ASH Oral History: Clement Finch

Finch: At that time I had little perspective of other schools and perhaps reputation. We thought it was great because the class was 42 students, I believe. We had very intimate relations with our professors. It was our impression that the professors that had been picked by Whipple were many of them outstanding people. On the other hand, we were very self-contained in Rochester. We thought it was traumatic, but a great experience going through the school. I don't think we could pass judgment then. Later on, I could see things, looking back or looking at a course at Rochester after that. I think that we felt that it was characterized by very close and very good community associations. Very inbred, to the extent that perhaps there wasn't as much active science going on. That would be my impression from ten years later.

Finch: I mean that the faculty was inbred. They really weren't looking as much for outsiders as I thought they should, and in later years I think that was particularly true the next 20, 30 years.

Finch: I think that's reasonable.

Finch: That's very hard to say. I think probably in the early years of any school, there's a tendency to take the new graduates and breed them back into the system as faculty. I think perhaps we're doing it to some extent here now at the University of Washington.

Finch: Probably later. I didn't actually have any strong contact with hematology.

Finch: Yes, it was.

Finch: The person who was the head of hematology at Rochester, who went to UCLA as the head of medicine, had a very active program at the time.

So, we're now in Boston. I had actually gone there with the idea that I wanted to be a surgeon. Before I left Rochester, I took a rotation through surgical pathology and felt I had a base for surgery, but I wanted to get a year of internal medicine before I went into surgery. Once in Boston, internal medicine became very exciting, with the faculty that was there, very unusual faculty at the time. Soma Weiss was the professor of medicine at the Brigham, and a number of people under him went to important posts in the country later on. Unfortunately he died, two or three years after I went to the Brigham, of a cerebral aneurysm. I had unusual clinical opportunities because at that time, the Harvard unit went off to war and it stripped the institution--Brigham included--of some of their key people. Those of us left behind were exposed to a lot more direct responsibility than would have been true otherwise. Just before I finished my two or three years of house staff at the Brigham, I got what was called atypical pneumonia. Now it's mycoplasma infection. That was followed by a period of bronchospasm that lasted several weeks. Because of that, I was rejected by the army. I'd been planning to go in the military. Now I had to look around for something to do. I got a fellowship with Dr. Joseph Ross, who was a hematologist at Boston University. At the Brigham, I'd become sort of a mini-hematologist because at that time they didn't have anyone very active in hematology. There was the Nobel Prize winner, [William P.] Murphy, but he had gone into practice and wasn't too active in teaching on the wards and wasn't entirely contemporary in hematology. So, I began doing bone marrow aspirations, which, to my knowledge, hadn't been done before at the Brigham, and other things relating to hematology, but in a very limited way. So, I spent a very good year with Joe in hematology. He included me in studies on blood preservation and took me to meetings at the National Research council in Washington, at which blood preservation was discussed. There was a lot of pressure from the military at that time to develop a better blood preservative, one that could be kept longer since the military use of blood required that. And I did a couple of other studies on my own. One dealing with complements levels in a variety of diseases, another dealing with high-dose aspirin therapy in rheumatic fever. In retrospect, the complement studies were rather interesting, but neither of these was ever published. The next year, George Thorn wanted me to come back as chief resident at the Brigham. One of the things that George did was to set me up with a laboratory at that time so I could do hematologic research. He wanted me to be responsible for the routine hematology at the same time that I was resident. I managed to attract two volunteer Junior League women as technicians. After the residency I stayed on as hematologist at the Brigham and took on the responsibility of running the clinical laboratories in hematology through the hospital, which were not entirely efficient, since there were labs in the outpatient, surgical service and on the medical service, all independently operating. But it did provide me with another technician's help in my research activity.

Finch: For the hematologist, for a long a time, looking at the peripheral blood was very important. Making blood smears. As hematology developed, it became evident that you could also look at the blood formation in the bone marrow by aspirating the marrow. It was just another step in developing hematology-- a better look at what was going on in that particular organ. Red cell production, white cell production, white platelet production.

Finch: I didn't originate it by any means. It was just being done. At that time, we did them all in the sternum, which is a little bit intimidating to have a physician get up and push a needle into your chest. Of course, it became a very routine procedure and I think was, in many places at that time, developing.

I got involved in several research activities while at the Brigham. The first few didn't have much to do with hematology, but as time went on, when I was a hematologist there, one of the important links that developed was with Jack Gibson and Robly Evans. Jack Gibson was at Harvard Medical School, working on iron metabolism and other projects. Robly Evans was at MIT and he was working with isotopes--radioactivity. So, we at this time--actually, this went back a little further because when I was with Joe Ross, we were working with radioiron as a tool to study red cell survival. Moving to the Brigham, that continued, but then the objective was to find out more about iron metabolism--internal kinetics of iron. I was at the Brigham from '41 to '49 with a year out when I was with Dr. Ross. There were a number of research studies that were interesting to us to at Brigham in hematology. In the area of iron, Charlie [Charles E.] Rath and I looked at the stainable iron in bone marrow aspirates. That was a way of evaluating iron stores in the body. Stuart Finch, Don Haskins, and I began looking at iron stores more directly by bleeding people. The use of phlebotomy proved to be a very important tool for many studies on iron metabolism from then on. One of the things that came out of it immediately, when we found that iron could be effectively mobilized by phlebotomy and iron stores could be measured, was the application of this to the disease hemochromatosis, where there is massive iron over-load. Really, Paul Hahn, who I knew at Rochester before--I think at the time I was at Rochester had the idea that maybe you could bleed the iron out of a patient with hemochromatosis. He started that on a patient, but the patient became more anemic and didn't do well and it was discontinued. We had done a little more experimental work where we loaded dogs with iron and took it out again. We thought that we were seeing a number of features that would be comparable to hemochromatosis in the very heavily loaded animal. At any rate, about that time, a patient came along with the disease. We bled him and found that the iron came out easily. So that started the series of studies of treatment of hemochromatosis by phlebotomy. Later on, I went back to Rochester and got out the patient's history that Paul Hahn had bled--a patient where it didn't work. I found that the underlying trouble in that patient was a hepatoma--cancer of the liver--and that, really, this was the reason for the failure.

Finch: Not really. It hadn't been done successfully at the time, to our knowledge, although later on, through another publication, the same observation was independently made.

Finch: Yes, this was one really useful form of phlebotomy therapy. Of course, later on it was evident that this would reverse a number of the features of hemochromatosis. Not all, but some of the very worst problems, such as liver failure, heart failure are reversed almost completely by phlebotomy therapy. That would have been the one great use of it, whereas some of the uses phlebotomy was put to were quite improper.

Finch: Whipple had been pretty much bound to animal experimentation in his work. One of my jobs when I was with him was to bleed dogs. We were bleeding them, taking off the red cells, and giving them back to our experimental dog that we were bleeding. So the net effect was we were taking plasma off. Plasmapheresis was the name of it. But maybe that was in the back of my mind when I got into doing phlebotomies. Through my experimental work, whenever possible, when there's been a good animal model, it has taken precedence over doing things on a person. We've done quite a bit of experimental work on animals.

Finch: No, but Brigham is right next to Harvard Medical School, and there were animal facilities there.

Finch: Perhaps. There were other things, too. I became interested in methemoglobinemia--that's when the hemoglobin molecule becomes oxidized and can no longer carry oxygen. Just by chance, we had a patient come in with congenital methemoglobinemia. It was a problem of an enzyme defect. I don't know how with--your medical background--should I go into details about things with--I mean technically or semi- technically?

Finch: This was a defect where about 30 or 40 percent of his hemoglobin was methemoglobinemia. At first everyone thought he had congenital heart disease, was cyanotic. But later on, with studies it became apparent that it was an enzyme defect. This got us into a lot of studies of what was going on; the therapeutic efficacy of ascorbic acid, which is a reducing agent for methylene blue which allows the cell bypass the defect and reducing methemoglobin to hemoglobin. We studied other kinds of methemoglobinemia: enterogenous, drug-induced. We ended up with a series of studies related to that.

Another interesting study was--occurred because a patient having a transurethral prosthetectomy developed hemoglobinemia and renal shutdown. They irrigate with distilled water--or did at that time. So, the water got into the circulation and hemolyzed the red cells. I had previously had worked with salicylate. It was a very good label, a good sensitive method for finding out how much there was in the blood. So, we were able to tell how much water got in; how much hemolysis was produced. We were continuing studies of iron metabolism and had developed a method for evaluating iron stores in the bone marrow, which I mentioned before. We also worked with the plasma iron-binding protein, which E.J. Cohn in the chemistry lab at Harvard had isolated through his fractionation of proteins. We developed a simple method of measuring it, depending on the development of a salmon-pink color when iron binds to the protein--transferrin, it's now called. We in fact injected this protein intravenously and tried to study its effect. However, the major thing that came out of it was the appreciation of the pro[thrombin] time, the plasmatransport of iron. However, about that time, we ran across a very beautiful study by Lorell in Sweden, which went beyond and was far more complete than the studies we'd done.

There are other things in my curriculum vitae that have to do with research--how much do you want me to go into all of these studies?

Finch: I think so, It always surprised me that, in Boston at that time, there didn't appear to be the communication between individuals who were very outstanding in hematology the way one would hope. In fact, that was an important item in my mind when I went West and we started up a new school. That there be more communication, at least within the city. I think there's always the likelihood, at least in those days, that after you have been doing things for a while, you get burned by someone who seems to be taking advantage of your open confidence in your work. I have the feeling that perhaps that had been true of some of the people in Boston and therefore that the cross-fertilization wasn't what it might have been. But there wasn't any question but that the Thorndike, with [William] Castle, [Hale] Ham, [James] Jandl, and Victor Herbert at that time, was a wonderful place for hematology. Then there were Joe Ross at the Evans and [William] Dameshek at Tufts. I misspoke before. So that there was a lot of hematology going on. I think I was in the neutral position and didn't have any ax to grind and was just a young man. So, when I was at Brigham as hematologist, we had association with all of those people. It was very productive.

Finch: Well, maybe I should explain that when I came in 1941, there was no laboratory at all at the Brigham. All of us as interns did our own cultures, did our own chemistries, our own blood work. At the time that I came, they had previously had a pupship where you did nothing but lab work for three months if you were an intern. But when I came on, everyone worked on their own patients for a period of time, for as long as you were an intern. Later on, while I was there, a chemistry lab was developed and hematology blood work was done in three different areas by technicians. I didn't have to supervise them, other than to originally set up the methods and to be sure that everything was running smoothly. But the procedures that were done were simple, routine procedures.

Finch: Red count, hemoglobin, hematocrit, retic[ulocyte] count, white count, differential--

Finch: Standard tests. In those days, these various tests that were put into the record, there were very few other routine tests. Urinalysis was the other thing. They were the lab tests. Now they've decreased in importance and other tests have taken their place.

Finch: I think I was away the year that they were getting technicians into these labs. I'm not sure how that developed. I wasn't really that much involved in hematology until after I was with Joe Ross. When I came back, that was the time when they were coordinated under me because I was the only person around who was specifically involved in hematology.

Do you have any other questions?

Finch: I supervised them, but they were pretty independent. The vials of blood were drawn and put before them and they did these tests and reported them. Really, there wasn't anything very systematic about it--I didn't have to check on anything at the end of the day, to be sure things were going right, if there were complaints. The other thing I was involved in somewhat was blood transfusions. The blood bank at Brigham was being run by Carl Walter who was the "Wal" of Penwal. Penwal being a commercial company. I think he used Brigham quite a bit as a pilot for development of blood equipment. We had a terrible time in those days. There were frequent reactions probably in one-quarter to one-half of the units that were transfused. The equipment very frequently had pyrogens in it. There would be times when I'd have to do some detective work to find out why an incompatible transfusion had occurred. I remember one time finding out that the bottles--two units had been switched and they required special studies to track these things down. I was also involved in control of radioactive exposure at Brigham. I found that there were white cell abnormalities in some of the people working in radiology. The radium was kept in a very thin-walled safe, next to working personnel who was being exposed to radiation. Things were very primitive. The concept of radiation exposure was just developing.

Finch: Yes, I wondered what I should go into after I got through my residency at Brigham. Although I was very attracted to cardiology and at one time ran Dr. Sam Levine's cardiology clinic when I was chief resident, I thought hematology had such a great opportunity. The cardiologist only listens with a stethoscope and so forth. Well, at that time, of course, they didn't have catheters--quite the opposite is true now. A hematologist had blood and bone marrow he could look at. He could see what he was concerned about directly. There was active investigation in the field. I think it was in advance of many fields of medicine at the time because the morphologic tools were perhaps more effective in hematology. I think those were the considerations, but also, as you say, animal research was further developed or at least was very active in hematology. But beyond that, clinically, hematology seemed a very broad subject. It seemed to interact with all of the other specialties. Blood going everywhere and having effects on other tissues. I think that when I was at Brigham, being a good clinician and having an exciting clinical life was one of the most important things to me. For those various reasons I was attracted to hematology.

Finch: Oh, I don't know. The Boston hospitals in those days were thought to be very good. I had been offered an internship at Rochester, but had the feeling it was good to get away. I was interviewed at both Massachusetts General and the Brigham. I was accepted at Brigham; I wasn't accepted at the Mass General. I might have gone there if I'd been accepted. But, it was a scary time to go to what we thought of as the "fountain of medicine" in those days.

Finch: In retrospect, Brigham was the place I wanted. I tend to be somewhat disorganized. I like flexibility. I think Brigham was unique at that time in having flexibility to do things that you wanted to do. I think that Mass General was more organized. I feel very thankful in retrospect that I got where I was. The faculty I got to know and the opportunities that developed.

Finch: Very much so. Yes, and it had a special approach. You had about half a dozen patients. Yet, I remember the first month of internship I was getting up about seven every morning and going to bed about midnight and busy every minute and never got out of the hospital for a month. Only had about six patients. There were so many consultants and it was so exciting and you were able to carry out special procedures. A number of things that really were research linked with clinical work. For example, a medical student, Howie Eader, and I infused a patient with nephrosis and massive oedema with amino acids to see what we could do to improve his condition. We followed his nitrogen balance. Things like that were a bit off the normal path for house staff--

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Finch: You'd have to deal with a very few patients, who could take a lot of your time. All of these people visiting you--Gene Stead, Charlie Janeway--many other people would fill you with ideas. It was like a tutorial system of education that was somewhat unique.

Finch: Yes.

Finch: Although after about a year, I was married and lived across the road, only about a hundred, two hundred yards away.

Finch: No, I knew her in Rochester. We got married about a year after I got to the Brigham. You had to have permission in those days to get married. I asked Soma Weiss if that would be alright if I took the weekend off and got married. He said he was delighted, I could do it, but to remember when I came back I was as if I were not married.

Finch: I think there were about a third married, as a guess.

Finch: I think a very high number would have gone on in academic medicine. I don't recall for how long. I haven't kept track of all of them, but I would have thought that three-fourths went on to academic position in the East, the South, the Midwest. It was very much of an academic center. That was one of the things that concerned me when I thought of leaving Boston was, ''Where could you get research fellows to work with in a way that you'd get them in Boston? '' Because I'd been fortunate. I had a number of fellows with me there, when I was there. I thought, "If I go to a distant place, who would be interested in academic medicine?They'll all be interested in practice."

Finch: Have you met Joe?

Finch: Joe is a very personable person who made you pretty much part of the family; he and his wife Eileen would incorporate you into things that were going on. My own father died when I was 14, and I'm sure Joe was a surrogate father. I was very fond of him and still am. He was a very good friend over the years. One of the major people, I think, that influenced me.

Finch: I think he introduced me, in many ways, to academic medicine. I mentioned before the National Research Council, meeting people there. I'd been influenced by Whipple before, since I was his fellow and worked in some contact with him. Whipple was one of these people who were kindly, honest and could see the main issue rather than details. To a considerable degree, although they were very different personalities, Joe was the same: Joe was honest and a forthright person, enjoyed academic medicine and imparted that to me.

Finch: I'd always had a desire to move. I pictured myself on the West Coast. I like mountains. I grew up in the Adirondack Mountains in New York State, and I think I would have had to go where there were some mountains. But I was very happy in Boston. I didn't have any thought of moving until 1948 when there was an isotope course I wanted to take in Los Angeles. About a month before, Bob Williams, who had moved out the preceding year, from Boston to Seattle, asked me if I'd be interested in a position and wouldn't I visit him there.

I knew Bob Williams. I had considered a fellowship with him in endocrinology at the time that I finally decided to go with Dr. Ross. At any rate, I thought, "Well, there's nothing to be lost by doing that." And so on the way to Los Angeles I visited. Of course at that time, there wasn't much in Seattle. They had some temporary buildings and didn't have a teaching hospital of their own. They were using the county hospital. But it was a new school. It had just started in '46. Of course, the northwest country was very appealing, the mountains, the ocean. But I really didn't consider the position there seriously at the time--until I got down to Los Angeles and spent a month there. It was a leisurely time. We were working a bit during the day time, but had evenings to relax and wander around. The more I got thinking--and it was a thinking time in terms of being away from Boston--the more I got to thinking, the more I thought that it might be a worthwhile venture. I got an offer at the same time Dr. John Lawrence, who had moved from Rochester to head of medicine at UCLA. But thinking about them, however, I thought Los Angeles was a pretty big and smoggy town, while Seattle was a very attractive town. So, I chose Seattle on the basis of the countryside, the setting of the place, and probably most important because it was new and you could set it up from scratch. At that time I didn't really appreciate how helpful Bob Williams would be in the future. He was certainly very important in my career, once I came to Seattle.

Finch: He was about five years older. He was head of the department I would be coming to. We had two young kids then, about one and three years old. We drove across the country. Three of my technicians came across, too. They drove a separate car. I could only afford two, but one of them went with Bob Williams. So, we brought out some help with us. I'd been very fortunate to get an NIH grant for research in hematology when I came out, plus the support that Bob Williams was able to give me; this got me off to a good start.

Finch: There hadn't been a medical school going, and so it might have been more difficult to find personnel locally, plus the advantage of bringing people out you've worked with, you get along with, and who know your methods. So, I saved a lot of time, I'm sure.

Finch: No, they left me after a couple of years.

Finch: For the technicians? I think they had an adventuresome spirit, too

Finch: I guess that is better expressed when I closed the lab two or three years ago, there were five technicians and they had been with me from about 18 years to about 12 years. Everyone had been there a long time. They'd worked together. You can find, when you get to know a person, what area they can work in best and what responsibilities they can take on. We still get together once a year because it was such a close knit unit. I think if you're fortunate enough to get a group of talented people who get along and if it's a happy lab--which we certainly had--it can be very important. But "important" has several meanings: Important for your pleasure in life, which is I think-and then important in scientific achievement. I think you want both of those. I'm not sure one can exist without the other.

Finch: We talked about standard hematology. Basically, they were very dependable at doing standard tasks, and then we had developed certain special things. We mentioned the examination of the bone marrow for iron, measuring iron-binding protein, serum iron. Tests that we had accumulated. One of the more important would be work with radioactivity and processing radioactive samples. But a certain amount of ongoing work that we wanted to continue here, with people who had been doing it, allowed us to go ahead without any breaks in time.

Finch: I think that was just at the early days of the NIH. After the war, the scientific development program, which was run for the war, was transferred to the NIH. The NIH, by Congress, was given the role of alleviating disease process, and they had set up some institutes. That all happened pretty much in the late forties and early fifties. I remember when I came out, I was told--I'm not sure this is correct--that the grant I had was something like the second largest. It was, I believe, for 20 thousand dollars. Grants were of small size then. But on the other hand, 20 thousand went pretty far. At that time, we as associate professors were making six thousand a year. Twenty thousand would hire several technicians, supply equipment and so forth. So, in fact, it was very nice support. I was very fortunate because I had NIH grants that just ran through for a period of about 38 years. That helps, when you have continued support of that sort.

Finch: It would be hard to say. It allowed the program to develop. It might have developed the same way if I didn't have the grant, because there was some fluidity of funds. There weren't many funds, but Bob Williams might have given me more if I hadn't had what I had. It allowed the laboratory to be more comfortable.

Finch: The iron work continued. That has continued as probably the backbone of our program through the years. When we came out here, we started up something that took much of our attention in the first ten years: namely, blood preservation. Having had associations with a group working on blood preservation during the war; it looked as though the major factor in limiting red cell viability--when the bottle is on the shelf--was that the metabolism of the red cell ran down. We called it a "storage lesion." We tried several manipulations to see if that was really it. I guess everything we did seemed to reinforce that. The studies that had been done before emphasized the role of adenosine triphosphate--ATP. That decreased appreciably, and the red cell went to pot. At that time, a biochemist--Beverly Gabrio--working with me and thinking how something might be done about that, took a bottle off the shelf--adenosine and later inosine, compounds that had to do with ATP--found in fact that they did improve preservation. A whole series of studies went underway. For example, we developed a rabbit model for transfusing stored blood and watching how long it lived in vivo. Adenine compounds and inosine improved viability of stored cells. Some of the results that we got weren't confirmed elsewhere and there was obviously something wrong with our observations. About that time, a Japanese investigator found that adenine worked. Probably what we had been dealing with was the contamination of our compounds with smaller amounts of adenine. Because it took very little adenine. Ernie Simon, who was a research fellow here, did further studies along with other people and established the fact that small amounts of adenine would increase the storage period from, say, 21 days to 35 days. So, this was useful and has been implemented in blood transfusions in many areas as an adjunct to the usual blood preservatives.

Finch: It depends on the blood transfusion system that's in operation. For example, I think the New York blood bank gets much of their blood for transfusion from Europe. When distances are involved or in regional blood banks where you can only have a little blood on hand--in Alaska for example--if you can keep it for 30 days as compared to 15 days, you can utilize a greater proportion of blood obtained for transfusion. Also you can speak of better preservation, where with time the oxygen dissociation curve of blood--the release of oxygen from hemoglobin to the tissues--falls. If you can improve that property, which adenine does, it is an additional advantage.

Finch: Very much. I'm sure I never would have even gotten into it if it hadn't been for that.

Finch: Yes.

Finch: I think that the 1950s were a time when people thinking biochemically. Actually, it was more than just Beverly Gabrio. Frank Huennekens from biochemistry joined the effort. Richard Czajkowski, who was director in the blood bank, set us up with research laboratories at the blood bank, so that additional biochemical people were brought in. The program was a combined one between the Department of Biochemistry and hematology. That continued for a long period of time. There still is a very close union between the blood bank and the medical school. That was one of the areas that, when I came to Seattle, I felt would be very important to develop. Even nowadays all but one of their five or six full-time academic people at the blood bank with an appointment at the medical school came through our hematology training program. I think of all of the things that have happened to me over the years, the most important since I don't give myself credit for most of the work that has been done, were a remarkable group of research fellows. They're the people who have generated a lot of the ideas and who have done the work. I think we've had in my immediate lab about a hundred. Then as people became relatively senior and headed different hematology units at the school, they have had fellows. So probably a total of about two hundred fellows have gone through the program here. I think the major contribution of our activities over the years has been to provide a scientific home for these people, to provide facilities and resources, and hopefully a proper overall environment. When I came to Seattle, I was determined that the program would be a coordinated one. We were faced with the necessity--much as in Boston, at Harvard--of working in different hospitals. We had a county hospital, veterans' hospital, children's hospital and finally a university hospital. That came last of the four, in '59. So we had hematology units going at each one of these hospitals, but we rotated around. All of us who were faculty rotated through the different hospitals and kept it a single clinical enterprise. I thought that was the tragedy with Boston, good as it was, the remarkable talents of the faculty weren't fully exploited.

Finch: Very much.

Finch: It required effort because instead of just sitting down in one hospital, the next month you'd be going to another hospital. To some extent, it attenuated your clinical contacts with patients. Because instead of having one hospital where you sort of attracted a group of patients, you were spending time going here and there. But the dividends from it were great, because a collaborative research would develop between this person and that person in different hospitals. The whole thing held together and I think that was one of the main features in making the program a very attractive one clinically for individuals looking for fellowship training. They knew the whole thing was working together.

Finch: There wasn't any hematology, is the best way to start to explain. There were very good doctors in Seattle, excellent internists. In fact, in Boston, I was very aware of superb doctors and some very poor doctors. The spectrum was very broad. Here--at least from the contacts I had--I was impressed that, in some ways, the calibre of general medicine was good, but the calibre of specialty medicine was not fully developed, certainly not in hematology. There were some specialists, of course, but not comparable with what it was after the university had been here ten or twenty years. So hematology was about the way it was when I came to the Brigham--a few simple tests were being done. We were fortunate because the intellectual center of medicine was at the county hospital under a man called Clyde Jensen, who was a pathologist and internist. Clyde would hold CPCs, where you would have a diagnostic problem presented to some discussant who would then say how he would go about making the diagnosis. The minute we came, Clyde said, ''What can I do for you? You take over,'' a really open door for putting in any innovations we wanted. That occurred at Harbor View where the greatest impact on town physicians could be made. Then Children's Hospital was developed later. I set up a technician over there and would make rounds. Later, research fellows, would go over and do those things. At Veteran's Hospital, Robert Evans from Stanford came as head of medicine, but he was also a hematologist. With his help, we set up hematology the way we would like to see it there. This is really what I came to Seattle for, to have the opportunity of setting up an integrated program.

Finch: It was the total spectrum. There wasn't any oncology when we first--so we saw anemias and bleeding problems; white cell problems that lead to infections or leukemias and lymphomas. Now, of course, the oncology input is very large in the area of hematologic malignancy. In those days, when you came from a place like Boston where you'd been chief resident, you started out with a lot of interest in general medicine, as well as hematology. Hematology in those days was a good vehicle for being involved in general medicine, but over the years things have changed. One gets pushed more and more into a smaller and smaller area of medicine. We tried to settle with oncology by saying it had to remain a single clinical service. We have two divisions, but the patients overlap. Even if you have leukemia, you have to have the skills in hematology. So, we said that even though there are two different divisions, we would like to have one clinical service on which there will be consultants from hematology and oncology and they can overlap. Again, we need cross-fertilization from oncology and hematology and vice versa. It's gone on that way. It's not as clear cut administratively when you say something like that. You do get into problems. Obviously, the oncologists know more about the malignancies--and those are most of the patients. So, as things developed, oncology took a bigger clinical load. Hematology became more of a research-oriented division, retracting some from clinic matters, but also has continued to be very heavily involved in the blood bank. The blood bank here is unusual in having a coagulation lab and treating all of the hemophiliacs in the state by providing antihemophilic globulin for them. As things have grown, there have been shifts in the total pattern. I know, personally, in the last years that I was head of the hematology division, I was not that competent in oncology.

Finch: Don [E. Donnal] Thomas was head of hematology and oncology. He started his division after hematology had been there for many years--ten or fifteen years. There was some jockeying back and forth. Don and I had worked together in Boston. We were good friends, but there were strains and stresses because he had to develop his division and that we probably disliked giving up some things here and there. I think some friction was inevitable, but was never major as far as I was concerned. His program was an exciting one. He focused on marrow transplant, whereas in hematology we had the feeling it was important to develop young people in broad areas of hematology to act as a reference point. When I say this, you have to appreciate that Seattle is really the reference point for Alaska, Montana, and Idaho as well as Washington. We have medical students coming from all those states in a WAMI program. For years there was a hematology postgraduate day when people would come in--occasionally from Alaska, but more from Washington, Idaho and Montana. We felt we had a responsibility for the whole area, there being only one medical school. Don's program was one which centered on hematologic malignancies and of course was remarkably successful after it got going. A really remarkable achievement that Don was able to pull through. The difficulties in the early years, when patients were dying in high frequency, to the point now where marrow transplant is established as a major approach in medicine to bone marrow disease.

Finch: Right. As a result of the success of the oncology program, most of the patients came under the oncology. Many of the patients were potentially marrow transplant, or if not, his program developed competencies in chemotherapies far more than ours did.

Finch: No, it was more a matter of bringing bone marrow transplant to a point where it could define its limits and to bring it to a point where it was highly successful. All in all, I think we've had remarkable coordination in the program. I don't think it could have been more awkward in the way we designed it to say that these two areas of patients are really a single service and that you had to set up rotations; that somebody else felt that that patient was in his province that you felt so, too, and the house staff would have to work it out. It's worked well. It's never taken a negative phase where it was harmful. I don't know of any better way because, if you know medical schools and departments of medicine, they only allocate so much space to one division. Research space comes hard and there's only so much of it. By having two divisions, I'm sure that each division got much more in the way of resources than it could have had if there had been a single division, which many places have.

Finch: Radiation is one form of therapy. Drugs were being developed. A treatment such as the folic acid antagonists were developed in Boston at the Farber Institute. Over the years, more and more different chemotherapeutic drugs have come along. It's been a graded process of developing the chemotherapeutic approach. Bone marrow transplant applied, first, to very sick patients; they were near terminal and not many of them lived with bone marrow transplant. But as the treatment moved back to an early stage, the mortality from transplant came under control. While it only covered only a portion of patients who had a compatible donor, it became a better and better option. What we were doing in Boston was just giving transfusions and trying to treat infections. In Boston we didn't even have platelet transfusions. That was more recent.

Finch: No, Don Thomas was really the pioneer in getting marrow by needle aspiration.

Finch: I think the latter. As a person developing in medicine, the Atlantic city meetings that are held once a year was one of the fabulous times where we would meet all of our heroes in medicine, the people we'd read about. Get a chance even to talk to them and so forth.

Finch: No, these are the Association of American Physicians and the Society for Clinical Investigation, the national meetings in Atlantic City. I'd been quite interested in teaching over the years, and to take this as an example, when I came out here, one of the things that we did relatively early was to do away with the laboratory work that students used to do. At least my feeling was that in the future, technicians were going to be the experts in looking at a blood smear and doing blood counts, and all of that. Of course, subsequently the technology has taken over and the technician just puts it in a machine. I think we were very correct in this. I know, in medical school, I was taught to make the perfect smear. The sort of thing you worked for a week to make it nearly perfect. But I thought that would never happen when they were in practice. In the early days in Seattle, we developed a line of studies that came out of iron kinetics. We began to realize that most of the iron went to develop red cells. If we quantitated the red cell uptake, we would know how big the erythroid marrow was: how many red cells there were developing. Then we used that technique along with several others to understand different kinds of anemia. We found that in some anemias, there just weren't enough developing red cells in the bone marrow; in others, there were a lot of developing red cells, but they were defective and they would die before they got into the blood. We called that ineffective erythropoiesis. Then the third category of course was that a lot of cells got into the blood, the bone marrow was working fine, but the cells were being destroyed in the blood; that was the hemolytic anemia. We got very involved in looking at different types of anemia and understand the physiology of
what was going on. That led to the development of a red cell manual, which was a teaching manual for the students. I've always been bothered that students are given books that are as many as 500 pages or a 1,000 pages in length. So, we made a 100-page manual and used that in our teaching. In those days, anemias were important. There were a lot of anemias around. Then, I had a fellow with me who was from Oslo who was a very brilliant man trained in blood coagulation. He and I wrote a hemostasis manual.

Finch: This was Peter Hjort. That manual has been taken over since by Art [Arthur P.] Thompson and Lorrie [Laurence A.] Parker. Both of these manuals are still being written now, some thirty years later, and have been used at a number of medical schools through the country. We had a more compact program where the student didn't have to read an awful lot, could get basic principles and hopefully physiologically related. We tried to write a white cell manual. But it didn't hang together for us. Our objective was to talk about an approach to anemia that the general physician could use. A specialist knows all of the little things. He can solve problems a dozen ways, but a general physician needs a simple system, sort of systematic way of solving problems. An outgrowth of our teaching interest was the idea that it would be great if teachers at different schools could get together, talk about their programs--what ideas they had. Before that happened, I found that Hale Ham, who was an outstanding educator and much better organized than I was, had penned the same idea. So, we all got together. For a period of ten or fifteen years, many of the U.S. schools were represented at an annual meeting, and we would have sort of a show-and-tell of what different people were doing. That was real fun, and I think it probably needs to be restarted now. About that time I dropped out for three years, half-time, to develop a more systematic approach to general internal medicine problem solving. Unfortunately, he meets almost nothing but specialists in medical school. For a specialist to tell a fellow who's going to be a general practitioner what to know, is apt to be a little overwhelming, because the specialist knows too much. So, we were trying to cull out the things that seemed to be central to the education of the general physician. I worked with specialists in every area, and finally got together a manual, but that's another story and not dealing with hematology. But just the point, I think, that much of one's fun--much of my fun--in medicine has been in teaching and trying to translate the information in the laboratory to clinical medicine and then to provide something that's appropriate for medical students.

Finch: I think an awful lot of what we did is now very common knowledge for every practicing physician. He knows how to handle to it. When I came to Seattle, there were many patients who had pernicious anemia--undiagnosed--and they were coming into the county hospital all the time. Now, it's a rare thing to see a patient come in with pernicious anemia, because hels been diagnosed and treated on the outside. That was also true of iron-deficiency anemia. Some of our early studies dealt with the diagnosis of iron-deficiency anemia and transferrin saturation and ferritin were useful diagnostic measurements which have been developed. There's just not enough of them around. Practicing physicians take care of them now, and they don't need a tertiary referral center. So really, we did ourselves out of business in a way.

Finch: I guess it's what should happen in medicine.

Finch: It's based on simple laboratory tests that can distinguish between possibilities. In a sense, it's a branching system. There were never more than three possibilities. If you start out and say, "Is this a failure of production, because there aren't any red cell precursors? Or is it ineffective erythropoiesis, where red cell precursors are dying in the marrow? Or is because they're being destroyed in the blood?" There's three. So, if you have a way of telling this, for example, the first branch can be done by a reticulocyte count. Retics are young red cells; the number of young red cells in circulation tell you how many cells are coming out each day. But, with a modification, which we had to work out--that is, when a person becomes anemic, instead of taking three or four days to develop in the bone marrow, the red cell will take only one day. And he can take three days in the peripheral blood and circulation. So, for a certain degree of anemia, there's a certain shift of maturation into the blood that will mean there are more retics--not only because there's more production, but because they're living longer. We developed a correction factor for that, which is practical, clinically. We had a retic index that would tell us what the production rate was; we would say, arbitrarily, if it's three times the normal index, it's hemolytic anemia, and you've got to look at causes of red cell destruction in circulation. Now, the other two possibilities then, you've either got a very few red cell precursors in the marrow, or you've got a lot of them but they're dying. If you find that the indirect bilirubin from broken down cells is elevated, but the retic count isn't elevated, it means that hemoglobin pigment is being broken down. This could be due to destruction in the marrow if the reticulocyte count is not increased. The easiest way, of course, to determine marrow cellularity is to do a bone marrow aspiration. If you see a lot of red cell precursors, it's ineffective. Then it could be something like pernicious anemia, or thalassemia. Or if there are not any red cells present, it's, aplastic anemia, then you think of what are the nonspecific causes.

Finch: Yes, if you have this sort of system, if the patient is black and has belly pain and something like that, you'd say, "Well, that looks like sickle cell anemia.'' You could always jump ahead, but if you don't get any real good clues, then you go to something like aplastic anemia--no red cells in the marrow-- you say, "Well, maybe this is a toxin, maybe the patient is taking medications, or exposed to a toxic substance." But some things you diagnose by a very careful history and physical. In hematology, if anemia is present, you really get your start from a program like this, and you come down to, "Well, there's something wrong with the stem cells in the bone marrow. They're damaged or they're abnormal." Then you go back and ask the patient whether he's been exposed to benzol or taking some medication that causes it. It was really an outgrowth of laboratory studies, in which methods were developed that would sort of make each branch for us. It was fun, and in a way that's what I've tried to do in other areas of medicine when I did try to develop approaches. Then I found that some of them are applicable and some of them not at all.

Finch: Such tests couldn't have been developed without a lot of work in the lab first, to establish that these methods worked. Like anything else, it takes time to get an acceptance. No system is ever perfect. This is just one way of doing it. Hematologists don't need it, but I think the general physician is helped by it. Most important, we gained insight into the behavior of the bone marrow.

[Tape stopped; restarted.]

Finch: I like to think that a lot of the reason that it was good was because of the insight provided by first-rate, experimental work. George Minot was a remarkable man and did an investigation that was ahead of his time. He introduced physiologic and biochemical thinking, and the idea that here you had a tissue that was available for the biochemist and for structural examination. I think people who had a bent toward investigation couldn't help but be attracted to hematology. In the same sense, hematologists were interested in teaching. I was delighted to see several of our fellows in a fellowship program have gone into education as a result of their entrance into hematology. I think it had broad implications experimentally, clinically, and for a teaching career. Then as technical developments came on, you could get tissues from other organs and chemical tests could characterize abnormalities without biopsy. Interest in experimental approaches shifted from what was traditional hematology to other fields. Techniques developed that opened large areas of research. A catheter which could go into the heart opened whole new arena for research and understanding of clinical problems. But I think even more, in the early days, you went into whatever seemed possible to do, and you didn't pay so much attention to what is the most important disease to conquer such as cancer and cardiovascular heart disease. When the scientific establishment became more potent they could look at something like coronary artery disease and say, ''This is something really much more important: look at the people who are dying here. A big program develops, and progress is made, and this whole area becomes the center of attention. As we've said, anemia was a big deal back then, but now it's sort of under the belt of the practitioner. He can handle it. So, the area of hematology that I was interested in has passed by now, and you need to move to molecular biology approaches to so many things that never could be approached before. It was a phase. I always think I was very lucky in just being in on something while it was the center of some attention.

Finch: It's so much fun for hematologists. We loved to look at smears. You can see a lot in them if you're really experienced, but we'd be better off if we didn't have that interest nowadays because we were not teaching something that's very useful to the doctor, and there are more precise methods available.

Finch: I like morphology, but I became much more interested experimentally in the physiology of anemia or other problems. Max Wintrobe probably carried morphology to the extreme of carrying a microscope right around the hospital wards, looking at .slides. We would sit under a multi-headed microscope, as long as I was active, and go over smears and marrows. But I think, if anything, we over-emphasize it. Only a hematologist would want to do it.

[END OF TAPE 2, SIDE 1; BEGINNING OF TAPE 2, SIDE 2.]

Finch: What we tried to do was to translate morphology into physiology. We'd see a "shift reticulocyte," and we could say, "That is due to a high level of erythropoietin stimulating the bone marrow.'' We could take it one step further: the morphology into functional aspects of marrow activity.

Finch: Yes, you could see more things, interpret more things from it. I think we certainly were interested in that, but there's a limit to how far you can go. I've always thought that there should this interplay. I think you should get some of your research problems from seeing a patient. Then you should go into the laboratory and the laboratory should give you help in either diagnosing or treating other patients with that problem. That was the level at which clinical investigators worked. At our particular time in the history of medicine, some resources have been available so that simple clinical questions could be answered.

This is not hematology, but I saw a patient who had renal shutdown. His heart sounded very funny, and I got an electrocardiogram which had a biphasic QRS pattern. We had a key to the Harvard Medical Library. In those days, you could just go in yourself. By two or three in the morning, I found what looked like a tracing somebody had done in a dog with potassium poisoning. Then we worked in dogs for the next year, producing EKG patterns and studying what happened. That was when I was chief resident at the Brigham. In those days, you could take something at the bedside and go back and hopefully find out what it was; manipulate it and find out how to handle it. In the period before that, it had pretty much bedside observation. But here was a time when there were research labs. They didn't start up until the turn of this century. There weren't many until the '20s and '30s. Then you could take something from the bedside, go back, work on it, and then come back again. That to me was the fun time of medicine. Now, it's much more difficult, because many people feel they have to be molecular biologists. By doing that, they're problem is quite a long distance away from the bedside, Maybe they can hit one target over a long period of time, but it's very hard to keep together the clinical side and the lab side. If we talk about phases, we went through the morphologic phase in hematology and then physiologic considerations in the '40s to the '70s. Nowadays, you have to become a molecular biologist or trained very highly in specialized area; to get back to a patient problem may take you years, if at all. I think my pleasure has been in the multiple interrelated facets that are available to the academic hematologist. The fact that you can do teaching and not just bedside talk-teaching, but you can develop teaching approaches that are meaningful. On the other hand, you can be a clinician: you can see patients and get the satisfaction of helping people directly. Then you can have an experimental laboratory and pick select problems that you want to work out, that could bounce back clinically. I had the additional pleasure of being involved with world health for quite awhile. This tied in with my studies on iron metabolism. Visiting developing countries where there were major health problems. The estimates were that five hundred million people had iron deficiency. So that was to world health an important problem. Then to see experimental opportunities in different countries and set up research protocols, and be part of such studies. In the late '50s and '6Os, I did quite a bit of traveling in Europe because of meetings and because of invitations to do this and that. But from maybe '65 on, I got interested in developing countries because there are such opportunities for improving health care. It's harder to do things there, but there are such great opportunities.

Finch: I think I became a consultant about '59. We had meetings in Geneva where experts from developed countries and representatives from developing countries would come and discuss problems of iron deficiency. That stimulated us. We went back to the lab. Iron is a unique substance in that it's been spoken of as a one-way substance: you get it in the body and you can't get it out. Which isn't quite true, but the exchange is very slow. Maybe 10 percent of your body iron a year is lost and is absorbed. Most iron deficiency in this country, where nutrition is good, is due to blood loss. But in developing countries, the diet may be extremely poor. You could grow food staples with radioactive iron--and we did quite a bit of this in the green house. Then you study how much of that iron would be absorbed. An iron deficient person will absorb more, but it was very clear that from these foods little iron is absorbable. Hemoglobin iron is the best absorbed, but the people who need it the most don't eat hemoglobin or myoglobin. You could measure absorption from one food, but what about a complex meal? One food influences the availability of iron in another. We developed a method-- extrinsic labeling method--which would allow measurement of absorption in a complex meal. Then we could look at different diets through the world and determine availability of iron in these different areas. In addition to these meetings then, I went as a consultant to Africa, South America, Asia. More and more I got interested in studies in such countries and had studies going on Venezuela, Thailand, and places that were very profitable in terms of the pleasure of being in different settings and having the feeling the problem was important. All of us in our generation were like general practitioners. We were never formally trained in research. We tried to bridge the clinical with the research lab. And certainly, by international meetings we had a good chance to develop friendships, collaborations with different people. It was a very broad aspect of medical life that was possible then. It's one that it seems to me is getting harder and harder to do. We were involved in quite a few things other than iron, but as time went by, we really couldn't compete that well unless we just stuck to our iron field.

Finch: There was a sequential approach. First of all, how do you evaluate the importance of iron deficiency in an area? Develop methods to identify iron deficiency. Even the surveys that have been done in the United States have essentially used the laboratory criteria that we helped develop for identifying iron deficiency. But these were then applied to other countries, other situations, modified somewhat according to that country. Then on the other side, having identified the question, how does one go about determining its cause? This involved first, determining the characteristics of the diet: Is it adequate? Is there blood loss due to hook worm infection? And then, if you're going to do something about it, what do you do? If it's nutritional, you need to know first what you're dealing with, what the dietary iron availability is. Try to decide how to modify this. Can we supplement the diet, can we fortify it with something that will greatly improve the availability of the iron? Or should we just put iron into the diet in some particular vehicle? Then, once you have done this on a laboratory scale, you run experimental field trial where you take a village in a country find this village and this village is the control. Then see if it's working. Experience over the years has been if somebody says, "Well, in Manila, there's a lot of iron deficiency, so we'll give them more iron this way, maybe fortify some food." It looks great, but you go back five years later and nothing has happened. So, somewhere between what you think is good and what happens, there are problems. One of the things that was done was to work out a sort of sequence to try to increase the probability that you would have a sustained improvement.

Finch: Yes, and you had to rely on people native to the country to see the thing go through properly. trying to establish the--

Finch: Yes, and doing pilot studies in our laboratory that would bear on questions that had to be answered. You learn how very difficult it is in another country. Here, things work predictably. You have control. In another country, the political aspects have to be right, the laboratory has to be right. In Medellin, Colombia, we went one year and thought we might get something started. The next year, there was sort of a communist takeover of the university. Now it's a drug center. These things in other countries can happen so frequently, that it becomes very critical to involve a sound place.

Finch: There have been lots of examples of failures in undertaking and trying to improve iron deficiency anemia. You can think of some of them in which what seemed to be wonderful results just plain couldn't be reduplicated. That seemed to relate to the investigative team. A big government program, for example, was started in Thailand, run by the radiology department of a university. I'm not sure whether it was salt or fish sauce that was fortified, but a prize was awarded by the government for great achievements. A few years later, nothing is working. I remember that in India, a study of nutrition which was undertaken by the nutritional institute involved a finger-prick of blood from some children and, a year later, a second finger prick. Half of them were given food supplements and half were put on a controlled diet. When the time came for the second sample, the people refused to give it. They said, "You're selling our blood, and we won't be part of this." So, the whole experiment, a year's experiment was lost. There are local prejudices that develop. There may be only one good investigator and he moves to a different part of the country. There are just innumerable things that can interfere with a successful outcome.

Finch: I've never been in favor of societies. I think Joe Ross would have told you what transpired at the beginning, how the Society was founded. I was not a member for a number of years I guess I didn't see the need, probably because I knew most of the hematologists then. It was a pretty small group in the early days. I don't know how many people came to the first few meetings. There were three or four hundred when they had the meeting in Seattle. By then I was convinced of the value of the society and had joined. It has been important to the development of hematology over the years.

Finch: I didn't know the early years that much. I didn't have that impression. I thought it was representative. Actually, I went to the International Society of Hematology in Buffalo before I ever went to an American Society meeting. The American Society of Hematology was almost entirely research in its early years. But research then was very clinical. By the time that when I was president of the Society--I think the meeting was in New Orleans-there was near revolt that year. At least, I interpreted it as such. The clinical people said, "If this isn't more clinical, we're going to form our own society. " That was very proper that they thought that way. Fortunately, the Society responded by setting up a clinical program in which people who were very knowledgeable in different areas would discuss the more clinical aspects of hematology. I think that part is a very important aspect of the Society. It brings together the investigator and the clinicians.

Finch: Research moved into moved into a more basic area. The Society opened its membership to pre-clinical people and PhDs. They wanted basic science disciplines because that was the way hematology was going.

Finch: Mostly biochemistry, but now it's largely molecular biology. Now many of the hematologists go only for the clinical program, but take in some of the research program, particularly the symposia.

Finch: Well, biochemistry became a favorite child around 1955. From then on, for the next 15 years, the clinicians began to see applications of biochemistry. Part of this was the influence of the NIH [National Institutes of Health], when they began giving a lot of money, many of the guiding committees thought that there needed to be more integrated research between specialties in both preclinical and clinical.

Finch: I think that it seemed less and less useful. The papers would be less directly clinical, less understandable.

Finch: That came up on the floor at the business meeting. Obviously, it wasn't anything that could be settled at the moment. I think the year that I was president, the whole machinery of the Society bogged down. It was just the result of enlarging the group of people and the small administrative group being not sensitive or not able to address the various questions that were raised. I remember Lou Wasserman, the next president, had committee meetings getting together groups of people to look at some of these problems. I think the feeling of the majority of people was that if you lost your clinical group, you would have lost an essential component of the Society. The majority of people, I believe, felt that it was a research society and they didn't want to infringe on the research reports that were coming through. The answer was then, "Let's add another component on the front end of it, and have a couple of days of clinical and then we'll have our three days of research."

Finch: That's what I'm talking about.

Finch: Really to provide them the spin-off of all that's going on that had clinical relevance. I think that's been done quite well.

Finch: We started before that, but it's still going. I think it will end after the current edition.

Finch: I think the worst thing was more personal. The Sung Hotel collapsed just at the time of the meeting. Things were very discombobulated. That's not the hotel the meeting was being held in, but it was an important hotel to house the membership. Many rooms were changed in our hotel. The president was in the habit of having a get-together in the evening. At that time, it was informal and very small. Now, it's a big, official thing. My wife and I had a big keg of ice and beverages. People were supposed to come about nine o'clock. Nobody came. We called downstairs about midnight and said, "Where is Dr. Finch's room?" and they gave us some other room. They had sent people to the wrong room number, so that we sat there and had an empty party that night. Nobody came.

Finch: I suppose they went to the door, I think, and when no one answered, they just left.

Finch: It was a very positive thing all the way through my academic career. There was always research support. I served at an early date on a study section, later on the council. My experience on the study section, which came in the early '50s-- made me feel that this was indeed a productive way to go about things. The peer review technique at least as it occurred at that time, seemed to be very appropriate. There wasn't any game playing in our study section. It really was an attempt to do your darnedest to get the best science that you could for the money. I always have believed in it. Year by year as you kept renewing your grant, there were progressive increases in the amount to keep pace with rising costs. The whole thing worked very well. I happened to be back on the study section just as a temporary member a few years ago. I found it much more difficult. In the '50s, we knew virtually every person who put in a grant. We had an idea of their abilities, the work they did, how they did it, how they ran their lab. Nothing was too complicated in the projected plan because techniques weren't that highly specialized at that time. We thought that we could make good judgments. Now, if you go on a study section, even in my own area, a project can be complicated, the investigator unknown to you. Also, now the percentage of grants that are approved is very low compared to what we dealt with. I think it's very detrimental to science, because it means that you're going to pick something that you're almost certain will work; and if you know it's going to work, it's probably not even worth doing. The fellow who is truly original and doesn't have data already to prove his point, is probably at a disadvantage.

Finch: I believe the emphasis now is on the project application rather than the investigator, and the effort is to obtain experts regarding the paper description of the project. Perhaps there is too little emphasis on the investigator. There are various ways to deal with this and one of the most prominent is to shift money to support young people of exceptional promise, support them on fellowships instead of talking about research grants. Maybe letting them work under somebody else's umbrella where there's some money and facilities. I think that has to be one way of getting around it. I think it's possible to identify truly outstanding young people.

Finch: Hematology never had a focus at NIH until fifteen years or so ago, where it came under heart, lung, and blood. In that context, heart and lung are big dogs and hematology is a little dog. Blood transfusion was left hanging in the air. It was in multiple institutes. Arthritis and Metabolic Disease at that time supported some of it; Heart supported some of it; Cancer supported some. To some extent I suspect that's still true, but the real focus is supposed to be heart, lung. I'm not sure if that makes so much difference, because the organization is that you have a hematology study section, but papers from that could feed to different institutes. It's not an institute-bound committee.

Finch: I think we touched on that a bit before: about the patient with congenital methemoglobinemia. I think what I said was I picked them out because they were either fun or because they were important. I think methemoglobinemia was fun because it was a phenomenon that developed from a number of causes, genetic, gastrointestinal disease, and from drugs. It so happened that we had clinical counterparts for all of these that we could study in some detail. The one I feel badly about missing was an abnormality of the hemoglobin molecule itself which can produce methemoglobinemia. I had an opportunity to study just a sample of blood, so I missed out on it. But it was the satisfaction of working out the whole problem clinically. Also to evaluate different forms of therapy. It's just really the satisfaction a clinician gets when he become familiar with a certain problem, and he's able to relate the laboratory and clinical side of it.

Finch: It's just the accumulation of an oxidized hemoglobin in circulation within the red cells. What happens is that normally there are oxidants in circulation, and they are changing hemoglobin to methemoglobin. They're changing it to methemoglobin and the enzymes in the red cell and/or oxidized reducing substances in circulation are changing it back. So that you or I will have only one percent methemoglobin. This balance between making methemoglobin and getting rid of it can be upset in different ways. Well water has been reported--people who drink this well water containing nitrates have been reported to develop methemoglobinemia in relatively large amounts. Or certain oxidant drugs will do it. A congenital enzyme defect will do it, and the entrance of oxidants generated in the gut will do it. We quantitated these phenomenon and put them on a sound basis in terms of knowing how to manage a patient. What your tools were.

Finch: He'd be blue. The only effect really would be that he not have as much oxygen-carrying capacity and he could be hypoxic. Some of the drugs that produce methemoglobin also produce red-cell destruction, so in some instances a drug-induced cause would be accompanied by hemolytic anemia.

Finch: I call it a condition because it has multiple etiologies. Congenital methemoglobinemia actually would still be of two types; it could be the enzyme type or it could be an abnormal hemoglobin. So, you really get down to define it as congenital-- let's say enzymatic methemoglobinemia--and those would be diseases. This is more--as a number of things--more physiologic in its connotations.

Finch: All of these studies--it should be emphasized--probably should be assigned to some other person than me. In that instance there was a remarkable group of people who were involved. We were a group, and in fact we wrote the paper by sitting around the table and getting ideas from each person. It was a group enterprise. We could show that some methods of measuring blood production and destruction showed very low rates of red cell turnover, and other methods showed very high rates. The ones that showed very high rates were bone-marrow derived. They were looking at the bone marrow, or they were iron kinetics studies, or they were bilirubin studies. Whereas other indices-- for example, the reticulocyte count was low. Anyway, from that type of study evolved the concept of ineffective erythropoiesis. They used to talk about maturation arrest. Whereas these studies showed that in fact cells were being produced very rapidly in the bone marrow, but they were also being destroyed in the marrow.

Finch: Dan Coleman was a chief resident at Harbor View who spent two years with me and went into practice after that. He's an outstanding practitioner in town. Arno Motulsky is a member of the National Academy of Science. Dennis Donohue went on faculty for a while here, became director of the King County Blood Bank, went to Washington, D.C. with the Food and Drug [Administration], I think responsible for blood products and now is retired. [R.H.] Reiff was a pathologist--a superb morphologic pathologist who had been at Minnesota before, who was a very close member of our hematology group. These are people who sort of came together and all participated in these studies. Arno tells me he was responsible for naming ineffective erythropoiesis. I had forgotten where it came from. I'm sure he's right.

Finch: No, that's a misnomer. I think the thing that we had fun doing was to write a book on iron. Dr. [T.H.] Bothwell-he's head of medicine at the University of Johannesburg in South Africa-

[END OF TAPE 3, SIDE 1; BEGINNING OF TAPE 3, SIDE 2]

Finch: He and I wrote the first edition, and then there were two additional authors on the second edition. But that was a lot of fun because we put all of our ideas together. I think that's probably the most fun for us. There are two types of things that give you pleasure, I think, when you're working. One is that you find something very special that wasn't known before. Perhaps the prostate hemolysis study where it was shown that distilled water got in the blood stream. But the other is when you put things together in your own mind and you think that's a good vehicle for people to understand what's going on in iron metabolism or iron absorption or whatever it is. In our work in blood preservation, we had a number of articles sort of getting to the point. But then, those, by themselves, are not worth very much to anybody who is a clinician, certainly. What he's interested in is what the practical implication of this really is. Does it really help?

Finch: I tend to underline those things that may have had a fair laboratory background, but which come to some clinical meaning. I thought a few years ago that we found something very exciting because we could show in studies on iron-deficient rats that they couldn't run well at all. We showed that that was because they became very acidotic. They couldn't burn glucose down all the way and developed a lactic acidosis. Stopped them from running further. Their body pH dropped way down. It was a beautiful study, by when it was applied to man, it was shown that humans really don't have that problem at all. As a piece of research, I thought that was great at the time. But when it had no clinical implication, it doesn't mean much to me.

Finch: Quite the opposite. I think I did more later on. You have to be a bit of a detective. The issue is not that animal observations are not relevant to the mechanism involved. It's just that you have to know what the differences in the animal are. In that instance, I think it was a function of muscle mass. We worked out a mechanism, and that mechanism is a valid mechanism and does apply to man. But not enough. I think if we could get a really, extremely muscular man and have him do that-- and make him iron deficient, we could show it. But its clinical relevance isn't significant.

Finch: That is what we need.

Finch: There are different components there. I grew up in the school where you did every experiment on yourself before you did it on anybody else. When it came to using radioactive isotopes, I couldn't do that from the standpoint of the radioactive burden that I would collect eventually. Things like bleeding, and methernoglobin production in myself, these studies I always did in myself before I did anyone else. This seemed a good way to evaluate the appropriateness for another person. The attitude about clinical experimentation has changed so that there are many things that we did years ago, which won't be appropriate now. What I'm getting at is, of course, that there are now protocols and things that really make you feel that you must be very, very certain of safety before you go to a clinical study. And a way to be much more certain is to try it out in applicable animal models. For most research of the type that requires clinical trial, use of animals gives additional protection to what you may want to do. Some studies can only be tested in animals. For example studies in pregnant women, fetuses, you surely can't approach these days. You need to go to animal models. The example of that is: can a very iron-deficient woman hurt her child by making him iron deficient? There are clinical studies that tend to say that in man, in women this really doesn't seem to happen, although you get some evidence on the other side too. We worked on animals. We could produce fetal deaths, fetal reabsorption, and so forth. Then when we worked out the calculation of how much iron was going. Ten fetuses growing at a tremendous rate, the requirements of those fetuses were maybe ten or twenty times that of the requirements of man per day. We had a clear explanation of why, in fact, it wasn't valid to say that the mother can hurt the fetus, unless she herself has cardiac problems or some other complication affected by iron deficiency.

Finch: Yes.

Finch: I think there should be a balance. It may be true that we did too much in humans and not enough in animals before. Of course, there are people now who say you shouldn't even do it in animals. You should use a test tube. I think the whole chain is the important thing. That each situation provides certain opportunities at each level. Hopefully, you should be free to pursue a productive line of research in the most indicated way.

Finch: I think that was the way it was done when I started. I know my mentor, Joe Ross, was of that philosophy. We did it also even before, when I was chief resident. We'd do things on ourselves before we would want to do it on a patient.

Finch: Yes. I can see the weakness of being overly motivated to find out something, but on the other hand, it may be better than nothing. I can say though, that in recent years, I've found myself psychologically reacting at times to experiments. I remember a time when we were studying the effect of removal of fairly large amounts of blood. I think I'd had 1500 cc [cubic centimeters] taken off. My cardiologist, whom I was working with, asked me if I was feeling any symptoms and I said, "I guess I am." He said, "Let me give you an injection that will level things off. You'll feel better." He gave me an injection and I felt better. Of course, it was a placebo. But you find yourself not always being the ideal subject. I think about then I stopped doing it because I felt I had invalidated myself as a subject. I don't think I had that trouble earlier, that I was aware of.

Finch: It's certainly changed. I think anything I'd have to say would pretty much be standard. We relied an awful lot on the fact that the patient had confidence in us and would accept the fact that if we said, "I think this is no problem here and it would help research," that they would say, "Yes," without having me really go through every possible complication that might have occurred. Now, of course, one has to be so revealing of every possible adverse complication that patients are not really given a completely unbiased picture of the thing. I do think we probably took too much on our own shoulders before. Now patients are much more qualified to make assessments themselves. They could probably be given in a little bit better perspective in some of the ways, but the possibilities of appropriate clinical experimentation have been improved by an informed population.

Finch: The Peter Bent Brigham largely had indigent people. It's a poor part of Boston. The county hospital here was similar. We did many of our studies on medical students, several hundred medical students. I think the racial derivation is not too different. They're both from northern Europe. If you have had little or no previous contact with the patient, the hard thing is if you just come in and say, "We're going to do this. Let me do this on you." I would be uncomfortable if I were the patient, too.

Finch: Certainly the more educated people are. Often ahead of you. What they've read or heard over the television set. What was very interesting to me--one time the army sent three or four of us over to ~Rssia to evaluate blood preservation? They were concerned because the Russians had reported keeping blood a hundred days, which turned out just to be in vitro observations. On the hospital wards, to the patients there, the doctor was practically a god. The doctor would say, "This is my friend from the United States, " and I would get the same respect. At that time, you asked a doctor, ''What do you tell the patient if he has an incurable disease?" And he'd say, "That he's going to get well. We wouldn't tell anybody he's going to die.'' I realized that the dependency of the patient on the doctor was based on his inability to participate. Whereas in this country now, patients think for themselves and are much more willing to take some responsibility for themselves. It makes a much more effective patient, in treating his illness.

Finch: I think that the attitude of people in terms of taking responsibility medically is almost unique in this country. What's your feeling?

Finch: It's a double-edged sword, but in the long run I think it's better.

Finch: No. I find it's a little awkward to talk about yourself. I have such a very positive attitude towards almost everything that's happened medically. It has been an unusual period in medicine, where a clinician could do research and teaching and not have to be highly focused on a very narrow area. It was a time when resources were available, all we could use and maybe more. I think probably, the good fortune that I had was to come to a medical school which within twenty years was in the forefront of the medical schools of the country. Also the countryside was attractive. Any accomplishments we did have were primarily due to the research fellows, the graduate-level people who came and spent a few years with us. The school itself is an in-house affair, where there are a few people, you see them a lot over the years. But when you have a stream of people coming in from all over the country and abroad, the stimulation that they provide is enormous. I think too little emphasis may be spent now in teaching, for providing an environment where people can learn. If there are good facilities, a flexibility, and people who are highly motivated, anything can happen. People go out and do important things. I think there is too little emphasis on teaching. One of the things that I thought was important was that our teaching program of the medical students in hematology be one of the best teaching programs in the school.

Finch: There are some wonderful schools, each with its own flavor. I forget how long ago, twenty years ago, I went down to San Diego. I thought I might go down there. I thought I'd leave here just because there was such a wonderful group of young people, and I thought, "It's not right for an old person to stay on when he's probably over the peak," which was, I'm sure, true. But they said they'd all leave if I left, so I didn't leave. I looked at San Diego. Marvelous opportunities there. They were different in that everyone was independent. We worked to get a cohesive unit, interdependent. I went down there and I said, "How can I fit in to this," and the answer, paraphrased, would be, "Well, just do what you want to do. We'll do what we want to do.'' In fact, they were awfully bright people, but with a different philosophy. I think that's a good school. My son is in Revelle, at UCSD, the state school, college, and wants to go there. I have encouraged him. Stanford is an excellent school, and it is unfortunate that its cost to the medical student is so great. Los Angeles is a very good school, but a very adverse environment. Yet very heavily supported. Much better than we are. We're the poorest school on the coast, as far as the state legislature is concerned, but well financed by grants. University of California at San Francisco is a first-rate school. I think all of these schools on the West Coast are very strong schools. You couldn't do better if you're a student.

Finch: I almost went down there, too.

Finch: I think it's probably a matter of timing. San Diego's the most recent school. They've picked people who are outstanding, such as the two presidents of ASH.

[END OF TAPE 3, SIDE 2; BEGINNING OF TAPE 4, SIDE 1]

Finch: The University of Washington Medical School was the first school in the Flexner mold since 1910 on the West Coast. Stanford was before then. Then there was a big gap. Then UCLA, then San Diego. I don't know where San Francisco came in. The California schools have all been supported well. It's rich state, heavily populated and they've had an opportunity to take in highly qualified people who were acknowledged to be good. I would say that the success of these schools at the present time is that they're new. That is really appealing: when you can come in and set up something. Looking back at the early days of this school, it was really remarkable how people were working seven days a week. Everyone was so excited at the beginning.

Finch: The older founders were dying off or leaving. It was over 40 years. I thought if a first hand--the opportunity of talking to people, trying to get their input--was going to happen at all, it had to begin right away. I spent about three and a half years talking with people and searching the archives. It was great fun. I had been working in an area and had my own objectives and so forth, but to look back at the school and its objectives. See how the early faculty was able to do what it did. The state gave so little money. Fortunately, the NIH came along. The timing was such that the NIH wanted to set up forward-looking committees to plan research. This school had picked young, promising people from all over the country. So it ended up that all of the committees seemed to have a lot of people from our school. Which meant that the ideas that the NIH would develop would be partly their ideas. They would also be impressed with what the NIH wished to develop and were in a favorable position to compete for grants. Everything went very well with the school. It was perfect timing. But to hear about the administrative problems and how various activities were funded. The book was written primarily for the alumni, who now amount to over 4,000. I thought they'd be interested in seeing the whole picture.

Finch: This school has the unique program of training family doctors. It's a coalition between Alaska, Montana, Idaho and Washington. About a third to a half of the class want to go in family medicine. About half of those take family medicine residencies. Most of those stay in the northwest. Concerning our own fellowship program, we had over two hundred fellows over the years. About two-thirds of them have gone into academic medicine. Of the other third, I guess it must be maybe 30 or 35 are in hematology/oncology in the northwest. I think, again, the strength of the school has been derived from the very extensive post-graduate training program. There are so many people going through the fellowship program that you can pick some really good people to stay around for awhile. That's different from going out and hunting. You know the people well enough to know you can get along with them. It was a lot of fun to do the history. In the process, I became aware that people in the northwest have little interest in what's happened. They're much more interested in what's going to happen. The documents that you would expect to find back east, about what has gone on with the school, you don't find around here.

Finch: Perhaps we are too young to be interested in history. Of course, when you go to Europe and see all of these wonderful pictures of past scholars on the walls of the lecture halls. Even in Boston and at [Johns] Hopkins you can see that. I asked the University if they didn't want to consider selecting an outstanding teacher and placing a picture in the library or some other appropriate places. But no interest in that. The Northwest is a very vigorous part of the world. Most of the people are still people who came from the East rather than were born here. That does make a different person. A little more hospitable to strangers. I think a lot more flexibility. I'm sure glad I had the opportunity to come out here. Just far enough away so that you don't get too many visitors but you enjoy them once you have.

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