ISN VIDEO LEGACY PROJECT

DR. ROBERT H. HEPTINSTALL
INTERVIEWED BY GARY S.HILL
JOHNS HOPKINS
BALTIMORE, MARYLAND 1995


GH: Iím Gary Hill and I have been given the privilege of interviewing Dr. Robert H. Heptinstall for the International Society of Nephrologyís Video Legacy Project. I suppose the best way to start, so that the viewers will have a skeleton on which to build, is for you to give us a brief outline of your career.

RH: Well Gary, you must remember that Iím speaking from about a hundred years back! Iíll do it to the best of my recollection. I went to medical school in London. I started medicine just before the War broke out. I graduated in 1943. The course was shortened, of course. And after a six month stint as House Surgeon or, I suppose, Intern in Surgery in American terminology, I went off to the War - I went to the Far East. I was there for about three years, mainly as a Regimental Medical Officer. Then, I got back in that cold winter - January 1947 - and took a three month vacation to recover from my "exertions" in the Army!

And I then decided to start looking for a job. I went up to London. I went to my old hospital, Charing Cross and told them that I did not wish to continue with surgery which I had intended doing originally. They were not very pleased at that. Did not like the idea of my doing pathology. So I went to St. Maryís Hospital in Paddington, where I did my training in pathology and was appointed to the Faculty there. I stayed there until 1954, when I took a yearís leave of absence to come over to Johns Hopkins - it was my first visit here - as a Medical Research Council Fellow, to work with Arnold Rich. In the event, I spent most of my time working with Fred Germuth, as we shall describe later. Then I went back to England. I continued at St. Maryís until 1960, when we decided to come over here permanently.

In 1960 I went as Visiting Professor to Washington University in St. Louis, where Stanley Hartroft was the Chairman of the Department. When Stanley left, I decided that I didnít really wish to stay there and I came back to Hopkins - that was my second trip - when Ivan Bennett was the Director of the Department of Pathology. You remember those days because you were working with me in the lab. They were very happy days between 1962, when I came back and 1966. In 1966, if you remember, Ivan decided that he was going to sit at the right hand of Lyndon Johnson in Washington and he went to the Office of Science and Technology and asked me if I would run the Department while he was away. He said he would be back in two years. Well, the devil never came back and I was appointed Director and Professor on a permanent basis in 1969 and I continued with that until, under the local age rule, I retired - well didnít retire - I was given the grandiose title of Distinguished Service Professor of Pathology. That was in 1988 and that is the title I hold. I still come four or five days a week but of course the days are getting shorter and I canít really say that I do very much that is meaningful. I teach the medical students, I help out with the renal biopsy service and in the afternoon go home to a well deserved rest!

GH: Tell me, what have your research interests been. I know some of these because I was part of them but tell us about the entire spectrum.

RH: Well, I suppose you can divide it up into three main areas: I have always been interested in infections of the kidney and their sequelae. I have been interested in hypertension, particularly as it relates to the kidney and to blood vessels and I have been interested in atherosclerosis. Those are the three main areas that I have worked in.

GH: Tell me how did you get involved in all of this because youíve outlined what you did but we donít have the history involved.

RH: all right. I got into the kidney and hypertension through George Pickering. George Pickering was the Professor of Medicine at St. Maryís. As you know, a very distinguished man in British medicine, well world medicine for that matter. His main specialty being hypertension. Well, Pickering, during the war years, had collected a series of kidneys that had been removed from people for the intended relief of their very severe high blood pressure. What youíve got to remember is that in those days the anti-hypertensive drugs had not really appeared in the profusion that they have now and the treatment of severe hypertension was usually very heroic. It was dorso-lumbar sympathectomies, chopping one and three quarters of the adrenals, and in certain circumstances, if it was felt that a unilateral disease of the kidney was responsible, removal of that kidney, and it would be hope this would alleviate the hypertension. So, Pickering had a series of these kidneys and although I was a very junior man in the Pathology Department, he asked me if I would look at those and that we would write a paper or two on the results of that.

GH: The heroic measures were demanded in those days because the survival of these people was less than a year if they werenít treated.

RH: Oh very much so. People with malignant hypertension - you had to number their days in terms of probably months - six months to a year. Very few survived over a year. That is why these heroic measures were adopted.

So, what happened next was that I was very flattered to be asked that by the great man but then when I began to think about it, I thought, "Well, you donít really know much about this matter." So, I started consulting various books and papers and I found that I wasnít singular in that respect because very few people did know anything about it. Anyhow, I cut a long story short, I looked at those kidneys and Pickering looked at them with me and we wrote two papers - one on the reversibility of malignant hypertension because in three of there patients, whoíd had malignant hypertension, the malignant hypertension was reversed and that was quite an achievement and the paper we wrote as a result of that was probably the first demonstration that malignant hypertension (that was proven histologically because we had material to verify the necrotic vessels) probably was the first case that had been described. The other paper that appeared in the Quarterly Journal of Medicine was just on the general business of the treatment of hypertension.

So, that got me interested in two things. It got me interested in infections of the kidney and it got me interested in hypertension. That covers two of the three areas that I mentioned.

Now, in addition to that, Pickering also, when we had finished that work, introduced me to a young Fellow that he had working in his Department. A young man called Brian Bronte-Stewart. Bronte came from Capetown and he had come to spend a year in Pickeringís lab. Pickering asked me if I would collaborate with Bronte in an experimental study to see whether hypertension accentuated cholesterol-induced atherosclerosis. So Bronte and I worked on that. We had a wonderful time together. We found that, in point of fact, it did accentuate it and that I suppose was the beginning of my life-long interest in atherosclerosis and we might talk about this a little bit later on but that was the introduction.

GH: Have you ever considered the fact that if you hadnít done this work that perhaps the diet in America might be a little different?

RH: Oh I donít know. I can tell you something about the cholesterol story but I was hoping to leave that for later. Yes, I will certainly touch on that.

GH: The aspect of infection - you havenít really laid that out for us. And that of course is where I first met you.

RH: Yes, well the early work I did on infections of the kidney was concerned mainly with finding out reasons why organisms localize in the kidney and the circumstances under which they did it. And then, what was the sequence of events after that. We were also particularly interested in studying from an experimental point of view whether in fact chronic infections - chronic pyelonephritis could generate hypertension and that was quite a lot of the early work and you were involved in a lot of that because you did those very elegant microangiographic studies which disproved one of the ideas put forward for the scarring in chronic pyelonephritis. An idea had been put forward that it was a function of the vascular narrowing. That the vascular narrowing came first, knocked out tubules and caused scars. I had shown that that was not the case with some rather crude angiographic studies but yours were just so beautiful - some of the best that have ever been done and this really laid that "old bogey" to rest - that the scarring is really a function of the destructive inflammatory process and the vascular changes, if they did appear at all, came later.

The other thing we did in pyelonephritis was to try and debunk the prevalent myth that chronic pyelonephritis was by far the commonest cause of chronic renal failure which was very widely believed in the 1950s. This, of course, stemmed from having rather insecure, loose criteria for diagnosing chronic pyelonephritis. So I spent quite a lot of time on that problem but really the main credit for that should be given to John Hodson, and weíll probably talk about "Hoddy", as he was usually called, later on. Hoddy showed (he was a radiologist) that there were certain radiologic criteria that had to fulfilled. On the pathologic side, we showed that in addition there were microscopic changes that were not specific, that had been thought in the past to be specific, that Hodson, being a radiologist, did not have access to.

I think we were successful in cutting chronic pyelonephritis down to size. As you know, its name was changed. It is now known, to certain people, not to me, as reflux nephropathy. If you let reflux nephropathy supersede chronic pyelonephritis, well I suppose chronic pyelonephritis is gone forever. But it hasnít. You know it hasnít.

GH: Itís interesting - I think you were the person responsible for, in a sense, taking a disease which was a sort of repository for huge numbers of individuals and making, what turned out to be, a fairly exclusive club, with rather stringent criteria for membership. Once you did, there was not much left.

RH: Exactly, exactly. But there was something left. I have no doubt that chronic pyelonephritis, particularly in children, is a very very common cause of severe hypertension and of chronic renal failure but it now sort of masquerading under this name, reflux nephropathy.

Now the other things you were also involved in. If we now come to the work on hypertension. You were intimately involved in those. When I came back to Hopkins, I spent most of my time from 1960 to 1962 in St. Louis working on kidney infections but when I got back to Baltimore in 1962, we put more emphasis on the hypertension work although, as we said earlier, we still doing the kidney infections. The main areas in which we worked were studying the juxtaglomerular apparatus - as to what part that played in hypertension, what caused the signal for it to undergo hyperplasia. But probably the most important things we did were on the reaction of arteries and arterioles to hypertension and the joint paper that you and I had together in the American Journal of Pathology showed very clearly that the old idea that the vascular necroses that are found in the arterioles and small arteries were thought a function of the intense vasoconstriction, which I suppose was imagined to strangle them locally and cause them to undergo necrosis. Again, as a result of your very elegant microangiographic studies, we were able to show that the necroses took place in the dilated segments, so the idea was advanced that rather than this constriction causing the necroses, it was the inability of the vessel wall to withstand the distending pressure that was responsible. This of course fitted in beautifully with the work that Geise had done in Copenhagen, where he showed that there was an undue permeability in the dilated segments in hypertension induced, I donít know whether he used angiotensin or some other chemical method, I canít remember. But, anyhow the two things fitted beautifully. Now, not only that, these studies also showed that it was the unrestricted passage of blood, in high blood pressure, into the glomeruli that was responsible for the glomerular changes and you christened this phenomenon that was seen microangiographically as the "sun burst" effect. This showed that the contrast material in the case of this experiment, was getting through in very large amounts and wreaking havoc with the glomerulus. Then you did a study that has received very little recognition but which for my part really clinched that matter and that was when you produced vascular changes and glomerular changes by the forcible injection of saline into the renal artery and the critical part of that experiment was when you then gave the animals some vascular relaxant - I think it was papaverine that you used - and then did the squirting, it accentuated the lesions enormously. This, of course, fully confirmed that here was a dilated segment that was allowing vast amounts of blood under great pressure to get through to the glomeruli and to damage them. As you know, this has now become terribly popular but it is a very pleasant thought to think that we were well to the forefront in that field.

The last area, the atherosclerosis part, as I told you, Bronte-Stewart and I showed that hypertension (this work was done in rabbits and we produced hypertension by chopping out one kidney and putting a silver clip on the sole remaining one - itís the best way of producing hypertension in the rabbit and then feeding them large amounts of cholesterol) did accentuate it. After Bronte had gone, I did various other studies on experimental atherosclerosis and in one of them, I collected together all the data that we had. They had all been treated exactly the same way. What we did, Ken Porter, Harry Barkley - two colleagues at St. Maryís - and I found that there was a beautiful straight line correlation between the amount of atherosclerosis produced and either the level of the blood pressure or the rise in blood pressure from its baseline. But once you got over a certain level in the cholesterol, it bore no relationship to the cholesterol level at all. So, we thought this was a nice bit of work and we sent it off to Circulation Research which we thought was a rather prestigious journal. Anyhow, in very short order, a letter came back saying, "Dear Dr. Heptinstall, I regret that we cannot accept this paper for Circulation Research. There are two main reasons for this. First, it conflicts too much with contemporary thought..." Can you imagine, turning down an article because it conflicted with contemporary thought. What, after all, is the purpose of doing research? And secondly, "the statistical treatment is inappropriate..." Well, the statistics were terribly simple and they were done by a young man called Peter Armitage, who at this very moment is the leading statistician in the United Kingdom. So, so much for this editor, who was a physiologist - I shall not mention his name - and his tame little statistician. And I was so angry that I just tore this letter up. I really wished that Iíd kept it because I would have loved to have had it framed as a sort of a "badge of honor". because it was absolute nonsense to turn a paper down for those reasons.

But anyhow, I abandoned atherosclerosis research when I came over to this country but when Earl Benditt proposed his monoclonal hypothesis - I canít go into the details of that - I decided that it would be something worth taking up. So, we put in and got an RO1 and did quite a lot of very useful studies, confirming first of all what Benditt had shown and extending them somewhat. By that time, I was getting a little bit bogged down with research in the Department and most of the work on that was done by Tom Pearson and Kim Solez.

So, that is really in a nutshell, the experimental work that I have done but [25:00] there are one or two other things that I like to think made significant contributions. One of them was a study on renal biopsies and these were old-fashioned renal biopsies. These were very large wedge-shaped pieces of kidney that had been taken out at the same time as the sympathetic chain was being stripped out. These were from, again, people with very severe hypertension and, we mentioned earlier, this was one of the few treatments available. The surgeon who was doing these things, a man called Dickson Wright, was sufficiently intelligent to realize that the kidney might have some clue as to what was going on and he very wisely did a wedge biopsy on every case that he did. So I had this wonderful series to work with - very similar to the series that Castleman and Smithwick had up in Boston. Ours was no where near as large but I think it was worked on much more diligently. That was because as there were fewer cases, you could spend more time on them. What did come out of that study was that there was a very clear cut off, i.e., those with vascular necroses and malignant hypertensives were in the upper register of pressures. And the other thing it showed very conclusively was that even in the presence of very severe hypertension, you need not have any significant vascular changes. This finally convinced me that in essential hypertension - this is what most of these people had - that the vascular changes were the result of the hypertension rather than the cause which many people including Harry Goldblatt believed in.

Then the second study that I think was an important one was the one that I did with Marc Joekes and we will talk more about Joe, as he was always called later. As a result of doing a large number of renal biopsies, we found that there was such an entity as focal glomerulonephritis. This had only been described previously in patients with subacute bacterial endocarditis. But we found in a wide variety of conditions - Schonlein Henoch purpura, patients with recurrent hematuria (probably many of these were IgA disease, but of course we werenít doing immunohistology in those days, so weíll never know). But anyhow, we put focal glomerulonephritis on the map in an article in the Quarterly Journal of Medicine and then followed it up with a very large number - I think it was 30 odd cases - at a Ciba Symposium that was held in about 1960 or 61. Anyhow, thatís what Iíve spent my time doing.

[28:43]

GH: I might say with regard to the focal glomerulonephritis paper that you were remarkably perspicacious in being able to recognize this lesion. If you had been able to the study with the benefit of immunofluorescence, which hadnít come on the market for another 7 or 8 years, it would have been even more mind boggling. But I think what should be noted is the fact that you recognized the lesions at a time when other people basically did not see and/or did not understand the relationship between the light microscopic view and what was happening in the urine and what was happening in the patient. The Ciba Symposium from that period - was it 1960, 61? [RH - 61 I think] was in effect the landmark symposium on the utilization of renal biopsy and the treatment of renal disease.

RH: Yes. I hope we will have an opportunity to say something about the renal biopsy later but youíre absolutely right in what you said and I, being a pathologist, was very skeptical about these and it was Joe who kept saying, "Well, look. These are focal. Theyíve got to be." So, I finally became convinced. Iíve always been rather slow on the uptake or slow to change my mind from what Iíve made it up to be. In fact. at a meeting once, Ed Kass referred to me as the "President of the Society that Perpetuates the Belief that the Earth is Flat"!

GH: First of all, I would like to disagree with that. I would say that I donít consider you slow on the uptake and one thing that you are absolutely not is you are not slow on the quick reposte! Because, I have been present for some absolutely devastatingly on-the-mark comments that you have made to people over the years that pierced rather large balloons that needed piercing.

RH: Yes. It made me a lot of enemies.

GH: Well I always think that itís gratifying, when you say something to somebody, and you hear, as though youíve put a pin-prick in a balloon, "psssssssss......" And you were very good that way.

GH: The area that most people consider you to be the ultimate master in, however, is the development of pathology of the kidney and although there had been books on renal pathology prior to your book, I think itís absolutely fair to say that your book was the first book on true renal pathology in the modern era. I would be curious to know, how it was you came to decide that this was a book that needed writing? How did you decide to spend the incredible amount of time that you did spend, because, in fact, I saw you spending some of it. You were writing it when I was a student in your lab.

RH: Well Gary, itís very nice of you to say those kind things [36:20] about the book. How did it come about? All right. While I was still in England, back in the 1950s, I had written various parts of books. I wrote, on two occasions, for a very good British series called Recent Advances in Pathology. I wrote on the kidney for that. I also wrote a fairly large section on the kidney for the new British textbook on pathology that was being planned in the late 1950s, edited by George Payling Wright from Guyís and Bill Symmers from Charing Cross and I wrote the kidney section in that. So that coupled with the fact that there was really very little else written; if you go back to 1914 Volhard and Fahr, Die Brightsche Nierenkrankheit was extremely good on what it covered. Then Fahrís contributions in Henke and Lubarsch on the kidney. Again, quite remarkable. But these were in German and most people were no longer able to read a German paper, let alone a book the length of Fahrís - it was over 300 pages, Iím not sure. And anyhow, it was getting a bit out of date you see because there was no renal biopsy contribution to it. There were book available - Elexious T. Bell from Minnesota had a very good book - Arthur Allen had an atlas, Joe McManus had a book which was really mainly extolling the virtues of the PAS stain, but nonetheless had some very good stuff in it. But none of those three was involved in renal biopsies and I thought that this - round about 1961, when I first started thinking about this - was this propitious time to do a book. So I started scratching around, consulting with publishing houses and I decided that I would do a book eventually and that Little, Brown would publish it and that was largely because of the most wonderful man Little, Brown had. Heís still alive. I saw him only about a year ago. Fred Belliveau. Fred persuaded me that Little, Brown should be the publishers and Iím very glad that I went along with them because they did a beautiful job.

Anyhow, that now takes us up to about 1962. This was the time I came back to Hopkins. I couldnít do very much in the first year because, as you know, I was setting up a lab and doing various other things. It wasnít really until 1963 that I started writing and I wrote and wrote and wrote, as you know. It was a terrible intrusion into my familyís life and I will say something more about this later. I had to work every evening because I was working in the lab. You say you saw me writing the book in the day time. It must be one of the very few occasions that I got to write in the day time but it consumed every weekend. Well anyhow, I had the help of John Kissane who I met at Wash. U. - John wrote a chapter on the development of the kidney and developmental defects, and Ken Porter, an old colleague of mine at St. Maryís. Ken wrote on renal transplantation. The book finally came out in 1966 and you probably canít remember as far back as that but it sold for the princely sum $28 if you can imagine that. The current one is about $325! - a tenfold increase in price. Of course it is a little bit bigger but I canít say that it is any better. Anyhow, there it was. That was the first edition. I did the second edition - the first edition, of course, did not too much electron microscopy - and of course it had no immunohistology - but between 1966 and 74, when the second edition came out, there had been quite an explosion in both of those. So we did a second edition and this time I got Bob McCluskey from Boston to do a section on immunologic injury on which he did a beautiful job. So, the second edition came out but I still wrote the great bulk of it. In fact, everything except four chapters. Well then there was a third and fourth edition. For the third edition, I brought some junior people in including yourself, Solez, Jean Olson, and goodness knows who else and we brought out a third edition. Incidentally, itís expanded up to three volumes - the second edition went up to two volumes - this was three. It looked as though each edition was going to correspond to the number of volumes.

Well, anyhow I did a fourth edition with the same people plus one or two more - Tony Risdon came in from England, Fred Silva, Mel Schwartz, Steve Emancipator, various others but even in spite of having all these other people, I still wrote half of the chapter and this edition came out in 1992 by which time I was getting on in years and I felt well this will probably be the last edition. When it came time to consider the fifth edition, I consulted with various people and we came to the conclusion that I was really getting too old because it is so difficult to keep up with things and even though the spirit is willing, the flesh really is not and I donít have the energy that I used to have nor do I have the inclination. Iíve got other things that I want to do. I am much more interested in the Peninsular War. Iíd like really to do some extensive reading on that. So Little, Brown very graciously agreed that in the future the book would be known as "Heptinstallís Pathology of the Kidney" and that I would recruit some junior people to be the editors. I was successful in doing that - Fred Silva, Jean Olson Mel Schwartz and Charles Jennette from North Carolina - those four. And I wanted you to be one of them but because of pressure of work and other problems you couldnít do it. It was a very great disappointment to me that your name is not on the book. [41:26]

Well anyhow, these four are employing great energy. I keep in touch with them.. Itís coming along very nicely. I agreed that I will write a farewell chapter on urinary tract infection. They cut me down to one chapter instead of two that Iíd had and thatís perfectly all right. Itís going to be a larger chapter than the other two and they have been very generous in the number of pages theyíve given me and I look forward to this new edition. I don't know when it will be coming out - two or three years time.

Giving up that book was really a great wrench. It was rather like giving away my own child, I suppose. Not that Iíve ever done that. But there comes a time when you have got to pass the torch or whatever one does pass on.

GH: I think that the manner in which youíre passing on the torch makes a great deal of sense. First of all, I think that although other people may do some of spade work, it will be perfectly apparent to the readers of the fifth edition that you are the guiding force. You may not have corrected every comma in the book and checked every reference, as I can guarantee you did in previous books, but you are still going to be the guiding force. But I should tell the people who are looking at this tape [RH: if anyone!] a little about the greeting that the book received in 1966 when it came out because it tells a lot about you in several different senses.

First of all, the book came out almost exactly at the time of the International Society of Nephrology meeting in Washington and Little, Brown managed to get copies of it to the convention and it was interesting because you were obviously very proud of this. There was no hiding that. Yet, you were very very modest about it when people would come up and compliment you, you would give a sort of a throw-away line, "Oh, itís very nice but...." You were very gracious about it but quietly proud.

That night we went to a banquet at the convention [RH: It was boring] Ah, but you were in fine form. First of all, you had a good deal of wine. Secondly, we were seated at a table with a number of Cubans and after dinner, one of the Cubans came out with an honest to God Cuban cigar. Now, this was 1966 - this was only three years after the Missile Crisis [RH: but the embargo was still on]. I could see your eyes dilate in the darkness. And you said to the man, "Is that a Cuban cigar?" and he said, "Si, senor." And you said, "What a tragedy that relations between Cuba and the U.S. have come to such a pass that you can no longer get a good cigar." And he handed you a cigar and you began smoking it. After about 15 minutes, you turned to him again and said "Senor, what a tragedy it is that relations between Cuba and the U.S. have come to such a sad pass that a man can no longer get a decent cigar." And you ended the evening with about six.

RH: Oh I remember that. Youíre absolutely right. And I even stooped slow low as to persuade other people who were non-smokers to try and get these Cuban cigars. What a good memory you have!

GH: it was a lot of fun. It was quite an occasion for you. It really was. I am sure you enjoyed the cigars in good health!

RH: Oh yes. Iíd like one now but they wonít let us smoke!

GH: Well, it occurs to me that you have been a part of nephrology as we now know it almost from the start. What changes have you seen? What accomplishments have we as nephrologists and nephropathologists made over the last fifty years?

RH: [45:15] I think weíve made very considerable advancements. Letís just try and go back in time. When I started out in the late 1940s, early 1950s, as I mentioned earlier, there were books available and the books made the best of what was available to them. But a book on the pathology of the kidney was entirely dependent on autopsy material because, at that time, the renal biopsy had not appeared. So, of necessity, what you were reading about was end-stage disease and there were all sorts of strange classifications of glomerulonephritis, subacute. Subacute, you remember, was used in two different senses. To some people, subacute meant a condition categorized by the nephrotic syndrome. To others subacute meant a rapidly progressive azotemic course. Subchronic overlapped with subacute. It was a terrible mess. As I mentioned, there was very little written about pyelonephritis then but then of course it all exploded later. So, we were profoundly ignorant. As Joxer Daley said in Juno and the Paycock, [things] " were in a state of chasis..." They really were. [46:56]

GH: In addition to being in a "state of chasis" I would comment that I was amused at something that applies directly here and that was that one of the heads of medicine at Mass General, when discussing pathology and its role in life, said something that absolutely infuriated me. He said "Learning about medicine from pathology is sort of like trying to learn about banking from the bankruptcy court."

RH: Oh no. I can imagine who that was but we wonít mention his name. Isnít that awful.

[47:37} Anyhow, there it was. We knew there was nothing in these books, you see, about the milder diseases, the ones that recovered. So, although we knew a great deal, it was all of an end-stage type and reflected the more serious conditions.

What happened next was that in the early 1950s, the percutaneous needle biopsy was developed. We wonít go into who developed it. It was brought out as a safe procedure by Iversen and Brun in Copenhagen, Nils Alwall in Sweden had employed it. It was a very great contribution and thus gradually spread all over the place. It came to the United States, where you had such great bioptists, if you like, as Alvin Parrish at the DC General, who worked with an old Hopkins man, John Howe. Do you know John Howe? - as a pathologist, Parrish and Howe. And then there was Kark, Muehrcke, Pollack and Pirani, the pathologist in Chicago. Jennings and Earl in Chicago. Must be something about Chicago. George Schreiner down in DC. In Britain, De Wardener and Mike Hutt at St. Thomasís and Joe Joekes, Ken Porter and myself at St. Maryís.

And we saw large amounts of material because, in those days, people would stick a needle in you just as soon as send you a bill! Doffed your cap! So there were a large number of biopsies but of course in the early days, very few were examined by electron microscopy. This was mainly light microscopy and of course you developed very good cutting techniques, using very thing sections. But very little EM and no immunohistology because, as you pointed out, that came along a little later.

So the first few years of the renal biopsy led to the differentiation between the various forms of the nephrotic syndrome. This could be dissected out. Lupus, the various different manifestations of lupus came out. Focal glomerulonephritis, as we mentioned earlier, was discovered. Conditions such as Schonlein Henoch purpura, where usually the patient would die. We were able to see what the lesion was there. And the lesion in recurrent hematuria. These were wonderful days of pathology, of renal medicine, renal pathology - in the 1950s.

Mark Joekes was a wonderful stimulus to this at St. Maryís. He did all the biopsies London was a great place to be in those days because there were many medical centres all within an easy bus or tube ride of one another and there was a splendid forum for presenting your cases, known as the Renal Association.

The Renal Association used to meet once a month, about 7 or 8 times a years at Ciba House. It used to start at about 4 oíclock in the afternoon with tea and then weíd have the scientific session and then there would be sherry to wind things up at end. All of that for the princely sum of one guinea a year! Anyhow, it was a great place to present your work and that was where Joe and I first presented the focal glomerulonephritis. It was received by Clifford Wilson, who was Professor of Medicine at the London Hospital, in a most malignant way. He attacked us savagely and it was all very unpleasant. I donít know precisely why. I think perhaps he felt that it cut across the LS classification that heíd had something to do with developing.

But we got over that and there is a very interesting sequel to it. When we had a Ciba Symposium in 1961, I think I was, at which the results of about 5000 renal biopsies worldwide were presented. It was a very good gathering. Arnold Rich was a wonderful chairman of that and it achieved a great deal by, I think, giving the renal biopsy respectability. Anyhow, there was this wonderful symposium and at this symposium, Joe and I presented the focal glomerulonephritis stuff again but now we had over 30 cases. We were on much stronger ground. We gave a dual presentation. Joe gave the clinical side and I gave the pathology. When I sat down we saw to our horror that the first man on his feet was Clifford Wilson and thought, "Oh my God. Here we go again!" But he didnít. He must have become converted. Must have seen the errors of his ways in the intervening years. He was very gracious and said that this was probably one of the finest contributions that the renal biopsy had made to date. That was the unfolding of the spectrum of focal glomerulonephritis. So honor was satisfied.

[54:06]

GH: Well, there is no gratification better than gratification delayed.

RH: I agree. Then, of course I remember another terrible incident at Ciba House at one of the Renal Association meetings. - the only time in my life I have ever been physically thrown off the podium. An irascible man called McCance, who was the Professor of Experimental Medicine at Cambridge, was presiding and McCance warned me twice that my time was up and then the third time he said, "Thatís enough" and he came up and he got hold of me physically and threw me off the platform. Very humiliating but I deserved it. If youíd known McCance you would have realized that he wasnít a man to trifle with.

[55:07] Letís proceed with the story. We have now seen how the renal biopsy made these initial contributions but then when electron microscopy became more widely used and when immunofluorescence in particular was applied, we really took off and the EM contributed to the discovery of the characteristic basket weave lesion in Alportís syndrome, to dense deposit disease, and numerous others. And of course, immunofluorescence led to the discovery of IgA disease that we talked about briefly earlier, light chain disease and various other things. [56:01]

[58:25] In addition to all those contributions of the renal biopsy, we must not forget what the experimental method has contributed and if you look back over the years, Arnold Rich, of course, was one of the pioneers in this field, followed by Germuth, Dixon, McCluskey, numerous other people, really worked out the immunological aspects of renal disease, so that when these were melded with the biopsy studies, made a great deal of sense and formed a basis for, not only our understanding, but for a reasonable classification too.

So there had been tremendous strides taken over the last 50 years. We know a great deal but there are still enormous gaps in our knowledge. For example, the emphasis has been on glomerular disease and on tubulointerstitial conditions, we are still very ignorant. But I have no doubt that in the fullness of time all these matters will be resolved. [59:52]

GH: It is our earnest hope that it will be. You know, it occurs to me that you havenít always been just a renal pathologist. There was a time, in fact a long time, when you were not just my boss but you were the boss of 200 other people as Department Chairman. Could you tell us a little about what it was like to be on the inside as Department Chairman because I always approached in a deferential fashion. How did it feel to be the big boss?

RH: First of all, Iíd rather be big boss than work under somebody. Let me put it this way - when I first did that job, and let me correct you - at Hopkins, heads of department are Directors - life was much simpler. During the summer, Committees and things stopped and you could get into your lab and do something that you really enjoyed doing. As time went by, it got to be a great drudgery. All these new approaches to delivering medical care, cost containment, NIH grants drying up, people coming and sobbing on your shoulders. It really wasnít very pleasant towards the end of my time and I was really very pleased to be able to step down and I should just hate to be a Departmental Director, Chairman, whatever you like, in 1995. I donít think people enjoy it anymore. I think it was very interesting when they were looking for my replacement. they offered the post to several people, mostly research workers, who turned it down. Good luck to them! They felt that in taking on a job like that, it would take them out of their labs and that was why they went into medicine and itís a thing that I think is happening with greater frequency. Itís very sad because somebody has got to be running the Department. But I think what you have got to do is to appreciate, as you know, running the show at Francis Scott Key, it does make tremendous inroads into your time and takes you away from the things that you are trained to do, the things that you do best and the things that you enjoy doing. So looking back, I obviously could have accomplished considerably more in the research line because I was only doing it with one hand. Sometimes that hand was behind my back. What I always felt was, "No, I could not give up prematurely, and work in somebody elseís department" because there are precious few people that I would like to work under. That I think is the big advantage of being Director of a department. That you are master in your own house and it would be very unpleasant to be a servant in somebody elseís. So does that answer your question satisfactorily?

GH: It seems to me that what youíre saying basically is that as opposed to the time when you took the job, when it was (a) a great honor and (b) a lot of fun to do and now you have to wonder about anybody who is willing to take the job. If theyíre willing, should you let them?!

RH: Thatís right. I often wondered how, Arnold Rich, for example, would have reacted to the duties of a present day director.

GH: Thatís an interesting question. I think Arnold Rich would not have been a happy director in 1995. I think he would have been very competent but not at all happy because it isnít a gentlemanly world that we live in anymore.

RH: Thatís right. Thatís another facet of it. Itís no longer a gentlemanly world that you work in. Just the very nature of the job, the things that youíd have to do, he would have quit.

GH: Yes, I think youíre right. Well, one of the other big boss type things that you did for six or seven years was to be the editors of Laboratory Investigation and that too was a major task and of course you brought to it your abilities as a pathologist. But it requires to me different skills. It requires somebody who knows, not just his field, but who has an appreciation for the basic spectrum of pathology research, in order to know what is appropriate, to get the appropriate people to submit, to get the reviewers.

RH: As you say, I was the editor with John Boitnott, a very able assistant. I couldnít have done without John. We did it for five years and I would not have done it for another six months even because it is a terribly tiring job. Itís rather, I suppose, like being a newspaper editor. Youíve got deadlines to meet, you fret as to whether youíve sufficient articles for a given number. Apart from that it is really a matter of bookkeeping because to do the various tasks that you have mentioned, you use your editorial board and I suppose that is part of the skill in choosing your editorial board, although we didnít really have much choice in that because we inherited an editorial board. We were able to get rid of some of them and to take some new people on. But I think we did a reasonable job on that journal. Nate Kaufmann had been the editor beforehand and Nate had built it up and I think we continued doing that. I think that perhaps it got a little bit too kidney oriented which is only natural but not inordinately so. We then handed over and really we were very glad to get rid of it. I think five years was about the ideal time. You see certain editors hanging on to a journal for far too long and you can see the quality of the journal decreasing. Youíve got to have new blood and I think about five years is the ideal time to be an editor.

GH: Another facet of your career has been the fact that you have always been very active in a variety of professional associations and one of them that comes immediately to mind is the American Society of Nephrology. Tell me a little about that because you must have been practically in your day, the token pathologist on many committees in that organization.

RH: [1:28:07] As you know, the American Society of Nephrology began in the late 1960s and it was predominantly renal physiologists, clinicians, nephrologists, if you like to call them that. Many of whom, of course, grew up in renal physiology. For several years, pathology was very very poorly represented. I think I was the first pathologist to be on the Council. I was the first pathologist to be the President and itís only this year that there is going to be another pathologist, which is a very sad thing. Ramzi Cotran, as you know, is going to be the President for the meeting in San Diego. He thoroughly deserves it. He is a first class fellow but it is really very sad that weíve had to go 23 years before another pathologist took over as President and I really do think that pathologists have made a very great contribution to the advancement of nephrology and I think they are really deserving of better representation.

On the whole, the American Society of Nephrology has been a great success and is I think a truly wonderful society. Its annual meeting is quite spectacular and I give it absolutely full marks - a great organization. [1:09:57]

GH: What about the International of Nephrology?

RH: Well, [1:10:04] Iíve had much less to do with the International Society. I was Vice-President of the International Society. I had hoped to be the President but some reason was found why I couldnít be. Just another of those wonderful examples of academic politics being so sordid because the stakes are so low! I have very largely forgotten about it but in certain moments, when Iím perhaps feeling depressed, I do think back that I would have enjoyed being President of that organization but it was not to be. [1:10:46]

GH: Whether you were the President of the ISN or no, you were the President of the ASN and the ASN and the NKF have both made major awards to you. Can you elucidate on that?

RH: Yes. I was very fortunate that some time back in the 1980s, I was given the David Hume Award of the National Kidney Foundation and I was deeply flattered to receive that and then only two years ago, so the boss and me think, I was given the John Peters Award which I shared with Priscilla Kincaid-Smith, which again, gave me great satisfaction - not just getting the Award but sharing with Priscilla who is a long time friend of mine and it was a wonderful event. Al Michaels was the President that year and various people, Mel Schwartz, Ed Lewis, gave me a very nice dinner. You were present. It was altogether a very happy occasion. Iím very honored to have received those two awards from the NKF on the one hand and the ASN on the other.

GH: First of all, the ASN presentation came equipped with a slide show and I saw you for the first time in your mid to late 20s and realized that you were not person who had lost his hair late in life.

RH: No. I lost my hair very early. I didnít lose it in the modern mode of having my head shaved, like these basketball players! No, I started receding when I was a schoolboy, in fact. I suppose, if you look at it, I really havenít lost very much over the last 20 years but youíre quite right. Iíve always been a balding person.

GH: Let me just say while weíre on that subject, that for me, you do not look appreciably different than you did on the first day I met you in 1961. You didnít have sideburns and I would say that you havenít aged a great deal. But the sideburns were a later addition.

RH: The sideburns came in, you remember, during the roaring 60s when people were growing their hair long and I found that they very satisfactorily hid two moles that Iíve got here so I kept them.

GH: There is a wonderful picture that you may remember of you at the gross table in the early 1970s - the year I was Chief Resident. You are playing a tug-of-war with Sharon Weiss over a piece of autopsy material. You have not really changed a great deal since then.

RH: I know that picture very well. I think Ramzi used it when he made the presentation in Boston. that is very interesting. You were talking of being a departmental director - what is it like? You were giving the impression that you always rather in awe of the head of the department and of course youíre not alone because this is true. And it is a thing you donít realize when you are the head of the department. I remember an incident - it involved you and David Page. The year that you were both the Chief Residents. I was talking to you both one day and I said, "What I donít understand is that at a gross conference I ask these intelligent young people, who are interns and residents, questions and they cannot give me the answers or if they do give an answer, they stutter it out as though they canít speak, as though theyíd never been taught to speak. Why is that? What is wrong with them? Are they no good?" And you said, "What youíve got to realize is that they are all terrified of you! " I just couldnít believe it. But, from what you said earlier, confirmed that.

GH: I would not say that I was ever terrified of you but letís say that I certainly entertained a healthy respect for you.

RH: Yes well respect and terror I think are rather different! You were terrified. I donít know why. I was the kindliest man!

GH: Itís funny but when I ask you about awards and honors, you mentioned the David Hume and the Peters Awards and you did not mention the Award that would be the most important for the pathologists and that the Maud Abbott Lecture because that is in a sense the highest honor that we, as pathologists, can pay to another pathologist. That and the Gold-Headed Cane Award.

RH: Well, I donít know whatís happened to the Gold-Headed Cane. I never won the Gold-Headed Cane. I would be rather embarrassed to use. I wouldnít see any point in having a cane unless you did.

A gave the Maud Abbott Lecture, youíre quite right. We had some fancy title for it that Gary Hoffmann, who is very quick at these things drew up. He took a quotation from Shakespeare: "There is a tide in the lives of all men..." That was the title of the lecture. then I think there was something added on - reflux of the kidney - or something.

GH: Those all tides that go strictly up the ureter.

RH: And of course, they are tides more often in women than men, so it really wasnít all that appropriate.

GH: One of the questions that I think is appropriate to ask in this kind of interview is to tell a little about the people who influenced you because that are, in a very real way, the people who helped to mold you into the person that you are today. Who would you include?

RH: The first person I would include is my wife who has had a very considerable influence on me. And what is good in me comes from her. She has been absolutely wonderful, absolutely selfless, allowed me to go off to meetings, allowed me to spend every evening, every weekend writing this book, doing other things. Whereas she had the job of bringing up the children and there were six of them. This was no mean task. Looking back, I treated her very very badly and I very much regret it. So if I have got to say who has influenced me, Iíve got to include that how I was able to do these things. Iíve got to put her very much, way ahead at the top of the list.

GH: Yes. I would say that she has, in a very real way, made it possible for these accomplishments to occur and I feel the same debt of gratitude to my wife. But the influences in terms of scientific interest and the thrust of your life are the areas in which I was directing my question.

RH: The first job I had when I came back from the Army was with Alexander Fleming. Fleming was very seldom there. He had just won the Nobel Prize. I think he won it in Ď46, and I went to work with him in the spring of Ď47. He was still doing a great deal of travelling. He was very seldom there. The thing that I do remember about him was that I went to him once. I wanted to do an experiment and I wanted a small amount of equipment and needed some money. It was a trivial amount - about 50 pounds. He shook his head and said in his Scottish voice, "Heptinstall, I canít let you have it. We have an equation in this Department: Brains X Equipment is a Constant." So that is the thing I remember mainly from Fleming. He taught me frugality.

GH: Or on the other hand, thatís very flattering. Because it is obvious that the equipment was zero.

Other people?

RH: Well, I learned pathology under a charming old man. I call him an old man, because he always seemed old although I suppose when I first met he was just in his 50s. A man called Wilfrid Newcomb. He was an absolutely superb - what in Britain- used to be called Morbid Anatomist. Nowadays I suppose heíd be a tissue pathologist, a histopathologist. He trained us by throwing us straight in. We were reporting on the surgical specimens the first day we were in the department. Somebody would be looking over your shoulder but he expected any sensible person to know an appendix had got acute inflammation. He taught us pathology absolutely wonderfully. He was very demanding in accuracy. He was a source of tremendous information, a very experienced pathologist. One of these people who never forgets any slide that he has ever seen and if you took him up a tumor that was rather exceptional, he would say, "Oh I remember seeing one of those back in Ď25 or something." He wasnít kidding you. Heíd go to his file and bring it out. Of course he collected everything. I learned an awful lot from the "Newcs" as he was known. I became a reasonably skilled pathologist but the "Newcs" was not at not experimentally inclined and that was the big drawback of that department and that was why I was so lucky in Pickering having picked me up at that very early stage.

GH: And of course, Pickering would have to be in a sense the next logical person.

RH: Yes. Although I wasnít in the same department - he was in the Department of Medicine - I saw a great deal of him and he obviously had a tremendous effect of me. He was the man who introduced me to experimental methods. Whenever we wrote papers, it was very apparent that he wrote that most beautiful English and he continually stressed the fact that you should express yourself in plain, simple Anglo-Saxon words, which of course, I knew beforehand but it did reinforce me. I had very happy recollections of George Pickering. He left St. Maryís before I did. I left in 1960. He left in about 1956 I think, to go as Regis Professor of Medicine at Oxford. I continued working with him until I left to come over here permanently.

There is one incident I do remember with Pickering that is rather like the Fleming business - something that he says - in this case something he wrote - that you never forget. After we had written that paper on the reversibility of malignant hypertension (it was in the Lancet towards the end 1952). The editor of the Lancet ran an editorial in the same issue. In Britain they call it a leading article. Weíll stick to the term "editorial". They had this editorial and the writer of the editorial had been given a copy of the paper beforehand so that he could comment on it. And it was a most scurrilous condemnation of what we had written. The Lancet, of course, came out on a Friday. I had read this going home in the train in evening. I was working in my garden when Ann called out through the French windows that led out into the garden. She said, "Pickeringís on the phone and he doesnít seem best pleased." So I went over to the phone and it was "crackling". You could feel it. He informed that some mischief-making b........... had written this terrible editorial or leading article and that it demanded an immediate reply and could I please get my carcass over to his house as soon as possible. Fortunately, he only lived about 5 or 6 miles away. We used to travel up on the same line every day. So I drove over there and there he was sitting in his kitchen. He was writing. He wrote very fluently. And he had got the reply all written and he just wanted me to fill in one or two technical details that he wasnít very sure of which I did and he said, "All right, if you approve, weíll sent it off." It ended up with a most wonderful sentence. I probably canít quote it exactly. Because we had been taken to task in this editorial because some of our findings didnít fit exactly with what had been found in the rat and we were both well aware that it was Clifford Wilson from the rival school of hypertension, who had written this editorial. It ended up with a sentence - now how did it go? It said, "After all, when human problems are being considered, the evidence from man is entitled to at least a little consideration." I thought that was absolutely wonderful and used that many times when I was reviewing grant down at the NIH because, as you can imagine, grants dealing with human things, we beyond the pale and if you were going to put anthrocine up a ratís rectum that was wonderful but the mere mention of doing anything to do with human material was not received terribly well. I think that summed it up absolutely beautifully.

GH: Well you mentioned earlier, Dr. Joekes. The two of you really sort of put renal biopsy on the map.

RH: Well, we did a lot of them. I donít know if we put it on the map. [1:28:05] Joe was an absolutely wonderful character. His hair used to fly all over the place. He was always rushing around. And he had made a very great reputation for himself at Hammersmith for his work on the conservative treatment of acute renal failure. Well, he left Hammersmith and came to St. Maryís. It must have been about 1953. So I came in touch with Joe straight away because he was such an attractive personality and when Bob Muehrcke came over to England (Muehrcke was the man who used to stick the needles in for Bob Kark in Chicago) in about Ď53-54 to demonstrate this technique. Joe learned the technique and did them thereafter. So Ken Porter and I used to interpret the biopsies and Joe did very very large numbers of them. He taught me a great deal about clinical medicine, because we used to have frequent meetings. He was also a very astute pathologist. I was telling you, he really got hold of this concept of the focal lesion very early on.

Joe and I had some absolutely wonderful times together. He, to me, was one of the best British nephrologists of that period and there were several very good ones. He was also actually one of the founding fathers of the International Society of Nephrology. He was involved in setting up the first meeting and he was also the man who needled Gordon Wolstenholme, who was Head of the Ciba Foundation into putting on a symposium on the renal biopsy and he played a very big part in that. Joe was a tremendous nephrologist. I canít speak too highly of him or speak too kindly of the relations we had.

In fact, I received a nice little note from him only a few months ago on my 75th birthday. He sent a photograph of Joe walking along with his dog. Underneath, "Joekes and associate".

[1:30:58]

GH: Well, the next person Iím going to ask you about I think would not have sent such a photograph and that of course is Dr. Rich.

RH: Well, Dr. Rich, you know, had a wonderful sense of humor but I doubt whether he had much affinity for dogs. I first met Rich when I came over to do a Fellowship with him 1954. He unfortunately was out of town . Wnen I got here, he was in Europe and I met Fred Germuth. It struck me that probably I would be well advised to do some work with Germuth as well as Rich. Well, in the event, it turned out I did most of it with Germuth? But I did a certain amount with Rich and saw enough of Rich to realize what a remarkable person he was. He was not only a first diagnostic pathologist. Only a man with his remarkable powers of observations would have noticed in doing routine autopsies that in what he considered children with lipoid nephrosis that those who were going on into renal failure would have a selective sclerosis for the glomeruli in the juxtamedullary region. Itís just one of the examples of his great powers of observation.

He was also a first class experimentalist. He did a great deal of work, as you know, on renal delayed hypersensitivity in tuberculosis. He did a lot of the early work on hypersensitivity lesions in arterial glomerular disease and thirdly he was just a most inspiring teaching who had a tremendous effect on generations of Johns Hopkins medical students and even the staff too. Oh no, youíve got to put Rich right up there. He was easily the outstanding pathologist of his day and probably one of the best of all time.

But I think youíre right. I donít think he liked animals. He didnít like exercise, which always struck me as being rather paradoxical when you consider, you had to climb about a hundred steps, if you remember, to his house.

GH: I only knew him in his older years, when he was partially and ultimately completely retired. But you have only to look at the pictures of Dr. Rich in our Department. In his first picture in 1919, he is wearing a three piece suit and when he retires in 1959, he has, what could be, the same three piece suit.

RH: It was a sort of light brown herring-bone suit. I remember it very very clearly.

GH: The other thing about Rich that always impressed me as a student, was that we nowadays think of Rich primarily in connection with his work on tuberculosis and hypersensitivity but Rich, at the time I came, in every chapter in Boydís Textbook of Pathology, there would be a reference of some sort, be it the spleen, the adrenal, the kidney, the lung, etc. So he was most remarkable.

RH: Because he believed in autopsies you see. And they got lots in those days. We used to do about 750 a year I think.

GH: Well what about Germuth?

RH: Germuth, again, was one of the brightest men Iíve ever met. Germuth, of course, was a different generation. Germuth was the same age as I was and we both considerably younger than Rich. Germuth had been Richís Chief Resident when he was in his training and then he went off to Washington University, where he did most of his best experimental work. Then he went up to The Brigham for about a year and then came back to Hopkins. Heíd just got back to Hopkins when I came for my Fellowship. We got on absolutely swimmingly.

I spent probably 80-90% of my time working with Fred on various aspects of arterial glomerular disease. We demonstrated - it was actually the first demonstration - of circulating complexes by immunofluorescent methods and we just had a great time and it was one of the greatest tragedies that Fred was not appointed to succeed Rich when Rich retired in 1958.

He reacted very violently to this. He quit academic pathology, you remember and went down to Charlotte, North Carolina to be Head of Pathology at Charlotte Memorial Hospital, where incidentally another great kidney pathologist had also been Head of Pathology. That was Paul Kimmelstiel. Fred said heíd never seen such wonderfully trained technicians in his life, whoíd been trained by Kimmelstiel in the true Germanic way.

To Fredís everlasting credit, he continued to do research. And then he made a comeback to academics. He got the Chair at St. Louis University but it didnít last very long. He then went to a private hospital in St. Louis, where the holy sisters who ran the hospital, were terribly good to him. They gave him research space and funds and to his dying day, because you know he died young, he was still doing absolutely splendid work. The work we did could have been very good but we were working in the wrong dose range. We were trying to produce a form of chronic glomerulonephritis by repeated challenge with both bovine serum albumin and bovine gamma globulin. But the animals were producing so much antibody that they werenít going to develop any lesions. We were just unlucky on that. I cursed Fred later. I said, "Look you were the immunologist here, you should have spotted that we were in the wrong dose range." But it didnít matter. We produced a very interesting granulomatous arteritis.

GH: And of course in the early 70s, Germuth had his own Little, Brown book which was the first real synthesis of immunopathology.

RH: Yes. I should mention that. It was very very good indeed.

GH: Other people that you worked with of course include the famous "Hoddy". Dr. Hodson was a very striking figure for me and he must have been for you since he chopped all your firewood every year.

RH: Oh he didnít do that....He chopped it one year. [1:38:40] I knew Hoddy of course in London. Hoddy had been at St. Maryís but when he came back from the Army, like me he changed hospital and he went to University College Hospital, where eventually he became the Head of Radiology. Hoddy was a very good example of a person who could do research without having research funding. There are very few people who can do that, who say, "I canít possibly do research if I havenít got a grant of $100,000 a year." Hoddy all that original work on tracing out the calyceal outlines of children with chronic infections and did all that on routine material, going through the radiology department. He did it all in the evening. An absolutely stupendous task and so much came of it because Hoddy quite literally revolutionized peopleís concepts of chronic pyelonephritis. He and David Edwards were the first to suggest that reflux was going to play a significant role in this and unfortunately, as we said before, reflux nephropathy has rather supplanted chronic pyelonephritis but Hoddy more than any single person, laid the foundations and built on them for our understanding of renal infections. It was a great privilege for me to be able to give a sort of, not a funeral oration, but a tribute to him at a symposium on urinary tract infections in Gothenburg in Sweden shortly after he died. [1:40:40]

GH: I still use one of his illustrations of the different arrangements of calyces that he drew from his radiologic and dissection work.

RH: He was quite a good artist. And he was the most wonderful raconteur - a wonderful storyteller. In fact, Hoddy could do almost anything he set his mind to.

GH: One of the other greats who we should comment on is Dr. Goldblatt.

RH: I met Goldblatt first when I was over as a Fellow. I had a letter of introduction to him from George Pickering and I went over to Cleveland, where he had just returned. He was originally at Western Reserve in Cleveland. Then he went down to the Cedars of Lebanon in Los Angeles. He didnít like that very much and he came back to Cleveland but instead of coming back to Western Reserve, he went to the Sinai Hospital, where he was Head of Pathology. So, I went over and I met him there and it was a very interesting meeting because during our conversation, suddenly his telephone would ring and heíd say "You can come down with me.. Iíve got a frozen section to read." And here was this distinguished investigators reading frozen sections. He was like Rich, you see, he was a well trained human pathologist. He knew his pathology.

I spent a day with him and it was such a fascinating day. And he said, "Look you must come back. Iíd like to do for you what Bayliss did for me." And I said, "Oh what was that?" Bayliss was a very famous English physiologist. It was Bayliss that showed that the blood vessel responds to increased pressure by contracting down. I suppose they give it some name now.

GH: No, itís still known as the Bayliss Reflex.

RH: Oh is it really? Well anyhow, Harry Goldblatt, as a young man, had gone over to London on a Fellowship and he spent part of his time with Bayliss. He said Bayliss taught him tricks with animals - how to deal with animals. "And Iíll do the same for you" he said. "Youíll come back one day and weíll have a good time together." Well, this didnít happen until I was over at a Henry Ford Symposium and arranged to spend a few weeks in Cleveland. Again, Ann was terribly forbearing about that. She gave me permission to do that. So I spent a few weeks with Harry when he taught me tricks. We did all sorts of things and I had to put these clamps on; how to debark dogs, which really didnít appeal to me a great deal, and numerous other experimental procedures and I had a great time with him. I have a tremendous admiration for Harry Goldblatt because he must just have missed getting a Nobel Prize for two completely unrelated topics: Goldblatt always claimed that the best work he did was not the hypertension work. Or to put it more simply, he said the problem he saw most clearly was his work on the anti-retitic factor because that is what he was doing at the Lister Institute in London on his Beit Fellowship. He got a Beit Fellowship. I think Beit was one of these people like Rhodes, who made a lot of money in South Africa. I may be wrong on that and he endowed Fellowship for people in the British Commonwealth. Harry Goldblatt, although he was American, had been to McGill as a medical student, so he qualified for a Beit Fellowship and he took his at the Lister in London where he worked on the anti-retitic factor. Then he went to work with Bayliss for six months. This was where he learned his tricks. Then he went over to work with Adheim for a year. So Harry was a much travelled man. Then he came back and did all his wonderful work on hypertension again, for which he could quite easily have got a Nobel Prize.

He was like Hoddy, a man of very fixed opinions and I suppose thatís true of all of us who think they are right! And Harry could not accept that in essential hypertension the vascular changes were a consequence of blood pressure. He thought it was some naturally occurring disease that was producing the hypertension. He was another great man and such a humble, such a nice man.

GH: There is a wonderful article about him in a recent textbook of hypertension. Itís called "Goldblatt Revisited" and not only does it discuss his very seminal work, but it shows Goldblatt himself and also his dogs. Thereís a picture of "Flossie". "Flossie" apparently was one of his stars.

RH: I think I know the book you mean. Isnít it Laragh and Brenner?

Let me say something about his dogs. There is so little pathology in Goldblattís work and the reason is that he was so fond of his dogs he could never kill them. One good reason why we perhaps work with rats or rabbits, that you couldnít grow terribly fond of.

GH: Yes. And of course, youíve heard the joke recently that it has been suggested, that rather than rats and rabbits, we should use lawyers, because one is even less fond of them.

RH: Shakespeare knew all about that you know. There is a line, I forget, where it comes in, "Kill all the lawyers..."

GH: Another name that I associated with you because I used to go down on occasion with you to Georgetown for renal biopsy conferences, is Dr. Schreiner.

RH: [1:47:10] Oh yes. Iíve no doubt George will be in this Series and George will be able to speak for himself but I should just like to say that I owe a lot to George because he had this wonderful renal biopsy service that I used to take advantage of. I used to go down there about twice a month, saw the most wonderful material and had great conferences, great discussions with George and Jack Maher, who unhappily, as you know, died a few years ago. they used to do the clinical side and they were absolutely great.

The other thing that I owe to George is that he was the person who gave me the entree to American Nephrology. If I hadnít him, Iíd probably been a sort of unknown name in Baltimore but he introduced me to all these people. He was the person who got me interested in the American Society of Nephrology and I have a great affection for George. Iím very fond of him. Wonderful man. Very similar to Hoddy. Wonderful storyteller, great sense of humor. [1:48:21]

GH: As a matter of fact, for a few years when it first started, the American Society of Nephrology basically worked out of his office.

RH: It did, entirely, on a shoestring.

GH: We have talked about all of these people but many of the people that weíve discussed, e.g., Goldblatt, Hoddy and Schreiner, were not pathologists. Since youíve lived through, as it were, the history of nephrology in the US, tell us about some of the people who have been actual nephropathologists. One name that comes immediately to mind because he once came to your lab when I was a student is Paul Kimmelstiel.

RH: Yes. You have a very very good memory. Kimmelstiel was rather like Newcome - a pathologist of the old school, well versed in human pathology. I donít think he did any experimental work but on the other hand, he made the most tremendous contributions by observing problems in man.

Kimmelstiel came over from Europe. He went to Boston and he did work in Boston on diabetes, the so-called Kimmelstiel-Wilson lesions. Wilson incidentally, is the Wilson who berated us at the meeting. He also worked on infections of the kidney and I differed with him on his interpretation of chronic pyelonephritis. He was much more lenient in its diagnosis than I was.

Kimmelstiel had a very great influence on American pathology. I always got on with him very well. Yes, Kimmelstiel - weíll give him full marks because of his using human material.

GH: Two of the standard in field when I was growing up in addition to yourself were Drs. Churg and Pirani.

RH: I knew, and still know, them very well. They are still both alive. [1:51:15] Jack Churg is now in his 80s and is just as spry as ever heís been. Again, Jack was no great experimentalist but made some wonderful studies in human material and as you were saying, Jack was just not confined to the kidney. Jack worked on the lung, he worked on blood vessels. An absolutely top class electron microscopist and Iíd say the chief thing that I like about Jack Churg is that he is just probably the kindest man Iíve met. He is the kindest and gentlest man. He would do anything for you. If you wanted a slide of a rare condition to show at a meeting or something, he would be sure to have it and Jack, God bless him, is an absolutely first class fellow and is doing very well. At least he was the last time I spoke with him. [1:52:20]

GH: I saw him just a few weeks ago and he was lecturing. He gave a super lecture and you are exactly right. He is one of the people of whom it can truly be said that he never stepped on a single back on his way up.

RH: Absolutely. Absolutely.

Now you asked about Pirani. [1:52:45] Conrad Pirani, again I have known for years and years. ( I first met Conrad when I was over on my Fellowship because I visited in Chicago and that was where Conrad came from.) He made his great reputation as the Pathologist to the Renal Biopsy Group headed by Kark? Conrad was the man who kept them honest and did all the pathology and he made great contributions.

Another thing that Conrad did that is in very widespread use now is he was perhaps the first to exploit the semiquantitation of tissue sections. This has been of tremendous help to us. A great man. [1:53:53]

GH: I remember when I was young, you waited every year because every year there would be a classic article in Medicine from the Chicago Group. One year one diabetes, next year on lupus, next year on subacute bacterial endocarditis. It was always superb.

I canít close though without asking you about my all time favorite and thatís Madame Habib, who has almost single handedly for France what all you were for the US and United Kingdom.

RH: [1:54:30] Yes. A femme formidable! Iíve know Renée for many many years and she WAS French Renal Pathology. In fact, you could probably put her as Europeís Chief Renal Pathologist. Renée was an incredible woman, the only word I can use to describe her; she had tremendous energies, tremendous powers of observation, being able to put things together; a great trainer of people. Just look at the flock of young people who came out of her Department. Renée has made a lot of contributions. I first knew her years and years ago, when she came over to spend a year with Martin Bodian at Great Ormond Street and that was really before she got into the kidney. My word, she did so well. [1:55:30]

GH: Yes, and has made the definitive contribution in so many areas. For example, many things she wrote about first. She really was the first person who analyzed large numbers of focal sclerosis but she turns out to be the only person really to have written about oligomeganephronia. It should be called Habibís disease. Sheís fantastic.

I canít tell you how much Iíve enjoyed this conversation. I had anticipated that we would sit here in some sort of wooden fashion and talk about old times, but in fact its been sensational. I have very much enjoyed it and I hope the audience does too.

RH: Thank you very much, Gary, for treating me so kindly.

GH: The pleasure was mine.

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