SC: Mark, we've always called you Jo, so I will call you Jo, if that's all right with you? Jo, Joekes is an unusual name in England, tell us a bit about that.
MJ: Well, it's a Dutch name and I in fact was, by the length of my nose, I was born in Holland, but my father was employed by the Medical Research Council over here, and I'm not sure what he was working on at the time. He was really a pathologist basically, although he had been a clinician, and he worked up in Hampstead in the old MRC buildings there.
SC: So that was some of your medical family background.
MJ: So that was my medical family background. Curiously, my mother also qualified as a doctor but never practiced. She was one of the earlier women to qualify as a doctor. They both qualified in Leiden, I think, and my father was a fairly well known athlete, he stroked the Leiden boat.
SC: So the family was from Leiden?
MJ: Um, well my grandfather was the governor of Sumatra and my father was born actually in Borneo. He was there for the first 15 years of his life, and then he had two brothers, one of whom became a well-known politician and had a lot to do with the Dutch East Indies. But I never lived in Holland at all.
SC: You did mention to me once that you were very distantly related through your mother's family to Pim Kolff?
MJ: I'm not sure if I am. I'm so vague about this. I'm not sure if this was through my mother or through my father that we were related, but he lived in one of the……, his father was a ship master and owned a fleet of fishing boats, which was the hareng [a herring] fleet over there where they got a lot of herring in those days. I don't know if they do still and this was on a cool day in Goree and Overflalsee, which was the Northern coast of the island in the mouth of the Rhine and he had a tower with a bell on the top of his house, where some poor citizen used to sit and tell him when his fleet was coming in. He didn't want any hokey pokey going on there when they arrived.
SC: But you were brought up and educated in England?
MJ: Afterwards. I never lived in Holland.
SC: And then you went to Bart's to train?
MJ: I went to Oxford, and then I went to Bart's.
SC: And after that you planned to join the MRC I believe?
MJ: Well, I was shoved into the MRC. I never knew how it happened. Anyway, I had this letter when I was down down in Chichester to say that I was appointed a MRC fellow, whatever it was in those days.
SC: But you were a registrar in those days?
MJ: I was registrar in those days.
SC: When, 1940?
MJ: 1941 too. Then I was sent to the unit which was based at Queen’s Square - the hospital for nervous diseases, where there was a MRC unit under Dr. A.E. Carmichael and I was part of that. As well as in fact, I think, one of the McArdle brothers, did you remember that?
SC: Yes. I knew both “Black” and “Red” McArdle of McArdle’s disease.
MJ: That's right. This was “Black” McArdle. The “Red” McArdle, I think he, did he work at Guy’s ?
SC: Yes. Both boys were at Guy’s
MJ: Yes well Black was there, but he then came across to the MRC and he was a very intelligent and very bright boy, and so then in a sense I was one of his easiest rivals rather than Carmichael and the first thing we had to do was to work on motion sickness for the Navy and the Army when they were transported. We did actually find out that there was a certain tablet you were given against seasickness. So we had two sources of this and one of these was a British source the other was a German source from Merck, I think it was, and when the trials were started we would have enormous swings in one of the red and gold halls in Queen Square. And we had great swings. We used to swing with ourselves. We swung the volunteers from the army until they puked, and then we gave them tablets and we found that one of the sets of tablets stopped them puking and the other one didn't.
SC: Practical research.
MJ: We were very practical researchers, not highly intelligent. We then thought it was very odd, so we had them analyzed because they were supposed to be exactly the same tablet, but one worked and the other didn't, and it was found that the British in the best tradition had failed to put in the hyoscine. And so it was then established that this particular thing, whatever it was called, and it is still used yes, and it was halocine, was the stuff that mattered and so all military establishments, navy, army and whatever have used it because it was tried out in the rough seas of the channel to see if it did really work and they were told that they must take this pill again for sea voyages. When they invaded, I think it was Sicily, or Southern Italy, I can't remember, our troops who were embarked on destroyers, were all as sick as hell and dropped all their small arms overboard and the whole thing was a disaster of the highest order So we enquired you know, how do they take their tablets? And it had turned out that nobody had issued these tablets and so all the swinging and all the work we had done was in vain.
SC: We still won the war.
MJ: Well yes, but the fact we had them puking soldiers arriving was too much I expect.
SC: And the rest of your war was spent really researching with the RAF.
MJ: I was then from the Queens Square unit, where I was also the registrar in Urology, which was a very interesting experience. I was sent over to Acubaral Rundal who was the head of the Medical Division in London, to do work with the RAF and eventually ended up in uniform, at Farnborough where we had all sorts of things. I was working on the problems of flying fatigue and had the great good fortune of working with Dr. Marthe Vogt who had moved from London. I can't remember if she was at Guy’s or not.
SC: No I don't think she was. She won the Nobel Prize, didn't she?
MJ: She was the expert on the adrenal cortex, and she was working at the National Institute for Dairy Research outside Reading, and I went there and she very kindly lent me labs and animals and I worked on rats and bilateral adrenalectomies and we did cold tests on them and then gave them hormones. So I set up how to test adrenal cortical hormone in human urine. At that point I got into, no I was already in uniform, and we then started using RAF volunteers for giving specimens. This was I think the first occasion that the adrenal cortical hormone was successfully extracted from human urine.
SC: The stimulus for this work was a bit unusual wasn't it?
MJ: Well, the actual stimulus was with the people. Dr. Mathews, who was the Head of the laboratory at the RAF, explained that they had captured a ship coming from Argentina full of ox adrenals going to Germany, because if you remember they switched sides rather rapidly after the beginning of the war, and it was felt that this had something to do with flying. They thought it had something to do with night flying and if you ate a lot of adrenal cortex that you'd be a better night flyer than if you didn't. You know “Cat's eyes” Cunningham [are cunning], and the idea was that he should be fed with large quantities of adrenal cortex later. But then because I was put onto flying fatigue rather than night flight, they switched them to flying fatigue and I did this work for a year or two, and used one or two fairly modern techniques to recognize this.
SC: This was very early work?
MJ: It was very early, in fact before the people from the United States came over, and only exclaimed that we seemed to be well informed on the subject and went away.
SC: So far, there is no mention of kidneys. How was it that your interest in renal disease was awakened?
MJ: Well, when I went to Bart’s as a houseman, which I did by telephone from Oxford, rather surprisingly when you think of nowadays. I rang up the Dean and asked him why he hadn't sent me a note to say that the jobs were up, and he was very hurt about this. Then he said did I want to work with him? And I said no. This cut him to the quick, but anyway I was then given, I got the house job to A.E. Gow, which was a well-known name, particular in physical science, and I knew at Bart’s you were a junior houseman, then a senior houseman. When I was senior houseman, and there was really nobody in charge as they had all gone off to war, so who was left running it was Dr. Gow, although he had lived at Bart’s for quite a lot of the time. He didn't really appear on the wards very much, so I was left on my own.
There was a bomb which fell into the opening of the sympose Underground, one morning in rush hour. It was after this that everybody on the stairs coming out of the underground station fell backwards. One of the people who came in from this was a boy from the country, a big strong lad of seventeen. He lay in the bed with a very bruised thigh and he seemed to be in a very well state, so I was not paying too much attention to him. On the 7th day he said to me, "I've not passed any urine!" or whatever he used for the time. And so I said, "Well go out then do it now and quickly", you see. He came back and said, "I'm very sorry. I can't pass any!" This must have been in '41 or '42, something like that.
The work on crush syndrome had just seen the light of day and I thought this is the crush syndrome to myself, which rather surprised me, and I went through literature and I saw the name Bywaters. Bywaters was one of the only people who had done any work, since the publications in the journal literature from the First World War on trauma kidney failure, and I had, before the war worked in Austria for a short time. There they were looking at people who died and were doing tests for the level of urea in tissue with a man called Conchack, who was working in a big pathology department in Graz where he worked [with skin grafts] in Austria.
And so I got Bywaters to come and see this boy who was a fit charming young fellow somewhere from the country who finally made it to London. So I said to Bywaters, "What do I do?" And he said, "Well there's nothing you can do!" And I said, "Well, what's going to happen?" And he said, "He'll die between the 12th and 14th day," which he did more or less. This thing was rankled in my mind really from that time on. When I later on went to work on malaria, then on the one side we had the interest of acute renal failure from malignant tertian blackwater fever, my interest was aroused again. I remembered this boy and then when the time came - I was still in the RAF in running this unit because James Reid with whom I'd worked as an interservice student on malaria - which had come about on not an unlikely work on the motion sickness because the 8th Army who ran from east to west along North Africa driving around all before them and his famous army. They all fell on their backs ill and somebody, a technician in fact by the name of P.G. Shute. Shute, who came from the tropical medicine school, was sent out to see if he could recognize what was the matter with them. And he found they all had tertian malaria.
Then it was inquired as to what had been done about anti-malarial drugs and Metatrine was the order of the day. So the senior medical officer of the 8th Army said, "What. Had this been a shoot", and nobody had had any Metatrine. Well he said, "Give them a triple dose." So they had a triple dose and then they went very yellow and got very ill and fell on their backs. And if it hadn't been that the Rommel army had had dysentery at the same time, they’d have gone back to Cairo as fast as they had come across or faster. So at that point the alarm bells went off. Of course we still had war in the east. Malaria was killing a lot to people in the east and so they were very………… I think it was Churchill himself who demanded that the interservices research unit look into malaria, and find a cure other than mepacrine as it wasn't safe to carry on the war in the Far East with a single drug and this is, and through that of course, I met the ideas, although we never had one in the country of acute renal failure due to Blackwater fever.
SC: So in 1946 you actually started working with Bywaters eventually?
MJ: In 1946, I wrote to John McMichael who was the Acting Head of the Department of Medicine at Hammersmith, asking if I could bring an artificial kidney and work there.
SC: How did you first hear about Kolff’s work on the artificial kidney?
MJ: I had sent to me by somebody, his thesis, which he wrote I think in 1942. Now I could read Dutch reasonably well, and so I read this and I was fascinated by this. It struck me rather than as it had been used by Kolff and by Nils Alwall at that time for renal failure of any kind, no matter what, that this might be a cure - might be a way of getting through with the problem of acute renal failure; and I went to Hammersmith with this particular thing in mind. And so I concentrated largely on getting patients who had acute renal failure.
SC: Did Kolff bring the kidney across or what?
MJ: He came over later.
SC: You were one of the first people to use it outside of the Netherlands?
SC: Before the United States and before elsewhere in Europe?
MJ: For quite along time, yes.
SC: You treated what, quite a number of acute renal failures?
MJ: We treated some but got one or two through. It was not an easy job, you had rubber piping and you had - it was full of all sorts of problems. They were very interesting, and I'm more sorry I never looked into this, but they all had a rigor after about twenty minutes, and they'd go blue and then they'd have a rigor, and of course this was because of all the horrible things in the rubber piping that we used.
SC: This was old-fashioned red rubber?
SC: No plastics in those days.
MJ: They had these lovely rigors and it was quite plain that this was a pulmonary shutdown of some sort. We had our hands full in dealing with acute renal failure.
SC: How long did the dialysis take from start to finish?
MJ: I used to set it up in the day and dialyze all night, then go to bed. And the patient would be a lot better and I’d be a lot worse and then we were woken at about midday, I think, to say that the patient was worse again because at the beginning we hadn't appreciated the vascular, the intravascular volume. And although with the bubble trap and things in the old Archimedes screw machine, we would control approximately the volume inside the machine and what was in the patient, which was very crude and I think we always overloaded them.
SC: You modified the machine, didn't you, to make the volume easier to control?
MJ: No. That was Andre who produced a metal container, which enclosed the coils of cellophane and stopped the thing... because you could actually get in 21 liters of fluid into the actual dialysis machine - an enormous extracorporeal volume. So it was no surprise that we had these problems. Some were at about midday, I'd be woken and say if it was patient A, B, or C. He was not as well as he was when I went to bed and they found him in left ventricular failure and we had to go through all this and try to get him through. We usually got them through, and managed to dialyze. I really can't remember now the biggest number of times we dialyzed anybody, but it was probably half a dozen but no more.
SC: I noticed in your paper, that early paper in 1948, that there was one patient with aspirin poisoning whom you had dialyzed, which must have been the first - or one of the first - times that dialysis was used for the toxin.
MJ: For that, yes.
SC: Since Abel and the dogs of course in 1913.
MJ: Abel and Rowntree of course. They showed you can get aspirin out and urea, which was almost incidental that they got urea out They didn't use sausage skin or cellophane for this. They had great difficulty with artificial kidneys. Then of course, in the 1930's the German people were working on artificial kidneys, but never really went through with it. They demonstrated that they could get urea out of people, but they didn't... Haas and all his group did a whole lot of work on it, but they never really got through to a clinical point in any major way, and so they, by the time there were war injuries, subsequently, the Germans weren't in the field at all.
SC: You said you visited Kolff in Kampen at one time?
MJ: Yes I did. I went across to Kolff in '47, and he used to work at his home a great deal and I think I told you that his children and his - this was in his sitting room at a little desk that he used to sit and work at - and his children would crawl under and over him and around him and he didn't recognize them I don't think. He had the most extraordinary ability to concentrate, but the thing that fascinated me most of all at that time, because we had already devised the oil and sugar emulsion for treating patients so they wouldn't have any nitrogenous substances.
SC: Lets talk a little about this because one of the things that is striking to me is that after this very early start - I mean the first dialysis - outside Sweden and the Netherlands were done in the UK, then Britain more or less abandoned dialysis for almost ten years, and you were largely responsible for that along with Graham Bull I think.
MJ: No. I don't think so.
SC: I know that’s not fair!
MJ: I was not responsible.
SC: I'm provoking you!
MJ: I was on the other side. The political issues arose and dialysis was thought to be a rather messy, unnecessary thing because we had demonstrated we could get patients through with very careful, conservative management.
SC: They were very different patients from what we see today.
MJ: But what was interesting of course was well over fifty per cent of the patients were those following abortion, mainly backstreet abortions, and then they got acute renal failure. And we scraped through with the very strict conservative management, which was very difficult to achieve actually, and ...
SC: Your mixture - a high calorie mixture was very difficult. Did you take it yourself to see what it was like?
MJ: I tasted it of course.
SC: I tasted it too – revolting!
MJ: A few of the patients drank it with pleasure and if they vomited we filtered it and gave it back to them so they didn't lose the electrolytes. They took it all in good part and there was a famous picture - I don't know if it appeared in one of the publications - of a girl whose blood urea was about 450 and she was on this treatment and she was very well, thanking me. We had got a German professor who came in to look at it and he saw this girl and we asked him what was the matter with her and he gave a long dissertation: anything but renal failure. We said her blood level is 450 and he frankly didn't believe it. Anyway, this girl made a complete recovery as did I think 7 or 8 out of 12 acute renal failures following abortion. We published this I think and I gave a paper on it with …………… in Belfast I think it must have been at the - what society was it?
SC: Could it be the Medical Research Society?
MJ: No, it was not really medical. It was a scientific association.
SC: Doesn't matter.
MJ: What? - It doesn't matter what it was, and we went over. And by that time first Bull came some time in 1947 and then Ken Lowe came in '48 and we then had three people working on this problem. But what was clear at that time was that the patients with failure following a back street abortion were anabolic, and it was relatively easy to control, because they could look after themselves. But as for the people following trauma, or surgery, or anything of this kind they were not anabolic, but catabolic and they were much more difficult to handle. And you couldn't handle them without dialysis in my view. But this was not the view taken by Graham Bull and the authorities at Hammersmith. So the ukase was issued, the dialysis stopped and so unwillingly, I turned to looking at acute renal failure in other ways, and looked particularly at the acute nephritic people at that time.
SC: So you weren't a particular enthusiast for the conservative regime at that time?
MJ: Oh yes, very much so. Oh yes we set that out straight away from the word go.
SC: It was a very influential paper and it certainly introduced…
MJ: Indeed it was...
SC: And it introduced dialysis in the UK.
MJ: I always remember a patient coming in with acute renal failure who said their drowning me. I'll always remember that, but in the early days before I was joined by anybody else, we already had conservative management in relation to water, but as I think we discussed yesterday, that when in 1956 I was invited over to Paris to work in the Necker with Professor Hamburger, he had working with him George Mathé and a book was eventually published, which Mathé wrote on water. And in this, he underlined the error in thinking a liter of water was what was safe to give people in anuria as about 600 ml of water was produced in the body by catabolic processes, and so the accurate amount that was free to give them was about 400 ml. But that was Georges Mathé who did that work.
SC: It is a very important observation.
MJ: Extremely important. And he subsequently went back to paediatrics where he came from, and became a haematologist in paediatrics and really didn't stay in the nephrological field at all. But he was a highly intelligent person.
SC: Of course you were also working for some time on transplantation during the 1950s.
MJ: In 1948-9, I remember having lunch with one of the surgical assistants of the Chair of the Pathology unit there, James Dempster, with Ian Aird who was the Professor of Surgery. At that stage there were some rumors that somebody in South America, and I can't remember who it was, was treating people with acute renal failure by implanting on their radial arteries an ox kidney. And Ian Aird said to me, "Now why aren't we doing that?" And I said to him, "Well nothing at the moment would persuade me to have a foreign kidney put into my circulation. If I was bleeding, if I had acute nephritis, which was not my idea of how to set about it."
"Well," he said, "Why don't you and James go down to Downe and solve this problem? I'll give you 6 months," he said. "Go down and solve the problem of transplantation.
SC: Xenotransplantation as well!
MJ: So down we went, and I went on certain days - I wasn't in his unit at all.
SC: We should mention that Downe House was Charles Darwin’s house.
MJ: Downe House was Charles Darwin's house, where he lived for many years before he died, and this had been bought by the Royal College of Surgeons and it had as a member one of these surgical urologists who was extremely crafty at passing a catheter on all the gentlemen with obstruction. And he made a large sum of money from this, which he gave to the College with a view that it should be altered to, Downe House and made a research laboratory. And this is where James was, with his greyhounds, which were the surgical dogs.
SC: This was James Dempster?
MJ: Yes. James Dempster. We started looking at what was considered to be the only way to getting a transplanted kidney - in the neck. We published a paper showing that these kidneys didn't work normally. There had been some previous work in the mid 30's in which somebody had tied a non-elastic ligature around the ureter, partially obstructing it and the kidney behaved, so far as you could interpret the older data, exactly the same way these kidneys in the neck. So we decided that the right thing to do was to implant the kidney, not in the neck with the ureter coming to the outside and stenosing, but it should be put into the iliac fossa with the ureter implanted into the bladder so you wouldn’t run up against this stenotic problem of the ureter. This proved to be so and this kidney, these kidneys worked perfectly normally. And it was largely James Dempster's really beautiful surgical techniques that made all this work possible. I was really there only looking after the functional and electrolytic point of view to see what was happening. We wrote two papers on this. One on the neck kidney, and then the kidney in the RIF [right iliac fossa] and tried to publish it in this country, but none of the journals would accept it. They said that transplantation was not for the likes of us, and that kidney transplantation was not I think, as I suggested, not quite… British. So we had to send it to the Acta Medica Scandinavica where the papers were published eventually. I think a lot of people thought for a time that this work was being done in Scandinavia.
SC: Of course Peter Medawar said several times publicly, as an immunologist, that transplantation could never become a reality even within his lifetime.
MJ: Yes indeed.
SC: This was at great cost to a lot of people.
MJ: This was to my great cost, because in 1956 I applied for a unit for transplantation from the MRC and they sought an outside adjudicator of this plan and went to Medawar, who said there was no question of kidney transplantations, immunotransplantations being sole , except at cell sole level, and so that my request was turned down. And so unfortunately, we lost another chance to solve the meaning of the world in transplantation because by that time Hume and Merrill who had come to see our work on the dogs had gone back and had started up transplantation without really a great deal of thought about it, and did a lot of transplantation. All his patients died, and by this time Dempster had demonstrated the immunology of an organ as opposed to skin transplantation, and they all died from organ rejection.
All of the work that James then undertook was that he would take a pair of dogs, he would transplant one kidney and from dog B into dog A, which was being nephrectomized... no he kept one kidney at that stage that's right, he kept one kidney and he implanted the kidney from dog B and this would reject somewhere between 10 - 15 days and with all the histology and the change in the plasma cells and the work that was going on in Sweden at that time on immunology of organ transplantation, which was certainly changed his entirely. And then after that had happened, he took the second kidney from dog B, transplanted it into dog A and this then was rejected in 48 hours, and by 24 hours the kidney had swollen to twice the normal size and was inuric. The temperature of the dog went up. And if this kidney was removed from the circulation, the dog immediately appeared to feel well, his appetite came back, he started running around the laboratory and was perfectly fit. And so here was the rejection, which was accepted as definite proof that this was a rejection on the basis of an immune phenomenon, particularly because the second kidney having hyper-rejection.
SC: Those very important experiments have been nearly forgotten, I think by many people in transplantation.
MJ: James Dempster had then a very large number of publications. He was unfortunately dismissive of other people's work and this didn't help in people accepting his work. And certainly... actually James Dempster was a very good painter, and he made a very nice painting of Medawar at one point. I don't know where these paintings have gone, but I don't think that Medawar got that one, or he is dead. He may have taken it with him.
But, he was a confirmed communist, and so it was very difficult to get discussions about factual observations on these kidneys with James and because he preferred intellectual discussions to factual discussions, which was very interesting.
This is why his work has not been as accepted, particularly because he went over - and this must be in about '52 I think - he went over to Egypt where he was promised the earth to start doing baboon kidney transplants into humans. Unfortunately their promises as to be expected didn't materialize. In the end he managed to transplant a single baboon kidney that didn't work. And during the year that he was outside the country, earning quite a lot of shekels in Egypt, he rather lost his place in the queue on the surgical side in Hammersmith, although he eventually became a Reader. He'd been sidestepped, as it were, and so his work with transplantation took very much second place to the artificial heart, which, what was his main name doing the work?
SC: At that time, I'm not sure.
MJ: I'm sure someone was working on the extracorporeal heart.
SC: So you left transplantation after.
MJ: I left transplantation at that point.
SC: It gave you time to do some very fruitful other things.
MJ: I then moved from Hammersmith to St. Mary's and I was really fortunate in the sense that Muehrcke, who had been working with Kark, came over and showed me how he'd been doing renal biopsies with needle and I started this, doing the transplants very soon after arriving from Hammersmith, at Mary's with biopsies, kidney biopsies and was really fortunate that I was interested at that time particularly in the nephrotic syndrome. And these were very easy kidneys to biopsy because they tended to be large and soft and so my results were very good indeed, high up in the 90% of successful kidney biopsies. It wasn't until later that I switched to being interested in acute nephritis, as it were, sidestepped from the nephrotic syndrome. It was I think in a way, I would be most impressed looking back, that clinically I recognized there were two types of acute glomerulonephritis. They were quite different cardiovascularily with the acute glomerulonephritis of the focal type didn't have the cardiovascular implications one saw with the acute nephritis of the typical poststreptococcal type that we had been taught. This turned in to be the acute haemorrhagic nephritis if you like, which Wilson and others at the London hospital had put down to a small and unimportant group and didn't really analyze very effectively in their pathology journal, in which they wrote about it, and then they never pursued it in any detail I think, at least Wilson didn't enlarge on this.
SC: You were lucky to have a marvelous team with Robert Heptinstall.
MJ: I was extremely fortunate that Robert Heptinstall was one of the Pathological Lecturers at that time. We decided that we would start looking at the renal biopsy material and I started learning pathology from him and he very reluctantly and unbelievably thought that there were two forms of acute nephritis and I said, well look clinically I can tell you which it is going to be. Eventually, because we had the proof before our eyes and he could see it, he believed we had two types of glomerulonephritis. But we first published a paper together on nephrotic syndrome.
SC: It’s a wonderful series of papers in the Quarterly Journal of Medicine.
MJ: Then we published a paper on acute glomerulonephritis and focal glomerulonephritis to be differentiated from the post streptococcal glomerulonephritis, and I still don't know, I have a lot of clues unfortunately because Heptinstall, although he had been promised the Chair in Pathology at Mary's, was not in fact given it for various reasons and went over to the States, where he made a very great name for himself, and became the head of the biggest pathology department in the world I think at John's Hopkins and was very happy there. But,
SC: He is still working on a new edition of his book on renal pathology, right now I gather.
MJ: After a bit he, well, lost interest in the kidney, which was a pity, but it was sad because I think between us we might have done a great deal.
SC: You did achieve a great deal I would feel.
MJ: But I don't think we achieved as much as we should have.
SC: No. Well, life is always full of regrets.
MJ: When Heptinstall went, I started working with the immunology work at the Middlesex with Deborah Doniach. But it was with very crude antigens that we used and so that one could see that there was some evidence of immunological work in some of them, but you couldn't say of which immunological type and I felt very disinclined to publish anything. She was all for publishing. It’s all a bit vague so we never published this. It's a great pity really because it was the first immunofluorescence work on the kidney.
SC: About when were you doing this work?
MJ: About, that must have been '59 -61.
SC: Yes that was very long ago. I think the first paper on immunofluorescence and renal biopsies was from Kark’s lab in '59 so that was...
MJ: When we arrived then with Deborah Doniach with what became eventually the purer antigens and antibodies were obtained which was possible to do these when they were just a crude graft all taken together. I didn't feel it was adequate to publish, but we disagreed on this.
SC: Just about that time of course, the International Society of Nephrology was founded. Had its meeting in Evian and you were involved in that.
MJ: At that time I was the Organizing Secretary of the Renal Association in this country, and we had everybody from all over the world of interest, except the people who came to talk to the Association.
SC: Let’s begin with the beginning of the Renal Association first, because it of course antedated the International Society by about ten years.
MJ: Yes it did.
SC: How did it start? What was your role in that?
MJ: I think “Bruin” Lewis who was at Middlesex. A.G.G. Lewis’s claim to fame was interesting. He I think was instrumental in founding it, and then we got Osman. Dr. Osman had had a unit for renal failure at Pembury and we invited him to be the Chairman, first Chairman of the Association, which he kindly agreed to do. Inevitably, his views on renal failure and renal diseases are very different from those that we now hold, but on the other hand he was the first person into this country rather like in Boston and Amsterdam, who was looking on renal failure as an entity and trying to treat it. And they both are credited, not with the control of water in the nephrolytes but by giving bicarbonate because of the acidosis. And so they both gave large quantities of bicarbonate to their patients and many of them were quite a lot better. And in that they were sodium-losing as well as being acidotic, they certainly were a lot better for being given bicarbonate.
And of course Borst was important as the Senior Professor of Medicine in Holland, and disbelieving dialysis, which Kolff started in Kampen, which was the second town, if you like city, in Holland and he fought against Kolff's ideas of dialysis and didn't make the path for Kolff as an academic in Holland easy. But that was not the main reason why he went to the States, because he as well as Jaap de Graaf in Leiden, who was the Professor of Medicine there, who was a nephrologist by inclination rather than by profession. And then at the end of the war, they were both so frightened of the Russians taking over Europe, or the greater part of Europe, that in fact Jaap de Graaf and some of his friends in Leiden had a boat with provisions for three months standing by so that if this happened they could immediately take off, get into the boat and sail away probably to America to stop the Russians moving into Holland! Which is interesting, because one doesn't think of that now - and Kolff went to America because of this fear which was quite common amongst people in Holland: that the Russians were going to move in and take over. So he didn't go because of Borst, whose actual claim to fame now lies not on management of kidney failure, but on his understanding of the cardiodynamics and the central venous pressure and having this little machine which measures the venous pressure in the neck, which he always demonstrated on his wife. She remained till I die as she had many good veins in her neck. And so he had a little thing and he measured the venous pressure in the neck to see, and he looked on this as assault phenomenon, which was all he looked at it entirely and solely, of course in some respects he was right.
SC: Yes indeed. But his understanding of volume regulation because he was the first person to think that Verney’s story was not the whole thing. One had to postulate volume receptors.
Coming back to the ISN though, what was your role in it, as representative in the Renal Association and in the Evian meeting?
MJ: I then became joint secretary with Bruin Lewis and both he and I were sent off as representatives from this country to the committee from nations for the first International Society of Nephrology. Now Bruin Lewis didn't speak any French and I spoke it reasonably well, which I no longer do, but...
SC: Only five other languages.
SC: Only five other languages.
MJ: I’m moderately polylingual so I was a useful person there and I had to speak from the British viewpoint and there was a Dr. Cottet, who was the doctor in charge of the Evian water, which was so good for the kidneys, so he felt, and he raised 40 thousand pounds, which in those days was a lot of money. He raised 40 thousand pounds for the first international meeting at Evian and wanted to view this as publicizing Evian water and it fell to my lot to argue the English case. And I said we withdraw if this is not a scientific meeting based on kidney function and one or two other things and this was not very popular with Mr. Cruze. We used to meet in Paris and he (Dr. Cottet) had a very grand flat. Was it Place Vendôme? Actually it was in the rue Saint Dominique, or one of these places, very grand flat and we used to have wonderful lunches, eight or so of use with Professor Mach from Switzerland. I think John Merrill was one from the States.
SC: I was going to ask you about John Merrill because you met him before he came to see you.
MJ: Yes. And we had a Japanese and on one occasion when we had a meeting in Switzerland, Monsieur Mach, who always referred to me as Dr. Jouques. "Ah Dr. Joekes" he said when I came in as usual a little late, "Ah Monsieur Joekes" he said, "Come sit next to this brown gentleman you see", he said in some useful language because he doesn't know what he is talking he said. I said, I tried in the only language that I knew and didn't get anywhere with him, but he kept on spouting about something. Well after about half an hour I realized he was talking English ! - so I had to inform the assembled company that he was speaking English and that I would translate for them what he was saying. So he, this was the first chap, asked me he brought some really dreadful electron microscopic pictures of kidneys, I remember that, and I'm wise enough to say I thought they were dreadful and so didn’t go down well down with Japan.
SC: I just was asking you a second ago, John Merrill is someone we can’t interview obviously. What sort of person was he because he had a major influence in the United States and International Nephrology?
MJ: Yes he was an outgoing personality, who didn't …. underestimate himself.
SC: Again, you’re being polite.
MJ: And he, when he came to see our work, I think he came with Hume, among other people from the transplantation point of view. One got the feeling that he was telling us what we should have been doing, which may well have been right mark you. But I remember when we asked a very good pianist of jazz music and really being extraordinarily good and on one occasion we were both invited to address the Iranian or Persian (as it was then) Society of Medicine in Tehran, and at that time he had his first little stroke, so he didn't turn up. And he was going to make an inaugural address. Unwisely, I had taken my wife, and suddenly I said well I'm terribly sorry but I said I'm giving the inaugural address about five minutes before hand and so I had no script - I had nothing. I had to speak for an hour. The talking has never been one of my major problems so there it was. She sat down listening surprised to hear about what we had been doing, she had never found out before.
SC: So, coming back to your own career of course, you’re principally associated with what we've always known as the Saintly Ps, the urological hospitals in London. When did you move there?
MJ: I was invited there in 1959, but I had been there to see some patient before. And it was an interesting case. He was a gentleman from Pakistan who seemed to be having a lot of trouble. He had a raised plasma calcium, but it didn't seem to be, that he had renal stones or anything, and so we biopsied him and he was very interesting, and I remember that shortly after I had moved to the Three P's and Roger Pugh was the pathologist and I said, we got the biopsy done and he had sarcoidosis. And Roger Pugh said "Rubbish" you know, "Rubbish" you see. So I had to go back and do a liver biopsy and we got some sarcoid out of his liver and so then this was it, and he did really well for several years on small doses of steroids, but then I lost sight of him. But because of this rather strange and diagnostic approach to a patient, at St. Paul’s it was I think that I saw him, I was invited to go there to start renal biopsies and rather reluctantly to consider the question of introducing hemodialysis at the Three Ps, because by that time I had been running the RAF meeting at Halton, which was very useful.
SC: The other thing of course you did there apart from pioneering dialysis and renal biopsy was radioisotopes in nephrology. You played a big role in that I think.
MJ: Yes I was very lucky there. As I said yesterday to somebody who came to work with me as a MRC scholar or whatever it was in those days, it was Tom Sherwood, he had a very incisive and precise brian and this was of great help to me. But I borrowed all the equipment from the MRC, the counters and the counting machinery and the writing equipment so it was very “hugger- mugger” renographic equipment that I had built. And then one day I was, a gentleman had come to see me because he wanted to give some money to medicine. So I said well that was very nice of him, it was someone I had been to Hammersmith with, who had gone into become a GP in the West End of London, and saw a lot of the rich people. So I thought well this sounds alright so he came in - he shall be nameless as he asked to be always - and he came in he had a little moustache, and a rose in his button hole and a lovely girl with him and I said how kind of him to bring his wife and he hummed and hawed, well mfmmffmf. So we got that clear, and then he said he wanted to give me what was in those days quite a large sum of money and I said that was very kind. And he said, "What would you do with it?" And I said," May I go and write you a report so that you know?" "No, no" he said, "I want to know now." And the angle camera I had at that time just written about - the angle camera, because if you remember cross wires were picked up. Really, it was an early gamma camera, but on cross wires as opposed to our iodine crystal, so I said I would like to have work on that and produce one. And he said what would it cost? And lucky I had made some inquiries already at the time, so I said it would be 10 thousand pounds, and he said oh well, and I thought well if he's as offhanded as all this about money I'll have some new renogram equipment, so I had some good new renogram equipment made at the same time, put it all down and it was all isotopic work, and he was very pleased. And I got him to actually to say in writing that he was going to do this, or I could see myself with a bill on my own account.
So we had this built, up in Edinburgh where two brothers had come across from Canada to start to build gamma cameras - I forget their name, but this was a long trial and there I was, as a highly uninformed citizen on, I worked with Norman Veall at Hammersmith on isotopes and did quite a lot of work with sodium. I tried to find out what happened to sodium in acute glomerulonephritis, and I had written a doctorate a paper on this and just as I was leaving the hospital one night, I was called back for an emergency. I left my car standing in the entrance to Mary's you know. But when I arrived in the morning, all my papers were gone, they had all been stolen, and I never published this work but I'd had the great opportunity to work with Norman Veall who was a great pleasure, because I was with him at Hammersmith when he was doing his early stuff, and Norman of course was a cannon as it were in this field so it was a great help.
So very little background, but nonetheless here I was with a lot of isotopic stuff going on and the gamma camera, which I barely understood. Then I was very fortunate in getting as a patient one Anthony Constable who'd been a lecturer in Canada in physics, and then Constable was a physics master at Bruton school in Somerset. He was there with some disease and I was sitting talking to him one day and he didn't really want to go on being a master at Bruton. And I said, well come and be our physics man in the hospital. He said “What a very good idea.” So I said, “Right, you’re appointed.” But it was not really how the administrators thought it should be done. So that may have got me into trouble. So eventually he was very very helpful and I never could have gone on with this without his help because of course he had all the problems about safety and all this that came in. But there was no doubt that with Thomas Sherwood working on the renography side with me, the clinical renography side, we were able to demonstrate the enormous value of this. And I was in fact asked at one time if there was one renal function test that I would keep and I had nothing else, what would it be? And I said renography, because I can tell how the two kidneys work, I can tell what is obstructed but they didn't go down very big in the world at large because his was published as an opinion in some review, you know some medicine review and the people thought that this was obviously this was a little off beat.
SC: Your work had a great deal of influence certainly in the UK in determining the introduction of radioisotopes and their use in nephrology. So you continued your career at the Saintly Ps until your retirement?
MJ: And after I retired, yes.
SC: Doing all these various things and still publishing actively into the 80's?
SC: I note from your considerable bibliography. Is there any other topics you wanted to raise with our audience during that period?
MJ: I think I've not emphasized enough the value of the renal units set up at the RAF at Halton.
SC: Tell us about that.
MJ: This was very interesting because Rumbol, who was the Director of Medicine at the RAF gave more or less carte blanche to set up a renal unit, because none of the services had a unit for dealing with trauma and acute renal failure which came from this. And after a certain amount of discussion and looking round Halton hospital, which was in the Vale of Aylesbury, was thought to be the most suitable to set this up, and it had quite a big medical team there. So I used to send the service patients down there in renal failure in order to get the general management of renal failure understood, then I had to think in the terms of what sort of artificial kidney we should have. About this time, Pim Kolff, who was in Cleveland, wrote to me and said that he had sort of a new artificial kidney, having recognized the problems of the external coil volume of the old Archimedes screw kidney. He said he was walking in the basement of the hospital in Cleveland and he saw, believe it or not large apricot tins, which were ladled out and fed to the patients, and it suddenly struck him that he could get through his dialysis loops one round using some sort of mesh to hold it in and put these into this with a light bulb fitting at the bottom and water coloring at the top and go flushing around altogether and that this would make a very good dialysis unit. So I wrote to him and said would he send me a few of these and let me have a look at them? I was, I think I was at Mary's still, when I got these and so we took one of these and we got a hold of a fish bath and fitted one of Pim Kolff's dialysis machines on to this and dialyzed the patient. It worked very well.
SC: This was the twin coil?
MJ: Right! This was the twin coil. So this was the twin coil that saw its life in Europe and I was very strongly against the big Scandinavian plate dialysis machines of which of course Claus Brun was the best known user. I felt that re-utilizing great big plates, which had been exposed to other people's blood and feeling, still in the terms of glomerlonephritis, this was not a very good thing. Having difficulty of sterilizing all this that one should avoid at all costs having a re-sterilizable kidney. And so I said, “Right let us build a kidney that would hold the twin coil and of course with the RAF building a little artificial kidney was no problem for them at all. They rustled up a twin coil artificial kidney. I think I had it first at... No I think they did it at Halton, and built several of these.
And so we sat there, developed the unit with ordinary re-utilizable coil kidney and because of the control of the extracorporeal volume, which Hamburger, with the Hamburger- Merrill kidney it was called, was stainless steel with a mesh round the big coils of, where they stopped the very enormous volume you could get inside there the kidney screw. But here we had it ready made, and so I was very grateful to Pim Kolff for sending me these over. In fact I had one and one of the people working with me was from Buenos Aires, and he took it over there and some years later he hadn’t put it into the museum and he hadn't used it so I took it back and it’s gone to the Science Museum as one of the original twin coil kidneys that I ... I don't know whether it is still there or not, but in the exhibition I remember they opened it all.
SC: Yes they have a Kolff kidney there which...
MJ: That was the original one from Hammersmith. You should wander round. I think that Bywaters had offered it around to various people. Although he never offered it to me as of course I never saw Bywaters in all this exercise that we did on... The only time that he turned up with a patient who was an interesting patient and in the long run it didn't matter, but he came in one midnight with some, some visiting professor from somewhere, from across some ocean and to show dialysis and how we were doing it and he came and he would fiddle with everything. And he started fiddling with it and in no time faster the lady was dead, she had termed to have acute cortical necrosis, following - but she had ante partum haemorrhage and not post-partum haemorrhage as I remember her. It was the only time I saw Bywaters near an artificial kidney.
SC: He did go back to Rheumatology of course.
MJ: Yes yes. He was not a clinician in any sense of the word. He had this stethoscope I remember which was very remarkable affair, which was rather like a seashell if you put it to your ear, you got a pleasant sort of noise coming.
SC: Of course, it’s sad that the Halton hospital has just been closed within the last year.....
MJ: All the services had their patients sent there and I used to go to the various military hospitals all over the country to see them. And then they sent them to Halton because they wouldn't deal directly with the RAF, the army and the navy wouldn't deal directly with the RAF. Of course theirs wasn't quite as nice.
SC: They were very useful to the British nephrology because they were able to move the kidney to places...
MJ: And of course, they developed a mobile unit and they were a very efficient team and both very hard working and pulled it off extremely well. We were very lucky. It was a very good unit.
SC: You were really associated with the RAF, on and off for a very long time.
MJ: Over a long period yes.
SC: Well Jo, it’s been delightful talking to you and I’d like to thank you on behalf of the International Society and the Video Legacy Program for giving us the benefit of your reminiscences and I’m putting on record your many contributions to nephrology. Thank you Jo.
MJ: Thank you.