ISN VIDEO LEGACY PROJECT

DR. MARCEL LEGRAIN
INTERVIEWED BY J. STEWART CAMERON
GUY'S HOSPITAL, LONDON
JANUARY 20, 1997


JSC: 9; Weíre here at Guyís Hospital this afternoon to talk with Marcel Legrain, one of the founders of French nephrology, on behalf of the ISN Video Legacy Project on the history of nephrology. Marcel, how did you come to take up medicine?

ML: I was born in Paris in 1926, a long time ago. Iím happy to be here with you and thanks for your invitation. My father was a physician. He was an expert in dermatology but he died very young, when I was nine years old and I have a sister and we lived with my mother and after my so-called baccalauréat (graduation), I really didnít know what I wanted to do. My mother was very anxious, being alone and she asked a very good friend of my fatherís to help me to decide on a career. So he said, "Why not medicine? You should come and visit my department to see what medicine is all about." A few days later I decided to go and meet him in a very old hospital in Kremlin-Bicêtre, close to Paris. This was in late 1941-42, during the War, and I discovered a big ward with 80 patients in the same ward and observed an examination of a patient by the Chief. The patient was an old woman, perhaps 80 years old, naked, horrible! And after that, the Chief said, "I have one more thing to do. I want to know if I was right yesterday." I didnít understand at all what he meant at the time but it was to go to the morgue to see if he was right in saying that the liver of another patient was big or small - I donít remember which. Anyway, in the afternoon I decided to choose medicine.

JSC: Iím surprised in view of what happened that day!

ML: So why medicine - I cannot answer!

JSC: You didnít feel under any obligation to take up medicine because of your father?

ML: No not at all. It was a free choice and I should say unexpected and I donít know the reasons.

JSC: Where did you go to medical school?

ML: The first year was not medicine. It was science, what we called PCB - physics, chemistry, biology. If you succeeded at PCB, you were allowed to join the medical school. There were six years of medical studies, including internship and residency. So thatís what I did.

JSC: And where was that?

ML: That was in Paris. But in the middle of that there was a War and after the landing of the allied troops, being a second year medical student, I joined the Red Cross in Normandy near the battlefield, to take care of the civilian wounded and practicing acute surgery in an old castle with the resident and a friend of mine, who was also a second year student. We were cutting legs, opening abdomens and so on.

JSC: It was a rough beginning!

ML: That was an experience. After that I joined the First French Army and I was engaged on the East front in France and Germany.

JSC: As a doctor or a soldier?

ML: As a doctor. What we call "medécin auxilliaire".

JSC: The same happened in Britain during the War. Then you came back to finish your studies?

ML: Yes. I succeeded the concours de líinternat. It was a very difficult selection. Only 10% of the students succeeded and it gave me the opportunity to be a resident for four years in a Paris hospital. That was a real experience.

JSC: I guess itís the French elitism, like the Civil Service and everything. You donít get in unless youíre very good. Where did you study next?

ML: It was at different hospitals in Paris and the opportunity which led me to nephrology was to be the resident of a department devoted to bone disease and arthritis and rheumatism and also there was a very good friend of mine who was a resident in the Department of Professor Dérot and one day at lunch time he told me I was lucky because a resident had given up place as resident in Dr. Dérotís department and he was sure that I would be interested in working in this department. The department expected in the following months an artificial kidney. I was interested in biology and he said I should ask the Chief to make the arrangements for me to join this Department the following year. This is what I did. I had an interview with the Chief. He said, "Youíre the first one to ask. The place is for you!" So in April 1949 I was a resident in the Dr. Dérotís Department.

JSC: He was an internist at that time wasnít he?

ML: Yes, he was an internist but he was already interested in both renal disease and diabetes but as an internist. He was interested in renal disease and sadly he saw a lot of young people dying of acute renal insufficiency. He could not tolerate that. So he had some information about Kolffís work on the artificial kidney. He said he must go and meet Dr. Kolff. He went to Kampen in 1948 and asked Kolff for the details of building an artificial kidney similar to Kolffís apparatus. Kolff agreed, and gave him the plans for the artificial kidney.

JSC: Kolff was very generous. Not only did he give away the plans, of course he built 12 or 14 kidneys and gave them away to different places, including Boston which we will talk about later.

ML: And the plans were used by the engineers of the so-called Assistance Publique in Paris and was exactly like the Kolff kidney with a few small differences, but really very similar.

JSC: This was 1949?

ML: That was 1949, yes.

JSC: Dérot was obviously a major influence in your training.

ML: Oh yes, definitely. This was the place where I discovered renal disease, and treatment of acute renal insufficiency and I was happy working to treat renal insufficiency.

JSC: What was Dérot like as a person?

ML: Oh, very nice. He was a part-time physician, as all chiefs of the departments at that time were. They partly in private practice in the afternoon but Dérot was much involved in his work at the hospital and asked us to work hard and to run the artificial kidney and perform peritoneal dialysis. He was a leader in the field of peritoneal dialysis.

JSC: Where did he get that idea from? Did he get that from Kolff as well?

ML: No. I think he was informed by Dr. Tanret, his previous assistant, who performed peritoneal irrigation very early. He introduced peritoneal irrigation at the Hôtel-Dieu and that is where I learned the technique of peritoneal irrigation and improved the technique by defining the so-called short-term peritoneal irrigation.

JSC: What sort of catheter were you using to put in the peritoneum at that time?

ML: Oh, big tubes used for other reasons. We were using the Potain needle used to go through the bladder. It was used by the urologists to go through the bladder.

JSC: We used to use one that was used for thoracotomies.

ML: Yes, thatís about the same.

JSC: A bit brutal but effective. So by 1948-49 you were already doing PD and hemodialysis?

ML: Yes, exactly. The main problem at that time with the Kolff kidney was bleeding, and bleeding was a major problem with serious cases of acute renal insufficiency and peritoneal dialysis was one way to avoid bleeding. Also, what we did with Jean Dausset, the Nobel Prize winner, was to have a combination of artificial kidney and replacement transfusion.

We needed six nurses. In one room we had the so-called replacement technique. We removed the blood from the patient and brought the blood back to the patient. So we had to receive the blood in one bottle - one nurse. One nurse had to go from this room to another room where the artificial kidney was. One nurse to supply the bottles of blood to the kidney - one blood and one nurse on the opposite side to receive the blood, giving the bottle to another nurse who went into the other room back to the patient. And we published it! The idea was to avoid bleeding.

JSC: In effect you were giving fresh plasma because, of course, until the 1970s or early Ď80s hemorrhage was one of the major causes of death.

ML: That was a big breakthrough made by John Merrill in Boston, using the so-called ?KLF cycling process. So instead of having iron or steel contact the blood, you had this with plastic and instead of huge tubes of heparin, (1 or 2 grams), you could use plastic tubes on the kidney using only 200-300 mg of heparin.

JSC: Many people have said that the whole business of treating acute renal failure, and then chronic renal failure was made possible by the introduction of plastics in the 1950s. Itís difficult to remember now what doing a dialysis with red rubber tubing and glass was like, which is what Alwall and Kolff had in the 1940s, might be like.

You did your thesis on acute renal failure, didnít you?

ML: Yes, exactly.

JSC: Was that on the work in Paris?

ML: No, all the cases were collected in Paris at the Hôtel-Dieu in Professor Dérotís Department.

JSC: I read an old copy - it was falling apart - in the Museum at the Royal Society of Medicine in London, with much pleasure.

ML: "Néphrites Aigües Anuriques".

JSC: Mille neuf cent quarante neuf.

ML: Printed in 1950.

JSC: That was an impressive document because here was somebody, you, who had experience of all aspects of acute renal failure, including hemodialysis and PD. Did the treatment of chronic renal failure cross your mind at this time?

ML: No, at that time it was just considered impossible. We felt that a disease like chronic renal insufficiency couldnít be really cured by using one square metre of cellophane! We had the feeling that it was definitely much more complicated than that. The first report by Scribner at the First International Society of Nephrology Congress in Evian was really something unexpected - completely new for us.

JSC: And yet Kolff and Alwall both started off with the idea of treating chronic renal failure and then found their machines were suitable for acute renal failure.

You had no contact with the Alwall machine or with Alwall?

ML: Some slight contact but very little.

JSC: Now obviously the whole question of treating people in acute renal failure raised the problems of electrolyte balance, which I know interested you. What were you doing with electrolytes at this time? How did you manage to measure this?

ML: The control of electrolytes was definitely important but the technique didnít fit very well with the clinical problem because only manual determinations were made and very often the level of potassium was determined too late, after the death of the patient! But I must say that those blood determinations permitted me to meet a wonderful friend, Claude-Pierre Pignard and I published a lot with him. And also, Colette Bonany, who became my wife. She was on duty when I was on duty.

JSC: So was it the determination of sodium or potassiumÖ

ML: Öof sodium and potassium first.

JSC: Well, thatís a very romantic side to the treatment of acute renal failure. And then later the flame photometer came and played a big role in your career.

ML: Yes, I learned to use the flame photometer in John Merrillís lab in Boston and I learned a lot and then introduced flame photometry in Paris later.

JSC: You mentioned John Merrill and your time in Boston which was clearly a crucial time for you. Tell us more about this. You went to Boston in 1950 or í51?

ML: í51-í52. I arrived in Boston in September í51. I received wonderful advice from Professor Hamburger. I wished to go to the United States and I was not his fellow, I didnít work in his Department but I knew that he was quite aware of many things that were going on in the United States and he advised me to go to Boston and to ask John Merrill if it was possible to visit him.

JSC: Hamburger was working with Professor Valér Radot.

ML: Yes, he was just starting to work at the Hôpital Necker.

JSC: So in fact the Hôtel-Dieu was well ahead of the Necker at that time?

ML: I think it was also the beginning of the Necker, but a little later.

JSC: So it was Hamburger's suggestion that you to work with John Merrill, and that you go to Boston. And a very good suggestion too!

ML: It was a wonderful experience. I started at the Peter Bent Brigham. I learned a lot with a wonderful Chief who became a very good friend and we worked together but we have also been sailing together, crossing the Channel. He was a sailor and, as you know, unfortunately he died at sea.

JSC: Yes, no one ever really knew where he was lost. But you had fun with him on the boat.

ML: Oh yes, and I learned a lot from him. It was a wonderful experience and we have some pictures here of him. This was the leaving party. We were the two first research fellows. Rolf Hoigné from Basel on the left and myself were the two first foreign research fellows working with John, and so for the leaving party we decided to hold a fondue in the lab and this is John Merrill making the fondue.

Here is another picture of the artificial kidney at the Peter Bent Brigham. It was a rotating drum, rolling the cellophane over the rotating drum.

JSC: How long did it take to prepare one of these kidneys?

ML: Oh I should say one hour.

JSC: Oh only one hour, because of course the Brigham engineers made a lot of improvements. Kolff, of course, had to make his kidney from wood because there was no metal available in war-time Holland.

ML: Exactly. That is the kidney we were using at the Hôtel-Dieu.

JSC: This was the winding of the cellophane. Then it had to be primed with blood and then connected up. By this time you were using plastics?

ML: Oh yes.

JSC: So that was an improvement over the red rubber because I think one of the problems with rubber was that it produced tremendous reaction in the patients, fever, chills, etc.

ML: Yes, that was terrible. Definitely the Brigham type was much different with more clinical tolerance. Definitely much better.

JSC: What sort of a man was Merrill? I mean he is one of the people we are very sad not to be able to talk with now.

ML: I should say he was a friend. As you can see on this picture, he was friendly. He worked hard and had vast clinical experience and doing rounds with him, hearing him speak with the patients, advising the patients, was a real experience. I think his clinical experience was really something very important. He was also well informed of the new biochemical problems involved in the analysis of electrolyte disorders and this was the beginning of the description of EKG abnormalities in relation to electrolyte disorders. The potassium EKG determination in a potassium disorder was something wonderful and we worked in Johnís lab on dogs with Rolf Hoigné and other American researchers and tried to describe the effects of changing potassium levels in the heart. So we had a bath for preparing the fluids, to change the potassium levels in the dogs and looking at the EKG. This was the first description of those electrolyte disorders.

JSC: You also looked, I believe, at the toxicity of urea at that time?

ML: Yes. We were all convinced that urea was not toxic but we thought that a good way to prove it was to dialyze the patient, everything being similar to the standard dialysis except that the control group had urea in the bath at the same level as the blood urea. I can tell you that prescribing to the pharmacist of the Peter Brent Brigham a bag of 500 grams of urea made him feel sick. He said, "You are crazy. This is just impossible. We are not allowed to prepare so much."

JSC: Iím sure that you couldnít do such an experiment today. You would never get permission.

ML: Of course, exactly.

JSC: Anyway, you did it and what happened?

ML: The patient was doing well, he was improving, with a high blood urea. We expected about 4 gms/l but it was improved. This was a wonderful experience!

JSC: Of course the causes of acute renal failure then were very different from those we see now in the Ď90s.

ML: Oh yes. We saw intoxication, acute renal insufficiency after surgery and dreadful cases of post-abortum septicemia and a few transfusion mismatches.

JSC: So abortion was still a big problem. Abortion was not legal I guess in Boston in those days or in Paris.

ML: Thatís right. There were definitely more cases in Paris than in Boston but there were cases in both cities.

But perhaps I could speak about a specific unusual case which brought me a car! I will tell you the story.

I was working in the lab doing electrolyte determinations and it was close to the person who operated the artificial kidney and very often I would go into the artificial room while waiting for lab results. One day I entered the room and the atmosphere was completely different than usual. The assistance in charge of the kidney was trying to convince the patient that he should have a catheter in the artery and a catheter in the vein and the patient said, "No. I donít want to be connected to this machine." The assistant said, "Itís essential." The patient was severely ill but conscious. "You are referred by your physician for treatment with the machine," the assistant said. "I donít want it," the patient replied. The assistant called John Merrill. When John Merrill arrived, he asked what the problem was. "The patient doesnít want to be connected to the machine." John said, "Now, take it easy, please. Listen to me. You have been referred to the only place in the United States to be treated by the only machine. You need to be treated. You are at high risk and you should be treated." "I donít want to be connected to the machine," the patient insisted. After a few minutes of calm, John got angry. "You still donít want treatment?" he asked. "No I donít want it". "OK if you donít want it, go back to the ward."

So, I heard all this and I was feeling a little sad about it and during the discussion, I had time to look at the medical chart, and I could see that the patient had an acute renal insufficiency in relation to acute pyelonephritis caused by staghorn calculi. I had some experience with staghorn calculi. So, I thought that it was a problem and that I should try to treat this patient. So I waited a little while and visited him in the ward. After half an hour, I went to the ward and said to the patient, "Now, you are wrong. You were referred for treatment by the artificial kidney and this was correct. You should have agreed to it. I hope that you will recover without the artificial kidney" and I said, "Goodbye, I will see you back here again" and I left.

During the night I thought about the patient quite a lot and next morning instead of going directly to the lab, I went to the ward to see how the patient was. I looked immediately at the urine bottle and there was one litre of urine in the bottle. So the effect of the antibiotics had a good effect on the renal function, treating pyelonephritis and the patient recovered.

Two weeks later, Johnís secretary called me and said somebody was asking for me. I went to the office and there was the patient and the patient said, "Dear ĎFroggieí you have been very nice with me. I am the chief mechanic of a big garage in Boston." (Iím pretty sure it was in December, snow everywhere, very cold) "Iím pretty sure that next Spring you will want to cross the country and youíll have to come and see me. I will help you get a car." I said, "OK, thank you very much." I must say that in that early April, I didnít think about going to see him, but at the end of April, the secretary called and said, "Marcel somebodyís asking for you." So I went again to the office. It was the patient. He said, "You donít remember what I told you when I recovered?" I said, "Yes, I remember but I didnít want to bother you." He said, "Look, come to the window. Looking at the parking lot. You see the blue car there. This car is for you. Come with me, come and see the car." I went and looked at the car. He said, "What do you think?" It was a Plymouth DeLuxe, blue. I said, "Itís just wonderful." He said, "Let me open it." So he opened the back door and said, "Now itís blue outside, but itís yellow inside. Itís a yellow cab. Do you see the counter?" I said, "Yes, itís 170,000 miles." He said, "No, itís more than 300,000 miles! But for $200 you will have a new engine." I thought it was wonderful - $200 for a car. We wanted to cross the States. There are four of us working in Boston and $200 is possible for us. We could afford that. He said, "OK come back in one week and the car will be ready." I went back in a week and he said, "Look at the car. Is it OK?" I said, "Oh yes, it is very good." I checked the car over and didnít see a jack. He said, "Oh yes, you need a jack to go to San Francisco. Donít worry." The car was close to a beautiful Cadillac. He opened the trunk of the Cadillac and said, "Here is a jack. Itís for you!" I said, "Iíll have to pay for that." He said, "No, no, no. They are so rich, donít worry." I sold the car in San Francisco for $150! So all this from acute renal insufficiency from renal stone acute pyelonephritis.

JSC: It just shows that not everybody needed dialysis.

So you came back from Boston to Paris again after one year in Boston and you brought back with you the flame photometer.

ML: No, I didnít bring back the flame photometer but asked the Chief where I worked to buy one. We had to meet with the Chief of the National Institute of Research to ask for financial help to buy the flame photometer. This was Professor Fey at the Clinic of Urology at the Hopital Cochin. Coming back from the States I decided to work with the team of Professor Dérot to run the artificial kidney and to perform peritoneal dialysis but I was asked by Professor Fey when he was in Boston to be the Chief of his Biochemical Lab at the Department of Urology at Hopital Cochin. There were two Departments of Urology at that time in Paris, one at the Necker and one at Cochin. So I worked both at Cochin and at the Hôtel-Dieu. I needed a flame photometer to study the electrolyte disturbances in relation to renal stone urology and contact of urine with the intestine, the Coffey deviation which was very often performed at that time.

JSC: So you were involved very much with urology as well as nephrology. Several units grew up around urological units and of course this link with urology had very big implications for you when it came to transplantation.

ML: Exactly and thatís the place where I first met Professor Küss, who was Professor Feyís assistant and who succeeded him.

JSC: May be we can come back to transplantation in a minute but perhaps we ought to finish the story of your involvement with dialysis first. You are still treating acute renal failure, itís the middle Ď50s. When did you first start treating long term renal failure by dialysis and by what techniques?

ML: Oh long term was definitely later, after 1960-61 this was the beginning of treatment of chronic renal failure using hemodialysis and the first case I treated was a Professor of Anesthesiology, a good friend of mine who had chronic endstage renal failure. He was the first one treated by hemodialysis at the Hôpital Foch using the artificial kidney. We had to treat acute cases and I was asked a few weeks later, because a few people had heard that we were starting treatment of chronic renal failure and the second patient was the first assistant of one of the major leaders of the motor car industry in France. He called me because I said I couldnít take the patient. Ití was impossible to treat two. I could treat one but I cannot treat two. He said, "OK, I understand. I will try to behave according to what you told me."

JSC: What shunts or access were you using? You said earlier that Scribnerís paper in 1960 was a revelation to you.

ML: We were using the system that we used for acute renal failure.

JSC: Still cutting down on vessels and destroying arteries. So you didnít have the Teflon or the silastic at that point?

ML: No.

JSC: And what sort of dialyzer were you using on these patients to begin with?

ML: We used the rotating drum.

JSC: You were still using a rotating drum in the Ď60s?! I didnít know they went on so long!

ML: The first cases used the rotating type, using first the Brigham type and after that the Necker type - the Usifroid. Also we used peritoneal dialysis.

JSC: At this time what catheter were you using because Mort Maxwell had described the plastic system in 1959?

ML: The one we used for venous and arterial catheterization was indeed the plastic type.

JSC: So it was a pretty rough beginning for you!

ML: Yes, it was a rough beginning but I started to use peritoneal dialysis in the United States for a patient with a transplant kidney in 1952. I was called at 2:00 a.m. when I was leaving downtown Boston, "Marcel do come and put your needle into the belly because otherwise the patient is going to die." It was a transplanted case, a non-functioning kidney, severe hyperkalemia and they didnít want to hemodialyze him because of the risk of bleeding and they thought that peritoneal dialysis was better. So that was the first case but it was an acute renal case.

JSC: But you were using intermittent peritoneal dialysis through the Ď60s in chronic renal failure and like everyone else during the Ď60s, you set up a long term dialysis unit that still exists and is still treating patients.

May be we should go back and retread our steps a little and go back to your involvement with urology and the beginnings of transplantation in your part of Paris because of course the first transplants I suppose in France were done at the Necker in the early Ď50s.

ML: The non-identical twin was performed early in 1959 at the Necker Hospital following the non-identical twin in Boston and Küss and I were quite aware of such good results and Küss wished to start a transplantation program and we worked everyday together at Cochin. I was a medical assistant of the surgical team and the Chief of the Lab, as I told you. He said, "Marcel, we have to start a transplantation program and I want you to help me as a nephrologist in taking care of the renal insufficiency of the patients." I immediately said, "Yes." I was working at the Hôtel-Dieu where the place to perform such surgery was not adequate. At Cochin it was the same and Küss was also working at the Hopital Foch where there was an excellent intensive care unit, with Nedey and Vourch who had vast experience of intensive care. We decided, Küss and I, to develop the transplantation program at the Hôpital Foch and we decided to do this as well as keeping our other activities. We were already full time. We decided to perform transplantations never before 8:00 p.m. and never after 4:00 a.m. and, if possible, during the weekends.

JSC: Our program started exactly the same way, as a matter of interest in Ď67 or a little later.

Today unrelated living donor transplants are very much in the news and people think they are something new but I know that you did such a transplant very early in the 1960s which worked successfully.

ML: The first one was from sister to brother and here I have a photograph of the sister and brother in this newspaper.

JSC: The original yellow newspaper and there is the recipient and here is the donor. She is the donor?

ML: Yes, the sister, and this was a very interesting and unusual case. The patient had had carcinoma of one kidney which was removed a few years before by Küss and he was developing carcinoma of the remaining kidney and Küss thought about transplantation but he did not wish to perform transplantation if there were clinical signs of metastases. He wanted to be sure that the liver was normal. So the artificial kidney was at the Hôtel-Dieu, the rotating drum, the patient should be operated on at the Hôpital Foch outside Paris at Suresnes, and total irradiation should be performed outside Paris at Villejuif under the supervision of Maurice Tubiana. So we decided to transport the patient to Foch to do surgery, laparotomy to remove the kidney, anuric patient; back to the Hôtel-Dieu for hemodialysis. After that total body irradiation at Villejuif! After that, Hopital Foch for transplantation. This is the patient two months after transplantation. So this was the first case. He lived about two years and developed metastatic carcinoma later and died from carcinoma.

JSC: Oh he did get a recurrence? It was not from rejection?

You we using, like everyone, I suppose, at that time in the very early Ď60s irradiation. How did you organize that? You said it was at another hospital.

ML: Yes, it was organized as a collaboration of Mathé and Tubiana. and Mathé was very much involved in that field and he had been in charge of treating the Yugoslavs who had been the victims of total irradiation after a nuclear accident.

JSC: So they had sublethal radiation?

ML: Yes, we started with 400 rads, with an additional 200 rads to the spleen. Definitely too much!

But the room we had in Intensive Care was a so-called sterile room at the Hôpital Foch where the patient was maintained for at least two weeks until the leukocytes were increasing again.

The second case was the first unrelated case. She was a patient who was going to die of renal insufficiency and his family wanted to donate a kidney. She had brothers and sisters and one sister really wanted to donate. I knew the family, who were very supportive, and the sister couldnít donate the kidney because she was ABO incompatible. She was there with her husband and her husband said, "But if my wife cannot give her kidney, I can give mine." So he was the brother-in-law, quite unrelated. He was ABO compatible and I said, "Why not?" And with Küss we decided to do it. It was definitely successful and it worked for a long time but unfortunately at the end we lost the kidney by chronic rejection but for almost two years it was really the first unrelated case surviving after total body irradiation and transplantation. It was a great success.

JSC: Tell me about Küss. It seems to me heís been one of the people who has been relatively forgotten. After all, the technique of Küss and Legrain is what, more or less, every transplant surgeon uses around the world and yet his name is not current I think amongst nephrologists.

ML: He was involved in the transplantation program very early. He worked in the 1950s on transplantation and he was in one of the first three surgical groups in Paris working on transplantation - Dubost, Servelle, and Küss. They performed transplantations on a patients using cadaveric kidneys, some coming from patients killed by the guillotine.

JSC: Thatís interesting in view of the recent debate about the use of executed prisoners as donors. Not everyone knows that executed prisoners were used in France in the 1950s as an organ source. It just reminds us that these ethical problems are not confined to developing countries.

ML: Yes, and there were also some of what we called the "Matson kidney, where one kidney was removed for urological diversion and the kidney, which was also used in Boston, was a "free" kidney and this was used at that time by Küss. He developed the technique using the so-called ureteral anastomosis. He was in urology a leader in that field. He was the only one who believed that this was a good technique. Because they heard the word "experimental" some people felt that the so-called ureteral anastomosis was no good and it was better to perform uretero-bladder anastomosis. But Küss didnít feel this way and he demonstrated that ureteral anastomosis was excellent and he put the kidney in the lumbar region and not in the thigh as they did at the beginning in Boston. So he was a wonderful urological surgeon, with vast experimental experience.

JSC: And a great innovator.

ML: Exactly.

JSC: So you were still using irradiation for immunosuppression. I guess you must have changed like other people did.

ML: Yes, exactly. We moved to corticosteroids, slowly decreasing the dose and using azothioprine when it became available and afterwards antilymphocyte serum and so on.

JSC: And again, your transplant program is still flourishing without you! You built up quite a big team in your hospital during those early years.

ML: In 1965 the Director of the Hospital told me, "Dr. Legrain, would you like to have a Department of Nephrology?" I said, "Of course I would like it because it would be better for patients to come for treatment (at all times) during the night or on weekends. So he asked a second question, "Do you want a big department?" I said, "No, I want a small department. Twenty-five beds would be just wonderful!" He said, "Thatís just what I have. If youíd asked me for more than that it would be impossible. If you are happy with 25 beds, itís OK." So they made arrangements and on the sixth floor of the Hôpital Foch? We had a Department, on one side Urology and on the other side Nephrology and the Transplantation Unit was included in the Nephrologyís own Department.

I have some pictures. This is on the sixth floor and this is the first unrelated transplant patient in the middle and young Marcel, and René Küss and the team.

JSC: But later the Unit got much bigger. Iíve seen a picture with 20 or 30 people.

ML: There is still a very active Transplantation Unit in the Hôpital Foch.

JSC: I see Claude Jacobs in the other picture.

ML: This is at the Hôpital de la Pitié. Later I moved to La Pitié.

JSC: Yes, letís move to La Pitié with you. Still in Paris, always the Parisian - you were born in Paris, you were trained in Paris, you practiced in Paris!

ML: And my parents were born in Paris and my four grandparents were born in Paris. This is unusual.

JSC: I was telling you earlier over lunch that in London, almost nobody who lives in London was born in London. But you are a real "un vrai Parisien".

ML: Yes, and happy to be, and my four children were born in Paris and seven grandchildren.

JSC: So you moved to La Pitié?

ML: That move was in 1965 and this was through the help of René Küss because he was operating in Hôpital Foch and in San Louis Hôpital and wished to go to La Pitie but said that he couldnít go because there wasnít a nephrology department close by. So they divided the Surgical Department, one-half of which was for heart surgery and one-half was for nephrology with Christian Cabrol, a good friend of mine and so we worked in La Pitié from 1965 to 1972 and we worked closely with Küss in La Pitie and I left in 1985 when I retired and left for Algeria.

JSC: So that was the time when you were at your peak in the main work. Now, your work during that time concerned not only nephrology but also a big interest from Dérot? I believe you inherited this interest in diabetes and diabetic nephropathy. Tell us a bit about that.

ML: The main reason was very simple. It was the influence of Professor Dérot because working at the Hôtel-Dieu, I was seeing many diabetic cases because Professor Dérot was involved in diabetology since the beginning of his career and when I left the Hôtel-Dieu for the Hôpital Foch, Professor Dérotís department was most exclusively a diabetic department. And of course I had some close connections with his department. So I was always involved in treating diabetic patients. So as any expert in nephrology, I had to make the decision to treat or not to treat diabetic patients. Definitely they were high risk cases and at the beginning of chronic hemodialysis or chronic peritoneal dialysis and transplantation, to take the high risk patients was not the right attitude. So between 1960 and 1970 we excluded diabetic patients from our program but starting in 71-72, we started to treat diabetic patients. We were able to report at the first International Symposium on Diabetic Nephropathy, with Professor Keen.

JSC: Professor Harry Keen, yes. He is an old friend of mine and Iíve worked with him since 1960 on diabetes. I started off in diabetes, not in nephrology and worked with Harry Keen since Ď60 and John Butterfield from 1960-62. So of course I know him very well. So you and he were co-chairmen?

ML: Yes and I was able to report 108 patients with diabetic nephropathy treated using hemodialysis, peritoneal dialysis and transplantation.

JSC: Apart from Minneapolis this must have been a unique experience at that time. No one in Britain was doing that as far as I know.

ML: Yes. We could clearly say that they were high risk patients but since the beginning you could have excellent results, mainly with the younger patients.

JSC: I think that sums up the situation in 1996 and 1997. So diabetes was a main theme in your life.

ML: And the La Pitié has always had a very active department in diabetes. Professor Dérot was working in diabetes before I joined the department.

JSC: Who headed the Diabetes Unit at La Pitié?

ML: Professor Grimaldi.

JSC: One of the themes that comes out of this is your ability to collaborate successfully with surgeons and diabetologists, to produce good results for the patients which is very important. But eventually the time comes around when everybody has to retire and most people look forward to gardening and listening to music and things like that but you took a rather dramatically different turn when you retired in 1984.

ML: Definitely. I took the decision to go to Algeria.

JSC: This is very interesting because now the ISN is very heavily concerned, as we discussed before, with developing nephrology in different parts of world including Africa, but at that time it was not something that people from Europe or from America did very much. What made you go to Algeria? Did you know them very well?

ML: I had no family connections and no personal connections at all with Algeria before its independence in 1962 and I was asked in í63 to give a lecture on acute renal insufficiency by Professor Drif working at Mustafa Hospital in Algeria and this was my first link with Algeria. After that I had different links. I was called as consulting physician in different circumstances including for example the disease of the President Boumédienne who we met there together.

JSC: Yes, we met over the Presidentís sickbed. Unfortunately, he was very ill.

ML: I was asked to give conferences and my Department in Foch first and then La Pitie was selected by many young Algerians wishing to learn nephrology. So such connections have been something that I did have to shape very much. It was just wonderful and they offered me the opportunity to go Algeria to teach nephrology for a two and a half year period and I think that was just wonderful to stay for a while in the country with which I had close connections from í62 until í86 and stayed there from October í86 until January í89.

JSC: What did you do while you were there?

ML: There was a lot of teaching. I taught at Mustapha Hospital and in numerous university hospitals around Algeria, on Mondays going to Kolea, on Thursdays going to Antaya, and every month I went to Constantine and Anaba for a one day nephrology teaching session. It was a wonderful experience.

JSC: You must have seen many different things in Algeria from what you see in Paris?

ML: Definitely. We tried to consider what type of nephrology do you most develop in countries with a low financial income and this is difficult because young physicians coming from such countries wish to learn the latest developments in the field and basic treatment is sometimes considered of no interest. So I had to fight against that.

JSC: This is still a problem.

ML: How to treatment hypertension, prevention of renal disease.

JSC: So you had a good time in Algeria. Do you keep contacts with them?

ML: Yes a wonderful time and still keep good contacts.

JSC: Things are politically difficult now but thatís another story. You kept up the personal contacts with the country.

The other thing you were concerned with in the Ď80s I believe was medicines and the regulation of medicines in France.

ML: Yes, this was completely unexpected. I was asked one day to have lunch with a very good friend of mine who was Advisor to the Ministry of Health, Madame Vey. He was a gastroenterologist. We had lunch together and he said, "Let me ask you to chair of the First Drug Licensing Committee in France." I told him that I had no experience at all in that field and his answer was very simple: "This is why I ask you!" It was thought that the Ministry of Health and his Advisor had taken the decision to change the system of drug licensing in France and to investigate what was done in other countries and to have a drug licensing system that could be competitive on an international basis because this was important to the industry. But this was definitely not the case. He wished to have something different with external advisors taking care of the files of the new drugs and he asked me to chair the Committee who were, of course, experts in the field. It was a fascinating experience because it was the boundary between the industry, and science and research and I appreciated it very much. It was difficult but very valuable.

JSC: And politically very important.

ML: And I did it until 1985 when I retired.

JSC: I guess every nephrologist has to have an interest in pharmacokinetics at least and the problems of introducing new drugs into the renal field.

ML: And the main field of research in my old Department, with Claude Jacobs as a leader, and some assistants specifically involved renal pharmacology.

JSC: Claude himself is now retiring - time passes.

We discussed the fact that you are a Parisian through and through. That means of course that you are the acme of Frenchness. You were saying that you were very embarrassed about your English but we actually love the French accent in English and weíve enjoyed hearing it. But one thing I would like to discuss briefly before we finish is; French nephrology was amongst the cutting edge in the 1950s and 1960s and yet much of what was done, I think was not appreciated adequately, especially in the United States rather than in the rest of Europe because so much was presented and published in French and for a while, as you well remember, the Gaullist Government insisted in all papers being given in French at international congresses.

ML: I fought against it.

JSC: Iím glad to hear it. Not because I donít love the French language but can you give me some idea of your feelings about what has happened to French as a language of scientific communication in the last 20-25 years. Do you feel sad, or neutral, or angry about it because, undoubtedly French has gone down as a language of communication.

ML: I donít feel sad. I think that France should be part of the world science and has to use the English language as a tool to exchange with other parts of the world. Itís because we were unaware of this exchange that we have been a little out of the system and I fought against that. I was among the very few young researchers going to the United States after the War. I founded and was the first President of the so-called Association of French Researchers to help young researchers to go to the United States to practice over there and to learn the language. So I do believe that the French language is important but I do believe that as a scientific language on a world basis, you need to use English. I fought in favor of that.

JSC: But you have no regrets that the beautiful languageÖÖ

ML: Je peux encore parler Français. Mon cher ami, Stewart, et vous dire un grand merci pour votre amitié on peut prendre un verve ou un café ensemble a nous levons fair a dejeuner.

JSC: Ou peut aller a Paris?

ML: Oui, bien entendre.

JSC: The last thing I wanted to asked you about - you had many honors in your career. Reading through your C.V., I suppose one of the peaks of that was your Presidency of the European Renal Association. Have you any reflections on the ETA-ERA and where its going and what it has done and what it might do?

ML: I can speak about the past. Iím not involved in the present process. But I think it was very useful for nephrology to have the Society and for Europe and for France because many countries were out of the scientific world and we fought against that and I think it was a success.

JSC: Two of the early meetings were held in France - Lyons and Paris.

ML: That was very important for French nephrology and very important for European nephrology.

JSC: We never met in Toulouse where Jean-Michel Suc works.

ML: He was a good friend of mine. As you know we worked together to write a book, the so-called "blue book", le petit bleu.

JSC: We will be meeting in Toulouse for the Society of Nephrology later in October but the EDTA never went to Toulouse but it went to Lyons before Paris. Traeger one must, of course, mention in the history of French nephrology

And finally of course the giant of French nephrology, apart from yourself and Gabriel Richet, was Jean Hamburger, with whom unfortunately we cannot talk to now. Would you like to tell us a little about how you saw Jean Hamburger as a man and as a nephrologist?

ML: He has definitely been the leader in the field of nephrology in France and, as I told you at the beginning, I was eager to receive his advice. And when he told me about John Merrillís work, I was most appreciative. He was definitely a leader with the first big Department really involved in kidney disease at the Necker Hospital, in the old section and the new building after that.

JSC: The "Palais du Rein"! It was quite without precedent I might say. There was nothing in the English-speaking world, either in America or in Britain or anywhere else in Europe to compare with what Hamburger had at the Necker in the Ď60s and Ď70s.

ML: And definitely he was recognized as a leader, as a leader by the nephrologists, but as a leader by the political powers and by the financial powers. So he was able to help us and I was also with him at the Commission Nationale de Hémodialyse et de Transplantation and we were developing a social approach on a national basis and he definitely was the leader.

JSC: I have met him many times but how did you see him as a person - easy, difficult?

ML: For myself not at all. But I was not a member of his group.

JSC: I think he frightened people!

ML: He did not frighten me because I appreciated him so much and I was thankful to him and we had easy conversations together and I asked him for advice on many occasions.

JSC: You used him as a source of advice. It was very sad that we lost him a few years ago. I think still the Anglo Saxon world does not sufficiently realize what theyíve lost and what his achievements were. We very much need to preserve his memory and in fact detail his achievements historically. Thatís why Iím asking you about him now.

Well, I think we have covered most of the ground.

ML: Thank you so much for your attention. Beaucoup grands mercis.

JSC: I think that all of you who have watched this tape through will agree that Marcel Legrain is a good raconteur in both French and in English. Before he did this he was worried about both the accuracy of his English and the accent but I assured him that we love the French accent in English! It has been a privilege, Marcel, to share your experiences with you and thank you.