DOE Openness: Human Radiation Experiments: Roadmap to the Project
HUMAN RADIATION STUDIES:
Early Training and Research
|MELAMED:|| This is September 28, 1994. We are interviewing Dr. Hymer
Friedell at Case Western Reserve University. The interviewers are Darrell Fisher
from Pacific Northwest Laboratory, and Elly Melamed from the Department of
Energy. Thank you very much for agreeing to spend time with us.|
As we [mentioned] to you before, this is meant to be an informational interview as part of the general initiative that we're working on; directed by Hazel O'Leary, the Secretary of Energy, to try to make as much information available about research involving human subjects. Our role is simply to locate records and give descriptions of where they are. And to supplement that, we're trying to interview people like yourself, who are involved in this effort; and just get your perspective on what went on and how you look back on it, and so forth.
|FISHER:||It's a privilege to be able to meet with you now, fifty years after the Manhattan Project. Can you believe that that much time has gone by?|
|FRIEDELL:||I think I can believe it.|
|FISHER:|| I had a chance to talk to you a little bit after your address
to the Health Physics Society, which was very interesting and well attended. It
was interesting to hear your perspectives on the work that you have doneboth
as a physician, as an officer in the Army [Medical] Corps and then your
perspectives on your work since then.|
As we read your biography and looked at some of the papers you'd published, and as I listened to your talk at the Health Physics Society meeting, I noticed that you had an early interest in radiation and the effects of radiation. Your earliest papers dealt with analysis of the functioning of the heart, using x rays. Do you remember this research, and can you tell us a little about it?
|FRIEDELL:||Yes I do, as a matter of fact. After I graduated from the
medical school [at the University of Minnesota], I decided that I would pursue
some postgraduate approach. And as you may possibly know, I first entered the
engineering school [there]. I was a good science student and good in
mathematics, and I thought it would be interesting if I entered the engineering
school. However, my family had already one physician, and there were others
coming along, and they sort of felt that I could perhaps pursue an academic
career in medicineinwell, I shouldn't say an academic career, but a
career in medicine. So I finally decided to switch, and enter the medical.|
So, I'd had a year of engineering, and I'd had a long interest in science. And I thought one of the things that would be interesting, and perhaps exciting because of the new things that were coming along, would be radiology.1 So I applied for residence at the University of Minnesota, where I graduated. And I was granted a residency, and I proceeded to pursue the appropriate curriculum. I also wanted to get an advanced degree, which was offered. So I then made arrangements to do some work in physiology.2 There I met Ansel Keyes, who was an associate of Dr. Vischer. Dr. Vischer was a professor of Physiology and also [was] interested in the heart. And naturally, they directed my interests into studying certain heart problems, that lent themselves possibly to x-ray examination. That's how I began my interest, and how I pursued research.
I was always interested in finding out something, so I didn't have the ordinary [clinical] residency. And they permitted me to do research as well. I did a lot of the research with Dr. Ansel Keyes. And our research really had to do with the physiological changes in the heart, particularly in athletes. Somewhere in the record, if you go back, you'll find Ansel Keyes's work. We, for example, examined all kinds of athletes who came to the University of Minnesota; especially those who were long-distance runners, or who were special athletes, of some sort, in the things that required strenuous activities.
I then decided to get a degree in which my minor was Physiology. So, under the guidance of Vischer and Ansel Keyes, I then proceeded to get an advanced degree; a Ph.D., as you may notice. So we did a lot of work on that. One of the interests we had is, we sort of devised a system whereby we could measure the heartsystole3 and diastole4and then try to correlate it with the actual blood propulsion; in other words, cardiac output. You may notice, much later on we even did some studies with radioisotopestrying to do some special studies. I'd had a fair amount of experience in looking into the literature, and so on.
|FISHER:||But those isotope studies would have come after.|
|FRIEDELL:||Much later. They were related, in a way, to things I'd been observing and pursuing in these early studies.|
|FISHER:||You published on the heart, both before the war and after the war.|
|FRIEDELL:||That's correct. That's how I got started. Naturally, when I got into radiologyin those days we also looked at radiation therapy.5One of the intriguing things was: "How does this radiation really do its work?" Slowly, slowly, we began to elucidate the mechanism of how this would happen.|
|FISHER:||Was this at the University of Minnesota?|
|FRIEDELL:||All at the University of Minnesota. I would say that the work in radiation biology then was, I would say, preliminary, maybe even superficial. Because no real study was pursued then, that could be identified in anyway as radiation biology, for example.|
Pre-War Radiation Therapy
|FISHER:||What sources did you use back before World War II for radiation therapy? What type of radiation sources?|
|FRIEDELL:||We used primarily x rays, usually around 200-kV6 machines, for
treatment. We used interstitial7 radiation and radium8
needles and radium plaques [for cancer therapy].9|
There were radium bombs, that they called them. We didn't have one, but I was aware that such existed. So I began to look into this more and more. I simply pursued the studies as they appeared. I found it very interesting, and I thought our cardiac output studies were very good. But they were a little laborious and cumbersome, and whether they could actually come to fruition in this way, from the point of view of being a practical application in the hospital, I think was uncertain. My main interest was to see if we could do it.
|FISHER:||Did you have a patient load for therapy of cancer?|
|FRIEDELL:||Yes, we did. The chief of the service was then Dr. Wilhelm Stenstrum, who
was under the general direction of Dr. Leo Rigler, who was the director of that
department, and who was a well-knownin fact a towering figure in
radiology, if you look into it. The main emphasis was on diagnostic radiology.
Because, after all, it did make an important contribution in the management of
Then, I got interested enough that someone, I think it may have been Dr. Vischer, who suggested that I might get a National Research Council Fellowship; because I ought to perhaps look around and see something more than what might be provincial in Minnesota. I'd really never been away from Minnesota much. So I accepted this, and I spent roughly three years, and I spent a year at the Chicago Tumor Institute, in Chicago. I was intrigued by that, because the director had, on the staff, Henri Cutard. Henri Cutard was one of the pioneers in radiation therapy. He came from France and had been working on special studies; particularly on the larynx.10 That was an interesting year for me.
I thought that he had many oddities in his approach to radiation therapy. He had an idea that there was an indirect effect. But his concept of an indirect effect, as compared to our biochemical approach, was a little strange. What he would do, occasionally, is that he would block off the tumor11 and treat the surrounding areas, which he considered possibly indirect.
Anyway, I observed this, and I thought that, after a bit, I'd learned what his general concepts were; and he was obviously a very dedicated individual. But I thought I ought to see what the citadel of cancer work was at that time, which was the Memorial Hospital;12 and they still [are]. So I got a year over there.
|FISHER:||In New York City. So you spent a year in Chicago, at the Tumor Institute?|
|FRIEDELL:||Roughly, and a year in New York.|
|FISHER:||How successful was radium therapy, back in those years before 1940?|
|FRIEDELL:||It was fairly successful, in the sense that, if you use interstitial13
radiation, certainly you could shrink down local tumors; without any question.
You see, the problem was: first of all, to get the very last nubbin of the tumorwas
somewhat uncertain. But, in many instances, if the lesion was reasonably
sensitive enough, you could obtain cures. The laryngerial studies that Cutard
did were very impressive. Indeed, what it did was save the larynx in many
instances. Because surgeons then were pretty aggressive. And if you had a
carcinoma14 of the larynx, you could consider this possibility.|
Now, it turned out, there's an anecdotal bit here: one of the patients at the Chicago Tumor Institute is a fellow by the name of Spencer Penrose. Spencer Penrose was an interesting man because, first of all, he was the brother of Boyce Penrose, who was then Governor of Pennsylvania, or had been Governor. I don't know the exact relations. Spencer Penrose had decided, when he developed a carcinoma of the larynx (he was, incidentally, a resident of Colorado Springs), that he didn't want the surgery. And had heard about Dr. Cutard. So he went to Paris, and was treated by Dr. Cutard. Dr. Cutard came to the United States, Spencer Penrose followed him, and he had a recurrence.
What happened then was that Spencer Penrose was a very wealthy man. Incidentally, he was the man who discovered the Crickle Creek gold mine. So, he owned about half of Colorado Springs. He was the man who built the Broadmore [Hotel] in Colorado Springs. In any event, he got tired of being in Chicago, so he bought a 400-kV [x-ray] machine from GE and had it put in his house. Somebody had to treat him, so they sent me there, because I had had some experience. I spent about a month, or three weeks, treating him.
In any event, it was an interesting side note in this history of how we did things in those days. But then, after that I left and went to New York, and I spent a year there. I was still interested in many things in New York, so I used to sneak off to the Neurological Institute and look at some of the things they were doing in regard to special studies in neural15 radiology. There I met Dr. Quimby and Dr. [Gioacchino] Failla, who were then on the staff.
|FRIEDELL:||Edith Quimby. And I got to know their approach to this. They were then
interested in interstitial radiation, in part, but also radiation therapy. And
that's where I discovered that they were using total-body irradiation for
various lesions. As a matter of fact|
(pulls out a book from his briefcase)
I brought this book alongI happened to look through it, and I found something that we will discuss at the appropriate timethat I had a list of the patients there, or I believe it to be the list, because I didn't note it very well.
Because, when I got into the Manhattan Project,16 there was a question of what we could learn about patients and their responses to radiation, especially total-body [ir]radiation, because we knew quite a lot about selected areas. After all, there was a fairly long history, with Bergonie and Tribondeau, who had done radiation studies on the sensitivities of various tissues.17 This had been going on for some time. There was a fair amount of gross studies in radiation biology. It was interesting to see whether there was any particular utilization of this at the Memorial Hospital.
|FISHER:||At Memorial, were tumors other than leukemia18 and lymphoma19 treated with whole-body radiation?|
|FRIEDELL:||Yes, they were.|
|FISHER:||Even solid tumors?20|
|FRIEDELL:||Oh, yes. Because it was really an experimental study. They abandoned the study, because they couldn't have any effect, usually. They couldn't give the patients enough radiation. Besides, they were terminal patients anyway. They selected some for terminal studies, and this became of interest to us, and we will discuss it a little later, since you've identified this in your letter to me. I can tell you something about this, and I'll give you some of the records that I have, or at least you can copy them if you like. They were interested in interstitial radiation. They didn't get a lot of it. They used to use a lot of what were known as radon seeds. Really, little fine tubes of gold tubing, which were sealed off at the ends, and contained radon. Then you measured them so you had an idea of the dose, and then you could insert them into the tumors.|
|FISHER:||They didn't last very long. Why did they choose radon seeds over radium?|
|FRIEDELL:||First of all, the radium had to be removed. The radon seeds could be left in there because they were decaying. The half-life21of radon, what is it, three-point-eight days, or something?22 They calculated the dose, and that's where Quimby and Failla were very helpful, in making these decisions about how to treat them and the distribution, and could make studies about how they should be distributed. That was intriguing too.|
|FISHER:||Do you remember which types of tumors, again, these capsules were used on?|
|FRIEDELL:||They were primarily used on solid tumors. Head and neck lesions were often used with this. Any localized tumor which would be accessible would be used. I think, rarely they did some surgery and found lesions that they couldn't do anything about, so they would implant seeds in them, as well. In general, solid tumors were treated this way. A lot of these were really confined to metastases23 in the head and neck.|
|FISHER:||Was there any successful use of whole-body radiation in New York?|
|FRIEDELL:||It depends on how you identify success. If you think of lymphomas or high-sensitive tumors or leukemia, there was no question that you could suppress the white count24 and suppress the tumors even. But you couldn't give them enough dose from whole-body radiation, as we could tell. The treatment for solid tumors was abandoned. They didn't use it. The only ones that were probably retained, and I don't remember this, certainly, were probably for highly sensitive lumps like leukemia with widespread infiltration or with, certainly, very sensitive lymphatic25 tumors.|
|FISHER:||How did you overcome bone marrow26 toxicity in these patients?|
|FRIEDELL:||We didn't. We simply made very careful studies of the bone marrow suppression by peripheral blood counts. Those were the major indicators of how far you could go with this.|
|FISHER:||Was the symmetry good enough to have a good estimate of the full-body dose?|
|FRIEDELL:||I think it was fairly good. Because Quimby and Failla were looking at this, and I think they had a fairly good idea. I wouldn't say that they had made careful studies. Because, after all, they were really guided by clinical responses as to whether they knew that radiation could interfere with cell proliferation or cell division.|
|FISHER:||Do you remember what some of the treatment protocols were at that time?|
|FRIEDELL:||I can't really recall them, but I think they treated them several times a week. Maybe three times a week, or something of that order.|
|FISHER:||What total dose did they want to achieve?|
|FRIEDELL:||That was, in partusually they went to about 150 or 200 rads27 for a total dose. Something on that order, as I recall. But they were guided mainly by what the responses were. And the primary response was white cell depletion, and probably the way a patient felt. Because, after all, some of them would get nauseated. These were the indicators. They were primarily clinical indicators.|
|FISHER:||Was the gamma radiation28 from radium sources?|
|FRIEDELL:||As a matter of fact, they were used very little. But at the Chicago Tumor Institute, which is affiliated with the University of Chicagoincidentally, Dr. Arthur Compton29 was the chairman of the Advisory Committee, which included Sir Lenthal Chettel, who had come from England; and Ludwig Hectom was a pathologist. So they had apparently decided that a radium bomb, which is really a large amount (I think it was 5 or 10 grams of radium), which was enclosed in a lead casing and shot when they used that.|
|FISHER:||So they used radium sources for whole-body irradiation. Did they use radium?|
|FRIEDELL:||I don't think we ever used it. I don't recall.|
|FISHER:||What did they use at Memorial for whole-body radiation? What sources?|
|FRIEDELL:||It was what they called a Heublein unit.|
|FISHER:||An x-ray machine?|
|FRIEDELL:||An x-ray machine. And I think it was at 200-kilovolt x-ray machine. And they simply used it elevated as high as possible, and the patients were essentially on the floor.|