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
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