ASH Oral History: Ralph Wallerstein

Q: Today's date is November 13 and this is the first part of an interview with Dr. Ralph Wallerstein at the Children's Hospital in San Francisco. I was wondering if we could start by talking a little bit about your early childhood and early educational experiences, how that might have influenced your getting into the field of hematology and medicine in general?

Wallerstein: I'm not sure that my early childhood influenced hematology. I'll tell you briefly what it's all about. I grew up in Germany and lived there until I was fifteen. As far as education is concerned, I considered myself a victim of the Montessori system, because I never learned to write and that's still one of my big problems in communicating. [Laughs] My handwriting has been worse than the average physician and I once was given the award of the worst handwriting of any physician on the staff of five hundred here at Children's Hospital. But as much as I enjoyed the Montessori system, which gave me a certain amount of free-wheeling and free-thinking, which may have been of benefit to me, I think I lack some of the traditional disciplines including handwriting, and possibly even study habits, that have haunted me, particularly when I compare myself to my much better organized wife. But I don't think hematology came in that early.

After we left Germany in 1938, my father settled here in San Francisco and started practicing internal medicine. I went through high school here and I, and to the best of my knowledge, in my one year I had of high school here, hematology was not something to which I had any--I had no knowledge of it to start with and high school was relatively uneventful.

Then I went to the University of California in Berkeley for three years, at which time I entered medical school. But those were the war years and this accelerated system enabled me to graduate from college in '43 and have my M.D., also from the UCSF, two years later, a usual event of those years.

But again I don't think there was any hematology there. The only guess I could make--I've had a lifelong interest in art and the way hematology first presented itself to me was under the microscope and fine distinctions of morphological considerations. There is a certain parallel in art. You have to concern yourself with line, color, structure and fine differences. I went to the museum many times when I was young in Germany and this has continued to be a major interest of mine, particularly modern art now. But if there is any early link between my interest in hematology, it's that. My hematology started under the microscope, viewing things that looked like they were interesting and fun. That is my initial entry into it.

Let me just go on with the rest of my education. After entering medical school--I went through medical school here in San Francisco pretty uneventfully and, again, hematology was not something--it didn't really start until my internship, when during patient care I looked at blood films. One of my residents, Dr. Frank Gardner, may have been somewhat influential in getting me interested in that. He was interested. I was interested. We looked at blood films together and discussed them, and I think that's probably when it started.

Q: What sorts of discussions did you have with him?

Wallerstein: Morphology. My entry into hematology was strictly morphology. Microscope. How cells looked; whether they looked abnormal or normal. If they were abnormal, what they were about, what they were trying to tell us, I always considered--and I still do, for that matter--microscopy an extension of the physical examination. There I see some human tissue, either red cells, white cells, platelets or something else. I see some human tissue under my eyes and it's very similar to a physical examination, albeit on a microscopic level.

So that was really what got me interested in hematology. The field has changed radically since then, but you asked me what entry--that's it. I always had a fascination for color. Still do. All my art collection deals with very colorful things, not so much drawings. I'm interested in photography. This room is surrounded by my own photographs, and they're all color. This thing behind you has nothing to do with me. This is the American Society of Hematology poster from 1969 from Cleveland. It's a spectacular poster, again emphasizing color, without trying to play hematology, just interested in color. That got me into the field.

Q: Did Dr. Gardner consider himself a hematologist?

Wallerstein: No, but he then went on to Boston to Thorndike Laboratory with Dr. [William B.] Castle and I actually followed him. Not so much because of Frank, but he was interested in hematology then and continued his interest, and so did I.

Q: Was it well established that hematology could play an important role in patient management, deciding on therapeutic options at that time?

Wallerstein: No. Hematology offered very few options. There was no treatment for leukemia. Iron deficiency and pernicious anemia could be treated very nicely and ITP could be treated very nicely. But you must understand, all internal medicine in the late forties, early fifties, was diagnostic, contemplative, differential diagnosis. Therapeutic nihilism was a virtue. Along with hematology, this has changed very radically since then. Now the emphasis is certainly much more in doing things and the diagnosis has become relatively easy through the tremendous advances in the imaging and chemistry and we rely much less on the kind of diagnosis an internist makes. My love affair with hematology is no longer shared by residents, and while for the first twenty or twenty-five years my major contribution to teaching at the San Francisco General Hospital was microscopy, the last few years there's been less interest and more emphasis on measurements, surface measurements, surface markers and so on, and this has also coincided with me getting involved in some other things. My tenure as chief teaching hematologist at San Francisco came to an end by mutual agreement. I became so heavily involved with the American College of Physicians and also some waning of this dying to sit down with me at the microscope that was my chief contribution for many years that it just had to run its course. I think if I had pursued it actively, I'd still be there, but I had my own new set of priorities and so did the residents. And it's not only true for San Francisco General Hospital, but at an army hospital, where I was a consultant for almost thirty years, until again the American College of Physicians involvement came along. And as you know, Letterman is closing next July, so even if I had not withdrawn, it would have come to an end.

So times change. I had a wonderful time with my deep involvement with teaching hematology. And even my investigative activities--I did a couple of things in investigative hematology that I'm proud of. One of them had to do with chloramphenicol, and I think I may have been one of the first to note under the microscope that patients who had received chloramphenicol lost most of the nucleated red cells and developed bizarre vaculated very early nucleated red cells, proerythroblasts.

It was quite unique, something I've never seen before, and I recognized--and what made it very interesting was we had a patient who was anemic, we were consulted to see him. I saw these vacuoles and thought for sure this was a patient headed for aplastic anemia from chloramphenicol and lo and behold, once we stopped the chloramphenicol, he made a spontaneous reticulocytosis and eventually returned to normal.

This led us into a whole series of investigations, which were published, and perhaps the best thing I've done in clinical investigation. Also some manipulations of chloramphenicol inhibiting the reticulocyte responses in pernicious anemia, things you wouldn't dream of doing nowadays with informed consent. I shudder that I did all those things, my group and I, but it was a nice piece of clinical investigation. I received a card from Bill Castle, my father figure in American medicine. He said, "A fine piece of clinical investigation." The nicest accolade I've ever had.

But, in retrospect, it was something one couldn't do today, because it involved giving chloramphenicol to patients who didn't need it, to inhibit the reticulocyte response.

Well, anyway, what I was trying to say was I got into this through morphology. I saw something in the microscope and pursued it.

Q: Can you talk a little bit about your early work in the Thorndike. What attracted you there? And your relationship with Dr. Castle.

Wallerstein: I'd finished my residency here in medicine. It was a residence, but--I think I must have been very abrasive at times. I tended to question authority, and my mentors were wise enough to say to me, you're not going to make a chief resident here because you're just too aggressive, but I think you have great talents and I think what would serve you better than being a chief resident would be to go to a major center, like Thorndike, Boston City Hospital, and take a fellowship there. Take some residency there first, then perhaps, if you're fortunate, become a fellow there. I think you need to broaden your education. The fellow who told me that was Dr. Gordon Meklejohn, who then became chairman of the Department of Medicine at the University of Colorado; he has had a very, very great medical career. And I've always thanked him for this any time I see him. I still see him from time to time, even though he's quite ill, and I thank him for pointing me in the right direction, because the trip to Boston changed my life.

Castle was certainly one major, perhaps the major piece, because I'd never seen anybody quite like him, who could look at medicine in such physiologic terms and ask--constantly ask questions about a mechanism. How did this happen? How can this happen? He started me thinking much more in physiologic terms than just the pragmatic clinical terms that I had. I had a very good education at the University of California in clinical medicine, but laboratory medicine and certainly clinical investigation was something I'd no inkling of. When I got to Boston I had a few months as resident on the Harvard service, but then went to the Thorndike Laboratory.

The different way of looking at clinical phenomena--he asking each time what is happening here?

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Q: You were talking about Thorndike, about Castle.

Wallerstein: Yes. Well, anyway, what was new for me was the way his group, his residents, his fellows looked at medical phenomena. How is this happening, why is this happening, what's the mechanism? And pursuing problems one step at a time in a very disciplined, highly intelligent fashion. Of course, primarily he set the tone, but we were surrounded by excellent people. John [W.] Harris was my immediate predecessor, eventually became president of the American Society of Hematology after me; he had a great influence on me. Bob [Robert F.] Schilling, whose job I actually took-- Bob left for the University of Wisconsin and I inherited his mantle.

But this group of people--Jane Desforges was there, who also became president of the American Society of Hematology. So it was a marvelous group.

And I'd never been exposed to anything quite like this in San Francisco. Since those days, the medicine in San Francisco has become entirely different. We did not have a good medical school in the forties and the fifties. It wasn't really until, first, Izzy [Isadore] Edelman and then Holly [Smith] came that this really became a major center, but during my medical school and residency days this was strictly a clinical place. Good enough at that, but with some really mediocre people posing as teachers.

So I didn't really have exposure to a truly academic environment till I got to Boston and that was the best part of it. And Bill Castle, of course, was the epitome of this, the questions he would ask and think of in these conferences we had, the questions he would ask of me. We wrote out the draft of a paper and the way he'd go over it, take it apart in a very gentle fashion, those were unforgettable experiences. Especially the insights he had into--not just clinical phenomena, but anything that went on around us. So he's perhaps the most intelligent human being I've ever met.

And at the same time he had this ability to be so keenly interested in what you were doing, fantastic memory for things that were said. Just a very nice man, who brought out the best in all of us, being very self-effacing. The only problem was, if you had a good idea when you were anywhere in that Thorndike empire, you never quite knew whether it was your own idea or something that Bill had said that you had metabolized, incorporated, and so on. That was a small hazard.

Q: How large a group was it?

Wallerstein: I'm guessing now. We may have been about eight or ten fellows all together. Not just hematology. Hematology was three fellows. Three fellows and--another important person was Geneva Daland, who was the head technician and had been there for a hundred years. I think she's still alive and she's taught generations of people about morphology.

And as I've indicated before, this always meant a lot to me, but it really sharpened under her tutelage. But it was three fellows in hematology, two fellows in coagulation, two or three in liver disease with Charlie Davidson. There were people in infectious disease and the heart station, and a few others. I think we were about eight or ten.

Q: And were there certain problems that the group was oriented toward?

Wallerstein: Well, no, we did not work as a unit. I mean, each worked in their own specialty. Even hematology, certainly we identified problems. My job was to work on the intrinsic factor, and my assigned task was something that was too horrible to contemplate nowadays in the time of informed consent. I had to give intravenous--I had to give gastric juice, neutralized to be sure and filtered intravenously. I have to laugh. Nobody ever asked if it was okay. We had no trouble, but some people got sick. But there was no human experimentation committee and the patients certainly were compliant.

We also didn't have DRG's, and a fellow with hemophilia who had been hospitalized for several years, Russell White was his name. So it was another era.

Q: You produced some work there with Dr. Castle? Writing?

Wallerstein: Yes. It was not earthshaking. It was part of a piece on the role of intrinsic factor of pernicious anemia. We basically showed that intrinsic factor, when given parenterally, played no role in Vitamin B-12 absorption. This was quite predictable, but a piece that had to be put in there to complete the unit. It was a minor piece, but a piece of investigation that had to be done. Illustration of the care that went into building a whole edifice.

I wrote a paper with Geneva Daland on subacute bacterial endocarditis, about histiocytes appearing in the peripheral blood, the ear lobe.

I can't remember whether we did anything else that was published or presented--but I had an abstract at Atlantic City on Vitamin C. I left Vitamin C then, but years later in San Francisco became interested in scurvy, and that may have had its beginnings right there.

Q: You mentioned that you particularly did come from a very clinical background, and this was one of your first experiences with this sort of research program. Was that true also of the other fellows?

Wallerstein: I don't think so. I think certainly John Harris and Bob Schilling had much more of a science orientation than I did. But Bob certainly had a very natural inquiry into the puzzles of nature. I've spent a lot of time with him over the years, a lot of it in Madison. He's just interested in all natural things. Much more so than I am. And I think he just carried this into this surrounding with him. I may have been a bit out of the ordinary there for them. I had probably more clinical training, but considerably less science training and awareness. I'm thinking of the other fellows. I think that's true. I had much less science training, awareness skills than the others. Possibly more clinical skills.

Q: Do you think that your colleagues, your mentors here were right when they said that for an aggressive person like yourself this might have been a good arena in which to practice?

Wallerstein: They were more than right. They were right for two reasons. One of them that I had to work on myself, and the other one, whether they realized it or not, this was a small pond here in San Francisco. It's hard to believe, when you look around here at the grandeur of the university, that this was a crummy department of medicine, and I had never really, with two or three really great exceptions, good clinical teachers, had not been exposed to much in the way of strength in medicine as a science. This may have been part of the reason. It wasn't all personality problems. It was, I think in part, that they wanted me to see the greater real world. They were absolutely right. Absolutely. If I had become a chief resident here, when I got into practice, I would have stayed on LMD and no more. That's where I would have spent my life. I think.

Q: How long were you involved in it?

Wallerstein: Two years.

Q: Was your role completely different the second year than the first?

Wallerstein: Well, yes, the first year was sort of a learning year and the second year I had learned some things. I depended less on others to do what had to be done. Took some initiatives. Oh, yes, the second year was a much more meaningful year.

Q: You were just mentioning informed consent and I was wondering, just to go off on a tangent, when that became a very central consideration?

Wallerstein: Well, the work with intrinsic factor happened in the fifties and I think we wrote our paper on chloramphenicol in the sixties. So it must have been the middle, late sixties, but I'm guessing right now. The data should be freely available, but the last few generations of fellows on our staff can't imagine that things were different. No, I think it's been around now for probably twenty years.

Q: So then after your experience in Boston, you came back here to San Francisco?

Wallerstein: Correct. And I did two things. I started in practice with my father doing general internal medicine. My father and I were very good friends and we practiced together for fifteen years. I think, in retrospect, there may have been some subtle--perhaps not so subtle--pressure to get started in practice and not pursue this academic career. But I always had a foot in both camps. I spent a lot of time in medicine, academic medicine, but also I have been very firmly planted in practice. And the things that drew me to practice were certainly my father's need to have assistance. It may have been also the realization that as far as a major contribution to scientific medicine was concerned, I didn't have that kind of talent. I did well in teaching, I was a popular teacher, and had a few nice clinical investigative pieces to my credit. But I was really quite honest with myself--I didn't think I had the knack or the discipline to produce something that was important enough to justify a career in academic medicine. I've never quite sorted it out. All this was revisited when my son went through exactly the same career. He went to MIT undergraduate. He went to UCSF medical school, did his residency at the Brigham, and suddenly had enough of being a student and went for two years--

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Q: You were talking about having come back to your--going into practice with your father.

Wallerstein: Oh, yes. Oh, I was saying about my son--my son moving to full-time practice. I'm trying to explain to you that this uncertainty, where you belong, I transmitted inadvertently to my next generation.

So he went into full-time general internal medicine practice and was phenomenally successful, but decided he'd had enough. So he went to--had two years in oncology at UCSF, took his boards and then he decided to join me in practice, which was wonderful. Perhaps the best time in my career. But then he decided this practice bit just was too boring and he went into academic medicine in Houston.

So it was the same problem that I had, He solved it in a different way. Anyway--

Q: Which years were those that you were practicing with your father?

Wallerstein: From '52 to '68.

Q: I gather he had a fairly well developed private practice?

Wallerstein: Yes. His was all in general internal medicine, and I did primarily in hematology, with perhaps about a third in general internal medicine.

I had to make a very difficult decision--during my residency here at the General Hospital, I was really very deeply into internal medicine. I wasn't a whiz, but I was a good clinician, knew everything, just like residents do. When I came back here I had to make a deliberate choice, and I decided for academic purposes I'm going to abandon all this and concentrate on hematology. I was going to tell you about my practice. The other major half, when I came back here for my activity, was the hematology in San Francisco General Hospital. This was all hematology and I deliberately decided I wasn't going to make rounds any more in general internal medicine.

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Wallerstein: Yes, the other major activity was hematology in San Francisco General Hospital and I had to create this department. We didn't have a laboratory. I created a tiny little laboratory in hematology. Got a technician. And just started seeing patients. I was greatly helped at that time by Dr. Paul Aggeler, the other major influence in my life, who had been one of the few shining lights of the university. As a matter of fact, he was one of the very few who epitomized medicine as a science when I was a resident. My contact with him as a resident was minor, but when I returned it became major, major, major. He and I developed a training grant together and we had fellows for a good many years. But he was the same mold as my Boston friends; true, full-blood clinic investigator. And while he was around I was much more attuned to clinical investigation.

So we developed the laboratory at the County [Hospital] and it was mostly dealing with patients, consulting on them. Eventually we gathered some data. We wrote up some and made slides for teaching from others.

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Q: You were describing your early work with Dr. Aggeler. Where was he from?

Wallerstein: He was from here.

Q: And his training?

Wallerstein: He trained here. Yes.

Q: Had he ever gone elsewhere for specialty training, do you know?

Wallerstein: No, he had very little formal training by modern standards, but he had the kind of a mind that--he'd always done clinical investigation. He was primarily known for his work in hemophilia--he was a coagulationist, he discovered Factor IX. He opened the whole field of hemophilia and it really was a major, major contribution. He was really one of the great men in American hematology. I'm sure Dr. [Oscar] Ratnoff spoke of him.

Anyway, he and I worked together and this was a wonderful association at San Francisco General. We trained residents, we trained fellows, to some extent students. I did two or three hematology lectures in the second year at the University of California, usually on various forms of anemia. It was a marvelous time. It was very good.

Q: Did you head the group in hematology?

Wallerstein: Yes. I became director of the blood bank there, a job I held for about twenty years. That helped me with support, to devote that much time, almost half-time, to non-practice related activities. Eventually this became a much bigger department and eventually had to be turned over to full-time people. But it was until about three years ago, this was a major involvement for me.

Q: When you say full-time people, you mean people who are entirely laboratory oriented?

Wallerstein: No, I meant full-time university time people. I mean, my major source of income and therefore my major activity was the practice, which was largely hematology at that time.

Q: What sorts of patients did you see?

Wallerstein: Anemia, leukemia, lymphoma, polycythemia. I became particularly interested in polycythemia, and polycythemia really has been my major effort in hematology and perhaps the area I know the best. I became part of the polycythemia vera study group with Dr. Wasserman, another former president, and this in its heyday was a really important activity. I answered some questions, and while I was interested in polycythemia anyway, this heightened it. My father died of polycythemia. My uncle died of polycythemia, or with polycythemia. It's not why I became interested in it. It's not why I became interested in hematology. I discovered my father had polycythemia when I returned to San Francisco after my fellowship, and I treated him. He didn't want anybody else. It's not an ideal setup. But anyway, I suppose it ran in the family and it's a disease that had intrigued him before then. And then with that and the study group, I really became very interested in it and I still have more patients with polycythemia now than I have of any other disease.

Q: Why do you think that is?

Wallerstein: They come to me because I'm known among all the members of this study group, when somebody moves to this area, they have them see me, and my colleagues recognize that I have the most experience, and in a difficult case they run them by me.

Q: Can you describe polycythemia?

Wallerstein: Polycythemia is a bone marrow disease. The marrow produces too many red cells primarily, to some extent white cells and platelets. And initially you have symptoms of too much blood, red in the face, you get tired, sluggish, you have headaches. Complications such as gout, ulcers, kidney stones occur. The disease is very nicely treated by phlebotomy and most patients can get by on phlebotomy for many years. Eventually it becomes a difficult disease. Fibrosis and later they may develop leukemia. The average life span is about thirteen and a half years, but a good many patients go longer. Some don't do as well. And once you have a patient, they stay with you for ten or twenty years. Big controversy--the reason the polycythemia study group was founded was whether radioactive phosphorus, the standard--then standard question was did treatment contribute to an increase in leukemia? The answer was yes, but. The but being that chemotherapy was worse in producing leukemia and phlebotomy alone doesn't always solve the problem.

Anyway, it involved me tremendously and has remained even now when I'm into so many other things, it has been remained the one constant love in my blood life, in my medical life, polycythemia.

Q: When did you first become involved in polycythemia research? Do you remember?

Wallerstein: When the study group was formed. I'm a little hazy on when that was, it may have been '78, but I'm not sure. It was a nationally funded group, representing at least ten and eventually twenty or thirty centers throughout the country, and I represented the University of California area. I think it was '78, but I could be off by a lot.

Q: Moving back, can you describe the circumstances of your work with chloramphenicol? You did a series of papers over a number of years?

Wallerstein: It was just a patient we saw in consultation who was anemic. He was on chloramphenicol. I saw the marrow on it, and I saw a nucleated red cell I'd never seen before and neither had anybody else. It had many vacuoles in its cytoplasm. Eventually presented it and published this with Dr. Parvin Saidi, and we were the first to do that. And that was perhaps the best of everything I've done.

But then the State Legislature got interested in chloramphenicol here in California. One of the legislators had a child develop aplastic anemia and he made tremendous efforts to find out just how dangerous this stuff was. And somehow or other I was put at the head of the commission to look into this. We did a very nice study about chloramphenicol in the state of California. One of my fellows, Carol Kasper, who became famous for her work in hemophilia, sort of spearheaded this effort. She looked at all the aplastic anemias in the state of California and we wrote a paper which is the most widely quoted of my papers, on chloramphenicol, in the JAMA. I had some awfully good experienced professional people with me. Epidemiologists and Carol. It was a good paper and it said, in effect, that chloramphenicol did indeed increase the incidence of aplastic anemia, but not by that much.

Q: What was chloramphenicol used for primarily?

Wallerstein: It's an antibiotic. And it was used for injections.

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Wallerstein: Chloramphenicol, antibiotic. Very effective, because it had no side effects except being fatal every once in a while. An antibiotic, and it was popular because it was free of side effects. It was used for--it was very effective for a very broad spectrum antibiotic. It was used a lot for things that it should not be used for, particularly acne, things like that. But people died with aplastic anemia from time to time.

Well, the risk isn't very great. It's a risk you don't have to take. Eventually chloramphenicol became restricted to typhoid fever, where there's no substitute, and some other infections that cannot be treated otherwise. It was a perfectly good drug. It's not used much any more, at least in the United States. But it got me interested in marrow toxicity and we discovered that chloramphenicol does two unrelated things. Number one, in large enough doses it will depress any marrow, reduce the blood cells. But when you stopped it, everything goes back to normal. That's the normal pharmacologic effect. But every once in a while, one in forty thousand I think, it causes aplastic anemia, which is generally fatal. But these are two different things. One doesn't turn into the other. With some people, there's some enzyme missing that makes them vulnerable.

Well, the chloramphenicol experience, and the fame which came with it, became very important in my subsequent career. I was asked to help in medical legal things that involved marrow toxicity. That's become a not inconsequential part of my daily activities. About five to ten percent of my work now is medical legal. A good deal of it is malpractice. Most of it has to do with marrow toxicity and my job is to set the record straight, usually for the defense, on things that can damage the marrow, all the way from the pharmaceutic agency to environmental agents. So I spend a disproportionate amount of time, although it's no more than ten percent, but it derives from there. People now know me by name. I have a certain notoriety among the lawyers who call me. One of the questions is "What makes you an expert? How did you get into that?" It's from clinical experience. So what was just the chance observation, followed up by a nice clinical study with very good help, blossomed into a not inconsequential activity.

Q: As a personal, private consulting physician, do you also deal with medical legal questions within the institution?

Wallerstein: No. They have a lawyer here. No, all I do in medical legal work is expert witness.

Q: Can you talk a little bit about the changing approaches to anemia over your career and the role that played?

Wallerstein: Well, it's the measurements that are available that have changed the whole thing. Let me take them one at a time. Iron deficiency anemia is the most common anemia. When I started as a resident, there was no way of diagnosing this, except using such crude measures as red cell indices, and they were crude because they were abnormal only in extreme cases. A lot of patients with iron deficiency anemia have normal indices. The next thing that came along--and something I took advantage of was Clem [Clement A.] Finch's observation that one could look at iron in the marrow and stain it. If you have somebody who's anemic, and there's no iron in the marrow, they're iron deficient. Well, for the first five or ten years you did a lot of marrows on anemic patients to look for iron. We were needed for that as hematologists. But then became available--I don't remember what year--the late '50s--serum iron measurements, they were quite accurate.

Well, once that was available and some of the bugs were out of the system, we had a very simple way of telling if somebody was iron deficient or not, and you don't need a hematologist. And then ferritin came along, which really closed the loop and made the diagnosis in those cases where serum iron was worthless, in hospitalized patients with fever.

So be that as it may, you don't need a hematologist any more to diagnose iron deficiency anemia. You go into the laboratory. To some extent this is true for pernicious anemia. The quickest way to make a diagnosis of pernicious anemia, or megaloblastic anemia, is to look through a microscope, and for that you need a hematologist. Nowadays with B-12-levels and folic acid levels available they don't need a hematologist. They may feel secure to ask one anyway after the diagnosis is made, but everybody and his brother has a B-12 level. I was still at Thorndike when the B-12 levels first became a research tool. John Harris spent an enormous amount of his time setting up a method for measuring it, but it didn't go into the demand, public demand, till later; anyway, that takes care of iron deficiency and pernicious anemia. They don't need a hematologist for it any more.

The other anemias, the hemolytic anemias, always were a small minority, and for those hematologists are needed most of the time, because they're difficult and troublesome, people don't get well.

There's been an enormous amount of clarity in all the anemias. The thalassemia field has been a career for many investigators, like my friend Y. W. Kan, who's president of the Society right now. That's been his major area of interest. But many of the best hematologists in the field right now have been active in thalassemia, so that's become an entirely different field. Paul Aggeler and I wrote a very simplistic paper on thalassemia. I'm embarrassed to look at it, how simplistic this was, knowing how complex this and all the hemoglobinopathies are. All the hemoglobinopathies, from thalassemic to sickle cell anemia and variants have been studied so well, they can be so easily characterized by appropriate laboratory management. So that has changed enormously.

Q: I suppose, that when you started your career, leukemias fell under the rubric of hematology?

Wallerstein: Yes. For one thing, leukemia was a death sentence and that was it. And CLL you didn't treat and CML you treated with myleran. That was all you had to know about leukemia, all the others died. But within the first few years I was here, there were some advances in childhood leukemia, and then everything I know about leukemia, I learned since I was a fellow.

Q: Thank you.

END OF SESSION #1

November 14, 1990

Q: Today's date is November 14. This is the second part of the interview with Dr. Ralph Wallerstein. My name is Keith Wailoo. Yesterday you spoke about your relationship with Dr. [Paul] Aggeler briefly, and I was wondering if you could talk a little bit more about the nature of your collaboration, both personal and private and professional?

Wallerstein: Privately, when I went East he came to me and said it was a great opportunity for me to learn something about clinical investigation, and he hoped that when I returned I would bring some of the acquired expertise to the San Francisco area, where so little of it existed. The collaboration was not so much at the bench, because he was interested in an area I knew little about, coagulation. While I certainly had a chance to review everything he did, and his manuscripts as they came along, I sometimes had a chance to look at them early and discuss some things with him, he was so much of an expert in that area and I was not that that was an unequal contest.

He was quite interested in what I was doing, iron deficiency, but again he felt that this was not his area. But he looked at drafts of my papers and drafts of my discussions and criticized and helped and had some pertinent questions. It was this kind of relationship. We ran by the other person either a working draft or some results and interpretations and got input and questions. It was very, very pleasant.

Then in the training grant that we obtained, we did a fair amount of formal teaching to our fellows and made ourselves available to them for questions and answers. And it was just customary for each of us to describe our medical clinical problems and have the other person have some input. Inevitably, we talked about some administrative concerns. It was pretty much at that level.

The relationship, which was primarily professional, did extend to some extent in our personal lives. We did visit with each other and our families from time to time. But it was mostly professional. Discussed some of the university politics. National medical politics. The future of hematology. So it was a very all-encompassing thing.

Q: And another relationship that I was interested in was the relationship with your father in private practice. I was wondering how much time was devoted to private practice as opposed to hospital work?

Wallerstein: About half. The afternoons we were usually at the office. Mornings were usually at San Francisco General Hospital, at least for many years. Eventually the practice became more demanding.

From my father I learned just the opposite. From my father I learned how to handle and take care of people rather than the diseases, and my life style, dealing with patients, their families, their problems, the kind of demands patients made, the kind of demands patients wanted to have satisfied--over and beyond the technical medical things. Father and I didn't really talk too much about technical medical things. He always assumed that my knowledge was more up-to-date. I felt that his knowledge was more practical, seasoned.

It was a very personal relationship. My father was very much of an extrovert person, unlike me, and things that had worked well for him didn't necessarily work for me. Also I was much more interested in hematology than I was in internal medicine. I think in a general way, the sicker the patient was, the better I liked it, and the less sick the patient was, the better my father liked it. He spent most of his time at the office and I felt much more comfortable in the hospital, where patients were good and sick and needed my technical skills. But I did learn in the office the enormous demands private patients make on physicians.

Seems like a generation ago, more than a generation ago, for now the demands are set and the styles are set so much more by payors than by anybody else. It seems almost nostalgic to talk about patient demands and granting them.

Q: You mean patients' demands in terms of your time and attention?

Wallerstein: Time. Attention.

Q: That's an interesting distinction between dealing with patients as opposed to payors. That is a theme that one sees frequently in modern critiques of medicine, the idea of attention.

Wallerstein: Well, it's almost a paradox. As I got older, I've become very much better at dealing with patients actually. I did quite well with that. But while I was learning all those new personal skills, medicine was marching in a different direction. When I first started studying hematology, but true for general internal medicine, there wasn't much you could do. You could analyze a lot and talk about prognosis. But since I started, there's an enormous amount of things you can do. Chemo is perhaps the epitome of this. Certainly the management of leukemias and lymphomas is an outstanding example. You can cure Hodgkins disease, which was almost a hundred percent fatal when I started.

But with this opportunity to do something for disease and with the relative ease of diagnosis--which I mentioned yesterday, we have so much imaging--diagnosis becomes much less of a task. But with the possibility of doing so much more for patients, more time is spent on these technical aspects and these technical skills are rewarded better by the payor. And for these two reasons, that there's so many things you have to do in a technical fashion and the fact that you don't really get paid for talking to patients, you do less of that. If you're really good at it, you explain very carefully what the implication of the diagnosis is and what you're about to do--I find myself less patient with patients who are not all that sick, who come with minor complaints. I feel like telling them, I have all those leukemia patients to take care of, don't take my valuable time with your minor problems. Patients nostalgically demand that you spend more time with them, but that's unrealistic. You have to do the work.

The work can be measured and your results are available. Your whole practice style, the outcomes are highly visible to payors and if you do something that isn't efficient and effective, you may be in trouble, and I think this will become much more so. Thirty, forty years ago it was much more difficult to measure what a doctor would do, because there wasn't that much he could do. But now what a doctor does is very measurable, the outcome is very measurable, and if you do not perform properly and efficiently, you may become embarrassed by not having patient contracts. It's just accelerating right now. I think, the ability to measure a doctor's profile, pick up an outline, examine further, is becoming much more available. I think in the next two or three or four years those physicians who do not practice intelligent and efficient medicine may find themselves very much embarrassed by what's going to be available to them.

Q: Where is that measurement being made?

Wallerstein: Payors. Payors can run a profile on your practice patterns. They can very easily obtain a measurement of how you approach disease. They can pick up the physician who does an enormous amount of testing at every visit and compare this physician with somebody who's much more efficient. While on a given case this may be difficult to criticize, if a whole pattern emerges, which is very easy for insurance companies to do, then this physician may not be part of this particular payor program.

In this area, in the San Francisco area, where so much of what we do is under some sort of contract, some sort of HMO, what we do is an open book, and I think it's going to be universal. It's going to be more each year. They'll reach other areas. The number of private, private patients, who pay the whole thing out of their own pockets, is vanishing small. They're still there.

There's some physicians can survive by having a highly private practice. But even the private, private practice, once they reach Medicare age, there will be some limitations on what they can do.

So the insurance companies, Medicare, have very easy access to our diagnostic and therapeutic patterns. If you don't measure up, you're in trouble.

Interesting--I was just thinking the other day--I spent so much time being involved in the American Board of Internal Medicine, eventually became chairman of it, but we spent so much time trying to develop a recertification program. We finally have it in place. Now in internal medicine, also pediatrics, certificates are time limited, and after ten years you have to take another examination. I have no quarrel with this. This was a nice little exercise. But the real recertifying agency has got to be the payors, who will not pay you or will not have you part of their panel if you do not measure up to standards. It's a much more effective recertification program than the voluntary ABIM. I'm sorry to say this, having spent so much time and effort on it, but when all is said and done, that's the way it's going to go.

Q: Would you say that in a case of leukemia, for instance, today that we're approaching much more sort of standardized form of therapy?

Wallerstein: I think when you get to the sub-specialties you do. It's very much getting to standardized therapy. If you do it right, most of your patients should be on protocols, some rationally devised protocols. You don't have the freedom to treat patients individually. There's a down side to this. You cannot individualize the patient's needs, desires, fears and anxieties. But on the other hand, and more importantly, by standardizing your treatment, you're more apt to do what works and not take short cuts at the patient's pleasure, that are really not in the patient's best interests. Patients may plead with you to reduce dosages, and while your heart goes out to them, your head should say, don't do that, you follow the protocol and maximize your chance of getting good results. I think the time when hematologists and oncologists made these personal adjustments is vanishing and that's a good thing.

Q: Do you think that the changes that you've pointed to have also changed the nature of clinical research? Remember you mentioned yesterday the sorts of work you would do at the Thorndike Memorial Laboratory?

Wallerstein: Well, research is quite different. Of course the informed consent issue that we mentioned yesterday has changed a great deal. But research is also much more a collaborative effort. You have so many people entering into a research protocol. The thing that I was doing at Thorndike, what we were all doing, of one man doing one job, that's pretty rare, a sort of simple clinical research. It's also an expensive way to do research, not only in terms of instrumentation, but also in the time that you can allot to it. So it's much more difficult today. I'm not sure I answered your question.

Q: I'm not quite sure it was a perfectly formed question. Let me take another track approach to that question. The safeguards, such as informed consent, how do you think they've changed the whole structure of clinical research? Has it influenced the kind of questions that--is it entirely a beneficial sort of development?

Wallerstein: Oh, probably. I think most of us did things that were at least potentially dangerous to patients without really thinking about it all that much. Patients had to be brave without knowing they were brave. It makes it more difficult in many ways, but it's probably the right thing to do. It goes along with the role of physician in society. The physician's not the only decision-maker. You bring others into the process. I think it's quite appropriate for--I'm searching for a word right now--

Q: Individualistic?

Wallerstein: No, it is not individualistic. There's another term I'm searching for right now. It'll come to me in just a second. It's a matter of ethics. Autonomy. The patient's autonomy is an important thing. It makes it more difficult, but you have to think a little bit harder about what you do.

The two things that fight with each other are the paternalism, the traditional paternalism of the doctor, and with the autonomy of the patient. Traditionally paternalism, the doctor made all the decisions about what in his or her mind was the best that went on. And the last couple of decades we've dealt much more with the patient's autonomy. They have to be brought into the decision-making process. They can do what they choose or not choose, with what is being offered to them. Those things are to some extent in conflict, they balance each other. It's probably a good thing in the long run.

Q: Would you say the doctors are much more managers?

Wallerstein: Managers? I'm not sure I understand the question.

Q: I guess what I'm referring to is the emphasis on sort of the rules of patient management, understanding that there are certain standard approaches to dealing with particular types of patients. It seems to me that that has been emphasized.

Wallerstein: I'm still not entirely clear what you're after. Well, doctors will have to present options to patients about therapy. If you want to call this management, so be it. The other management position doctors have--I don't think that's what you asked me, but it's nevertheless an important thing. Most medical encounters are so complicated that when a patient is sick--most medical encounters with a sick patient are so complex that it involves not just one, but multiple physicians, and there the original doctor, the internist perhaps, is a manager. I don't know if you meant it in that sense. There is some management function involved by a primary care physician, when he manages all the other consultants. Up to a point, that's a management function.

The other management function is to present multiple choices, multiple options to patients.

Q: How would you characterize your collaboration with your son in private practice? You mentioned that you seemed to be happier than your dad when the patients were sicker.

Wallerstein: By the time my son came to join me, I was just as happy when people were not terribly sick, and if they were, let him take care of them. This is a generation problem, particularly in his field. The oncology part was thrust upon me.

I started hematology because I kind of liked red cells and anemias. As the years went by, I found myself treating breast cancers, ovarian cancers. I generally wasn't terribly comfortable with it. I don't do it any more. I had no formal training in it. The only excuse one had to do this, that it involved using very similar agents, such as you would use in leukemia, where I had become with ease with using them. But I never really felt completely at ease without formal training. Formal training was not available when I went through my training, because the field didn't exist. But my son, who had very good formal training, a very high personal standard, was very much more at ease, and when I had a difficult--in the last few years, when I had a difficult oncology problem, I introduced my son to the patient and let him take care of it. This worked exceedingly well. The elderly patients, who needed somebody to talk to, or the patients who were referred to me by other physicians, with oncology problems, were--I sensed that neither the doctor nor the patient wanted to be treated, but wanted somebody of authority to say, well, it's okay to give only palliative treatment. Those came to me. And I think it was a fair division.

Now I enjoyed my son's extremely high standards. He would absolutely not compromise. Much less than I ever did. He told it like it is to patients and doctors. Sometimes perhaps to his detriment, but nevertheless he was always right. He's always right. And he is an extraordinarily good student. Any new problem, what he doesn't know, he finds out the information. Not by asking some authority, but by thoroughly studying the problem and the possible solutions from the available literatures. Very learned, very much more scholarly than I ever was. Has written a great deal. And I enjoyed seeing that in him. I couldn't tell if I ever had it to that extent. I sure as hell don't have it any more.

Q: Which I guess brings us to your early involvement with ASH. How did you first-- (?)

Wallerstein: Well, I was just an ordinary member and liked the annual meetings. The first started going primarily to listen to the plenary session of the case presentation. Not case--paper presentations. Simultaneous sessions. And felt that the educational sessions were something I need not attend, because I knew all that stuff.

As years went by, I sort of went the other way. I needed the educational sessions, the simultaneous sessions. I frequently didn't understand what was going on anyway. But I'm talking about a very long time spent. In between there, before I reached the stage I just described, I was really intimately involved in everything. I think my involvement with leadership may have started when I was asked to be the local arrangements chairman in 1971, the year before the San Francisco meeting. I think they asked me because I was more highly visible than other members of the community. By that time I'd reached a certain amount of seniority stage and it was natural they ask me. Paul Aggeler had already died. So I was the senior person here and I had some of those skills. Anyway, people really did a first-rate job on this annual meeting. It was a much smaller society and we could offer things you can't offer right now. But we also did something that we felt should never be done again. We did all the registrations, collected all the money and all this kind of stuff, but perhaps the major contribution I made to the Society was, when, this meeting was finished, I said, no one should ever do that again. And we went out to recruit and hire Charley Slack, who became our office. It was an absolutely wonderful relationship with the superlative job Charley did. His heirs apparently have been less successful, but that's neither here nor there.

One of the first jobs for the Society I had to interview Slack. I went to New Jersey to see his organization and asked a million questions. I finally decided he was our man and I presented these views to the executive committee of the Society. And they bought that. Everybody agreed that we should have outside help. It was sort of the way to go. And in retrospect it was absolutely essential perhaps a year or so later. Nevertheless, I guess they liked what I did, and a year or so later Sam [Samuel I.] Rapaport asked me whether I would be interested in becoming a member of the executive committee, which was about the first time I'd ever been involved in anything of national significance. And I liked that a whole lot. I felt that I could perhaps bring a practitioner's perspective to the discussions. I could involve myself in discussions, and I guess I listened well enough and didn't talk too much. What I had to say was reasonable, that I could sort of feel myself moving up in the Society, the nominating committee, once chairman of the nominating committee. So I gradually sort of moved through the chairs, as it were, and I was perhaps not totally surprised when they asked me to stand for election. Now when this came up--and it's still true for the Society--the key election is that of vice-president, the vice-president in this organization becomes the president-elect. So that's the key election. That's very unlike most societies I know, where to become a vice-president, it's not hello, it's goodbye. But in the American Society of Hematology the vice-president has been the first step of a three-year term, as it were. Not officially, but in practice.

So when they asked me to stand for election, I was delighted, even though the nominating committee, which was Wendell Rosse, told me that this was a real election and the other candidate was Paul Marks, who was and still is a formidable figure in American medicine in general, hematology in particular. And I was very flattered to be put in the same box with Paul. I didn't think that it was deserved and I didn't really count on being elected. But it turned out there were quite a--I had more friends than I thought and perhaps Paul had some people that didn't want to see him elected. Be that as it may, there was a public election at the first, maybe the second business meeting. You sit there when the votes have been counted, there at the ripe old age of--let's see, what was I, fifty-five, six, something like that? You sit there and have to be told in front of everybody else who won the election. It was an interesting, stimulating day, and while I could have survived perfectly well without having been elected, once you get that close, you want to win. And it was an interesting day, having to stand for election, and I was very pleased I was elected. Paul congratulated me. He had much more experience relative to me, but this was not only the first time that I'd been elected, I was the first practitioner the Society had ever elected.

So I was very pleased and I had a very good year as president. I dealt with all sorts of issues and was surrounded by a superb group of other physicians.

Q: What kind of issues?

Wallerstein: Well, for one thing we had to select the papers for the program and there were some policy issues dealing with government and so on. I don't remember some of the details.

Q: Did you do any lobbying?

Wallerstein: Lobbying, I did a fair amount of going to Washington. It's very difficult for somebody who lives on the West Coast. It was sort of a handicap. They would have been better off with somebody who lives in the East, but I was willing to travel.

Q: You mentioned a couple of times the significance of your being a practitioner and I was wondering if you could talk about that. What is the practitioner's perspective on ASH?

Wallerstein: Well, the risk in the national society is always that the only voice that's heard is somebody who's full-time university. For one thing they have a much higher profile, much more visible, much more electable.

END OF SIDE ONE, TAPE TWO; BEGINNING OF SIDE TWO, TAPE TWO:

Wallerstein: Full-time people at universities have a much higher profile. They know each other from appearing in print and in person throughout the United States. They have a much higher profile than practitioners, who don't do this sort of thing ordinarily, so that practitioners are hard to elect.

But that's perhaps not the important thing. The important thing is that the university people may make some decisions that affect training, practice, diagnosis, therapy, testing, that are, in the view of practitioners, impractical, out of step, irrelevant, threatening, or something like that. So while I sort of wouldn't want to have people in practice set the standards, they do have to do a bit of reality testing in some of the edicts that come from academic medicine.

Something else about practitioners. It is more difficult for somebody in practice to participate in national organizations. It's the time element. If you're not home, you still pay the overhead, but you don't make any money, whereas if you're on salary, it doesn't matter all that much. So academicians can always out-meeting the practitioner. But again that's a minor point. The main importance is that the practitioner can say to those who are in academic medicine, I hear what you're saying, but if you translate this into practice, you may run into these difficulties.

Q: Can you give me an example?

Wallerstein: Well, if you ask for too many tests to be done prior to beginning therapy as a standard, you might point out that these things are not acceptable to patients. They're very expensive. They're delaying. I must say these differences are disappearing for two reasons. One is that most people in academic medicine have to do private practice and learn some of the realities. And those of us in practice must follow protocols as I said earlier, that over the years have limited the dangers and expenses and have been very effective medicine. So the differences are becoming somewhat less profound. But twenty years ago--fifteen years ago--when I was so heavily involved, this made a difference. And also what you teach, what needs more emphasis.

Q: From a practitioner's perspective, what should the emphasis be?

Wallerstein: Well, I'm not sure this will resolve it. There's still much of a discrepancy right now. I think when it comes to management of leukemia, it's the same for everybody really. Trainees certainly have to be able to take care of patients. They can't spend all their time on basic research and dealing with hemoglobinopathies and things they never see in practice. So while I don't wish for one second to belittle the importance of understanding medicine fundamentally, one needs practical tools, but I think those problems have disappeared. As I said, most people in academic medicine have to take care of patients. They see what is needed and what isn't needed quite as much. But things have changed.

And there were some practice issues, governmental regulations that had been harmful to people in practice in the late seventies. May not have affected people in academic medicine all that much. We had to make sure that the society nevertheless dealt with those issues of regulations. Laboratory supervision, something of that nature.

Q: Do you remember the particularities of those regulations?

Wallerstein: It had something to do with supervision under the CLIA Bill, of private office laboratories. I don't really remember the details right now. It's coming up again right now. But setting standards that are fairly impossible for small offices to meet, and also not really all that necessary. Those are some of the examples I can think of.

Q: Can you think of any other--before I get to that, has there been a significant change in the nature of the membership of ASH?

Wallerstein: I don't think so. Those figures are available. I don't think so. I think quite a few people in practice, but as I say, the practitioners have become more disciplined on the one hand, having to follow protocols, and the academicians have become more involved in medicine. So the differences have been diluted somewhat. I don't--I also played with the format of the annual meeting. They had for years--they had a Henry Stratton lecture. Henry Stratton was one of the benefactors to the Society when it was quite small, and as a reward for the benefits that we derived from him, which were--something, he gave something for the lecture, not really all that much--he was given a prominent place at the annual meeting and he gave a little talk. And it always bothered the hell out of me, because it seemed to be out of proportion to his tangible contribution. So I engineered having them stopped and we were successful. They gave him an honorary something or other and blocked his way to the microphone. It was one of those carefully engineered things, but never again did he get up to the podium after that. It was a minor triumph.

But my skill as a president was considered sort of administrative, managerial, rather than being pioneering or innovative. But the Society--some of the things that we were doing needed a little straightening out. I think I helped to streamline some of the procedures.

Q: At the time of your presidency, was the journal Blood published by ASH?

Wallerstein: No, I think that came a little later. There were negotiations going on. I know that Paul Marks headed a committee that dealt with Grune and Stratton. He was enormously successful in getting a better contract, but I think they still owned the journal. I'm not quite sure when that--I think this came after my time. I'm quite sure it did. But during my time we managed--not through my doing, but through Paul's doing--to have a very much more favorable contract with the publisher. (Note: Blood became the official journal of ASH in 1976.)

Q: And after your presidency, did you continue to participate in the national executive committee?

Wallerstein: Well, there's a council, which is a sort of noncommittee, only half the people show up, ex-presidents plus a few ad hoc members, I felt it was pretty meaningless. I always felt, when you've served as president of an organization, you ought to get the hell out. Well, it's not difficult to delude yourself that your wise counsel is worth something. The truth is it isn't worth all that much. And also, if you're any good at all, you get involved in something else. When you're the head of the group--the president, the chairman, whatever it is--you give your all and you solve all time conflicts in favor of the organization. When you're through, you don't do this any more. Then you find that you've neglected all sorts of other work that was going on while you were the head of the previous group, and you solve subsequent time conflicts in favor of the new group. That's happened to me. Immediately after my presidency--actually some time during my presidency--I became much more heavily involved than I had been in the American Board of Internal Medicine.

I should have said--I told you when I started ASH in 1971 as the local arrangements chairman, there was one more element to that. In 1970 I'd been asked by the American Board of Internal Medicine to participate in a small group of hematologists, six of us, to create the boards in hematology. There never had been boards in hematology, and in 1970 I was asked, along with five or six other people, to form a test committee to create the first boards in hematology. That really was my first national thing. I think that to some extent may have helped me in my ascendancy, let me put it that way, in the American Society of Hematology. During those years--between '71, when I was the local arrangements chairman, till I was president--I eventually became chairman of the Hematology Section of the American Board of Internal Medicine, and in 1976 I was elected to the parent board. So I was involved in hematology in a very meaningful way. In two different ways. President in the American Society of Hematology and head of the test committee for hematology for the boards. Now then, the moment I finished the presidency of the American Society of Hematology, I went on the executive committee of the American Board of Internal Medicine, which was an enormously time-consuming task. More so actually than the presidency had been. And as you know, eventually I became its chairman in 1981, which I thought, at that time, was enormously time-consuming. It took me some fifty-plus days away from home.

Q: What was your function on the Board of Internal Medicine?

Wallerstein: As chairman of the Board of Internal Medicine? Well, initially I was chairman of hematology only, but when you become chairman of the organization, you are chairman of medicine with all its sub-specialties. You get appointments to the key committees. You become a member of the Test Committee, you write some more examination questions and determine policy of testing and other evaluation. So you deal with all those issues of training. So that was pretty time-consuming.

Q: How long were you involved?

Wallerstein: With the board altogether? Thirteen years. That isn't possible any more. I had two separate appointments. The hematology sequence and then the board sequence. Nowadays the chairman of the sub-specialties, including hematology, would sit on the parent board as a regular member and this would then count towards the maximum six years on the board.

In my case, I finished my entire hematology tenure without sitting on the board, because the chairman of the sub-committee wasn't sitting on the board yet. So I laid them end to end, as it were, but now they overlap to a considerable extent. Be that as it may, I devoted my entire energies, outside of practice, to the American Board of Internal Medicine. There wasn't any time left for the American Society of Hematology.

Q: Were there any major issues that you dealt with during your tenure at the American Board of Internal Medicine or were they many small issues?

Wallerstein: Well, one major issue was not to go forward with computer testing, and somebody had to say, "Enough, it isn't working." And I take credit for doing that, at least being very instrumental in stopping the money losing CBX project, which the board was heavily involved in. That wasn't the CBX--it was the Merritt Project. The CBX fell later. But it was a form of testing. I became chairman of the sub-committee and I finally decided it ain't working, forget it, and it stopped. This was sort of a negative thing.

A positive thing I supported, time limited certification, although it didn't come to a vote at that time.

I supported involvement of the sub-specialty society in some of the board activities, but they were largely managerial things.

Q: And then you subsequently became involved with the American College of Physicians?

Wallerstein: Yes. In 1977 I was asked to stand for Governor of the American College of Physicians. The job description--well, I said, I haven't got time for this. And the people who'd persuaded me to run for office said, it doesn't take any time, it takes a couple of trips to Philadelphia a year. That was a flat lie. But anyway, perhaps I wanted to hear that. Be that as it may, in 1977, I guess--I'm not sure about that--I had to stand for election once more, this time to become governor of northern California. And that led to four years of being governor, including being chairman of the Board of Governors, to the Council of Sub-specialty Societies as their first chairman. And there my contacts with hematology, with the American Society of Hematology, and my feeling for sub-specialties stood me in good stead, because of the effect of meaningful interchange between the professional societies, like the American Society of Hematology and the American College of Physicians, was very nice.

And then to the Board of Regents. That tenure in the college moved me away a little bit from hematology. There were so many other issues to deal with that I had to sacrifice some of my hematology expertise.

Q: Just in terms of time, or were there issues involved?

Wallerstein: The time demand. In order to stay on top of your specialty, you have to give it your all, and I couldn't do that. If you haven't done this for a few years, you lose enough footage to--then when I got into the presidential chairs, as it were, I even had to give up my activities at the San Francisco General Hospital. I told you yesterday what it was. I had such a good time with microscopy, morphology, the residents sort of flocked to our sessions and I enjoyed that. I had to give that up. There simply wasn't enough time. My year as president of ACP I was gone two hundred days and traveled two hundred thousand miles. That certainly interferes with anything else, in that it sort of cost me in a way, my involvement with hematology. I have regrets about it, but you have to make some deliberate choices and I did make this deliberate choice. You don't get asked to be president of the American College of Physicians with sixty thousand members very often. And I enjoyed that. But it took me out of the active participation. Not just in running the Society, but being familiar with the issues, and, to some extent, actually with the expertise in hematology, and I haven't quite recovered that.

And when the college year was over, all of a sudden I found myself with these two hundred extra days on my hands. The immediate past presidency wasn't nearly as involving. I had to decide what I was going to do next. The obvious option was to assume all my previous activities, teaching and practice. While I was still trying to decide what to do, the president of this hospital came to me and said, "You don't want to go back to what you did before. We need your help here in the hospital with the merger of Presbyterian Hospital and Children's Hospital. Would you help us with administration?" And I thought about this for a while and I said to myself, that's something I haven't done yet. I'd done research and then teaching and then practice, then had national involvements. Here's an opportunity to do something non-practice at the local level, which I had ignored for almost twenty years, and deal with health care delivery. Not in a global fashion, but in a city in a specific hospital, requiring some management ability and knowledge that I hadn't acquired previously.

So I felt this to be a new challenge and to some extent it gave me some pangs of conscience, because I moved away from my previous colleagues and involvements. And I feel it very acutely right now. My good friend, Y. W. Kan, is the president right now. He invited me to a black tie dinner in Boston, and there's a dinner in his honor, a presidential reception to which I'm invited, and I can't go to Boston. I just can't. We have the merger here, the oncology center. We have so many issues here right now in regard to some other things, that I simply cannot go this year. And I feel that this is a major non-event in my life, that I cannot go to the annual meeting of the American Society of Hematology, where my very close friend and colleague is presiding. And all sorts of people called me, trying to get together in Boston, and I had to say sheepishly, :I'm not going." I feel I've lost something here. But time moves on. You can only do one thing. If you want to do it well, you'd better be there.

Q: Would you say the same thing about microscopy, morphology, those parts of research?

Wallerstein: Well, I still enjoy--I've given up seeing new patients unless they're hematology, and in hematology I still get a fair number of very interesting problems, and I must say I still enjoy using the microscope, which gives me a quick answer to complicated questions a good part of the time. But I have almost no one to share this joy with. My son is gone. And he wasn't all that interested in morphology anyway. And my young associate, he's sort of interested, but not very. So it's almost like a lost art. It's like quilt-making, I suppose.

Anyway, for my personal enjoyment I'm still very--I love to look at slides of my own patients. New problems. Some years ago a grateful patient of mine gave me a wonderful Leitz microscope with a photography setup. In a good year I take fifty rolls a year of film. I still have exactly the same equipment. I don't think I've taken a roll of film for the last six months. As much as I enjoy it, I don't enjoy it as much as I did before, mostly because the competing other things need my attention, have my attention. A long ways from hematology. Some of the skills I developed in dealing with issues stand me in good stead here in administration, although there's some new things I have to learn. The discipline is the same. I'm trying to learn as much about a problem as I possibly can. Then make a decision and act on it. I do that. Especially if they're hematology problems. But these are a different set of problems.

So I perhaps have moved further away from ASH than any of the people you will interview, but I tried to warn you about his ahead of time, but you said, well, it's just as well, because you get some variety. So that's your problem, not mine. I'm happy doing what I'm doing and I still enjoy what hematology that I do. But if I had to choose right now between getting up and resuming any of my other activities, even at a most favorable level, surrounded by students and residents, I wouldn't want to go back. I feel I've done this, and I do like switching careers. I think switching careers is rejuvenating. Learning new skills is kind of fun. And while I've always admired those of my friends who devoted their whole lives to sitting at microscopes and talking to students, it isn't very interesting to me any more. I think students and residents in general need somewhat younger teachers than I am now. And I felt this the last two years, while they're nicer and nicer and more and more deferential to me, it was not as productive a relationship, and I felt that I was getting just a little bit too old to be taken all that seriously.

Q: On the topic of microscopy, in 1976 you wrote an article in the JAMA on "The Role of the Laboratory in Diagnosis."

Wallerstein: Yes.

Q: Can you tell me why you felt it was important to...?

Wallerstein: This was an invited article. [Lundberg], who was then the head of the--I think he still is--chief editor for the AMA, JAMA. Had read some of my stuff. I'd met him. He may have listened to some of my talks. I'd done a pretty nice set of talks on diagnosis of anemia, which I gave to second-year students and residents on the lecture circuit. It was a talk that I thought was damn good, was very practical, it was from the consumer's point of view rather than from the teacher's point of view. In other words, I tried to deal with problems as they appeared to the bedside clinician rather than the instructor, who can categorize all those things.

And Lundberg must have heard me or talked to somebody who had heard me and asked me to do just that. That was the origin of this article. I put microscopy front and center on this, because I felt this really sort of helps you decide where you are. And I made a list of useful tests and when to use them, categorized anemias, and I felt it was a very useful exercise. I still think it was a nice article. My son has written a similar article since then in the Western Journal of Medicine, which is perhaps much better, much more up-to-date, but when I wrote mine, that was the way to do it.

Also people congratulated me on still being up there with a highly sophisticated--although I had to admit I hadn't written it. My son is Ralph, Jr. That's why the confusion is obvious.

Nevertheless I was pleased with the article. I think it reflected the state of the art at that time and I think it was very user friendly, and there was an enormous request for reprints, which I was very happy about.

Q: When you say consumer's point of view--?

Wallerstein: The doctor. I meant the doctor. I meant the general internist. When faced with anemia, how should he or she think about anemia problems. This was at that time a useful guide. And also paying some attention to having a working concept of medical probabilities that went into it, rather than being all that complete. And I enjoyed writing it and I was pleased with the response to it.

But that was the origin of it and reflected my years in practice. How I saw problems, how I had to explain problems to people who referred patients to me, and to patients.

Q: You mentioned yesterday to me that you really looked at blood microscopy as an extension of the physical examination. Is that a widely held point of view in medicine?

Wallerstein: I don't think so, because there are not a whole lot of doctors who look through a microscope. They haven't got the time. If you don't do it every day, you lose some sharpness. I use the scope virtually every day, even though I'm doing other things now. Because I'm here all day at the hospital. And if I haven't looked through the scope for a couple of weeks, I'm not quite as quick, I'm not quite as firm. No, I think you have to do it all the time, otherwise it doesn't mean much. And I'm afraid that our recent trainees rely more on quantitative non-subjective measurements rather than on microscopy. I wouldn't want to force it on anybody.

Q: Mostly on measurements done elsewhere?

Wallerstein: In the laboratory, yes.

END OF SIDE TWO, TAPE TWO; BEGINNING OF SIDE ONE, TAPE THREE:

Q: I was wondering what sorts of techniques--have the staining techniques changed much?

Wallerstein: Not the basic staining things. The new staining techniques I'm not that much of an expert on.

Q: Just to step back to your early work at the Thorndike Memorial Lab for a moment. Can you talk about the relationship between Thorndike and its role within Boston City Hospital?

Wallerstein: It was a very intimate relationship with the Harvard Service. As you know, there were fellow services at the Boston City and the relationship was pretty much confined to the Harvard Service. Most of the people at the Thorndike, the teachers taught on the wards. Some of them taught general medicine as well as their sub-specialty medicine. We constantly had people rotate for some of their training--some of the residents, I think some of the students--through the Thorndike. It was physically right there. Highly accessible. And highly integrated with the wards.

The research was very clinical really. Some very sophisticated measurements were done. They all dealt with clinical problems. They were not basic research. It was just an intimate arm of the Harvard Medical Service. Castle was a Professor of Medicine at Harvard. So was Dr. Max Finland, Dr. Davis, and everybody else, on the full-time faculty of the university.

Q: That was not true of the entire staff of City Hospital? They weren't all members of the Harvard faculty?

Wallerstein: No. It was mostly Harvard; Boston University, and Tufts were the others. But the people at the Thorndike were all full-time members of the Harvard faculty, at the Boston City Hospital. The Thorndike really was just one building and it was the City Hospital complex.

Q: How was it determined that patients from some other service should be members or should become part of the Thorndike research?

Wallerstein: Dependent on what diseases we were looking for. Patients with certain diseases would be transferred to Thorndike. Believe it or not, we had in-patients with pernicious anemia. My God, that really dates me. In-patients with pernicious anemia. Yes, when somebody had a certain disease that was being studied, then they were simply transferred to the Thorndike. It was sort of--but nowadays it's a metabolic ward. And this really was to have easy access to them.

Q: What sorts of arrangements would be made with those patients?

Wallerstein: Well, the reason they came over was--I think perhaps diet was a major part of this, because they had to be on a special diet. They gave them something to eat that didn't contain this or that. They had to be at Thorndike. So we called some patients from the open wards, but if we wanted to study somebody seriously, if we wanted to treat the pernicious anemia with intravenous gastric juice and I was told it was my job, then we damn well better have them at the Thorndike ward, where we could see them and monitor them very closely. The same was true for the other sub-specialties. I don't quite remember all that much. There were not that many patients that were there, but the ones we studied either had to be followed extremely closely or were on a very special diet, usually missing some key ingredient on purpose.

Q: Well, it's generally thought in the history of medicine that pernicious anemia was effectively treated by liver extract. Why did you still have in-patients with pernicious anemia?

Wallerstein: So we could study something or other on them. That's why I say it was bizarre having in-patients when you come to think of it. No, we looked for patients with pernicious anemia and put them on some sort of protocol that we were doing. We wanted to observe their daily reticulocyte response. For that you need to have--it seems like a different era. I mean, not only DRG's, informed consent, nevertheless this was before those restrictions.

Q: I'm just wondering, how did you convince the patient that it would be in their interest to participate?

Wallerstein: Our patients did what they were told. Also we were very nice to them and they enjoyed our company. Some of them were in Boston City Hospital--as a city hospital, we had a lot of indigents. They were probably better off in the hospital than not. But this may be a paternalistic view. Basically they did as they were told. This is only thirty years ago, forty years ago. Seems hard to believe that those things prevailed then. God! We had a little study group--this was out-patient--where instead of getting Vitamin B-12, they got saline. This was one of Dr. Castle's and we used to see how quickly they'd relapse into pernicious anemia. God! This, of course, was the sort of thing that would be absolutely inconceivable nowadays. Nevertheless, the results were interesting. Some of them didn't relapse for the longest time, over a year. Nowadays, when we treat someone for pernicious anemia, if some of them are a week late for their therapy, they get terribly nervous. They know better, but--anyway, so that was medicine then.

Q: You actually saw patients for a year at a time?

Wallerstein: In the clinic. Yes, I was there two years. So some of the people we'd see twelve to twenty-four times. Then we had an out-patient department. Some even come to the out-patient clinic, where there'd been liver or Vitamin B-12 shots since Minot's days. You know Minot won the Nobel Prize for pernicious anemia.

Q: Is there any other issues that we haven't touched on, that we might have left out, that we have not given a full feature of your career?

Wallerstein: One of the most important things is that I met my wife at Thorndike. Dr. Max Finland always said that Betty was a fringe benefit and should not be counted in evaluating my training at Thorndike, but it was important.

Q: She was...?

Wallerstein: She had graduated from Wellesley and she was thinking of a medical career. In the meantime she decided she wanted to work as a technician. She came to work in our laboratory. This was at the start of my second year and we got married after that year. But that was probably more important than anything else I did at Thorndike.

Q: Were those lots of college graduates working as technicians?

Wallerstein: There were several. John Harris married his technician, and I gather this had been going on for years. She had just graduated from Smith, I'm not quite sure. Any one of the women's colleges. No, this was not unheard of. There were college graduates working there for slave labor wages.

Q: But this was conceivably a route to medical school?

Wallerstein: Yes.

Q: Did many of them go on to medical school?

Wallerstein: I don't think so. This was well before medicine was a major field for women. That didn't come until later. It was still unusual for women to be in medicine. In my class there were about six out of seventy-two.

Q: I was talking to Dr. [Helen] Ranney and interestingly that was also her past. She worked as a technician at Babies Hospital in New York before she went to medical school.

Wallerstein: Some technician! I met at Thorndike many of the people that preceded or followed me as president of the American Society of Hematology. Well, yes, one thing I should mention in hematology, the Aggeler lecture. Did I mention that to you? When Paul died, we established a lectureship in his honor. They went to all his friends and some people in industry. We collected a fair amount of money to make a decent annual stipend and expenses at the University of California, San Francisco General Hospital, where we both worked. And we've had a really prestigious group of people lecture every year. At least half of them either have been or most of them were about to become president of the American Society of Hematology. So when you look at the C.V. of the people you interview, a good many of them have been Aggeler lecturers. For the first ten or fifteen years they all knew Paul personally and could say something about him. At first we restricted the topics to coagulation and knowing Paul. Sam Rapaport was the first speaker. And Ratnoff was an Aggeler lecturer. Lockhard Conley was a lecturer. Don [E. Donnall] Thomas, the only Nobel Prize winner we have in the lecture series. Phil Majerus was a lecturer. A lot of people--Jane Desforges, [Ernest] Beutler. Myself. I was lecturer last year. I was extremely pleased to be asked. Y. W. Kan has been a lecturer. So that is something I'm still involved in, in determining who's going to be a lecturer. I attend the functions that go with this. This has meant a great deal to me, because I'm very grateful to Paul as my mentor and a sort of conscience of the University of California here. This has been a nice way to honor him, this prestigious lectureship. And we all attend it.

That's the main thing I left out, I think.

Q: Well, thank you very much.

Wallerstein: Thank you.

END OF SESSION

©2008 Columbia University

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