Q: Please.
Tullis: --a half-overcoat on that had my caduceus on the outside. But I quietly sat there so these important people, when they got on the plane, would not see me. The plane took off, and after it got up--it was still dark, it was now about three or four in the morning--but after it got up over the Atlas Mountains and over the desert, the temperature changed, and then it began to warm up at that point, because of the heat of the sun. So I got up to take off my overcoat, and, as I took it off, I saw this man lean out, way down the aisle, and spot my caduceus. Pretty soon he came running up and he said, "You're a doctor!" I said, "Yes." He said, "Well, I'm Baird Hastings." And I didn't know the name, which I'm embarrassed to say, but Baird and I joked about this subsequently. He talked to me a while: where was I in medical school? what was I doing? and so on, and I told him about my experiences thus far. I was just a plain lieutenant in an Army field hospital and evacuation hospital, and we chatted maybe ten or fifteen minutes while he was squatting on the floor next to me, and then he went back to his seat, and said nothing more.
About four hours later, we were over a place called Marble Arch, which is an interesting spot. It's just nothing but desert, but a gigantic marble arch which Mussolini built to commemorate the division between Libya and Egypt, which was settled during the time of Mark Antony, which I had not known about, but apparently, in those days, the way they settled the border between Egypt and Libya--this is two thousand years or more ago--was to start a runner, one from Tripoli and one from Cairo, and wherever they met would be the border. So the fastest runner got the most land. Apparently, the Egyptian was a pretty poor runner, because it's further from Tripoli--Libya--than it is Cairo. Anyway, Mussolini wanted to celebrate this event, because in those days Libya was part of Italy, and he built this huge arch, and there's nothing there! It's just total sand, and there's this arch sticking up!
Shortly after we flew over that, we were near the area where Rommel's forces were, and, to make a long story short, we were forced down. The plane landed. It was a little bit damaged in landing. We were right out in the desert, so we knew we were stuck there for a while. They had some pup tents on board, to bunk in, and the general, who was the head pilot of the plane, said he had made radio contact and he knew we would be rescued and everything, but we would have to bunk up. They only had three tents, and we had to choose up sides, and so on, as to who would sleep with whom for the two or three days we'd be there. And we had provisions, so nobody was worried about running out of water, and stuff. Then Dr. Hastings was kind enough to ask me if I would bunk with him, in this little pup tent, two people!
Well, for the first couple of days, we just talked about standard things. But each day he asked me more about, "what is it that your research is pointed towards?" So I got an opportunity to discuss with him my concepts of cell permeability and action exchange in relation to water, and tonicity, and so on. And he said, "Young man, I want you to work in my laboratory on this when the war's over." Well, I thought nothing about it. I thought it was like one of those shipboard friendships that I'd never hear anything more about. Then, that last night, when we knew we were going to be able to get out the next morning because somebody was coming for us, he pulled a watch out of his pocket just before we put the lantern out in the pup tent, and it was an old fashioned pocket watch like my father used to carry. You may never have seen one. It has a front that's glass, and you wind it at the top, and it has a back, a gold back that opened up, that sometimes would say, you know, "From Grandfather," or something, "to Grandson." So he showed me the watch. He said, "What do you think of this watch?" I said, "Well, it's full of mold." He said, "Yes, young man, and that's going to change your career in the practice of medicine." I said, "What do you mean?" He said, "This is the original culture of Fleming's penicillin and Roosevelt wants to teach the Russians how to make penicillin, and I am on a mission going to Russia to teach them how to do deep-vat cultures of penicillin, because most of the casualties from Stalingrad are deaths from infection." Tens of thousands of people were dying of sepsis, and they had nothing with which to treat it. Well, it turned out that this man Hastings, who was professor of biochemistry at Harvard and with whom I was tented, was head of the National Research Council Division of Biochemistry. And when the English, about two years earlier in the war, before America actually had gone to war, became afraid that England was going to be invaded, they wanted to get knowledge of penicillin someplace else, so that it could be developed there, rather than in Germany, and they had come over to the Division of Science in Washington and asked for help in learning how to make penicillin more avidly, because they were growing it just as a culture on top of vats, and you didn't harvest much penicillin that way. This man Hastings had conceived the concept of deep-vat culture, where you culture all the way down, you see, and magnified by a logarithm of three, three logs, the amount you could produce in twenty-four hours. So Hastings was selected to take this knowledge to Stalin for Roosevelt. It was a very secret mission, and one of the people with them was somebody who was from the NIH who spoke both Russian and English, and then there was Baird, and two other back-up people. That's why they were manacled to their briefcases, because of the knowledge that they were taking with them, all the formulae, and everything, for what to do and how to do it, and they didn't want to leave this in some washroom along the roadside, because you tend to forget briefcases. But anyway, that was just one of those episodes, you know.
Later, three years later, two years later, when I was discharged, I was surprised at the time of discharge to have a message there from Dr. Hastings saying, "Please call me in Boston and come to see me." And I came to see him, and I never have left.
Q: Just as a small digression, what happened with Hastings and his Russian adventure? Did they--?
Tullis: Oh, it worked!
Q: It worked; they got to establish--
Tullis: Oh, sure, sure, sure. Yes. After he got to Russia--and he told me this years later; he's now out in La Jolla and retired; he's in his high eighties, almost ninety--he spent three weeks there. He didn't travel by air but by rail, entirely. And they sent him to different areas that still were not invaded and had some industry, and he talked with biochemists and biologists md so on in these different places about how to do it, so they could make their own, and they did. And they started with that vial that he had.
Q: That's fascinating.
Tullis: All inside a watch.
Q: That's fascinating. That I didn't know- Were there other examples of that? The huge push to produce penicillin, and is there something that you could comment on, the types of cooperation?
Tullis: No, no. There's a recent book that's just come out on that. I'll give it to you later this morning; I have it here someplace. The Lactams. It describes it all.
Q: Okay; that's a little digression, but it was really fascinating. Okay, so, upon your exit from the Army for-
Tullis: I came straight here; still had my uniform on. I got out of the Army, I came straight here!
Q: Okay. And this was in 1945?
Tullis: December of 1945; right after the bomb in Japan. They knew they wouldn't need us in Japan, and our hospitals disbanded in southern Germany. I came straight here, and went to work using blood cells to apply the same studies that I had evolved in the Paramecium, you see. So I began to study the permeability of the white blood cell, because that was a single cell that you could work with, like an organism, something very simple. It's the only reason I was interested in blood, was because I wanted the tools, and the tools, the end product, were blood cells. So I studied this in Dr. Hastings' laboratory for three years.
Q: And Dr. Hastings was in which department?
Tullis: He was professor of biochemistry at Harvard.
Q: Okay. And what sort of techniques, methodologies, did you follow in your studied in permeability?
Tullis: Well--
Q: Were they standard for the time, or--
Tullis: Yes, they were standard for the time. I didn't use anything novel.
Q: And how did the work turn out?
Tullis: Well, there are publications on it.
Q: Just for the record, would you like to just summarize briefly.
Tullis: Well, we showed that one of the effects of circulating cells in the blood was related to the tonicity of the extra-cellular fluids. If you produce a hypertonicity from any mechanism--I did it with dogs, I did it with humans, and so on. And it can be, in a dog, deprivation of water, for instance. In a human, it can be diabetic ketoacidosis--anything that gives total colligative properties that are increased, results in an outpouring of polymorphonuclear cells. Anything that produces a hypotonic state, such as an excessive sodium diuresis and so on, things of this nature, we found would produce a depression of neutrophiles and an increase in lymphocytes, and this was based on the observations we made, just in vitro.
Q: Was this your first work in hematology?
Tullis: Oh, yes, yes.
Q: And your first contact with blood cells.
Tullis: Yes. Now, the next step, then, was that in the next building at Harvard Medical School, where Dr. Cohn was located. Edwin Cohn's work had been in plasma fractionation, the separation of blood into its component parts, or the separation of plasma into its protein parts. That work was based on Naval support. The U.S. Navy was desirous of getting an oncotic fraction that it could use to treat shock. Its submarines and so on would sometimes be out from base for weeks at a time, so they couldn't keep plasma, or anything of that nature, very well. So they wanted something that would be small, compact, easily transported, light, and not require refrigeration. The concept was that perhaps albumin would do this. So they came to him with a contract to produce albumin, which he originally did from bovine plasma, and then he later did it from human plasma. Being a superb individual, and a brilliant person, he said, "All right. I'll do this work for you on one guarantee." And they said, "What's that?" He said, "I will have total control over all the other parts that I get out of the plasma." He was smart enough to know that the gamma globulin and the fibrinogen and so on would be very much more valuable than the original albumin, which is really only something for use in disasters, and things of that sort. So he indeed did, and developed this huge program, and was made what's called a University Professor, which is different from being a professor in the department of a school, because a University Professor reports not to a dean but only to the president of the university. His budget is totally free, in the sense that he can go out and raise any funds doing what he wants to.
He, then, got together a multi-disciplinary group to work, and he decided in the late 1940s, primarily because General Marshall had then become head of the Red Cross after he retired, and he began to realize there was a little more to blood than just plasma, and he wanted to broaden it into a total blood program of support, and storage, and all of this business, and he went to Baird Hastings in the next building, and said, "Do you know anybody interested in blood cells?" And Baird was kind enough to say, "Yes, I have somebody working here with me, and that's why I was asked to head up a division for cytology in the Department of Physical Chemistry.
Q: Just for the record, I have you down as from 1945 to 1948 as a Research Fellow in Biochemistry, and this carries us until 1948?
Tullis: Yes. And then in 1948 I went with Cohn.
Q: Okay. You were also, at that time, a Fellow in medicine, and a Research Fellow in pathology, is that--?
Tullis: That's right, and now, the reason for that, again, relates to what I was doing. We needed blood to find blood cells for these studies I was doing. Well, leukemics have more white blood cells than normal people, and I said to Baird Hastings, "Where can I get a stable of leukemic patients?" "Well," he said, "Shields Warren, who's Chief of Pathology at the Deaconess Hospital, has just come up with something called radioactive phosphorus," because he had helped design the linear accelerator over at the M.I.T., and they were developing many isotopes to work with, so he had P-32 as an isotope to work with in acute leukemia. So he had quite a collection of leukemic patients there. And I came to Shields, and Shields said, "Yes, indeed, I'd like to have you work in the department here." So I split my time between the two departments. I got the raw materials here at the Deaconess and did the work at the Medical School.
Q: Could you provide some more background on, first of all, Hastings, and then, possibly, on Shields? Your impressions of them, and--?
Tullis: Yes, yes. They both had a profound influence on me as did Dr. Cohn, too.
Baird Hastings was sort of like a father figure to me in the sense that he was from the Middle West; he had gone to the same high school my brother had gone to, and that sort of thing. He just sort of took me under his wing and helped me get established. And without his help I wouldn't have achieved it.
Shields Warren, with whom I was partially assigned, had just been made the head of the Division of Medicine of the Atomic Energy Commission, because when the bomb was shot off in Hiroshima, Shields headed up the team to go in immediately after the capitulation by the Japanese to assay the biochemical, the pathologic, and the medical changes in survivors. This was because of Shields' early work, if you look in the literature in the 1920s and 1930s, he had studied radiation biologic effects with animals, and so on. He had been interested in what effects radiation had, because the Deaconess Hospital, at that time, had the only supply of radium--from the Curies--the first supply that came over to this country, from Madame Curie, and was being used for treating carcinoma of the cervix, and so on. So there was so much radiation going on as therapy in this hospital, he felt, as Chief of Pathology here, it was his duty to become skilled in the knowledge of how radiation affects tissues biologically. So a lot of his reports have been in that field. Hence, after the atom bomb affair, they picked Shields to head up the medical team to decide, actually, what took place. So he was really essentially never here. The three years that I worked with him my only real contacts with him of a scientific nature, where I would ask for approval for what I was doing and whether he thought the research made sense, would be as I'd drive him to the airport to fly back to Hiroshima or someplace like that. He was really very rarely here. But, he was a very charming, modest man, whom, in later life, I had as a patient and got to know very well, and admired greatly.
Q: You were also at that time a Fellow in Medicine? Were you practicing--?
Tullis: At the Brigham. No, no, I was not practicing. But, you see, I had originally been trained in medicine, and I wanted to complete my training, get my boards and so on, which I did. So, I worked one or two mornings and two afternoons a week, over at the Brigham, right across the street from the Department of Physical
Chemistry where Cohn was and Baird Hastings. That kept me involved in medicine enough so that I was able to get my certification and my boards as a specialist, and that sort of thing. But I was not practicing at that time, no. I didn't.
Q: Could you please talk about Cohn, and give some of his background?
Tullis: Edwin Cohn trained as a physical chemist in the early 1920's and he was greatly influenced by the Swedish school of chemistry, which was studying protein separation based on charge effects, and, similarly, the ultra-centrifugal approach to separation of proteins on weight characteristics and electrophoretic identification and so on. In the 1930s, he had been asked by George Minot to purify the liver fraction that Minot had found would bring people with pernicious anemia back from the edge of the grave to full life. These people had to eat pounds and pounds of liver every day in order to maintain their blood counts, and he went to Cohn and asked him to use his knowledge of protein chemistry to try to concentrate the fraction, which he did and which was brought out and used by physicians in the 1930s as a liver concentrate, and later on was found, of course, to be the B-12 fraction. But Cohn was working on those separations of a physical system, trying to separate the different proteins until he found one that had the concentrated material.
At the time, as I mentioned a few minutes ago, when the Navy decided it wanted to take plasma, and separate it, and try to get albumin, because, again, albumin, could be packaged in such a way that it would draw on the water of the recipient to attract water from the extra-vascular bed into the blood so you wouldn't have the weight of the water to carry around in the submarine, or tank, or airplane, or wherever. It did prove to be a very stable product, and so on, and so stable that it could be heat-treated and hence was free from hepatitis, and so on.
So they came to Cohn, and Cohn was a very interesting man. He was brilliant, and, at the same time, a very, I won't say, irascible person, but very difficult, as some brilliant people are, to relate to. And I'll never forget--I had no problems relating to him, but I think it's because I was in a different discipline from his. I'll never forget the afternoon that I was asked to be interviewed by Cohn--
[End of side one of tape one; beginning of side two of tape one.]
Baird Hastings apparently had recommended me to Cohn, and Cohn was never one to be bothered with details, and so, he just assigned it to some secretary to set up an appointment. They didn't know how to reach me, so they called the man who was chief of Hematology at the Children's Hospital, Louis K. Diamond, because Lou obviously knew me, since I was doing hematologic research. Lou called me on the phone and said, "You know Edwin Cohn, in the next building?" I said, "I know who he is." He said, "Well, he wants to see you about a personal matter, but before you go to his office today, come by and see me." So I went by, and Lou said, "Jim, I don't know whether he's going to offer you a position, but I want to warn you, the highway to success is littered with the wrecks of people that have hit head-on against Ed Cohn." Because he was such a powerful figure. So I said, "Well, thanks for the tip." Well, I went over to Dr. Cohn's office, and he described this very attractive idea that he wanted to broaden his department from just a plasma fractionation thing to a blood fractionation thing, to design equipment that would separate blood cells, to learn how to stabilize blood cells, to preserve them, totally to characterize them chemically, and so on, and offered me the opportunity to start this. I said, when we got through, "There's just one thing I have to say, Dr. Cohn, and that is I'm trained as a physician. I'm not trained as a scientist or as a Ph.D. physical chemist. And I am going to continue, no matter what I do, to maintain contacts of some type with clinical medicine, because someday that may be what I want to do." And he said, "What does that mean?" And I said, "Well, I go to the Brigham a couple of days a week and see patients in the outpatient clinic, and go on the rounds, and do a little teaching." He said, “Young man, you have to learn, if you're working for somebody, you're working for somebody. You're not working for somebody else. Thank you just the same." I said, "Well, thank you, Dr. Cohn," and left. So I thought that was the end of that. When I got back to Newton, about fifteen minutes later, the phone was ringing. It was Dr. Cohn's secretary. She said, "He wants to see you again." So I turned around, went back, and he said, "All right." He said, "You'll learn one thing, and if nothing else, you'll learn that the man that's paying you the salary is where your loyalty will be. I expect you to be available to me any time of the day or night that I want you." And I said, "Yes, Sir." And I made myself available. Whether traveling abroad with him, or whether working in the laboratory, or what, I was careful to keep any clinical medicine out of my time commitments in such a way I could be available to him. Now, I did do increasing amounts of involvement with clinical medicine, but I'd get to the Brigham or over here at the Deaconess, where I was also doing some clinical practice then by seven in the morning, so I could be in the laboratory by nine in the morning. That way it worked out all right.
Now, Edwin Cohn would have been successful in business, as well as in science. He was a great organizer. He ran a department that was like a corporation would run today. There was a sort of "corporate luncheon" we had every Thursday, a brown-bag luncheon, around a large desk in one of his conference rooms. It would sometimes last an hour, sometimes it would last till six o'clock that night! And everybody would sit there: Dr. Scatchard, from M.I.T.--all of the very famous people in science--Dr. Edsall, from the Department of Biochemistry over at the undergraduate school, Dr. John Enders and people of that type. Dr. Gibson, from Red Cell Studies at the medical school. People whose names would have meaning to you. We would sit there and just interact in an interdisciplinary fashion, and it really was excellent! I'd never seen anything like it before or since. Again, we had Cohn, because of what he had done in regard to plasma fractionation, he had unlimited research funds available to him; the Rockefeller Fund said they would support whatever he wanted to do. You know, when he wanted to hire somebody like me, it was just a question of hiring, you know. No clearance, no committees, nothing. Just boom! And he would make these empiric decisions free of administrative control. It worked very well, and it led to a dissemination of people who had been partly touched by him in a good sense, scientifically, who then ended up some in industry, some in universities, some in governmental positions, all over the world. It was just a procession of people through that department: visitors, students, Fellows, et cetera.
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