Work With Soley to Diagnose and Treat Thyroid Disease With Iodine-131 |
| MILLER: | No: let's start again. Ken called me up one day and said, "We've
got some radioiodine." Mayo Soley and Joe Hamilton had done some real
pioneering work on this on the thyroid. He said, "There's a lot of this
radioiodine around; do you want some, do you want to try it?" I thought
about it for a long time, like 30 seconds, and I said, "Yes. That sounds
like a real interesting thing." So radioiodine appeared, and I had to learn
about how it was measured, how it was detected, what effects could be expected,
etc. Dr. Mayo Soley had worked with Joe Hamilton on the fate of radioiodine in
the bodies of animals. Soley was an expert in thyroid disease. He furnished the
patients after thorough study and I gave the radioiodine. That's how it
developed. |
| HERKEN: | Soley was your colleague? |
| MILLER: | Yes. |
| HERKEN: | He was not a radiologist? |
| MILLER: | No, he was an internist. He later became dean at [State
University of] Iowa. Became the dean of the medical school at Iowa. |
| HERKEN: | Is he still alive? |
| MILLER: | No, he shot himself.27 That's why you should never become
a dean. |
| HERKEN: | For reasons of ill health, I hope. |
| MILLER: | Nobody ever knows. |
| HERKEN: | Did he die young? |
| MILLER: | Yes. |
| HERKEN: | Soley would find the patients who might be good. |
| MILLER: | His patients. He was an internist with particular
interest in thyroid disease. That's how this got together. |
| HERKEN: | Then he would contact you as the radiologist. |
| MILLER: | Yes. We would work together on this. |
| HERKEN: | He would actually administer the iodine, wouldn't he? |
| MILLER: | No. |
HERKEN: | You would; that was putting the radiologist to work. |
| MILLER: | He furnished the patients, he did the history and physical
examination of the patient to decide whether the patient did or didn't have
thyroid disease. Many of his patients had hyperthyroidism,28 and some had
cancers. |
| HERKEN: | This was before he died. |
| BERGE: | Did you ever do any of the diagnoses yourself? |
| MILLER: | I became good at it, with practice, but the clinical
responsibility was Soley's. They were his patients, and he [had] studied and had
done work on thyroid disease forever and he knew a lot about it. So it was his.
Later on, as time went on, I became pretty good at it, too. |
| HERKEN: | Was this only use of radioiodine, not other nuclear
materials, phosphorus? |
| MILLER: | No, only 131I. |
| BERGE: | I just want to do a little more with the radioiodine studies
that you did. When you were working with Low-Beer, he was doing the
hematological29 stuff, and you were doing the radioiodine studies. |
| MILLER: | The work of Low-Beer and me was totally separate. |
| BERGE: | How did that work? Was he using the blood from patients that
you were studying? |
| MILLER: | No. He had his own project. I do know that I was much aware
of his work on phosphorus, but that was his. |
| HERKEN: | Just to confirm something: The iodine that you used had been
produced on the 60-inch [cyclotron]? |
| MILLER: | Yes. |
| HERKEN: | It wasn't from Oak Ridge? It was cyclotron-produced? |
| MILLER: | Yes, right. I think that was all we had at that time. |
| HERKEN: | I didn't get the date straight on this, but you say this
would have been after the war[, in] '46 or '47? |
| MILLER: | That's my remembrance. I could look up my first papers.30 |
| HERKEN: | There are not a lot of documents on this whole period. One
of the documents we found here in this case [is] from 1951. But, this is an
AEC31 project. |
| MILLER: | "Question on the Thyroid Disease and Radiology,"
1951. I was going to say I thought 1950ish was about right. That's the only one
you have for me? |
| HERKEN: | No, that's the only one I brought with me. |
| MILLER: | If it's important I'll get my bibliography out. |
| HERKEN: | Is that the first paper with Soley in 1948? |
| MILLER: | Yes, January 1948. Low-Beer and I apparently wrote a paper
together, "The Biological Effects of Radiation from External and Internal
Sources." Oh—that was a UC Radiation Laboratory [(UCRL)] report. (He
wrote the section on his work and every UCRL report contained a progress report
on 131I by me.) |
| HERKEN: | What's the number on that report?
(phone rings; tape interrupted) |
| BERGE: | Another question about the radioiodine project: Were you
doing this independently? |
| MILLER: | Independently. |
| BERGE: | So, this was not supported by the AEC? |
| MILLER: | The iodine [project] apparently was supported—getting
iodine etc., was supported—by AEC. For instance, I wasn't paid to do
anything. This was my own research. Does that answer your question? |
| BERGE: | So, it's very much like applying for a grant and then doing
whatever you want to do? |
| MILLER: | There was no grant involved here: We were treating patients. |
| BERGE: | Were you working with anyone else on this or was this,
again, independent? |
| MILLER: | I told you this earlier with Soley. Soley and I worked
together for years on this project. When Soley took the deanship at Iowa, Morrie
[(Maurice)] Dailey took over Soley's practice and the project, and we worked
together. |
| HERKEN: | When Soley would find a patient who seemed suitable— |
| MILLER: | —They came to him as their primary physician. |
| HERKEN: | But, he would notify you if he found a subject who seemed to
be suitable for radioiodine? |
| MILLER: | Exactly. |
| HERKEN: | Was there a consent procedure here, since you were involved
in administering radioiodine? |
| MILLER: | Wait a minute—we developed a consent thing. I don't
know when; not at the beginning. For instance, a patient who comes to a
physician for some heart disease doesn't sign a consent form for digitalis. In
this case, this was exactly the same thing. This was a kind of treatment that
prevented a lot of people from having operations. (See Dr. Miller's
preceding textbox, "About Consent Forms," under "Human
Applications Committee and Informed Consent.") |
| HERKEN: | But, this was not tracer amounts. They were in fact— |
| MILLER: | —They were tracer amounts for diagnosis of thyroid
function and larger amounts for the treatment of hyperthyroidism. In the case of
carcinoma32 patients, we made very clear to patients that they were going to
get a big slug. That meant 100 millicuries per dose. |
| BERGE: | What were the criteria for having patients undergo
radiological treatment? Was it anyone who had hyperthyroidism or cancer of the
thyroid, or was it people who hadn't responded to other therapies? |
| MILLER: | This was the therapy of choice for hyperthyroidism.33 In
our mind it was the therapy of choice to begin with. Certainly Soley and
Hamilton felt that way. What we were doing was to prove this was the case. Not
only that, but the job was to see how little we could give and still have the
patient get well. We were calibrating the dose and the severity of the disease,
and I wrote about this. It depended on who saw the patient. |
| BERGE: | How do you mean? |
| MILLER: | There is no specific laboratory test that would divide
those who were hyperthyroid or hypothyroid34 or euthyroid.35 Somebody had to
say that the patient had that. This was a part of my interest in the philosophy
of medicine, if you will. It turned out that, if for instance, a patient was
jittery and kind of stressed, and he went to a physician; this physician said, "You've
got hyperthyroidism, you have to have your throat cut." You didn't like
that, so you went to another physician, who said, "Well, I'm not sure you
have hyperthyroidism." Now in the one case you had it and in the next case
you didn't. But, you[r thyroid condition] didn't change. I was very interested
in that, because it turned out that we got pretty good at separating those with
and those without. There were a lot of things to suggest it. But there was no
single, objective, critical way to tell the difference. |
| BERGE: | What about using iodine as a diagnostic tool? |
| MILLER: | Yes, I developed that. That was a corroborative thing. It
didn't prove it; it was just another strand of the rope. |
|
Patient Consent; Contradicting Perceptions |
| HERKEN: | Coming back to the consent procedure: Can you tell me about
how that worked? (See Dr. Miller's preceding textbox, "About
Consent Forms," under "Human Applications Committee and Informed
Consent.")
(phone rings; tape interrupted) |
| MILLER: | At some time, some forms were developed. I can't remember
anything really more than that. I don't remember when it happened. I don't
remember what was in the form. There was a form. As I remember, that was
way after the war.
This, I think, came about because people other than radiologists were using
radioisotopes for studying physiology, possibly treating patients; I don't
remember that. But the people who got involved in this late had not had any
training in this, or very little, and they needed to be monitored by people who
knew what it all was about. This, I remember, was how it came to be. |
| HERKEN: | I think it was by spring of 1947 [that] the AEC had a
regulation that there be consent confirmed in writing by two attending
physicians as to the understanding and consent of the patient. |
| MILLER: | It could well be. That sounds reasonable. |
| HERKEN: | The one thing that's curious is that there is some evidence
that the AEC, itself, initially proposed that there be written consent by the
subject but that the physician or the intramedical advisory committee, that
Stafford Warren headed, actually balked at it and urged that instead of there
being written consent upon the patient, there be consent by the two attending
physicians. I've never quite understood why that would have been important. |
| MILLER: | I don't know. This is my interpretation now. You're a
patient and a layman. You don't know from nothing about radiation. You're going
to sign this consent form saying it's okay to take this radiation, or it is not
okay to take this radiation, without knowing a single thing about it. This
didn't make sense to Staff Warren, and it doesn't to me. |
| HERKEN: | Do you remember any conversation you might have had to that
effect? |
| MILLER: | No. This was my own feeling about this. I still feel that
way. They say that the doc should explain everything. You take a person with no
training and no matter how it's explained, he still doesn't know. These are the
things you have to do in order to make a decision. The patient would have to go
through medical school and internship and residency [to have enough information
to completely understand the risks and benefits of a proposed therapy as well as
the prescribing physician] and then they would be able to sign it with truly
informed consent. |
|
Wartime Plutonium Injections |
| HERKEN: | Getting back to the case of the plutonium injections: Is
that something that Stafford Warren would have authorized from his position? |
| MILLER: | I have no idea. |
| HERKEN: | We haven't found any documentation one way or the other on
that. |
| BERGE: | How much interaction did you have with Staff Warren after the
war? |
| MILLER: | Very little. In fact even during the time I was working
presumably for him, I saw him about once every six months. I just got turned
loose. He was recruiting. |
| BERGE: | That's right at UCLA. |
| MILLER: | If he got somebody to do his job, he was off. Are we getting
somewhere? |
| HERKEN: | Yes, we're going down the list here. Just changing gears
again, I had an interest in the strontium therapy work that would have been
done. |
| MILLER: | I don't know anything about that. |
| HERKEN: | You're not involved in that. Somewhat of a bureaucratic
question—I don't know if you'll know the answer to this: Initially, the
work that was done at UCSF was done under Contract 48, which was the contract to
LBL, and later…? |
| MILLER: | You mean this. (holds out a report, cover forward,
toward Herken) Go ahead. |
| HERKEN: | (studies the cover of the document) This was
actually the MED, the Manhattan Project funding. But later, by 1947, there was
something known as Contract 10, which is something that Stafford Warren—which
is an AEC contract to the University of California for therapeutic work
involving the use of radioisotopes. [My question is] if you remember [a]
changeover in funding. |
| MILLER: | I don't remember anything about that. What was the time of
that? Oh, Maurice Dailey was the guy that took Soley's place. |
| BERGE: | How do you spell his name? |
| MILLER: | Dailey, Maurice. |
| HERKEN: | Is he still alive? |
| MILLER: | I don't know. Looked just like Abe Lincoln. |
| HERKEN: | This is work with radioiodine? |
| MILLER: | (scanning the document) I was just trying to find
the last paper I was involved with. I think '55 might be it.36 |
| BERGE: | After about 1950, did you work with the Radiologic Laboratory
that was in a separate building? |
| MILLER: | No, that was Dr. Stone's baby. |
| HERKEN: | Besides radioiodine, what other radioisotopes would you have
done? |
| MILLER: | None. (Don't you ever listen?) All of my work was primarily
as a diagnostic radiologist. |
| BERGE: | Did you conduct experiments per se, rather than just
therapeutic work? |
| MILLER: | I didn't understand your question. |
| BERGE: | You said your primary work was as a diagnostic radiologist.
Did you do any experimentation? |
| MILLER: | With patients? |
| BERGE: | Yes. |
| MILLER: | No. My work was primarily as a physician—interpreting
radiographs—and a physicist dealing with the physics of machines and of
radiation. |
| BERGE: | Would now be a good time to ask about— |
| HERKEN: | —Let's wait a little bit. |
| MILLER: | What were you going to do? |
| BERGE: | At some time later on—I'll let him ask his questions
first—I understand that you were responsible for a number of inventions and
I just wanted to ask. |
|
Hamilton's Research on Effects of Cyclotron-Produced Radioisotopes |
| HERKEN: | Getting back to Hamilton's work, and Hamilton is such a
special interest of mine. As part of his work for the Manhattan Project to see
how radiation, internal radiation, affected workers, he was proposing by the end
of the war to essentially go down the periodic table, the transuranium37
periodic table, and try different means of how people would be exposed to these
elements, either by injection, ingestion, inhalation, were the three methods. He
became especially interested in the danger through inhalation, which he
determined was the greatest danger. And yet we know about the injections, of
course. But, we can only find one case of an inhalation experiment, and that was
involving zirconium with Ken Scott back in 1945.38
(Dr. Miller inserted the following textbox during the editing process.)
|
| MILLER: | I never heard of it. You remind me of the fact that dimly,
I was aware of the fact that Joe's work was part of this fantastically designed
long-term experiment in going through the whole periodic table [of radioisotopes
and studying their effects and distribution and excreta in animals.] That's
special work. |
| BERGE: | Do you know if there was any order? What kind of order was he
employing when he was going through the periodic table? |
| MILLER: | What was available off the cyclotron. If he got a Z first,
like zirconium, and then he got carbon, then it would be Z, [and] C—whatever
was available. |
| HERKEN: | Wasn't he initially responsible for running the 60-inch
[cyclotron]? |
| MILLER: | I know, but nature decided what came off of it. |
|
| [Textbox: Dr. Joe Hamilton (April 21, 1995)] |
|
|
Research With Patients From Laguna Honda Home |
| HERKEN: | I had a question, as well, about the work that Stone and
Hamilton were doing up at Laguna Honda Home. Did you have any patients coming
from Laguna? |
| MILLER: | I did some work at Laguna Honda with Dr. Howard Bierman.
What they did was special. I think it could have been phosphorus work for all I
know. |
| HERKEN: | The only thing we have is really a letter from Ken Scott
back to the AEC, I think it's dated 1948, saying that the work that Hamilton and
Stone are doing at Laguna Honda is not funded by the AEC. I think it was funded
by National Cancer Institute. |
| MILLER: | That makes sense. A lot of Stone's stuff was [like] that.
Because he was a cancer therapist. |
| HERKEN: | I think what Stone was doing was taking patients from Laguna
Honda and actually treating them at San Francisco at UCSF. I assume that was it. |
| MILLER: | It could well be. I don't know. |
| HERKEN: | When you had patients at Laguna Honda, you would take them
to UCSF? |
| MILLER: | Me? No. We simply used a fluoroscope.39 |
| HERKEN: | At Laguna Honda. Did they have an x-ray machine? |
| MILLER: | They had a fluoroscope. |
| HERKEN: | There was something known as the Laboratory for Experimental
Oncology40 at that time at Laguna Honda. Michael Shimkin [ran it]. |
| MILLER: | Shimkin, right. |
| HERKEN: | Did you have any work with him? |
| MILLER: | I worked with Dr. Bierman, who was on Shimkin's staff. In
fact, one or two of the papers were [written] with Bierman. What we did was to
examine [the patient] under the fluoroscope with a catheter41 and use an
opaque material. We studied the arterial supply of every organ in the body, with
particular interest of those where there was metastatic42 cancer. |
| HERKEN: | These were not necessarily Laguna Honda patients? |
| MILLER: | [Nearly none of them were from there.] It turned out that
that's where the work was done, because Bierman and Shimkin were there and a lot
of cancer patients were referred there. The only reason it was at Laguna Honda
was there wasn't room at UC for a place to [put the Laboratory for Experimental
Oncology.] |
| HERKEN: | The patients would not all be geriatric patients, is that
correct? They would be a range of people. |
| MILLER: | They would be primarily people with carcinoma, some kind of
malignant disease. That tends to be in the later years, but not limited to that. |
| HERKEN: | As I remember it, as I understand, Laguna Honda was a city
and county-run home, still is, for the indigent. |
| MILLER: | But, again, it's not because they were indigent; it was
because they had a cancer. [You must understand that the patients who were
referred for treatment to the Laboratory for Experimental Oncology came from
everywhere. All regular treatment for their disease had been tried.] These
people came from anywhere; [they were referred to the laboratory. Get this in
your head!] |
| HERKEN: | But the only equipment that you had at Laguna Honda was this
antique fluoroscope. |
| MILLER: | That didn't have anything to do with that. As a radiologist,
I helped in lining up that catheter and then, later on, interpreted the
radiographs that we got. [This was work I did with Dr. Bierman.] |
| HERKEN: | Again, this was using radioiodine as a tracer? |
| MILLER: | No. Don't get it mixed up. We used a [material] called
diadrast, which [contains iodine, but] was not radioactive. It was
radiopaque.43 Going, for example, into the cervical artery, we could profuse
the whole liver and differentiate the blood supply of the normal liver from
[that of] the metastatic cancer in the liver.
This was important work. Because it turned out that any cancer therapeutic
agent, given by vein, was diluted through the venous44 system and the arterial
system of the whole body. [In our work,] a catheter was put into the carotid
artery, and guided to all the organs under fluoroscopic control. It went
directly to the cancer, and the calculation at that time was that the dose to
the cancer was 20,000 times greater than a similar dose given by vein. That [was
Bierman]'s important work. |
| HERKEN: | Let me get this straight in my mind: This was not work you
did at the Laboratory for Experimental Oncology. This was not something under
Shimkin's direction. |
| MILLER: | Bierman worked under or with Shimkin. This was part of the
business of understanding the whole phenomenon of neoplasia.45 Blood supply
was part of it. [This was Howard Bierman's project, and I helped him with it.]
(phone rings; tape interrupted) |
| HERKEN: | (glancing at the wall) You have a picture of Stone
on the wall [of your house]. |
| MILLER: | Yes; those people on the wall there were the people that
influenced my life. |
| HERKEN: | Who was the individual to the left? |
| MILLER: | The bald-headed? |
| HERKEN: | No, down to the bottom right. |
| MILLER: | I don't know. (Dr. Miller amends: That was Dr.
Ernest Pohle, professor of Radiology at the University of Wisconsin. He gave me
a job.) |
| HERKEN: | We were just talking about Laguna Honda. I think I have it
straight now. You in fact did not know very much about Stone's work at Laguna
Honda, which I think basically involved taking patients from Laguna Honda to UC
Medical Center and using the 70-MeV46 machine there, the bevatrons.47 |
| MILLER: | The patients came from the Laboratory for Experimental
Oncology that was housed at Laguna Honda. They were not patients who were in the
hospital. There was no bevatron at UC. Wait a minute—yes. |
| HERKEN: | Not at Laguna Honda, but at UCSF. |
| MILLER: | In what he called the Radiological Laboratory. I've
forgotten that even had existed. |
| HERKEN: | And the Radiological Laboratory is something that he created
himself after the war, is that right? |
| MILLER: | Exactly. |
| HERKEN: | About 1947? |
| BERGE: | 1951. |
| MILLER: | He got funding for that from the National Cancer Institute.
|
| HERKEN: | Is Bierman still alive? |
| MILLER: | I don't know. Great guy. Inventive. He was so inventive that
he couldn't get along with Shimkin or anybody else. He finally got to work down
in L.A. someplace. |
| HERKEN: | Shimkin has written a little history of the Laboratory for
Experimental Oncology and calls it [(the history)] The Lost Colony. He's
fairly open in the history about his disagreements with Stone. I should say he's
open that he disagreed, but that it's a little unclear what the disagreement was
about. |
| MILLER: | I don't know. I remember that it existed. I wouldn't have
remembered until you said it. And I don't know what it was about. Whether it was
a matter of him getting too big for his britches, or I don't know what. People
are human, even doctors. |
HERKEN: | (turning to Berge) Do you have any questions on
this? |
| BERGE: | I'll have some questions later, but not on Laguna Honda. |
| HERKEN: | In fact, the laboratory at Laguna Honda was shut down in
1953. I think Shimkin left at that time, although I'm not really sure. |
| MILLER: | I think that's [about] right. I don't know the date. I don't
even know what happened to him or where he went. |
| HERKEN: | Did he do any work with John Lawrence on radioiron? |
| MILLER: | I don't know. I wouldn't be surprised if they had done some
work together, but I have no solid information about it. |
| HERKEN: | But you were not involved in doing work for John Lawrence? |
| MILLER: | No, the only involvement I ever had at Laguna Honda was this
vascular48 study, studying the difference between the blood supply of the
normal tissues and the cancer. |
| BERGE: | Somewhat on the same track, but different hospitals: What
kind of involvement would you have had with Langley Porter?49 |
