Oral Histories: Radiologist Hymer L. Friedell, M.D., Ph.D.

DOE Openness: Human Radiation Experiments: Roadmap to the Project
Oral Histories

Oral Histories

Radiologist Hymer L. Friedell, M.D., Ph.D.

Foreword

Short Biography

Early Training and Research

Pre-War Radiation Therapy

Pre-War Experience at the University of California

Amount of Information Provided to Patients

Prominent Researchers Working at Berkeley

The Army Medical Corps and the Manhattan Project

Work at the Chicago Metallurgical Laboratory

Inspection of Manhattan Project Facilities and Proposed Sites

Search for Data on Human Exposure to Radiation

Purchase of a Cyclotron; the Manhattan Engineer District's Early Biomedical Program

Plutonium Injection Studies

Patient Consent in the Plutonium Injections

Advisory Role in the Early AEC Biomedical Program

AEC Isotope Distribution Committee

Advisory Role in the Early AEC Biomedical Program
FISHER:	You continued to serve the AEC¹⁰⁰ as an advisor and consultant?
FRIEDELL:	I did. And I served on a number of committees. If you look through the record, you'll find my name scattered—all kinds of things I didn't know I did.
FISHER:	One of the things that I'm curious about, and you'll have to forgive my insatiable curiosity—the 1947 Biology and Medicine Research Plan of the Atomic Energy Commission outlines the next five to ten years of essential radiation research, and divides up responsibilities among the laboratories and universities that were affiliated with AEC. The mission identified for you and for Western Reserve University was work on the toxicity of thorium.
FRIEDELL:	Yes, we never did it.
FISHER:	Was it not funded?
FRIEDELL:	I don't know why, but we never really pursued the program. It may have been that the University of Chicago was working on the thorotrast¹⁰¹ problem, as you may know. It may be that we decided we had plenty of other things to do first, and finally dropped it.
FISHER:	What was your major radiation-related research with isotopes?
FRIEDELL:	First of all, what we wanted to do was to see if we could develop some new approaches to the utilization of radioelements for diagnostic purposes, and perhaps therapeutic purposes. We did a number of studies. First of all, we did—most of our work was done on animals. We really did real studies on biological effects. Because it became intriguing to see if we could find special ways in which we could identify the mechanism, and maybe interdict it by various agents. In the process, we began to look at some new approaches. One of the things that was of interest to us, was the fact that we were able to prepare—we had a biochemist, I think it was [G.W.] Buckaloo. We had a biochemist, who was able to prepare (under the direction of Dr. Lavette, who was a biochemist also, who came on our staff before Dr. Nygard, as a matter of fact), in which we could make [radiologically] tagged [(labeled)] protein. One of the intriguing things with tagged protein was that if we could get a tagged albumen,¹⁰² we could then study blood volume very easily. Because all we would do is put something mixed in the blood volume and then take a sample, know what we put in, and what the dilution was on the blood volume. We did all this in animals, and then we came to our clinical staff. I need to point out that the radiologists didn't have a pool, or patients, on its own. We would go to the clinical staff, show them our data, and say, "Wouldn't this be a very useful thing for you to do in your clinical study? Because now you can measure blood volumes. After all, what are you doing now when you assess the amount of any element in blood? You don't know whether his blood volume is low or high. You ought to be doing it at the same time." It seemed rational. So we did some patients in which we used, in effect, tracer studies of albumen to study blood volumes. At the same time, somebody was doing something elsewhere and using tagged red cells. I think we may have done some studies to see which one was better. I think they tagged it with phosphorus. Again, it was the same kind of study. These are the only kind of studies. We never did any biological effect studies on humans.
FISHER:	Do you recall any radionuclide¹⁰³ metabolism studies at Case Western?
FRIEDELL:	Actual metabolism?
FISHER:	Radionuclide metabolism studies?
FRIEDELL:	You mean excretory studies?
FISHER:	Sure.
FRIEDELL:	Well the only studies we did—yes, we probably did some studies on thyroid patients, in which we wanted to measure the excreta and we wanted to see whether the data that was on the literature compared to our own, or whether we could develop special measures. We undoubtedly did some of that.

AEC Isotope Distribution Committee
FISHER:	You served as an advisor to Paul Aebersold and his isotope distribution efforts. Can you recall that work?
FRIEDELL:	I thought I was the chairman for a while. As a matter of fact, I do. I and Dr. Quimby, I believe were the committee. I think it may have been that Robley Evans¹⁰⁴ was also on the committee.
MELAMED:	This is the Committee on Isotope Distribution [of the AEC]?
FRIEDELL:	Isotope Distribution. It may have been Paul Aebersold that we responded to. If you say that, I believe it to be so.
FISHER:	I'm recalling from my memory, which may not be as good as yours.
FRIEDELL:	All I remember is that I served as the chairman and we received requests, which were sent to the AEC. The AEC, in turn, would send them to us for approval. I think I met once or twice with Edith Quimby. But the way we did it was: she would get a copy and I would get a copy, and then we would review this. And it may be that Robley Evans was involved as well, but I'm not sure about that. In any event, we would then decide: yea or nay. And our usual decisions were generally [based upon], what kind of experience did they have? What kind of facilities were available for them to do what they said they would do? Generally, if there [were] no obvious objections, we would approve it. It [be]came, before long, [a] somewhat onerous duty. And so we thought that perhaps they ought to do it formally, on their own. And if they needed an advisory committee, maybe we could form an advisory committee to see where the overall program was going. But for us to decide on each individual one, didn't appeal to us. Because it meant so much work. It was beginning to burgeon.
FISHER:	As more and more of these studies proposed human injections of radioactive materials, what was the committee's viewpoint toward this? More and more of these applications proposed the use of radioactive materials in patients for studies where there was no diagnosis or treatment of a condition.
FRIEDELL:	Generally we didn't approve them unless they were done for, "What are you going to do with it?," "We're going to try to study something to do this." One of the things that I recall is they wanted to see if they could identify the pancreas¹⁰⁵ by appropriate tagging of certain proteins. We said, "That's a good idea; it's hard to see the pancreas." If the doses were reasonable, we would approve it. Obviously those were a kind of metabolic general experimental background, so that we would approve it. Otherwise, it would look as if we were—after we were doing it, other people were doing it that were associated with the Manhattan Project—it would look as if we were keeping this all to ourselves, and we don't [want] anybody else to have anything to do with it. Generally, we were ready to approve any program that looked reasonable.
MELAMED:	I guess underneath the Advisory Committee on Isotope Distribution, there was a special Committee on the Allocation of Isotopes for Human Use. Was that the same people that you just mentioned, who were involved with you on that?
FRIEDELL:	I suspect that was special. Otherwise, we didn't want to be involved in somebody using carbon-14¹⁰⁶ for studying whatever it—fossils. So it must have been for humans.
MELAMED:	Human use was what you focused on?
FRIEDELL:	One of the questions that we started on was: "What do we do here in which we use humans?" The major ones we did was, first of all, we pursued that 32P [(phosphorus-32)] study that we started in California.
FISHER:	Intravenous 32P?
FRIEDELL:	Intravenous 32P. And we found some successes here in which we were able to ablate,¹⁰⁷ or in effect, eliminate some of the metastases to bone. We used radiophosphorus, and it's published. The other thing that we did—we thought was interesting. I still think it's interesting. I had worked with the heart originally, way back a million years early-on. One of the things that we thought was interesting was: a man by the name of Tinsley Harrison had introduced a system for measuring cardiac output by using a dye, in which he cannulated¹⁰⁸ an artery and then just took samples at periodic intervals, and then determined the dilution characteristics, and then could measure the cardiac output, which was something like what we wanted to do originally with x rays. We got the idea using the iodinated protein, albumen, which was injected. Then we could study in some isolated arterial area, the dilution characteristics, which would do the same thing; and therefore [was] a simple way of, in effect, sampling really what was kind of awkward if you did it by doses. And you wouldn't have to cannulate the artery. If you could isolate it, then you could look at it, and you could see the dilution curve. We published that, and it's in the reports. That dilution curve now told you what the cardiac output was. It was kind of clever. Because if you used iodinated protein, presumably it eventually came into equilibrium. Then, you see, you've got a fixed level which represented the final dilution level. We looked at the curve of dilution and the period of time at which it was obtained. By integrating this curve and comparing it with the final level, you could now determine the amount of the blood volume that had flowed during that interval of time. And therefore, you had the cardiac output. Now, if you wanted it in cc's [(cubic centimeters)], you just took a sample of the venous blood. So we thought it was great stuff. The problem with it was that isolation of an arterial pool was very difficult. We finally decided, by looking at a certain part of the aorta, we thought that would minimize venous pools. That's what we had to do. You had to look at an artery, the same pool all the time, and not seek after pools. Then, later on, we discovered that a good way to do it would be to arterialize¹⁰⁹ the ear. You do that by heat. You warm it up. You get the circulation going. Anyway, we did that in patients. Of course, we went to the clinical staff and they thought it was great stuff, or at least they thought it was good to do in patients. We did that and we also did arterial interference. That is, we found patients who had obstructions to flow. And now, that was a very good way of immediately identifying it; by simply putting counters¹¹⁰ over the feet. We thought we were doing a lot, but other [(pharmaceutical)]¹¹¹systems came along and the use of radioisotopes required more and more care and management. So eventually it petered out. That's what we did.
FISHER:	Was there, associated with these studies, concern for radiation side effects, irradiation of the thyroid?
FRIEDELL:	The doses were so small that you would have no chance in finding anything. The only side effects we ever looked at were those which we use in phosphorus, and widespread bone metastases from breast, primarily; in which we looked at the hematopoietic system. There, we monitored this very carefully in order to make sure that we didn't do more harm that we did good. That's the kind of studies we did. But we never pursued the patients for a long period. They were terminal patients, so it was really an approach for effective amelioration.
FISHER:	Were terminally ill patients normally selected to participate in tracer studies, or did you use—
FRIEDELL:	Well, we really didn't do tracer studies just to be doing them. By then, the literature was replete with all kinds of studies. We wanted to do something that was different. So we did these studies with the albumen. We did one other thing. We pancreatized some dogs, and fed them this albumen, and found, of course, that they couldn't metabolize it. And we thought that was a great thing for possibly looking at enzyme deficiencies and gastrointestinal studies. We introduced this to one of the clinicians who wanted to do it. So we fed some of it to patients and made some studies. This is the kind of work we did in humans here.
FISHER:	I [can] think of one more question.
MELAMED:	I have one more.
FISHER:	(to Melamed) Why don't you go ahead, and then I'll ask one?
MELAMED:	I just have a curiosity. This isn't an area that in any way shows up in the material that we've read of your involvement. But, after the war, there was a lot of discussion about the potential for developing radiological warfare¹¹² weapons, using these new procedures. Did you have any knowledge of what was going on in that area?
FRIEDELL:	The only knowledge I had was during the war. You may possibly know that there were reports that came out of the University of Chicago, in which there was a report which identified the possibility of using massive doses of fission products to occupy certain areas, or make areas uninhabitable. At the same time it said, "We must look at this because we don't know that the enemy may not be considering the same thing." That report came out, and then I never saw any report again. The question came up and I do remember the man, I don't remember his name. If I looked at the records, I would remember. I do remember the man who wrote the report. He was one of the physicists who was looking in general at these problems. Afterwards, I knew of no such program. The only thing that I was involved with was the Project Plowshare.¹¹³ The Project Plowshare, which was then being considered, the idea was to use nuclear explosions as excavation elements across someplace, maybe Honduras or someplace like that, to build another canal. The AEC director who was involved in this was a fellow by the name of Spoffard English. You may come across his name; if you go back and look at the records, you will find that he was the director. We probably met for a couple of years. There were military officers. As a matter of fact, one of the officers was the fellow who led the raid on Tokyo, the air officer. What was his name? Jimmy Doolittle was a member of the committee. There was another Army officer, who I think was an engineer, who was a member of the committee. Then we had other members of the committee who were interested in marine activities. And the two biomedical people who were involved were Louis Hempelmann and I. Before long, it became clear that it wasn't a tenable thing to do, and it disappeared. The other possible thing having to do with warfare, was the fact that there was a committee formed, I think in Cincinnati, but under the auspices of the AEC, with regard to considering flight by nuclear energy.¹¹⁴ The question came up, "Can you fly this great big thing and shield it? How would you do it?," so on and so forth. After a little study, it became pretty clear that it was a very difficult problem. It petered out, the way it should.
FISHER:	Did you have any involvement in the assessment of potential biological risk from this nuclear energy propulsion in the space project, or in aircraft?
FRIEDELL:	No. The only contact I ever had, surprisingly, was: One day one of our professors of Neurology came to me and he said, "We're going to go to the moon." I said, "What else is new?" It was years before we did it. He said, "They're going to the moon." I said, "What are you talking about?" He said they were going to have a program that they were going to moon. Apparently, there were some neurological studies that were being involved, and he was involved with it. He said, "Who do you know that would be free to work on space radiation?" I gave him the name of Cornelius Tobias.¹¹⁵ There were several others, but they liked Tobias. I think they contacted him, and I think he did work on it.
FISHER:	He's made a career out of studying interactions of high-energy particles with tissue.
FRIEDELL:	Right, I know that. I knew Toby very well and I kind of liked him. I felt he was a very sincere, honest, reliable individual.
FISHER:	I don't remember what year you first started working with the NCRP,¹¹⁶ the National Council on Radiation—
FRIEDELL:	It must have been in the '60s.
FISHER:	Was it?
FRIEDELL:	I served on their radiation study section. Wait a minute. The NCRP—It must have been about—I can tell you exactly when it was. It was about the middle, early '70s. That's not quite right. I was put on their board, or made a member; I've forgotten. I may have been a member before. I guess I [had] better retract. Maybe it was early as the '60s. But in the '70s, I was put on the board, and that's when I became more intimately involved. And I was on the board of the NCRP until I became its vice president. Then I was vice president for about six or seven years. I resigned because they said they wanted younger people. They said, "Anybody over 65 ought to be out." I was already 72 at the time. I felt, at 72, to show the flag, the proper approach. I resigned at 72.
FISHER:	Now in 1955, a report from the University of Chicago described incidence of thyroid cancers in children treated earlier in the '30s and '40s with radium tubes and radium applicators. Do you recall this report coming out, and what was your response to it? How did you feel?
FRIEDELL:	First of all, I think it was due to radiation. You say "radium." I think it was due to x rays. Michael Reese, the radiotherapist [after whom the Michael Reese Hospital and Medical Center in Chicago is named], I think was [originally] a European; and they were, in a way, even more cavalier than we might have been in the use of radiation. They treated a lot of conditions around the head and neck for relatively benign conditions. Patients that would likely have long survival rates [if left untreated], not for carcinoma or anything of that kind. I think also they treated patients for fungus diseases in children. Reports came out in which they reported tumors of the thyroid. I don't know whether it was carcinoma of the thyroid. I must confess, I was a little skeptical because I felt the doses—I think most of these were kids and the treatment for kids would have been on the skull, and they were usually 100-kilovolt x rays, which really were quite superficial. I was skeptical, but as the reports came on, I said, "It may well be that the thyroid is susceptible in some way." I felt sort of strongly about some of this, anyway. Because here, when I came here to the university, they used to make a practice of treating newborns with 25 to 50 rads over the thymus,¹¹⁷ because they thought that thymic deaths occurred. Because they would see enlarged thymus, and of course they had nothing to do with it. Here they were delivering pretty serious doses.
FISHER:	What years were those: in late '40s?
FRIEDELL:	No, they were done in the late '30s and early '40s, during the war and maybe during the '30s. When I found out about it, I stopped it. I think they muttered and fussed. I kind of wielded a lot of authority because they hadn't encountered radiation the way I had, and they thought I must surely know what I'm talking about. So they demurred, but they didn't always listen.
FISHER:	There was concern that enlarged thymus would inhibit breathing.
FRIEDELL:	They found crib deaths and they would often attribute it to the enlarged thymus, which wasn't correct at all. Children often have enlarged thymus normally. And they would see this by x ray, and say, "Yes, we have a treatment." So they did it routinely. I'm glad I had this impact.
FISHER:	Was that at this university?
FRIEDELL:	And probably done at other places. It may have been done at Michael Reese, as well. I've been interviewed by NBC, when the Eileen Welsome report got started [in 1993]. I have been interviewed also by a couple of Japanese outfits. More recently, who else? I think a German outfit wanted to interview me, but we never did make the arrangements, thank goodness. On two different occasions, Japanese came to interview me; TV broadcasting agents. They came once to my house and once, I have a place in California and they came there. They asked me questions. They were really interviewing me. The recent one interviewed me because they were going to have some kind of special program in 1995, which is 50 years after Hiroshima, and they prefaced this by saying, "One of the reasons we're conducting these interviews with you and others"—they had fellows like Phil[lip]Morrison¹¹⁸ on the program and [nuclear physicist] Hans Bethe.¹¹⁹ They used some others that are still around. They said that the reason was that the Japanese people feel that Hiroshima nuclear explosion was really a demonstration; that the war was over, that the Japanese could no longer resist, and the Americans either knew it, or sensed it. And we did it only to show that we could accomplish it. I pointed out to them—as I think you know, I went to Hiroshima and I was involved in various things—in any event, I pointed out to them that I had been stationed with the Third Marine Division, and for some of us to go into Japan after the war. But the Third Marine Division was all ready to invade. We would have had enormous casualties, and they would have had enormous casualties. Even though a tremendous number of casualties occurred, perhaps even more would have happened if we had invaded. From everything I knew, which is really—I had no special responsibility or authority—it looked to me that the end of the war was a desirable thing. We left it there. But then they asked me other questions.
FISHER:	What's the most remarkable memory you have of the Manhattan Engineering Project?
FRIEDELL:	I guess I would have to say my trip to Alamogordo, just before the explosion.¹²⁰ But a close second is my trip to Hiroshima, and the period I spent there. I think one of the remarkable things—also from a broad general point of view, it had little impact—was the idea that this enormous project was going to go forward with determination and earnestness when I got to Chicago. I said to myself, "Good heavens, are we really going to do all that?" And we did it.
FISHER:	There's few people who live today who have had these experiences that you have had. Certainly I missed out by a few years. We appreciate the opportunity to obtain an oral history with someone [with] as remarkable career as you had and so much to share. We want to thank you for it.
FRIEDELL:	I'm glad to do it. I think I probably should have written my memoirs at some time. I always feel that somebody else should write it.
FISHER:	Maybe in conclusion I could mention that you gave a paper just after the war to a small medical society in Pennsylvania on radiation and cancer. I don't know if you remember that?
FRIEDELL:	Yes, I did. The reason I remember it is that I had some slides that had to be specially protected because they were made of flammable materials. They had to encase the projector with all kinds of things. Yes, I remember it.
FISHER:	That was a very good paper, and as I read it now, almost everything you said was right-on with forty more years of experience. I want to congratulate you for that.
FRIEDELL:	Thank you very much. Can you think of anything that you would like to share with us that we haven't covered, that might be good to have on this tape about your experiences?
FISHER:	The only thing that was interesting in a way was the Hiroshima experience. But I don't know whether this is germane to the interests you have. If you want me to, I can tell you something about it, because it was kind of interesting as the way it was conducted and what we did, and what the problems were. It's just an interesting episode. Whether it had significant impacts, I doubt.
MELAMED:	I guess we're worried about time.
FISHER:	We're worried about time.
FRIEDELL:	We have to get out of here.
FISHER:	We could move to another place.
FRIEDELL:	What about lunch? Do you want to have lunch?
MELAMED:	Why don't we stop for now.
FISHER:	Can we take you to lunch?
MELAMED:	Thank you very much.