Oral Histories
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DOE Openness: Human Radiation Experiments: Roadmap to the Project Oral Histories |
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Oral Histories
Health Physicist William J. Bair, Ph.D. Biochemist Waldo E. Cohn, Ph.D. Dr. Patricia Wallace Durbin, Ph.D. Radiologist Hymer L. Friedell, M.D., Ph.D. Health Physicist Carl C. Gamertsfelder, Ph.D. Dr. John W. Gofman, M.D., Ph.D. Radiation Biologist Marvin Goldman, Ph.D. Hematologist Karl F. Hubner, M.D. Oral History of Radiologist Henry I. Kohn, M.D., Ph.D. Medical Physicist Katherine L. Lathrop and Physician Paul V. Harper Pathologist Clarence Lushbaugh, M.D. Health Physicist Constantine J. Maletskos, Ph.D. Radiologist Earl R. Miller, M.D. Health Physicist Karl Z. Morgan, Ph.D. Physiologist Nello Pace, Ph.D. Cell Biologist Don Francis Petersen, Ph.D. Radiobiologist Chet Richmond, Ph.D. Physician James S. Robertson, M.D., Ph.D. Biophysicist Robert E. Rowland, Ph.D. Biophysicist Cornelius A. Tobias, Ph.D. Biochemist John Randolph Totter, Ph.D. Oncologist Helen Vodopick, M.D. Donner Lab Administrator Baird G. Whaley
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DOE/EH-0470 HUMAN RADIATION STUDIES:
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Education and Early Training (1950s, Early '60s) | |
| CAPUTO: | Dr. Hubner, I would like to start off with your educational
background. |
| HUBNER: | Do you want me to start at high school? |
| CAPUTO: | Sure, wherever you want to start. |
| HUBNER: | I went to school in a small town, Tauberbischofsheim, which
means "the bishop's home on the river Tauber," in Germany. I graduated
from high school in 1954. Then I went to the University of Heidelberg straight
into [premed and] medical school. In the German system, the last 2 years of high
school are equivalent to the first 2 years of college. The average graduate is
20 years old; by then you are ready to go to the university. You could go into
law, medicine, or whatever. I went to medical school and graduated in 1959. As part of the graduation requirements for medical school, back then, we had to write a thesis. We had a choice between experimental work or some sort of analysis of data. I chose to do a rather lengthy project: two-and-one-half years of experimental work in bone marrow1 transplantation in animals. I started that in 1957, under the guidance of Dr. Fliedner, who spent quite a few years at the Brookhaven National Laboratory [(Long Island, New York)], working together with people like Dr. [Victor P.] Bond2 and Dr. [Eugene] Cronkite.3 At any rate, I was working on the thesis, which involved total-body irradiation of rats and transplantation of bone marrow and spleen4 cells to save them. This was in the early days of bone marrow transplantation ideas. Back in Oak Ridge,5 Dr. Charlie Congdon was one of the first to do bone marrow transplants in mice; and Dr. Stodtmeister, Professor Stodtmeister of the Medicine Clinic in Heidelberg, and his assistant Dr. Fliedner (both hematologists),6 were very much interested in [developing bone marrow transplantation]. So, with my interest in hematology,[I started my thesis work with Dr. Fliedner and] I became interested in bone marrow transplantation in humans. Dr. Fliedner at the time indicated that there may be something developing in the United States that I might [be interested in]. But first, of course, I had to do my internship, which in Germany is a two-year [program]. I did my internship in the Second General U.S. Army Hospital in Landstuhl, Germany, for 12 months and then rotated into the 86th Tactical Air Force Hospital [for the second year]. |
| CAPUTO: | So, was that a U.S. Hospital? |
| HUBNER: | [Yes], United States Army and United States Air Force. I did
12 months' rotating internship at the Army Hospital, which is a big hospital
(2,000 beds), the biggest in Europe. Then I switched over to the Air Force
Hospital and did family practice for a year. That was in 1960 and 1961. Then I
came to the United States as a [research] fellow to Oak Ridge. |
| HARRELL: | Was nuclear medicine7 work being done at the Air Force and Army
Hospitals? |
| HUBNER: | [Only in a limited way at the Second General U.S. Army Hospital]. I wasn't
involved. I was doing my basic medical training, just out of medical school. |
| HARRELL: | With Dr. Fliedner being from Brookhaven, was there other AEC8 involvement
with a lot of European doctors at that time? |
| HUBNER: | I think the University of Freiburg in Germany may have had some
collaborative common interest in hematology. Dr. [Ludwig] Heilmeyer, a very
famous hematologist, and Dr. Hoffman in nuclear medicine, in the early days and
at Freiburg, had relationships with the United States. |
| HARRELL: | But were there other members of your program at school who were involved? |
| HUBNER: | Who went to the United States? |
| HARRELL: | Or who were doing AEC work, was there any— |
| HUBNER: | I don't know of anybody. |
| HARRELL: | No? |
| CAPUTO: | I was just curious about the availability of radioisotopes in Germany
during the 1960s and where they came from. You don't know? |
| HUBNER: | I think it may have come from England. |
| CAPUTO: | Okay. |
| HUBNER: | I think most of what we had in Europe back then, was essentially
radioactive iodine. I remember in the basement of the radiation therapy unit,
which was a betatron,9
there was an early diagnostic imaging program being developed. This was in 1956,
'57, and we started to develop these dot counters10 and rectilinear scanners.11 This
was in the earlier days of nuclear medicine. |
| HARRELL: | You worked on that, too? |
| HUBNER: | I was peripherally involved. I saw those people everyday. So I knew about
it, and Dr. Scheer, who was in charge of that program. He's passed away,
unfortunately, prematurely. |
Research in Bone Marrow Transplants (Early '60s) | |
| CAPUTO: | How was your thesis? You did the rats and bone transplants. How successful
were you in achieving— |
| HUBNER: | We could clearly demonstrate that we could rescue these animals—not
all of them, but we could save a fraction of them by giving bone marrow
transplants. |
| HARRELL: | At that time, were there bone marrow transplants being done on humans in
Seattle [at the Fred Hutchinson Cancer Research Center]? |
| HUBNER: | No, not yet. No, much later. In the '70s, late '60s. |
| HARRELL: | Really? |
| HUBNER: | Yes. |
| CAPUTO: | Okay, so then you decided to go to— |
| HUBNER: | The bone marrow transplantation really started to pick up around 1965 to
'66. |
| CAPUTO: | So you decided to go to Oak Ridge because of— |
| HUBNER: | Well, because there was some indication that they are going to do bone
marrow transplants. |
| CAPUTO: | How did you have that indication? |
| HUBNER: | What happened in Oak Ridge that sort of pushed the issue, was the so-called
Y-1212
radiation accident. Dr. Lushbaugh13
may have talked about that. In June of 1959, eight men accidentally were exposed
to neutrons in this criticality accident,14 when they put enriched uranium into this
55-gallon drum. It reached a critical geometry and soon we had this small
nuclear excursion.15
[At] any rate, they got exposed to a range of doses from 28 rads16 up to 365
rads. Those people were admitted to the Medical Division of the Oak Ridge
Institute of Nuclear Studies [(ORINS)]17 in Oak Ridge. That hospital actually was opened in 1950, '51. Dr. [Marshall] Brucer was the first chairman, and they developed nuclear medicine. Eventually they had a patient research unit; I think it started with 35 beds and it was then scaled down to 28 and 25 beds.18 There was this so-called expertise in treating radiation injury. Nobody had confronted the situation up to that point. Nobody [had experienced this type of accidental radiation exposure], aside from the atomic bomb in 1945; that's a different issue. Dealing with fissionable material, you take the risk of having accidents. So, the question is: How do you save somebody's life who has been accidentally exposed [to potentially lethal doses]? The answer is: The best thing you could offer is a compatible bone marrow transplant. So, in the late '50s, I think the Y-12 accident really pushed the need for bone marrow transplantation. At the same time, the treatment of leukemia19 was a very unsuccessful effort, and we treated children and lost most of them. Translating accidental radiation exposure and rescue with bone marrow into medical applications in leukemia, aplastic anemias,20 and so forth—it's a logical step. So, the Biology Division of Dr. [Arthur C.] Upton and Dr. Congdon, they started to grind out the basic approach to bone marrow transplantation in animals after total-body irradiation. It was all there in Oak Ridge: the basic biology, radiation biology, and hematology, in this small clinical unit. So, that's why I went to Oak Ridge to get involved in bone marrow transplants. My appointment in Oak Ridge was limited. I got there in 1962, for one year, but then it was extended. I finally went back [to Germany], and my goal was to do pediatrics. So I went back to Germany in 1964, and did my residency in pediatrics at the University of Tübingen. Now what happened in Oak Ridge, to get back to 1962 and '63, and early '64, [was] they didn't do any bone marrow grafts. They weren't ready. |
| HARRELL: | Had they done some previously on animals? |
| HUBNER: | Animals, yes. But this went on outside the Medical Division. It was in the
Biology Division of the Y-12 plant, the weapons plant at Oak Ridge. There was a
huge basic biology program directed by Dr. Alexander Hollaender. He did the
basic radiation biology; huge program, one million mice in one building. I guess
[the] AEC put a lot of money into its facilities and programs. |
| HARRELL: | Was the clinic feeding off of their data and their research? |
| HUBNER: | No, not really; not really. There was some collaboration, and some of the
scientists who started at the Y-12 Biology Division in the Medical Division
developed and started a basic research program: like Dr. [Nazareth] Gengozian
and Dr. Urso, who was one of his associates. Later on, I worked with Dr.
Gengozian for two-and-a-half years in his lab. That was in the late '60s, early
'70s. Anyway, there was no bone marrow transplant during my first stay in Oak Ridge. What I did was learn nuclear medicine, which was [being] very strongly developed in Oak Ridge. I did a quasi-residency in nuclear medicine, and took care of cancer patients. |
Development of Nuclear Medicine at Oak Ridge | |
| HARRELL: | What kinds of things were you learning in nuclear medicine? Did they have a
set curriculum that you would go through? |
| HUBNER: | Well, back then there was no formal training at all. You see, one of the
missions of the Oak Ridge Institute of Nuclear Studies was to train people in
the applications and the use of radionuclides in industry; agriculture and
research; and chemistry. Nobody had that experience. It just became available in
1948 and 1949 when President Eisenhower suggested this peaceful ("Atoms for
Peace") program. They had people in Oak Ridge from all over the world, from all over the country, going to Oak Ridge to the Institute of Nuclear Studies. And they had these courses that trained thousands of people in the use of radionuclides. As far as medicine and nuclear medicine goes, there was this strong relationship to Harvard Medical School. They sent their third-year Radiology residents to Oak Ridge for half a year to learn the basics of nuclear medicine. So, they took the basic introductory course at ORINS, and they learned to do the liver scans and brain scans [and other] nuclear studies. |
| HARRELL: | All types of equipment? |
| HUBNER: | Oh, yes. Some of this equipment was homemade, prototypic-type equipment,
until then, finally, there was commercial equipment. The Ohio dual-head
rectilinear scanner was one of the first ones into Oak Ridge. Then in the '70s,
the gamma camera21
became commercially available. So anyway, in the '50s and '60s nuclear medicine
evolved slowly. In the '70s and early '60s there was no formal training program
[in nuclear medicine]. All these early nuclear medicine people, Dr. Henry Wagner, they came to Oak Ridge. That's where it was done. They went and took it back to Harvard, [The] Johns Hopkins [University in Baltimore], [University of Alabama at] Birmingham (Dr. Tauxe), etc. For many years, annual symposia on nuclear medicine were held in Oak Ridge. Everybody came back to Oak Ridge. Some people call [Oak Ridge] "the cradle of nuclear medicine." And certainly, Dr. Marshall Brucer was one of [the pioneers of nuclear medicine]. |
| HARRELL: | So that was a productive and busy time? |
| HUBNER: | Yes, everybody felt good and it was wonderful. There were no limitations.
Funding was a lot easier to get in those days. |
| CAPUTO: | Who did you work with during the 1962, '64 time period? |
| HUBNER: | The chief of medicine of the clinic was Dr. Beecher Sitterson. Dr. Gould
Andrews was the chairman of the Medical Division. Dr. [Ralph] Kniseley22 was the
associate chairman. Shortly after, I think it was after I came, we were joined
by Dr. [Helen] Vodopick23
and [her husband,] Dr. [Francis] Goswitz, who came as hematologists from Salt
Lake City. They, together with a fellow named David White, did the hematology
work at the Institute and assisted in testing radiopharmaceuticals24
being developed at the Medical Division. Dr. [G.] Kyker, who just died last
week, was director of the chemistry program. Shortly after he started, he was
joined by Dr. Ray Hayes, who later on actually built up the radiopharmaceutical
development program. |
| HARRELL: | During that period in '62 and '63, they were doing ingestion studies with
various nuclides. Dr. [George] Leroy25 did one with lanthanum and [S.R.] Bernard
with iodine-131. Were there other studies in that vein? |
| HUBNER: | Oh yes, there were thorough genetic studies. A lot of thorough genetic
studies. Dr. Bateaux did a lot of iron turnover26 studies. |
| HARRELL: | With iron-59? |
| HUBNER: | Iron-59 kinetic studies,27
and vitamin B12, and cobalt studies. The Schillings test, and these things, were
used quite heavily, like you would expect in hematology. Now, the iron
kinetics are only done in special studies. We don't do them here. We send our
patients to Nashville and other places, like [the University of Utah in] Salt
Lake City. |
| HARRELL: | Were all these studies related to cancer therapy or were they general
educational studies? |
| HUBNER: | They were not only related to cancer. Some of these things are basic
hematology. You see, one has to distinguish between three different types of
research. One is a clinical investigation for the purpose of developing a new
diagnostic agent which may benefit the patient down the road, or develop[ing] a
new therapeutic application which may benefit the patient down the road. Even
the patient who's getting the experimental treatment [as a participant in] a
stage 128
or stage 229
study, might [benefit from it]. That's one thing. If you do basic research just to find out how a certain tracer30 behaves in vivo [(inside the body)], its kinetics, how it is excreted—just for the sake of science—that is of no obvious benefit to the patient. But it might add to some more basic biochemical questions down the road that might help us to develop something that is of benefit. But if we use a patient just for this basic research, that's a different issue. You really have to determine the risks involved, very precisely, to make sure you don't do any harm. The doses they used are in the same range as being used today in accepted FDA [(Food and Drug Administration)]-approved tests. I don't think there was recklessness, in terms of the doses. That's the nice thing about radionuclides: You don't need a big dose to trace the radioactive material. That's what Dr. [George von] Hevesy31 did when he went and studied, in London, I believe. He had the sneaking suspicion that the kitchen was recycling the food for tomorrow and the next day's meal. So he put some radium on his plate when he was finished, and then he proved the next day—the radium was all over the place [because Hevesy's leftovers had been mixed back in with the kitchen supply]. For the tracer studies you can really use a tracer [(a small amount)]. |
| HARRELL: | The human subjects for those studies during the '60s; were they using the
patients who were in the Medical Division? |
| HUBNER: | Yes. |
| HARRELL: | About how many studies would they do in a year? |
| HUBNER: | Do you have copies of the annual reports? |
| CAPUTO: | Sure. Yes we do. |
| HUBNER: | All of the numbers are in there. There weren't many patients, the numbers
are very small. |
Experiment Protocols and Consent (Mid '60s) | |
| CAPUTO: | Were you ever involved—I realize you were still in your residency —but
do you know how an experiment would be approved during that time period? Who
would make the decisions and would propose experiments, how the actual
decisionmaking process occurred? |
| HUBNER: | The mechanism was something like—this was before human use committees
were in place anywhere. |
| CAPUTO: | Right, before. |
| HUBNER: | The first stipulation of protecting experimental subjects officially was
announced in 1948 in Nuremberg[, Germany]. Then in 1964 [the Accord of]
Helsinki, and in 1966 the American Medical Association suggested to develop
institutional review boards.32
So in March of 1966, Oak Ridge Associated Universities Medical Division
instituted an institutional review board called the Committee on Human Studies
of ORINS and the National Laboratory. Up to that point, and this was 1966, they
used a sort-of consent form; they had a general agreement when the patient
signed it. You have the copies in the [hearings of the U.S. Congressional
Committee].33 |
| CAPUTO: | Right, I've seen them. |
| HUBNER: | There were some general consent forms that had to be signed when the
patient was first admitted, and then more-specific consent forms developed, as
the program developed, that were signed and kept with the patient records in
addition to the global consent form that anybody signs—even coming to this
hospital you sign a consent form. Now the mechanism of developing the project was, there were lots of clinical conferences. Clinical conferences were typically every Wednesday morning—went on for several hours. That was the place to make suggestions, to come up with ideas; and then they would be discussed. A protocol could be developed and discussed extensively, then it would be approved and done. But the decision to develop, let's say, radiopharmaceuticals and put them in a patient, and [to determine] a dose and so forth, was a great, lengthy process. There was radiation dosimetry,34 [and the] radioisotope committee needed to look at the dose problem before it could be considered as part of the clinical protocol. Then it was by consensus, more or less, that something was implemented. |
| CAPUTO: | So there was no AEC involvement, it was purely—internal? |
| HUBNER: | Internal—yes, because the AEC knew exactly what was going on because
there were annual reports, progress reports, and budget requests. Each budget
request needed to be accompanied with a progress report: what have you done,
what were the results, and so forth. |
| CAPUTO: | Did the AEC provide feedback? |
| HUBNER: | Oh yes, sure. They discontinued certain projects, suggested to do other
things. But they—I'm sure they knew exactly what was going on [at]
Headquarters; they knew in Oak Ridge, and in Washington. |
| HARRELL: | During that time, in the early '60s, they were using the METBI35
facility quite a bit. Was there cancer therapy? |
| HUBNER: | Yes, quite a bit. They used maybe a total of 150 to 200 patients over the
years. |
| HARRELL: | They were also using chemotherapy? |
| HUBNER: | Yes. |
Bone Marrow Transplants at Oak Ridge (Late '50s and Early '70s) | |
| HARRELL: | How was the development of bone marrow transplantation being talked about
at that time? Was that something on the horizon that they were hoping to do? |
| HUBNER: | This was during the time when I was in Europe doing my pediatric training. |
| HARRELL: | When you were there earlier, was that talked about as something they were
going to do? |
| HUBNER: | Yes, but there wasn't a single patient they were trying while I was there.
I think the first ones they did were in the late '50s. There were [11 patients
with leukemia, who were treated with radiation and bone marrow infusion in 1957,
1958, and 1959. That was before I came to Oak Ridge. The results of those early
marrow transplants were published in ACTA Haematologica in 1961]. |
| HARRELL: | I thought there were four bone marrow transplantations. |
| HUBNER: | Yes, that was in 1970, '71, '72, '73. That was different. But that was a
more modern approach to bone marrow grafting. That was after we had learned
about the HLA36
antigens and matching histocompatibility37 of mixed lymphocyte38 cultures. Those things were not there in
1965. There was no white blood cell testing or match. Someone took a sibling, or
a mother or father, as the donor. The only thing we could match, or they could
match for, was the blood type. But there was no lymphocyte typing or HLA typing
and no mixed lymphocyte culture. That was available in [the late '60s]. |
| CAPUTO: | So when you were in West Germany in 1965, they did do some transplantation? |
| HUBNER: | In Oak Ridge? [I do not think so.] |
| CAPUTO: | Do you know who was involved with the bone transplantation in the 1965 time
period? |
| HUBNER: | Dr. Andrews was chairman. Dr. Sitterson was the clinical chief or chief of
clinical services, and Dr. White was in [outpatient] hematology. Then of course
[there were] Dr. Vodopick and Dr. Goswitz. |
| CAPUTO: | Do you know how successful they were? |
| HUBNER: | They were not very successful at all. So they stopped doing it.39 |
| HARRELL: | Was this similiar to other programs that were going on throughout the
country at the time? |
| HUBNER: | There may have been some attempts at other places—rudimentary. I don't
think anybody had a big program. A lot of the problems with these earlier
attempts in bone marrow grafting was, typically, a patient would be treated as
best as they could with chemotherapy—maybe some radiation therapy—until
all of the means were exhausted. And at that point, when you had a very sick
patient, who was immunosuppressed and defenseless as far as infection goes—at
that point they attempted bone marrow grafts. That was not the best way to do
it. Today we bring [in] patients in good shape and do the bone marrow grafts on patients in excellent condition; not handicapped by infections and other things. But back in those days, to justify an experimental approach like that, you had to exhaust the conventional wisdom and procedures and then reach that desperate situation, and then say, "Let's try it." So there were just 20, or 22, or 23 cases tried. When I came back in 1967, '68, they didn't do any bone marrow grafts. By that time, Dr. Gengozian had developed the immunological40 basis for bone marrow grafting as we do it today. The HLA typing became available. Dr. Gengozian and Dr. [Gayle] Littlefield—especially Dr. Littlefield, who's still at ORAU—developed and set up the mixed lymphocyte culture so that we could type and select the proper donor. |
| HARRELL: | This preceeded the attempts at immunotherapy41 that went on later with Dwayne Sexton?42 |
| HUBNER: | No, that was after [Dwayne Sexton]. |
| HARRELL: | But the bone marrow transplantation preceded that? |
| HUBNER: | [There were] two attempts [to develop a bone marrow transplantation
program] at the Oak Ridge Institute of Nuclear Studies or Medical Division with
bone marrow. One was in [1957 to '59,] the earlier phases. They did some
total-body irradiation, very modest doses, and injected bone marrow cells from a
sibling or relative. |
Total-Body Irradiation | |
| HARRELL: | They were using METBI in that program? |
| HUBNER: | [No, they were using a teletherapy43 cobalt-60 source in the '50s]. METBI, if
I'm not mistaken, opened up for business during 1965. LETBI44
was built in 1969. |
| HARRELL: | I thought it was built in 1967. |
| HUBNER: | Okay, okay. Then the second phase of bone marrow grafting was in the '70s.
So they did, or we did, one graft [each] in 1970, '71, '72, '73 and no more
afterwards. So there were four bone marrow grafts done, with appropriate
modern-type testing of compatibility and whole-body irradiation as the primary
immunosuppressive means. Actually, the total-body irradiation has two objectives. One is to kill all the leukemic cells that might still be around. The philosophy was to bring the patient into remission when the tumor burden or the load of leukemic cells is as low as possible. Then, if you come in with a large dose of radiation exposure, hopefully you can kill the last leukemic cell. So you have a clean starting point, and then you give the bone marrow and hope there is adequate immunosuppression to assure a take to supply the patient with the blood elements needed. So the protocol for those four patients at Oak Ridge was 500 Roentgen (R)45 whole-body exposure. They had a high dose rate, and concomitant immunosuppression with antithymocyte globulin (horse antihuman or goat antihuman thymocyte globulin) to augment the immunosuppression, followed by the bone marrow graft. Actually, the sequence is: you give 7 days of immunoglobulin, followed by the total-body irradiation at the end, followed by the bone marrow graft within a few hours after the total-body irradiation. So we used 500 Roentgen, the high dose rate of approximately 45 to 50 R per minute. Today, in 1994, the doses are 1,000 to 1,200 R given in fractions over a few days. But the total dose is 1,000 or 1,200. The reason we used 500 in Oak Ridge is that Dr. Gengozian had shown that a radiation dose delivered at a high dose rate is more immunosuppressive than a larger dose given at a lesser dose rate. That was shown in animals; there was no doubt about it. It turns out that, shortly after we started talking about 50 rads per minute of exposure, the [group at M.D. Anderson Hospital at the University of Houston] upped their dose, too. They went higher, up to 26 R per minute. So you get the same immunosuppressive effect with a higher dose rate, but a lesser [total] dose. Then you put the patient at a lesser risk, because we know that with the properly [matched] bone marrow you can save anybody who's basically healthy—with a matched bone marrow graft. We know we can save somebody with 500 or even 750 rads. With today's sophisticated techniques of isolation, laminar air flow units, antibiotics, sterility, we can save [patients] with a matched bone marrow donor. We can save somebody after these high doses. |
| HARRELL: | Was this using the CARL46
facility for these doses? |
| HUBNER: | Yes. |
| HARRELL: | Was some of the research that indicated that higher dose rates would be
effective [based on] on the METBI experience? |
| HUBNER: | No, that was, [I believe, a cobalt-60 source]. |
| HARRELL: | Animal Reserach? |
| HUBNER: | Animal research, and I forgot what Dr. Gengozian used. There were two
teletherapy machines there. One was a cobalt-60 and the other was a cesium-137
machine. They could both be used to deliver high dose rates to a cage of
animals. For those experiments, METBI doesn't make much sense because the dose
rate is 15 [R per hour]. |
| HARRELL: | 1.5. |
| HUBNER: | 1.5 R per minute [for METBI] and for LETBI, it was 1.5 R per hour, a factor
of 60. So METBI would not be a good machine to use to get high dose rates. But
if you have a radiation therapy [machine] (teletherapy that we use in oncology47 today), if
you put that cage close up, you can have a very high dose rate. |
| HARRELL: | At what time were these experiments done indicating that the higher dose
rates were effective? |
| HUBNER: | Well I guess it was in 1966 and '70 that—there are some papers that
were published. |
| HARRELL: | At the same time, you were going to higher doses for bone marrow
transplants and— |
| HUBNER: | Higher dose rate, [not higher doses]. |
| HARRELL: | LETBI was going to lower doses at the same time? |
| HUBNER: | Yes. |
| HARRELL: | Was that because you were treating different cancers with the two methods? |
| HUBNER: | Yes, the high dose rate was considered to be necessary for preparing
someone for a bone marrow graft—that's one issue—in the process also
killing the last leukemic cells. But the lower dose rate was an attempt to treat
slower, less aggressive processes like lymphoma,48chronic lymphocytic leukemia,49 and
polycythemia vera.50
They're not as aggressive as acute lymphoblastic leukemia.51
They're chronic blood diseases, proliferative diseases, that can be treated with
a less aggressive form of radiation therapy that does not put [the patient] in
jeopardy, as far as infection is concerned. Excessive suppression of the bone
marrow, that's the idea to give as much as needed to keep the chronic
lymphocytic leukemia in control, but give as little as you can [get by with], in
order to save the bone marrow. That's the philosophy behind it: low dose rate
that doesn't cause any side effects. If you go to a higher dose, you get nausea,
etc. So that was the philosophy. |
| HARRELL: | Were there animal experiments that used low dose rates that demonstrated
this? |
| HUBNER: | Yes. |
| HARRELL: | The effectiveness of this therapy? |
| CAPUTO: | Any potential effectiveness? |
| HUBNER: | Yes. I don't know of any animal model for chronic lymphocytic leukemia. I
think dogs may have it, but I know that they didn't do any dog [leukemia]
experiments [in Oak Ridge]. You really have to ask someone else. I don't think
there is a rat model for chronic lymphocytic leukemia. But I don't think anybody
did therapeutic experiments with animal disease models [at ORINS or ORAU]. |
| HARRELL: | So they built the new LETBI facility just on the theory that this would be
more effective? |
| HUBNER: | Yes. I think so. |
| HARRELL: | The CARL facility was already built for other uses? |
| CAPUTO: | That was the University of Tennessee facility. |
| HUBNER: | Yes. That was AEC. That was in '65 and later in the '60s with ERDA.52 |
| CAPUTO: | Right. The CARL facility was built for agricultural and animal studies. |
| HUBNER: | Yes. They had one facility, I guess it still exists, with six huge cobalt
sources. Originally each was 75 curies of cobalt. The room was large enough to
bring large animals in for radiation exposure experiments. |
| CAPUTO: | Why do you think, in the 1970 bone marrow transplant effort, that it was
not successful—or do you think it was successful in some terms? |
| HUBNER: | After the '70s? |
| CAPUTO: | Right, in the '70s, the ones at Oak Ridge? |
| HUBNER: | Well, we had success in those four transplants. I didn't say we were never
successful. One of them survived [for] a year. He died from a heart attack and
he was still free of leukemia. |
| CAPUTO: | Okay. |
| HUBNER: | A local man from Knoxville was a successful transplant. Another one was
successful, in the sense of sustaining that woman's life between six and nine
months, pretty much disease-free. These were early successes. Two of the
patients developed a reaction called graft-versus-host reaction.53Which
is the same problem today if you don't have the perfect match; you run the risk
of killing a patient with graft-versus-host reaction. That's even true today.
This is just the basic biologic consequence if you don't have a good match. The
lymphocytes of a donor can easily attack the recipient, or kill, and this is
classical graft-versus-host disease. So no, we were very happy about what we
achieved. |
| HARRELL: | Was there hope of setting up a successful long-term transplantation
program? |
| HUBNER: | Have you been to the Medical Division? |
| HARRELL: | We haven't visited that facility. |
| HUBNER: | One of the criticisms of the past of this medical division was [that] it
was disconnected, isolated—it was not associated with a major medical
facility. It did not have patients, didn't have the resources to maintain—it
was very expensive to do this kind of clinical research. So, that was one reason
it was eventually closed down. As clinical investigations were concerned, it was
not [the] only one that was shut down; [the] Brookhaven [research hospital] was
shut down, Argonne [Cancer Research Hospital in Chicago],54 Navy
Hospital in California. |
| CAPUTO: | So it was part of a national— |
| HUBNER: | Oak Ridge was one of the last ones to be shut down. Now, in the
state of Tennessee, there is not a single medical center with a clinical
investigative unit. There is no way to do clinical investigations like they did
then. There was a place and role for these laboratories in Brookhaven and
Argonne and Oak Ridge and Los Alamos to develop nuclear applications in biology
and medicine. |
| HARRELL: | Were there any institutions that were using what you learned in your bone
marrow transplantations to develop their own program? |
| HUBNER: | Surely, they read our paper and they knew what we were doing—and Dr.
Mortimer Bortin, I guess he's now in Seattle [at the Fred Hutchinson Cancer
Research Center]. We adopted Dr. [E.] Donnall Thomas's55 method of procuring the bone marrow. We
used his method of preparing bone marrow exactly the way he did it. As a matter
of fact, he came to visit and told us how to do it. We were happy to see that
the Nobel Prize for bone marrow grafts involving total-body irradiation, finally
[was given to Thomas]. It was two or three years ago. |
| HARRELL: | You were all very happy to— |
| HUBNER: | Sure, because we were part of that development. Nobody had the solution,
but we tried and we were very happy for [E.] Donnall Thomas to get the Nobel
Prize for bone marrow transplantation. |
| HARRELL: | When you went back to Germany to work on pediatrics, were you working on
pediatric cancer therapy? |
| HUBNER: | Yes. Leukemia and immune deficiency syndromes. We had also ideas about bone
marrow, and we did bone marrow grafts in Germany. It was not very successful;
that was in 1966, '67. A young patient, named Romanoff, had immune deficiency
syndrome. One aspect about these experimental investigational approaches to
blood diseases or leukemia or immune deficiencies is the problem of the danger
of infections: how do you isolate the patient? The patient we had was isolated in a bubble-like sphere. You know David, the bubble boy [in Houston]? We had a smaller bubble for our immune-deficient child in Germany. In Oak Ridge, for the bone marrow transplantations, they had built a very fine, up-to-date, cutting-edge, isolation facility called the Laminar Air Flow Unit, where the patients were kept under practically sterile conditions. The food was sterilized— everything that went in, and there was constant filtration of the air to keep the air clean, to prevent the patient from getting infections. Because, following the total-body irradiation, you get this severe depression of the bone marrow which lasts for about three to four weeks before you can see quick recovery. So you have to protect the patient from infections. That was well-done in Oak Ridge, and it was a shame that this facility was taken out. The costs, [according to] Dr. Baylisch, the microbiologist on the team, to keep the patient in a sterile environment back in 1970, was $10,000 a month. |
| HARRELL: | Is that high by today's standard? |
| HUBNER: | Sky-high, just to keep the environment clean. |
| CAPUTO: | How long would they normally be in that room? |
| HUBNER: | Well, fifty, sixty days. So there was every effort made to make this
clinical experiment safe, safe as possible. |
| HARRELL: | That money just came out of the overall budget? |
| HUBNER: | It was budget. By today's standards, talking about health costs and
research money, it couldn't be done. |
PET Scanning and Imaging | |
| HARRELL: | So when did you get into tomography56 and imaging? |
| HUBNER: | Oh, that was—I had also learned nuclear medicine in Oak Ridge. |
| HARRELL: | Was that in '62 when you first— |
| HUBNER: | Yes, right: that's when I— |
| HARRELL: | —learned about that? |
| HUBNER: | Yes, and I got back into it with Dr. Hayes when he and Dr. Washburn
proposed to use positron57
emitting and radionuclides and radiotracers for the detection of cancer. See
that's the way I got into what I'm doing today—is pediatric, pediatric
oncology; leukemias, other cancers. And now I have got into how to detect
cancers [and methods to] measure the response to treatment. So with positron
tomography, as proposed in the mid-70s by Michael Phelps at [the] UCLA58 group
and Hayes and Washburn in Oak Ridge, they proposed to use carbon-11–labeled
radiotracers, amino acids59
in particular, as tumor-imaging agents. And the reason they used carbon-11 is
because that was the only thing you could make at the 86-inch cyclotron at Oak
Ridge at the Y-12 plant. They developed the synthesis methods to tag amino acids
with carbon-11, and I did the clinical part of it with positron tomography. We
finally got a grant from DOE. Actually we had a grant from NIH60 to buy
a positron tomograph. |
| CAPUTO: | What year was this? |
| HUBNER: | It was 1977. Then the grant was $240,000, and we were $40,000 short. And
DOE chipped in $40,000 so we could pay for the machine. These machines today
cost [between 1 and 2 million dollars]. |
| HARRELL: | That machine was given to what organization? |
| HUBNER: | That was given to the Medical and Health Sciences Division of ORAU. By that
time it [(ORINS)] had become ORAU. So that was the first, actually it was the
second, commercially available PET61 scanner. We were supposed to get [the]
first one, but our site wasn't ready. So the first one went to UCLA. |
| HARRELL: | Did ORINS assist in developing the prototypes of that machine? |
| HUBNER | No. That was developed at the Mallinckrodt Institute in St. Louis and then
taken over by EG&G ORTEC in Oak Ridge (a company that makes a lot of
different radiation detectors). A core group of people who were associated with
the development of positron cameras bought out that part of EG&G ORTEC and
established an independent company here, between Oak Ridge and Knoxville on
Pellissippi Parkway (CTI, Computer Technology and Imaging). They are now,
together with [the German industrial giant] Siemens, building cyclotrons62 and SPECT
cameras.63 |
| HARRELL: | What kind of machine would they use for gallium tracer work? |
| HUBNER: | For gallium, we used a whole-body rectilinear scanner, which was originally
developed by Ohio Nuclear. It was a dual-head detector, with one detector on top
of the patient and one below the bed. The detectors would move across the whole
patient and scan the whole patient. That's what we used for gallium. Today
nobody's using rectilinear scanners anymore. Today we use whole-body gamma
cameras. Gallium is still used; and that was—I should [have] mentioned
gallium was one of the radionuclides, tracers, with gallium citrate, developed
at Oak Ridge— that was one of the early good successes. |
| HARRELL: | That was developed right near the end of the Medical Division program—early
'70s? |
| HUBNER: | Late '60s early '70s, you're right. There was this multi-institutional,
collaborative study with the Oak Ridge [National] Laboratory [(ORNL)].64 Ray Hayes
would distribute the gallium that was produced at X-10 [(an early name for
ORNL)] and ship it to these different collaborating sites, for the purpose of
getting a large number of patient studies with gallium-68 citrate, to get a
statistically significant number in a short time to promote the tracer. Now it's
[in use], worldwide. We do gallium scans every day here [at the University of
Tennessee Medical Center]. |
Immunology Research at Oak Ridge (Late '60s) | |
| HARRELL: | So when you first returned to Oak Ridge from Germany [in 1967], what kind
of work did you start out doing? |
| HUBNER: | That first time, I spent two and one-half years, I believe, in Dr.
Gengozian's laboratory. I did basic immunology. |
| HARRELL: | Were you assisting with immunotherapy research? |
| HUBNER: | Not with immunotherapy, no. |
| HARRELL: | He was doing that at the same time? |
| HUBNER: | He never did immunotherapy. His interest was primarily: number one,
immunosuppression, amino therapy, immunosuppression for preparation for bone
marrow grafting. He was basically interested in the mechanisms of
immunosuppression, basic science. The other thing he was interested in was the
biological and cytological65
basis for chimerism.66 He developed this marmoset67 colony, and these marmosets, 85 percent of the time have twins which are chimeras. That is, each twin has hematopoietic68 cells from the other, a brother. Since they are chimeras, you can transplant bone marrow between those two very easily, 85 percent of the time. So, part of his research was focused on trying to break this chimerism to get an understanding of how to establish tolerance. Dr. Gengozian wanted to disturb this tolerant state to better understand how to establish tolerance, to make somebody accept somebody else's bone marrow. Those are [some of] the things that Gengozian was working on. |
| HARRELL: | He was trying to develop a technique to make somebody who wouldn't
ordinarily accept material from the donor— |
| HUBNER: | You want to understand how can you disturb this tolerance. If you
understand that, you may be able to find a way to establish tolerance. Dr.
Gengozian is still here. He has an appointment here at this hospital in
pediatrics, and he's head of the bone marrow transplant program at the Thompson
Cancer Survival Center in Knoxville. |
| HARRELL: | So who did the work leading to the injection of the irradiated cancer
cells? |
| HUBNER: | That was the Sexton case? |
| CAPUTO: | Right. |
| HUBNER: | That was—who was in that, Charlie Congdon? They said that, I think,
[on] the front page of the paper on this; in the hearings. |
| CAPUTO: | Right, it's a whole list of researchers involved. |
| HARRELL: | When did you work with Dr. Lushbaugh? Or did you work with him? |
| HUBNER: | He was the chairman [of the Medical and Health Sciences Division at Oak
Ridge for nine years]. |
| HARRELL: | Did you assist him in his research? |
| HUBNER: | He was chairman, became chairman in 1975. I was assistant chairman, became
director of REAC/TS69
in 1976. And so, between 1975 and 1984, he was my boss. |
| HARRELL: | Did you ever do work with the NASA data?70 |
| HUBNER: | No. |
| HARRELL: | That was before your time? |
| HUBNER: | That went on while I was doing—let's see. Most of that went on when I
was doing immunology with Gengozian. I was doing basic immunology when the
Sexton case was an issue with LETBI, and NASA of course, in the late '60s. |
| HARRELL: | Then after the immunology where did you focus your attention? |
Return to Clinical Service (1971) | |
| HUBNER: | Well in 1971, I went into the clinical services again. |
| HARRELL: | Were you treating patients? |
| HUBNER: | Yes. But the clinical program was soon phased out over the years. I think
it was done in 1972 to cut down [on expenses]. Finally, it was shut down in
1975. So, after the last bone marrow graft in 1973, things sort of slowed down
as far as hematology is concerned and therapeutic investigations. So, finally it
was closed down in 1975. And so here we were: we got this big grant, we've got [this] big PET machine, we had the positron tomography program going, and everything shuts down. No patients, no beds. So that was poor planning. We had to hustle to get patients to try these amino acids for diagnostic purposes. |
| CAPUTO: | Where did you get them from? |
| HUBNER: | We got them from Knoxville. I established a very nice collaborative
relationship with Dr. Buonocore at UT Hospital, with Dr. Krauss, a medical
oncologist, and with Dr. Solomon, who is primarily practicing at the Baptist
Hospital down the street. I got them interested in sending us patients for
diagnostic investigations. That's the way we sort of limped along with the
program. |
| HARRELL: | So you still kept a small program going? |
| HUBNER: | Yes. We had patients [come to Oak Ridge], did the scans, and sent them back
here. We started the clinical applications of PET in 1977, on an outpatient
basis (an arrangement primarily with UT hospital). I did this until 1984. What
happened in the meantime? Dr. Buonocore, chairman of the department, is my boss
here now. He left UT Hospital in 1979 and took a job at the Cleveland Clinic. Early in 1984, he asked me whether I would be interested in going to Knoxville, and he would come here and restart the radiology program, and whether I would be interested in [taking a position in] positron tomography and nuclear medicine. I said, "Yes." So, that's when I started here. We started and renewed the nuclear medicine program here and then in 1986, '87, we developed plans for the PET center. The PET center finally opened in January of 1988. |
| HARRELL: | What happened to the equipment that was at ORAU? |
| HUBNER: | You want to buy it? |
| HARRELL: | It's just sitting idle? |
| HUBNER: | It's sitting idle. It's going to be mothballed. |
| CAPUTO: | Is it outdated, at this point? |
| HUBNER: | Yes it is, but I think it could be used for some experimental work. They
offered it to the vet[erinary] school across the street, but they don't have the
money to even move it. |
Closing of ORAU Medical Division's Clinical Program (Mid '70s) | |
| HARRELL: | So when they closed it down in '74 or '75— |
| HUBNER: | The clinical inpatient facilities. |
| HARRELL: | —what were the main programs that were going on? Was there more LETBI
work being done? |
| HUBNER: | In 1975, when the clinical part was done, they tried to maintain basic
radiopharmaceutical development. Dr. Fred Snyder, a biochemist, still has a
research program in lipid71
chemistry. Lipid chemistry was developed as a program, early on in the early
days of ORINS, when certain lipid changes in the bone marrow were observed after
radiation exposure. That's how Dr. Snyder, as a lipid chemist, came into the
institution; and he's still there. So, after the inpatient activities stopped, there was a program in radiopharmaceuticals (Dr. Hayes), that continued the lipid chemistry; and Dr. Gayle Littlefield, a cytogeneticist,72 continued her program. But there was change in direction of the whole division. In 1976, [ERDA] decided to establish this Radiation Emergency Assistance Center and Training Site in Oak Ridge—critical ward in the hospital, next to the emergency room. That started up the REAC/TS program, the training and the assistance program. I [was Director of REAC/TS] for a few years, and then Bob Riggs took over. I think it's a worldwide, well-known facility, program. That's about what's left of the [Medical] Division. |
| HARRELL: | If the reports in 1974 hadn't come out, if they hadn't done that review
that finally led the closing of the Medical Division, how do you think it would
have continued? What programs do you think were successful there that would have
continued, and what ones would not have? |
| HUBNER: | I think radiopharmaceuticals definitely could have continued if it had been
possible to organize a collaborative program between the Oak Ridge National
Laboratory (for radiopharmaceutical development), ORAU, and UT hospital. There
were attempts in the past, several times, to pull things together—never
were successful. |
| HARRELL: | Would the bone marrow transplant program [have] continued, or would they
have developed new therapy? |
| HUBNER: | No, I don't think so. I think [ERDA] back then decided that it was just not
feasible to support programs that provide free treatment. That's what they
actually did. That treatment was free, chemotherapy, all of the… For
instance, they had the one project on ovarian cancer, and they had a very nice
operating room there; they did hysterectomies and cancer surgery and a lot of
thyroid surgery. That was all [done] there for free. That couldn't be done
today; no way. |
Preparation of Protocols for Human Use Committees and the FDA (1970s) | |
| CAPUTO: | Going back, did you ever have to present a protocol to the [ORNL] Human Use
Committee? |
| HUBNER: | Yes, I have had an opportunity to do that several times. |
| CAPUTO: | Can you describe the process and how that worked? |
| HUBNER: | The proposals that I submitted to the Human Use Committee, were all on
positron-emitting radiopharmaceuticals for diagnostic purposes. These proposals
were developed in collaboration with the chemists, because you need, for the FDA
[(Food and Drug Administration)]. Eventually, since we had to apply for IND
investigations73
into a new drug complication, you need to provide very precise information on
how you make it, what materials go into the product, where you buy your gas
containers, and all the chemicals, and so forth. I couldn't do that. So Dr.
Washburn and Ray Hayes prepared the chemistry statement on the product that
eventually goes into the patients. |
| CAPUTO: | So this is [in the] 1970s? |
| HUBNER: | Yes. |
| CAPUTO: | Okay. |
| HUBNER: | So, in essence, it meant to write an IND application for the FDA chemistry
part. The second part is, you have to work out the dosimetry: what radiation
dose is the patient going to get from this radiotracer? What is the dose to the
eyes, to the gonads, to the bone marrow, to the whole body? All of this
dosimetry has to be worked out. Now there's good expertise to do that in Oak
Ridge. There's the Medical Internal Dosimetry Center, which is used [by most
researchers] in the United States; that's in Oak Ridge. So we had that expertise
to do the radiation dosimetry. Then we had to write a research proposal, assuming that the [chemical] compound is going to be a very good compound for brain tumors, to detect brain tumors. If there is no prior knowledge about this compound, having a higher affinity for brain tumors, you have to provide that information, at least to indicate that there is good reason to believe that this is going to happen. |
| HARRELL: | Animal experiments? |
| HUBNER: | Right. So you need—the other thing you need is a lot of toxicity
information. The compound should not be toxic; [it] should be chemically inert.
Also, it should not cause any pharmarcological effects. All of that goes into
writing a proposal. Then you have to [write the] research protocol, and submit
this proposal to the radiation safety or radioisotope committee to review the
dosimetry. Then it goes in front of the institutional review board (IRB). The review boards usually have—well, every member gets a proposal, at least two weeks before the meeting. Usually two experts on the institutional review board do an in-depth review of this proposal and come up with the recommendation. Then it's presented to the IRB board, discussed and approved, or disapproved or postponed; because you have to submit it with the proper consent forms that go along with it. So you do this for each compound and for any new applications if you want a product, let's say EDTA,74 for renal75 studies, you may have to go back to the board and submit that [again because you are going to] use this compound for something else. You don't go through all the toxicity anymore, but you have to justify the use for that particular purpose. |
Research on New Imaging Compounds | |
| HARRELL: | Do you do research anymore? |
| HUBNER: | Yes. What happened to me when I came here—I had to write all of the
INDs for the compounds we're using now in PET: 2-deoxyglucose, palmitate, 13 N
ammonia, the amino acids. So I had to write all of these and go through the same
processes and stuff in 1984. So I did a lot of writing proposals. |
| HARRELL: | So was PET still fairly new then, when you started out here? |
| HUBNER: | Well, I'm very happy, very proud to say, that this is the first clinical
PET center in the United States. That's acknowledged. We are the first who did
it clinically. Since the radiotracers are all FDA-approved, we do need consent
forms [for each study], although the applications in 80 percent of everything we
do are strictly clinical. The doctor calls up and asks for PET scans. We're not
beating the drums and asking for patients. We have come to a point where the
surgeons and the oncologists ask us for PETs. |
| HARRELL: | Your radiopharmaceuticals are fairly tried and you've been using them for
quite a while? |
| HUBNER: | Yes. (knocks on the table) We haven't had a single untoward effect
or reaction to any of the products. But the quality control is very strict. If
there's the least bit of doubt about the product, we don't give it to a patient:
we cancel everything. |
| HARRELL: | Are there new ones being developed all the time? |
| HUBNER: | Yes. Right now we are developing oxygen-15–labeled butanol, an alcohol
for blood–brain profusion studies. |
| HARRELL: | You do that work here? |
| HUBNER: | Yes. We are in [the] process of implementing the method. We are tagging
L-dopa76 for
Parkinson's disease.77
We are in the process of labeling phenylalanine, a natural amino acid, with
fluorine-18 to work together with the folks in Brookhaven for the [boron]
neutron capture therapy78
of brain tumors.79
Those are two proposals I have to write, the L-dopa and the phenylalanine. |
| HARRELL: | So, it's still a pretty dynamic field? |
| HUBNER: | Yes. |
| HARRELL: | Your work hasn't changed all that much from the last days at ORAU to here? |
| HUBNER: | No, that's right. As far as radiopharmaceuticals and imaging is concerned,
this is just a continuation. |
| HARRELL: | Except for who's paying for it? |
| CAPUTO: | You originally went to Oak Ridge for bone marrow transplants and now you're
more into imaging— |
| HUBNER: | Imaging and diagnosis. |
| CAPUTO: | Do you know how that change occurred, or why, or did your interest just
change? |
| HUBNER: | Well, as I said, I was coming from pediatrics, pediatric hematology, and
that sort of got me into, got me interested in, detection of soft tissue tumors
and how do you do that with x rays and with radiotracers. I had no idea 20 years
ago that is where I'd end up. |
| CAPUTO: | You thought you'd be doing bone transplants? |
| HUBNER: | I thought I was going to be a hematologist, oncologist in pediatrics—like
what they do at St. Jude's [Hospital in Knoxville], but I branched out into the
imaging part. |
| CAPUTO: | Have you accepted ever self-administered radioisotopes? |
| HUBNER: | To, me? |
| CAPUTO: | Yes. |
| HUBNER: | That's a no-no. (laughter) |
| CAPUTO: | That's a no-no? |
| HUBNER: | Some of our colleagues do that or have done that. |
| CAPUTO: | Right. Do they currently do that? |
| HUBNER: | You'll have to ask them. |
| CAPUTO: | (to Harrell) Do you have more questions? |
| HUBNER: | We have very strict rules here. For instance, if we wanted to use any of
these compounds for normal controls, we have a department rule that a resident
or any employee of the department cannot volunteer to be a normal control for
any of our work. It has to be outside the institution or at least outside the
department. |
| CAPUTO: | Okay. |
| HUBNER: | That's a conflict-of-interest situation. |
| HARRELL: | Is that because these drugs are expensive? Are they're being developed by
the companies? |
| HUBNER: | No, no. [It's because] if I[, a physician in a position to hire and fire,
were to] ask a resident to volunteer to do a stress test back there with
carbon-11–labeled acetate,80
he may want to do it to please me. |
| CAPUTO: | Do you think that there is anything that we missed that we should have
talked about, but we haven't, especially about that early period when you first
hit Oak Ridge? |
| HUBNER: | Well, the big issue is for the DOE right now, is to find out if there were
any of these early tracer studies, or total-body irradiation studies, which were
done in an irresponsible way; unjustifiably poor science, or poor research.
Those questions—how good was the science, how safe was it, how safely was
it done—those questions should be presented to the program directors [from]
back in those days. The biomedical program directors at AEC and ERDA, the
original officers, and the department chairman. |
| HARRELL: | I'm going to be speaking to Dr. Totter.81 |
| HUBNER: | Oh yes, John Totter, yes, yes. |
| HARRELL: | Did you have any dealings with him? |
| HUBNER: | No. |
| HARRELL: | He was just much higher up? |
| HUBNER: | He was way up, in Washington and then in Oak Ridge.82 But I think
in his late days, after he had retired, he had sort of a small office in Oak
Ridge in the Medical Division. I don't know what he did; maybe some late-night
reading. |
Public Perceptions of Radiation Research | |
| CAPUTO: | Right now, the general public, when they hear the term "human
radiation experimentation," generally people think, "Oh, that sounds
so horrible!" So what would you like the public to understand about human
radiation experimentation, if you can make them understand? |
| HUBNER: | Well, number one is: [ranked] after surgery, radiation therapy is a very
effective way to treat cancer. So [radiation therapy is] not going to go away.
[We need radiation therapy]. We're just going to try to make it safer, to
deliver the radiation in a more focused way in order to avoid damage to the
surrounding healthy tissue. I think the whole-body radiation protocols for bone
marrow transplantation—those protocols are safe, and one issue you didn't
talk about with leukemic children is the whole-brain irradiation that's still
[the] accepted standard of care in treating acute lymphoplastic leukemia. |
| HARRELL: | Very high levels? |
| HUBNER: | Yes. Even though we do know that there's the danger of [brain] damage. The
least of it being, maybe—well, we know that if children under the age of
four with acute leukemia get whole-brain irradiation, they end up having mental
problems, behavioral problems, intellectual deficits, and so forth. That's part
of the price you pay to survive. You question how can we justify additional
radiation experiments. I don't think anybody is—well, I guess we do new
things like the proton83
therapy that was discussed last night on PBS [(Public Broadcasting Service)] at
great length. |
| CAPUTO: | I know they're doing immunotherapy with labeled isotopes. |
| HUBNER: | Yes. [Edward B.] Silberstein84
at [the Uiversity of] Cincinnati [Medical Center]. That is something we are not
into here at this hospital. We don't use monoclonal antibodies85 for
diagnostic purposes, because we have PET. We're very content and successful with
fluoro-2-deoxyglucose in oncology. So we don't use monoclonal antibodies. But
it's going to be better, safer, in the future. But there are risks involved in
anything like monoclonal antibodies—they're still not where we would like
for them to be. But the idea for using it for therapeutic purposes is
intriguing. |
| CAPUTO: | This human radiation experimentation has received a lot of public attention
this past year. There was a Presidential Executive Order, ordering all of the
departments and agencies of the Federal Government to open up their records. The
Presidential Advisory Committee [on Human Radiation Experiments] was
established. What do you think about all this activity this past year? |
| HUBNER: | Well I think it's perfectly in order. The only thing I was sort of
astonished about was the very sudden request by [Energy] Secretary [Hazel]
O'Leary. The [DOE] regional offices, and the institutions involved, all of a
sudden were confronted with a request to immediately have all of those records
in order and available for inspection. You know, these cases, some of them have
been shut down. You are talking about 15 or 20 years of inactivity, documents in
boxes and file cabinets in warehouses, and the staffs of these institutions
whittled, [and] the budgets down. Secretary O'Leary maybe could have eased into
this to be better prepared. Because to me, nobody looked good in the public eye.
The institutions look bad, and even DOE looks bad. |
| CAPUTO: | Thank you very much for your time today. |
| HUBNER: | You are welcome. |
| CAPUTO: | I appreciate it very much. |
n
December 1993, U.S. Secretary of Energy Hazel R. O'Leary announced her
Openness Initiative. As part of this initiative, the Department of Energy
undertook an effort to identify and catalog historical documents on radiation
experiments that had used human subjects. The Office of Human Radiation
Experiments coordinated the Department's search for records about these
experiments. An enormous volume of historical records has been located. Many of
these records were disorganized; often poorly cataloged, if at all; and
scattered across the country in holding areas, archives, and records centers.