Tullis: Yes, because what was called the Protein Foundation continued to operate, you see, and it supported my research, both there and then later when I was over here in my own department. We changed the name of it, because everybody thought as Protein Foundation, that we had money to give away instead of to get! So we changed the name of it; it's now the Center for Blood Research. For a very short period, it was called the Blood Research Institute, and then, eventually, the Center for Blood Research. It's been there ever since then, and it's a superb, very efficient, very effective, high quality institute, and one of my patients--well, this is how, again, things cross-fertilize.
A woman came along, was hospitalized by a physician at this hospital, the Deaconess, with thrombocythemia, which is a malignant disease of the platelets, that resembles polycythemia in the red cells, or leukemia in the white cells, but it's a disease that's compatible with many years of life. The problem is they have too many platelets, rather than too few, but instead of clotting, they bleed--almost always, occasionally one of them will clot. The reason they bleed is that most of the people with this disorder have non-functioning platelets, even though they have lots of them. So they present with bleeding episodes. Well, there was a very wealthy woman with the name of [omitted]. She was a widow, had no heirs, nothing else, and she kept bleeding, and being hospitalized all over the United States. They were trying to find out what was the matter--and finally, they made the diagnosis. And she would need platelets to support her. Well, I had been working on the separation of platelets in such a way that they can be used for transfusion purposes, and the storage of platelets. So I made these platelets available to her. This woman was so grateful that she used to call up regularly. I remember one time, changing planes in Chicago and getting a message that she was on the phone. She said, "I'm filling out my tax return. Now, I must give you some money for your research," which was just very helpful, to say the least, because this was now getting into the era where money was in short supply to support laboratories, and she would buy equipment and do all that sort of thing. Then, before she died, she asked me to come out to her home one last time, just to talk, which I did, and she said that she was going to leave instructions in her will, which the trustees would not have to follow but they probably would follow, and she divided her estate so that about a quarter of it came to the Deaconess Hospital and a quarter of it would go to my original research laboratories, which was the Center for Blood Research. The Center for Blood Research needed that money. They bought a building right up the street here on Francis Street, across from the Brigham, and established new laboratories there, and they have had a very successful laboratory ever since. Now it's all NIH-supported, because it's good, high-quality research, but the buildings and all of that, and all the overhead and everything, was originally supported at a critical time by this money.
Q: The research, in a review article--if I recall correctly--that you did, you said the research in platelets really took off in the 1950s in many different labs.
Tullis: That's right. Because they were available, you see, for the first time, for people to study. How did they function? How did they enter into clotting? How did they enter into work on sealing off blood vessels? And things of this sort. Because, you know, platelets were just one of these tiny little things you looked at morphologically, but you never had your hands on them, never had enough of them to work with them.
Q: And this was a result of the Cohn fractionation and--
Tullis: I think so. As an example of that, one of the diseases I was interested in, published on, is idiopathic thrombocytopenic purpura. We devised a test to make the diagnosis, and so on. Well, nobody could get enough platelets from a person with idiopathic throbmocytopenic purpura--because they have so few platelets--to do any chemical studies on them. And I wanted to analyze them. So we took this equipment of Cohn's, which permitted continuous flow, and brought from the Deaconess here across the street to my laboratory right up on the next floor over this office, brought patients over here that had ITP, and would let them be on this machine for several hours at a time, perfusing their entire blood volume through there. And even though they had a tiny platelet count, we would end up with enough platelets at the end of several hours, to do chemical studies on them. Then we found out that the sertonin was absent, the histamine was low, catecolamines were normal, and so on. Well, these were studies that one couldn't have done without having that other equipment simultaneously available.
Q: I would like to ask your assessment about your involvement with the Department of Defense and the role that both military and wartime has played in your work in hematology and work in general in hematology. You were in the Army during World War II. You were a consultant to the Department of Defense, as you mentioned before, and then, once again in 1968 and 1970, I believe, you were again a civilian consultant. I was wondering if you could speak about that.
Tullis: Well, I'm not a hawk. On the other hand, I feel there's nothing bad that doesn't have a little bit of good in it. There's no question but what medicine, in particular, has benefited from some of the tragedies of war, because under wartime conditions, you'll find people will work together who ordinarily are not very companionable.
One of the questions you asked me earlier had to do with the interaction between government, for instance, and the university, and so on. There's a book that's just recently come out--I think it's called Lactams or something. I have a copy of it sitting here can give it to you later on. It deals with the manner in which, under wartime conditions, penicillin was able to be developed by cooperation between the federal government, which had a need for it and the industrial concerns, which ordinarily would be so concerned about patent rights that they wouldn't disclose what they were working on. They were willing to throw all of this into a pool, which they decided they would settle after the war as to who got how much, and what percent, and all of this, and put all of their best scientists together to work on the same project at the same time. That's a type of cooperation you don't get in peacetime conditions, because people's parochial interests override their national interests.
The role during peacetime that I played in the Department of Defense, obviously, was that of the policy of Berry, the man who was the Assistant Secretary of Defense and the one who had asked me to be a member of his committee. His principal concern had been the misuse of physicians during wartime conditions, wherein they would be placed into administrative positions where they were not using the talents that they had been trained to use. They would be assigned to collecting statistics on something that had no relevant value, just to get them out of the way, and that kind of thing. So our committee, for example, one of the things we came up with was a plan, which we were able to put through Congress--that was later called the Berry Plan, wherein during peacetime, physicians who were drafted into the armed forces would have a prior opportunity through lottery to determine whether they would go in immediately after medical school, before their internship, or after their internship and before their residency, or after their residency, when they're Board qualified. They could pick the first, second, third, fourth or fifth year to serve their two years of obligated service, because there was a peacetime draft of physicians, which you may remember. That, then, was a concern of ours, after we got this Berry Plan adopted: to be sure it was applied properly. So that our meetings--we met every other month, six times a year--always were held in an armed forces installation somewhere where we could check on what was actually going on. And it was a small committee; there were about half a dozen of us on the committee, plus a couple of people to assist us. We would meet in Panama, Alaska, Nevada, wherever there was either an Army, Navy or Air Force base to check on, we would go out and actually talk with the soldiers, and we'd talk with the
physicians: were they practicing medicine, or were they counting beads, or buttons. I think it had a salutary effect. We had very little to do with the actual policy decisions about the way medicine was practiced, because there are Surgeons General in the Army, Navy and Air Force who are responsible for that. Our policy was more global and more in terms of total manpower use, and that type thing, but we could, from time to time, bring new concepts in, like the frozen blood one that I mentioned to you.
Q: That's another, it would seem, fairly obvious influence that war itself, along with all its tragedies, had blood preservation, transfusion, blood bank development--
Tullis: No question of it. And immunizations! Never has there been an easier way to study the effects of vaccines than if you have a control body of a million soldiers, you know, or ten million, as it was in World War II. These, you give this amount of vaccine, these, you give that, and we'll see who gets sick and who doesn't get sick, and that sort of thing. So it's a superb study in public health. I'm not in public health so I don't have a basic knowledge of it, but it's good from that standpoint.
Q: All right. Moving along, 1954, I have you as attending physician at Deaconess Hospital--
Tullis: That's right. That's when I was first beginning to practice, you see.
Q: Was there a change in your research interests, or priorities, at that time?
Tullis: No, not a bit. And I was able to keep it, if you will, subservient to my basic science background, which I was determined to carry on.
Q: You moved on to be Chairman of the Independent Medical Section.
Tullis: That's right, which was a small group of independent physicians.
Q: 1958
Tullis: That's right. It was the physicians who were not part of either the Lahey Clinic, which was also using the Deaconess, or the Joslin Clinic, which was also using the Deaconess. But then, in 1963, I think it was, they--the trustees of the hospital--wanted to change the character of the hospital, and make it a university-affiliated hospital. So they got the staff to vote to have new by-laws, and to organize a set of traditional departments. I was still working full-time, salary-wise and everything else, at the Center for Blood Research. It was then the Protein Foundation, but later the Center for Blood Research.
Q: Did that, once again, I would ask, did that in any way change your research interests, or did it spread your research interests to other--
Tullis: No, it really didn't, because what I did was bring back the part of the work at the Center for Blood Research that was under my personal supervision, bring it over to the Deaconess, and set it up in departmental laboratories. The financial support continued to come through CBR: my grant support, contracts, all of that business. I operated it as a separate division of the Department of Medicine here. Now, I continued that way until I retired in 1982, and the present chief has it all as part of his Department of Medicine. It's just administratively easier, that's all.
Q: The people who had worked in the basic research aspects under yourself, would they be recruited from among physicians, or would they have been trained in biochemistry, cytology?
Tullis: Primarily outside, not physicians. The Fellows were all physicians. The Hematology Fellows were all physicians who were, in part, getting their training, and they would divide their time between clinical hematology and research hematology, a year of each. But the persons who worked full time with me, like Francis Chao, who is a Ph.D., M.D.; Dr. Kenny is a Ph.D., she's still with me, these people are basic scientists.
Q: Did you see yourself playing the role of influencing physicians in any way, moving towards basic research, or--?
Tullis: I think so. I didn't do it with intent. But in talking with people and meeting people now, at meetings, who have trained with me, I see that they tend, some of them do, to stay in basic work.
Q: One of the points that Dr. Barry Coller had raised was he felt that hematology developed so rapidly in the post-1950 period was because of the close association with basic research, even in its clinical aspects, and that, more than most fields, was able to have, so to speak, a transfer of technology.
Tullis: That's right. I think there's no question of that. Plus the fact that blood is such a diverse fluid. Well, you remember that--I don't know whether you're an opera buff, but Goethe's Faust, you remember Dr. Faustus, says, "Blut ist ein ganz besondere zast." It's a very strange liquid; it's got everything in it! It, therefore, has to interact with so many disciplines of science, you see.
Q: Could you speak about how both the basic research aspects and the clinical aspects might have impinged upon your own work during this period, going from 1954 through the 1960s?
Tullis: Yes, I think so. Let's take some of the clotting work, for example. I was interested in having a prothrombin complex that would be stable after it was isolated from the blood. Prothrombin complex
consists of four closely allied proteins: Factor 11, which is prothrombin, Factor VII, which is SPCA, Factor IX, which is Christmas factor, and Factor X, which is the so-called Stuart Prower factor. These four factors influence both the intrinsic and extrinsic clotting system. If they're deficient, as is the case if one takes coumerin, the so-called "sweet clover disease" of cattle, called warfarin. There are certain disease states where there is one or more of these four proteins consumed; more would result in bleeding diathasis. So I was interested in having some of prothrombin-complex to study, and I asked Marshall Melin, who was a Ph.D. who was working with me in the Center for Blood Research, if he would attempt to do this chromatographically. Chromatography was a new concept at that time, a way of gently isolating proteins without damaging them. He devised a system, a flowing system, of removing the prothrombin from plasma, because we had still the resin way of collecting blood, which didn't have chelate in it. You couldn't do chromatographic techniques in the presence of citrate, you see, or oxylate, things of that sort--
Q: What years would this be?
Tullis: About 1960. There was another stumbling block. At this point, hepatitis had begun to rise on the horizon, and blood transfusions that previously had been present in World War II had been whole plasma, as opposed to albumin, but people began to be concerned about it. So I knew that any prothrombin fraction made from pooled plasma would tend to have hepatitis in it, because you were making it from a large pool. So I went to the NIH and told them the problem, told them what I wanted to do, and they supported the concept of plasmaphoresis. Now, that was a brand-new term, which we developed in our laboratory, because we had this equipment where we could hook a person up, run his blood through, and give back everything except what we kept. If you're only keeping the plasma, you can take large amounts out without harming the individual, you see, whereas if you take the whole blood out, you can only do it maybe four times a year, something of that sort. So I said I would be willing to identify some hepatitis-free donors that we could certify were free of hepatitis, that it would be costly, because we'd have to go through a pedigree one-year testing period, and find these people. They said, "All right, do it." Then I had to find some stable donors that were not gay blades and I went to the police department, which was then very much in the doghouse in the City of Boston because the Superintendent of Police had been found with his hand in the cookie jar and they were trying to improve their image, and I said, "Would you like to select some of your best stable officers from the community, and let them be blood donors for a plasmaphoresis program." Well, they'd never heard of that, nobody else had, so I explained what it amounted to, and we took a hundred volunteer policemen, said we wouldn't pay them for anything except for the time that they were actually out of work--just for their time on their days off, when they'd have to come to the laboratory. From that, we honed it down to forty people--eliminated some on the basis of blood tests, and other things, that made them look like they'd been sick--took forty of them, then, and took a unit of their blood,
and gave it to voluntary recipients, and followed the recipients for a year to see whether they developed hepatitis, and they didn't. So we knew that their blood as of that time was free of hepatitis. Because one didn't have tests, then, like the antibody tests and the radioactive tests now available that show you who was exposed, and so on. Then, those forty people who passed this screening, I asked them to promise they would never donate blood, or receive blood or anything outside of our program unless it was an emergency situation. These were stable, middle-aged men with families and everything---we knew they weren't, you know, gays, if you will--and they entered into this plasmaphoresis program, and I still have access to three of them today. Now this was 1960, so that's twenty-five years ago. So, we took their plasma, we would plasmaphoresis these policemen every week. Each had a day off, and so we'd do it on his day off. And we took their plasma, and then Melin fractionated with chromatographic techniques and produced a concentrate of this prothrombin material. Then, I was able to use that here for the treatment of people with Christmas disease--including the boy Christmas, the first one that ever had it; he came down from Toronto for his injection--and also to treat people with liver disease, or people who were going to surgery when they were on the coumarin and had to be reverted to normal clotting for an emergency period, that sort of thing.
So this was a, if you will, cross-fertilization, where some of these basic ideas you were asking about came into direct application to clinical medicine. And it's been in the clotting field and hemostasis that my interests have been, primarily, ever since.
Q: Could you comment on some of the other work where the cutting-edge issues would have been in platelet work, during that time period, late 1950s through the 1960s?
Tullis: Late 1950s through the 1960s, we were primarily working on the fractionation of the globulins that were present in people with immune thrombocytopenic purpura, primarily the autoimmune ones, and trying to identify what the proteins were, and also in the immune neutropenia, what the globulins were: were they gamma, or were they alpha, and so on. It was later on that I got into platelet work that's of much greater interest to me. That I can come to later on, if you're interested.
Q: Okay, no, we'd like to--I just wanted to fill in the gaps along the way. All right. During this period that you became chairman of this independent medical section, in 1958, then, in 1964, Chairman of the Department of Medicine, Physician-in-Chief of the Deaconess Hospital.
Tullis: The hospital was re-organized.
Q: Re-organized. Right. Were there changes in teaching, in training of hematologists?
Tullis: Oh, very much.
Q: Could you comment on that, and what the possible influences were?
Tullis: Well, at that time, for the first time, we had federal funding to support Fellows. This was a tremendous asset, because, if a young man went through his basic internal medicine in the program here at the Department of Medicine, and at the end of three years qualified as an internist, if he got the spark of hematology--and a lot of them did because it was one of the interests; we obviously taught a lot of hematology--it was easy. Anybody that wanted to do it, I knew we could fund his salary as a Fellow, you see, without going to hospital funds or hard money. And it was very easy to get a federal grant specific for the Fellows. We even had grants that we could use from the American Cancer Society and other places as faculty development grants. So if I identified somebody who I felt had a real future, I could get him a grant that would cover up to five years after his basic training was completed, while he was further developing as a young person in the department and in the field, and he could do research, because his time would be supported. He would also have to do some practice in order to remain au courant in medicine, but it wouldn't be his source of support, so he would be able to devote lots of time to research. So, I think, primarily, financial support was the thing I would say--as I look back on it--made the biggest impact on our ability to train large numbers of people. So the persons who had interest in and knowledge of hematology grew along with me. Just, from essentially nobody to--as Barry Coller told you--in ten or twenty years scores of hematologists! It was interesting that many of the chairmen of the departments of medicine in the medical schools and hospitals throughout America were hematologists. Lots of them were, and I think this had an influence, you see, in the training of the next generations. Dr. Doan at Ohio State, he was Chairman of Medicine there, Dr. Moore in St. Louis at Barnes Hospital; Dr. Sprague in Charity Hospital, down in New Orleans, and so on. All around the country.
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