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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Support for Research Withdrawn by Department of Energy | |
| CAPUTO: | Today is November 11, 1994. This is
Marisa Caputo from the Office of Human Radiation Experiments, Department of
Energy. I'm here with Dr. Darrell Fisher from Battelle, Pacific Northwest
Laboratory. Today we're interviewing Dr. Patricia Durbin from Lawrence Berkeley
Laboratory. The purpose of this interview is to get Dr. Durbin's memories and
recollections on human radiation experimentation that occurred during the Cold
War.
What we'd like to start with is [when] you retired a few years ago? |
| DURBIN: | 1 October 1991. |
| CAPUTO: | Why did you retire? |
| DURBIN: | Because my support was withdrawn. I was perfectly willing to go on working, literally until I dropped. |
| FISHER: | Withdrawn by? |
| DURBIN: | Department of Energy. |
| FISHER: | Office of Health and Environmental Research? |
| DURBIN: | Office of Health and Environmental Research. |
| FISHER: | What project were you working on in 1991? |
| DURBIN: | I was working on the final compilation of three large bodies of data that had been collected over a long period of time, dealing with the metabolism of strontium-90 and americium-241 and plutonium-238 in monkeys. The compilation, which we did complete, was preparatory to a formal analysis of the data, much of which had been at least highlighted in publications. But, the [basic materials] had not really been explored thoroughly. Nor had it ever been all brought together in one systematic way, which is really the requirement for an appropriate analysis of information of that kind. The analysis of the data is now supported in the sort of piecemeal fashion through the archives at Battelle.1 |
| FISHER: | This is the National Radiobiology Archives? |
Dr. Durbin's Current Research | |
| DURBIN: | Yes, that's currently being managed
by Dr. [Charles] Watson. It is supported in a rather curious way, in that when a
job is finished or a manuscript is presented, a small amount of money is
provided to cover the costs. It's a very difficult thing to do, because in a
laboratory environment like LBL [Lawrence Berkeley Laboratory] I have to borrow
from my ongoing [National Institutes of Health] research account in order to get
certain kinds of services and then pay the research account back. It's very
difficult. That material is in process.
There have been some difficult and unpleasant diversions, namely the first three months of this year, for example, that were heavily occupied by interviews and presentations with respect to the plutonium-injected people and the immediate post-World War II work at the old Crocker Laboratory. I have an ongoing project which is supported by the National Institutes of Environmental Health Sciences to do biological evaluation of new actinide2 chelating3 agents, which are being designed for therapeutic removal of actinides from contaminated human beings. That work is very consuming in terms of time and mental effort. I'm not paid by either account. |
| FISHER: | You are retired from LBL. What is your title here at the laboratory? |
| DURBIN: | I'm a Participating Guest with the classification of Senior Scientist. |
| FISHER: | You essentially put in full workdays even in retirement. |
| DURBIN: | Right. |
| FISHER: | Do you have any current Department of Energy research support? |
| DURBIN: | Only when I produce a manuscript on the monkey material. |
| FISHER: | Through which office? |
| DURBIN: | It comes directly through the National Radiobiology Archives. |
| FISHER: | On a subcontract? |
| DURBIN: | I guess, I suppose so. |
| FISHER: | Is that through Battelle, [Pacific] Northwest [Laboratory]? |
| DURBIN: | Yes. |
Radiation Research With Monkeys, 1954-1981 | |
| FISHER: | Could you describe when the monkey injections took place and when these animals provided the data that you're working with now? |
| DURBIN: | The strontium sequence was initiated in 1954, and the last animals in that group were injected in about 1981. The americium series was started around 1960, and the last animals were injected in that sequence in about 1981. The plutonium studies were started about 1974, and the last animal in that sequence was injected in 1980. |
| FISHER: | So this represents forty years of research that you're now finishing up, compiling data on. |
| DURBIN: | The data are essentially compiled. The data have been converted to a computer archive and [are available] in tabular form [as] hard copy. |
| FISHER: | What are the major outcomes of this research? |
| DURBIN: | Many of the major outcomes are still
buried in the results. As I said earlier, some modest summaries have been
prepared based on preliminary examinations of parts of the information. But, in
the case of the strontium information, what I have to work with is not only our
own work, but a substantial body of data that we received in the form of
unanalyzed radioactivity measurements, clinical records, and eight live animals
from a study started by the late Lawrence Tuttle at the University of Rochester,4 [and] then moved in about 1963.
Although we also have the information and the data-much of it unpublished from a
small number of studies that were done at Rochester before 1963, beginning
around 1954-we cared for those live animals for a number of years after they
came to us in the middle 1960s.
The strontium data represents the culmination or fruition, if you will, of two very large studies. The Rochester information is essentially unpublished. It was not included in any of our summaries. The material was sent to us with the understanding that we would incorporate both the animals and the measurements in an analysis of our own material and bring the two [sets] into one coherent whole. I still hope I can accomplish that. |
| FISHER: | How long will it take to complete this work? |
| DURBIN: | Every time I've been asked that-and
I've been asked it many times over the years-I have obviously seriously
underestimated how long it's going to take. A great deal depends upon whether or
not I work on this material steadily or whether I work on it sporadically. There
is [one] piece almost ready to incorporate into a usable manuscript, but there's
an enormous amount of material.
The strontium study incorporates radioactivity measurements continuously or [at regular] intervals after injection, of excreta, blood samples, and [external] radioactivity measurements [of whole body retention. At autopsy, the strontium was measured] in all of the individual bones, many of them subdivided into anatomical subunits, so that we can get information about compact bone versus spongy bone. Except for a few [early] animals, a sample set of six bone types [was studied by] gross autoradiograph[y].5 The autoradiographs have been completed to our satisfaction. The plutonium and americium studies have these same kinds of information plus autoradiographs of soft tissues. The slide files for these animals occupy a commodious cupboard. One of the things that was done quite recently was to take the slides from each individual animal, which were filed by animal, and reorder them by tissue, filed in order of increasing days post-injection, so that we now have for each tissue a chronologic sequence of the autoradiographs. They've been examined once in a cursory fashion, but all of these are going to have to be reexamined. The autoradiographs of the bones are going to have to be examined carefully and evaluated. It isn't just the numerical data that requires this kind of attention. I may not finish this in my lifetime. |
| FISHER: | These studies focus on not just biodistribution of strontium in the bone over time, but also with the radiobiological effects? |
| DURBIN: | No, these were never designed as
bioeffect studies. The dosages were designed, within the [scope of] information
that was available at the time the injections took place, [to be nontoxic!]. The
dosages were designed so that over long periods of time, with the kinds of
radioactivity detection equipment we possessed, we could make accurate
determinations of radioactivity in one week or pooled two-week excreta samples,
[and] that a more refined technique could still detect over background, the
quantit[y] of radioactivity in a small blood sample.
As far as we can tell, in the strontium studies there is one equivocal [soft- tissue lesion]. In close to one hundred animals that were [studied at] Berkeley and Rochester, two of the longer-term animals developed cataracts, but these are not uncommon in aging monkeys. Not very much is known about aging monkeys. One carcinoma6 of the gingiva7 [was identified] that conceivably could have been related to the strontium in the mandible8 and around the roots of the teeth. There is no pathology in the plutonium study, and we have one obvious osteogenic9 sarcoma10 in [one] animal in the americium studies. This was not intended as a bioeffects study. Anybody who looks at the almost randomness with which animals were injected and incorporated into the study would shudder, [should we] have the temerity to analyze the data and make comments about radiation effects, because it simply is not that kind of a study. |
| FISHER: | You've done both in your career. You've looked at radiobiology, pathology, radiation, incorporated radionuclides as well as [bio]distribution. |
| DURBIN: | My personal involvement with studies designed specifically to look for radiation effects is really quite limited. My central purpose [and] strength has been the biodistribution [and] biokinetics11 work. |
| FISHER: | [Radionuclide] metabolism. |
| DURBIN: | Yes, if you want to use that term. |
Potential Influences of Monkey Studies on Strontium Metabolism in Humans | |
| FISHER: | Do you expect that these monkey studies will result in any changes in our current thinking on strontium metabolism in man? |
| DURBIN: | I'm not sure anything changes the current thinking on the metabolism of anything in anybody. But, the taxpayers paid for this work; they deserve a report on it. The Government agencies, the AEC, the Energy Research and Development Administration, Department of Energy, [and] the Nuclear Regulatory Commission, all provided money support for these studies at one time or another. They deserve a report. I do think that what will come out of this is that there will be some refinement in thinking. |
| FISHER: | Perhaps [you will recommend] a new model for strontium metabolism? |
| DURBIN: | The data certainly are there to do that. I don't know that I'm qualified to do it. I know that the data are there. This is the only set of data in existence in any species where we have continuous measurements of body retention based on [both] excretion [and] on in vivo12 counting, for animals that are mature [of] both sexes, [and] juveniles [of] both sexes, over extended periods of time. We also have an internal skeleton distribution, not just whole bone or whole skeleton content, but [also] the relative contents of different kinds of bone. One of the things that these data do do, and you can see it in the information as it comes out, [is] that there's substantial variability. |
| FISHER: | From one animal to another. |
| DURBIN: | From one animal to another and
between the two colonies. The initial deposition in the skeletons of the
Rochester animals was substantially larger than in the animals that were
injected here at Berkeley. There wasn't very much difference in the ages of the
animals. So it basically had to do, we suppose, with diet and with the kind of
exercise they were getting.
Our animals were housed individually, they were on a very high-calcium diet. [For] the Rochester animals, it is not possible at this stage to reconstruct what their diet really was. All the people who were involved in the management of the monkey colony at Rochester are either dead or unavailable; or they've forgotten; or they didn't pay any attention to it in the first place because it wasn't [considered] important. Their animals were housed in gang cages so that they got a great deal more exercise. These things could have influenced [strontium deposition]. But, the thing that makes this set of information important, is that each animal can be followed as an individual. It's not grouped data. In fact, it's almost impossible to group [these data], because of the variable of the injection times. But when the individual's body retentions are plotted, there are variations in the intercept coefficients in a multiexponential analysis, [but] there are no real variations in the slopes of the individual components of the retention curve. The retention curve has a fixed number of components. We're not absolutely certain what each one of those means. Probably [most] of them are averages or composites of more than one process. But the same components emerged; it's just that they tend to be displaced. The other thing that comes out of the strontium data, unequivocally, is the relatively faster loss from cancellous13 bone than from compact14 bone. Because strontium is sufficiently discriminated against and therefore reasonably efficiently excreted, once it starts circulating, there is relatively little reutilization, compare[d] with plutonium or americium where there is substantial, almost quantitative, reutilization. |
| FISHER: | Can you explain that? |
| DURBIN: | Strontium doesn't form strong
complexes with serum proteins.15
It's not as firmly bound in bone mineral as calcium is, and it's not absorbed
from the gut as well as calcium is. It can pass through the glomerular16 filter. There appears to be a
discrimination at the kidney level for reabsorption. Calcium is preferentially
reabsorbed over strontium. The strontium that gets secreted in the GI
[(gastrointestinal)] tract is discriminated against. It probably also is
discriminated against at the bone level, because the ion is a little large, and
it doesn't fit quite as neatly into the crystal lattice [as calcium]. So that
once the strontium circulates, it has a high probability of being excreted. All
one needs to do is to look at data for injected strontium at, say, one day or a
week. At that [time] in the adult animals, some 80 percent has already been
eliminated on average.
In the case of the actinides, there is significant [serum] protein binding, which inhibits renal excretion, and the[re is a] tendency to form strong complexes with both the iron-binding protein, transferrin,17 with ferritin18 in the liver. We assume that transferrin-bound actinides can participate in the iron transfer mechanism that moves iron from the serum into liver cells. In my judgment, the strong complexes that [actinides] form with the mineralized surface of bone provide an almost overwhelming [opportunity] for the actinides, even if they [are] recirculat[ed] to be redeposited at new sites and not eliminated. One of the difficulties in utilizing the monkey data as stand-in for humans, is that the monkeys possess a[n] efficient biliary19 outlet for actinides. There isn't any evidence for an efficient biliary outlet for actinides in people. There is an outlet, but it seems to be rather restricted. |
| FISHER: | Can you explain that a little [further]? |
| DURBIN: | It appears to be a species difference [and the mechanism remains to be explained]. Dogs don't excrete actinides through their bile to any significant degree, and people don't, and hamsters don't, and rabbits don't. Monkeys, mice, rats, I guess those are the only animals that we've looked at, do excrete [actinides in the bile]. |
| FISHER: | That wasn't known before you started working with monkeys? |
| DURBIN: | No. |
| FISHER: | That's something that you've learned through this research. Monkeys were chosen because they represent a suitable model for man. |
| DURBIN: | That's right. They're the best model there is. |
| FISHER: | They were used in place of human research. |
Initiation of Animal Studies as Part of Project Sunshine | |
| DURBIN: | [That was the underlying] notion for
the instigation of the strontium studies [in monkeys] begun in 1954. It was
apparent to the people who had information when the fusion weapons were tested
[in the atmosphere] that a substantial amount of strontium-90 [would be]
dispersed worldwide. There was reason to be concerned about the potential
consequences.
The studies were started at Berkeley and at Rochester for the purpose of using an animal that was the closest relative to man that you could manage in a laboratory. I don't think that animals like chimpanzees or orangutans were even considered. Monkeys were available, [and] people had experience working with them. There were small colonies in existence at both Berkeley and at Rochester. |
| FISHER: | Was this early work ever associated with what has been called the Sunshine Project?20 |
| DURBIN: | It was part of it. |
| FISHER: | Can you elaborate on how it was a part of Project Sunshine? |
| DURBIN: | It was my understanding that all the work that dealt with strontium-90 fallout was a part of that project. This dealt with strontium-90 fallout, specifically and exclusively. |
| FISHER: | Did you think of it in terms of Project Sunshine back in the early '50s, middle, [or] late '50s? |
| DURBIN: | The initial results were secret. We ha[ve] a file, still in existence, on a couple of the [first] injected monkeys, labeled as Project Sunshine animals. |
| FISHER: | The term "Project Sunshine" was quite familiar to you back in those days? |
| DURBIN: | Oh, yes. |
| FISHER: | Did that seem unusual to you in any way? |
| DURBIN: | Look, we lived in a classified world.
When I started working as a dishwasher in [the] laboratory, I [was] required [to
have] a security clearance. We were cleared; everybody who worked in Crocker was
cleared. When I went to work there, we had guards at the doors; there was barbed
wire around the building and [around] the building across the alley from us;
there were alarms; there were lights all night. It was a thoroughly secure
installation. We expected, when we worked there, to be working on secure work.
Sometime in the middle '50s, the Livermore Laboratory was established. It was established, as I understand it, for the specific purpose of moving classified work off the Berkeley campus, off the Lawrence Berkeley Laboratory Hill. There was some pressure on the part of faculty members to open up the hill to noncitizens-to be able to bring foreign guests, graduate students, [and] undergraduate students into the research facilities. To do that, all of the classified material or classified work had to be removed from the premises. And that's what happened. By roughly 1965, it was decided that it made no sense to "Q clear21 everybody at th[is] laboratory anymore, and the practice was stopped. I'm sure that there are some people who still have "Q" clearances [at LBL], but the great bulk of us no longer do. |
| FISHER: | Including yourself? |
| DURBIN: | Including me. I haven't had one since the '60s. |
| FISHER: | Do you recall, back in those days or since, discussions of [the] potential differences between human metabolism of strontium and the metabolism [by] monkeys or other species that you worked with? |
| DURBIN: | Unfortunately, the monkey strontium
data were not coming out very rapidly. The monkey colony was always small. The
data generated by each animal vari[ed] from the [others in the] cohort. To be
honest with you, we couldn't make a whole lot out of it. But, by 1973, when I
produced a summary report, it began to look as though, at least for adult human
beings, in some cases there [would] be similarit[ies] and in other cases there
might not be [similarities] with the monkey material.
But, by that time, [the atmospheric test ban was in place, and] enough information had been gleaned from a variety of sources dealing directly with human material that there really wasn't [much] policy interest from the management at Headquarters [in] press[ing] the point of analyzing and utilizing the monkey information. It now appears that when all of the animal information has been bulked together and every animal is accounted for, (among those that are fully mature, skeletally as well as sexually mature [and for] both sexes) that the overall body retention curve and the human model that's presently in use by ICRP22 are a very good match. It's gratifying, but in some respects, it's a little surprising. |
Human Strontium Injection Studies | |
| FISHER: | Were you aware of the human strontium injection studies that took place [at San Francisco or Berkeley] early in the '40s, in the '50s, [or] in the 1960s in human patients? |
| DURBIN: | Even though I possessed Dr. [Joseph]
Hamilton's bound reprint collection, I hadn't looked at those materials very
carefully. I knew that there were people who had been injected with strontium.
The famous amputated-leg autoradiograph is a[n] important piece of
radiobiolog[al], nuclear medicine,23
[and] mineral metabolism information, as [is] the little girl with the crude
Geiger counter across her neck for thyroid24
uptake determination. Those are probably two of the most widely published
pictures. You couldn't not be aware.
I didn't pay a great deal of attention to the specific data [from] those early studies. There was one [by] [Anne] Treadwell and [another by] [Charles] Pecher. I didn't pay particularly much attention to [the human data] because the Pecher work was [more] relevant to what I was interested in: rodents. The Treadwell et al. work didn't seem at the time to be informative to what we were looking for in the monkeys. In retrospect, when and if I get around to reporting the differential distribution and retention of strontium-90 in monkey bones, I will revisit that information because I think it does have some [relevance]. But, there is an enormous amount of fallout data that also informs on that issue. |
| FISHER: | Do you remember discussing these studies with Dr. Hamilton? |
| DURBIN: | No. Let's set the stage for what my
relationship was with Dr. Hamilton. I was, I think in his judgment because he
had no children, one among several of his pseudochildren. He had a pleasantly
paternalistic attitude about the people who worked for him. One of the pleasant
parts was that he genuinely encouraged [us, and] this was long before anybody
had rigorous policies of compensation time for education. All you had to say
was, "I'd like to take some classes, and it takes this much out of my day.
Can I make up the time?" And he'd say, "Oh, yes, do that, I really
want you to take more classes."
He provided a great deal of encouragement in terms of studies. He provided encouragement in careers-finishing a bachelor's [degree], going on to graduate school, finishing graduate school, finding a job. But I don't think that he would have discussed such matters [as the strontium injection studies] with anybody except his medical peers. I think he looked on Kenneth Scott as a peer, because they were about the same age, and they had worked together for a long time. What he and I discussed were the ins and outs of experimental designs, the preparation of manuscripts. We maintained the relationship (and it didn't last very long, because he didn't live very much longer,) of the graduate student and the major professor. Unless the major professor was sort of unburdening his soul, there wasn't very much likelihood that we were going to be discussing such things. When the strontium studies were starting, he announced that we were going to start strontium studies. We then began to plan how we were going to go about it and what we were going to do and what kind of samples and what kind of animals. Then he just turned over the execution of the project to me. We knew it had to do with fallout and so on, but that part of it wasn't discussed. We'd been asked to do it by [AEC] Headquarters. He said he would get it done. He gave the instructions to do the work, and we then set about executing on the experiments. We would discuss periodically how it was going and what the results were and what the outcomes were. When [a] manuscript was prepared he would read the manuscript and make changes. In the paper that was prepared on the first strontium-injected monkeys, which was part of a conference that was held joint[ly by] DOD-AEC he was a coauthor, but he didn't pay a whole lot of attention to what was going on. He enjoyed the fact that we had a baby monkey. My colleagues, Muriel Johnston and Sybil Cole devised diapers for this monkey, so that we could collect his excreta and [they] devised ways to try crudely, using in vivo measurements, [to] decide how much [strontium] was in the [whole body]. [Eventually,] we had three infant monkeys. He thought that was fun. He also thought it was funny that, as the oldest of them began to grow up, Muriel and Sybil fitted him out with a collar and harness and a leash and took him out into the Mining Circle to play. I don't know exactly who complained, but somebody eventually complained [and the outings ceased]. |
Study of Calcium and Strontium Metabolism in Human Infants | |
| FISHER: | This leads into another experiment that was conducted, that many people don't understand. Maybe you can explain it and clarify it. That [was] the study on calcium and strontium metabolism in three infants. |
| DURBIN: | There were six. |
| FISHER: | There were six infants. You had quite a bit of involvement in this study in conjunction with Justine Berg. |
| DURBIN: | Let's put it this way: It was my study, and Justine Berg was my technical assistant. |
| FISHER: | Describe this experiment, what you did, and the technical outcomes. |
| DURBIN: | [It concerned] one of the large
questions with respect to fallout strontium. One of the central questions was: "If
the discrimination factors at the gut level, kidney level, and bone level for
adults are such-and-such, and if they're influenced by the presence of calcium
in the diet in various forms-some increasing absorption, some decreasing
absorption-are these same discrimination factors present at the same degree from
birth to death?"
Calcium absorption is a very difficult thing to measure if you're just dealing with stable calcium. Calcium balances are something that many people [tried to measure over many years]. I think they invested huge quantities of time and effort before tracers were available. Some of the answers [about] influence[s on] calcium absorption were still unavailable. But, it did appear that calcium absorption was more efficient in infants and growing children than it was in adults. That being the case, you could make the same assumptions with respect to strontium. |
| FISHER: | By discrimination factors, you mean the preferential uptake of calcium over strontium? |
| DURBIN: | I think that that's backward. Calcium
is utilized in the normal course of animal physiology. And, certain precise
mechanisms have been incorporated into animals to get the amounts of calcium
that they need to have and to retain the amounts of calcium they need to retain
in the face of what their dietary intake is and what their growth needs are.
Strontium is present in all calcium preparations. It's ubiquitous in nature. But, it's not present at the same concentration in animals' bones and tissues as it is in nature. The concentration of strontium in animals is substantially less than it is in rocks or in plants, which indicates that strontium's ability to penetrate, if you wish, ride on, the calcium-absorbing, -transferring, [and] -utilizing mechanisms is not equivalent-it's less. Basically, this is because the ion size is somewhat larger. We know that all these transport mechanisms involve proteins, they involve complex formation, they involve crystal formation, and in every case ion size is an important factor. "Discrimination factor" was nice shorthand to say that calcium was used and strontium was not used. Anyway, back to the original question, which was about the baby experiment. I'm not sure whether this was our idea or whether it was a request from Headquarters. But, I do know that there were regular meetings of biomedical directors and, at those meetings, the central management, Division of Biology and Medicine (DBM), laid out their laundry lists of things that they needed to know. Sometimes they would point out a laboratory that had the best facilities to do a specific chore. Sometimes it would go to somebody in one of the laboratories who had already accumulated some information on a particular point. Sometimes they would just sort of broadcast, "We need assistance on this matter." And I rather think that the baby study was a result of that last kind of call for assistance and information. The concept of the study was quite straightforward. We would enlist the cooperation of some women who were not going to nurse their newborns. The period from birth to six months was supposed to be the most critical. We would then provide them with a standard source of milk. In the original case, it was Carnation canned milk. We would provide them with diaper service and with all of the solid food that would be required (juices, cereals, canned fruits, teething biscuits, canned vegetables, canned meat). We had quite an array of things. At that time, the array of these kinds of dietary constituents was not as great as it is now. We also enlisted the cooperation of the Gerber baby food people. We were going to be able to provide them [(Gerber)] (this is cooperating with the Government) with the calcium balance data when it was all over because we planned to do calcium balances as a sort of side issue. The design of the experiment was that we provided cloth diapers and all of the food and all the milk. The participants in the study had only two tasks and one prohibition. The prohibition was that you don't use any other food, nothing off the table, nothing you buy at the store. The requirements were, [first,] that you record what kind of food and how much on every day. [Second,] we provided them with big plastic-covered diaper pails. When diaper changes took place, [and] the infants were wiped, the number of wipes (which we also provided) was recorded, the number of diapers used was recorded, and [all wipes and] diapers [were] rolled up and put in the diaper pail to be picked up. We delivered food and milk and diapers and picked up dirty diapers and records. Justine Berg's third daughter was a participant in this. Marshall Parrott, who was working at the laboratory, [had a] son [who] was a participant in this. The four other people were friends. |
| FISHER: | When you say "participants," were they the infants? |
| DURBIN: | They were the fathers and mothers of the infants. Their children participated; they and their children participated. |
| FISHER: | Do you recall the others? |
| DURBIN: | I don't recall who the others were.
Justine [Berg] made the contacts. They were students' wives, the children of
students' wives. I think she lived in student housing at the time. As far as I
know, the participants were encouraged, if not required, to tell their
pediatricians that they were participating in this study, to get the
pediatrician's permission to use canned milk as a [sole] milk source, and to get
the pediatrician's advice about how much of each one of these foods to feed and
when to feed it. We weren't just hanging loose.
The first round was with cloth diapers. I have the data books that I could go to. But, it's my best recollection, what we were going to do was analyze the diaper ash, milk ash, and mixed-food ash, and then the dirty- diaper ash. The ashes were ground up finely to make a good mixture and weighed. A weight fraction was removed. That weight fraction was run through a standard calcium oxalate procedure for calcium analysis. The calcium analysis was recorded, which gave us the calcium balance data. |
| FISHER: | Stable- |
| DURBIN: | -Stable calcium data. Another weight aliquot25 was put into a glass bottle and sent to an analytical laboratory that had the capability of very low- level strontium-90 detection. We didn't have that capability. |
| FISHER: | Do you remember where that was? |
| DURBIN: | Do I know where it was? Menlo Park, [or] Palo Alto. I could find all the information. It was the same laboratory that eventually analyzed our long- term strontium monkey [excreta] samples, [and] long-term monkey blood samples. [That laboratory] changed hands many time and ended up as Teledyne Isotopes or something like that. The idea was that we would analyze the excreta, the food, the milk, the diapers for fallout strontium. |
| CAPUTO: | You added nothing to the products? |
| DURBIN: | No, nothing. The procedure [and] the
mathematical concept [were] utter simplicity. If you add the number of diapers
times strontium-90 per diaper, number of food [items] times strontium-90 for
food, number of milk [cans] times strontium-90 for milk, and then you subtract
the diapers from the excreta to get excrement [strontium], and you eliminate the
diapers' [strontium] and just have food and milk [strontium], and you subtract
the out[put] from the intake, you should get some notion about what the
absorption was.
Simple, beautiful concept. It should have worked beautifully, except for the milk source that we selected. Again, this was because we've always operated on the cheap. The milk source, we also got donated by the Carnation Milk Company. After the strontium-90 results came back from the analyst-and I could show you the outcomes, but my recollection is that then we had it week- by-week so we could have done this-we only sent sample[s] for the first analytical round. We looked at the data and the strontium-90 content of the milk was low and the strontium-90 content of the food and the diapers was also very low. We expected the diapers to be low. Milk was supposed to be the main source of the fallout strontium. That was what everybody was worried about, strontium-90 in the kiddies' milk. The quantities in the milk were so low and the quantities in the excreta were so variable that we got absorbed [fractions] ranging from zero to about 40 percent. We were doing something the statisticians abhorred: [We subtracted a large number] from another big number and got a very small difference. The reliability of that small difference is very low. Only after that did we make inquiries about where did this supply of milk originated. It turned out [that] it originated on the west side of Fresno County in Los Banos, California, one of the places where fallout strontium was the lowest of any place in the Continental United States. We were just appalled, shocked, distressed, almost in tears, because the milk levels in places like Missouri and New York were high enough [that] such measurements could have been made. A lot of work, essentially down the drain. We then tried another tack, which was to [be] based on stable strontium. The stable strontium content [of] the diapers was very high, [because it was] plant material, and [it was] also highly variable, because the diapers did not all come from a single job lot. We couldn't buy the whole supply all at once; we had to keep buying them in batches. We got bedeviled by the job-lot problem. So we tried another tack. That was [in] the second round where the fundamental study design was identical to what the first one had been. [For the second round,] we elected to use disposable [paper] diapers, which were just coming on the market, [on the assumption that the extra processing of wood pulp to paper would reduce the stable strontium content.] |
| FISHER: | Rather than cotton [diapers]? |
| DURBIN: | We used disposable diapers and Similac rather than canned milk. [The maker was interested in] how people liked the product. So it was a bit of test marketing. |
| CAPUTO: | Similac is formula? |
| DURBIN: | I think it was Similac. I would have to look at the paper to get the precise brand name, but I think that's what it was. Everything proceeded happily. We prepared the samples for [stable] strontium measurement, not strontium-90, [but] stable strontium measurement [by] spectroscopy.26 We prepared clear solutions that could be used for spectroscopy. [George Shalimov], in the Applied Chemistry Division, ran huge numbers of samples [for us]. Again, we found that, even though we kept track of the job lots o[f] the disposable diapers and kept track of the job lots o[f] the Similac, there was a terrible variability in the stable strontium content of the paper (the cellulose fiber that went into making diapers) and such a tremendous variability in the stable strontium content from batch to batch of the Similac and [from] batch to batch of the baby food, that again we were stuck with this big number minus another big number and a very small difference which didn't mean anything. We tried to salvage some of this by using x-ray fluorescence,27 where we could get a better measurement. The [stable] strontium levels in all these things were so low, [that] spectroscopy gave us a lot of zeros. Samples were prepared of [a] calcium oxalate precipitate mixed with lecithin28 to make little wafers which went into holders, which we then took up to [University of California,] Davis to measure the stable strontium fluorescence using x- ray fluorescence. At that point, we realized that the outcome was [still] just lousy. Because the samples that gave us zero on the spectroscopy [also] gave us very low values on the x-ray fluorescence. We gave up on being able to make any kind of reasonably useful statement about the absorption of strontium-90 fallout or the absorption of stable strontium. We did finally publish the calcium balance data and calculate[d] what the sodium and potassium intakes were, based on the given analyses by the manufacturer, of what was in each can [of formula]. |
| FISHER: | There was never any effort to deliver a known amount of isotope? |
| DURBIN: | No, it was all stable. It was either stable, or it was from the vagaries of wherever the fallout was coming from. |
| FISHER: | Even if the levels of activity had been sufficiently low that there wouldn't have been a risk to an infant, the deliberate administration of an isotope wasn't considered? |
| DURBIN: | We were not in the business of doing human studies. We were in the business of making what amounted to environmental measurements. It never even crossed our minds [to administer an isotope]. Eventually Bernd Kahn and his colleagues did devise a satisfactory infant strontium balance study. But, to do that, they had to enlist the services and pay the cost of having a manufacturer make for them a special run of disposable diaper material which was deliberately treated to eliminate the calcium and the strontium from the fibers, so that they had low- background diapers. |
| FISHER: | Where was that work done? |
| DURBIN: | I've forgotten. I could find out; no problem. |
| FISHER: | [Perhaps at] Oak Ridge? |
| DURBIN: | No, I don't think so. |
Direction for Future Department of Energy Research in Metabolism and Biology | |
| FISHER: | We're changing the topic just a little now. Considering this work and the work [during] your career, [and remembering] the conference [on internal dosimetry research needs] that was held in Atlanta, organized by CIRRPC,29 what do you think the future research directions of the Department of Energy and radionuclide metabolism and biological effects should be? |
| DURBIN: | I'm not convinced that the present research agenda at OHER30 considers radionuclide metabolism and biological effects as an agenda item at all. I'm not even sure it's on their list; it's fallen off the bottom of the list, if it were on the list. |
| CAPUTO: | Should it be on the list? |
| DURBIN: | I think so. I think that it's part of
an ongoing obligation, as part of an ongoing compact with the public. This is an
area where the U.S. was once the unchallenged leader and is now the tail wagging
the dog. There is a place for a focused effort.
As far as I can see, OHER is the only place that has the financial mandate. NRC31 and EPA32 have regulatory mandates, but I don't think that they have the financ[es] to do these things. I rather like the original notion that the [AEC's] Division of Biology and Medicine [(DBM)] , while it had some of its own research interests, was at the beck and call of what was then called Operations. If the Operations people had a problem, and there were environmental people in Operations, (and there were regulatory people in Operations) or questions that they wanted answered, they could go to DBM and say, "These are our problems, help us do something about it." Those links have been broken. All the other agencies can do is to go to CIRRPC and all three together go to OHER and sort of plead and say, "These are what our problems are, please do something." And, then, OHER can decide whether it's going to do it or not. [In] the old days, it was [an] obligation to do it. I think that the link has been broken there. There were a number of things that came up at the CIRRPC meeting. I have not seen a final draft of the output, and I suspect one of the reasons is that everybody is so discouraged about the fact or about the prospects of it going anywhere. Certainly, provision needs to be made for the people who did work [to report it]. This is personal horn tooting in some respects, but it makes sense; it's logical. Data that [were] considered to be of value, or generated under the auspices of the old agencies-things that were considered, at the time that the experiments were begun, to be valuable-have not automatically become devalued, [just] because somebody's priority list has changed. They're still valuable. And, the taxpayers are still owed a report. Extra effort needs to be made to see that data on-hand are made available and analyzed-not just made available. It took me the better part of two years to make something out of the stuff I got from [the University of] Rochester [-and] I know the material. I've workedwith comparable material. It was just so fragmented, and so scrappy, and in many ways so unclear. The recording system was so variable that it took a tremendous amount of effort to codify and regularize and put into [a] system that [stores] information. Somebody coming in cold, ten or twenty years from now, is going to have ever so much more difficulty making something out of people's data. Everybody's data taking, no matter whether you've got a good computer program or fine hand-done files, is idiosyncratic. The idiot who synchronized it in the first place is the best one at least to give you a roadmap as to what it means. This dancing around human data, at this point, this notion that human data is somehow dirty, is self-defeating and foolhardy. We now know that because of the longer human life span-[there are] some fairly [human- ]specific aspects of metabolism-that animal data, while they are informative, are not quantitatively exact when it comes to describing the behavior of something in people. There are data enough now in monkeys [and] dogs, so that comprehensive metabolic models can be constructed for those two [animals]. You wouldn't expect great variations in the structure[s] of the models. You do expect variations in the rates of transfer. And, plugging in what human data are available should give us much more reliable and, certainly physiologically, more realistic protection models. Because of severe restrictions in other areas, whether that alters permissible levels [of radiation] or not is something that's unclear. You can't know until you do it. [With] the present tendency to go down to zero [acceptable risk], maybe you don't need any permissible levels at all anymore: You just scrub until there's nothing left. Development of a realistic, comprehensive, physiologically more reliable or [more] believable model for every element (all pretty much [the] same shape, [the] same size, [and the] same basic system) would be a valuable contribution. Then, there's the analysis of the experiments that were designed specifically to study bioeffects. Until you've got good models for the dogs, for their biokinetics, I think the dosimetry that's being used to analyze those bioeffect studies in the dogs are suspect. They're certainly harder to describe and harder to interpret. One of the things that the monkey data do, because they are so complete, is to inform the dog models. As a statistician once put it, [and] I think this is a valuable lesson in dose-effect relationships, "You can be ever so good at locating and describing effects, but dose is the independent variable." If you don't have a good handle on the independent variable, your dose-response [relationships] are mushy. The whole business about internal emitters and internal dosimetry is not just valuable for standard setting: It's invaluable for interpreting the internal emitter bioeffects data, or invaluable for predicting the bioeffects of internally deposited radionuclides. Without good dosimetry, you might not have bothered counting tumors. |
Why She Perceives That the Department of Energy Lacks Interest in Nuclide Studies | |
| FISHER: | What's your perception of the current direction of the Department of Energy [toward resolving] some of these issues? |
| DURBIN: | I don't think they're interested. I think they are working as hard and as fast as they can to eliminate all the nuclide studies, except possibly radon, and as fast as possible. |
| FISHER: | You've seen this evolution over the years. What [has] been the major factor? Is it competing priorities, such as the Juneau Project? Is it a change of personnel? |
| DURBIN: | I'm not sure you could put your finger on a single thing as being a major driving force: Budgets. [Expense. Animal use.] I think a substantial contributor was the general fright of the populace, and DOE and ERDA33 didn't really want to be seen as being participants in something that frightened the populace. I think that's a substantial contributor. As the [U.S.] nuclear power industry goes down, the perceived need for information goes down. I think there's a perception that the standards are so low,34 nothing's going to change anything. |
| FISHER: | New information isn't going to change things? |
| DURBIN: | New information isn't going to do anything. The shift, [to the] Office of Basic Energy Sciences reemphasized and reinforced the notion that the research that OHER should support should be "basic" rather than "applied." I think that the general attitude, particularly about nuclide studies, was that it was applied research and therefore now beneath their dignity. |
Rationale for Studies of Human Metabolism of Radionuclides | |
| FISHER: | Your mentors and colleagues [beginning with] the 1940s here at Berkeley and at UC [(University of California)] San Francisco were, in large part, physicians who could do human studies, [or] who had done human studies. |
| DURBIN: | Yes. |
| FISHER: | A number of human studies were done prior to World War II-for example, Dr. Hamilton's, Dr. Stone's, maybe even Dr. Low-Beer's experience working with radiation x rays and the early isotopes, phosphorus and iodine. Were there reasons why these people were interested in the metabolism of radionuclides35 in man, starting with the Manhattan Project36 and continuing afterwards? |
| DURBIN: | I have to answer that long, involved question with a simple word: No. The driving force for the nuclide studies dealing with elements that are not known to be normally utilized by mammals was the need to know [how to predict] the possible outcomes of [people] incorporating fission products and fissionable elements and nuclear-reaction byproducts, specifically for protection purposes. The big thrust, the big studies, began as part of the Manhattan Project Health Group effort to define what the worker hazards would be, to work out techniques to measure nuclide content of workers, specifically for protection purposes, and to determine what the worker protection people were going to be up against with this incredible array of elements, about which almost nothing was known. |
| FISHER: | The physicians selected to work on the secret project, the Manhattan Project, were those who had experience with radiation before [being called]. In almost every case, these physicians had been involved in human experimentation of some form. |
| DURBIN: | Please. The words "human
experimentation" have come, in recent times, to have a very bad odor.
The investigations, which I prefer to call them, investigations among the pre-World War II physicians, who were basically radiologists and physiologists and their successors, had to do with three things. The first thing was the use of radiation as a therapy source, whether external or internal. The second was the understanding of the processes of disease. And the third was diagnosis of the presence and severity of disease. The first one is radiation therapy, the third one is nuclear medicine, and the second one is physiology37, pathology,38 toxicology,39 or whatever; all those things rolled up together. There were individual investigators who were interested in various aspects of these things. Hamilton got into the fission-products metabolism business because he was running the 60-inch cyclotron.40 There were no separated fission products: You had to make [radio]isotope[s] of the same elements that had been laid out as "these elements will be present in the fission product mixture." And, you had to make isotopes of those elements on the cyclotron, which is what they did [using] the only transmuting system that was available. Stone knew Hamilton professionally. He knew he was an enthusiast in terms of the uses of radioisotopes, applications of isotopes. He'd sold a lot of people on the Berkeley campus on the utility to their own research, whatever it might be, of using radioactive tracers. There were detection devices available to Hamilton and the people who worked with him. Detection devices were rare. They were only present in a few laboratories in a few people's hands. It was an absolutely natural match for Stone to go to Hamilton and request that fission products be made on the cyclotron, that their fate in [mammals] be studied in small animals, one by one, in a systematic way. That information would then be used for radiation protection proposes. When the war was over, that effort was extended to include as many elements in the periodic table as had useful measurable isotopes that could be made, either on the cyclotron or through neutron activation, which then became available, because of the availability of reactors. That body of data, which is severely underpublished, is or was the original base for [measurements and] National Bureau of Standards,41 National Council on Radiation Protection [and Measurements], [and] International Commission on Radiological Protection's guidance books on internal emitters. The bibliographies and the sources of information for a large number of elements have increased over the years, but the war and postwar work at Crocker Laboratory is still the fundamental foundation of all of this, and apart from a few minor glitches or some modest species-specific alterations, the work stands today as accurate, and as well-conducted as possible under the circumstances that prevailed. That was the single most important contribution that Berkeley Biology or any of the Health Group's biological efforts, possibly apart from Rochester's uranium effort, made to the problems of radiation protection and internal dosimetry. There were some people when that work was finished, [and] after the periodic table had been more or less complete[d], using rats, who held the view that it wasn't necessary to do anything more, because we had all the information we needed. I think to some degree that's the attitude of the present OHER management, that we have all the information we need. A lot of it is empirical. We really don't need to know what the mechanism of binding of actinides is in bone. We really don't need to know how actinides get into the liver or how they get out. My contention and the contention of a few of us stalwarts that are left around, particularly Ray Guilmette and Bruce Boecker at the Inhalation [Toxicology Research] Laboratory in Albuquerque, is that the more you know about your enemy, the better off you are in terms of understanding what's going on. Not only in understanding what's going on, but in providing appropriate countermeasures and in proving appropriate protection models and making appropriate predictions of outcomes, after you've cleaned up sites, or [when] something is leaking from a waste site. It's important to know what the mechanisms are. As a matter of fact, you need to know what the mechanisms are. To some degree, we're still working on that, in our modest way. |
Doctoral Research on Fluorine-18 | |
| FISHER: | The fact that you were a [biochemistry] postdoctoral student working with physicians limited your experience, thereafter, primarily to animals rather than human studies. You weren't a physician. |
| DURBIN: | No. |
| FISHER: | Your interest was primarily in animal research. Did you do further human studies of any kind in your career thereafter? |
| DURBIN: | I didn't initiate any studies. When Hamilton was still alive, he arranged to have some people, who were going to undergo thyroid surgery, injected with astatine-211. |
| FISHER: | That's coming up [later]. |
| DURBIN: | Marshall Parrott and I, and I guess Muriel Johnston, too, as laboratory assistants and helpers. |
| FISHER: | Your doctoral research on fluorine-18 in rats, which I think is remarkable work-did this ever get done in humans? [For example,] did you ever investigate fluorine-18 uptake in [tooth] enamel? |
| DURBIN: | No. Howard Myers, who was at the dental school, might have. I have a fluorine reference file and that reference is in there. He may have done some, whe[n] somebody was going to have a tooth pulled; he may have done it in animals; I don't remember. |
| FISHER: | Is it interesting to you that fluorine-18 is now one of the most widely used isotopes in medicine, [at least] one of the most important for PET42 studies? |
| DURBIN: | It's interesting, yes. I just hope, I suspect, that they have a more efficient way of making it than we did. The things that I'm pleased about, or was pleased about and continue to be pleased about, on the fluorine studies that constituted my Ph.D. thesis, were that we had to devise a way to make the isotope, to make up the targets, to do the simple chemistry, concentrate the material so that it was at an appropriate concentration to do a study and get the animal work done, all in a very short space of time, using relatively crude equipment at every stage. Somebody doing that today would call up and arrange to buy ready-for-injection material and utilize much more efficient, easier-to-use, rapid, semiautomated or automated detection equipment. |
| FISHER: | And analyzers. |
| DURBIN: | Analyzers and all those other good things. We were plowing ground, not just in examining physiologic or biological hypotheses: we also had to be chemists and know enough about the physics of the making of the material to get it made. It was the jack-of-all-trades kind of training. |
| FISHER: | That's what you want for a doctoral dissertation. |
| DURBIN: | I'm not sure that it would pass muster today as a doctoral dissertation. |
Dr. Joseph Hamilton's Astatine Research | |
| FISHER: | One of your most interesting publications in 1954 [described] the accumulation of astatine-211 by the thyroid gland in man. Do you remember that? |
| DURBIN: | Yes. |
| FISHER: | The Proceedings of the Society of Experimental Biology and Medicine. Can you talk about that work just a little bit? |
| DURBIN: | Actually, the impetus for that was Hamilton's abiding interest in astatine43 as a potential therapy source. |
| FISHER: | Therapy for thyroid disease? |
| DURBIN: | Yes. Because of the short range of
the alpha particles, which would then spare surrounding tissue from damage and
be very specific for the thyroid. I don't really remember a great deal about the
study itself. It was very straightforward. The individuals were all going to
undergo some kind of thyroid surgery. The astatine was made. It was hustled to
San Francisco [before it had a chance to decay].44
After the thyroid surgery was performed, after the pathologists got their share
of the surgically removed tissue, we got the rest [of] the thyroid. They were
total thyroidectomies in all cases. The tissues were weighed. The pathologist's
fraction was accounted for by weight. The tissue was hurried back to Berkeley. A
small piece was taken for preparation of autoradiograph[s]. Then the rest of it
was radiochemically analyzed for astatine content. Those were the reports; those
were the results that were reported. I'm not sure whether Hamilton was
encouraged or discouraged by the results, but it wasn't pursued.
I'm not certain-I'd have to look at all the injection books and the chronologic sequence of studies-but there were animal studies in progress. The big distribution thyroid uptake in pathology studies in rats. The small accompanying study on thyroidectomy by astatine was in a small number of monkeys. Another study that was underway, that was done at our place, again using monkeys, [was] done by an ophthalmologist, who was interested in seeing whether the short-range alpha particles could be used effectively if injected into a cyst in the eye, to therapeutically destroy the cyst, without damaging the eye. Astatine was put on to the eyes of monkeys and the ophthalmological outcome was measured. The short-range alpha particles did severe damage to the eyes of the monkeys. I guess he decided not to pursue that. That ended with one paper. Some additional studies were done in an ongoing sequence, a long sequence of studies was done with astatine in rats, looking at how the animals faired later on after an astatine injection and looking at what the influences on astatine uptake were of manipulating thyroid physiology with propythiouracil45 with protective iodine injections, hormonally altered animals-ovariectomized,46 adrenalectomized,47 hypophysectomized.48 In the long-term effects study, one of the outcomes was a surprising increase [in the] number of breast tumors in the astatine-treated rats (all females), [and] some substantial pituitary49 pathology, [not] real tumors, [but] pituitary hyperplasia.50 Even so, the pituitary being encased in bone, pituitary hyperplasia is very drastic. Those results rather dampened Hamilton's enthusiasm for the potential use of astatine as a specific [internal radiation] therapy source. That led us, then, to dose calculations based on the distribution and release of astatine from rat tissues, [to] calculat[e] the doses to tissues [other than] the thyroid. We were able to demonstrate that there was, as one would expect, presence [of astatine] in the glandular tissue of the breast, and dose calculations to the breast tissue cells [were] based on that. |
| FISHER: | Did you do measurements of activity [in tissue, such as looking for astatine] uptake in breast tissue? |
| DURBIN: | Yes, I think we did. It was not large. |
| FISHER: | Was this effect of breast cancer induction unique to astatine, or did you see this with other alpha emitters51 as well? |
| DURBIN: | We never looked at any other alpha
emitters. We did look at iodine, but I think that this was the initial
demonstration of radiation enhancement of breast tumors in rats. Other
investigators at other places, either because of this or because they were doing
other kinds of radiation studies, made the observation that external radiation
sources produced the same effect. [Chemically,] dibenzanthracine52 could produce the same effect.
The controversy went on for many years. I'm not sure it was ever actually resolved, as to whether it was direct radiation of the breast tissue or whether it was radiation plus alternation of the hormonal cycle of breast increase and regression, as a function of the levels of the estrogenic53 and progestogenic hormones, [which] change during the estrous cycle54 of the rat. But, eventually it was [generally agreed] that it was probably both and that there was a substantial hormonal component. [While] you [destroyed] the thyroid, there was also a substantial direct radiation dose [to] the ovaries. Our astatine-treated animals were essentially radioovariectomized as well as thyroidectomized at the higher doses. |
| FISHER: | You published that work on induction of tumors in the rat by astatine-211 in 1958. |
| DURBIN: | The first observations were made about four years earlier. |
| FISHER: | Does this imply in any way that alpha emitters would not be useful for therapy in other forms? |
| DURBIN: | I think there was some work that Chuck Sanders at Battelle published [on] inhaled americium, where he thought he had seen a statistical increase in breast tumors in the [female] rats. These [were rarely] carcinomas,55 [but rather] fibrous adenomas,56 that are hyperplasias, [sometimes] enormous, of the breast tissue. That led us to look at normal animals. We did a long sequence of serial sacrifices of untouched female Sprague-Dawley rats. It involved oocyte57 counts [in] the ovaries, breast tissue sampling, [and] histopathology58 of the pituitary, thyroid, [and] adrenal.59 [We] learned that the outcome of the normal[ly] aging, female Sprague-Dawley rat, is that almost every animal, eventually developed a pituitary hyperplasia and hyperplastic breast. That certainly said that there was a very large hormonal component to th[e] phenomenon. |
Human Study With Astatine | |
| FISHER: | Back on the human study with astatine with Hamilton, do you recall many of the details of the patient aspects of this work? |
| DURBIN: | None. |
| FISHER: | This took place at UC San Francisco. |
| DURBIN: | I don't know any of the details about the patients, except their names, their hospital numbers, their histopathology numbers, and the diagnoses of disease, [which are on file]. |
| FISHER: | Was that information retained by you? |
| DURBIN: | Yes. |
| CAPUTO: | Were there consent forms? |
| DURBIN: | No, not in my files. There might well be in the files in the hospital, but I don't have that. |
| FISHER: | One of the questions with each of these identified experiments, involving the administration of radioactive materials to humans, is [whether] there [was] informed consent. Astatine was an alpha emitter. It was administered presumably as a sodium astatine complex? |
| DURBIN: | Probably sodium astatine. |
| FISHER: | Into the bloodstream? |
| DURBIN: | Yes. |
| FISHER: | With uptake in the thyroid and perhaps substantial nonthyroid distribution in these patients. |
| DURBIN: | Before it either decayed or was excreted. |
| FISHER: | It has a seven-hour half-life, so it's not going to stay around for very long. |
| DURBIN: | No, and the excretion is very efficient. |
| FISHER: | Very efficient. Was there any interest or follow-up in these patients? |
| DURBIN: | Not to my knowledge. |
| FISHER: | Do you know of any other humans who have been administered sodium astatine? |
| DURBIN: | No. |
| FISHER: | In all of your experiments? |
| DURBIN: | Certainly not here. |
| FISHER: | Was there just one study done of this type? |
| DURBIN: | Yes. |
| FISHER: | Have you thought about it much since then? |
| DURBIN: | No. Astatine has not been one of my lifelong interests. It's miserable to make and hell to work with. |
| FISHER: | It is being used on a very limited scale as a label for monoclonal antibodies60 in cell-directed therapy. The idea of using an alpha emitter, and particularly astatine-211, is still an [interesting] one, [even] after 40 years. |
| DURBIN: | Yes, but those monoclonal antibodies, if they're injected directly into the circulation, are going to wander around, and every astatine that decays in the circulation is going to deliver the same kind of radiation dose as sodium astatine did or does on its way around. |
| FISHER: | And it tends also to dehalogenate61 from the protein. |
| DURBIN: | I'm not surprised. But the files have been presented to DOE, the names of the people have been made known to them, the existence of the files is known to them. I believe the existence of the files, [is] known to the Human Experiment Investigating Group at UC San Francisco. I'll find out next week if they have this, if they want this. They can go to the warehouse and look for the patient records if they choose to do so. |
| FISHER: | Were those papers in the collection that you recently turned over to DOE? Do you remember? |
| DURBIN: | The contents of three file cabinets [were] copied by the Archives [Department] here at LBL. Those files were in that collection. |
Research on Use of Iodine-131 | |
| FISHER: | You continued doing iodine-131 studies in the rats? |
| DURBIN: | Yes. |
| FISHER: | Even long after you discontinued your astatine work? |
| DURBIN: | Yes. |
| FISHER: | [Would you] amplify a little on that? |
| DURBIN: | We were interested in the internal
dosimetry of iodine. I'm not sure it shows in the publications, but there was
some anxiety about the use of very large doses of iodine-131 as a therapy agent,
and what the tissue doses might be in other organs and what the biological
outcomes might be in other tissues. This predated, I believe, what groups like
the Medical Internal Radiation Dose group62
eventually tackled for estimating internal doses for something like iodine.
One of the outcomes of at least the dosimetry aspect was that when you gave very large doses, you got very bad outcomes. There was a substantial dosage-related, or radiation dose-related, impact on the longevity and the health of the rats. To a large degree, you had to attribute this to internal radiation of tissues other than the thyroid. You had to attribute it to radiation bioeffects, other than the influence of the thyroid on depressing bone marrow productivity. What we were trying to do was to sort out the various influences of the hormonal problems which are a consequence of thyroid ablation63 [on the one hand] with iodine and the direct radiation effects on other tissues of iodine decaying in the circulation [on the other hand]. One of the things that came out of this was the demonstration of the cycling of iodine through the gastrointestinal tract, a factor which hadn't really been examined very carefully. A great deal of iodine is secreted, and the gastric secretions are then reabsorbed by the small intestine. Some radiation dose is involved in that. The direct effects on the kidneys, we observed at the high dosages of iodine. Renal64 atrophy65 increased [the relative] quantities of fibrous connective tissue, decreased quantities of tubules,66 and [caused] shrinkage and disappearance of glomeruli,67 [among the] dose-related consequences. There were plainly radiation effects caused by the circulation of iodine in the blood and the secretion of iodine by the GI tract and the excretion of iodine by the kidneys. |
| FISHER: | Was mucositis68 one of the effects that you observed? |
| DURBIN: | I don't know that we [called what we] observed by that name. I'd have to go back and look. |
| FISHER: | Because of the reabsorption of iodine in the gastrointestinal tract tissues? |
| DURBIN: | If I remember correctly, and I'd have to go back and look at the paper, I think that in the animals who were long-term survivors, that was not something that caught our attention. |
| FISHER: | Were these all studies in rats, primarily? |
| DURBIN: | Yes, all rats. |
| FISHER: | Did you every involve yourself in human studies of iodine toxicity? |
| DURBIN: | No. |
| FISHER: | Whatsoever? |
| DURBIN: | No. |
| FISHER: | Do you wish that you had? |
| DURBIN: | No. Under the present circumstances, I'm grateful I didn't. |
Research on Chelating Agents | |
| FISHER: | I noticed that about as early as 1960, maybe even before that time, you were interested in complexing agents. |
| DURBIN: | It wasn't me, [as] much as it was the people that I worked with. |
| FISHER: | For example? I was thinking of-if I'm not mistaken, your first publication dealing with a chelating or complexing agent was about 1961 with curium-242. Had you worked with DTPA69 or EDTA70 before that time? |
| DURBIN: | No. But this is an interesting piece of history and I'd like to incorporate it [here] because I believe in giving credit where credit is due. In the early 1950s, a physician named Harry Foreman came to the Crocker Laboratory as, I guess, a postdoctoral fellow. He had come across-I've never been quite sure of how it was that he came across it-he had come across the existence of an interesting compound called versene. It was a proprietary agent that was made by the Bersworth Chemical Company. Maybe he knew Mr. Bersworth. In any case, he came with this versene, which we all know as EDTA, ethylene diaminetetraacetic acid. He began looking at the complexes that [it] formed with curium. There was a substantial amount of interest at that point in fission-product and actinide removal therapy, because there was nothing available. He began some experiments with removing plutonium. I've looked up the date of the publication. It was 1950. |
| FISHER: | What's the citation? 1950? |
| DURBIN: | 1950. |
| FISHER: | What publication? Where is it? |
| DURBIN: | The first citation was in UCRL
Progress Report, Number 960. Then he and Hamilton published a paper in 1952,
I guess it was; I don't know the date. There's another one and again, UCRL
Report 1351, in 1951, called "The Use of Chelating Agents for
Accelerating Excretion of Radioelements." Then, after he left, Hamilton and
[Kenneth] Scott engaged in some studies of the ability of EDTA to remove
plutonium from rats. That piece that you refer to, which is part of, I believe,
a UCRL Progress Report, [the] curium citation was a follow-on to see
whether or not EDTA could be used for actinides other than plutonium.
We didn't get very good results. You could demonstrate that there was some complexation71, but the results in terms of body actinides were not dramatic. You could certainly increase the excretion, but the [amount] that you increased [the excretion] was not large enough to have a dramatic effect on total actinide retention. Therefore it wasn't really going to be very useful in reducing total radiation dose. That work kind of just quietly died. Kenneth Scott severed his ties with Crocker [Laboratory], in the general neighborhood of 1952, 1953. He still came over and he was still a participant in some things, but he basically moved his operations to San Francisco, where he took a tenured position, setting up and running their radioisotopes laboratory. |
Recollections About Dr. Joseph Hamilton | |
| DURBIN: | Hamilton's real interests were
radiotherapy and medical diagnostic techniques. That led Hamilton back to
astatine and iodine, in preference to a lot of other matters, although he still
maintained a lively interest in some things that some other people were doing,
such as examining autoradiographically the differences in distribution of, say,
actinides and lanthanides72 on
the one hand and strontium on the other hand in bony structures, like the
junction of the cartilages73 in
the rib, to see whether or not one of these was so mineral oriented that you
would see it in the mineralized cartilage core, or whether you saw it only on
the interior of bone surfaces.
That work was being conducted with another Ph.D., Harold Copp, who was at that time a professor of Physiology at Berkeley and later left to become the chairman of the Physiology Department at the Medical School of the University of British Columbia in Vancouver[, British Columbia, Canada]. [There was] also another M.D. who was an anatomist, who had a great deal of specialization in bone, C. Willard Asling, who was in the Anatomy Department at UC Berkeley, [but] when the first year [of] the medical school was moved to San Francisco, he moved to San Francisco and our association essentially disappeared. He started us out looking at the skeletal x rays of monkey[s] [to] determin[e] age. The only thing I wanted to say about Hamilton's attitude about things was that he was not an experimentalist in the way we now view experimentalists. He didn't latch onto a topic and pursue it to some sort of conclusion, even though to do that [(to explore a variety of avenues)] meant the conduct of a great deal of work and sometimes the pursuit of side issues. Although, I guess you could say that the astatine and iodine studies were more [of an effort] to look at something in-depth. But, he said on several occasions that what he liked to do was "get in there early and skim off the cream and then go on to something else." I remember [his saying something like that] when he was very ill and sitting in his office. |
| FISHER: | He was ill with? |
| DURBIN: | Leukemia. Aleukemic myeloid leukemia, which meant that he [had] a large number of circulating undeveloped cells, or incomplete cells. It meant that both his total myeloid74 white count and red count were just gradually disappearing. His marrow was full of these stem cells, but they weren't maturing and nothing was being delivered to the circulation. |
Decompression Studies at Donner Laboratory | |
| CAPUTO: | Let's change courses for a second. What do you know about the decompression studies at Donner Laboratory? |
| DURBIN: | Only that they took place. One of the women at Crocker, I'm not sure [if] she was employed at Crocker at the time those studies were being done, or whether she came to us after they were underway. Anyway, she was one of the subjects in the decompression studies. She volunteered to be a subject. |
Relations Between Donner and Lawrence Berkeley Laboratories | |
| CAPUTO: | What was the relationship between Donner and LBL? |
| DURBIN: | Well, LBL didn't exist at the time.
It was the University of California Radiation Laboratory which was under the
general management and auspices of the Physics Department on the campus. [The
lab was a] creature of the Physics Department.
Donner Laboratory was fundamentally a locus for people who were interested in nuclear medicine, human physiology, decompression studies, iron metabolism [in] health and disease. There [were] some burn studies, the clinic where the 32P [(phosphorus-32)] was used to treat leukemia and polycythemia.75 Crocker housed the 60-inch cyclotron, and laboratory space for chemical preparations of materials made in the cyclotron and for the conduct of experiments using isotopes and so on. The 60-inch [cyclotron] was a separate administrative and financial entity, but the funding for the Crocker experiments, the chemistry, the making of targets, the follow-on biology, and so on was AEC-funded. Joe Hamilton and John Lawrence were sort of adversaries [(directors of the Crocker and Donner Laboratories, respectively)]. I don't know why they should have been because each one had a different sphere. John Lawrence was basically a promoter of nuclear medicine aspects and Hamilton was the manager of the cyclotron. [Hamilton was] caught up in vast numbers of Government consultative bodies and committees, advisory groups to several Government agencies, and [he] did a great deal of traveling and met a lot of luminaries and consulted at the highest levels of Government. But Hamilton still wanted to remember some of the glory days of the first demonstration of utility of iodine as a diagnostic agent for thyroid disease and some of the other early great stuff. He did want to go back into experimentation having to do with astatine and iodine and so on. What went on at Crocker and what went on at Donner were administratively and intellectually totally separate. They were two islands, really. Apart from the fact that the directors of the two laboratories sat together as codirectors of the group on bio- and medical physics, which was the degree-conferring arm of the Physics Department, I don't know that they even communicated much. They may have communicated a great deal more than I was aware of, but I got the feeling that there was not an awful lot of interaction. |
| FISHER: | Didn't the Donner Lab depend on isotopes from the cyclotron? |
| DURBIN: | For a while. But, they began to get things like [radio]iron from Oak Ridge, and I'm not sure what their 32P source was. But, large quantities of 32P were not made on the 60-inch cyclotron for very long after I went to work there in 1946. Possibly, by 1948, some other source for their 32P had been developed. |
Wartime Animal Research on Plutonium Metabolism | |
| FISHER: | Were you part of the organization when Hamilton was working on his studies on zirconium, niobium, and other materials were produced? |
| DURBIN: | You mean the fission-product work? |
| FISHER: | Yeah. |
| DURBIN: | No. The basic fission product work was completed by about mid-1944. |
| FISHER: | This is part of MED [Manhattan Engineer District]. |
| DURBIN: | Yes. And in February of 1944, the
first plutonium source arrived and, from looking at the data files in
chronologic order, it appears that there was almost no additional
fission-product work from February of 1944 until after the war was over in 1946.
The great push was on plutonium: injected plutonium, orally administered
plutonium to a very small degree, plutonium in different forms, all in rats; the
development of the technique[s] for cutting [un-]decalcified bone [and making]
autoradio graph[s], [and plutonium] inhalation studies, huge quantities of
small- scale inhalation studies with rats, which formed [much of] the basis for
[the first] ICRP-NCRP76 lung
model.
But, I suspect that there were fission-product studies, at least injections that had to have gone on in that time frame, because the sliding microtome77 for making the un-decalcified bone sections and production of slides of element 61, promethium, and zirconium and cerium may have been made in the 1944-to-1946 frame. |
| CAPUTO: | Would these be in animals or in man? |
| DURBIN: | All animals. All work is animals, unless otherwise s |
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.