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This oral history is one in a series of interviews conducted by the Columbia University Oral History Research Office in the late 1980s to early 1990s documenting the history of ASH and the development of the profession of hematology in the United States. Columbia University holds the copyright to this oral history, and anyone interested in quoting this transcript must first contact the University for permission.

ASH provides the following oral history for historical purposes. The opinions expressed by the interviewees are not necessarily those of ASH, nor does ASH endorse or make claim as to the accuracy of any of the information included here. This oral history also is not intended as medical advice; you should always seek advice from a qualified health provider for your individual medical needs.

The following oral history memoir is the result of two tape-recorded interviews with Dr. Ralph Wallerstein, conducted by Keith Wailoo on November 13 and 14, 1990, in San Francisco, California. Dr. Wallerstein has reviewed the transcript and made minor corrections and emendations (both in 1990 and again in 2007). The reader is asked to bear in mind that the following oral history is a verbatim transcript of spoken, rather than written, prose.

November 13, 1990

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?

[TAPE RECORDER TURNED OFF]

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.

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