ISN VIDEO LEGACY PROJECT

DR. NEAL BRICKER
INTERVIEWED BY DR. MARC HAMMERMAN


MH:

Today is July 16th, 2004. I’m here in the Washington University Renal Divison together with Dr Neal Bricker to capture the living history of nephrology as part of the International Society of Nephrology Video Legacy series. It’s a beautiful in St. Louis; it’s about 90 degrees and 90% relative humidity. Just the way you like it, right Neal?

NB:

It was just about the same in California when we left.

MH:

Are you ready?

NB:

Let’s do it.

MH:

Let’s start at the beginning. Where were you born? And where did you grow up?

NB:

I grew up in Denver; I was born in Denver, Colorado. My family goes back several generations on both sides in Denver, and I left home when I was sixteen to go to college.

MH:

When did you first think you might be interested in medicine?

NB:

When I went to college I was going to be an engineer. I was in the navy and the navy told me I was going to medical school and that’s when I first thought that I might like to be a doctor.

MH:

The navy told you, you were going to medical school?

NB:

Yes, and they assigned me to a physician at the University of Colorado Medical School.

MH:

So you had no choice?

NB:

No choice, no.

MH:

How old were you when you received you degrees from the University of Colorado?

NB:

Going backwards, when I graduated from medical school I had just reached my twenty-second birthday. When I graduated from college I was eighteen, and sixteen or so from high school.

MH:

That’s pretty young.

NB:

Yeah. There was a war on and everything was accelerated.

MH:

You were the recipient of the Gold-Headed Cane Award.

NB:

That was an award that was given by the University of Colorado Medical School to the outstanding graduate and I must say it came as a great surprise and I was delighted to have it. I might mention that I had written a paper on extra-cellular volume and there I think was my first official, expressed interest in nephrology and at that point a prize with the Gold-Headed Cane.

MH:

Was the Gold-Headed Cane Award a gold-headed cane?

NB:

It actually was not, but apparently I should have gone to my own graduation because they had a gold-headed cane for me to march with, but I was a no-show, so I never had a gold-headed cane. I have a nice plaque though, and I have a book, called the Gold-headed Cane.

MH:

Would you have had to return the gold-headed cane?

NB:

No, I wouldn’t have…

MH:

So that’s a real loss.

NB:

It is, really.

MH:

You did residency training at Bellevue in the late 1940’s and early ‘50s, that was Homer Smith’s department.

NB:

It was connected. Bellevue had four medical schools that were involved in its clinical activities. One of which was New York University, and Homer Smith was the head of the department of physiology at NYU, so I was able to spend a few months in Smith’s laboratory during my second year of residency. I got to know him and ?Fudemeyer greatly. I admired him before that, but he was a great man.

MH:

What was it like working with Homer Smith?

NB:

Well, there wasn’t too much conversation, but as I say he was brilliant. He is now known as the father of renal physiology, that brilliance emanated broadly. The laboratories were a tradition to the old Washington University, suffering for suffering’s sake. No longer the case, I should say, here; I don’t know about his laboratories, but it was exciting to work with him.

MH:

Neil you spent two years as chief of renal physiology at Fitsimmons Army Hospital. I understand you did polycystic kidney research and a tuberculosis laboratory.

NB:

Yes, I might just tell you how I got there. This was during the Korean War, because the navy had sent me to medical school I owed them time, and I was taken back into the service. This time the army and a 160 physicians were in our group sent to basic training at Fort Sam Houston and San Antonio. It was real basic training: live machinegun, bullets, crawling under barbwire. But the worst part of it was that they…first day we arrived we were told we were going to frontline battalion aid stations in Korea, and a shooting war was going on. I dreamed most of the nights I was there about lying on the ground and having enemy soldiers coming at me with knives. One of the people there who was a physician who happened have been Yogi Berra’s partner on railroad trains, Yogi Berra being the very famous third baseman I’m sure everybody in this anyhow knows about him, had the upper bunk when they were going from city to city for the New York Yankees. And the person who was a doctor, his name Bobby Brown, he had the lower bunk and he was at Toulane Medical School. According to him, he would Grey’s Anatomy and Bobby Brown would read comic books but they got along very well, but Bobby Brown was the man who had the highest World Series batting average then and I think he still holds that record. The commanding general wanted very much to be seen with Bobby Brown, either digging a latrine, or using one, or whatever the activities were. So when the day came to cut the orders, to send a 160, actually it was a 159, of us to Korea, Brown had already been told he was going to Fitsimmons, but because of all the publicity he had, they couldn’t do that. So alphabetically it was Brown and they went up to Bricker and I went to Fitsimmons. Because I had the experience with Homer Smith and had published two or three papers, they decided I should go to the research and development branch of Fitsimmons, which as you mentioned, instead of microbacteria and tuberculosis about which I knew little and cared less, but they had a lot of money and a lot of space, so they said, “Do what you want.” And for two years I did. I had technicians… The studies on polycystic kidneys were done on young GI’s with overt polycystic renal disease. At that time, there was a procedure, which allegedly improved renal functions, involved decompressing the cysts, cutting off the top of them, needling the rest of them, the ones that could be reached with a needle. A urologist, at Fitsimmons, allowed me into the OR; we infused ?indulin and perimenohypburate into the patients during the procedure and needled the cysts. What happened was that the indulin appeared in cyst’s fluid immediately. PHH did not and we studied a group of patients with simple cysts and the PHH diffused in at the same rate in polycystic diseases in the simple cysts. But the indulin was obviously filtered, we had measured renal function before and after the surgery. Function went down substantially, from that we concluded that the cysts were attached to functioning nephrons and that the procedure of choice was not the surgical procedure. I think things have turned around somewhat in recent years but that was a polycystic experience at Fitsimmons.

MH:

Was that the first demonstration? The cysts were actually connected to the nephron?

NB:

Yes.

MH:

So that was very important. You served as resident in Howard Hughes Investigator at Peter Van ?Brighum during the early and mid 1950’s. I know you measured renal function of individual kidneys post-transplantation in identical twins.

NB:

The first set of identical twins to have a transplant from one to the other had been done and it was successful. I had the opportunity to do serial renal functions studies on them over a period of many, many months. The GFR of the two kidneys ultimately reached the same level, stayed at the same level. We challenged them with many different things, xelon loads and phosphate loads, etc. There were essentially no differences between the donor and recipient in terms of renal function. The only difference between the two of them after the studies, after the transplant, was that the two never liked each other to begin with; they liked each other less afterwards. The final phase of this was that the recipient developed glomerulosclerosis after about two years and died but the donor was still alive.

MH:

Who recruited you to St. Louis and why did you decide to come?

NB:

Well, the name Carl Moore is extremely familiar to you and to me and to many, many people. He was the incoming chairman of the Department of Medicine at the time. He was essentially responsible for the recruitment plus the fact that, as I’ve told you before, my salary went down from Harvard. From nine thousand to eighty-five hundred a year, I think, in Harvard I kept my fees from a few private patients I saw, and in Washington University I turn them in to the to the school. So I guess I was the feeling of contribution. I was glad I made the change however because after I had been there in the renal section, it was actually the cardio-renal section, I was told by the then-chairman George Stern that if I stayed I would become the director. Shortly thereafter I learned that the person who was the director had just added a large addition to his home and wasn’t going anyplace. I think that may have contributed to my decision.

MH:

What were your impressions of Barnes Hospital in Washington University in the mid 1950’s?

NB:

Inside or outside?

MH:

Both.

NB:

Outside it was hot in the summer and cold in the winter and it took me two years, as I think it does many people, before I began to love St. Louis. I think I liked Washington University from the very beginning. The esprit was extraordinary. There weren’t all of these beautiful buildings that you have now but it was a solid faculty which has gotten better and better and better over the years. And I was very happy there. I had a family, it involved sacrifice on their part too but I think they too came to feel it was a very wise move to come to Washington University.

MH:

Have you ever been to St. Louis before?

NB:

Yes, but not for very long. I came out here during the recruitment process. Living was easy because the residential areas were not very far away were quite nice; the schools were very nice. It all fit.

MH:

Tell us how you formulated and tested the intact nephron hypothesis.

NB:

It’s kind of a long story, Marc, but I’ll try and make it brief. At that time, in the sixties, the extent view of the function of the diseased kidney was most poetically expressed by Jean Oliver, who was a pathologist, who did nephron dissections. By some of his nephrologic colleagues, and it was that the processes of disease ravaged the kidney so that no “nephron was like another, no kidney was like another, and there is no kidney in chronic renal diseases.” It is a vestige of what it was in health. Trying to find the basis for this other than the morphologic changes, which obviously are devastating. There was no scientific data, information, there were no physiologic data. You couldn’t study a patient with bilateral renal disease and compare it to a normal person. For one thing the extra-cellular fluid was so strikingly different, the levels and hormones and acidosis and so on. So the approach we took to try and decide whether the diseased kidney was not a kidney anymore was to use a technique that we used in Harvard on transplanted dogs. The urologist by the name of Joe Murray developed this technique; he subsequently won a Nobel Prize for being involved in kidney transplantation. What it consisted of was dividing surgically the urinary bladder into two and then exteriorizing both Hammy bladders using a polyethylene tube that came out through the anterior abdominal wall. We then with the help of colleagues here, at Washington University, first had to learn to produce the disease in one kidney. We developed five different techniques that produced unilateral renal disease and spared the contralateral kidney ranging from palonephritis to a form of glomerular nephritis and ultimately to the remnant kidney, which was a normal kidney with three quarters of its arterial supply tied off, which left about a small *noven of that kidney. The contrakidney kidney was left intact and we would steady the tube. Hundreds and hundreds of tests were done measuring at what all the available renal functions that were amenable to measure at that time. When one corrected for glomerular filtration rate differences, there was no difference between the two kidneys. When the arithmetic was done and everything was canceled out, the results were that for every mole of inulin filtered by the nephron of the normal kidney that the ratio of a tubular function to the inulin one a molar basis was identical bilaterally. It was a great surprise but it was what led us to the view that though the nephrons are distorted morphologically that physiologically either they function normally, function as if they were normal by compensation in glomerular tubular balances, or they didn’t function at all. Subsequently we were able to establish those facts by measuring the number of functioning glomeriali, using a technique that involved injection of a dye that was lodged into the glomeriali to count the number, and then a dye that was filtered and we counted both profuse glomeriali and filtering glomeriali. To this day we have pretty much confirmed the basic validity of their hypothesis. The approach to teaching of pathophysiology of renal disease is now consistent with the hypothesis in Brenner’s and Rector’s new text volume the ?Ledoff bears testimony to that point. There aren’t to my knowledge any major disagreements with it. There certainly are exceptions in certain diseases where concentrating ability may disappear early than other functions but by and large there is homogeneity of glomerular tubular balancing. After that we went on to study the adaptations that take place in the diseased kidney by removing pieces of the normal kidney, segments of its populations of nephrons and then repeating the same functions including how there is progressive hypertrophy in the residual nephron population of the diseased kidney.

MH:

Tell us more about the adaptations.

NB:

They’re fascinating. First of all, GFR goes up in the residual nephrons. Secondly, sodium excretion per nephron, or per diseased kidney, goes up but it goes up very passive; it goes up with the intake. In other words, if the intake sodium in a RAD is fixed to a given level and then you decrease the number of nephrons progressively, the excretion remains equal to the intake, which means the excretion per nephron has risen inversely with the number of nephrons. The same is true of all over the other solutes that are controlled by the kidney: potassium, phosphate, calcium, magnesium, and so on. If you double the intake of sodium and half the intake of potassium, it would be a disaster if there were adaptations because you would either die of a surfeit of sodium or the progressive loss of potassium, but in fact balance is maintained by the diseased kidney down to most of the natural history of the disease. Sodium and potassium, the adaptations are able to control extra-cellular fluids concentrations until GFR is very, very low, until the number of nephrons is perhaps less than five percent of normal. In the case of uric acid, its about fifteen percent of normal; in the case of phosphate its about fifteen percent of normal. In the case of sodium now, we know that the end organ sensitivity to the events that regulate transtubular transport of sodium is increased. If there is a hormone or a series of hormones involved in the biologic control of sodium excretion that the levels are very much increased as the number of nephrons decreases. These adaptations have override capability, so that, as the example I used: doubling sodium intake and decreasing potassium intake, if the increased sodium excretion starts to increase potassium excretion, there comes a point when there are cutoffs and patients do not develop progressive hypokalemia. They will with drugs, but they will not on the basis of their diet.

MH:

Why do you think these adaptations are in place?

NB:

If we can take the example of sodium as a key extra-cellular fluid solute. If you halved the number of nephrons, maintain the intake constant, say the person was on two hundred milli-equivalents of sodium a day, a high salt diet, and the nephron population went from two million to one million and that patient was excreting two hundred milli-equivalents a day until he or she lost one kidney, then the excretion would go down to a hundred. And if you continued that for a week, the patient would died of pulmonary edema, heart failure. So that the same is true of the adaptations all of the so-called other control solutes. We define a control solute as one that has a biologic control system, where there is some means of recognizing the input into body fluids, a signal that there is transduction of that signal and it’s sent to it. If there is an intermediate organ it secretes a hormone, like parathyroid hormone for phosphate, that signal is associated with an increased rate of synthesis to the hormone, and this is a gross simplification, and then that hormone will, along a distant signal, will reach the kidney where the receptors are uploaded and it will excrete more phosphate per unit of PTH, more sodium per unit of a sodium excreting hormone. It’s called gain in other disciplines, particularly in engineering disciplines. The increase in output per unit of input is a definition of an adaptation. The biologic control system maintains regulation over that adaptation so it doesn’t go haywire. And I come back to the question, why is there adaptation? I think there is adaptation because it has to be in place at birth for each solute. However it’s not activated. If you triple the intake of sodium you don’t activate gain. It’s only by losing nephrons that this happens and how that happens is unknown, the dead nephrons don’t send a signal, and its not due to the fact that if you give a sodium load, in the case of sodium, there’s a delay in excretion, but there is an increase in the end organ receptivity and responsivity.

MH:

Did you have any difficulty getting this work funded or published?

NB:

Well the funding was okay. We did get a program project grant. I think it was fairly early on. You review this recently, you can tell me if we were turned down?

MH:

No, no.

NB:

And that program project grant is still, I believe, in existence. It’s about to phase out, but it is about to be phased out. But it is the longest lived program grant in the NIH history. Publication was a little different. We had sent in some manuscripts, a couple of manuscripts, to the journal of clinical investigation based on research at one end of the formulation of the hypothesis, but I put the intact nephron hypothesis into a major work and sent that to a major journal. The editor recognizing that this was in contrast to the opinion wrote back and said, “Can you get somebody?” He was going to send it to his reviews, and he did; they were not too kind. “Could you send it to Homer Smith?” and so I did. I sent the paper to Homer Smith, “Would you be so kind as to review this manuscript?” About a week later, I got a single spaced typed letter from Homer Smith, which I can summarize in a few words. It said, “You are on thin ice, be careful.” Then a few days later, two of the papers came out in the Journal of Clinical Investigation and three days after that I got another letter from Homer Smith, which was single spaced hand-typed from him, “Please redact what I said in the first letter, you might as well have cut those nephrons out with a knife.” That sort of launched it.

MH:

How was the hypothesis accepted by your peers in the scientific community?

NB:

Not well, I can give you a lot of anecdotes, but perhaps the one that struck me. I was then thirty-one, thirty two, I used to spend my summers in a marine biological laboratory in Mount Desert Island Biological Laboratory in Maine. One summer, shortly after the paper was published, the collaborator who worked with Gene Oliver and who was the foremost proponent of the so-goes structure, so-goes function, and he was a renal physiologist, came to visit me. I had been at the laboratory for many years and he came to visit and I saw him, very striking me. I went out to greet him and I said, “Dr So-and-so, I think there’s some things we might want to talk about, things about which we disagree.” And he said, “Yes, what is your name?” And I had my hand out and I said, “My name is Neil Bricker.” And he looked at me for what seemed to be an eternity then abruptly, with my hand still out, turned his back and walked away without uttering a sound. I would estimate that somewhere between fifty and seventy-five percent of world nephrologists would have done the same thing if they had the opportunity. So it was not well received. That’s enough said of that.

MH:

You worked for a year with Hans Using at the Institution of Biological Chemistry in Copenhagen.

NB:

Yes, I have a sabbatical there from Washington University. I was an established investigator of the American Heart Association, so they paid the salary there. I worked on sodium transport in isolated membrane, frog’s skin primarily, and it was a very worthwhile experience. Using was a very brilliant man, probably should have won the Nobel Prize, but it’s experience that changed the direction of my career. I became more and more interested in mechanisms of sodium transport, did a lot of work on transport of shark red blood cells at the Marine Biology Institute.

MH:

What are your memories about the early days of dialysis and renal transplantation?

NB:

Mixed. My concern was that all of the funding that the national institutes of health was providing for biological research would be diverted and that dialysis, which needed funding, might ultimately impair the methodology, the methodologists, and the pursuit towards some means of preventing the diseases that occurred in end stage kidney disease. On the other hand, my experience at Washington University was that we needed a dialysis unit and didn’t have one. At that time the dean of the medical school was not anxious to have one. I did one of a few end rounds with some money from private services and we set up a couple of dialysis units and started to do chronic dialysis. Well, you know what’s happened since. How many beds do you have here now and how many patients?

MH:

About 600. That was the Chromalloy American Corporation?

NB:

Actually not, the Chromalloy American Corporation came later when we wanted a larger dialysis unit and I had lunch with the then president of the Chromalloy American Foundation; he gave us a quarter of a million dollar, which was a lot then, and we were able to set up the first dialysis unit of substance and size. It just kept growing and growing. The same man, I think, continued to contribute, and you sit in his chair now.

MH:

What was it like to work for Carl Moore?

NB:

You’ve brought up all the giants in my life, and you brought up one of them, and he was one of them. We didn’t have much room, laboratory space, and less space for our dogs. So I ultimately was given permission to build, to have built, steel cages in the hall of the ?Woel building. It was on the sixth floor and Carl Moore’s office was on the sixth floor. One morning I got a call from Carl Moore saying, “Neil could you shut those dogs up, I have a donor in my office.” By and large, he was totally supportive and just a wonderful person to work with and for.

MH:

Were you able to get those dogs quieted down?

NB:

Yes, but only through laryngectomy.

MH:

Who were some of your colleagues and trainees at Washington University?

NB:

Oh there’ve been so many of them and so many have done so well. On you faculty you have: Dr Sladapolski, Dr Clarr, Dr Perkerson, and I’m afraid to go on because I’m gonna leave some important names out. But we have them spread out all over the world and heads of divisions, heads of departments, a few deans, and overall maybe that’s been one of the best parts of the position is to have seen these people. Of course when we began when weren’t very many nephrology units in the country. There were in other countries, especially in Paris. So we got the best people. We were able to get funding for them. I’m still working with Steward Shankle who is a fellow here for two years, became chairman of the Department of Medicine with Norma Linda and now has worked the same institution. Allen Robson who was a Pediatrician and ultimately became chairman of the Department of Pediatrics. Dick Graselbacker became chairman of the Department of Medicine. I hope the people that I’ve forgotten, and there’s some outstanding ones, don’t look at this tape.

MH:

Whose idea was it to establish the American Society of Nephrology?

NB:

I guess I was mine. The American Heart Association had a renal section, but nephrology didn’t have its own voice in that section although there were some pretty prominent nephrologists in it: Bob Berliner, Lou Welk, Don Seldon, George Schreiner. In any event this was a meeting held after six months of back and forth struggling, a meeting held in Washington held around a round table and the vote was to establish a society of nephrology, an American Society of Nephrology. I remember Lou Welk nominating me for the presidency and I was sitting between Welk on one side, Berliner, and then Seldon. Not only were they ten years my senior, but thirty years my intellectual seniors, but that carried and that’s how I became the first president.

MH:

What were the challenges for the ASN in the early days?

NB:

The question of dialysis versus research funding was a major challenge and a presidential address I gave was…I don’t have the exact wording of it, but it was a search for balance; both have to be supported. I believe it was well received and I think it may have done some good for dialysis and not for basic science research. It’s a pretty one-sided presentation I’m giving you, you know.

MH:

You were presidency of the ASCI in 1973 can you tell me about a famous phone call that occurred?

NB:

I wasn’t in my lab in this building, I was home in bed with a flu and a 104 fever. The telephone rang and I answered it and the voice said, “Neil? This is Norm Lavinsky.” Norm Lavinsky is very well known nephrologist and learned, not that day, that was he was the head of the search committee for the president of the ASCI or Young Turks. He said, “Would you consider being president of the Young Turks?” and I said, “Of course I would.” We exchanged some niceties and hung up and I fell back asleep. The next morning, I thought I recollected a telephone conversation but I wasn’t positive. I couldn’t call Norm Lavinski back because to say, “Did you really nominate me to be president?” and I went for six months, without really knowing if I was to be president of the ASCI or not. The major battle during that period had to do with training grants. That was during the Nixon era and Weinberger was then called to the Office of Management and Budgets, OMB, they were both against the continuation training grants, saying that the number of dropout from government supported trainees made the program worthless. I had access to data from the naval academy, from the airforce academy, from Westpoint showing that the number of dropouts was twice what it was from training grant graduates. Weinberger was aware of the speech, as was the New York Times. Weinberger was invited to speak, there were at least five thousand people, these meetings were in Atlantic City then, and he refused. I’ll never forget the New York Times, very, very, fine reporter, science reporter, but he covered a lot of things but he had a copy of the speech and he said, “Now I can’t publish this until this speech is delivered. Call me as the minute you’re finished.” I did and it was published and it came out the same day that ?Erlikson and … were fired. His call back was, “Well we got it on page 15 even though the government fell the same day.” The Times supported editorially very strongly and I think we did win. I don’t think training grants took the hit they were going to and we still have them.

MH:

Tell us about the Atlantic City meetings in the 1960’sand 70’s.

NB:

Well, they really took place on the boardwalk in Atlantic City rather than the meeting halls where the papers were presented. What they consisted of was a flesh market where assistant professors were bought and sold. Two assistant professors for one associate professor and a fellow. Everyone came there; it was the essential meeting place for all academicians in internal medicine related areas.

MH:

Do you think it’s been quite the same since the meetings left Atlantic City?

NB:

No, I think the advances in science have been remarkable, exhilarating, rewarding; not my advances the advances, but I’m afraid that the whole system has been politicized, particularly in the last three years, maybe it was before then. So that political affiliations, political considerations of congressmen and donors and so on now make an impact on the system for defining who gets grants and who doesn’t. It’s not a happy thing to see and I think the healthcare delivery system has changed in an unhappy way, but this is one person’s opinion. And it applies to the United States, as this is an international society. I keep on speaking of what’s going on here without regard to other countries.

MH:

You were chair of the NIH General Medicine Study section in the mid 1960’s. How is the NIH different then from now?

NB:

Well I alluded to the major differences. We never were told what to do with any given grant application. The decision was made by having two members of the study section, there were perhaps twelve or fourteen, review each grant. We reviewed sixty grants three or four times a year and then all of the members would discuss the merits of the application and then we would grade them. We would first approve or disapprove and then grade them, and the cutoff was related to the amount of money we had available. But there was never any consideration given to what political position would state what senator or what member of the house and so on, what was involved, was connected, so in fact I don’t think we would of continued if there was that kind of interference.

MH:

What prompted you to leave Washington University?

NB:

Well, I’ve asked myself that same question. I’ve had a number of opportunities to leave and turned them down. The offer from Einstein was a good one. The faculty was outstanding, its record of accomplishment was outstanding, the students were very, very good, but nevertheless I took an unconscionable long period of time without answer them and I remember so vividly, it was about six months into this thing. I got a call from the head of the search committee saying, “Neil, are you gonna take it or not?” and I said, “I’m leaving for Mexico City in the morning; I have to give a talk there I’ll let you know when I get back.” And he said, “We have to know today.” And so my first wife, who died in the middle of my tour of duty at Einstein of ?pancreas, and I took a walk past Forest Park and past the zoo. She was then was an attorney and she was working in juvenile court and was slated to become a judge and so there was no way I could say, “Yes I want to go.” And we walked in silence and she, after a few minutes, took my hand and said, “Take it.” And I went home and took it. And that’s how it happened.

MH:

What was it like being Chair of Medicine at Albert Einstein College for Medicine?

NB:

Well I had two rules I think characterized the job. One was that no one came to see me when they were happy, and the second was that you never fight the same battle once. That was a tremendous amount of kind of thing that I like the least. With a huge budget I think I had something like three executive secretaries and six regular secretaries, two co-chairmen and vice chairmen, and big political battles about who gets what part of what hospital and who gets how much space and where. None of those things I had really aspired to. I guess I really was not born to be an administrator, but there were many rewards there too, the students, the house staff, fellows, the science, my laboratories went on. I failed to mention Jacque Bruganier among the people who trained here and he came with me to Einstein and we had a very good group and continued to be productive there. So overall I guess I would say it was a good experience except that my wife died halfway through the experience and then it became intolerable and I stayed another two years then left.

MH:

Tell me about never fighting the same battle once.

NB:

Well they were pretty tough guys. They’d been waging war over space for long, long periods and who’s this new guy coming and telling us what to do. This is our space and that is. So a definitive decision remained definitive for a very short time and then negotiations resumed.

MH:

Tell us about years you spent at the University of Miami.

NB:

Well it’s kind of a stopgap. The chairman and the vice chairman were both friends of mine. They’d both been on the faculty over here. I went there to regroup basically. We did have a productive laboratory and I did teaching. I perhaps would have stayed but for the fact I got an offer I couldn’t refuse and left after less than two years.

MH:

You were nominated for the Nobel Prize.

NB:

Well the anonymous nominator sent me anonymously the form and it was for being the father of a new field of renal pathophysiology. I don’t often talk about it because, first and foremost, nothing came of it, but it was nice.

MH:

But you are the father of renal pathophysiology.

NB:

But I guess that’s not the same as some of things that win Nobel prizes there. It was, among other things, not molecular, and only earthshaking to me.

MH:

Tell us about the California years.

NB:

I went there, as a distinguished professor with the intent of developing an international institute of nephrology that would bring together people of different disciplines of whom would eat lunch together in essence and hopefully exchange thoughts and ideas. Not a new concept. And it was a very high priced undertaking. We came close to getting 15million dollars, at the time a lot of money. We had a building and so on, but didn’t quite get there. I was spending too much of my time meeting with very distinguished board and lots and lots of people from show business and other areas, but it was cutting into my intellect activities, what I wanted to do most. I, for better or for worse, took early retirement from UCLA after eight years.

MH:

What were some of the challenges you faced in planning the 1984 Los Angeles International Congress of Nephrology meeting?

NB:

Huge. They range from interpersonal problems, which were major league, while trying to create a program that fairly represented the whole world of nephrology. We had things like arranging buildings and hotels and auditoria, and it essentially took a year, a sleepless year, to put that on. I wouldn’t do it again.

MH:

How did you feel when told you were to receive the John Peter’s award from the ASN?

NB:

Well I was thrilled and I was honored and then I think they didn’t give enough money and the medal was too small. No, it was very, very exciting.

MH:

Tell me about natriuretic hormones.

NB:

Well it used to be believed that the control events regulating sodium excretion were too full. One was changes in GFR and the second, changes in the so called physical factors, pressures around the tubule. Hugh DeWardner was the one who did this work. He suggested that there must be a humoral factor because he could restrict the renal artery of a dog, keep the blood pressure down, give a salt load, connect the dog via a cannula to a second dog; and the second dog had a natriuresis when they gave the salt load. The suggestion was that there was a natriuretic hormone. He went in search of it, a lot of people went in search of it, and we did because the fact that the excretion of sodium per nephron in renal disease can exceed any other by orders of magnitude. Patient on average salt diet with a GFR of 4 or 5 can excrete 25 or 30% of the filtered sodium. As I mentioned earlier, we felt there probably was an undiscovered and probably presumably humoral factor and thought it might well be the same thing that Dr Wardner had speculated about. We started our studies in the late 60’s. The first paper was published in Nature in 1965. If I can just inject one quick anecdote, we had to see if our assay system was uptake of PAH by rabbit kidney cortical slices would be inhibited by volume expanding a mammal. A former associate here, now a deceased, Dr Ravioli arranged with a farmer to let us give four litres of saline intravenously and we got the blood, and the assay turned out beautifully but the cow died and the NIH refused to pay for it, so it was an expensive experiment. But we went on from there to develop techniques of isolation and get increasingly pure material using the urine of uremic patients under the assumption that the end organ sensitivity is increased, which we subsequently proved through injections into the uremic artery of normal and uremic rats. And that production must also be increased in response to a fixed challenge of sodium because if you give an amount of saline equal to ten percent of the ECF volume to a normal versus a uremic rat, the uremic rat excretes it faster than the normal rat. So our model has been the remnant rat, uremic rat. Through the years we’ve published this material in search of this material. We thought we had it about ten years ago, but there was a problem with the molecular weight and synthesis. In the last few months we’ve come, what I think may be, the last mile, but after forty years I’m very cautious. We have isolated and characterized a substance. This is not a protein, by the way, this is not an ?atreitic factor or an brain atreitic peptite. We know its structure, we know its biology, we know its very active. Atreitic not ?caleoretic. Active by mouth. If we’re able to synthesize it in the next two or three weeks I’ll send you an addendum.

MH:

What was your reaction when you learned that the third director of the renal division at Washington University is your third cousin?

NB:

It was a little bit like getting the Peter’s award. First of all I was very proud. Secondly, I wondered about the second director Dr ?Sallo Clar and tried to do a genealogical search on him to see if he was also a member of our family, but he wasn’t but nevertheless I am happy that you’re the director and that we are cousins. What more can I say?

MH:

It’s a dynasty.

NB:

It’s a dynasty, right.

MH:

Of which of your many accomplishments are you most proud?

NB:

The twenty-five years with my beautiful second wife. My family. Scientifically, two things: natriuretic hormones, second, and intact nephron, first. I left out one scientific point and I’ll make that very briefly. It’s called the trade-off hypothesis and what it says is that there must be a price to pay for these adaptations that we talked about. For example in the case of phosphate when parathyroid hormone levels go way up and phosphate excretion per nephron is enhanced, there is a price in terms of bone disease. There may well be a price in terms of some of the other adaptations if they’re humorally mediated. Sodium in addition, for example, in this hormone acts on a membrane receptor, could cause some of the symptoms and signs of advanced ?geremia. that’s just a speculation.

MH:

Tell us more about your family.

NB:

Well, my wife is multitalented. At the present time she is writing a book on the founding fathers and their real estate and material acquisitions, which turns out to be an extraordinarily interesting area. From George Washington and the fact that he had the largest amount land of any of the presidents down to the current debate on Jefferson versus Adams. I’ve learned a great deal from it and am amazed at how much she has learned, how much she knows, and the stack of books she has, many of them written in the 17th and 18th century. I have three biologic daughters and she has one biologic son, we have four children between the two of us. Our son is a musician, lives in New York, has a band. Oldest daughter is married to an attorney; she has a promotion and public relations company, which has accounts with firms such as the Economist magazine and she represented the United Nations for a while. She’s a sweetheart. Her husband is a wonderful guy and great attorney. Second daughter is a professor of law at Temple in Philadelphia, does a lot of teaching of lawyers and law students on trial techniques. Third daughter lives not too far from us in California, Southern California, and she is also a teacher. We had a little doggy but the coyotes caught him about two months ago. That’s the family.

MH:

What are your children’s names?

NB:

Dann, Dusty, never officially changed to Dusty but she’s been known as Dusty for many, many years, Kari, and Suzanne, and Ruthie, of course, is my wife.

MH:

If you had to do it all over again, what would you do differently?

NB:

Nothing. Thank you Mark, very much.

MH:

What advice would you give to someone starting out in biological research today?

NB:

Think very, very carefully. Take a close look at what’s happening to the research establishment in this country and other countries. Take a look at the healthcare delivery system and what’s happened to it. Look at your other possibilities and good luck.

MH:

Dr Bricker is currently Professor of Medicine at the University of California at Riverside and vice president of the Naturon Pharmaceutical Company. He divides his time between teaching and research.