ISN VIDEO LEGACY PROJECT

David: John, it is an honor for me to interview you, to explore your distinguished career in Nephrology, but quite frankly I see it as an exciting and at times perplexing story, really a mystery story if I may say, which demands answers. How does one stumble into a life of nephrology, do so much pioneering work in renal transplantation, and then pursue relentlessly an ever-widening commitment to higher ethical values in kidney disease and medicine in general? So lets start with the beginning of your story and reveal the events, which steered you from one chapter to the next. First question: What was medical ethics to you as a medical student and junior physician?
 

John: Well when I was a student, which was in the 50’s, 40’s actually, late 40’s and early 50’s, medical ethics as a subject really did not exist. It was assumed that ethical behavior by physicians was one of the parts of the ‘art of medicine’ that when learnt as an apprentice by walking the wards with seniors who pontificated a little bit and who were very important, but from them one was meant to learn what was needed for ethical behavior in the what was then the centerpiece, ‘the doctor patient relationship’. So many things have changed since then, but ethics was essentially a subject that was not talked about.
 

David: Now, as a young man you found yourself in the military in India.
 

John: Yes. After I’d graduated in London at Bart’s  Hospital (St Bartholomew’s H.), I was called up. The war was over actually, but military service continued and I had the good fortune of two years in the army most of which were spent as a medical officer in India. And there I was with the Gurkha brigade and, at that time, Nepal was not an open country to Europeans so the recruitment of Gurkhas was carried on the border. At each end of Nepal, there was a British Army border post, and I was in both of them at different times.
 

David: You must have seen some real, raw medicine?
 

John: Broadly speaking the Gurkha troops were fairly healthy and well. When we recruited them they had to walk out of the valleys, which involved roughly 11,000 feet up, 11,000 feet down, every day for a few days. The ones that got to the camp were fit and broadly speaking there was not a problem. The area of India that we were in had no medical coverage at all for the local people. Zero. So the other medical officer and myself would see every local villager who was sitting under the shade of a certain tree at 9:00 in the morning, after we had seen the ‘sick parade’of Gurkhas, and we’d see them for free using the equipment provided by the Queen, or rather the military, and we did actually have some extraordinary medical experiences there.
 

David: And then you became aware, I guess perhaps painfully, of humans with absolutely no opportunity, no access to health care.
 

John: Yes. It was an extraordinary experience. We were the only people there. We were the surgeons, the anesthetists, the physician, the lab person, the whole lot rolled into two and we felt justified and this is where some of the sort of innate hubris of medicine started to come through. We felt justified in doing things for which we were not trained.
 

David: And then from India soon thereafter you find yourself on the wards with Sheila Sherlock and another test of your developing medical values I suppose.
 

John: Yes. Let me just lead to that by saying that I had the experience which I should admit to, in India before leaving, of trying to do something for a woman who had an enormous goiter, and she was having trouble breathing. We thought that she would not live long with this so we actually operated on it and she died on the operating table from hemorrhage.. And that was a very humbling experience. We were trying to do good and we did a lot of harm. And that made me very cautious about using the power that medicine unfortunately, or fortunately, gives to physicians when they are in situations where people have nothing else. I then formed the resolution that I wanted to go as far as I could in learning the art of medicine and lead into a life in research. And with that in view, when I came out of the army, I obtained a position as junior to Dr. Sheila Sherlock at the Hammersmith Post-Grad. Medical School, in London. She was the queen of the liver, both in Britain and indeed worldwide for many years. She told me when I took the position that I was responsible for everything that happened on the ward, on two wards while I was there, even if I wanted to take a day off I was responsible for what happened when I was away, so in fact there was very little time off!!
 

David: How much were you paid then?
 

John: One was given one’s keep, I mean one was fed and housed. The money was nothing. I’m not sure it was absolutely zero, but it was trivial. One didn’t look to it as an income.

David: And as you look back were there some formative value experiences?
 

John: There were and it’s a little difficult to describe it exactly because it was an experimental unit. There were 50 beds, all people with liver disease and gathered from all over the U.K. and so in addition to treating them for their problems, there was also a very high level of research activity. And one of my jobs I was told was to protect the patients from the researchers. How well I did that is one of my problems. Some years later a paper was published in the New England Journal -- in 1976 -- by a man called Beecher from Harvard.  He had 20 examples, subsequently reduced somewhat to 17 I think, of unethical research activity carried out in hospitals and to my horror I found -- not that my name was on the paper -- but that I was resident at the Hammersmith Post-Graduate School when a certain project, named by Beecher,  was identified as being unethical. At the time, and that’s the worrisome part, we really didn’t think it was unethical. I mean it horrifies me to think how unethical it was without us realizing it.  Our research was to show the deleterious effect of dietary protein in people whose liver is not working well.  So patients, without consent, were given increased protein intake that would make them more confused and, in some cases, go into a coma and then the protein would be stopped and they would come out of hepatic coma. It was then found if you sterilized the bowel with an antibiotic and then fed the protein then they didn’t go into coma. This was because the actual ammonia intoxication was due to bacterial fermentation in the gut,  rather that the absorption of food by normal digestion. That may now sound very easy to explain, but the principal is still used, I believe, in the management of hepatic pre-coma. But at that time the concept of “informed consent” was totally……
 

David: So there we are in England with Sheila Sherlock, deep in the liver and then somehow or other you find yourself in Canada very much into kidneys. How does that happen?
 

John: Yes, it sounds a bit strange but I came to Canada because, after Hammersmith, I went back to Bart’s Hospital to work on the service of the then Chief of Medicine , Prof. Ronald Christie, who, the following year, went to McGill as the Chief of Medicine at the Royal Victoria Hospital. And although he didn’t bring me in any sense -- and he was very emphatic that I should not give that impression -- he did tell me about a position, a Hosmer teaching fellowship at McGill and asked me if I wanted it. He gave me 24 hours to make up my mind. I asked a few friends who came from Canada and they all said it was a good place to be so I took it for a year. Its now 45 years later, but I came for just one year, in 1955.
 

David: I think you said somewhere in the notes I read that ‘every opportunity needs an opportunist’!
 

John: Well, yes! And let me just answer your other question, which was "Why the kidney?" Well when I’d finished being teaching fellow, and then Chief resident at the Royal Victoria Hospital, Christie said, "Now what are you going to do now to justify your continued presence around here?" And I said, "Well what about the liver?" And he said, "Oh well, we’re not ready for the liver in a formal specialized sense. What about the kidney?" And I said, "Well what do you mean?" He said, "Well, we need somebody in this new area of the kidney and what we planned to do, if you were willing, is to send you to Chicago to Drs. Kark and Pirani where you have to learn kidney biopsy because that’s what we need. We need someone who can do kidney biopsies around here." So I was sent off to Chicago for a week and traveled by bus in order to save some money on the very inadequate grant that they gave me and came back knowing how to do kidney biopsies. From then on I was one of two people who would answer consultations around the hospital at the Royal Vic on electrolyte and acid base and kidney problems. And the liver sort of faded into the background and has remained there ever since!
 

David: And you embraced your emphasis in kidney nephrology as in retrospect a lifelong ambition from that point on.
 

John: Yes from there on, but there was something that cemented it which I should tell you about. It was in the late spring of 1958 that an extraordinary event occurred which happen to control my life thereafter. A young teenage girl of 15 years was admitted to the Montreal Neurological Institute with convulsions , hypertension and was in a stupor. I was on call that weekend and she had a high potassium and she was acidotic and she was in renal failure. The resident who was very sharp in getting the history of this young girl from her mother came along quite excitedly, saying, "You know that girl over there has an identical twin.” You can probably guess the rest.  We quickly established that the young girl had shrunken kidneys and chronic kidney disease, and there had been five transplants between identical twins in Boston. This was long before any other type had been tried, so we said to the mother: “Would you like to go down there? We can arrange a grant to cover it”. The mother said “No, we will take our chance with whatever can be done at McGill.”. So we decided to do a kidney transplant, and my role was to coordinate the medical-surgical team. This was in 1958. It was the first kidney transplant carried out in the Commonwealth. You might be interested to realize that, in 1958, dialysis was still a dangerous undertaking. So dangerous was it that we elected not to dialyze this young person. She was in bad shape, but she no longer convulsing. So she was actually submitted to major surgery under conditions of advanced uremia. It was one of the things I’ll never forget, the speed at which urine came out of the ureter when the vascular anastomosis had been finished but the rest of surgical site hadn’t been tidied up.  Yet, already, there was a flow of clear, golden fluid into her abdominal cavity which demanded suctioning.. That was an exhilarating moment for us all, actually, for everybody there!
 

David: Perhaps the high urea stimulated an osmotic diuresis?
 

John: Exactly. She had eleven litres of urine in the first day and, of course, that was where a lot of skill was needed. We were doing three hourly total electrolyte balance with estimates for free body water and insensible loss and the whole thing. It involved a team of people wielding slide rules working out what the fluid intake should be for each succesive three-hour period.
 

David: Well, there you were then with this marvelous success, committed for life to kidneys, and was there any other formative, medical, ethical event at the Vic in the 1950’s at McGill?
 

John: Well, we’ve discussed this and yes there was. While all these things were going on in the kidney side, I was also one of the junior physicians. And when I had been Chief Resident I was responsible for doing consultations at night in the Allen Memorial Institute, the psychiatric wing of the Royal Victoria. The now infamous, though then famous, Dr. Ewan Cameron was carrying out research on psychiatric patients. Again I have to say, as with my experience in Hammersmith Hospital, the lack of ethics in this research of Cameron was not appreciated by anybody, myself very much included. The fact that he was giving people excessive doses of electroconvulsive therapy (ECT) to try and ‘deprogram the brain’ hoping thereafter, having got rid of the psychosis, to be able to reprogram the brain.  It was really an extraordinary piece of medical hubris. This was being carried on without any patient consent, without any review, they had no research protocol rthics review -- it was based on trust. The patients trusted him to be doing things in their interest.
 

David: But let me ask you though, you say that you really weren’t aware that this wasn’t optimal, but yet you are obviously a kindly, caring person, indeed the son of an Anglican minister. Surely part of you sensed that there was something that perhaps wasn’t the way it should be?
 

John: I suppose, but no I have to stand condemned by a failure to be sensitive to what was going on. The part that concerned me most was the insulin coma. He had another program that was was keeping patients with psychiatric illness as a very low blood sugar for a week at a time and I couldn’t believe that that was good for the brain, that “depatterning the brain by hypoglycemia” seemed to me to be outrageous. And I did say that. But you know, everyone said, "Look, I know this man Cameron, he’s writing the new book on psychiatry. We’re going to look back and say how proud we are that we were at the Royal Vic when Cameron was there!"
 

David: But you did some experiments of your own didn’t you trying a new way of doing dialysis?
 

John: Yes. Yes we did and that is an interesting story, which I must come clean on. This was way back in about 1961, before dialysis was firmly established, I should have mentioned that between 1958 and 1961, dialysis really came home. Belding Scribner, in Seattle, found that if you did it frequently -- and particularly if you started earlier --  that it was very effective treatment. By the way its very expensive and it was envisioned that there were would never be enough money for everybody with renal failure to have dialysis. It turns out that for Western countries that is probably not the case. There probably is enough money for everybody to get dialysis. But in those days it was not conceived that it would be possible to raise the $35,000 a year to keep a person alive on dialysis so one had to look for other things. The one we looked at was called “intestinal perfusion”. Why not use the membranes that line our body cavities or our gut, particularly the small intestine, as a means of trying to get the poisons out? And we did this by constructing, with patients’ consent I might say, openings into the small bowel, the first at the upper end just beyond the duodenum and the second at its other end, just before its enters the colon.  These two holes into the bowel were then used for perfusion for six hours a day. During the rest of the time the bowel was used for digestion.  Intestineal perfusion could control the urea, completely control the electrolyte and  acid-base balance, but still the patients died afte about 6 months.. They died unfortunately from uric acid accumulation in the heart. Uric acid crystals were seen there in the autopsy. Uric acid would not come out.. Moral of the story? Why wasn’t it done in dogs first? It’s easy to say, "Well here are patients that are dying and we know we can’t afford dialysis for them all. Why not try this and see if it works?" And of course there’s the enthusiasm to go ahead and do it and of course you know that patients, when desperate, will agree to things that perhaps one shouldn’t have asked them. So the problem this time,  was that it was research that had not gone through rigorous animal testing. We would say that the existences of the situation were so acute for these patient that there wasn’t time to do the animal testing, but that’s not a valid argument. In retrospect I consider that whole episode unethical.
 

David: John, the joust to position of dialysis versus transplantation reversed itself as you said. You have noted that early on dialysis was dangerous and transplantation was very experimental and then a few years later the reverse perhaps was true, that dialysis was well established and safe. In view of that, what made you continue to this big, full steam ahead thrust to make Canadian renal transplantation so vibrant?
 

John: Yes and your right in saying that there was a controversy going in medical circles as to whether transplantation was justifiable if there was dialysis. The reason for saying that transplantation should be persisted with, despite the fact that dialysis was getting better and better, was two-fold. Firstly, in Montreal at the time, the Montreal General and the Hotel Dieu and Notre Dame Hospital were all doing long term dialysis and no other hospital was doing transplant. But that by itself would not be a good enough reason. The other reason was that there was very little going on in Eastern Canada at that time in treating renal failure. I’m one of the nephrologists who, unfortunately, can remember when most of the patients died in two to three months. We would be sent patients from right the way down to St. John’s, Newfoundland, who were ‘in extremis’, and who could not come and live in Montreal -- there being no dialysis down there. The extraordinary success of the identical twin transplant made one realize that there was a vision there. But, in 1962, Roy Calne, working with Joseph Murray (who later shared a Nobel Prize) at the Peter Brigham Hospital in Boston , showed that “Imuran” combined with “Actinomycin C.” and radiation could cause kidney transplants to persist in dogs. This soon then led to the same medicaitons being used in patients, using non-identical kidney donors. When this was published in the New England Journal of Medicine in 1963, we at the Royal Vic then decided we would put emphasis on that mode of treatment for human patients, using kidneys from deceased patients. Now, how well did it work? The answer is not very well. So poorly, in fact, that there was a meeting in Washington, I think, in 1965, put on by the Ciba Company where there were serious questions as to whether kidney transplants were being used prematurely on humans. There was some talk on a moratorium. That all changed when Tom Starzl showed better transplant survival with kidneys from family members, (and from some prisoners who received parital reduction of their sentances – another serious ethical dilemma!).
 

David: Yes. Very interesting because not only did you go from liver to kidney and pass the early rocky stages of dialysis, but you were significantly committed to renal transplantation to even get into basic immunology.
 

John: Well of course what happened was that we started doing kidney transplants between unrelated people and we got into rejection and a whole lot of different problems. And the immunologists, who were consulters, and they said, "Look, this is not our type of immunology. We can’t really help you with this. You’re going to have to work this out more or less for yourselves." And it’s a fact that the allergists, who were basically the immunologists of the days, were not that interested in getting involved in kidney transplant immunology.
 

David: Well then why didn’t you just rely on the exciting and successful immunology work, which was taking place elsewhere? Why did you feel you had to do it?
 

John: Well, because even the places elsewhere weren’t doing transplant immunology at that time, so there was nobody to call virtually speaking. You had to figure out a way, along admittedly with others who were facing similar problems, and try and find your way through this. So we rapidly developed what expertise we could in studying the antibodies that developed after transplantation and after dialysis or after blood transfusion and tried to put together and one of the most exciting events of course was finding out the deleterious effect of antibodies directed against kidney tissue, tissue groups, the HLA antibody and question of acute rejection. For example, a transplant that carried out at the Montreal General Hospita caused yheir transplant program to drop in its tracks.  Byill luck, the first transplant that was carried out there was between a wife who received a kidney from her husband. But, because of previous pregnancies, she already had developed antibodies against those factors in her husband’s tissue profile which were foreign to her. because of the fact that these factors were carried on the fetuses. So she was immunologically sensitized to her husband through pregnancy and when they did the transplant it went black on the table and had to be taken out within an hour. Now that is transplant immunology! No allergist will tell you that you couldn’t do that.

David: Well nothing seems to have intimidated you?
 

John: Well…
 

David: You did what you thought you had to do.
 

John: I think it was a feeling in those days, now we’re going back along way, that we had gotten away from the fact that when you developed chronic kidney failure you always died. Admittedly hemodialysis was establishing a better track record, though still considered enormously expensive and it was just a persistence to carry on with this and the fact that we were getting patients from elsewhere who couldn’t be accommodated on long term hemidialysis.
 

David: Could you tell me briefly this remarkable story or chapter, an hour-long mystery story…tell me about the circumstances that led you to do this human cross-circulation experiment?
 

John: Yes. In the early part of “dialysis with a view to transplantation”, which was the program that the Royal Victoria adopted, we were using a lot of blood in dialysis. Each dialysis patient would get four units of blood a week as the dialyser (in those early days) had to be primed with two units of blood, each time it was used. We found, once  we started doing transplants on dialysis patients, that those who had received over a 100 units of blood in the preparatory period actually did better than the transplants that were carried out on people who hadn’t been on dialysis long, and hadn’t been transfused very much. So much that the paper that we presented to the Transplant Society in 1966, we claimed that our policy was, and indeed it was, that you didn’t get a transplant until you had had a 100 units of blood!! Now you might say “Surely they would be fully sensitized” This question has never been fully answered as to why if you give blood directly into the vascular system it does not sensitize, indeed it produces antibodies that may be beneficial. This was the basis for thinking that blood transfusion was beneficial and indeed many people, many units around the world prior to cyclosporin used to use blood transfusion as a preparatory aspect to transplantation. Were we inducing “stem cell proliferation?” Who knows!  Then a doctor called me from St. John’s, Newfoundland. He said, "I have this lady who lives at Burgeo on the south coast of Newfoundland." At that time it was accessible certain times of the year only by sea. She had kidney failure and I said, "You know we can’t do anything for that really. That lady is…it’s a lack of access to medical facilities that is limiting her opportunity." He was a deontologist, I’m happy to say, so he just put her on a plane with a little note attached to her saying, "Please see and advise", and she finished up on the ward in Montreal! We didn’t know what to do with this lady. She had a number of kids and she was a mother of a family of five I think and there she was. We had more or less decided that all we could do was to give her peritoneal dialysis until she was feeling well and then discharge her. There was no question of the family translocating to a dialysis unit, to a part of the country where there was dialysis. And then another resident, and I must say both stories I’ve told about this sharpness of residents are striking! A resident said to me, "You know, that lady there who has hepatic disease and is dying and this renal patient here – they bith have the same blood group." He said to me, "You’ve been prattling on about blood being good for transplants and things."
 

David: Prattling on!
 

John: Yes, well I don’t know whether she used those terms, but this resident said, "If one was to use this patient…if these two patients were to come into some sort of association, would there be any possibility?" The protocol rapidly formed that given proper consent, and by now we were getting proper consent, could these two people live in some sort of symbiosis, the liver of the uremic patient taking care of the liver problem for the other lady and the kidney’s of the liver patient taking care of the uremia of the first patient. We decided with Lloyd McLean, Chief of Surgery at the Vic., who very much supported this, and both families agreed to a trial of intermittent cross circulation. Both the patients were stuporous. It was carried out in Intensive Care Unit. They were on bed scales and arms were connected by silastic tubing. The volume of the two patients’ were adjusted by just a simple screw clamp on one of the connecting tubes. You could make the wight of one go up and the weight of the other go down to get back into balance. The kidney of the liver patient was excreting urine quite fast and the skin of the uremic patient became a bit yellow and they both sort of woke up and said, "Where am I?" It was a remarkable experience. They became alert!!
 

David: What year was this now?
 

John: This would be about 1966 – 67. Then we carried this on for a day or two…then we were in the dilemma that this was working. We disconnected them and they lived their separate lives for about three or four days and then it didn’t look so good so we hooked them up again and again both improved. And the question was how long could this go on? And we tentatively said well look we’ll do it for six months and see how everything looks at the end of that time. Built into this agreement, I should say, was that if one died then the organ that the other needed would be provided by her cross-circulation partner. And that happened on Labor Day weekend, 1966 I guess, when the surgeon was in Algonquin Park having a good holiday. The liver lady died from variceal bleeding into the bowel and so there was a considerable delay in putting her kidney into the uremic patient from Newfoundland. But this did eventually take place and there was a 19-day period of oliguria during which time, I must say, people were looking at me as if I was a bit of a monster! Then the kidney started to work and she went home. She lived for nine years and she had a baby called Victoria after the hospital!
 

David: Well, here you are working on Labor Day, working many nights, we won’t even speculate what the cost was to your family, but still you weren’t satisfied. You got involved with helping the formation of the Canadian Society of Nephrology and perhaps even more so the Kidney Foundation of Canada. Why would you have done that?
 

John: Well, I think the Kidney Foundation one I can answer more directly because it was clear that what one needed was research. I mean we were involved in things that we barely understood that had vision of a future and yet was also fraught with all sorts of dangers and mistakes. I was looking after a young Montreal architect, called Morty Tarder, and he had Goodpasture’s syndrome and he was not doing well. We tried to dialyze him but he was bleeding into the lungs and generally speaking he had a very stormy course and he died. He was about 35 or so. And his father said, "This is unspeakably tragic. Isn’t there anything that someone can do about this? I mean why do we have to have this sort of thing?" Not then, --  but a little later I got in touch with him and said, "You know, what we need is research and is there any possible way in which you can think how one might raise money to do research?" And he was enthusiastic. He saw this as bringing closure in some way to his grief. He had a shop on St. Andre district in Montreal. He was part of a group of people there. He got them all together and one in particular took a lead and said he would get involved and they formed a group, which was going to form a kidney foundation. Now there were problems getting the kidney foundation started. We didn’t know how to do it. I was working with Dr. Guy Lemieux from the Hôpital Hotel Dieu and we sounded out opinion across the country, urologists and nephrologists, and they were all keen, at least most of them were. Some of them said they thought it was unnecessary believe it or not. And then this lay group got in touch with the National Kidney Foundation in the States and there was some dialogue there. So the conclusion was that we should form a society to raise money. In the first three years they raised $3,000 a year. Last year, 1968, they raised 3 million dollars and I understand that the figure has been comparable to that in the last few years. It’s an extraordinary cause of quiet satisfaction to see how this thing eventually grew. We had opposition. We had opposition from the heart group. They said, "Why can’t you just be a part of the heart?"
 

David: And why can’t you just be part of the heart group? Why does every disease have to have it’s own patient advocacy group?
 

John: I think the answer is that the problems are unique and expensive and the direction of research is not the same. There was absolute agreement amongst those who were supporting the Kidney Foundation in the early stages. And one of the strongest supporters was Yves Fortier, subsequently Canada’s ambassador to the United Nations. It was actually he that staved off that question as to why shouldn’t it be part of something else.
 

David: Can you say a brief word about the Canadian Society of Nephrology?
 

John: Yes. That actually formed three or four years after the Kidney Foundation. Originally the urologists who were well organized, offered to have a medical branch of the Canadian Urological called Canadian Nephrological and they invited us to join with them, they gave us honorary membership, and six of us went to their meeting at St. Andrew’s, New Brunswick in 1964 I think. But the six who were there had various interests as you know. I mean people who go into nephrology at that time came from all over the shop. Some were interested in calcium and bone metabolism and then electrolytes and then kidney and some were coming from other directions, endocrinology, hypertension into the kidney and they didn’t really have that much in common with straight urology. So the decision was then made to form a separate Canadian Society. The first meeting was at the Chateau Laurier here in Ottawa I think in 1965 and the ultimate charter I think dates from 1967. By that time there was about 60-70 people who called themselves nephrologists in Canada.
 

David: Well, so we have now the picture of a minister’s son, experience in India, liver experience in England, Montreal, pioneering kidney transplantation, undaunted by being a self-taught immunologist, stimulating patient advocacy, and then why would you want to move all across this big country to the Rockies?
 

John: Yes. Well, again I had to make a choice. Up to now it was opportunism. I grabbed at opportunities. I was made a career investigator of the Medical Research Council in 1966 and I think it was and 1967 or 1968 I was visited by a MRC’ team led by Frank Dixon, a famous nephro-pathologist at La Jolla in California. He nailed me and said, "Here you are. You’re fooling around with immunology and transplants and you are also trying to be the big clinical doctor in nephrology. You can’t go on doing these two things. You have to choose. You either stay with the MRC and do research or let that slide a bit and continue to run a clinical service."
 

David: He said this to you during a visit?
 

John: He’s intimated it and in a little conversation we had and then I had emphasis on this from the MRC.
 

David: From his written report?
 

John: Yes. And I decided I would take the research route.
 

David: And give up seeing patients?
 

John: Well not give them up altogether, but no longer be sort of prominent in that area. And so I made certain demand of McGill, which they couldn’t meet or refused to meet. I said, “You know, I need a proper lab, I need a quarter of a million dollars for special equipment and stuff like that” and at that time Lionel McCleod went from Edmonton to Calgary and Lionel had been fairly big in the Canadian Society of Nephrology.   Walter McKenzie, who was Dean of Medicine, wanted kidney transplants in Edmonton at the University of Alberta. He had a lot of influence. He’d been President of the Royal College, he’d been President of the American College of Surgery I think, and he got the government of Alberta to say that they would underwrite $300,000 for a lab in transplant immunology at the University of Alberta if Walter knew the right person. It so happened that Malcom Brown the President of the Medical Research Council also intimated to me that if I made this move and started something in transplant immunology out in Alberta that this would be a very suitable place for them to site a MRC group, a research group, financed entirely by a Medical Research Council. And so he sort of said if you make that move then you get on with putting in an application and I should also mention that the University in Alberta also recruited Erwin Demer from Melbourne, Australia, who was a basic immunologist at last! So the idea was that there would be two directors of this unit, one more clinical but looking toward basic, and one basic and hopefully looking a bit clinical. And the MRC then funded that and we had it for ten years. It was very well funded and we were very fortunate.
 

David: But let me repeat if I may a question. Leaving your patients, leaving this close contact in a large measure, didn’t that foster in you some discomfort? Was there any sense of abandonment in the heart of this Anglican minister’s son?
 

John: Yes there was. I think it was reflected by the fact that I didn’t actually take up new patients in Alberta for a couple of years. I did entirely the research thing. That difficulty in academic medicine between dedication to patients and the problems of dedication to research, and you can’t do them both fully is a dilemma for academic medicine. You may have experienced it too. And nearly everybody who does research here in academic medicine as physicians finds this problem.
 

David: What are some of the highlights of your early years in Alberta with the MRC group?
 

John: The focus was quite different now. I was not responsible for patients with clinical problems. We started to look into the whole question of tissue typing, histocompatibility is the fancy word, but it’s really tissue groups as distinct from blood groups, and we were looking for special populations because one might expect their different tissue groups to be simpler, and more restricted.  So we decided on the Arctic and went up to study histocompatibility amongst the Inuit -- in several expeditions funded by MRC.  The Inuit are in a sense an inbred strain of human. They have been inbreeding or interbreeding in relatively limited number of people for 20 thousand years and we found in fact that there were a whole lot of families where they all typed the same. We were able to find what at that time was important in histocompatibility, namely homozygous cells for use in mixed lymphocyte culture, MLC.  We found a number of people with homozygous HLA antigens on their cells and we actually sent these frozen in their liquid nitrogen ampules around the world to the histocompatibility labs and workshops. That was very expensive of course, but it was worthwhile and we did do skin grafting there. We were very much helped by somebody who could speak the language, Dr. Otto Shafer. Then I did similar work with the Hutterites in Alberta who had had close breeding for 2-3 hundred years since they went from Germany out to this continent. They also had a limited number of tissue antigens and were able to give certain insights into histocompatibility. Those were two of the areas, but the main area I suppose was immunological monitoring of the events going on in the blood of patients after transplant, both cells that were trained to be killer cells to the transplant as well as antibodies.
 

David: Now nobody was immune from your inquisitiveness, in fact you yourself fell pray to your own curiosity.
 

John: Yes, I have to admit to that. We were looking for “enhancing antibody” -- antibodies that would help grafts survive and we thought we’d found one. And it happenned to react with my cells. It lead to a protocol that we thought was worth doing and we didn’t want to go through all the rigmarole of an ethics board, so we decided on human experimentation between the two investigators. Well, with the other investigator, it went pretty well. I gave him some of my skin and some of the serum. Unfortunately the lab had misread part of the test in my case so that when the serum was run into my veins -- following his skin graft -- I developed an anaphylactic reaction. I’ve said this a number of times. “If you ever want to see the head of your department and the Dean of your faculty in short order, this is one way of doing it” because I remember waking up in the emergency room and there were these two faces looking at me somewhat anxiously! But it all went off…nothing much…there was no residuum, but it did teach me about the ethics of auto- or self-experimentation. It is a serious matter not to be undertaken lightly and does require ethics review and that's the part that I think is very important.
 

David: But you knew that before you started the experiment?
 

John: Yea I guess.
 

David: Well then here you are at about the age of 60 when most people want to have a summer boat and slow down and play golf and read and then you made another big move.
 

John: Yup. By this time, and we had been in Alberta for  a period of nearly 20 years. I had moved more or less back into clinical work and some of the research had metamorphosed into other things and I was no longer primarily involved in that, though I was still supported by Medical Research Council. One day there was an article in the Edmonton Journal and subsequently in the Globe and Mail where one of the patients had said, "I will give anybody $5,000 if they will give me a kidney."  He had been on dialysis or several years.  He was a very intelligent businessman actually who just got fed up and  said, "I want out of this!" and he developed this stratagem for doing so. He had 200 people from across the country offer to be tissue typed for giving a kidney for 5,000 bucks. Seems absurd. Then we pointed out to him that this was against the law!. So he said, "Fine, I’ll ask for a kidney out of sheer love!" And he did so and he had about six people who were very keen to give him a kidney ‘out of love’ whom he’d never seen. And he came along and said, "Now what are you going to do about it?" And I said, "You know this isn’t our policy." And he said, "Who made you the policy maker? By what right do you as a physician involved in this game, make social policy for Canadians?" And of course he was quite right. We do make these presumptions and it caused me to think very much just who does empower physicians and the medical world to make enormous decisions on strategy and policy. And the answer is nobody. There is obviously trust that the medical world will do the right thing in the long run, but it made me very interested in the interaction between public policy and medical practice. At the same time I was also concerned about the fact that I thought people were making difficult and wrong decisions, particularly older people, in going on dialysis and not being able to do anything about it when it didn’t go well.  So we formed a Quality of Life committee that didn’t actually interview patients but did discuss their problems at length.  On this committee were non-medical people, including clergy, and we tried to see how societal values could impact medical decision-making in such a difficult decision  -- where one’s life was at stake and yet if you made a mistake your life becomes miserable. All these things combined with the fact that I felt my fire for research had burnt out pretty much; this made me determined to take a sabbatical and that’s where I must say the academic life is wonderful in being able to give you an opportunity to go off and do something quite different.  I wanted to do medical ethics. . . .

David: How old were you at that time?
 

John: I would be 61.
 

David: 61. So you went off to Hastings Institute for Ethics.
 

John: Yes, I first went to David Roy at the Institute for Clinical Research in Montreal for a short time and then to Al Johnson at the San Francisco for a month or so.  He’d been there for many years teaching medical ethics. And then, but by far the best experience was the Hastings Center in New York and the Kennedy Institute course in Georgetown University. During all that time I put together a proposal for a bioethics initiative at the University of Alberta, which Dr. Doug Wilson accepted.  He, as you know, David, is a nephrologist.  He was then Dean of the Faculty of Medicine and Dentistry at the U. of A. He said that they wanted this so I was sort of mandated to develop it and so on.
 

David: And what is it called today?
 

John: Well, today it is called the John Dossetor Health Ethics Centre. They gave me that honor of renaming it when I left last year.
 

David: Now John, despite your kindliness and compassion, you’re rather feisty. You have some strong views on purchasing or vending kidneys and you haven’t hesitated to express them. Do you think people should be permitted to buy and sell kidneys?
 

John: To be quite frank I think that people should be able to do with what they want with their own bodies. I happen to not want to do that, but if someone felt that they should I see no reason why just as I don’t see that somebody who wants to prostitute themselves for money should be put in jail or somehow inhibited. The question is, who has the right to get involved in such a transaction?  I don’t think the medical world should ever get involved in a monetary transaction involving tissue or organs. I’m not saying that I don’t think that if someone is convinced they should have the right to sell part of their body that is their right. They own their own body. But I do think for society to get involved in this, and particularly the medical society, they are betraying the trust that the public has every expectation and right to have in the integrity of the medical people.
 

David: Well, we’re coming to the end of this at least this spiritual and value inquiry into your development and helping others. What effect do you think you have had and your centre had on young physicians in Alberta and on others?
 

John: You know that’s a difficult question.
 

David: That’s why I asked.
 

John: I think the answer to the question is…”We’ll just have to wait and see.” I think my initiative in bioethics is part of a wider of initiatives that are going on elsewhere in bioethics. Bioethics or ethics in healthcare delivery is a growing subject. It’s a rapidly growing area. The old authority, apprenticeship by young physicians learning their ethical behavior from their paternalistic mentors, all that’s going, or has gone, hopefully!   There is now a new way of looking at decision making, with patients participating, in fact even the word patient is a bit of a problem I think. Its still widely used and I still use it, but its people who have illnesses should participate with their physicians in a joint development of a comprehensive treatment, which they comprehend. It’s more than consent. I’m personally a believer in comprehended consent rather than informed consent. And I think all that is part of a movement that is hopefully improving and one might even say cleansing some of the paternalism and all that out of medical practice.
 

David: Now there’s a practical contribution, which you have made. You’ve been called upon to look at organ donation and organ retrieval in Canada. It’s not a coincidence that you’re a nephrologist and an ethicist. Could you comment on that? They’re useful things that come out of your work.
 

John: I think that in a sense there is recognition that I have made certain commitments in my life and why not use it? I think its natural that people should want to at least have that viewpoint represented and I have been flattered actually by the fact that people still are interested in having me participate in those things even though my contact with the bedside problem is rapidly receding and my knowledge of medicine has decreased considerably. It’s now nearly ten years since I practiced medicine. I don’t have a license any more so I really am only qualified to speak on values and that component of the process and I’m happy to do that.
 

David: Well its decreased from a stunningly high level!
 

John: Well I don’t know about that!
 

David: Members of the International Society of Nephrology might say that your career would only have been possible as a nephrologist. That is to say your achievement in medical ethics, your inquiry into medical values, into patient advocacy really is inimically related to the fact that you had early experience watching so many patients die. You are aware of rationalization of scarce resources and we spoke of this question of organ vending. Do you think a non-nephrologist or had you been a dermatologist or a neurosurgeon you would have had the same trajectory in this story of your professional life?
 

John: I can only speculate, but I think I agree with you that I believe that I have been enormously privileged to live through a period of medical development that happens to be most acute in the kidney field where I started from, 100% failure and finished up with 95% success either in dialysis or transplant. All through that period I think nephrologists have been very fortunate and their experience…Whether this will happen in the future you know one hates to think that the future for others cannot be as  rosy as the past was for me.  I think it probably is, but one can’t foresee that at the moment. But I do believe that nephrology has given a group of people considerable opportunity that would not have necessarily come from neurosurgery or dermatology.
 

David: Who will carry on now in the future John?
 

John: I don’t know. As far as ethics is concerned in medicine, I think that’s going to carry on, that’s in a growth phase. It’s going to be partly with physicians and I hope increasingly so, although there are problems financial in going to ethics for physicians because its not as well paid. I think women in nursing should fully share their experiences and their decision making with medical ethicists, and although there are laws concerning who can write drug prescriptions, etc. -- all that is going to go or be modified.  I think dialysis units are a very good example of how there is shared decision-making between nurses and physicians. So I think there are movements afoot that are going to go on developing and maturing.
 

David: John, perhaps as our last question, which of course we can edit out. If a young John Dossetor of 24-years old could sit beside us and listen what might he comment on your remarkable life?
 

 John: Oh! I think that the person should say to herself, well this is just one man’s experience.  This was just one phase of the development of medicine and of healthcare and of health, creation of health, which is a lot different from delivering healthcare.  These guys can’t see the opportunities that are going to come my way just as no one could foresee the opportunities that were going to come to him! and I hope they’d come my way so I can 50 years later say, well no-one me this past fifty years, but I hope that they will be as worthwhile!
 

 David: Well John, Dr. Dossetor, on behalf of the International Society of Nephrology thank you ever so much for sharing this insight into the mystery and the joy of a distinguished career. Thank you so much!