ISN VIDEO LEGACY PROJECT

DR. DONALD SELDIN
INTERVIEWED BY DR. LEON FINE AND DR. ROBERT ALPERN

 


LF: It is a great privilege to interview Dr. Donald Seldin for the Video Legacy Project of the International Society of Nephrology. My co-interviewer is Dr. Robert Alpern, who is Chief of the Division of Nephrology at the University of Texas, Southwestern Medical Center. I am Leon Fine, Head of the Department of Medicine at University College London and Royal Free Hospital Schools of Medicine, and Chairman of the Commission on the History of Nephrology of the International Society of Nephrology.

With that very brief introduction, Dr. Seldin letís start talking. The best place to start talking is at the beginning. So letís talk about Donald Seldin, the man, and if you could tell us a little about your very early career and take it as you wish, and we will interject and ask questions as we go along.

DS: My initial interest in postgraduate education was in a direction of philosophy and poetry, but I grew up at a very critical time in New York City. The depression was over everyone. It was difficult to get along and there didnít seem to be any possibility of making a living in these domains. Medicine seemed to me a pathetic third choice! So I went into medicine thinking that I had to have some sort of source of income, some profession, or some job that might facilitate supporting a family, and I applied to medical school and was ultimately accepted at Yale Medical School. Yale Medical School was a very interesting institution at the time.

LF: What year are we talking about?

DS: We are talking about 1940, 1939 really. At that time, there were 39 students in my class. There were no examinations except one at two years and one at four years. The system was entirely a tutorial one. No books were assigned. No lectures were printed. The system encouraged one to operate and think on one's own. It was only after two years that there was a comprehensive exam that lasted about four to five days and then one entered the clinical years. Here it was my encounter with Dr. John Peters that stimulated really my interest in both nephrology and metabolism and the domain that then existed. At the time, there was no such thing as a nephrology program. At Yale anyway there was the program of the Metabolic Division of the Department of Medicine. Essentially the Metabolic Division concerned itself with anything that was amenable to the techniques of clinical chemistry. So people who were interested in clinical chemistry would be seeing patients all over the hospital with liver disease, kidney disease to be sure, heart failure, endocrinology, and the like. Now obviously a component of this was the renal component and it was this area that interested me the most. So since one had to have a thesis and I worked in Dr. Peterís Department, I became primarily interested in renal function, although I have to confess that the whole area of metabolism including endocrinology was a major focus of my concern.

LF: And what distinguished these metabolic medicine doctors from the other general physicians was the fact that they also had a foot in the chemistry laboratory and were doing analyses really.

DS: Yes, and really in the certain conceptual sense, were more orientated toward quantitative clinical medicine. You will recall that the landmark publication of Peters was Quantitative Clinical Chemistry. The title was deliberately abrasive and was meant to emphasize quantatation as a critical component of medicine. And the people who were attracted to this area really found this rather inspiring.

LF: The name Peters comes up a lot in talking to people in your generation. What was special about the character and personality of Peters?

DS: Well, on several different levels, Peters was a remarkable man. First of all, he was a person of impeccable intellectual integrity. He fought for his ideals; he stood for something even though he stood for something in a setting where he might be penalized greatly.

LF: Specifically?

DS: Well, for example, he was the butt of a McCarthy investigation. He was serving on one of the first committees of the National Institutes of Health when they started to issue grants and was on a peer review committee. He was accused of being a security risk and therefore expelled. He sued the federal government and ultimately his case was decided in his favor. But it wasnít decided on in his favor on the constitutional issue and he was disappointed. It was a tragic phase of his life. Apart from this, he was a very well educated and cultivated man. He knew a great deal about music, about literature, about political science, economics and the like. He was culturally very sophisticated, and he was also socially responsible. He was secretary of the physicians committee and was probably the principal architect in the writing of the Wagner Murray Dingle Bill which constituted the first attempt of the United States to set forth a broad social program for medical care. Now on an educational level, he was an enormous scholar. A very learned man. He conducted a program in the Department of Medicine, which encouraged and stimulated and insisted on research as a component of medical education. So at that time all the students at Yale had to write a thesis. The thesis had to be based on experimental work. Everybody in the Department of Medicine was attuned to research as a component as education, not merely as a search for new knowledge, and the atmosphere was exciting and electric.

RA: If a patient had renal failure in those days who saw them?

DS: Well, the patients were not segregated to a metabolic ward or into a renal ward. They were admitted on the general medical service and they were taken care of by the physicians who were the attending physicians. The metabolic service would act as consults. By the way, I may point out that the armamentaria that someone in metabolism or nephrology could bring to bear on such a patient was pitifully weak. The flame photometer was just being introduced at the time we speak. Prior to that time you could measure chlorides, sodium was almost impossible, potassium was hardly known. The therapeutic armamentaria that you brought to bear would be a hypertonic saline, glucose and water, and few other things. There were hardly any antibiotics available and no therapeutic modalities. You didnít dialyze anybody. You certainly didnít transplant anybody, and the skill that nephrologists could bring to bear was trivial because the knowledge base was weak.

LF: Do you recall whether there was any healthy dialog internationally in the area of metabolic medicine? One had Fuller Albright, one had Charles Dent in London. There was Peters. Were they living relatively isolated existences or was there a sense that there was a community building? I know itís hard to be able to put oneís finger on that but what is your sense?

DS: Well, there was a continuous stream, it was a scantly stream, but a continuous stream of visitors to Yale from all over the world. For example, the ammonia diffusion method was developed in Ireland. Methods to measure ammonia. I am ashamed to say I have forgotten who it was who did it. He was very distinguished. He came. Of course Albright visited. So did a number of other people. So there was a stream of visitors - the beginnings of an international community - but the network was essentially weak.

RA: At what point did you realize that academic medicine was something that you would do rather than just practicing medicine?

DS: I would guess it was in the third year in medical school when I took medicine and worked with Dr. Peters, and I found academic medicine a very inspiring domain. And it was at that point that I thought I would try to enter academic medicine on graduation.

LF: And so you did.

DS: And so I did.

LF: Tell us a little about those early days.

DS: I graduated from Yale in December 1943, it was in the middle of the war. I was actually in the army at the time but assigned to Yale and allowed to continue post-graduate education through the 999 program. The house staff and faculty were skeletonize. There was a Yale unit in Asia, and the remaining faculty was very few. So there was very little in the way of research or academic work as this had been know in years prior to that.

I actually did a study on rheumatic pneumonia at the time. We were seeing some pulmonary infiltrates in patients with rheumatic heart disease and the question was, "Was this a congestive state or an actual inflammatory state?" And I did a study also on diabetic acidosis where the study was focused on the affect of hyperglycemia and throwing water out of cells the effect of glycosuria in promoting salt depletion. In the course of that study we also studied normal subjects and the like. So we tried to exploit our clinical experience for academic purposes. This was wholly in line with the tradition of the department. We had to do all our own analyses, and it was difficult because among other things, Dr. Peters insisted that everybody do their own chemical work from top to bottom. So we started out by calibrating pipettes and burettes going through all the methods of the laboratory and then ultimately embarking on a project where things like blood sugars and the like were done by each individual without any technical help whatsoever.

LF: And this was protected time or was this piggy backed on to the clinical time?

DS: No this was piggy backed on house staff work, so youíd work through the night and let me tell you doing the Kjeldahl's for nitrogens, and the blood sugars and the like was tough, and youíd of course preserve the blood on the mercury so that you could subsequently do a bicarbonate by the van Slyke method and so forth. But it was exciting nevertheless. Exciting and thrilling. There was a sense of animation that went though the house staff. There were no fellows at the time, just the house staff and the faculty.

LF: So it was salt and water, and if Iím not mistaken, there was a Salt and Water Club, which arose. Now was that around that time?

DS: It was a little later.

LF: Tell us a little about that.

DS: Well, the Salt and Water Club was organized - Iím not sure this is exactly the right date Dr. Fine - sometime around 1946. The main points of contact were Boston, New Haven, and the National Institutes of Health.

LF: And who were the personalities?

DS: Well, Alex Leaf, Bud ?Relman, Bill Schwartz, Frank Epstein, Robert Berliner, Jack Orloff, others.

LF: So it was a very elite company.

DS: It was elite.

LF: A very elite, elite company. And what did you elite people do? Gather once a year?

DS: We gathered once a year in a sort of informal way and there were three or four presentations and the meetings initially rotated among Boston, New Haven, Washington. Then the Salt and Water Club became more formalized and structured and it gained and lost thereby.

RA: So was it at this point that you were beginning to consider yourself a nephrologist rather than an endocrinologist?

DS: Yes. Let me straighten out some chronology so you are not confused. I graduated medicine from medical school in 1943. Then I was allowed by the army to continue house staff training until 1946 and then I left for the army and went to Europe for two years and I returned in 1948. Now I returned because I received a letter. On the last day I was in Munich, Germany, from Yale, I accidentally went to the mailbox to check my mail prior to embarking on the ship to the United States at Bremerhaven and there was the letter from Yale. I opened it and it contained two sentences that went like this: "Dear Don, I would like to offer you a position as Instructor of Medicine at Yale with a salary to begin at $2500 a year." And the second sentence was "Why havenít you written? Sincerely yours, Jack". I never called him Jack.

LF: Now JackÖ Jack Peters?

DS: Jack Peters. That was his name amongst his colleagues. So for that reason I was able to return to Yale.

LF: And you did?

DS: And I did. I stayed at Yale from 1948 to 1951. In 1951 I came to Dallas and Iíve been here ever since.

RA: What are some memories from those three years at Yale on the Faculty?

DS: Well, in those three years at Yale they were pretty exciting times. Darrow had just begun his studies on potassium, which opened a major area for clinical studies at any rate. Lou Welt had just returned from South East Asia. Heíd been in the army. I returned from the army in 1948 and we began collaborative studies Ė some of those I mentioned to you on osmotic diuresis, diabetic acidosis, acid/base balance, and the like.

LF: And how did the Southwestern story actually start? What was the very first provocation?

DS: Well, you know some of these decisions are complicated. It is difficult to resurrect every single fact that went into it. Yale was a very exciting place when I was there and I regard the time that I spent there some of the best years of my life. Dr. Peters was very gracious, so was everybody else, and I had a wonderful time. It was a crowded place. Although the metabolic section was only one section it dominated the Department of Medicine. Maybe if there were fifteen members of the department, perhaps ten were in the metabolic section. It was clearly the driving force in the Department of Medicine. Peters was not Chairman, Blake was. Blake was in Infectious Disease, we had one or two cardiologists, and then the rest of it, Winkler, Denowski, Alkington, Levities, Welt, myself, were all in the metabolic section of the Department of Medicine. So it was an exciting place but it was crowded, and there were, at that time you have to remember, very few medical schools in the United States. It was after the Second World War that genuine medical schools of the type that we recognize were being disseminated throughout the country. Yale was an established institution, like Harvard, like say Michigan, like Hopkins, but there were very few others, and when Chuck Burnett went to Dallas and offered me a position it seemed like an exciting opportunity.

LF: Who is Chuck Burnett?

DS: Burnett was the Burnett of Burnettís syndrome (hypercalcemia, hyperphosphatemia, without hypercalciuria in patients who take milk in alkali. Anyway, when he came to Dallas as Chairman of the Department, he asked me to go with him. The attractive features were the fact that I would be able to have my own laboratory, I could have a metabolic ward and develop a program. Now you should realize that at Yale there was no metabolic wards or metabolic units or study units of any kind because Dr. Peters felt that it would be unwise to segregate clinical research in any one area so patients were seen all over the hospital. This was done for what was regarded as educational reasons. Everybody should be a research project in a University so he thought, and in consequence, until much later there was never any research unit. You just studied patients and tried as best you can to make collections. Now remember, collections in those days were important because the major technology was the balance study and the clearance study. Here it would be a better opportunity to do something in a more structured fashion. Moreover, since I was the only person here, it would be easy to develop something of the kind that appealed to me.

LF: And at what age did you move to Dallas?

DS: I was 31.

LF: So it is clear from what you have said that a really formative influence in your early academic career was Peters without any question and a lot of what you learned and saw at Yale was going to become the substrate of this.

DS: Oh yes. He was a great man.

RA: When you arrived at Southwestern - comparing it to Yale...

DS: Thatís a very interesting comparison. Itís hard to believe, but I had never visited Dallas before I accepted the position. This was a long time ago and people didnít move around as much as they do now. So when I got to Dallas I remember driving with my wife and my daughter down a main street, and I couldnít wait to see the medical school because Iíd never been here. I was directed by a gas station attendant to an area on whatís called Maple Avenue and ?, and all I could see was a series of wooden, abandoned army barracks and garbage strewn all over the place. I went back and asked the attendant where the medical school was. I thought I had been misdirected or at least I had misunderstood. He said there was no misunderstanding thatís the medical school. And that was my introduction to at least the physical facilities here.

LF: And there was a hospital?

DS: Yes. There was a hospital, Old Parkland Hospital. It was on Maple Avenue. It had been built in 1935. It was obsolete at the time it was built. By the time I got here it was worse. The students called the emergency room "the black hole of Calcutta".

RA: So how many students were there?

DS: There were 100 students in the class. At Yale there had been 39. It was only much later that the class size was increased. But a 100 students a class.

LF: So your designated role as a young faculty member was what?

DS: Well, I made ward rounds, developed a research program and did a lot of the teaching. There were only three faculty members in the Department of Medicine. It wasnít crowded. So I was doing a lot of clinical work at the same time.

LF: When did the recruiting start? Youíre recruiting?

DS: When did I do any recruiting? Dr. Burnett arrived in Dallas probably in October 1950. I arrived on January 8, 1951. In April of 1951, an abstract Iíd submitted was selected for the main program in Atlantic City. That was a huge event in those days. There were no specialty societies, and the main forum for academic work was Atlantic City. I went to Dr. Burnett and told him about the fact that I was on the program and he congratulated me, and at the same time, indicated that he was considering an offer from North Carolina. In June of 1951 he left. His total tenure was considerably less than one year. And shortly thereafter I was appointed Chairman of the Department of Medicine.

Now as for recruiting, the medical school here had just been taken over a few years before I arrived by the University of Texas. Prior to that it was more or less a proprietary school owned by the Southwestern Medical Foundation. It had been founded in 1943. The resources were extremely meager and the physical facilities were dreadful. I told you they consisted of abandoned army barracks with plumbing laid on the ground so that when it became cold the school would have to shut down because there was no water or any other facilities. We had no resources for recruiting in the sense of what you are thinking of. So most of the people whom I worked with were medical students. Some of those you know. Floyd Rector, who subsequently became Chairman of the University of California and San Francisco, Norman Carter who became Professor of Medicine here, Jerry Mitchell in Pulmonary Disease, Gene Wilson, Dan Foster, and a number of others. These were medical students with many of whom I worked with personally. Then I sent them away for training and ultimately tried to get them back. And almost all of those who were asked to return did so. So the faculty early on was largely composed of former medical students or house officers whom I had worked with or identified, whom I sent away and then they returned. And then over a period of say five or six years the students who came back were the ones that I mentioned Ė Floyd Rector returned, and Norman Carter, and that formed together with myself the basis of the nephrology program. Gene Wilson returned, Jerry Mitchell returned in heart disease, John Fordtran who was a house officer returned in gastroenterology, Norman Kaplan came back in hypertension. A whole variety of students came back, and at the same time there was some recruiting at a very junior level. For example, Marvin Siperstein was early recruited here from the National Institutes of Health and he was the force around which a metabolic program started. Carlton Chapman came from the University of Minnesota and developed the cardiac program. Abe Broudy developed infectious disease. So we had three or four or five individuals who were established in various ways who would be guide posts to development of various areas while at the same time the bulk of the faculty was ultimately comprised of students and house staff and fellows who returned after training.

RA: Let me back track a second. When you were offered the position of Chairman of Medicine, what was on your mind?

DS: First of all, I enjoy very much the academic milieu in some rich sense of the term. I enjoy the combination of teaching, of clinical work, of research, of the elucidation of problems through investigative methods. The opportunity to take a position of leadership in developing an academic program to me was very exciting and the issues that beset most people these days, were not in the forefront of my mind. Remember that we had almost no money to begin with and we had assembled a faculty nevertheless. It was mostly a medical student faculty, not entirely, but mostly, so the resources we had went a long way. The costs of research programs were very modest. Moreover, there was intense sense of loyalty at the time. There was an electric excitement because we were housed in shacks. Most of them were former students. We all, so to speak, had a mission, and the program advanced in a very exciting way.

LF: I canít resist asking someone who thought of starting life as a poet and found himself very shortly in Dallas what the experience of coming from the "sophistication" of New York and to move into the middle of Dallas was like?

DS: It is obvious that the kind of rich, intellectual life that a University like Yale or a city like New York could provide could not be duplicated in this environment, particularly at that time. Nevertheless, there were things that were of some interest. For example, itís undoubtedly the case that the New York Philharmonic was a more talented group of musicians than the Dallas Symphony. But they were excellent musicians in the Dallas Symphony and we knew them personally. So whereas in New York everybody would scatter to their home and youíd never see anybody, here they were our friends. So my wife who is a pianist, the principle cellist, the principle violinist, we used to visit together and play and in a certain sense there was a rich and musical experience that could be obtained here more than in a more lavishly populated environment such as New York or New Haven. There were a talented group of young architects whom I got to know, again no towering figure like Louis Con or the like, but a very good group of architects.

The biggest single intellectual area that was missing, I am talking about outside the medical school and medical sciences, with things like philosophy and logic of which there was very little. But one could forge slowly; a very cordial group of friends and one could forge a kind of interesting, intellectual life.

RA: At the risk of getting ahead, when you tell us about all of these medical school classes that lead to the Gene Wilsons and Joe Goldsteins and Floyd Rectors, itís hard to think of other institutions or subsequent years that have had such a high percentage of academic stars. What do think the difference was between then and now and between then and other institutions?

DS: Well, itís hard to say, but a few of the qualities ought to be borne in mind Ė one is that I was working with most of these students, they were my students in a sense. And not just in a marginal way. I was on the wards constantly, out of necessity perhaps, and I could interact with them, and I got to know them on a personal level. So for example, Joe Goldstein wanted to be a neurosurgeon and ultimately gave up a promising career to win a Nobel Prize! Gene Wilson wanted to write about the ethos of the American community and ultimately decided to go into metabolism and endocrinology and is now a member of the National Academy. It was possible in short to develop a tutorial system. You know, thatís not given much credence these days, but itís a very powerful modality for developing academic interests. And the tutorial model was very small. We had ward rounds of four people, a student would be interested in research, I would get to know him very well, most of them were students whom I knew personally and I could influence them to at least try academic medicine and many of them who went into other domains initially started with me. For example, Gene Wilson wrote his first paper on ammonia excretion and adrenal activity with me before he started to work on diabetes, protein metabolism, ultimately cholesterol and whatnot. So I think the tutorial model was a very strong one. Itís after all an old renaissance model. If you wanted to be a painter you worked with Leonardo. You just didnít go to school, and itís a very powerful model for the development of academic talent and I think that was the dominating force.

Now there are also, you have to recognize, and be honest about it, social forces lying far outside the medical school that nevertheless impinge upon it. If the model in the community, and the community at large, is money generation or other activities, private practice and so forth, this has an effect. Thereís no question about it, and in that time I think it is fair to say that the model of the University Professor was a rather revered one.

LF: On the east coast was it not true that many of the full-circled, full-time professors did sustain their income by virtue of quite healthy private practices?

DS: Yes. This was here a real full time system, rigid in Dallas. It loosened up in recent years.

LF: Was that something that you felt that you needed to impose or did it seem to happen naturally?

DS: No, this was something that I forced.

LF: And that was because you didnít want people toÖ

DS: Well, this gets to a philosophy of medicine. Some people think a medical school is like a public utility where physicians are available to mitigate community and other problems, serious problems, but the medical school is regarded as a public utility to address themselves to these problems. I donít share that view. I always felt that a medical school was an integral part of the University even though this school was only lately assimilated to the University. At the end of medical school was the MD degree. The MD degree was not a license to practice, it simply certified that the command of the domain of medicine. The responsibility of the medical school was not to take care of as many sick patients as possible. In some vague sense but nevertheless genuine sense; the patient load should be accommodated to the requirements of teaching and research. Now obviously this for complicated economic and social reasons can never be an exact match. But at least the idea would be that one wouldnít seek to expand indefinitely clinical responsibilities beyond these requirements. If that is so, it is important to make certain that one recognized the focus of the institution and therefore I thought at the time that the full time system was a very healthy device although it imposed certain penalties on the faculty. But nevertheless it was healthy and we did it for a long time.

LF: You obviously take, and have always taken, great pleasure in the successes of your disciples and students. It certainly must have put a lot of pressure on you to pull back from the hands-on research activity just given the fact that the whole enterprise was growing that more and more people needed to be looked after. How did you handle that transition, or did you perceive it as such at the time?

DS: Well you have to realize that the renal division was a very tiny division for many, many years. Essentially it consisted of three people Ė myself, Floyd Rector, and Norman Carter.

LF: What years are you talking about roughly?

DS: From about letís say 1954-55 until around 1970, in through there. Now there may be some overlap, but by and large it was a very, very small division. Later on, the deficiencies of size was recognized. There is no question about it. We had nobody, for example, in immunonephrology for a long time and we tried very hard to make up for various deficiencies and ultimately we did but they were deficiencies we recognized. But with a small unit like that, and with a focus on certain principle themes, and with a very coherent group it was easy to participate and direct and do the research that was the core research and other things as well. The core research centered around things like acid-base and potassium metabolism. But we did other things. We tried very hard to make certain that anything that we dealt with in clinical nephrology, we tried to transform into a research problem. We werenít always successful in this but we tried very hard. We did some studies on calcium, on red cells, and other things. Outside the core issues where we were penetrating rather deeply, I think, and considering the time I would guess more or less in the forefront, I donít say this with any sense of arrogance, but we were really trying to examine very basic problems in acid-base balance and potassium and so forth. But we also tried to do other things to exploit the clinical material so that we could come to the wards with the assets that it seems to me an academic person should bring - above and beyond what an experienced clinician could bring to bear.

Now I never personally was upset by the administrative and financial responsibilities that seemed to agonize everybody these days. It never seemed to me such an overwhelming problem. Now that doesnít mean that I didnít have crises, we had plenty of crises. But nevertheless, if I look back on the whole thing, the crises were isolated episodes where other things were going well and I thought it worked pretty well.

LF: So it was very small until 1970, and there was literally an explosion thereafter.

DS: The rest of the department was growing very rapidly, you understand. Iím just talking about the renal unit that was very small.

LF: And what accounted for the sudden growth? Was that NIHís money?

DS: The rest of the department was growing fairly rapidly and I tried in every way to make certain that the specialty areas would appear. I thought we ought to be able to approach every problem on the medical service with high scientific dignity, and in consequence the students who came back, the ones I talked about, aside from Floyd Rector and Norman Carter, all of them went into other disciplines. So we had an emerging gastroenterology unit which ultimately I think became very distinguished. An emerging endocrine unit under Gene Wilson; an emerging diabetes unit under Leonard Madison and Dan Foster; an emerging hypertension unit with Norman Kaplan; a pulmonary unit; cardiac unit, all of these were developing outside of the renal unit.

RA: Obviously as the department evolved, you had to make many different decisions and deal with different issues. Are there certain guiding principles that guided you from the beginning to the end that always seemed to apply?

DS Yes, they are very old fashioned. I always thought that a clinical department of medicine is just that, a clinical department of medicine. There are places in the University, and indeed in the medical scene, which are ideal for pure research. And there are places where pure clinical work can be done. So if one took a look at the Department of Medicine you had to ask what you want that is unique to a department of medicine that gives it its definition. And I always thought the model should be what I would call the clinical scholar; someone who is interested in medicine and competent in medicine but can illuminate it with first rate research and teaching. So there is always an imbalance in one way or another. Obviously we want someone who would be surpassingly brilliant as an investigator, a dazzling clinician and a marvelous teacher. That doesnít happen usually. Occasionally it does but usually not. But in some sense the marvel, like absolute zero, was one in which one had someone who is interested in medicine, in clinical disease, in patients, and at the same time wants to illuminate that experience by research as basic as he or she is capable of. And who finally enjoys contact with students because if you define a medical school as an institutional device for the transmission and generation of new knowledge, then that has to be incorporated in people who can take new knowledge and transmit it. I always felt therefore that it was very critical for people in medicine to make meaningful medical science.

And finally, there is a prejudice here. I thought the necessary condition of medicine in general is a mastery of biomedical science. Now this is often misconstrued. I donít mean to sound heartless and I recognize that there are many other aspects of medicine, but the necessary condition for a physician is the mastery of biomedical science. Now that is not a sufficient condition. There are many other qualities we look for but that would be critical. There is no other domain in society where a mastery of biomedical science is required.

LF: You were obviously playing a very broad role within the medical school, probably with fingers in many, many pies. Were you not tempted to move into the role of Dean, either at Southwestern or anywhere else by virtue of a broad interest?

DS: Well, I have had over the years, many offers for positions as Dean or Vice Chancellor of Medical Affairs, and these never interested me, largely because the notion of disembodied administration, administration that is without an actual participation in the carrying out of any policy simply did not interest me. I thought that the position of Chairman of a department of medicine or the Chairman of a unit was a far better position for the kind of interests I had. So I never looked into Deanships or Vice Chancellorships or things like that, although they had come my way from time to time.

LF: So you must have seen out quite a few Deans at this medical school.

DS: Yes, yes quite a few.

RA: I guess that leads one to ask what do you think about the recent trend in medicine where Chairmen are becoming more disembodied.

DS: You are talking about the turnover of Chairmen?

LF: No, Iím mean the Chairmen administratively running departments but not doing as much direct teaching.

DS: Well I always had the idea that the Chairman, to the best of his or her ability, let me say the Chairperson, should be a scholar. And the notion that a Chairperson is a medical manager, a simple medical manager, seems to me to be against everything the University symbolizes. Now Iím not trying to be unrealistic. I realize that help may be needed for large departments, which have enormous administrative and financial responsibilities. Fine. Then an administrative assistant or two, or whatever is necessary, may be the case. But the leadership should be in the hands of a clinical scholar, someone who has a presence clinically, in teaching and in research. This is the model one would want to set before the student. And if the administration of a department, the leadership of the department let me say, is in the hands of someone whose sole talent is medical managerial skills, I think the entire enterprise suffers even if itís financially stable.

RA: Why donít we move back to the 1950ís in the transition from metabolism to the formation of the discipline of nephrology. Could you tell us how that happened and what were the key forces that led to this?

DS: When I became interested in nephrology, essentially it was a discipline routed in two approaches; one was light microscopy and the other was renal physiology where renal physiology was largely the examination of urine and blood for their concentrations. So the technology available at that time was very simple and limited. In the case of renal physiology, the examination of urine and blood took the experimental form of clearance and balance studies and I think they contributed a great deal, but they were essentially limited studies. In the case of renal physiology, a monumental step was the development of micropuncture. Thereís no question in my mind that this allowed for the reductions of balance and clearance studies and whole kidney studies to a penetration of a black box into segmental analysis, glomerular analysis, and the like so that an enormously powerful tool became available. This is a technology and just like the flame photometer allowed for the exploration of potassium, so the development of micropuncture, which as you know was the technique of Richards and associates before the war, resurrected by Gottschalk after the war, developed here quite independently as an isolated development. So this allowed for a tremendous advancement in renal physiology.

Now at the same time other disciplines were developing in flanking fashion. The electron microscope appeared on the scene and light microscopy became transformed. There was now electron microscopy, immunofluorescence and a whole variety of other techniques. This allowed for the definition of causal relationships. In other words, most of kidney disease prior to the development of, let's say, the area of immunonephrology was physiology and description, whereas disease states began to be explored when the immunologic basis of disease became available for investigation with the development of immunonephrology. And then at the same time renal endocrinology became a major discipline. So the field of renal physiology and light microscopy as a very, very narrow area became enormously powerful with the development of these new domains.

I should say that along with these technological advances were what I would call conceptual advances and they are very important. Most people when they think of fundamental work they think of the discovery of a disease cause, but what has happened in electrolyte metabolism, renal physiology, which is I think equally thrilling, is the development of general laws. Such that, to take a simple example, the notion of the free diffusion of water through the cell membrane to the body such that it comes to diffusion equilibrium with a few minor exceptions. Thatís an enormously powerful law. It tells you a great deal about hyponatremia, hypernatremia, it even tells you something about therapeutic devices without the requirement of memorizing the street level things. Now in renal physiology in particular, these general laws have become very powerful. We donít see much of that in medicine in contrast to such disciplines, lets say as physics or physical chemistry. But they are developing with power and one of the thrilling things about nephrology is that the conceptual framework of nephrology is becoming very, very powerful. As is not only in renal physiology but also in other areas. The burgeoning domain of immunonephrology is impressive.

LF: I wonder whether if the same question had been asked of a European about the origins of nephrology, you place the emphasis on an understanding of how the kidney functions. When the early international community got together were the Europeans as focused as you've suggested the Americans were on function of the black box? Do you have any sense of that comparison?

DS: Well, of course, Dr. Fine, in view of your many interests and hobbies, you know that renal physiology conceived as an operation of flows and pressures was developed in Germany by Ludwig and the like. I think itís fair to say that probably the interest in things like acid-base balance and the like, Iím thinking of Henderson, Gamble, and many others, really came to the fore in the United States. So that perhaps the implication of your question that perhaps there was a disproportionate concern with renal physiology as a homeostatic regulatory organ was more prominent here but Iím not sure that thatís completely fair.

LF: What I was getting at was that here you had clinical nephrologists, I donít even know if they were called clinical nephrologists, you had doctorís interested in kidney disease, who was starting show a profound interest in how the kidney worked. I was just wondering what doctors who were interested in kidney disease in Germany, France, England were concerned with?

DS: Well the people I was in contact with were coming into nephrology so to speak from renal physiology. Iím thinking of Karl Ulrich for example. Klaus Thurau. These are Germans, and a number of others. What was the name of the leader of this group, it slips my mind. You know whom I mean.

Anyway, there was a group that was coming into nephrology so to speak from renal physiology in Germany. In Denmark, again, the monumental breakthroughs of ?Osing were developing quite independent of what we ordinarily would think of as a clinical nephrologist with the two membrane models that he had. And in England, I would say, the focus was on clinical nephrology in a more empirical sense. But on the continent, in particularly in Denmark and in Germany, renal physiology was emerging into nephrology.

RA: Was there some point at which a nucleus of individuals got together and said we need to accelerate the process of developing nephrology as a discipline?

DS: Well it didnít emerge that way. The major defining feature of nephrology came with the development of dialysis and transplantation.

LF: Why do you smile?

DS: Because it didnít emerge from this burgeoning intellectual world that we have been discussing thus far. No, it didnít emerge from that. It emerged from the tremendous impact that dialysis and transplantation had on clinical medicine, and that, so to speak, constituted a necessary call for nephrology. You couldnít have a nephrology program. There was one at Columbia, but short of that you couldnít have a nephrology program without a program in dialysis and transplantation. It didnít matter whether if you interested or not interested or the like, you must have that. Otherwise itís not a nephrology program. You are not addressing diseases of the kidney with therapeutic modalities. You could have it without renal physiology. It may not be sophisticated in certain ways, but you could have a nephrology program that way. But itís hard for me to conceive a nephrology program in an academic center that didnít afford dialysis and transplantation. So the force leading to the definition clearly of this discipline was the development of dialysis and transplantation.

Now to get to the question you mentioned. Why was there, so to speak, an American Society of Nephrology? What was the driving forces? I was part of the original organizing group and it was quite clear that one of the driving forces was the fact that Congress was looking on the scene for advise on matters having to do with nephrology and who would it find. It would find various dialysis groups, very often dominated by people who werenít even physicians. There was nothing on the scene. And it would be very important to many people for an organizational structure to exist that represented the best work or the best minds in the country who could represent the needs of the nephrologic community.

And second, there was the circumstance I mentioned earlier that all of a sudden nephrology was much more than a narrow domain of electrolyte metabolism. There was immunonephrology; there was renal endo-crinology. These tended to be in various diverse places. Increasingly specialty societies arose. And if there was no Society of Nephrology which gathered these various disciplines together, it would be impossible at one place to, so to speak, get a look at what nephrology was like. I think these two driving forces were very important in persuading people that there is a requirement for an American Society of Nephrology. In this respect the Europeans were much ahead.

LF: So when did the Europeanís get into the act?

DS: There was what was it called, Dr. Fine? The Renal Association in England and there were a few associations in Europe. They had talked about and started an International Society of Nephrology when in the United States there was only the Renal Division of the American Heart Association. So I think that in terms of recognizing a specific nephrologic organization, separate say from heart disease, the Europeans were ahead.

LF: Can I push you a little bit? You indicate that Congress was looking for advice, and presumably Congress was looking for advice about patients with kidney disease who were dying, and there was a new technology. And yet the people who came into leadership roles in the American Society of Nephrology were not the people whose primary interest was in that but rather in how the kidney worked. And I recall in the 70ís when I happened to enter the field that there seemed to be lots of tensions in the air between what were two polarizing communities. What are your recollections of that scenario?

DS: Exactly as you described it. There were people how felt that dialysis and transplantation were good things. Less so for transplantation, more so for dialysis, I believe. Something that should be done 'but we didnít have to do that here', so to speak. And thereís one of our most distinguished medical schools at least in this country, which until remarkably late had no dialysis unit whatsoever. And where if a patient with poisoning came they would be referred elsewhere. There was that feeling which rippled through the academic community to a certain extent and there was a hostility toward a certain amount - I donít think that this should be overstated - but a certain hostility to the incorporation of dialysis in the central role within nephrology.

LF: Was it in intellectual elitism that was evolving?

DS: I think so. I honestly think so. I think it was regarded as a crude, empirical enterprise without any intellectual aspects. And I think it was an expression of intellectual elitism, exactly as you put it. Anyway, it was quite apparent very soon that this was untenable because you could not afford clinical care without incorporating these two modalities. And early it was dialysis. As a matter of fact at that point, roughly at that point, there was the formation of the Bureau of the Budget Commission of Dialysis and Transplantation which was familiarly called the Gottschalk Commission to look into the whole matter of federal funding. The people on the Gottschalk Commission were very heterogeneous. Carl Gottschalk himself was principally a renal physiologist but unlike others he was very sympathetic to the whole problem of dialysis, although his personal experience was obviously limited. Others were much more experienced and out of this Gottschalk report came a recommendation for the support of dialysis by the United States Government, which was subsequently enacted.

LF: Can we take you into the International Society of Nephrology now? What role did you play in the earliest days of this Society? How did you become increasingly involved in the activity of the Society? Where were the tensions, and where were the most productive areas evolving?

DS: First of all, I wouldnít want to exaggerate my particular role. I was a member of the International Society for a long time and interested in its development, but I wouldnít say that I was a driving force there. I tried to do what little I could. Early the International Society of Nephrology was ridden by what in the long view of things I have to say were trivial problems. Like, should the cost of the Journal be part of the cost of subscription or not? Should we accept this or that area because they are impoverished or not? Should the Journal be distributed or not? Should we pay so much for the Journal and on and on and on endlessly and with a great deal of violence behind it. Now this is a substantive problem, I donít deny that. But in retrospect anyway, it seems to me that the amount of time taken up by considering issues of that sort was enormous and the international quality of the Society was, so to speak, dormant. Very gradually I think the Society began to assume a major stance in several different directions and Iím sort of proud of the way it has evolved.

In the first place its international status is recognized so that the Journal, Kidney International, is not only a first rate journal but it represents in a genuine sense an international flavor. It encourages contributions from all over the world. It goes to great lengths to ensure that help is given where language difficulties and the like are encountered and so forth. Thatís tribute to additives like Ike Robinson and Tom Andreoli, who have done an heroic job in making this, not only a Journal of the highest intellectual quality, but also one that is international and also representing in the broadest possible sense clinical nephrology, basic science, and so forth.

So one contribution of the International Society of Nephrology was the development of the Journal. A second was various initiatives. The Society was responsible in large part for the founding of what was initially called the Pan-African Society of Nephrology. Various programs, workshops were instituted. Exchanges were developed. Fellowships were sponsored so that the society in a genuine sense became an international society. And on a more elite and intellectual level the Forefronts Program was deliberately initiated in order to bring allied disciplines, which were not in nephrology, into nephrology, so as to advance the field in various directions. To take an example, one of the forefronts had to do with optics, optical measurements deliberately designed to make people in nephrology aware of various technologies which were not prominent. And there may have been a whole host of others. So on an academic level, a clinical level, an international level, I think the Society has done well.

LF: Did the Society in its earliest days know what it was all about?

DS: I donít think so. It took some time to define itself and there were major concerns of the Americans trying to take over the universe and things like that. But I think that was never really the Americans' intent or wish or anything.

RA: Coming back to the American Society of Nephrology, how do you feel about how itís evolved since it was formed?

DS: Well the American Society of Nephrology has evolved in a very exciting way as well. In a certain sense it has become a world society of nephrology. You can see this by virtue of the contribution of foreign investigators to the program, their prominence in the program, and their attendance. Here too I think the American Society of Nephrology has been very good in broadening its coverage and in insisting on high quality. And moreover I think that itís been adventuresome in the way itís developed its programs. All told, I think itís a dignified society and I like the notion that it is seeking to amalgamate some of its program with the International Society so that they mutually reinforce each other.

LF: There has always been the undercurrent that the ASN is the real scientific meeting. The ISN, by virtue of the need to pander to such a broad membership with such diverse levels of knowledge and interest, never quite in the early days managed to get that spark at its meetings. What was the sense at the time?

DS: I think people are aware of that and are trying to correct it. For example, the model of themes is an interesting one. It was deliberately designed to develop so to speak vertical strength so that if you are dealing letís say with a form of glomerulonephritis you would examine it from the very basic immunologic levels to the clinical level so that you could satisfy all the constituencies. I thought that was an imaginative approach. It was good. I think that the meetings where state of the art speakers of the highest caliber have been invited have been very impressive. I think they have been of the highest caliber and I think theyíve done very well. I still do not think the density of talent in the International Society of Nephrology equals what goes on in the American Society of Nephrology, but the International Society is advancing. And maybe some of the joint programs will make yet further benefits. So I am sort of optimistic about both. Itís true that in the early days there was no comparison, but I think the International Society is advancing at a very rapid rate.

RA: When you described the formation of the American Society of Nephrology you stated, it sounded like the renal physiologists were starting something to make sure that they had a say. As the ASN has grown in its attempts to be inclusive of all elements of nephrology, renal physiologists no longer dominate the scene. And as a matter of fact when you go to the meetings now, which may have 6000Ė8000 attendees, itís even hard to find renal physiologists. Do you lament this change, or this good?

DS: When you come to think of the fact that the dominating themes in nephrology are dialysis and transplantation, if you regard transplantation in the broadest possible sense, as a branch of immunonephrology, which I think is reasonable, then it seems to me that inevitably people in these disciplines will burgeon to the fore. Now renal physiology needn't be neglected, but I think its power is much less in the broad field of nephrology than can be contributed by a combination of renal endocrinology, immunonephrology and allied disciplines. So if you formulate this in terms of power, it seems to me the major intellectual input at the start of the society was in fact renal physiology or physiologically oriented nephrologists. And now I think that the balance has shifted and maybe its equal or tilted in one direction or another but I canít think that thatís necessarily bad unless you say that the individuals who do this are no longer rooted in the best quality of work. Now thatís another question and is not necessarily subject matter dependent. In other words, I would not say that someone who is invested in immunonephrology is an inferior scientist or a superior scientist to someone who is a renal physiologist. But if you select people in immunonephrology who are not of the highest quality, if for political reasons or financial ones they emerge into power, then I think the Society will suffer. Yes. But I donít see why because renal physiology was in a certain sense the foundation that it should remain so. Look at the Journal of Clinical Investigation. When I was starting here that was dominated by electrolyte metabolism. I mean you could just leaf through the early pages and see that that was the dominating thing. I mean infectious disease was nothing. It was all electrolyte metabolism. Now, even in the renal section, renal physiology is modest. Thatís not a plot on anybodyís part.

LF: Well to some extent, I mean, what you are describing is a successful venture that has in fact been able to transmit its knowledge to a good internist who can handle these problems.

DS: I think itís terrific. I would hope that if renal physiology advances in the way that it does, most of what was previously sophisticated narrowly based knowledge would become, as Dr. Fine says, the common property of everybody.

LF: You intimate that perhaps the dialysis community didnít counterbalance the intellectual strength, letís call it, of the physiology/pathophysiology community.

DS: In the Society or in society at large?

LF: Well, I suppose in society at large.

DS: It was very powerful in society at large at the start. Very powerful because they commanded a lay constituency that was enormous. But in intellectual circles, I would say at the start the renal physiologists, the physiologically minded academic people dominated the scene. There was a disparity clearly.

LF: To play the devil's advocate - I mean these were the people who were looking after patients with kidney disease, patients who were dying. These were people who were looking for new technologies which were life saving. And there was this sense that their work was not being appreciated in the early days. Iíve heard that from a number of people.

DS: I think there is more than an element of truth in that. Sure. Just as you might say the pendulum has swung to the point where people who are in renal physiology might be regarded effete intellectuals, remote and disembodied, unconcerned with the welfare of the sick. Whereas the firing line is on the transplantation and dialysis. And I think thatís similarly an extremely distorted view.

RA: Related to this the American Society of Nephrology has moved out for its meeting to be more educational to the practicing physician. While continuing the scientific interchange itís been diluted. And that in many ways has led to the large increase in attendance at the meeting, which is viewed by many as a major success. Some scientists feel that theyíve lost their forum for getting together. Do you have thoughts on that?

DS: First of all I donít share that view. I think the incorporation or the consolidation of the National Kidney Foundation with the American Society of Nephrology is a very good thing. I think it means that we donít have competing polarizing groups, and I think that the absorption of the clinical arm for the American Society of Nephrology is very healthy. So I donít share the view that the incorporation of a large constituency rooted in clinical care is a bad thing for the American Society of Nephrology. Now the second point you mention - is the quality of the Society deteriorating? By virtue of this, I donít see any evidence of that. Now maybe Iím too remote now to make a judgement but I donít see any evidence, and neither does anybody in Europe see any evidence. Because if you look, well you are better acquainted to assess than I am, but if you look at the papers which are submitted by the best European Universities and laboratories to the American Society of Nephrology, they are very impressive. And I think about one-third of the papers on our programs come from Europe. Even more. So itís obvious, at least looked at from afar, the American Society of Nephrology is still valued as a podium for the finest kind of work. Now whether it will deteriorate in the future, I hope not. It will depend on people like both of you.

LF: Nephrology is entering a very difficult time in that thereís been no leveling off of the escalation of the number of dialysis patients. The need for nephrologists is constantly growing. The nephrologists are not being trained. There just simply are not enough of them. And many people ask perhaps weíve reached the point where a lot of the duties of nephrologists should be subsumed by other types of doctors and that maybe the new nephrologist is a different type of species. Is that anything youíve thought about?

DS: Well that comes up all over medicine. Where specialization advances, then people increasingly say we ought to have a new domain and that has happened. After all, at one time internal medicine subsumed all the categories we now recognize as separate and distinct units; cardiology is a separate unit, and some people want cardiology departments independent of medicine departments. Infectious disease. They are all separate where previously they were united in one core. Now it seems to me that in nephrology a great deal would be lost if dialysis was separated out of it because I think one can make a distinction between some of the requirements of dialysis and its geographic locus. It seems to me that there could be individuals who are focused on dialysis principally, but they ought to be in the setting where a nephrologist is in charge I would say. I think that model is healthy just as I believe that one can use - you know there is a great movement in the United States for nurses to assume medical responsibilities. I mean important medical responsibilities. Now, I donít find that terribly distressing except when itís isolated and remote. I think if a group of nurses, properly trained, took care of patients under the supervision of a physician that would be fine. And I would take the same view of dialysis. There is a healthy distribution of labor here that may help all the way around. I donít think a highly trained physician who spends 4 years in medical school, 3 years for house staff training, another 3 years in post-graduate specialty training, a total of about 12, 13, 14 years should apply himself or herself to things that could be done by anybody. I think itís wasteful. I think one should look for ways to apply that talent where that talent is needed where the education and society has built into such a person at great cost is used. So I donít find it so distressing where there are, letís say junior people or other individuals who specialize in dialysis, who are under the overall supervision of appropriately, highly skilled and dedicated nephrologic physicians, I think that's good. I doesnít bother me at all.

LF: Now other than the tangible advances in dialysis and transplantation, would you have predicted when you got into this business, that we would have made more headway in understanding the etiologies of renal diseases than we have up to this point. Has there been any sense of an unfulfilled mission?

DS: Well, I think that when Dixon and others developed the models of complex disease and linear immunofluorescence and the like, I think that was a monumental advance for medicine. Not only in nephrology, just monumental. Now the fact that it hasnít resulted in the complete clarification of all these underlying diseases is a little disappointing. But still, I think thatís almost a qualitative leap from what existed before. And the emergence of the entire domain of immunonephrology has contributed, I believe, in a major way to basic understanding of disease processes. And I really think that the Dixon work, itís not only Dixon but many others, is a path breaking thing that originated in nephrology and spread to many of the disciplines. One would have hoped that by this time perhaps a more narrowly causal sequence would have been defined between an antigen, letís say, or some derangement and so forth, but nevertheless, with cytokines bursting out at every street corner, I think that a great deal of progress has been made.

RA: Dr. Seldin you spoke earlier about the importance of the clinician scientist. I was wondering if you could tell us how the clinician scientist has evolved from the days when you went to medical school through into the 1990ís.

DS: Well I think this model is in the midst of a crisis. There are two difficulties that seem to be setting academic medicine at least in this country. One is the impact of money generation. Where previously we discussed earlier the full-time system, now almost everywhere there is a requirement to generate resources through largely clinical activities and this has imposed a tremendous burden on any clinical faculty member.

The other polarizing influence is the rise of molecular genetics on a scientific level. Where previously most of the things one did on an experimental level were automatically translated into clinical work. You did a cardiac catheterization - that was not only a necessary investigative tool, but it translated rapidly into clinical consequences. At one time it was impossible to get a paper published in the Journal of Clinical Investigation without an immune clearance whether it was necessary or not. But clearance studies gave one a familiarity with certain aspects of how the kidney functioned so you became a more skillful nephrologist for knowing something about clearance.

Now the most powerful tools in everybodyís hand are the tools of molecular genetics and how to translate that into a meaningful, clinical activity is difficult. Iím not saying it canít be done. Everybody is wrestling with this notion. So here we have the clinical scholar poised on the one hand between the pressure of money generation through clinical activities, and on the other hand mastering a domain of learning; both technical and conceptual which has no immediate overflow in any massive sense into his or her clinical activities. So one begins to demand a great deal of such a person.

Moreover, itís not clear what the reward system is doing. Previously the reward system was focused largely on scholarship. Not only scholarship, but scholarship principally. But now, issues that are seemingly remote from scholarly activity like money generation begin to assume a dominating feature of the scene. So that mixed messages are being sent to the faculty. Do teaching, but we wonít reward you for teaching. Do research, but you better generate clinical income. And the net effect is a certain schizophrenia. So the model of the clinical scholar which is something I believe one should have but one should realistically recognize that it is endangered, and consequently the skillful educational leader or the leader of the unit should try to develop devices such that individuals who are dedicated to clinical scholarship be protected.

LF: The model you are describing is the situation in the USA. Most European countries donít have this need for personal income generation in an academic environment. Do you think that that has been reflected in a higher level or quality of clinical scholarship across the Atlantic?

DS: Well itís often been said that American academic figures are not clinically as skillful as their European counterparts. Thatís not been my experience. You would be in a better position to judge having worked both in the United States and in London. But thatís not been my experience. I have been elsewhere and I think that varies with talent. Some people are very skillful and others less so. But I was not aware that there wasnít a pressure for money generation. In my times in Germany - for example, I have a von Humboldt Award and Iíve been in Germany for two months a year for a period of five years - I find they are under great pressure.

LF: This pressure, and I donít mean to consume any of your time on this, is certainly pressure to generate money to support research. What you are talking about in the United States is the additional pressure to support your own salary when you are young investigator, which is not part in parcel of most European systems.

DS: Well, to the extent that that is true I think the Europeans have a better model.

LF: That may be because they havenít reached the same stage of evolution thatÖ

DS: Whatever the reason, I donít think an academic setting, take a physics department or an English department, why should the department of medicine be any different? I donít think any academic studying should require that the academic physician be a money generator. And that wasnít the case until relatively recently. In our school which is a rather old fashioned school these pressures are much less. In other words, we get support from private resources, from the state and so forth which allow for a rather, I would guess, generous underpinning of salary structures.

RA: So how was this different when Dan Foster and Floyd Rector were joining the faculty?

DS: There was almost no pressure for money generation.

RA: So how were their salaries paid?

DS: Well in this school, as you know, they were largely paid from grants and the state budget, and not derived from clinical income at all. As a matter of fact, it is very difficult to generate clinical income from the kind of hospital that we worked in. And moreover in addition, there were very sharp caps on what you could keep as a result of clinical activity. And finally there was a strange rule in place such that you could not have private patients. You could only have private consultations. Now the consultations might last a long time, but nevertheless, they were finite and at the discretion of the referring physician. So there were very sharp limitations on money generation through clinical activities. Very sharp. And I gather from what Dr. Fine is saying, this prevails at least for young faculty members in Europe. I was not aware of that. Thatís not been my experience.

LF: Youíre not aware of the...

DS: I have the impression that in clinical departments there is a pressure to generate money.

LF: There is, but itís the generation of money to do the research. Where I think what we are arguing about or talking about is the fact that your very survival personally is dependent on making sure that the salary comes in. And if the grant fails then there is a fall back position and that fall back position often has been the need to do private practice, where as I think that in most of the European systems those were in academic settings. At least they have the guarantee of that as a security. I think that that may be just a subtle difference.

RA: One of the differences that I see looking at the medical schools of 30 years ago to now is the size of the faculty. The enormous expansion of the faculty has led to in many ways to these financial pressures. Do you have a sense for why medical schools have become so much larger?

DS: I think it is specialization and I think it is all to the good. Now having said that, I donít need to say that one may not overdo a good thing. But, the reason we have a gastroenterology department, frankly, is that the domain of gastroenterology is complicated and for you as a nephrologist to command all the conceptual analytic techniques of gastroenterology would be practically impossible. So you need a gastroenterology unit where previously there was no need for one. And if you go right down the line Ė cardiology and so forth and so forth Ė one doesnít have to elaborate, you are talking about what was once assumed in the case of one or two people. Now you have huge divisions and then you have subspecialties within the division. We have individuals who are particularly skilled with tubes. They like to insert tubes in people and are very good at it.

LF: But arenít the economic forces at the moment, in fact, pushing things in the reverse direction?

DS: And that may not be all bad. But even when we reach the steady state if you look at the requirements, the requirements are enormously greater as a result of the advance of knowledge then they ever were before. And I think that by and large that is a good thing. I think that one can over simplify it by pointing out the burgeoning technologies and what not, but the fact of the matter is that to afford patients, the best in diagnostic and clinical care, you need varied skills. Now I would hope that in an academic department, everybody could master the simple core of medicine but that is another problem and many people donít agree with it anyway. But I just give you my own view that the central core of medicine should be at the command of all faculty members. By the way that is very easy for nephrologists because that discipline involves in part hematology, immunology, cardiology, as well as renal function.

LF: We are all aware of the increasing difficulty, and I think this is an international problem, of trying to maintain a vital and viable interest in the general aspects of medicine. And one can see that reflected in the falling attendance in those sorts of meetings - in this country the ASCI, the IAP -is that something we should just be willing to accept as an evolutionary process? Is it healthy? Is it unhealthy?

DS: ell, if you look at it from the point of view of the academic institution and start to focus on the medical student, clearly the needs of the medical student are different from the needs, let us say, of some specialty physician. Then you begin to ask yourself how you present clinical medicine. How you educate someone in clinical medicine in an appropriate fashion. Now if everybody were a narrow specialist, everybody, it would be impossible to educate anyone. So you have to in certain sense, even if you donít do this consciously, intuitively you have to have some concept of a central core of medicine. And then you have to ask yourself who is to minister to this central core. Now some people think that there ought to be specialists in the central core of medicine. That is individuals who specialize in everything and nothing. And I donít agree with that. I think the model we have is healthy if it were, so to speak, insisted upon, encouraged, helped, and rewarded. And the model would be the one weíve discussed. That someone defines for himself or for herself a domain of expertise where they are the consultants, so to speak. They are the resource for the department and can also participate in the central core of medicine. The textbooks that are available are fabulous these days and they help everyone. All you have to do is spend a couple of nights and read them; think about them, and then you become pretty good. Most people donít agree with that, but Iím just giving you my own view.

I would hope that we donít get to a point where the finest intellectual resources of the medical school are systematically screened away from students because of the requirement to educate them with someone who is comfortable with medicine. I hope we donít get to that point.

LF: Letís talk a little about teaching medical students. What are the best formulas in this world of technology for not keeping this away from the medical students, but also allowing them to partake of it and learn about it?

DS: Well my own view is that the greatest contribution of the United States to medicine, and thatís perhaps too broad because the scientific advances are very impressive. But one of the greatest contributions is Flexner's insistence on the clinical clerkship. And I still believe that the clinical clerkship is the best model that has ever been devised for the education of medical students. And it doesnít necessarily involve computers, and it doesnít necessarily involve access to the National Laboratory, but it involves the model of someone intensely interested in medicine bringing the finest biomedical science to bear and encouraging students to read about and get excited about it and think about it. I would say that the preservation of this model requires certain structural things and this gets complicated. It requires a general medical ward, at least something resembling a general medical ward and that conflicts with other pressures. It requires someone who knows something about medicine. And that conflicts with things. So to just give the model doesnít solve the problem, but, in a nutshell, if you ask me what the real requirement for educating a medical student, I would say, it would be a vigorous clinical clerkship.

LF: What have you observed in your travels in Europe and Asia in terms of medical student education?

DS: Well, in many places, in Europe in particular, medical student education is very formalized in terms of lectures. When I first interacted principally in Germany, I have to say, there were huge lectures which constituted the bulk of the educational process. I think that is receding, and right now I was in Munich recently, and Schoendorf is there, he was educated in the United States, and there is every attempt to institute an American model, and I hope that becomes generalized. But I think in Europe until very recently, you can correct me, the applications to medical school were virtually limitless.

LF: Well Iím not sure that the British would be happy with you quoting this an American model. They didnít have a Flexner, but they certainly have always taught clinical medicine in exactly the same style.

DS: All right, I donít mind. I have always regarded this as the Flexner model because it was examined in such explicit detail, criticized, evaluated, insisted upon. But maybe in point of fact there existed such activities. Flexner really studied the United States and Canada. He had a model of the European university as something that the medical school should aspire to. That he did, but Iím not aware that he ever studied, say, England in detail. Although Oxford, Cambridge, the great German Universities at the end of the 19th century inspired him. He wasnít even talking about medicine. He was talking just about educational institution. But Dr. Fine you may be right. It may be a matter of fact that the British had tutorial systems of the kind that Iíve mentioned in force without discussing too much. Thatís possible.

RA: If you were the Dean of a medical school would you expand the clinical clerkships and decrease the number of lectures?

DS: I would allow that to the department. After all if you were the Dean of a medical school you are not intervening in the details, but I would certainly try to encourage the development of clinical clerkships very widely. And if you want my honest opinion, I would expand, rather than contract, the role of the department of medicine. At one time, in this medical school, the third year consisted of six to eight months of medical clerkship. But that is where they learned to take a history and do a physical examine and then learn something of pathophysiology and diseases. It didnít hurt surgery or anybody else. Who else would spend the time? Surgeons were in the operating room most of the day anyway. And still are. But that has shrunken. It's shrunken not for reasons of a great educational vision, but because people want access to students, to recruit them as house staff or fellows. And they feel that the third year is the best time and that's what happened.

LF: One canít go to a major meeting and hear a keynote address that doesnít talk about the dismaying, disappearance of clinical scientists. Somebody has to have the answer. What is the answer?

DS: Well, education is part of the answer. I think it is very important not to misunderstand what has happened in science. When you ask questions, you are in a reductive cascade, which requires that you master a complicated domain of science that resides at a very basic level. What you would like to do is take such people who are equipped in this manner and put them into a clinical context. You would like to ensure that there scientific base is secure and then make sure that they can cope with clinical questions and clinical problems. And certain people have been very successful at that and others less so. The CRC Ė Clinical Research Center is essentially to my mind a healthy devise, but it should be much more widespread than that. And we should have devices, and there are devices now ongoing, to try to ensure that scientifically sophisticated physicians are encouraged along clinical lines.

LF: Does a scientifically trained clinician have to be one who doubles in molecules and cells or are you prepared to acceptÖ

DS: No I donít think he has to double and he can work with other people. Certainly collaboration is the order of the day. But if he doesnít understand what goes on heís simply a technician. And in order to participate integrally it requires that the, letís say the scientifically trained clinical investigator, be a knowledgeable participant in the entire research process. Yes, I would say thatís almost mandatory.

LF: There is a burgeoning interest in epidemiology, biostatistics, infomatics, which is really taking itself on as almost a separate branch of science within a clinical context, and that is receiving increasing interest, and within the nephrology community is becoming rather important as one simply looks at the abstracts being submitted to international and national meetings.

DS: Well I think increasingly one is looking at domains which has a curious hybrid status. If the British epidemiologist, ?Petou, is a necessary requirement, heís not even required to see patients or to be a physician or anything. But he sets up the studies and monitors them and has a major input and many people are entering this domain and increasingly becoming remote from any clinical context, I donít think thatís bad. I think thatís good. Maybe that will make some of these epidemiologic studies worthwhile. You saw the recent article in Science which summarized the opinions of the best epidemiologists in the world by starting out to say why one week do we get one report of 50 million patients with this result and the next week the same number with another result. Why is that? So I think thatís a healthy development. The same thing is true of other modalities. Education, for example. Is education a medical modality? Should physicians have anything to do with educating people? Is that an intrusion on personal liberty? What status does that have? But yet that seems to be a form of certain kinds of medical therapy. Who should do that? What about the care of people in old age homes? What they need is, I would think, is care and kindness. And the physician can be a consultant for disease. Iím not sure the physician is the best person to do that, to do that as the principle focus. So I think these arrangements are very sensible because they deploy the physician in what the physician can do.

LF: Weíve covered a lot of ground, havenít we. Are there any issues, points, ideas that you think we should have touched on that we havenít? Anything that you feel passionately about at the moment?

DS: Feel passionately about? Well, if I were to take one feature I would say that a society should look very carefully at what it expects of the University, including the biomedical school, and come to some conclusion as to what itís role is. I have always thought that the role of the medical school, like the rest of the University, is to develop a program, the successful completion of which is acknowledged by a University degree. The MD degree. Thatís its principal role. And that requires a structure which should be supportive appropriately, which should acknowledge the kinds of people who are involved in doing that, which requires that one should look at other branches of the University and see how that started. Physics department, English department, whatever you want. And support it appropriately and insulated to a certain extent from the pressures that we discussed which deprive the University of the capacity to focus on its principle function.

Now I realize that that conflicts with certain economic imperatives and the like, but at least the model should be there so that one thinks about it and tries to develop institutional devices to help. After all, if itís true that the health care system consumes a trillion dollars a year, the fraction that is used for education and research is almost vanishingly small. If it were any business we are told about six percent is put aside for development. We should have a certain sensible amount put aside to insulate the University against the impact of some of these requirements. There are very few voices speaking for the integrity of the academic community and the University. People are embarrassed, especially in the United States, with the neglect of some 50 million people without health insurance, with inadequate health insurance elsewhere, with complaints of HMOs and the competitive environment. That seems to consume everybodyís attention and that should. Iím not against that. But lost in the shuffle is the notion of what the University does. We exercise an absolute monopoly over the entrance of physicians into the health care system. The only way you can get in is to get an MD. Iím talking about physicians. An MD degree, and the only people grant it is universities. It should be a careful thought of what we expect.

RA: Dr. Seldin, what fascinates you about nephrology?

DS: Well, many people become interested in an area of medicine because of itís, letís say, curative powers or its capacity to mitigate suffering, and I think these are all noble ideals. I believe that any physician who takes care of patients must have that in the forefront in his or her mind. But underlying that, there are certain specific features of nephrology which fascinate me. And that has to do with the role of the kidney in its homeostatic function in controlling the internal environment. How feedback systems operate to maintain constancy. How in the face of salt deprivation, salt depletion is prevented? How in the face of salt excess, salt overload is presented? How does the kidney deploy various signals and various intrinsic mechanisms to regulate these processes? And they are very pervasive. They go all the way from cardiac function to hypertension to electrolyte composition and the like. And I personally think that the explanatory and reductive principles that are developing in nephrology are extremely powerful. More so than in almost any other discipline that I can think of. So that one can say a great deal about acid-base balance by understanding the accumulating laws and one can trace this back to specific transport systems. And then the interaction of how one system influences the net effect becomes utterly fascinating. One isolates a transporter and sees its effect and its never reflected in the urine so that obviously other transport systems contribute. And then the aggregate of these functions is obviously controlled with immense precision so that the whole manner in which the kidney functions as a regulatory organ, responding to the internal environmental signals is fascinating. And that is why I think the role of volume is such a central question in nephrology. Nobodyís interested in it because itís very hard to define the signals. But what we have done now, what renal physiology has done, is define more and more mechanisms and transporters which respond to signals in various ways. But itís quite clear that the organism is so set up to protect certain vital functions of which one of the most critical is the circulation of the blood, and that there is a complex array of innumerable transporters which are designed to maintain and protect it. And itís the unraveling of this system that fascinates me most. And I must say in recent years the executives, the renal transporters which are involved, have been enormously elucidated. That progress has been immense. But what controls them, how they are controlled, and how they feed back their answers is much more elusive. And yet the whole system is absolutely fascinating and I think that is one of the great areas of renal function.

RA: Well this is very interesting and I think it would be nice to finish where we started by posing this question: If you were to meet a young, high school or college student, who was interested in a career as a poet or a philosopher, would you advise him to consider a career in medicine?

DS: I would. I would. I gave you the perspective I had when I was in college, but I think medicine has turned out to be an incredible discipline. First of all it allows you to move in so many different directions as your interests evolve. You can become a clinician; you can become an investigator; you can become an educator; you can go into public health service, all with the MD degree in the background. But it also allows the intellectual excitement of looking at an area of human experience, which can be explained and predicted by powerful laws. And this to me is one of the wonders of modern medicine.

LF: Well Dr. Seldin, Iím almost sure that your great wisdom and vision will be appreciated by future generations through the Video Legacy Project of the ISN. I canít thank you enough for being this forthcoming and as entertaining as you have been. It has been a wonderful pleasure and a privilege to have done this interview. Thank you very, very much.

DS: It is a pleasure to talk to you both.

LF: Thank you.

Bibliography of Dr. Donald W. Seldin

Seldin DW, Kaplan HS, Bunting H. Rheumatic pneumonia. Ann Int Med 26: 496-520, Apr 47.

Seldin DW, Tarail R. Effect of hypertonic solutions on metabolism and excretion of electrolytes. Am J Physiol 159: 160-174, Oct 49.

Sim EAH, Seldin DW. Reabsorption of creatine and gluanidoacetic acid by renal tubules. Am J Physiol 157: 14-20, Apr 49.

Seldin DW, Tarail R. Metabolism of glucose and electrolytes in diabetic acidosis. J Clin Invest 29: 552-565, May 50.

Trail R, Seldin DW, Goodyer AVN. Effects of injection of hypertonic glucose on metabolism of water and electrolytes in patients with edema. J Clin Invest 30: 1111-1119, Oct 51.

Welt LG, Seldin DW. Pathologic physiology and treatment of edema. Veterans Admin Tech Bull TB 10-69 pp.1-18, 12 Jan 51.

Seldin DW. Glucose in development and treatment of diabetic acidosis. Texas J Med 49: 738-743, Oct 53.

Walser M, Reod AF, Seldin DW. Method of counting radiosulfur in liquid samples, and its application to determination of S35 excretion following injection of S3504. Arch Biochem 45: 91-96, Jul 53.

Goodyer AVN, Seldin DW. Effects of quiet standing on solute diuresis. J Clin Invest 32: 242-250, Mar 53.

Walser M, Seldin DW, Grollman A. Evaluation of radiosulfate for determination of volume of extracellular fluid in man and dogs. J Clin Invest 32: 299-311, Apr 53.

Burnett CH, Seldin DW, Walser M. Observations on electrolyte and water metabolism in Addisonís disease during oral salt loading. Tr A Am Physicians 66: 65-71, 1953.

Walser M, Seldin DW, Grollman A. Radiosulfate space of muscle. Am J Physiol 176: 322-324, Feb 54.

Seldin DW. Electrolyte and water balance: management of congestive heart failure; management designed to avoid serious disturbances of electrolyte and water balance. AMA Arch Int Med 95: 395-299, Mar 55.

Seldin DW. Symposium on parenteral fluids, nutrition, and electrolytes; development and correction of electrolyte disturbances associated with salt retention. Minnesota Med (supp.) 38: 21-25, Mar 55.

Rector FR Jr, Seldin DW, Copenhaver JH. Mechanism of ammonia excretion during ammonium chloride acidosis. J Clin Invest 34: 20-26, Jan 55.

Walser M, Seldin DW, Burnett CH. Blood volume and extracellular fluid volume during administration of ACTH and cortisone. Am J Med 18: 454-461, Mar 55.

Seldin DW, Welt LG, Cort JH. The role of sodium salts and adrenal steroids in the production of hypokalemic alkalosis. Yale J Biol 29(3): 229-47, Dec 56.

Seldin DW, Rector FC Jr, Teng HC. Effects of prolonged administration of diamox on excretion of acid and carbonic anhydrase and glutaminase activities in the kidney. Am J Physiol 189(3): 551-6, Jun 57.

Seldin DW, Teng HC, Rector FC Jr. Ammonia excretion and renal glutaminase activity during administration of strong acid and buffer acid. Proc Soc Exp Biol., NY 94(2): 366-8, Feb 57.

Wilson JD, Seldin DW. Effect of adrenalectomy on production and excretion of ammonia by the kidneys. Am J Physiol 188(3): 524-8, Mar 57.

MacDonald JR, Perry GE, Madison LL, Seldin DW. An electrical analogue for analysis of tracer distribution kinetics in biological systems. Radiation Res 6(5): 585-601, May 57.

Madison LL, Seldin DW. Ammonia excretion and renal enzymatic adaptation in human subjects, as disclosed by administration of precursor amino acids. J Clin Invest 37(11): 1615-27, Nov 58.

Seldin DW. The clinical teacher: scholarship as the heart of the educational process. Med Educ 34(10) pt2: 81-5, Oct 59.

Seldin DW, Portwood RM, Rector FC Jr, Cade R. Characteristics of renal bicarbonate reabsorption in man. J Clin Invest 38: 1663-71, Oct 59.

Rector FC Jr, Portwood RM, Seldin DW. Examination of the mixing hypothesis as an explanation for elevated urinary carbon dioxide tensions. Amer J Physiol 197: 861-4, Oct 59.

Carter NW, Seldin DW, Teng HC. Effect of diamox on plasma and urine acid-base composition during chronic respiratory acidosis. Amer J Physiol 196(4): 919-23, Apr 59.

Portwood RM, Seldin DW, Rector FC Jr, Cade R. The relation of urinary CO2 tension to bicarbonate excretion. J Clin Invest 38(5): 770-6, May 59.

Carter NW, Seldin DW, Teng HC. Tissue and renal response to chronic respiratory acidosis. J Clin Invest 38(6): 949-60 Jun 59.

Rector FC Jr, Seldin DW, Roberts AD Jr, Smith JS. The role of plasma CO2 tension and carbonic anhydrase activity in the renal reabsorption of bicarbonate. J Clin Invest 39: 1706-21 Nov 60.

Carter NW, Rector FC Jr, Seldin DW. Hyponatremia in cerebral disease resulting from the inappropriate secretion of antidiuretic hormone. New Engl J Med 264: 67-72, 12 Jan 61.

Goldsmith C, Beasley HK, Whalley PJ, Rector FC Jr, Seldin DW. The effect of salt deprivation on the urinary concentrating mechanism in the dog. J Clin Invest 40: 2042-52, Nov 61.

Seldin DW, Ziff M, Degraff AC Jr, Fallis BD, Burns RR. Raynaudís phenomenon associated with pulmonary hypertension. Texas J Med 58: 654-61, Aug 62.

Seldin DW, Hodges SE, Ziff M, Smiley JD, Carter NW, Barnett JA, Rector FC, Dutcher TF. Cyroglobulinemia associated with malignant hypertension. Texas J Med 58: 755-62, Sep 62.

Clapp JR, Rector FC Jr, Seldin DW. Effect of unreabsorbed anions on proximal and distal transtubular potentials in rats. Amer J Physiol 202: 781-6, Apr 62.

Rector FC Jr, Buttram H, Seldin DW. An analysis of the mechanism of the inhabitory influence of potassium ion on renal hydrogen ion secretion. J Clin Invest 41: 611-7, Mar 62.

Rector FC Jr, Seldin DW. Influence of unreabsorbed anions on renal threshold and Tm for bicarbonate. Amer J Physiol 202: 313-8, Feb 62.

Goldsmith C, Rector FC Jr, Seldin DW. Evidence for a direct effect of serum sodium concentration on sodium reabsorption. J Clin Invest 4: 850-9, Apr 62.

Bloomer HA, Rector FC Jr, Seldin DW. The mechanism of potassium reabsorption in the proximal tubule of the rat. J Clin Invest 42: 277-85, Feb 63.

Rector FC Jr, Bloomer HA, Seldin DW. Proximal tubual reabsorption of potassium during mannitol diuresis in rats. J Lab Clin Med 63: 100-5, Jan 64.

Rector FC Jr, Bloomer HA, Seldin DW. Effect of potassium deficiency on the reabsorption of bicarbonate in the proximal tubule of the rat kidney. J Clin Invest 43: 1976-82, Oct 64.

Rector FR Jr, Carter NW, Seldin DW. The mechanism of bicarbonate reabsorption in the proximal and distal tubules of the kidney. J Clin Invest 44: 278-90, Feb 65.

Suki W, Rector FC Jr, Seldin DW. The site of action of furosemide and other sulfonamide diuretics in the dog. J Clin Invest 44: 1458-69, Sep 65.

Suki W. Eknoyan G. Rector FC Jr. Seldin DW.Patterns of nephron perfusion in acute and chronic hydronephrosis.Journal of Clinical Investigation. 45(1):122-31, 1966 Jan.

Brunner FP. Rector FC Jr. Seldin DW.The mechanism of the urinary concentrating defect in potassium deficient rats. Pflugers Archiv fur die Gesamte Physiologie des Menschen und der Tiere. 290(3):202-10, 1966.

Rector FC Jr. Brunner FP. Seldin DW. Mechanism of glomerulotubular balance. I. Effect of aortic constriction and elevated ureteropelvic pressure on glomerular filtration rate, fractional reabsorption, transit time, and tubular size in the proximal tubule of the rat. Journal of Clinical Investigation. 45(4):590-602, 1966 Apr.

Brunner FP. Rector FC Jr. Seldin DW. Mechanism of glomerulotubular balance. II. Regulation of proximal tubular reabsorption by tubular volume, as studied by stopped-flow microperfusion. Journal of Clinical Investigation. 45(4):603-11, 1966 Apr.

Lehmann JD. Schenker S. Combes B. Sanford JP. Seldin DW. Fallis BD. Clinicopathologic conference. Texas Medicine. 62(6):76-83, 1966 Jun.

Seldin DW. Some reflections on the role of basic research and service in clinical departments. Journal of Clinical Investigation. 45(6):976-9, 1966 Jun.

Soteres P. Christensen E. Foster DW. Johnson RL. Pierce AK. Seldin DW. Nicholson D. Reynolds RC. Clinicopathologic conference. Texas Medicine. 62(9):83-91, 1966 Sep.

Peacock G. Winga E. Davis JT. Kaplan NM. Madison L. Foster DW. Seldin D. Ketchersid JB. Clinicopathologic conference. Texas Medicine. 62(11):93-9, 1966 Nov.

Seldin DW. Eknoyan G. Suki WN. Rector FC Jr. Localization of diuretic action from the pattern of water and electrolyte excretion. Annals of the New York Academy of Sciences. 139(2):328-43, 1966 Nov 22.

Rector FC Jr. Brunner FP. Sellman JC. Seldin DW. Pitfalls in the use of micropuncture for the localization of diuretic action. Annals of the New York Academy of Sciences. 139(2):400-7, 1966 Nov 22.

Rector FC Jr. Sellman JC. Martinez-Maldonado M. Seldin DW. The mechanism of suppression of proximal tubular reabsorption by saline infusions. Journal of Clinical Investigation. 46(1):47-56, 1967 Jan.

Carter NW. Rector FC Jr. Campion DS. Seldin DW. Measurement of intracellular pH of skeletal muscle with pH-sensitive glass microelectrodes. Journal of Clinical Investigation. 46(6):920-33, 1967 Jun.

Seldin DW. Coleman AJ. Carter NW. Rector FC Jr. The effect of Na2SO4 on urinary acidification in chronic renal disease. Journal of Laboratory & Clinical Medicine. 69(6):893-903, 1967 Jun.

Eknoyan G. Suki WN. Rector FC Jr. Seldin DW. Functional characteristics of the diluting segment of the dog nephron and the effect of extracellular volume expansion on its reabsorptive capacity.Journal of Clinical Investigation. 46(7):1178-88, 1967 Jul.

Carter NW. Rector FC Jr. Campion DS. Seldin DW. Measurement of intracellular pH with glass microelectrodes. Federation Proceedings. 26(5):1322-6, 1967 Sep.

Goorno WE. Rector FC Jr. Seldin DW. Relation of renal gluconeogenesis to ammonia production in the dog and rat. American Journal of Physiology. 213(4):969-74, 1967 Oct.

Falls WF Jr. Carter NW. Rector FC Jr. Seldin DW. Familial vitamin D-resistant rickets. Study of six cases with evaluation of the pathogenetic role of secondary hyperparathyroidism. Annals of Internal Medicine. 68(3):553-60, 1968 Mar.

Kunau RT Jr. Frick A. Rector FC Jr. Seldin DW. Micropuncture study of the proximal tubular factors responsible for the maintenance of alkalosis during potassium deficiency in the rat. Clinical Science. 34(2):223-31, 1968 Apr.

Rector FC Jr. Martinez-Maldonado M. Kurtzman NA. Sellman JC. Oerther F. Seldin DW. Demonstration of a hormonal inhibitor of proximal tubular reabsorption during expansion of extracellular volume with isotonic saline. Journal of Clinical Investigation. 47(4):761-73, 1968 Apr.

Levin ML. Rector FC Jr. Seldin DW. Effects of potassium and ouabain on sodium transport in human red cells. American Journal of Physiology. 214(6):1328-32, 1968 Jun.

Suki WN. Schwettmann RS. Rector FC Jr. Seldin DW. Effect of chronic mineralocorticoid administration on calcium excretion in the rat. American Journal of Physiology. 215(1):71-4, 1968 Jul.

Rodicio J. Herrera-Acosta J. Sellman JC. Rector FC Jr. Seldin DW. Studies on glomerulotubular balance during aortic constriction, ureteral obstruction and venous occlusion in hydropenic and saline-loaded rats. Nephron. 6(3):437-56, 1969.

Suki WN. Eknoyan G. Rector FC Jr. Seldin DW. The renal diluting and concentrating mechanism in hypercalcemia. Nephron. 6(1):50-61, 1969.

Seldin DW. Special issue dedicated to Dr. Robert F. Pitts. Nephron. 6(3):161-3, 1969.

White MG. Carter NW. Rector FC. Seldin DW. Drewry SJ. Sanford JP. Luby JP. Unger RH. Kaplan NM. Shapiro W. Eisenberg S. Pathophysiology of epidemic St. Louis encephalitis. I. Inappropriate secretion of antidiuretic hormone. II. Pituitary-adrenal function. 3. Cerebral blood flow and metabolism. Annals of Internal Medicine. 71(4):691-702, 1969 Oct.

Rosin JM. Katz MA. Rector FC Jr. Seldin DW. Acetazolamide in studying sodium reabsorption in diluting segment. American Journal of Physiology. 219(6):1731-8, 1970 Dec.

Cunningham JN Jr. Carter NW. Rector FC Jr. Seldin DW.Resting transmembrane potential difference of skeletal muscle in normal subjects and severely ill patients. Journal of Clinical Investigation. 50(1):49-59, 1971 Jan.

Bailie MD. Rector FC Jr. Seldin DW. Angiotensin II in arterial and renal venous plasma and renal lymph in the dog. Journal of Clinical Investigation. 50(1):119-26, 1971 Jan.

Mandin H. Israelit AH. Rector FC Jr. Seldin DW. Effect of saline infusions on intrarenal distribution of glomerular filtrate and proximal reabsorption in the dog. Journal of Clinical Investigation. 50(3):514-22, 1971 Mar.

Blantz RC. Katz MA. Rector FC Jr. Seldin DW. Measurement of intrarenal blood flow. II. Effect of saline diuresis in the dog. American Journal of Physiology. 220(6):1914-20, 1971 Jun.

Katz MA. Blantz RC. Rector FC Jr. Seldin DW. Measurement of intrarenal blood flow. I. Analysis of microsphere method. American Journal of Physiology. 220(6):1903-13, 1971 Jun.

Andreucci VE. Herrera-Acosta J. Rector FC Jr. Seldin DW. Effective glomerular filtration pressure and single nephron filtration rate during hydropenia, elevated ureteral pressure, and acute volume expansion with isotonic saline. Journal of Clinical Investigation. 50(10):2230-4, 1971 Oct.

Wallin JD. Blantz RC. Katz MA. Andreucci VE. Rector FC Jr. Seldin DW. Effect of saline diuresis on intrarenal blood flow in the rat. American Journal of Physiology. 221(5):1297-304, 1971 Nov.

Andreucci VE. Herrera-Acosta J. Rector FC Jr. Seldin DW. Measurement of single-nephron glomerular filtration rate by micropuncture: analysis of error. American Journal of Physiology. 221(6):1551-9, 1971 Dec.

Wallin JD. Rector FC Jr. Seldin DW. Measurement of intrarenal plasma flow with antiglomerular basement-membrane antibody. American Journal of Physiology. 21(6):1621-8, 1971 Dec.

Barton LJ. Lackner LH. Rector FC Jr. Seldin DW. The effect of volume expansion on sodium reabsorption in the diluting segment of the dog kidney. Kidney International. 1(1):19-26, 1972.

Wallin JD. Israelit AH. Rector FC Jr. Seldin DW. Intrarenal plasma flow distribution during micropuncture in the dog. American Journal of Physiology. 222(3):649-52, 1972 Mar.

Herrera-Acosta J. Andreucci VE. Rector FC Jr. Seldin DW. Effect of expansion of extracellular volume on single-nephron filtration rates in the rat. American Journal of Physiology. 222(4):938-44, 1972 Apr.

Seldin DW. Rector FC Jr. Symposium on acid-base homeostasis. The generation and maintenance of metabolic alkalosis. [Review] [66 refs] Kidney International. 1(5):306-21, 1972 May.

Andreucci VE. Rector FC Jr. Seldin DW. [Glomerular pressure, effective pressure due to filtration and glomerular filtration per nephron in the rat]. [Italian] Minerva Nefrologica. 19(3):187-93, 1972 May-Jun.

Wallin JD. Rector FC Jr. Seldin DW. Effect of volume expansion on intrarenal distribution of plasma flow in the dog. American Journal of Physiology. 223(1):125-9, 1972 Jul.

Blantz RC. Israelit AH. Rector FC Jr. Seldin DW. Green JM. Relation of distal tubular NaCl delivery and glomerular hydrostatic pressure. Kidney International. 2(1):22-32, 1972 Jul.

Rector FC Jr. Andreucci VE. Herrera-Acosta J. Seldin DW. Potential sources of error in measuring single-nephron glomerular filtration rate. Yale Journal of Biology & Medicine. 45(3):193-9, 1972 Jun-Aug.

Levin ML. Rector FC Jr. Seldin DW. The effects of chronic hypokalaemia, hyponatraemia, and acid-base alterations on erythrocyte sodium transport. Clinical Science. 43(2):251-63, 1972 Aug.

Blantz RC. Wallin JD. Rector FC Jr. Seldin DW. Effect of variation in dietary NaCl intake on the intrarenal distribution of plasma flow in the rat. Journal of Clinical Investigation. 51(11):2790-5, 1972 Nov.

Wallin JD. Brennan JP. Long DL. Aronoff SL. Rector FC Jr. Seldin DW. Effect of increased distal bicarbonate delivery on free water reabsorption in the dog. American Journal of Physiology. 224(1):209-18, 1973 Jan.

Barratt LJ. Wallin JD. Rector FC Jr. Seldin DW. Influence of volume expansion on single-nephron filtration rate and plasma flow in the rat. American Journal of Physiology. 224(3):643-50, 1973 Mar.

Wallin JD. Barratt LJ. Rector FC Jr. Seldin DW. The influence of flow rate and chloride delivery on TcH2O formation in the rat. Kidney International. 3(5):282-90, 1973 May.

Blantz RC. Rector FC Jr. Seldin DW. Effect of hyperoncotic albumin expansion upon glomerular ultrafiltration in the rat. Kidney International. 6(4):209-21, 1974 Oct.

Kawamura S. Imai M. Seldin DW. Kukko JP. Characteristics of salt and water transport in superficial and juxtamedullary straight segments of proximal tubules. Journal of Clinical Investigation. 55(6):1269-77, 1975 Jun.

Young Q. Schwartz H. Halberstam M. Sidel V. McLachlan G. Seldin D. Markle Scholars Symposium. Panel Discussion 1. Archives of Internal Medicine. 135(7):933-8, 1975 Jul.

Seldin DW. Rosin JM. Rector FC Jr. Evidence against bicarbonate reabsorption in the ascending limb, particularly as disclosed by free-water clearance studies. Yale Journal of Biology & Medicine. 48(4):337-47, 1975 Sep.

Barratt LJ. Rector FC Jr. Kokko JP. Tisher CC. Seldin DW. Transepithelial potential difference profile of the distal tubule of the rat kidney. Kidney International. 8(6):368-75, 1975 Dec.

Seldin DW. Specialization as scientific advancement and overspecialization as social distortion. Clinical Research. 24(4):245-8, 1976 Oct.

Jacobson HR. Seldin DW. Proximal tubular reabsorption and its regulation. [Review] [141 refs] Annual Review of Pharmacology & Toxicology. 17:623-46, 1977.

Imai M. Seldin DW. Kokko JP. Effect of perfusion rate on the fluxes of water, sodium, chloride and urea across the proximal convoluted tubule. Kidney International. 11(1):18-27, 1977 Jan.

Seldin DW. The syndromes of non-edematous mineralocorticoid excess. Nippon Jinzo Gakkai Shi. Japanese Journal of Nephrology. 19(3):189-95, 1977 Mar.

DuBose TD Jr. Seldin DW. Kokko JP. Segmental chloride reabsorption in the rat nephron as a function of load. American Journal of Physiology. 234(2):F97-105, 1978 Feb.

Emmett M. Seldin DW. Disturbances in acid-base balance during hypophosphatemia and phosphate depletion. [Review] [19 refs] Advances in Experimental Medicine & Biology. 103:313-25, 1978.

DuBose TD Jr. Pucacco LR. Seldin DW. Carter NW. Direct determination of PCO2 in the rat renal cortex. Journal of Clinical Investigation. 62(2):338-48, 1978 Aug.

DuBose TD Jr. Pucacco LR. Seldin DW. Carter NW. Kokko JP. Microelectrode determination of pH and PCO2 in rat proximal tubule after benzolamide: evidence for hydrogen ion secretion. Kidney International. 15(6):624-9, 1979 Jun.

Schwartz LB. Lewis RA. Seldin D. Austen KF. Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. Journal of Immunology. 126(4):1290-4, 1981 Apr.

Seldin DW. Presidential address. Transactions of the Association of American Physicians. 94:lxxv-lxxxvi, 1981.

Wingo CS. Seldin DW. Kokko JP. Jacobson HR. Dietary modulation of active potassium secretion in the cortical collecting tubule of adrenalectomized rabbits. Journal of Clinical Investigation. 70(3):579-86, 1982 Sep.

Esser PD. Seldin DW. Nichols AB. Alderson PO. Spatial calibration of digital scintigraphic images: work in progress. Radiology. 144(4):901-4, 1982 Sep.

Jacobson HR. Kokko JP. Seldin DW. Holmberg C. Lack of solvent drag of NaCl and NaHCO3 in rabbit proximal tubules. American Journal of Physiology. 243(4):F342-8, 1982 Oct.

Geringer AM. Berdon WE. Seldin DW. Hensle TW. The diagnostic approach to ectopic ureterocele and the renal duplication complex. Journal of Urology. 129(3):539-42, 1983 Mar.

Stone DK. Seldin DW. Kokko JP. Jacobson HR. Anion dependence of rabbit medullary collecting duct acidification. Journal of Clinical Investigation. 71(5):1505-8, 1983 May.

Stone DK. Seldin DW. Kokko JP. Jacobson HR. Mineralocorticoid modulation of rabbit medullary collecting duct acidification. A sodium-independent effect. Journal of Clinical Investigation. 72(1):77-83, 1983 Jul.

Jacobson HR. Seldin DW. On the generation, maintenance, and correction of metabolic alkalosis. [Review] [57 refs] American Journal of Physiology. 245(4):F425-32, 1983 Oct.

Alderson PO. Dzebolo NN. Biello DR. Seldin DW. Martin EC. Siegel BA. Serial lung scintigraphy: utility in diagnosis of pulmonary embolism. Radiology. 149(3):797-802, 1983 Dec.

Seldin DW. Esser PD. Nichols AB. Ratner SJ. Alderson PO. Left ventricular volume determined from scintigraphy and digital angiography by a semi-automated geometric method. Radiology. 149(3):809-13, 1983 Dec.

Razin E. Ihle JN. Seldin D. Mencia-Huerta JM. Katz HR. LeBlanc PA. Hein A. Caulfield JP. Austen KF. Stevens RL. Interleukin 3: A differentiation and growth factor for the mouse mast cell that contains chondroitin sulfate E proteoglycan. Journal of Immunology. 132(3):1479-86, 1984 Mar.

Abramson SJ. Barash FS. Seldin DW. Berdon WE. Transient focal liver scan defects in children receiving chemotherapy (pseudometastases). Work in progress. Radiology. 150(3):701-2, 1984 Mar.

Rosen JM. Biello DR. Siegel BA. Seldin DW. Alderson PO. Kr-81m ventilation imaging: clinical utility in suspected pulmonary embolism. Radiology. 154(3):787-90, 1985 Mar.

Schwarzberg RJ. Seldin DW. Alderson PO. Johnson LL. Peak regional acceleration: a method to identify subtle regional ventricular dysfunction from gated blood pool scans at rest in patients with coronary artery disease. Journal of the American College of Cardiology. 6(3):589-96, 1985 Sep.

Seldin DW. Heiken JP. Feldman F. Alderson PO. Effect of soft-tissue pathology on detection of pedal osteomyelitis in diabetics. Journal of Nuclear Medicine. 26(9):988-93, 1985 Sep.

Johnson LL. Seldin DW. Yeh HL. Spotnitz HM. Reiffel JA. Phase analysis of gated blood pool scintigraphic images to localize bypass tracts in Wolff-Parkinson-White syndrome. Journal of the American College of Cardiology. 8(1):67-75, 1986 Jul.

Rosen JM. Binkert BL. Seldin DW. Fawwaz RA. Martin EC. Scintigraphic criteria for the diagnosis of renal arteriovenous fistulas. Clinical Nuclear Medicine. 11(12):847-50, 1986 Dec.

Addonizio LJ. Michler RE. Marboe C. Esser PE. Johnson LL. Seldin DW. Gersony WM. Alderson PO. Rose EA. Cannon PJ. Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab. Journal of the American College of Cardiology. 9(3):555-64, 1987 Mar.

Johnson LL. Lerrick KS. Coromilas J. Seldin DW. Esser PD. Zimmerman JM. Keller AM. Alderson PO. Bigger JT Jr. Cannon PJ. Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab. Circulation. 76(1):181-90, 1987 Jul.

Jaffe RM. Alderson PO. Seldin DW. Esser PD. Bartholomew RM. Hyman GA. Evaluation of metastatic melanoma with planar and SPECT scintigraphy using ZME 018 and 96.5 radiolabeled monoclonal antibodies. Cancer Detection & Prevention. 12(1-6):303-12, 1988.

Seldin DW. Esser PD. Alderson PO. Comparison of bone density measurements from different skeletal sites. Journal of Nuclear Medicine. 29(2):168-73, 1988 Feb.

Seldin DW. Simchon S. Jan KM. Chien S. Alderson PO. Dependence of technetium-99m red blood cell labeling efficiency on red cell surface charge. Journal of Nuclear Medicine. 29(10):1710-3, 1988 Oct.

Alpern RJ. Star R. Seldin DW. Hepatic renal interrelations in acid-base regulation [letter]. American Journal of Physiology. 255(4 Pt 2):F807-9, 1988 Oct.

Johnson LL. Seldin DW. Becker LC. LaFrance ND. Liberman HA. James C. Mattis JA. Dean RT. Brown J. Reiter A. et al. Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial. Journal of the American College of Cardiology. 13(1):27-35, 1989 Jan.

Seldin DW. Johnson LL. Blood DK. Muschel MJ. Smith KF. Wall RM. Cannon PJ. Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy. Journal of Nuclear Medicine. 30(3):312-9, 1989 Mar.

Antunes ML. Seldin DW. Wall RM. Johnson LL. Measurement of acute Q-wave myocardial infarct size with single photon emission computed tomography imaging of indium-111 antimyosin. American Journal of Cardiology. 63(12):777-83, 1989 Apr 1.

Silverberg SJ. Shane E. de la Cruz L. Dempster DW. Feldman F. Seldin D. Jacobs TP. Siris ES. Cafferty M. Parisien MV. et al. Skeletal disease in primary hyperparathyroidism. Journal of Bone & Mineral Research. 4(3):283-91, 1989 Jun.

Turken S. Siris E. Seldin D. Flaster E. Hyman G. Lindsay R. Effects of tamoxifen on spinal bone density in women with breast cancer. Journal of the National Cancer Institute. 81(14):1086-8, 1989 Jul 19.

Johnson LL. Seldin DW. The role of antimyosin antibodies in acute myocardial infarction. [Review] [33 refs] Seminars in Nuclear Medicine. 19(3):238-46, 1989 Jul.

Johnson LL. Seldin DW. Keller AM. Wall RM. Bhatia K. Bingham CO 3rd. Tresgallo ME. Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk. Circulation. 81(1):37-45, 1990 Jan.

Heller LI. Tresgallo M. Sciacca RR. Blood DK. Seldin DW. Johnson LL. Prognostic significance of silent myocardial ischemia on a thallium stress test. American Journal of Cardiology. 65(11):718-21, 1990 Mar 15.

Silverberg SJ. Shane E. Jacobs TP. Siris ES. Gartenberg F. Seldin D. Clemens TL. Bilezikian JP. Nephrolithiasis and bone involvement in primary hyperparathyroidism. American Journal of Medicine. 89(3):327-34, 1990 Sep.

Johnson LL. Seldin DW. Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent. [Review] [13 refs] American Journal of Cardiology. 66(13):63E-67E, 1990 Oct 16.

Moe OW. Tejedor A. Levi M. Seldin DW. Preisig PA. Alpern RJ. Dietary NaCl modulates Na(+)-H+ antiporter activity in renal cortical apical membrane vesicles. American Journal of Physiology. 260(1 Pt 2):F130-7, 1991 Jan.

Yemul S. Leon JA. Seldin DW. Link MJ. Kramer P. Mesa-Tejada R. Estabrook A. Tumor localization in nude mice bearing human breast carcinoma xenografts using 111In-DTPA conjugates of monoclonal antibodies.International Journal of Radiation Applications & Instrumentation - Part B, Nuclear Medicine & Biology. 18(3):295-304, 1991.

Seldin DW. Preisig PA. Alpern RJ. Regulation of proximal reabsorption by effective arterial blood volume. [Review] [71 refs] Seminars in Nephrology. 11(2):212-9, 1991 Mar.

Seldin DW. Nuclear cardiology: myocardial perfusion and function. [Review] [41 refs] Current Opinion in Radiology. 3(4):561-8, 1991 Aug.

Antunes ML. Tresgallo ME. Seldin DW. Bhatia K. Johnson LL. Effect of infarct size measured from antimyosin single-photon emission computed tomographic scans on left ventricular remodeling. Journal of the American College of Cardiology. 18(5):1263-70, 1991 Nov 1.

Johnson LL. Rodney RA. Vaccarino RA. Egbe P. Wasserman L. Esser PD. Posniakoff TA. Seldin DW. Left ventricular perfusion and performance from a single radiopharmaceutical and one camera. Journal of Nuclear Medicine. 33(7):1411-6, 1992 Jul.

Antunes ML. Johnson LL. Seldin DW. Bhatia K. Tresgallo ME. Greenspan RL. Vaccarino RA. Rodney RA. Diagnosis of right ventricular acute myocardial infarction by dual isotope thallium-201 and indium-111 antimyosin SPECT imaging. American Journal of Cardiology. 70(4):426-31, 1992 Aug 15.

Vaccarino RA. Sanchez JE. Johnson LL. Wang TS. Seldin DW. Marboe C. Egbe P. Bhatia K. Rose EA. Khaw BA. Imaging of cardiac transplantation rejection in primates using two new antimyosin agents. Journal of Nuclear Medicine. 33(11):1994-9, 1992 Nov.

Seldin DW. Presentation of the 1993 A.N. Richards Award to Gerhard Giebisch by Donald W. Seldin. Kidney International - Supplement. 44:S106-11, 1994 Jan.

Klahr S. Schrier RW. Seldin DW. Proceedings from the symposium in honor of Neal S. Bricker. Denver, CO, May 7 and 8, 1993. Introduction. American Journal of Kidney Diseases. 23(2):167-70, 1994 Feb.

Slonim SM. Molgaard CP. Khawaja IT. Seldin DW. Unilateral absence of right-lung perfusion with normal ventilation on radionuclide lung scan as a sign of aortic dissection. [Review] [9 refs] Journal of Nuclear Medicine. 35(6):1044-7, 1994 Jun.

Kahn D. Williams RD. Seldin DW. Libertino JA. Hirschhorn M. Dreicer R. Weiner GJ. Bushnell D. Gulfo J. Radioimmunoscintigraphy with 111indium labeled CYT-356 for the detection of occult prostate cancer recurrence. Journal of Urology. 152(5 Pt 1):1490-5, 1994 Nov.

Seldin DW. Andreoli TE. The International Society of Nephrology years: a perspective. Kidney International - Supplement. 57:S105-6, 1996 Dec.