Radioactive Iodine Uptake in Schizophrenia Patients |
| MILLER: | Only when I wrote a paper with Bowman, who was the head of
Langley Porter. He was interested in knowing whether people with schizophrenia
had any possible thyroid involvement. He sent patients over, and we did the
tracer studies on the rate of uptake, which was the most effective way of
separating the "normal" from "abnormal" rates of absorption
in the thyroid. The study was done during the three-hour uptake period, and we
did it at one, two, and three hours. The people who were hypothyroid [had low
uptake rates]. The normal group lay in the middle [of the uptake-rate
distribution curve], and the hyperthyroids [had high and rapid uptake of the
radioiodine]. So you could actually make the corroborative study. Finally it got
to the point where the thing was so good that it could be used later on as a
diagnostic tool. Then they didn't need it anymore. "Miller's Law"! |
| BERGE: | What kind of results did you get from that? |
| MILLER: | There was nothing, no correlation. They were all normal,
except they were crazy. The thyroid wasn't involved. Soley did the clinical
stuff, and I did the radioactive iodine uptake stuff. |
| HERKEN: | When did Soley leave San Francisco? |
| MILLER: | When he went to Iowa. I don't know when that was; I don't
remember dates. It was sometime early.50 |
|
Recalling Dr. Joseph Hamilton |
| HERKEN: | In thinking of papers, did you have any collection of
papers and correspondence with Hamilton or Stone?51 |
| MILLER: | I don't think I ever wrote to Joe, ever. But Joe and I
became good friends. (See textbox, "Dr. Joe Hamilton," in "Hamilton's
Research on Effects of Cyclotron-Produced Radioisotopes," preceding)
The only time I saw Joe was when I was making my rounds over at Berkeley, and
later on, when I visited his home when he was dying; I saw the artwork of his
wife. Great artist. My [ten-year-old] daughter was with me and she said, "What
are you trying to do?" She said, "I'm breaking up space with color." |
| HERKEN: | This is on a personal note, but I noticed in the obituary
for Hamilton you mentioned that he nursed his wife through an illness and in the
end she acted as his nurse. |
| MILLER: | If I remember correctly, she became psychotic; I've
forgotten. |
| HERKEN: | Was that treatable with drug therapy back then, for
psychosis? |
| MILLER: | No. He loved his wife very much. He just took care of her,
and he endured that time. |
| HERKEN: | I read that he diagnosed his own leukemia about 1955. |
| MILLER: | It doesn't surprise me at all. I think it was the massive
doses of radiation that he had. And they were massive. I think they actually
started it [(the leukemia)]. |
| HERKEN: | Did he ever keep a diary or journal? |
| MILLER: | It's just like I wouldn't know about you having a diary. |
| HERKEN: | I talked with someone who said that he had a gold-rush
cabin, up in Auburn, [California], and he used to go up there and pan gold on
weekends. That was his form of relaxation. |
| MILLER: | I did hear about that. Who was this that went there? |
| HERKEN: | I think it was Bill Douglas who was [with] the [unintelligible]
lab. |
| MILLER: | I don't know anything about that. |
| BERGE: | Did you ever go over there [to the Hamilton house] for social
occasions? |
| MILLER: | No. [The only time I went to the Hamilton house was to visit
Joe when he was dying.] My young daughter was with me at the time. |
| HERKEN: | They didn't have any children, did they? |
| MILLER: | I think not. |
| HERKEN: | Did she ever remarry? |
| MILLER: | I don't know anything about her. |
| HERKEN: | She's no longer alive; I've gone through my list [of
historical figures to contact]. |
|
Invention of a Baby Holder (1951) |
| BERGE: | I wanted to find out a little bit more about your
inventions. We came across a series of pictures in which you were credited with
the invention of the "brat board." |
| MILLER: | The BRATT BORED [sic].52 It's [the] one of them I'm most
proud of actually. In the department, when this radiation consciousness became
acute, we started to use film badges53 to determine whether our people were
overexposed. It was very interesting that the only people whose badges ever got
black [from overexposure] were those who took radiographs of young children.
That's because they held them [(the children)] when the film was taken.
I gathered the technicians together and I said, "Look, this is a
problem. Now, I want you all to think about this and come up with any kind of a
baby holder that you can come up with." They came up with the screwballest
notions you ever saw.
Finally, I decided maybe I'd take this on. I got to thinking about this
[and] remembered how the American Indian women carried their papooses. I went
down to the shop and cut out a [flat] piece of one-quarter–inch plywood in
the shape [(silhouette)] of a child, with a headpiece, a body with two
upstretched arms, and two legs. We used Ace54 bandages to immobilize the child
on the board.
So, then, I offered a prize for a name for this. The prize was a doughnut. I
mentioned it to my wife one day and she said, "It's a BRATT BORED."
She was a journalist; she would come up with something like that! It was
spelled BRATT because you never called a child a brat. And it was BORED, because
they went to sleep on it.
This device is now still used in certain places in the United States for
immobilizing children for intravenous studies, for x-ray studies, for all kinds
of stuff. That's an invention, cutting out a piece of plywood. I got a prize for
it. |
| BERGE: | (smiling) I hope it was a good doughnut. |
| MILLER: | The prize was: becoming the Gadgeteer of the Year from the
Radiological Society. |
| HERKEN: | There's actually a Mickey Mouse plaque. |
|
Technique to Produce Infinite Laminograms |
| MILLER: | Actually, from that day on, when we started to use those
boards, there was never again an overexposure of a technician.
I thought you were going to come up with the one [(the invention of mine)]
that I liked best. It was having an infinite number of laminograms from a finite
number of films. |
| BERGE: | How do you do that? |
| MILLER: | The patient is lying down, and—do you know what a
laminograph is? |
| BERGE: | No. |
| MILLER: | A laminogram is a radiograph, let's say of the chest, in
which only one level, or layer, or lamina is shown sharply and everything else
is blurred out.55 That is called a laminogram. The apparatus for making a
laminogram consists of a slotted metal bar connecting the x-ray tube holder to
the film-holding tray. At the side of the table there is an upright piece to
hold a pin, which pierces the bar. The height of the pin is adjustable. It acts
as a fulcrum56 for the opposed motions of the tube and film.
During the filming, the tube stand is moved about 2 to 3 feet along the side
of the table in about 3 to 4 seconds. Note that when the tube is moved up
the table, the film moves down the table. Only the level of the
fulcrum has not moved, and the images at that level have not been blurred. All
images above and below the level of the fulcrum are blurred because they moved
during the filming. This procedure produces the laminogram.
I then appreciated the fact that during the exposures of the 3 to 4 seconds,
with full-wave rectification,57 you are taking 120 radiographs per second in
order to make one laminogram. I said to myself, "Well, how about doing it
with 7 unblurred radiographs instead of 3 times 120 or 360 x rays?"
So, we got a skeleton and took seven radiographs of it, each with the tube
at equally spaced distances over a total distance of three feet, using the
laminographic machine. The seven unblurred radiographs were superimposed in a
device that slides the radiographs upon one another. The x rays are lined up so
that all the images taken with the tube at one extreme end are properly
superimposed to create an unblurred image. A lever with clips to hold the films
and a fulcrum in the lever permits the radiographs to slide upon one another so
that successive layers of the exposed body are presented sharply from the front
to the back of the body. Movement of the lever provides the viewer with an
infinite number of laminograms from a finite number of films. Each film was
underexposed, so that the total exposure for all of them equaled the amount of
radiation required to take only one unblurred ordinary radiograph. |
| HERKEN: | [unintelligible] |
| BERGE: | No, I have only the ones that we have from the pictures.
There were a number, such as the image orthicon tube.58 |
| MILLER: | I didn't invent that, I used it. |
|
Introduction of Stereoscopy to X-ray Film Making |
| BERGE: | Or the Bi-plane Simultaneous Therascopic Serialograph
Apparatus. |
| MILLER: | This apparatus was to be used during the making of carotid
angiograms59 to show the blood vessels of the brain in the diagnosis of brain
or vascular disease. [(I never published anything on this.)] When Dr. [Ed]
Boldrey and I did the first cerebral60 angiogram done at UCSF, Dr. Boldrey
exposed the carotid artery surgically and injected the contrast medium.61 I
ran a team that took a series of films of the head during the passage of the
contrast medium through the vessels of the brain.
Shortly after the first angiogram, I introduced stereoscopy62 into the
film-making. This meant that the x-ray tube had to be moved back-and-forth
between exposures. The amount of movement equaled the interocular63 distance
of the final viewer of the films (two-and-a-half inches). Films 1 and 2 made a
stereo pair, films 2 and 3 made the next stereo pair, films 3 and 4 made the
next pair, etc., etc. The tube was moved by a technician, using a long pole
attached to the tube housing. Films were changed by hand.
When the department was moved to Moffitt Hospital, a Special Procedure room
was set aside to do cerebral angiography, and the special apparatus was
installed. The patient would lie supine64 on the x-ray table. Above him were
two x-ray tubes, called tubes 1 and 2, whose focal spots were two-and-a-half
inches apart in the horizontal direction at a distance of 36 inches. The focal
spots were aligned toward the head and toward the feet of the patient. Films
were housed in automatic film changers.
When all was ready, contrast material was injected into the carotid artery
via a catheter. Two seconds later, tube 1 and tube 3 fired simultaneously,
taking a frontal and a lateral65 film of the head from the first positions.
The film changers placed new films in position. Two seconds later, tubes 2 and 4
fired, making a frontal and lateral film of the head simultaneously from the
second position. The film changers changed films, and two seconds later tubes 1
and 3 fired, making a pair of films from the first position again. This
procedure was repeated till the end of the series.
Films 1 and 2 from tubes 1 and 2 made a stereo pair in the frontal
projection from the first and second tube positions. Films 2 and 3 from tubes 1
and 2 made a second stereo pair two seconds later from the two tube positions.
And so on from both the frontal and the lateral views. The stereos provided
three-dimensional views as a function of time, which gave the fourth dimension.
Two four-dimensional views make an 8-dimensional study with one injection of
contrast material. |
| HERKEN: | I had a question about Ken Scott. Scott eventually left
UCSF, did he not, and Berkeley, and went down to UCLA? |
| MILLER: | Did he? If so, I don't know. |
| HERKEN: | Do you remember—I was curious why he left. |
| MILLER: | Joe [Hamilton] died and the [Donner] Lab kind of folded,
didn't it? I think there was no place for Ken. |
| BERGE: | At one point he switched from the Radiation Lab to UCSF. Do
you have any idea why he did that? |
| MILLER: | UCSF? |
| BERGE: | He went from Lawrence Radiation Laboratory66 to UCSF. Do
you know why he would do that? |
| MILLER: | I don't know when he did it. Unless, did he work with Stone
or something? |
| BERGE: | He might have. I don't know. |
| MILLER: | I think probably the [Donner and the] Crocker [Labs] kind of
folded up. Now I'm guessing completely. And if he did come over—Now that
you mention it, I think he did spend time at what was called the Radiologic
Laboratory, which was Stone's. (For remembrances about this, see the textbox
"About Consent Forms," preceding.) |
| HERKEN: | (scanning a list of UC Radiation Lab reports from the
war and postwar era) Schimpkin is one of the authors here of a paper; that's
a name I reckon you've seen before: J.J. Schimpkin. |
| MILLER: | What about him? |
| HERKEN: | Tell me, was he a colleague at UCSF? |
| MILLER: | This was a study of error in interpretation of radiographs.
Schimpkin was a chest man. He was a very good one. [Jacob] Yerushalmy was the
statistician. The rest of us worked on this project on the study of error
interpretation for a long time: in fact, I'm still working on it. (Dr.
Miller later adds: This is an error; I didn't know a J.J. Schimpkin.) |
|
Postwar Preference for Unclassified Research |
| HERKEN: | There was one paper here, (scanning the list) a
UCRL report, [about] experience when you were in California when you were
treating patients with hyperthyroidism. Did that involve the Langley Porter
patients? |
| MILLER: | No, I did only diagnostic studies on patients from Langley
Porter. That was a Radiation Laboratory report, probably [written] during the
war. After the war, I said I would never again be involved with any secrecy
project. |
| BERGE: | Why? |
| MILLER: | [Secrecy] was important during the war, not because I was
treating patients with hyperthyroidism, but [because] I was a radiologist
involved in a project and somebody [from the Axis]67 is going to figure out
that that's somehow related to radiation and that's the bomb. |
| BERGE: | Why didn't you want to be involved in [work that was to be
classified]? |
| MILLER: | That's not my bag. [As a scientist I wanted to share
anything I learned with whoever wanted it.] |
| HERKEN: | A number of interviews, articles, [were] published in
refereed journals. There's also a number of UCRL reports. If it's a UCRL report
does that necessarily mean it would have been classified? |
| MILLER: | [During the war], it was classified. |
| HERKEN: | A lot of these are reports, for example, (glancing at
the list) in a 1949 Medical and Health Division Quarterly Report.
Why would that be classified? |
| MILLER: | I tell you, they'd classify anything. Part of the answer to
your question [is that] I got sick and tired of having to write reports to
people. I wanted to do the work. |
| HERKEN: | (scanning the list) The first date I've seen here is
1948. So, the first biomedical reports done by the Radiation Laboratory would
have been in that time frame? |
| MILLER: | Was my name on that? |
| HERKEN: | Yes. |
| MILLER: | I suppose it was one of the first [of the reports on the
131I studies]. Low-Beer and I, and maybe Stone, all gave separate portions of a
report. I'm sure this had to be radioiodine-related in some way. |
| HERKEN: | That would probably be receiving AEC funding? |
| MILLER: | I don't know. |
| HERKEN: | How do you divide first the division of labor as to what
portion Low-Beer would write, what portion [you] would write? |
| MILLER: | Your own work. Our work was separate. I guess the reason, if
any, if this was an AEC thing, was because I was being given radioiodine and he
was given 32P. |
|
Zirconium and Plutonium Injections |
| HERKEN: | One report with us—and this is UCRL 68, your name
actually isn't on here, but Low-Beer, Scott, Hamilton, Stone [are]68—gives
[an account of] an injection that was done January of 1948.69 |
| MILLER: | I don't know about that. One would think that all these
injections, whatever were done, were with therapeutic [or diagnostic] intent. |
| BERGE: | Do you know how they selected the patients that they were
selecting with, say, zirconium or plutonium? |
| MILLER: | [I don't know how they made the selection. My guess would be
that they would select a patient to be injected because they could acquire some
very important information from the test or that it was injected with
therapeutic intent.] |
| BERGE: | I've noticed that there seems to be a general pattern that
they would inject, say, plutonium or zirconium into a patient a day or so
[before] they would actually amputate or take something out. |
| MILLER: | How else would you do it? |
| BERGE: | I guess my question would be, then why would you need the
radioactive substance?70 |
| MILLER: | [Because you use the radioactivity of the isotope to tell
where the isotope is.71 If the isotope emits gamma rays, these can be detected
by a Geiger counter aimed at the body from the outside. Gamma rays penetrate
tissue very well. Alpha and beta particles emitted by a radioactive isotope
travel only a short way through the tissue and in general do not get out of the
body. Then, to detect the amount and the location of the isotope in the tissue,
it is necessary to remove some of the tissue, make a microscopic slide out of
it, and expose a film in contact with the slide. The radioactivity blackens the
film where it lies and shows its exact position of the isotope in the tissue.
Luckily, 131I emits both gamma rays and beta particles. Does that clear it up?] |
| BERGE: | I think so. |
| HERKEN: | Though in 1948 there was less sensitivity [about] the bomb,
people knew the bomb existed. I'm surprised that this work would have been
apparently classified back in January 1948. |
| MILLER: | I don't know anything about that. The original work on
radioiodine was, number one, to find out about it, and also to calibrate the
doses and see that you get the greatest good with the least harm. |
|
Research With Healthy Volunteers |
| HERKEN: | I know that Hamilton in 1950 was proposing what he
identified [to become] his early experiments with healthy subjects. He wrote to
Shields Warren using [radiation] in healthy subjects, in prisoners, for example.
Hamilton himself was considering doing experiments on human subjects.
Experiments with prospective therapeutic benefits. |
| MILLER: | I think you've left something out: These were volunteers. |
| HERKEN: | Yes, he specified they would be volunteers. |
| MILLER: | That's mighty important. In other words, they weren't guinea
pigs, in that sense. They were willing to accept the risk for what good they
could do humanity. |
| HERKEN: | Did you do any similar such work with volunteers? |
| MILLER: | Unless you talked about the [Langley Porter Clinic director]
Bowman ones. These people, if I remember correctly, signed a consent form.
Because there was no clinical evidence of active thyroid involvement one way or
another, these studies were to see in what range their iodine uptake would fall.
The patients didn't have any evident thyroid disease, but they might have.
Bowman's concern was that if the thyroid was involved and if the radioiodine
could be involved, it could help treat their schizophrenia. |
| BERGE: | Earlier you said that there wasn't at that time a good way of
diagnosing thyroid disorders. |
| MILLER: | There still isn't, [but there is an excellent correlation
between the thyroid function and the rate at which radioiodine is absorbed in
the thyroid.] |
| BERGE: | What led Bowman to believe that there might be a link? |
| MILLER: | I don't know what was in his mind. One thing about the
schizophrenia [patients], they're pretty hyper; so is an active [hyper]thyroid
[patient]. So, they had this in common. Was the thyroid in some hidden way
involved to create this jitterness? [That] was the question we tried to answer. |
|
Tracing the Records of Patient Consent |
| HERKEN: | [Did he see to it that] some form of the consent form went
into the patients' records? |
| MILLER: | I don't know. It was bound to, I'm sure. |
| HERKEN: | I'd be interested in finding out who the [unintelligible]
was, because the Committee72 is interested in finding the course of consent
and are not quite sure where to start looking. I suppose that would be in the
patients' charts. Are there enough records at UCSF kept under the doctor's name,
or were they always in the patient's name? |
| MILLER: | There were no computers at that time, so if you wanted to
find a patient, [or to] get a patient's chart, you got it by his name,
not the doctor's name. The doctor, undoubtedly, had a record of
which-patient-is-who. |
| HERKEN: | It would be very helpful to us if we could find the doctors'
records and went through the doctors' records and then patients' records. |
| MILLER: | I thought these people made pretty good records of follow-up
on patients, didn't they? I know the Stone stuff was magnificent, and the
records we kept on our patients were really complete. |
| HERKEN: | The problem is, they're not under Stone's name at UCSF. |
| BERGE: | Do you have any idea where either Stone's records, or even
earlier records might be? |
| MILLER: | No; I think that stuff all went down the drain. |
| BERGE: | You didn't turn them over to the archives73 or to the
medical school? |
| MILLER: | No. I turned my bound reprints of articles I wrote over to
the archives, but that's the only relation I ever had with the archives. None of
that would go. They would go with the charts. With time, the charts occupy so
much space that they either throw them all away or try to pick them; so if the
patient doesn't come in again for five years, then they go. |
| HERKEN: | Did you do work in your house [unintelligible] |
| MILLER: | No. |
| HERKEN: | I know Pat Durbin74 has a painting by Leah [Hamilton] in
her office. |
| MILLER: | Probably very "far out" and beautiful. Very
abstract, and that's why I loved that. I never would have remembered that, but
you brought it up: "I break space with color." |
| HERKEN: | What was your work with Pat Durbin? How do you happen to
know her? |
| MILLER: | I've never heard of her. Who's Pat Durbin? |
| HERKEN: | Pat Durbin worked for Joe Hamilton. |
| MILLER: | What, as a secretary or something? |
| HERKEN: | She was initially a glass washer. |
| MILLER: | I never dated her or anything. |
| HERKEN: | She got her degree in Radiobiology later on. She's the one
in 1974, who turned up [the fact] that some of the plutonium subjects were still
alive and alerted the AEC to that fact, and [that] resulted in the subsequent
interest of the AEC in reconstructing the case. |
|
A Career in Research |
| BERGE: | I just have two finishing questions I'd like to wrap up with
it. If I understand correctly—actually, I don't understand correctly! Was
your primary interest when you started your studies in medicine to do research
or to diagnosis? |
| MILLER: | I might tell you a little story about that. Ed Chamberlain,
who was a professor of Radiology at Temple [University in Philadelphia], came to
visit Dr. Pohle at [the University of] Wisconsin. I never saw Pohle quite so
mad, because Chamberlain came down and spent the whole time with me in my lab
instead of with Pohle. As he was going out the door he said, "I can tell
what your life is going to be like: You're going to work yourself out of this
laboratory and get into medicine, and then you're going to work yourself right
back into the laboratory for the rest of your life."
And he was so right! [I was always involved in research.] All these
memories. For a guy my age, that's all you have left. |
| BERGE: | I don't know; this house is nice. |
|
|
| BERGE: | One more question for me to sort of bring it all back
together: What do you see as the results of your work over the past forty, fifty
years, in terms of what you were able to produce with your research? |
| HERKEN: | Did you finish with that document? Can I make a copy of
this? |
| MILLER: | You may have that. |
|
| [Textbox: Recollections of Research Activities (April 11, 1995)] |
