
But you were doing an MD, weren’t you?
I was doing an MD degree while they were undertaking a degree at the end of their third year of the medical course. It was extremely rewarding. Peter Bishop knew that I was interested in movement and movement disorders whereas he was working on the optic nerve and vision. He suggested that I start working with him in order to get to know the methods and how to use the equipment. It was very daring equipment in those days, like storage oscilloscopes and things of that sort. In fact, initially we didn’t even have storage oscilloscopes; there were coated photographic plates and one had to wind them down each time to capture a single oscilloscopic sweep. Then the great advance: we had storage oscilloscopes, so we could have a number of sweeps before we photographed them. Anyway, he introduced me to all of the technology.
I then plunged off into the pyramidal tract and wrote five papers on it, including one on an attempt to regrow the severed pyramidal tract. It is interesting: they’re still working on attempts at regrowth of the spinal cord and the motor tracts. We were using a thing called pyrogen to cause a fever that was said to stop the glial cells growing that were preventing the neurones from branching out. But that was negative too.
It is also true that some of the work that you did on stimulating the pyramidal tract was a forerunner to work that has since been done by people like Vahe Amassian, in stimulating the corticospinal system in human subjects.
I think it threw a lot of light on the pyramidal tract in cats, which certainly has some implication for human work.
While you were doing the research, Jim, did you do any clinical practice?
I felt it most important to keep up with my clinical work. At that time George Selby was a neurologist at the Royal North Shore Hospital. I think he was the first person in Australia who was allowed to call himself a neurologist, after a considerable battle, because the aim was to keep us all as general physicians with an interest in a specialty. George Selby was the Superintendent of the Northcott Neurological Centre, which was run by the Returned Soldiers League for the families of ex-servicemen with neurological problems. I used to go there one day a week and initially sat in with him and then I ran my own clinic, which he supervised. At the end of that time, I felt I had a good, sound grounding in clinical examination and history taking. This stood me in very good stead in later years when I specialised in neurology. I must say that I regarded George Selby—with Peter Bishop—as one of my mentors. George was a consummate physician and neurologist, a very good clinician and a great influence on me. Peter Bishop, of course, was an outstanding influence in leading me along the scientific field in physiology.
We will come back to George and Northcott Neurological Centre a little later, Jim, if we may. But at this time you were finishing your MD thesis.
That’s so. I wanted to go to England to train in neurology. In those days it was not really possible to train in any specialty wholly in Australia, so I obtained an appointment as a ship’s surgeon to work my way over to England.
You didn’t get on an aeroplane?
No. In those days it was a threeday journey to get to England in a propeller-driven aircraft. One had to fly to Singapore and overnight there and then spend two days hopping across Asia and Europe to get to London, and it was prohibitively expensive. No, no. I signed up as a ship’s surgeon on a shilling a month. I also got my return trip to England in return for my services.
Your promised pay: did you cash that in?
I didn’t get my shilling a month. I went to claim it in the office of the Orient Line in the City of London early one dark morning and I was told that, in order to claim my shilling, I would have to join the Seamen’s Union at the cost of £10. So I decided not to collect my shilling. I might say that it had been snowing heavily in London and, as I left the office of the Orient Line—this was right in front of the Tower of London and Tower Bridge—all was covered in snow. Having been brought up in the British tradition, I just sort of melted when I saw this wonderful, snow-covered scene with the Tower Bridge and Tower of London.
Was the trip to England direct; how long did it take? We are used to flying there within 24 hours these days.
First of all, I had to sign up for a cruise for a couple of weeks to Noumea. Then the trip to London took a month, first of all around the coast of Australia to Melbourne and Fremantle, then across to Colombo, through the Suez Canal into Naples, Gibraltar and then to London. I must say that it was a most enjoyable month because the ship that I was on, the Orcades, was first class; hardly anybody was sick and I was virtually a first-class passenger.
By way of contrast, coming back I was on the Otranto, which was on its last legs. It was a terrible old dump of a ship and it served as a migrants ship—the £10 Poms, as they were called in those days, and their children. The children were in cramped quarters below decks and they got every conceivable illness, like gastroenteritis, chickenpox and German measles. We put a rope across the poop deck and had the kids with German measles on one side and those with chickenpox on the other and we trusted that they wouldn’t meet in the middle. It was a terrible, terrible trip. I had to sew up heads of the crew almost every night. Not a good trip, that one.
Post-graduate work at Queen Square
Let’s talk a little bit about that time in London. You were on the house at Queen Square?
I was officially an assistant house physician—and how did I get this job? First, I did a threemonth course in neurology, which they ran at Queen Square, in order to get known, really, to the senior staff. Then I applied for this job. It was the custom in those days to go around to the consulting room of each of these specialist neurologists. I had to trudge around Harley Street and Wimpole Street—in the snow, as it happened—and be interviewed. It was quite startling—the difference in the offices of these people. Sir Charles Symonds, who was the doyen of neurologists at that stage, had quite simple, austere rooms, rather like I imagine Sherlock Holmes might have occupied in Baker Street. Dr Ellington, I remember, had an extremely elegant townhouse. I was ushered into a library with thick-pile carpet, the waiting-room for the patients, and then through into his office with a lovely big desk. I seem to remember that there was a decanter of sherry on one corner of the desk—very elegant consulting rooms.
Were there any outstanding personalities at Queen Square during your time there?
Certainly on the clinical side, with people like Sir Charles Symonds and Sir Francis Walshe. Sir Francis had officially retired at that stage but had half a dozen ‘grace and favour’ beds, and I was allocated to be his houseman. The joy was not only in the neurological side but in his command of English. I can remember him on one occasion picking up the nicotine stained fingers of one of the patients and saying, ‘Ah, cremating yourself on the instalment plan.’ On another occasion there was a dear old lady; every time he asked her to open her mouth and say ‘ahhh’, she’d open her mouth and her denture would fall down, clonk. After several repetitions, Sir Francis said, ‘Ah, the portcullis effect.’
Macdonald Critchley was doing his work on the parietal lobes and he was also interested in headache at that time—and remained interested all the rest of his life. But I think the only person on the consultant staff who was really interested in research was EA Carmichael, whose dictum was ‘the proper study of mankind is man’. He said that the basis of all clinical neurology was physiology. That, in fact, has been a principle that has guided my career throughout my life. There were other people there who were research fellows, like John Walton, who later was knighted and is now Lord Walton.
After your time in London, you came back to Sydney and I understand that it was back in Sydney that you met your wife, Judith. Can you tell us about your first meeting?
I’d first met her when she’d got a post in physiology; she was a medical student. Her father, who was a house master at The King’s School, got in touch with me and asked whether I would give her some tutorials in physiology, which I did. I was entranced by her at that stage; but I was an old man of about 26 or 27 and she was about 19, so nothing came to pass for several years.
When I came back from England after two years of post-graduate work, I went to a dance at St Paul’s College at the University of Sydney. I met her again then, and this time it really took off.
You have four children?
Well, we have five children and now we’ve got 16 grandchildren and two lovely step-grandchildren as well. I’ve had a charmed life. I have a happy marriage, family life and a satisfying career. I’ve enjoyed every minute of it.
Did any of your children follow in your footsteps?
Indeed. Fiona is a medical graduate and married an orthopaedic surgeon, Craig Waller, and she assists him as well as having had her four children and leading an extremely active life.
Bridging the gap between clinical and research work
Jim, when you came back to Sydney, how did you find the medical scene?
I first went to Peter Bishop and asked if I could combine physiological research with clinical work, and he said, ‘Regrettably, no.’ He said, ‘I’d love to have you as a senior lecturer in physiology, but there’s no mixing with clinical medicine.’ He said, ‘You’re either a physiologist or a clinician.’ I, of course, wanted to bridge the gap and be both, which I subsequently did. Anyway, I did lecture in physiology for five years, when Peter Bishop became Professor of Physiology at the University of Sydney, so I did maintain that close link with Peter and his department.
I also went to Ruthven Blackburn, who was the Professor of Medicine, and he said, ‘Well, look, there could be a vacancy as a senior lecturer coming up in a few years time,’ and he said that I’d be welcome to apply for that. But this seemed a rather sort of slow track and there was no guarantee then that I could have any beds of my own, so to speak. I could have beds in the professorial research unit, but that wasn’t what I envisaged; I wanted to set up a clinic and a department. But, failing that, I took a job as Superintendent of this Northcott Neurological Centre, where George Selby was still a consultant; he continued to be a very strong influence during the years that I was attached to it. I was also appointed to Sydney Hospital as an honorary assistant physician, because we couldn’t call ourselves neurologists in those days.
With George Selby you wrote a famous paper on migraine.
He really started my interest in headaches particularly. We had a large number of headache patients attending that clinic and he encouraged me to analyse the case histories, in detail, of 500 patients. That was easy to do because all of the case histories were typewritten and there was a set format for the history. We took a very detailed history, including all the precipitating and relieving factors and accompanying factors of headache. It was a herculean task, going through 500 records in detail—but it served a useful purpose. He and I published this paper in 1960 on the analysis of 500 case histories of migraine.
I gather that at about that time you took a year off and went to Boston. Can you tell us how that came about?
During my time at Sydney Hospital, there was no opportunity to be solely a neurologist. I wasn’t asked to lecture on any of the neurological topics; such lectures were given by senior general physicians. I had a yearning, of course, to establish something myself.
I did have one very interesting family that I analysed at Sydney Hospital, which had repercussions later on. This was a family of four delightful young adults with a very unpleasant condition called Familial Myoclonic Epilepsy. These kids were the result of a consanguineous marriage between cousins, both having the recessive gene. I studied these very carefully and they all had these myoclonic jerks, which are sudden jerks. What intrigued me was that, after some of these jerks, they would simply fall to the ground as though lifeless. Usually the jerks were followed by falls. Sometimes the falls occurred on their own and sometimes the jerks occurred on their own. This intrigued me and I wondered just what was happening. Was the jerk throwing the patient to the ground, causing the fall? I later had an opportunity to investigate this when I was in Boston because I had patients there with somewhat similar symptoms and signs.
Can you tell us how you came to go to Boston?
At that stage a new medical school was formed at the University of New South Wales. It was to start its departments in 1959 and take medical students later on—I think eventually it was in 1964. They were advertising then for foundation chairs. Ralph Blacket was appointed to the foundation chair in medicine. I thought that, if I broadened my academic experience at a good centre, I could apply for appointment as director of the department or division of neurology. So I applied for an overseas travelling fellowship, which I obtained.
Bob Noad, later Sir Kenneth Noad, very kindly wrote to Raymond Adams, who ran the department at the Massachusetts General Hospital of the Harvard Medical School. Ray Adams, who died only very recently, was a wonderful man, a leading neurologist, and he wrote a magnificent textbook of neurology with Maurice Victor. He was admirable in every way as a clinician, as a pathologist and later as a friend. When I arrived there, I told him that I was interested in movement disorders. He said, ‘Well, Jim, I’ve got four interesting ones here that puzzle me,’ and he introduced me to four of his patients who had suffered cardiac or respiratory arrest and I saw that they had the same clinical syndrome as my family with myoclonic epilepsy. As soon as I saw them, they seemed familiar—the same jumping and jerking, the same falls. This time I really could do something to find out what was doing it.
By means of various neurophysiological methods, including checking spinal reflexes, like the H reflex, during the falling attacks, I found that there were two separate entities. The jerks in these people were coming from an enhanced reflex which involved the cerebral cortex (in others, it involves the reticular formation of the brain stem). But, in these particular ones it involved the cortex, you could actually trace the stimulus-to-touch up to the brain, where you saw a spike-wave complex, and that would then lead down to the jerking of the limbs. On the other hand, the falling attack was quite a different thing: it was caused by inhibition of the normal tonic control of muscle posture and something would happen to switch it off and they’d fall to the ground like a stone. We later published a paper on this posthypoxic myoclonus, which has become a standard paper.
This is the Lance-Adams syndrome.
It has been called the Lance-Adams syndrome, yes—or, otherwise, ‘posthypoxic myoclonus’.
Can you tell me a little bit about the department at Massachusetts General and the environment in Boston?
It was quite extraordinary. I conducted some research into Parkinson’s disease at the same time by courtesy of Bob Schwab, who ran an enormous army of Parkinsonian patients. But, more than that, the people who were the other registrars and research fellows at the time I was there all later became outstanding neurologists in America and heads of their departments all over the States. That has led to my close association with the American Neurological Association. I was on the foundation board of their journal, Annals of Neurology and I am an Honorary Fellow.
Annals of Neurology, which started with you as one of the foundation editors, is now one of the leading neurology journals in the world.
It is true to say, that while these people in Boston were leaders of their field, also your personal friendships and contacts with them have opened up something in terms of Australian science and the opportunities for people after you to get training in the States.
I think that is the case. It led to a number of visiting professorships in America, including the University of California, San Francisco. I became generally known among American neurologists and that, I think, was probably beneficial for those who have come after.
You mentioned work with Bob Schwab on Parkinsonian tremors; and Movement disorders and motor control have been one of the strengths of your academic career. Can you tell us a little bit more about that particular study?
It was well known that Parkinson patients often have a resting tremor, sometimes called a pill-rolling tremor, which is an alternating tremor between opposing muscles at the wrist. When we looked for rigidity or stiffness of the limbs, there was a cogwheel effect that was at the same frequency as this tremor. But what intrigued me was that some patients had a cogwheel effect with no apparent tremor at all. To shorten the story, I found that, when they were actively contracting the muscle, they developed a different sort of tremor, a much faster tremor but very characteristic, and that tremor was the same as the frequency of cogwheel rigidity. In other words, the factors causing rigidity from the extrapyramidal system were broken up by whatever tremor was dominating the motor neurone pool at the moment.
So the frequency of cogwheeling was determined by their dominant tremor?
By the dominant tremor, whether it happened to be in an action tremor or a resting tremor. This was quite a useful clinical point because you’d see patients not swinging one arm and there’d be no sign of any tremor; but, if you got them to pull up against you, you’d find that the non-swinging arm had an action tremor.
How did you find Boston as both a social and a scientific environment?
It was brilliant, really. We had a wonderful year in Boston. It was a difficult one for my wife, Judy, because we had our little daughter Fiona with us and Judy became pregnant with Sarah while we were away. In fact, we had our second daughter, Sarah, in Boston with a wonderful Canadian obstetrician at the Boston Lying-in Hospital. But she had to drag herself through the snow of the Boston winter, dragging Fiona along with one hand, to do the supermarket shopping. She’d leave it at the supermarket and I’d have to pick it up on my way back from the hospital. I had to trudge back to the bottom part of Beacon Hill where we were living and, on really bad days, I had to wear ski gear into the hospital. Sometimes everything stopped in Boston for days at a time and some of the surgeons had to ski in to do their operating.
Back to Australia to start a department of neurology
It must have been quite different to life in Sydney. You came back to the University of New South Wales?
While I was away I applied for, and was appointed to, a senior lectureship. I was given the brief to found an academic department of neurology at the Prince Henry and Prince of Wales hospitals.
It must have been a pretty barren academic environment in those days.
Well, it was a challenge. The Prince Henry was really a rundown fever hospital; it was mainly an infectious disease hospital. I think, offhand, they had a couple of hundred beds—a hundred for infectious disease and a hundred for general medical and surgery, but it had a very fine name for treatment of infectious disease and it had an unparalleled site overlooking the Pacific Ocean. It was the only hospital in the world, I think, that had its own eighteen-hole golf course. It was a lovely setting but very unfavourable for building up as a teaching hospital. Nevertheless, we were able to do that.
I would pay tribute here to the first neurosurgeon appointed, Alec Gonski. Alec was a tower of strength. He was a wonderful neurosurgeon, a charming man; all his patients did well. We had a very happy and friendly relationship over all those years, building things up. We very soon attracted patients from other centres and became extremely busy. I might mention that Alec Gonski’s son, David Gonski, is now the Chancellor of the University of New South Wales and an outstanding businessman and philanthropist. Anyway, Alec and I built up this department. I started a headache clinic which was soon flooded with patients, so much so that we had to cut it down eventually and just have general neurology clinics. We were extremely busy and built up the clinical side very rapidly and the research side at the same time.
A revolution in migraine management
In those days your research work involved exploiting the opportunities that were presented from the case material that you saw, in terms of the patients there, and you had two main themes, I understand.
One was the headache theme that we followed all the way. There had been reports from Florence, Italy, by Professor Sicuteri that serotonin excretion products in the urine increased in headache, so this gave us a clue that serotonin was involved. A paper from New York from Kimball, Friedman and Vallejo also said that the giving of serotonin as a therapeutic measure could be helpful in stopping a migraine attack. We appointed Don Curran as the first research fellow in headache, and he confirmed the observation that serotonin excretion products were increased. Michael Anthony took over and demonstrated, by very careful estimations of serotonin, that there was a sharp drop as the serotonin was discarded from platelets and that, if that occurred spontaneously, the migraine headache developed. If one injected something that made the platelet discard its serotonin, it would also produce the migraine type headache. We confirmed the New York observations that injecting serotonin would ease the headache.
So these sorts of studies led to animal experimental work on the mechanism of migraine with the investigation of the effect of serotonin on blood vessels and the central nervous system that continues until the present day. That, in a sense, led to the development of the triptans, which have been the most outstanding development in treatment of migraine. These observations of ours and similar observations by others led to Patrick Humphrey taking an interest in the whole thing. He was a chemist in the Glaxo Laboratories in London. In those days, when we made our observations, there were only two receptors known for serotonin. Nowadays there are many; there are about seven or more major divisions and many subdivisions. Anyway, this was all becoming known at that time. Patrick Humphrey devised a substance that affected the correct receptors to stop the migraine without stimulating other receptors that gave rise to side-effects. The first one was sumatriptan, and that is the forerunner of all the triptans that are still now the first line of defence in treating acute migraine. So that has been a success story.
I have heard Pat Humphrey refer to the research that you started at Prince Henry as the catalyst for his work on sumatripan, Jim.
He has actually told me that, yes.
The headache theme has been ongoing all your life; it is still an ongoing research program. Can you tell us a little bit more about it and who is leading the charge?
I’ve been terribly thrilled with the way that it has developed. An outstanding member of our group, Peter Goadsby, became an associate professor at UNSW and Prince Henry, first of all, with this work and then he went to London, where he set up a clinic at my old alma mater, Queen Square. He has now gone to the University of California, San Francisco, and runs a world-leading research laboratory and clinic in headache. Professor Sandrino Zagami and Dr Geoff Lambert have continued the work here in our own university. So I feel that it is still in good hands and I can just sit back and admire it from afar.
Investigations in motor control
But the migraine field was only one of the themes of your research work. Can you tell me about the motor control side?
I’d always been intrigued by the fact that, when one tapped a tendon in a person who had spasticity, as well as the particular muscle contracting, one observed muscles all over the body contracting. Why was this? The current thought was that the impulse went into the central nervous system and spread up and down the cord and, therefore, triggered off the motor neuron pool of all these other muscles. It seemed a very unlikely sort of description. It was thought that a tendon jerk was dependent on the direct stretch of the muscle and a little sensor within it, called the muscle spindle. Again to make the story quite short, we showed that, in tapping the knee jerk, it didn’t have to lengthen or stretch the muscle at all. If we had a piezoelectric crystal on the skin to detect vibration, the knee jerk increased in amplitude as the vibration wave increased. The more the tendon was tapped with greater force or particularly the rapidity of the impact, the muscle was not necessarily lengthened; maybe it would be shortened. But the vibration wave induced was responsible for triggering off the reflex.
This led to a study of the radiation of reflexes in spastic patients. By ‘spasticity’, I mean somebody who has suffered spinal cord damage or cerebral damage that gives them very brisk reflexes. Even if a patient was going by on a steel trolley—and you banged the trolley, the patient would get these jerks, like the myoclonic jerks that we were talking about earlier. The reason for this is that, as you tap, one sets up a vibration wave that travels through the particular limb, even over to the other side of the body, and initiates jerks there. So the vibration is the essential thing that triggers off the ordinary tendon jerks that the neurologists test and not the direct muscle stretch.
We then thought it would be fun to see what would happen if you applied a vibrator to the muscle to see whether this would produce a tendon jerk. We applied the vibrator to a muscle, assisted by Peter Nielsen, our very able technician, who became a doctor of science and a professor; but at this stage he was an assistant research worker. I placed this heavy vibrator on my thigh—I think it might even have been a floor sander or something of that sort—and, to my amazement, it didn’t produce the knee jerk at all. What I felt was a very strange cramp in the muscle and I observed that my leg slowly rose up, beyond my control. By concentrating, I could deliberately relax it; but the moment I was distracted it came up again. This was a tonic reflex. You see, a knee jerk is what we call a ‘phasic reflex’; it is just very brief. But muscle tone is the thing that is increased in spasticity and Parkinson disease. We wanted a tool to examine muscle tone and here we had one. This was subsequently called the ‘tonic vibration reflex’. It raised an enormous amount of interest in physiologists but not, curiously, among clinicians.
This interest in vibration led to a collaboration with colleagues from Sweden. Can you tell us how that came about?
Sir John Eccles was visiting my department and I told him, with great excitement, about this. He said, ‘Oh, I’ve just come from Sweden. A chap called Hagbarth presented a very similar phenomenon.’ So we communicated with Hagbarth. Noone had ever described this reflex before, but he had reported tonic contractions of muscle when it was vibrated. We exchanged letters, and this was the start of a very wonderful friendship and collaboration between us and Sweden. You [David Burke], later went to work with Hagbarth and Hagbarth came to do work in our department. So that was the start of a very fruitful investigation into aspects of tonic control.
And you pursued that work on vibration, Jim, in both humans and animals.
This is true. It was a very easy thing to elicit the tonic vibration reflex in the anaesthetised animal. This helped us to determine just which parts of the brain were responsible for the maintenance of muscle tone and how it could be inhibited. I don’t want to go into the technical aspects of it, but it gave a very good animal model of what we had found or surmised in humans.
The development of this theme of your research work is what ultimately led to the development of the Prince of Wales Medical Research Institute.
Well, yes; but let’s say that it’s because of you and Simon Gandevia, who formed the motor control unit of our research work. Of course, you became a member of the Academy and so did Simon Gandevia. Then the two of you were invited by Ian McCloskey to join together to form this Prince of Wales Medical Research Institute. So I think that our motor group was really the foundation of the New South Wales medical institute, a fact that they have not always acknowledged.
Books for clinicians, patients and children
Jim, I recall that you’ve incorporated a lot of the understanding that your research work has brought into a book, A Physiological Approach to Clinical Neurology.
The guiding light of my research and clinical career has been to try to explain clinical phenomena in physiological terms and apply that to treatment. I wrote this book and, in the last two editions—the last edition was back in 1981—I invited Jim McLeod to join with me to write sections that he was particularly expert in. Even now, some clinicians in America come up to me at meetings and say that they remember reading this and it helped get them through their boards of neurology. So it did make some sort of impact.
But this is not the only field. You have written books on the scientific basis of migraine for both researchers and clinicians and also for patients, haven’t you?
I’ve kept on with this. The last edition, the seventh edition, was in 2005, and in this I invited Peter Goadsby, a former student, to co-write with me because then he was at the very cutting edge of medical research and I provided some sort of wisdom and historical perspective; he had all the latest discussions of genetics to support his views.
But it is not just the scientific field; you have also written books in trying to convey the insights that you get into headache for people who suffer from headache.
This is true, yes. Simon & Schuster published a series of these books on headache—popular books explaining headaches and what to do with them. They’re now out of print.
Can you tell me about The Golden Trout?
When the kids were small, I wrote this little book, The golden trout. I used to tell them stories before they went to bed. I turned this into a little book, which was published in 1977 when the children were quite small, because I remember the introduction is a picture of me sitting there with my son, Robert, on one side and my little daughter, Sophie, on the other. It’s a fantasy about the Great Golden Trout and the way that one of the golden trout’s children was caught by a rather vicious bullyboy. This caused a drought in the valley and bushfires and all sorts of drama and it was only restored when the golden trout’s child was returned.
I seem to remember that that was very well reviewed.
Yes. The funny thing is that I wrote several stories after that and submitted them to a lot of publishers and I was told that fantasy had no part to play in children’s stories. I was told they had to have social content—a bit of incest or being an only child or some sort of childhood challenge like that. Shortly after this, of course, the Harry Potter series and Lord of the Rings came out. So it just showed that that was a lot of nonsense. That remains my solitary children’s book.
One thing that has marked your career, Jim, is that you have taken the opportunity presented by patients of studying the mechanisms underlying their conditions. Can you tell us about some of the conditions that you’ve studied?
Look, there’s an old saying that ‘one patient with a new symptom is interesting, two is a coincidence and three is a paper’. I have always been a sort of collector of unusual things and have put them on the back-burner. They include all sorts of odd things, like neck-tongue syndrome, sex headaches and funny postures assumed in dystonia. Visual hallucinations is another interesting one and Harlequin syndrome, where people flush and sweat on one side of the face and not on the other.
The Harlequin syndrome: can you tell us a little bit about it?
This started off with my daughter, Fiona, actually, when she was working I think in general practice shortly after she left hospital work. She said, ‘Oh, this will puzzle you’—and this was a woman who, whenever she played squash, flushed brilliantly and sweated on one side of the face and didn’t on the other side. This resembled very much the traditional painting of Harlequin in Commedia dell’arte, so we thought we would call it Harlequin syndrome. Eventually we accumulated a number of others with this.
Peter Drummond, who is a very talented research worker—now Professor of Psychology at Murdoch University in Western Australia—worked with me in elucidating this syndrome. Essentially, it appears to be part of an autonomic neuropathy. At first we thought it was compression of the fibres that left the upper part of the spinal cord to supply the face with the sympathetic supply. It hadn’t been realised, before we did a whole series of investigations, that the sympathetic nerves, which were thought to constrict blood vessels and make people pale, also had fibres in them that made people flush. So this was quite a useful scientific endeavour—explaining this so-called Harlequin syndrome.
How about visual hallucinations?
This was fascinating. A level headed farmer reported wild animals of all sorts creeping into his left visual field. Every time he would look to the left, the animals would retreat; and, when he would look forward, they would come out again. This, we found, was caused by a blackout in his field of vision in that area caused by, in his case, a stroke affecting a limited part of the primary visual cortex. I eventually collected about 12 such patients; they all had these hallucinations from a lesion in an area affecting the primary visual cortex. If the normal input into the visual cortex is not there—if it’s taken away—the association cortex which surrounds it, manufactures fantasies or memories to fill the gap. The most striking one I remember was Her Majesty the Queen, who emerged from the left side of the ward, went across the middle and just disappeared. The person who had these hallucinations described her exactly, with her handbag and hat and so on.
This led to a landmark paper in Brain, didn’t it?
On a form of visual hallucinations and their causations, yes.
Jim, I think you have said that the measure of an academic lies in the success of the students that you have trained, who have gone on to develop academic careers and become professors in their own right. Looking back on your career, can you tell us about some of your highlights?
I’ve described really how your own work has led to the development of an institute and how headache work has led to Peter Goadsby being outstanding in his field. Thinking of others in the motor field, there is Peter Ashby, whom you know well, who was a professor in Toronto. Right throughout the world there are people like Tassinari in Bologna in Italy, who came to us from Gastaut in Marseille; and Mike Welch, who came from London and then Houston. We’ve got scattered representatives, so to speak, in different parts of the world who have become outstanding in their own right—and there is an enormous sense of pleasure and pride in that.
As well as showing insight into the black box that the brain was when I graduated.
I think you and I have been very lucky to have spent our lives in a field like neurology, which has not only given us intellectual stimulation but also been such a source of pleasure. I’m still working part time and derive enormous pleasure from doing so.
Jim, I think we are both very fortunate in being able to work in a specialty that has been growing, and I’m particularly grateful for the opportunity of working with you during this period of time and for the opportunity of conducting this interview. Thank you very much.
Thank you, David.
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