ISN VIDEO LEGACY PROJECT

DR. PAUL MICHIELSON
INTERVIEWED BY PROF. MARK WAER


MW:

Paul your father was a physician. Did this influence you in your choice to become a physician as well or in you in your vision upon medicine and medical practice?

PM:

Oh, that’s a difficult question because you certainly will agree it’s the unconscious factors, which are most important. The fact is that my father was a general practitioner and he had this special view on his duties as a doctor, and it’s likely that this influenced me in one way or another. He also worked in Paris and I happened to have worked in Paris also, but really I think this could be due to chance.

MW:

So what does it mean, he worked in Paris did he tell you something about it that really appealed to you and that made you decide to go to Paris later on as well?

PM:

Yes it was during the war during 1970. He was a student in medicine when the war began and he was put to work in a hospital in Paris. I still remember that in his office there was a photograph of himself in front of the Ecole de ?Metie surrounded by a lot of people with bloodstained clothes and this always impressed me.

MW:

Later you went to medical school. Now knowing what medical practice means from the experience of your father, did medical school fulfill you expectations or was it rather disappointing to you?

PM:

Well I’m afraid that it was rather disappointing, with a few exceptions. I found that most of the courses I had to follow and things I had to memorize were boring. I had a lot of interests outside of medicine also, so I just passed my exams as it should be. I did not feel much concerned about what I had learned.

MW:

So after ending your medical school you decided first to go to what, at that time, was still called Belgium Congo, after while Zaire, and then Congo again. So what was actually for you the most important argument to go to the Congo?

PM:

It was probably the desire to leave everything and start something new and go to a totally unknown world and see how it looked.

MW:

So what was the most enriching experience in Congo? From the personal view of point and also regarding your vision upon medicine and from the medical point of view

PM:

Well it was quite an experience. Because after very ?habit training and surgery during one week, which was obviously enough, they put me on a truck and I became head of a bush hospital with 200 beds. There, was the only doctor there, with only a few black nurses. Well, I had to do everything starting from surgery, obstetrics, and had to care also for a region 100 kilometers or 200 kilometers on the border of Angola. So I had to do all things and for the first time I felt useful and I saw the real meaning of medicine and I became fascinated by the profession at the time. So it was really a turnabout on my view on medicine that occurred during this first year in Congo in this bush hospital. Then after one year, I was called back to Desanto, which was the main centre, and became responsible for blood and the radiology department. I realized that, in fact, I knew nothing about medicine and I decided to start training in the field, which I did not practice in Congo; it’s internal medicine.

MW:

While you were a resident, so you came back to Leuven, you decided to become a resident and an intern in the Department of Internal Medicine. So suddenly you became attracted by the artificial kidney. Now at that time, if I know well, the artificial kidney was not very well accepted by clinicians. Can you explain a little bit why, first of all, you became attracted to this machine, the artificial kidney, and what reason was it, at that time, hemodialysis and artificial kidneys were not very popular amongst clinicians.

PM:

Once again it happened by chance, I must say that when I came back after these very active years in the Congo, I felt very, again, totally useless trying to learn the principles of internal medicine and following endless discussions, which were sometimes to the point and sometimes not so much, so I again felt bored and by chance a colleague trainee, Dr ?Veigmunds, and myself; we found in the basement of the department in an old disaffected, cold hall, we found an early model of the Ulrich Jarvis Kidney, which was not being used. In fact, we became interested in this machine and thought well it could be maybe of interest to try to have it work again.

MW:

Sorry to interrupt, but can you tell us how did you commandeer that machine when it was not used.

PM:

It had been a gift to the university, made by a pharmaceutical company, years before and it had never been used. So, the fact it was not used is not special to Leuven, because if you look at what happened with the other machines that were built, the Kolff original ones, were given to the Dutch universities. When Kolff had left the Netherlands, none of these machines were ever used and dialysis had stopped entirely in the Netherlands. It is also not the industry, which lagged behind because there were a lot of companies whom manufactured these machines. One was Horace Chalmers, in Milwaukee, which made fourteen of such devices but abandoned in 1950 because there was no interest of the medical profession. Westinghouse also tried to put a few of these devices on the market without any success. Laid a thin wall of the same experience, we know from ?backed laboratories, we put on the market a very easy to use machine using disposable filters, also designed by Kolff. They wrote that between ’56 and ’59, they sold 123 such units but nowhere near the number, I quote what they said, “Nowhere near the number were ever used, few were even uncrated.” So why this disinterest of the medical profession? Especially because it was a time there were a lot of interest in other topics. The main interest was in the use of antibiotics in the treatment of, until that time, fatal diseases, tuberculosis, tuberculus, meningitis, and so on. It was the time that the invasive cardiologists ?orbit, so all the interest was focused on these diseases. Kidney diseases were, in fact, also not so frequent. Another factor was that the knowledge on the electrolyte metabolism was limited. The flame photometer was not yet introduced to clinical practice, so it was extremely difficult to have data which could be used and this explained, I think, the lack of interest. So it was not technical difficulties, it was not the lack of interest of the industry, it was due to circumstances

MW:

So after being in Leuven for a while, you decided to change horizons once again and to go to Paris for training in the Au Batalle Nacarre…

PM:

If I may interrupt you, before we decided to go to Paris, we put this Horace Chalmers kidney, which was in the cold hold, put it to work, but it was not evident because there was no possibility to know exactly how it worked and had to be used and also there were a lot of pieces missing. For that reason, we, Ikemond and myself, went to ?Campen because Kolff had worked in Campen and we met there one of his previous assistants, Dr Batiste, and Batiste spent several hours explaining us how exactly it worked with the Kolff kidneys and draw for us the missing pieces, which were then blown in a local glass factory in Leuven. So we were ready to use the machine. We first tried it on a dog. When it seemed to be a success on the dog, there just by chance was a patient who came in with acute renal failure and we dialyzed him during the night because we had no lamp to put this artificial kidney and we could hardly dialyze a patient in the cold hold. So he was dialyzed in the waiting room of the outpatient department during the night. Fortunately we have a film of this. Our first problem had been to obtain cellophane. For this we had been tipped by a local butcher who had bought this cellophane in a German firm, ???, so we bought a huge quantity of this cellophane, then we had to boil this and this was done in a huge basket used by farmers to feed their cattle. As we had only a very small gas fire to warm it up, this took several hours. Then the cellophane was mounted on the rotating drum and afterwards we had to test this for leaks. When there was a leak part of the cellophane loops were resected and an intermediate piece was included. At the end of the rotating drum the cellophane loops were more spaced because the cellophane tended to keep during dialysis towards the end of the apparatus. Our patient was in very poor condition. A catheter had been introduced in the radial artery after cutting the artery and due to the heparinization this gave a lot of bleeding after the procedure. The blood entered the apparatus through the arterial pressure. It was return by pump to the outlet. Before returning to the patient it was filtered. One of our main problems with the apparatus were the rotating couplings because they tended to jam so that canula in the arm of the patient so that it tended to turn with the rotating drum. You have seen the ? pump near the famous rotating canella. We always had to put some glycerin on it to prevent jamming. Another problem was of course the dialysate. Several leaks could occur during the dialysis procedure and we had to interrupt it. One of the problems was the accumulation of foam in the dialysate. The other problem was, of course, after two hours, we had to change the dialysis baths. Because we were dialyzing in this outpatient waiting room there was no drain available. A lot of people had to help to bring buckets of warm water and we had to add electrolytes and test the composition of the bath before continuing the procedure. Another problem was the value of volume contained in the cellophane. This was dependant on the blood flow of the apparatus. We had to dialyze our patient twice and afterwards he recovered as you can see and took up his normal activities as a patient, playing cards.

MW:

So did you do several of these dialysis procedures in several patients or did you realize at that time that you needed some extra experience and bolstered a major argument to go to Paris?

PM:

No it never stopped. You see, at that time we dialyzed all the acute patients in the department. I still remember one young boy with acute glomerular nephritis who was dying of acute renal failure. He recovered and later became a doctor of medicine and I took his examinations.

MW:

Why did you go to Paris then? So that was at the Hopital Nacarr. First of all can you tell us something about why you did go there and can you give us some more information on the Hopital Nacker? Did nephrology exist already by then? Were there some fantastic facilities? What was going on?

PM:

The reason to go to Paris was…first, insight that locally nobody could help us handling these problems of the kidney patients, so we had to go somewhere else. Paris was nearer to Louven and this made it possible to come over when there were problems with the artificial kidney. I happened to take the car and four or five hours at that time, it was in Louven, could help and see what was going on and then go back to Paris. This would not have been possible in the United States or somewhere else. There was another reason, it’s that Hamburger was already interested in electrolyte metabolism and he was also active in intestinal dialysis. I had a presentation by Hamburger ?Terre Velaise a Dos department in ’55. I extremely impressed by the way he presented his data. He really was a master from the deductive point of few. So I was extremely impressed, well I’ll go see what I can learn there.

MW:

So it was not only nephrology or renal insufficiency but it was also clearly the personality of Hamburger that made you decide to go to Paris. By the way, besides Paris, at that time, were there other centres in Europe and/or the States that were famous for treating renal insufficiency

PM:

Well you had Merrill who, would some years later, wrote a book on acute renal failure. This was the main unit as far as I know. You had Joekes was in London was interested in the same topic. In Sweden, you had Orwell but in fact in nephrology as such did not exist, although Hamburger in ’55 already, I quote him:
“Depuis vingt ans, autour du problème crucial de l’urémie, une discipline nouvelle est née, qui mérite de prendre rang aux côtés de l’urologie chirurgicale et qu’on peut nommer nephrology.“
-translation: Since twenty years, surrounding the crucial problem of uremia, a new discipline is born, who deserves to take its place alongside the surgical urology and that one can name néphrology.“
So he already used the name nephrology but his own department was not a nephrologic department; it was the Clinique de Maladie Metabolique and his chair to which he was nominated in ’57 was the chair of the Clinique de Maladie Metabolique. The Hopital Necker was a remarkable place. It was founded before the French Revolution and was a gift of the Madame Necker, the wife of the finance minister of Louiseilles and Louiseilles paid, in part, this hospital. Madame Necker was the mother of Madame de Stalle, who was famous for other reasons. And since the Louiseilles period, my first impression when I came to Paris was that the Hospital Nacarre did not changed that much. It had the charm of all those classical buildings of that time. But it was hardly what you would imagine as a modern hospital. For instance the men’s ward was a series of aligned beds in a huge place. The women’s ward, on the other hand, was already renovated. There was one small research lab. I happen to have picture of this. It’s approximately two metres fifty or four and it’s all the research lab of this department of Hamburger with one chemist in charge. There was a small office for Hamburger and also small office for all the other doctors of his staff. There was also a small library with all the main recent journals, especially in English. There was outside in the backyard an old barrack, accessible from outside by a wooden staircase. This was in fact, in earlier days, a stable for horses to pull the ambulances and in this place laboratory of pathology of Hamburger’s department.

MW:

You said the facilities seemed rather limited in Paris. As you told also, you mainly went there because there was Professor Hamburger. So can you tell us something about how he was as a person and what his vision was of clinical training?

PM:

He was a brilliant personality, extremely clever, accurate; he was a master in using the French language. It was a real aesthetic experience just listening to the way he used his language. He also was a man with multiple interests in all kinds of fields: paintings, music, arts, and of course also writing. He later became a member of the French Academy of Literature. But there was something which struck me from the first moment I came in his department. It’s the kind of emotional binding which existed between Hamburger and his close collaborators. It was a very, very special; in fact Hamburger has this attitude with all his collaborators. You felt immediately considered as a person and as a member of the family and he always had this very small special attention for everyone. If you look at what he himself said of his own master, his teacher, who was Pascal de Leriadeau, I see in his Leçon Inaugurale when he received the Chaire de Clinique de Maladie Metabolique in ’57, he said:
“De quelques élus parmi vos élèves innombrables, vous avez fait des fils qui vous sont unis par des liens si sûrement tresses qu’aucun lien de chair et de sang n’en peut dépasser la valeur.
-translation: Of some elected among you innumerable students, you made bonds that united you by links so surely intertwined that any bond of flesh and blood cannot surpass its value.
Well for me this was totally unusual coming from the cold northern part of Belgium, this kind of emotional link which was obvious and which made all this group of Hamburger work together as family, with the disputes and problems that characterized a family, but with this very special link. This was quite an experience.

MW:

This very specific ambiance was that typical for whole Paris or do you think it was mainly related to the personality of Hamburger?

PM:

It certainly was linked to Hamburger’s personality.

MW:

So could you tell us something about the other personalities that were running around in the laboratory and the department?

PM:

The second person after Hamburger was Richer. He combined a bright critical intelligence with an encyclopedic knowledge of renal physiology. He had an extraordinary diagnostic acumen. He had an excellent clinical insight and above all, he was extremely stimulating at the bedside, always pushing his interns, challenging them, provoking them, so that his tour de salle pour la visite de Richer was quite an experience. And he saw all the patients of his department every day together with the ?. Richer was also extremely concerned with all the young trainees in his department and he developed those lasting friendship with many of them, among them, Claude Amiel, ?Alle Dayoux were well known as becoming later the cornerstones of Richet’s department. There was also Grenier who was a excellent clinician, Fran Bruntaleau who was especially interested in laboratory and in dialysis.

MW:

What about your own clinical research and activities in that period.

PM:

Paradoxically, my first task there was to translate the text of Arthur Allen’s book of the kidney into French because the pathologists did not speak or understand a single word of English. As I understood a few words, I was put in charge of translating these data into French. The young pathologist, his name was Lacont de Fleuris, had his main duty to do the autopsies but he was soon replaced by Yessin de Montera. Yessin de Montera was a charming lady, a young student of Renee Habib, Habib was the pathologist of the Enfant Malade, the childrens hospital in the same Nacarr. Later Burger whose name became associated with the idea of nephrology joined the troop, so we had a very friendly collaboration between all of us. So this was my first duty there but very happy that Hamburger introduced me to the laboratory of Auberlin. Auberlin was head of the cancer institute of Bonjuif and he had there a large unit of electron microscopy where William Bernard worked on the five ? of cancer. It was, not withstanding the introduction by Hamburger, extremely difficult to be accepted there. They finally accepted my presence, or was tolerated, on two conditions. One, I would come only during the night and the weekends. Two, I would work without any assistance, of technicians, of whatever, and use only an old RCA machine. After several months…

MW:

May I ask you, did Hamburger advise you to go to that laboratory of Auberlin specifically to study the glomerulus or was it more in general to study the kidney from the electron microscopic point of view?

PM:

To learn the technique of electron microscopy and I started there, of course, already working with kidney preparations, but the main purpose was to get some knowledge and some technical skills with electron microscopy and then to introduce this in his own department. We very soon bought a Phillips electron microscope, which was certainly not the best one, but it could not have been possible to put a Siemens microscope, for instance, in these bags as they existed at that time in Necker. Then the systematic renal biopsies were introduced in the department and all this material was examined, on the one hand optically under Montera, in the fluorescence by Berger, and I did the electron microscopy, I became in charge of the electron microscopy, in fact of the department. So the confrontation of the data from these view points gave interesting discussions. I remember that Renee Habib frequently dropped in to add a passionate flavor to these discussions.

MW:

So through the electron microscope you became very interested in the glomerulus and more specifically in the mesangium part of the glomerulus, which then became one of you major research topics. Could you tell us something about what was known about the mesangium and what your own contribution to that field became?

PM:

Well the notion of mesangium was introduced by ? in the early ‘30s. It was not universally accepted but most pathologists accepted that there was one or another form of a third cell type in the glomerular tuft until 1954. Vincent ?Home published that in electron microscopy that it was absolutely clear that the mesangium cells did not exist and what had been accepted or seen as mesangium, in fact, were tangential cuts to ?endoterial cell from capillaries lying above or under the section fluid. The prestige of electron microscopy was such that all the other data from literature were ignored. And it became an accepted fact that the mesangium did not exist. In my work on the electron microscope, I had to look at the data of the biopsy specimens but of course if you want to understand what happens in pathological conditions, this presupposes an exact knowledge of the normal conditions. For this reason I became interested in the structure of the normal glomerulus and went back to the original descriptions. You knew the book of Allen which was the bible of the nephrological pathology at that time, but if you look at the description of the glomerulus, it does not contain any mesangium. On the other hand, Goormaktig published extraordinary drawings because the photography was not that good at that moment, made drawings of what they saw on the microscope and they have drawn exactly the same things as what I saw in electron microscopy and described it as mesangium and ?? said these were modified smooth muscle cells in contact with juxtaglomerular nephritis at the vascular hilus. So I studied this systematically in the electron microscope and came to the conclusion that if ?? was absolutely right I could demonstrate ?miophybranes in the cytoplasm of these cells. They made ?never contact with the capillary lumin etc, etc so definitely the mesangium existed, but was unable to convince anyone. I presented my data at the International Society of Nephrology in Avion, the first congress. At the same congress, Farquhar said and I quote,” again the question as to the existence of a possible cell type is still highly controversial” All the other main pathologists present ignored totally the existence of mesangium. The same if you look at the precedings of the CIBA formations in ’61, you will see that the mesangium is not included in the registry. So I disagreed with the official data, on the official opinion on the existence of mesangium and I found also that in certain circumstances you can find selective pathology proliferations of mesangium cells, which were responsible for glomerular nephritis which later became known as mesangial capillary virus. I presented this also in French at the Congress of Avion it made my ???status which was the equivalent of PhD but I had to publish this in Dutch at that time in ’62. It was never quoted and totally ignored. In retrospect, I think that my failure to convince the others was due to several factors. One factor was that the quality of the picture with the Phillips electron microscope was definitely worse than those produced with the Siemens which was used in all renowned. It was also very difficult for an unknown clinician with no formal training in pathology to challenge a famous pathologist such as Farquhar, and then the language problem. So the combination of all these factors was responsible of my failure to convince anyone of the existence of mesangium cells and its special nature.

MW:

At the time you were in Paris and also for several years thereafter, French was a very important scientific language in the field of nephrology and renal disease. Was this really actively stimulated?

PM:

Well the answer is of course yes. Personally, you are certainly aware that my knowledge of English is far from perfect. In fact, during my college years, I stayed ?latent in French and Dutch, but no German, no English. All the people of my age, or most of them, learned English by going to congresses, reading medical journals, magazines and in France the situation was similar. Most papers were published in French; presentations at the International Congresses were made in French. This was a matter national pride to have French recognized as a scientific language at the same level of English and this was actively supported by Hamburger, if I quote from his Leçon au Bureau, “…” So it was only a problem of money and a problem of facilities that French was to become one of the main scientific languages for the future. This reflected the fact, when the ISN was founded at the initiative of Hamburger and ?Gratis, it was a bilingual association. The first congress in Avion was also half-French, half-English and it was impossible for us to present something in English, it would not be acceptable. Also the first two journals, Nephron and Kidney International, were bilingual. Also the proceedings of the EDTA were French and English. So the non-English speaking community was confronted with a dilemma, either you speak and publish in your original language with the consequence of having your message largely ignored by the larger part of the scientific world or use an unfamiliar language which makes it additionally difficult to transmit your message.

MW:

So ironically the availability of ? stimulated an interest for the living kidney. So you already mentioned to us that the name nephrology was an invention of Professor Hamburger and that very soon after discovering this name of nephrology also was one of the cofounders of the International Society of Nephrology. So can you tell us something more about the origin of this society and your own role in this scientific society?

PM:

Two questions, one is the term nephrology. When it was first formally used for the Congress of Avion in ’61 and when International Society of Nephrology was founded. It’s clear that the name was not entirely adequate as nephrologists are supposed to be experts in the function of the normal pathological kidney. The paradox is most nephrologists now treat patients without functioning kidneys as the consequence of the increasing number of chronic renal failure patients who had to be kept alive by dialysis which has led to increasing the number of centres doing dialysis. As the number of really specific nephrological patients was limited there was only spread of smaller centres specialized in dialysis, and this limited the expansion of the real nephrology units, the general nephrology units. So the label nephrology covers a heterogeneous group, which by far the largest number were active in dialysis. Renal transplantation was largely enhancive surgeons, and representing the transplantation society. And the clinical scientists with a strong interest in basic sciences who enlarged concept of nephrology were the members of a small minority joined by a limited number of renal physiologists and this created a series of problems for the future. These problems were enhanced by the existence of the Iron Curtain between East and West. International Society of Nephrology intended to be a worldwide organization and the EDTA to cover all ??. Representatives of eastern countries were, however always linked, to some extent, to the political regime. For some, the political merits were more evident than the scientific merits. Ignoring them with whoever who kept all contacts with those who tended more liberty in exchange of scientific information. An additional problem of this Iron Curtain was difficulty of transferring money to pay for the membership fees. These two factors had an influence on the International Society of Nephrology and the EDTA. First the ISN, the first publication linked to the ISN was Nephron founded by George Heinrick and Richer, it was clinically oriented. When Kidney International was initiated as the official journal the major focus shifted towards fundamental science and physiology. This was, of course, a danger because this covered only a very small part, a quantitative aspect, of the nephrological community. And Ike Robinson understood very well the risks of the situation and tried to attract papers on nephrology and dialysis without jeopardizing the higher scientific level, but in fact the ISN started and remained for some time an elitaire club of physiologists and scientifically oriented clinicians. On the other hand, the journal could only survive with the membership fees of the large number of dialysers who had a limited interest in the scientific papers. The high membership fee precluded also younger scientists to join the society and this was virtually impossible for nephrologists from the Eastern Countries. It’s against this background that one must see the much disputed attempt of the presidency of Priscilla Kincaid Smith to separate the membership fee from the subscription to the Journal of ISN. For reasons unknown to me, as I had not been a candidate, I was elected to serve as council member of the ISN from ’69 to ’75. It became rapidly evident that this was an honorary position without any impact on the decisions which were taken among a small number of prominent nephrologists. I was a spectator of the battle, which was formed in the backstage to separate the ISN membership from the subscription to the journal. At that time the tension between the scientists and the ordinary clinicians was impressive. This resulted in the departmental committee to study revision of the constitution. After a preliminary meeting in Europe, ?, Klaus Thurau, Don Seldin, Georgy Heinrick, and myself, we spent a week in Rome to work out a proposal for magnication It was clear that a true democratic society based on the one-man-one-vote principal was incompatible with a geographically equilibrated society within which all disciplines would be represented. We then tried to work out a compromise for a society of high scientific standing, a proposition for a society of high scientific standing, this was one of the main points we were trying to achieve, but at the same time representative of the different tendencies and disciplines in nephrology. Intermediate decision making structures were created and increasing role of national societies was anticipated by allowing member to ISN through the affiliated national societies. Its purpose was to safeguard the specific supernational role for ISN. Au compromis proposition was accepted after some modifications and the new constitution was adopted by the scientific committee in ’78.

MW:

So not very long after the foundation of the International Society of Nephrology there was second society created dealing with renal insufficiency and renal diseases the EDTA, European Dialysis and Transplantation Association, so what was the reason of founding another scientific association at that time?

PM:

I think it, this is my personal view, that it reflected some frustrations of the second class nephrologists, the dialyzers, who did not feel at home in the ISN. This idea to create a society, especially for those interested in dialysis, this grew in September ‘63 symposium of acute renal failure in London immediately after the Prague Congress of ISN. It was first planned to have a West European Dialysis Association, WEDA, but at a preliminary meeting, foundation meeting in Amsterdam in ’64, it was decided to include all of Europe and the adjacent countries, and transplantation was also included. This last move was not readily accepted, neither by nephrologists, by active transplantationists - Hamburger, nor by the transplant surgeons. There was a strong feeling that the field of transplantation with a specific and logical background was too specific and too difficult probably and that the transplanters would be overwhelmed in a society with a large number of dialyzers. In fact, transplantation remained always a marginal field in the EDTA. For the same reason, prominent renal physiologists strongly opposed it and to broaden the scope of the EDTA by adding the European Renal Association. In a nutshell many physiologists and some of the most influential clinicians, feel that the EDTA was a dialysis club and as such it could not represent the European nephrology. At the time of the Cold War all the representatives of nephrology behind the Iron Curtain were more or less linked to the regime. Decisions on the venue of the congress were emotionally and politically exploding, especially because in the EDTA structure there was no president of the society because the president of the congress would, for two years, become, at the same time, president for the society. This created unexpected problems. From ’66 to ’68, I was a council member of the EDTA and I personally supported the idea of having a congress in East Berlin. It had been decided to have this congress in ‘69 and a president of congress automatically became president of the association. Harold ?Doutze was said to have been the personal physician of Walter ?Albreicht, I’m not sure if it’s true or not, he became president. At that time the Dubchek attempt to introduce a kind of more humane form of socialism had resulted in the Spring of Prague. When this collapsed in the invasion of Czechoslovakia by the forces of the Warsaw pact, an emergency meeting of the council was arranged in October 26. This was a rather dramatic meeting; there were three members of the council from the Eastern Countries: Doutze, from ?Charete in Berlin, Varlek, from Prague, and Orloffski, Russia. At the opening of the meeting there was a feeling of impending drama. Varlek rose and accused the East Germans of invasion of his country and refused to have the next congress in East Berlin. Doutze remained silent. Orloffski rose and accused the West of hypocrisy, “You sold us to Russia at Yalta, you are responsible for the consequences and you have to accept these consequences“. Compromise was found, the congress was relocated in Sweden with Doutze as president. In ’71 the congress would be in East Berlin and under the presidency of Knowles Ulward. Nothing leaked out of the ?carriages, but the politically dangerous attitude of Varlek, but this incident contributed certainly to the decision to have a permanent president of the society separate from the president of the congress.

MW:

Although the first dialysis at the University of Leuven was performed by you in 1955, the real expansion of hemodialysis occurred in the ‘60s. Can you tell us something about the milestones that allowed this expansion of hemodialysis?

PM:

Well the milestones were, of course, the possibility of having chronic dialysis this has led to the expansion of the field and chronic dialysis only possible if you had a permanent access, vascular access, and if you had the technical facilities for dialyzing simultaneously a large number of patients. These were the two prerequisites. In Louven we had used ?Chalmer’s kidney until 1960, 5 years approximately, then we replaced this with the ?Travenol unit, which was named Standard Travenol, which used the twin coil disposable filters of Kolff. This facilitated greatly the treatment of acute patients, but it was not possible to treat simultaneous several patients with this kind of apparatus, because you have to replace the dialysis fluid, the dialysis bath, every two hours, so on; it was impossible. There was another possibility it was the development of the Keel kidney, parallel dialyser, but this was not possible for us because we did not have the facilities nor the staff and the dialysis with the Keel kidney was very long. We also had nearly no money at that time so it was impossible to have a unit built just for the specific purpose of chronic dialysis. When in ’63, the transplantation program with cadaver kidneys started in Louven; we were obliged to start chronic dialysis just to keep the patients alive until they would be transplanted. So we had two major problems to solve; one was access, the second was the logistical problem. Problem of access, for the rotating drum we had used glass candelas which we had put in the radial artery which was cut, ligated after the procedure, and for the next procedure it was cut somewhere higher until it was not ?trombost and then you could dialyze for a second time I’ve been able to use one radial artery up to six times but of course this is totally irrelevant for chronic dialysis. In ’60 Scrimmler had describe this deferens elastic shirt, but this device was not readily available, it was also very expensive. We therefore used another method, which was inspired by from the work of ?Charledon, it was a ?teflon catheter, which was put permanently into the vena cava and it was kept open by a continuous profusion of a heparin solution. We used a driving force and inflate the rubber tubing which the patient could inflate again when needed. This was far from satisfactory we had a lot of ?thrombosis with this catheter. In ’66 I was in New York and I saw in Simeno’s department, in the Bronx, this ingeneous AV fistula, and from then on we have used systematically this technique on all our patients. The other problem was the problem of logistics. How could you dialyze simultaneous quite a number of patients, four, five six, if you have to replace the dialysis bath every two hours, one hundred litres for each of the kidneys. The only solution to the problem was the continuous flow of fresh dialysate at the low flow of one litre per minute, but this was insufficient for the twin coils we used. For this reason, we enclosed just the canister; the twin coil in a canister, this closed canister contained approximately two litres of fluid. We recirculated this fluid at the flow of thirty litres per minute, and to this closed system we added, on one end, one litre one per minute of fresh dialysate, and there was an overflow of one litre per minute on the other side. So we had a single pass system of one litre per minute, which was what we were looking for in order that we could have several dialysers in parallel and at the same time we have a sufficient flow of thirty litres per minute on each unit. We name this system the recirculating single pass, we published this, we gave the rights to Baxter; it was put on the market and the and the name ?compact Travenol. And in this publication in the ??? of the apparatus. The rights for this new system were given to Baxter and in exchange Baxter gave us the equipment for the new chronic dialysis unit, with the possibility of having six simultaneously in dialysis. So we solved our financial problem and our logistics problem at the same time

MW:

1963 was another important year for the nephrology activities at the University of Louven. It was the year that the first kidney transplantation was performed by Dr Alexander, who was trained at the United States. Very soon you decided also to refer your patients to him for renal transplantation. Can you tell us at that time what your vision was on the collaboration between you, yourself as a nephrologists, and certainly surgeon ? at the United States.

PM:

There are two aspect in your question, first is my position referring to transplantation. From the beginning I was convinced that the real solution to chronic renal failure was not chronic dialysis, but transplantation. I had a very, very limited experience in Hamburger’s department, already he had done his first transplant, the results there showed already what could be obtained with a successful transplant, which was so much better than the best results of chronic dialysis. In my opinion, the solution to the problem was there So when Alexander coming back ?Merde’s department started the transplantation in Louven in the department of his boss Morel, who was in fact a neurosurgeon, I immediately contacted him and my patients were immediately put on his waiting list. So the first transplants were already done in ’63. From then to ’66, he transplanted 16 of my patients. Second aspect of the second part of your questions was that there was this collaboration. Well it was difficult because in his view the person responsible for renal transplantation should be the surgeon who did the procedure. I was not convinced by that. He was probably influenced by the situation; I influenced probably by what I had seen in Aubergene. In fact I think it is more reasonable to accept that if an internist has some expertise in the domain of ?immuno-supression and the management of an immuno-compromised host, he’s probably the most appropriate person to follow a transplanted patient, especially on the long term. On the short term there are a lot of typically nephrological problems which can be also be better handled by a physician. There’s a reason that in ’66 I stopped the collaboration with Alexander. And since then all the transplants were done in the surgical department of the institution by professor Cruir. The patient was prepared in my department and immediately after the procedure, he came back to my department, and the follow-up that was done was entirely my responsibility. There are two elements which were very critical for the success of transplantation in Louven; one is the insight in the concept of brain death, and the second is the systematic use of the presumed consent principle. And the first one, the brain death, was in fact already solved in ’59 when ?Molaire, in Paris, had described a situation in which he named ?cormade passé, which in fact, the brain of the patient had died while with the reanimation techniques, the heart could be kept functioning, artificial ventilation and so on. So this was well described. It’s the merit of Morrel, Alexander’s chief, who was a neurosurgeon and realized all the implication of this notion, of this concept of comrade passé, to have said, “Well, let us use the kidneys for transplantation before stopping the reanimation techniques. So from the first transplant in Louven was done with a heart-beating donor with brain death. Morrel was helped in this respect by a young neurologist and specialist in electrohancive photography, Eric Freeman, had quite an expertise in this field and who took the immense responsibility to accept these criteria of brain death to permit the retrieval of organs. The second point which was decisive is that once you accepted that the donor was dead, the rules you had to follow when removing organs were in fact the rules for autopsy. For autopsy in the teaching hospitals in Belgium, we had not a law but a tradition that all the patients dying in this university hospital would be subjected to autopsy unless the family took the initiative to propose autopsy, and in fact this unwritten law goes back to a rule imposed during the Austrian rule in Belgium when Marie Anteresia, from Austria, decided to follow the advice of a Dutch physician, whose name was Van Sweten, who was disciple of Buhavard in Laden, and Van Sweten became the personal physician to Marie Anteresia He reformed the medical studies in Vienna. It was he who decided that for the advancement of science there would be autopsy performed on all the patients dying in teaching hospitals. This rule was also applied in Belgium and in fact it was applied also in most teaching centres of continental Europe. We just used the existing rules and performed or retrieved organs without having to ask explicit permission from the family. We did this during more than thirty years. It’s only after that, that a law was passed in Belgium making official the presumed consent principle and this was voted by a large majority of the parliament in 1986. The reason why finally we had a presumed consent law, strictly speaking, is that there was an increase in ? organ cultivation, which was difficult to do without a specific law and also from the necessity of having to cultivate organs from outside the teaching hospitals because many of the intensive care units were started in peripheral hospitals, not in teaching hospitals. For these reasons, a specific law was passed. It is a combination of the presumed consent law and the systematic application of the brain death principle, which permitted the rapid expansion of the kidney transplantation in Belgium.

MW:

Coming back to this rapid expansions, so about fifteen years after the first kidney transplantation that means in 1978, already more than 250 kidney transplantations had been performed in your department with an overall five year graft survival of more than 50%. At that time you realized or you decided to further take care of all these patients in a concept of clinical network. Today, obviously, all clinical managers are talking about clinical networks but at that that time that concept was rather revolutionary. So how did you develop about that idea and what was the major argument to think about the network as an optimal way of taking care of these patients?

PM:

In the early days of transplantation, we followed all these patients and I did it personally. I knew all these patients individually and they had to come to Leuven for all their ?follow up controls. Belgium is a small country and that’s not so difficult, but as the number of patients increased, it became increasingly difficult to follow us accurately and thus personally, as we would like it to be, these patients. On the other hand, it became clear that one of the main reasons of loss of the kidney in the long term was non-compliance, a non-compliance which was probably due to insufficient motivation of the patient, insufficient follow-up. For this reason, I decided to come to an agreement with a lot of peripheral dialysis centres with responsible physicians who had more time than we had to follow exactly the patients. They also knew very well because they treated them before they went to Leuven for transplantation, so there was close contact with these people and the chance of having non-compliance was much reduced. There was an additional reason; it’s that there was tendency in some places not to put their patients as rapidly as would be advisable on the waiting list for transplantation, because the responsible physicians had the impression of losing their patients to another centre. So by making this network, they became personally directly involved in the transplantation procedure. They did not lose their patient, they got him back immediately after the procedure as soon as possible, and the only thing we asked them was to use the same medical report and to keep in touch by computer, modem, and so on, so that we would have the file of all these patients in Leuven and we could correspond with them to adapt treatment whenever needed. This was the fundamental idea and I must say it worked very good. The motivation of the nephrologists in peripheral institutes improved and also they were motivated to look for donors, so that our donor supply increased. The results were that we had a five year graft survival of 50%, for patients transplanting, between 63 and 77. For the next period of ten years, our graft survival was better than 50%. Ten years. This was far better than all the results published in literature and much better than what had been achieved with living donors in most centres. This increase in the number of donors also allowed us not to make use of living donors while our waiting list remained stable.

MW:

So as you always tell us yourself, nephrologists usually take care about two kidneys and that also explains, in their life, why they usually have more than one laugh. Now besides kidney transplantation and dialysis, one of your other great nephrology laughs was certainly the treatment of chronic glomerular nephritis and more particularly the potential of using indomethacin as a treatment procedure for glomerular nephritis. So can you allude somewhat more on how you came to that idea to use indomethacin and also on your reluctance to perform controlled clinical trials in the field of treatment of chronic glomerular nephritis?

PM:

The idea to try treatment with indomethacin in glomerular nephritis came from the fact I was struck by a paradox. When you have arthritis, which is a immunologically defined disease, you treat it with anti-inflammatory drugs and everybody accepts that this improves, decreases the damage. When you have an immunological disease to the kidneys, nobody treats them with anti-inflammatory drugs. Why not? Because it’s not painful. It’s only reason I could find. And my question was would a treatment with antiflammatory drugs not be efficient also in the inflammatory response of the kidney, of the glomerulus, to an immunological aggression? So I tried indomethacin and much to my surprise, I saw, in many of these patients, a dramatic decrease in ?contranuria, some patients with nephrotic syndrome had a complete disappearance of nephrotic syndrome. And this was reversible when the treatment was stopped, ??? out immediately. When the treatment was given again, the ?contranuria disappeared again. So that in indomethacin was efficient in reducing contranuria. This was proven by interruption and resumption of the treatment. I did not need a controlled trial for this. On the other hand the other question was: what is the significance of this in the long term of these treatments? For this, well, it is extremely difficult to say this, because most chronic glomerular nephritis has a spontaneous evolution over many, many years, sometimes decades, so to start a controlled trial under these circumstances was extremely difficult, if not impossible. That was the main reason. There was also another reason; it was the idea that treatment has to be individualized. You cannot give the same dose of indomethacin to someone who is young, who doesn’t have a preposition to complications, as in older patients. Some patients respond to low doses; you don’t have to increase the dose. Others do not respond to higher doses, so in these patients we added small doses cytophosflomide. So we added all combination of protocols which could impossibly be tried out in control trials because you need a large number of patients. So the only thing I can say is that, after thirty years of experience, when we look at the patients who had a decreasing contranuria, well their prognosis was excellent. Those who did not respond to the treatment at prognosis as is usually so, we noted high contranuria but we never could establish this in a controlled trial, which was fashionable to accept that nothing can be achieved in clinical medicine without a controlled trial. So nobody believes or tried this treatment except a few individual who tried also in individual treatments and confirmed my findings but it was not generally accepted.

MW:

So finally you have had the opportunity and even the privilege to be there when nephrology was born and to be there also when major milestones in this fascinating field occurred. So what, today, after ’40, ’50 years later, what is your own vision now of modern nephrology and modern kidney transplantation if at least you feel that these fields have indeed developed considerably and become modern nowadays?

PM:

It’s a difficult question. It’s the situation as it is. I think I already made it clear that clinical nephrology covers only a very small part of what is usually included under the name nephrology. You include dialysis; you include transplantation, to some extent. Is this justified or should you change this progressively? I have no strong feelings about this. I think there will always be something as a clinical nephrology with its immunological background and this could be linked to the development of transplantation with all the immunological problems involved, even the problem of immunology, and if someone feels strong enough to include also, for instance, outer immune diseases in this, why not? This is equivalent entity. And you could oppose to that another equivalent entity, which could be salt and water balance with all the fundamental aspects of this homeostasis, intensive care medicine, and you could include chronic dialysis, and management of acute renal failure in the group of intensive care medicine. It would not be illogical. If this will occur that’s another question, I’m no prophet.