ISN VIDEO LEGACY PROJECT

DR. PAUL TESCHAN
INTERVIEWED BY PROF. RAYMOND HAWKIN


RH:

Paul first let me tell you how delighted am I to be participating in this project that the ISN has organized, called the ISN Video Legacy Project. Itís really a well-deserved recognition of the things youíve done in nephrology and in all the things you have contributed to nephrology and to your peers and to the students who have followed after you. Itís really a great pleasure for me to be doing this. And I wanted, perhaps, to ask you to start by telling the audience the highlights of your professional career, sort of the stages that you went through. In a sense, frame your professional careers for me, and then weíll come back and ask about each one of those specific areas in more detail.

PT:

Well I appreciate you spending your time on this and the answer of the question, I see myself in three careers. The first was twenty-one years in the regular army medical core, medical department, mainly in research and development. Secondly, twenty-four years as a professor as medicine in Vanderbilt in nephrology. And more recently the last seven years so far as assistant to the Bishop of Tennessee, the ??? diocese of Tennessee. That really involves leading congregations and congregational leadership through long range planning or comprehensive stewardship or evangelism in order to make new and good things happen in the church. The other piece of the last seven years has been to continue giving grand rounds at Vanderbilt. Most recently in a new project that has to do with evidence based disease management what we call in this version of it, health assurance coaching using the coach-player model. I hope we can get into that because that I think that is one of the most exciting things thatís going on in healthcare in the world today and its fun to be part of that

RH:

Before we get into that, perhaps we canÖI wanted to ask you to start even with your high school career and your university career and how you got into the army. I think you had some notable achievements when you were in high school with Westinghouse.

PT:

Yes I graduated as a valedictorian of my high school of Shorewood, Wisconsin. Born and raised in Milwaukee really, Shorewood being a suburb. Then in the summer after my senior year, I had won a trip to Washington in the Westinghouse Science Talent Search and found myself rather astonishingly as having won the Westinghouse Grand Science Scholarship. And that gave me essentially four years of college education and I went on to Carlton College. Then of course we were in the Second World War. I was deferred in the doctor draft and went to medical school and at that point really finished medicine, as the form of medical training. But I felt by then, it was about 1948, that we would be in war with Russia and I felt that having been deferred during the entire Second World War, because of our medical studies, that I would be obviously drafted. So I volunteered for the army medical intern and resident training programs. Then after about two years of that I thought Iíd better get into uniform and my first assignment was then at the Army Medical Service Graduate School, later became the Walter Reed Army Institute of Research. Well about that time an order came down that we were going to establish a dialysis unit and being the new kid on the block, I was the newest arrival in the unit. So I was placed on temporary duty to go to the Peter Van Brigham Hospital on John Merrillís service and that of course was the time we met John Merrill for the first time, and all those colleagues, to learn about fluids and electrolytes and renal failure and dialysis using the rotating drum dialyser. Willhelm Kolff invented this machine back in Holland in 1943, Ď4, and Ď5 and put the design in the hands of George Thorn. It was an exciting to be at the Brigham because you see George Thorn was a professor of medicine, was working on adrenal function and hypertension. Francis Debour was the Bosley professor of surgery and was actively engaged in his metabolic studies in response to surgery. And at the same time, John Merrill had with him William P Murphy Jr. and Carl Walter in surgery who were biomedical engineers before there was a field like that. And of course the instrumentation genius Edward Olson, up Echelon, Massachusetts, was the person who fabricated, in stainless steel and plastic, the original Kolff rotating drum design, and that was the instrument that I trained on. Then we ultimately got one into the Walter Reed General Hospital, the Brooke General Hospital at Fort Sam Houston in San Antonio and of course that was the unit we used in Korea.

RH:

So your interest in nephrology really came by orders of Uncle Sam in a sense.

PT:

Yes, it was nephrology by appointment. I was the new kid on the block and because I got this TDY that really was the start and continuation of my whole career.

RH:

TDY?

PT:

Temporary duty. Military Jargon.

RH:

And had you had an interest in nephrology before then or was it really something that came out of nowhere. Had you heard anything about dialysis?

PT:

No none of that, fortunately weíd had a very systematic review of James Gambleís work The Chemical Anatomy of the Body Fluids, that monograph, and we took our medical students, while I was a resident, through that. And fortunately I had that experience or otherwise the Brigham would have been total confusion, but we knew our way along already and it was just adding on the understanding of dialysis and the skills about assembling the machine, things like that.

RH:

So you took us to the start of the war in Korea and your knowledge of the Kolff dialysis machine. Tell us what you did and how you transported things to Korea and what you did in Korea.

PT:

Well the story in Korea really begins in 1951 or so. When Dr Simeoni from Casewestern Medical School, Curtis Arts, major at that time, and our captain George Schreiner, our nephrology colleague, and lieutenant Russell Nelson, the urologist, made a tour of the wounding situation in Korea at that time, and I have it to show you how that began. This is Sandbag Castle with the artillery burst, which is indicating the main line of resistance. The front line was just behind that ridge. If a casualty were encountered, he would be put in a litter jeep, as you can see here coming along the road, and then his first stop would be to be unloaded from the jeep and entered into a first battalion aid station. If the wounding was severe enough then the patients would be evacuated by helicopter and they were transported in that canopied outrigger and brought to the forward surgical hospital, the Mobile Army Surgical Hospital, the MASH. Here was a MASH operating room, these operating room tables would go 24 hours a day as long as casualties were coming in and it was a very exciting piece of surgery. If in the post-operative period, various wounding problems would, of course, then occur, the survivals of patients thereafter, and then if acute renal failure supervened, then instead of about a 10% post-operative mortality that would rise to about 90%. So the survey team documented the variety of surgical problems, including acute renal failure. The decision was therefore made to deploy a surgical research time attached to a MASH hospital and to establish a lab and a dialysis unit; it turns out the 11th Evacuation Hospital. The surgical research team I have assembled in this group, left to right is Mac Olnie, and then myself, and then Captain John Howard who was a commander of the team, then in the middle of the group is Dr Francis Moore, a professor from Harvard who came out work with us to see how the injury was not in the surgical operating room in the Peter Van Brigham Hospital but the way it was under tents in real-life combat. Bob Host is the next one, moving to the right, Michael Lad and then Russell Scott, a urologist. Michael Lad was a very interesting person, he was a protťgť of Homer Smith; now I never met Homer Smith unfortunately, but I do have his book. This is a book called the Kidney Structure and Function and Health and Disease. I consider it anything you ever wanted to know about the kidney but didnít have the temerity to ask. It turns out this book was published in the 1951. It has 898 pages of text and 23 hundred references and its all here, and itís the closest Iíve come to knowing the father of nephrology in the United States. Mike contributed, coming back to this, some fundamental understandings of post-traumatic renal failure that impacted on the way we conducted the situations at the 11th Evacuation Hospital. Essentially what I have here is some data. Itís the graph of Mike Laddís data, which I donít think has been seen in the light of day up Ďtil now and I think itís so important that I wanted to include it here. This is a clearance of PAH on the ordinate vs. time post-operate on the abscessive. There are several things to be seen by inspection here. First of all you have to know that the patientsí data, who were less severely wounded, are seen on the open circles and the more severely wounded are shown on the closed circles. What this basically says is that every person who is traumatized in any significant way will develop renal insufficiency. So ever person responds with a degree of renal shutdown; the less the renal shutdown the quicker the recovered. The greater the renal shutdown, the greater depression of clearance, the longer it takes for those patients to recover. These are all non-oliguric, in other words the human lesion is primarily a diuretic lesion, not an oliguric lesion, which is one of those things. Now there are five or six points right down on zero down on this graph and Mike decided that with a clearance of zero they really need to be evacuated to the renal centre with a dialyzer because he thought they would shutdown and we would need to dialyze them. Well it turns out the only patients that were ever admitted to a renal centre by a virtual CAPH clearance, you see thatís not a usual way of referring people to dialysis but this came from there. All of those patients were non-oliguric and we published them ultimately as non-oliguric acute renal failure, had never seen that that way before. So we concluded that oligury was an unusual or rare exception to the total picture of renal insufficiency. That oliguric disease we estimated ultimately that it was about one in two hundred casualties that made it through evacuation, made it through surgery, and into the post-op period. So itís a very infrequent thing. Unfortunately or fortunately, depends, itís the oligurics that make the literature in nephrology and we donít have the literature really seeing the entire picture of acute renal failure, which we have here.

RH:

This ratio of oliguic and non-oliguric that you mention with the war casualties, it sounds a little bit much more non-oliguric than what we see in the hospitals. Is that because of they had any IV administrations or protocols for wounded at that time?

PT:

The main issue had to do with type specific compatible blood and thorough energetic resuscitation. We did not have any particular pharmacological interventions for these folks. It was as we saw it a very interesting development. It was a very exciting time. Lloyd H Smith the lately Professor of Medicine at San Francisco, he and Bob Host came out and set up the unit, and that was running. I took over an operating situation and then ran it through 50 some patients and reported those in the American Journal of Medicine in 1955, it was when the publication was. So that was a pretty exciting time.

VideoÖ.

RH:

So you did how long a stint did you do in Korea?

PT:

About nine months.

RH:

And this was toward the end of the war?

PT:

No, this was í52 í53. Combat went on a little bit longer.

RH:

And then what did you do?

PT:

Well, I finished my residency with Dr. Barry Wood and Dr Carl Moore at Washington University in St Louis and then got the invitation to take over the kidney centre of the Surgical Research Unit, so called SRU, or Institute of Surgical Research, which is it now at Brooke Army Medical Centre, Fort Sam Houston, San Antonio, Texas. Then I joined the research unit there, so you see my career continued in R&D really.

RH:

Before we go onto that subject, tell me your recollection of Merrill, who I got to know a little bit also, and tell me the impression you had.

PT:

John to me was...outstanding characteristics are his good humored, low-key, gentlemanliness. I had a sense that this was a person who was inquisitive, highly intelligent, gentle with the people he worked with, encouraging, and just a lovely person to work with. He and Barry Wood and a few others that Iíve met in the course of time had that marvelous characteristic of creating an atmosphere around him that of course one did ones best. One wouldnít think of doing less than oneís best, to do a sloppy piece of work. Not that he would be critical and obnoxious about it, but it just wasnít the level of work that one wanted to turn in. Aside from his skills later in French and the fact that when we visited Paris that Gabriel Richer then drove us about the corner and said that is where John Merrill lived when he was here. Now it doesnít sound like a very exciting comment but it indicated that for the people who knew John well in Paris that his presence was a major contribution, of course they were working on transplant primarily in John Hamburgerís organization. And weíll get into some of that because that is exciting too.

RH:

Letís go back then to your stint at the Brooke Army Medical Centre in Fort Sam Houston.

PT:

Well when we arrived, we were out of the rice paddy and we now could do the rotating drum dialysis and really have a wonderful time. You just read the literature, you just do this right, they do well, and it turns out it was worse. We had about an 80% mortality in our first selection of patients and my associate and I looked at each other and the question is, is this unique? What are we doing wrong here? Whatís going on here? So with about a yearís advanced preparation, I invited, obviously with the Surgeon Generalís strong support, convened then for a three day closed meeting in October 1957. It was a called the Study Group On Acute renal Failure. Reading really from left to right at this meeting, the first morning, we had Dr George Schreiner, Dr Hadley Khan, Dr Garland Hernden, Dr Paul Dulan who was my counterpart in the navy, Dr Bill Blumly, Dr Graham Bull, and Dr Wilhelm Kolff the inventor of the rotating drum. From right to left standing is Milton Rubini, then Gabrielle Richer who brought John Hamburgerís experience of Hopital Nacarr, and then John Merrill, and then next to him Dick Mason my first associate, Arthur D Mason Jr., and John Kylie and myself. Essentially we had in that one room all the people in the world who had published on acute renal failure by that time and the idea was to close to doors and to say, ďNow what really happens?Ē You can see data on the tables. And we all got the data out and combined on the first morning the incidents of mortality data we had on acute renal failure of four or five categories. And you see we that we had a thousand forty-four cases with an average mortality of 49% and the post-traumatics that we were interested in was about 66%. So we knew that our experience was not unique that all of this did contrast with the contemporary literature and we knew that something had to be different. Right then we had the choice, were we going continue to do as we always did just to get what we always got or were we going to do something fundamentally different. Thatís what I call a paradigm shift, thatís the new way of thinking. Thatís the exciting thing, when youíre not locked into something youíre always doing when itís unsatisfactory and of course what we were doing that was unsatisfactory is indicated on this classic slide from that era. During an oliguric phase obviously the blood chemistries get abnormal and the patient gets sick and the EKG begins showing bad signs of potassium intoxication and then you dialyze with this big dialyzer as infrequently as possible and the patient wakes up, feels better, chemistries are better, and as long a oliguria persists, you dialyze as often as you need to, but as infrequently as possible. Until diuresis recovers and the kidneys take over the extracellular fluid composition again and the patient recovers. That was the situation, but you see, some of the patients didnít live that long and had all the complications and post-traumatics of wound dehistances and infections and undermalnutritional wasting, a bad disease, more overly dialyses were emergent at 2 in the morning; we thought the patient would last Ďtil morning, oops, no, we had to come in and do that. It was a really tough scene, well obviously we needed to do something different and that really the paradigm shift. Well what was the paradigm shift? The argument was rather simple. If a big dialyzer can reverse a developed syndrome and chemical abnormalities then a little dialyzer used every day should be able prevent those. So we called it prophylactic daily dialysis. The idea was to prevent all these things and as soon as we began that you can image the whole scene changed; dialysis became routine and we stopped having emergencies and a number of things Iíll mention in the meantime. But there was another feature of this that interested me and that is that if chemistries got better and the patient felt better, whatever this intoxication was might indeed intoxicate other body cells and tissues and organs and functions and biochemistry. The possibility was that if the symptoms went away, that is if we relieved those elements of intoxication, maybe other elements of intoxication would go away too. To put it in sort of the bottom line, a patient with acute renal failure should be taken through his acute renal failure, his post operative course, his post onset course as if he didnítí have renal failure. The consequences of acute renal failure should be eliminated from the post operative course of these folks. That was the vision and our first experience, as we published in í59 and í60, were absolutely dramatic. This was our revolutionary change in our experience. And as you see the little dialyzer, in this case the McNeil Collins one in a square meter or so, this young fellow, I think with a transfusion reaction I donít remember now, he could eat hamburger and ice cream during dialysis and weíd never seen that before. And in the patients we had across the top of this picture, these are people, persons left to right, are 14, 18, and 27 days following onset of their renal failure. The two in the lower panel are patients with bilateral renal cortical necrosis, they did not survive obviously, but theyíre at 48 and 86 days post onset and weíd never seen patients look like that after that length of time in oliguria. We felt we were on to something. Legacy-wise, I think what we were seeing here, the legacy of this is really in the intensive care units, the continuous therapies. We now have intensive care units. I think the maintenance hemodialysis three times a week in chronic renal failure instage is a consequence of this, but more specifically is the daily short dialysis, the overnight dialysis everyday of patients with instage, with chronic renal failure. Essentially what I see is forty years later, we are doing for chronic what we were doing for acute and it makes me think that renal failure is all one story and we simply need to do dialysis right and thatís everyday. I think this is now a major change that weíre just now beginning to see.

RH:

So what weíre doing now for acute renal failure is really rediscovering the data and the work that you have done in the past.

PT:

Well I think that the idea gets around, whether it relates to a particular piece of literature. The key thing is that we need to prevent the illness and the abnormalities. Carl Shelstrom probably says it as well as anybody. He says early on in dialysis we found that two dialyses a week was better than one then we found three dialysis was better than two and he says, ďWhy, oh, why did we stop at three?Ē and of course he is well on along with colleagues, primarily in France and Italy, are now doing the daily story. Itís exciting to see those results.

RH:

While at Fort Sam Houston, if I recall, you had also done some work in the lab to supplement or to corroborate your clinical observations. Can you tell us a little bit about this?

PT:

Well the stimulus for the lab work was really Arthur D Mason my colleague, who was so tired of doing dialysis and having these terrible results, although he appreciated the daily dialysis and recognized the change there. His interests were really towards the lab. The question was, how can we study the pathogenesis and prevention of acute renal failure in the lab? It critical you can see that the army interest is not only in taking care of sick troops and wounded troops, but it has to do with anticipating whatever their needs might be wherever they are deployed in the world. And so the issue here is how can we deal with this acute renal failure and prevent it. Well first of all we had to have a model to work in and a quantity. At that time you have to remember that in the late Ď50s that it was generally agreed in the field that ?ascemia was causing renal shutdown, was causing acute tubular necrosis. We ourselves felt, as we thought about it, that ascemia is a very slippery term. It implies, but the use of the term in the literature is very imprecise, that there is an oxygen or nutrient debt. That the necrosis happens because the demand for oxygen and nutrients in the kidney exceeds their supply in situations of reduced blood flow. Well it turns out that because of the assumption that it was reduced blood flow without thinking of the oxygen debt issue, this led to models that had to do with clamping the renal artery, and pouring the ?norapa nephron into the renal artery. The problem with all that was it was based on an assumption that we felt was insecure but also that these procedures produced infarction in the kidney and in the autopsies of our combat casualties, even in the severely wounded ones, we did not see infarction. So to me, anything that had to do with clamping the noropa nephron was irrelevant. The other issue maybe wasnít but thatís the way we thought about it. The other issue was the fact that the people who published, unless we missed the literature - we could have, on these ascemia models had never documented the analogy between that model, whatever it was, and a spontaneously reversible acute renal failure in people. And so essentially we just took another tack entirely. In fact it may be a new paradigm shift there. Because that was the prevailing view, we took it exactly the opposite. We looked for a model primarily in rats because we knew to study many of them and we found through the work primarily of Dr Lolleck in Sydney, Australia, we found a pigment lesion, which we then used and documented. It required sodium water depletion for about forty-eight hours prior to the injection of the pigment to induce the lesion. Well the advantage was that we could study that and that went on, but back to the ascemia story. I presented the arguments against the ascemia at the first International Congress of Nephrology in Avion, in France. That was of course was the birthday of the ISN and we were situated in this lovely hotel across from Lasang in Lake Geneva and it was Del Royale and we were in the midst of this and that. Really I remember it because of two signal events; Iím pretty sure these were together and the same thing. One was an encounter with Gene Oliver whoíd done the nephron dissections of course and had indicated that in shock you have the Isk Murich episode. Well Gene Oliver and I, and a couple of other people, all got in this little French cage elevator. You know there are little cages that open and the thing goes up and so on, and as we talked I was this far away from him and he said, ďYou canít look at the pathogenesis of renal failure with just little keyhole peeps through microscopic slides.Ē I was sort of under attack but I said I thought we had a pretty good model, but that was a direct point that voted against ascemia and that was perhaps was built into that. The other was John Hamburger because I had a chance at that meeting, either that or the Fourth International Congress, Iíve forgotten quite which, to meet him and to hear him talk. After that presentation of his at that First International, I think thatís what it was; itís obvious that this was an outstanding presentation. His colleagues were thrilled with that presentation and they pointed out what elegant and beautiful French it was, well of course I couldnít understand a word of it but the point is that listening to it, it sounded like music. I thought that I was hearing something a cross between a Mozart and a ?Sasens piano concerto It was musical and later when I got to meet him, there that conversation was in English, itís obvious that here was a bright mind, inquisitive, forward leaning, absorbing in the conversation, asking questions, and a thoroughly charming individual, extremely bright; you could see the excitement it must have been to work with him. Of course we got to meet Gabriel Richer, his protťgť, in the study group that we just saw. So essentially we took the pigment nephropothy, just to finish that story; we could study platoons of rats in the gathering and follow all of their characteristics. We could look at their urinary flow by collecting it then we could see that, in exactly the same as the human situation, a given inciting episode would produce a large variety of responses in the kidney, some oliguria, mainly diuresis, more or less pigment, things of that sort, so it was an exciting development. That then gave us the next piece which gave us the behaviors of these animals. The point of all this rat model business led on to the next paradigm that we encountered and that was the sense of looking at these animals. Well, if you get a group of dozen or so rats who are ready for their injection or blood drawing, we noticed that, you know how rats do, they sort of mill around and we noticed a couple of them were reclusive and less mobile, different observable behavior. And it turns out then that they are the ones that had the hypercholemia and more severe asetemia, the more severe evidence of renal lesions. Well, it turns out then about that time an experimental psychologist came along and happened to drop in the lab and wondered whether he could do some experiments while he was faculty member at the field school and work with us in his spare time and we said sure. So we built him a t-maze, a simple maze, that the rats could be put in and we could run to a food reward and we said weíll do that if you will take some of our animals with acute renal failure and run them. Lo and behold, when we did we found that the prolongation of the running time was really superimposable on the BUN curve. All of a sudden it began to occur to us that thereís a difference between disease and illness. The disease in the kidney happened within minutes of the induction, injection, at zero timeliness, but the illness manifested in the delayed running time occurred forty-eight hours later. So you see, disease and illness are two different things and that really has focused our attention and has carried us really forward from that time on, and that brought us to our new paradigm number two in the behavioral studies, the basic notion that illness in an organism is really detected by illness behavior. Once we focused on that, it led to us to the point that illness behavior like other behavior is mediated by the central nervous system, and then it followed that instead of writing subjective progress notes we might be able to quantify the abnormal CNS function that produced the illness behavior, and we would have then a quantitative way to look at the degree of impact for the illness in an individual beyond all the things about chemistries and the other kind of things we normally look at. Could we use the CNS as an intrinsic marker or monitoring system to see the development of the illness in these folks? That was sort of where we went. I retired, moving from Brook to Walter Reed. We were hooked up with the department of psychiatry there, and in that particular situation they had operate condition monkeys, monkeys who would push levers in response to a stimulating program and we were able to put an EEG montage on the skull. We were able to acquire the EEG as well as well as measuring lever pressing and we could occlude the ureters, or take out the kidneys, and do peritoneal dialysis as you can see in the sitting, conscious, lever pressing monkey. And essentially as weíve shown before in some of the publication, but just to summarize here, you can see as the ureter was occluded toward the left end of the picture, the BUN in the lower panel continued to rise and inversely the level pressing behavior deteriorated and the proportional slow waves in the EEG increased, slowing being a characteristic finding. But when we did peritoneal dialysis in that vertical panel toward the right end of the picture then you can see that the lever pressing behavior improved, the slow waves began decreasing, that is the proportional faster waves supervened in the EEG but the BUN didnít change and thatís because we put urea in the dialyzate at the level that was in the blood before dialysis. Now the fact we had behavioral and EEG improvement without change in the plasma urea gave us our first indication. See how exciting all this is? Weíd never done that before. It was our first indication that urea has nothing to do with the concentrations that normally occurs with clinical illness and we began seeing possibilities of separating, of getting at, the solute parameters, causes, solute-wise, why the patients get sick the way they do in uremia and how dialysis makes them better. You see this was a major new step and at that point I retired from the army.

RH:

What year was that?

PT:

This was 1969.

RH:

Then what did you do?

PT:

Then I came to join Earl Gian at Vanderbilt and then hooked up quickly with Dr John Born, who is in biomedical engineering, and with his set of colleagues and graduate students and the result was that we were able to develop a new set of these measures. We were supported in that time by the NIH in the Artificial Kidney Chronic Uremia Program, stimulated by the work in the EEG by John Kylie and George Schreinerís paper on the mental and personality changes in the uremic syndrome. All that seemed to come together plus, of course, the background we brought to this thing experimentally. Our new behavioral measures were put together on a new mobile unit which could be rolled around in the dialysis unit to the chair-side for the recording of both the EEG and psychometric tests administered by a TV monitor; the patient would respond by button pressing, must like the monkeys. We wouldnít say that of course. Essentially the button pressing and response to stimuli gave us the choice reaction time, various kinds of measures that would do that. Well the EEG of course was tape recorded and reduced by computer and digitized so that the power of the EEG could be detected in each of the major frequency bands and ratioed one to another so we could see the preponderance of slow waves increasing or decreasing. So the more severe renal failure had the slower waves, a fundamental response improvement to dialysis and a further improvement to transplantation that is we could see that change in both the psychometrics and in the EEG power spectrum analysis. Well this gave us the chance then to look at dialysis and various doses of dialysis. We found that when you dialyze more, the brain is working better by these methods than if you dialyze less. Again there is the intrinsic marker system does not have to do with chemical measures of one sort or another but does have to do with the expression of the illness in terms of uremic symptom methodology. And that intrinsic organic participation in the disease and in the illness to me was really crux of this issue and it was so exciting to see it work as we had suspected.

RH:

Tell me about some of your colleagues at Vanderbilt that helped you do this work.

PT:

Well the primary people who helped along were John Born as I indicated in the biomedical engineering and that set of graduate students. I had marvelous support by Earl Gian originally and the work seemed to continue because of the support. I remember Grant Little, professor and chairman at that time, mentioned to us that given the possibilities that we might indeed reinvestigate all of internal medicine that is symptomatic illness because we developed this integrating hypothesis that we showed here that is any disease that makes symptoms that we can see as illness behavior suggests that the CNS is generating those symptoms. So our thought was that the central nervous system is sort of like a black box. The disease, if it makes symptoms, does so via the CNS. So our idea was that neuro-behavioral probes should be able to detect those changes in the CNS regardless of what the symptomatic disease was. And if therapy then would improve the disease and make the symptoms go away, then the CNS measures should also show that particular change, but in objective terms instead of in the subjectivities of the progress notes. So the integrating hypothesis when Grant saw that he said, ďYou can investigate the rest of internal medicine in that way.Ē We were never far along with it. Then we went on to the notion of how to pursue this in the lab and we had at that time the association of Dr Jonathan Lipman a very ingenious and very skilled physiologist peritoneal dialysis in rats and at the same time were able to acquire the EEG in those rats allow the rat, the bilateral nephrectomized rat to deteriorate his EEG and then we were able to do peritoneal dialysis and we got therefore into the next paradigm that had to do with solute specific dialysis because you see the dependant variable is the dialysate composition. The dependant variable is the EEG effect. We have a compressed spectral array here of the EEG and the TAR in the right upper corner is theta alpha ratio that is the ratio of the power in the theta range from 3 to 7 Hz to the power in the alpha range, 7 to 13 Hz. So theta to alpha power ratio is shown on the top graph as the sham operated animal and you see that the ratís normal power is around 67 Hz. But if the animal then gets nephrectomized and begins to deteriorate, you can see the waves slow to around 3 to 4 Hz and you can see the theta alpha ratio rise from 165% to almost 290, almost three times the amount of power in the slower range. So this gave us the quantitative estimate of how to get at that.

RH:

And these rats were dialyzed with peritoneal catheter?

PT:

Uh, yes, indwelling peritoneal catheter and we had them lined up 7,8,9,10 of them and the computer would drive the switching box that would then access the EEG serially from the ten rats one after another twenty-four hours a day except when they were being dialyzed twice a day. So we were able with equilibrated peritoneal dialyzate to approximate or to estimate the blood levels in those animals, so we had a beautiful system for that.

RH:

Were you able to continue this work while you were at Vanderbilt?

PT:

Well we ultimately had to stop. We decided first of all, this was a hugely labor intensive as you can imagine; what we needed was some funding and therefore we applied, of course, to the General Medicine Studies Section B on three occasions and the Biophysical Studies Section in NIH on one occasion and failed all four times. Now you can imagine that that was a pretty significant disappointment. Now I canít really fault the Medical Studies Sections because the nephrologists were focused correctly on the kidney but their focus on the disease in the kidney left very little room for the illness in the patient, and we felt that that had some claim for further exploration. We found that the neurologists in the biophysical group were not interested in the kidney anymore than the kidney people were interested in the brain. And so I decided that this was really a peerless application. It occurred to us much later that we should have asked for a special study section and didnít, and the data was certainly there we published again in the ISN journal, the Kidney International, in 1979, and again in 1990, this entire sequence. So thatís where all that lasted.

RH:

I know when I joined the faculty here you were also involved with clinical activities at Vanderbilt. Tell us a little more about that and specifically the MDRD study.

PT:

Well Iíd spent about a dozen years as cold medical director with Dr Keith Johnson in the Dialysis Clinic Incorporated, especially the dialysis unit here in Nashville. I was impressed increasing with the dependancy and despondency of the endstage kidney patients on dialysis. What impressed me was the fact that I was somehow responsible for everything that happened to them and I got tired of that and I felt that what we really needed to do was to prepare people for endstage much better than we regularly did. So with that about that time, fortuitously I guess, the modification and diet renal disease study came along. Here was an opportunity for us to get in early in progressive renal disease. That was a marvelous experience because we learned from the patients a whole new approach. The most successful patients that we had, as a matter of fact, managed their own disease. I think quite aside whatever we did with progressive renal disease, the main learning for us, for the MDRD, was what the patients taught us, namely they became believers in their self worth and concluded in effect that it was worth working on staying with the program, that is to say to be with the regimen, when they believed that they were worth something. Then it follows and adhere to the protocol, was worth it. Thereís no point in doing that unless one thinks itís worth doing. So we finally learned that the main contribution we made was, all of us in the team, reading from the same page was that you are worthy, its worth the effort, and the person that going to win is the player, not the coach, and that turned the whole situation around. The example I like to quote is if I see, in the clinic, a patient a half hour, if me and my team see a patient for a half hour every three months, it would be not a study but a clinical operation. If I see a patient every three minutes there would be 2880 waking half-hours between visits. Since my half-hour is 0.3% of that waking time, who is managing the patient? Itís quite obviously the patient is managing the patient in the 99.7% of the time when heís awake between visits. If thatís the case, then it follows to get good management, patients have to become believers; they have to become competent and by becoming competent they become confident. It places responsibility for chronic renal disease, not only renal disease but all chronic medical disease, right where it belongs, in the player. Itís the player who makes the touchdowns and the home runs and the baskets and so on. But you see what it does is it takes the doctor and the patient away from their opposite situation, the one up doctor and the one down patient. All of a sudden in the coach player model they come around in synergy so that it becomes both the coachís and the playerís interest to win the game. The coach wants the player to win but doesnít do the playing. The player does the playing so itís in the coachís interest to increase the skills and the understanding to make a good player out of that situation. Now I think we can begin to see some of this happening in the evidence based disease management literature, which of course is of course burgeoning, but you see all of those educational interventions are still external to the patient. The coach-player model of what we now call health assurance coaching, as the name of this thing I think itís a neat term for this, health assurance coaching that embodies evidence based management places the responsibility on the player and uses the coach-player approach. I think it is the wave of the future in medical care in general and particularly for chronic medical disease. I think itís one of the most exciting developments, itís a new paradigm shift, it goes beyond so-called educational interventions because it evokes adherence from inside the patient and avoids the mindset of the prescripted directive health care provider attitude. I think this is a new paradigm number four and this is really the way this needs to go

RH:

So in a sense, not making the patients just know about the disease but take control of their lives, take controls of their illness, and manage it and with your coaching.

PT:

This is what we learned. You see, the MDRD study could never have produced the adherence, at least in our experience that it did, without the patients coming aboard as believers. All the time they had to be away from us, they had to be on the regimen and we have evidence that was the case and the successful ones did just beautifully. And itís interesting isnít it that they taught us it could be done.

RH:

Before we get off the Vanderbilt era do you remember any particular fellows that you trained in your programs that you want to mention or talk about?

PT:

Well I donít recall very specifically the Vanderbilt fellows because thereís a whole series of really able folks. I think that Arthur Mason back as the beginning of the story back at Brook was outstanding, he became Chief of Lab. We had of course a number of marvelous people at Walter Reed: Bob Schrier, Carl Knoff, Craig Tescher. They were all at the same time. What a powerhouse that was, and to have those as colleagues, and Bill Sirks was of course active in the micropuncture field and so on. So the pathogenesis of renal failure was expanded by the studies that he did, and the association here with Earl Gian was mighty fine because he was very much concerned with doing the dialysis right

RH:

Coming back to the issue of the coach-player paradigm that youíve talked about, I wondered whether as you look at whatís happening right now both in terms of the patients acceptance of the idea and the physician acceptance and then as we all deal with this societal insurance provider, how do you see all that playing together?

PT:

The crystal ball does get a little murky about that time. Iím not sure how itís going to play out. I would imagine that the healthcare financing administration would be unhappy about increasing the amount of dialysis. I think that a back up in the progressive renal disease pre-endstage area, that the pressures, the economic pressures of having to run many patients through the system of decreasing number of healthcare personnel of lesser and lesser educational quality, then having to spend less and less time per patient is exactly opposite to the initial investments that are necessary to get patients to come around to be their own managers. My guess is in the long run that a couple three things will triumph, now I donít know how to get there exactly but I think itís going to be evident that the basic purposes of all chronic medical care are going to be achieved by the coach-player model through health assurance coaching. That is to say, improved access to quality care at reduced cost. And I think when the truth of that is borne in on enough folks that weíre going to see the change. After all, the patient has access to him or herself all the time, that is all waking hours. So there is improved access. The quality care comes from coaching that is adhered to as the personís understanding and confidence and competence builds in taking care of himself. Patients tend to avoid doing dumb things when they understand the consequences of doing dumb things. Now not all patients do this all the time but the tendency is going to be for quality healthcare when it is well instructed and gets into personal practise of self-maintaining patients. Now the assumption is when that care is competent and well coached the likelihood is, and if the patient understands finally that he is worth enough so that he doesnít have to do dumb things that are self-destructive, then it follows that the patient ought to be healthier and as such might see the provider less often and might use health resources less and therefore the cost goes down. I would think providers would be delighted to have patients be so competent that they are just in touch by phone when they get into questions when intercurrent events turn up and that they wouldnít turn up in emergency rooms and having to be admitted to hospital because they already know how to stay out of those things.

RH:

Well Paul, I only hope that as the new thoughts and the new paradigm shift that you have helped crystallize in terms of the treatment of acute renal failure and the preventative and acting on the illness, before it is completely manifested at the level of the disease and before perhaps the illness manifest, will finally catch on with the current state of healthcare in the world and particular in this country because empowering the patients is clearly a way in which we can all benefit from and save a lot of cost to society. Thatís been a wonderful career and Iíve learned a lot from it. If you were to look back and pick one or two things that you want to highlight and recognize in your careers, what would you say those would be?

PT:

Well thatís an interesting question. Usually some people have focused on that Korean War business and using the artificial kidney on a rice paddy. I consider that preamble. To me the most important thing thatís happened is the paradigm shift to daily dialysis that is to say the preventing the illness and the chemical abnormalities and allowing patients to go through their renal failure as if they didnít have renal failure. That idea to me was the most important thing, prophylactic daily dialysis, and to see how thatís eventuated. Itís still touch and go but itís still very promising. I think that the second issue really had to do with sort of a different paradigm, rejecting the ascemia idea and going for an acute renal failure model that works and document the fact that its analogous to a human and then get on to it. I didnít mention before that we found that any agent with a couple of exceptions that produced diuresis before the injection that induced the lesion, the diuretic producing agents would prevent the lesion. The ones that did not produce diuresis did not prevent the lesion. So we got into the preventative part; we never did work out the pathogenetic issues that were involved. We tried and there were some publications, but thatís not a completed issue. I think the next big insight or change in thinking had to do with recognizing that illness behavior is produced by the central nervous system and that objective measures of central nervous function could detect the function of the marker system, which generated the symptoms. So therefore, we could use this intrinsic marker or detector system as a way of seeing what the impact of therapy was. So that construct that said the CNS was fundamental to understanding the way the illness worked was really a new development which no one seemed to be excited about but we were excited about it and thatís why I considered it sort of important. That then led to the solute symptom connection. That is to say to the possibilities for solute specific dialysis, that we could prevent dialysis of selected moieties or we could add single ones and see if they had anything to do with the marker system.

RH:

So instead of having a whole barrier of tests, the whole Chem 22 items, you measure EEG and that would give you a comprehensive look atÖ

PT:

See our basic assumption was nothing we measure in the lab has nothing to do with it, the illness. So the question is what does? Well it turns out our first experiment, which was the last of the series that we could do, showed that it was a little of both. Something that is already measured contributes something but there also other things that we donít measure that contribute something and we have to leave it there unfortunately, and then the final thing which is really a work in progress, thatís a legacy primarily for me; I think the term health assurance coaching and the term in the sense of using the coach-player model and hooking those two together is a departure in a sense. I think itís beyond where disease management literature is currently operating and so I hope when we really get to that and use the MDRD learnings and put that into general practice for chronic medical disease then I think that might be a terribly important legacy but itís much too early to tell. Itís sort of a legacy that you look to in the future, which I think is a contradiction in terms but then that alright. Itís been an exciting time, and I donít think weíre through yet.

RH:

Thank you very much Paul.

PT:

Well thank you.