Alpha Emitter Studies Using Radioactive Isotopesr |
| HARPER: |
Yeah. Well, it's sort of in parallel to the alpha emitter studies. |
| FISHER: |
Which I would like you to talk about a little bit now. |
| HARPER: |
Atcher189 was running this. |
| FISHER: |
Robert Atcher. |
| HARPER: |
And the gynecologists, mostly Jacob Rotmensch.190 |
| FISHER: |
Rotmensch? |
| HARPER: |
This group was working at Argonne for eight or ten years, I think and were
hopefully bringing it to clinical use. I got into the act when they were doing
biodistribution studies here. They hadn't done them out at Argonne; they did the
toxicity studies.
[They were working with the thorium-228,
radium-228, lead-212, and bismuth-212 in dogs.] |
| FISHER: |
Dogs. |
| HARPER: |
And what turned up was a vastly irregular localization of their [agent in
the peritoneal] cavity, such as one I showed you in the rats. |
| FISHER: |
With iodine-131? Yttrium-90; I'm sorry. |
| HARPER: |
No, the ones that I showed there are yttrium-90 and gold. |
| FISHER: |
Gold-198. |
| HARPER: |
We looked at the 32P localization as chromic phosphate. There are some
publications in the literature showing images that are, again, vastly irregular.
That, plus the fact that our technologist came to me and said, "Gee, this
sample that's supposed to have a 10-hour half-life is"—this was
lead-203 and -212—"is still hot [(radiologically active)] after
several months! What will I do with it?"
So he went back to the
chemists at Argonne who [had] made the generator, and it became obvious that
what we were dealing with was thorium.
And we calculated [that] a
microcurie of thorium, had approximately the same energy emission over its decay
period as 10 millicuries of the lead-212, due mostly to the half-life
difference. That didn't seem like a good thing to put in people.
The
people in Argonne came up with an answer to this [problem]. Using the Spec
resin, which binds strongly to lead, made it possible to milk the radium
generator that made the lead. Then, after the lead came off and went through the
column, the lead was fixed and the impurity traces could be washed off
successfully. [Finally,] the bismuth daughter could be removed from the lead,
or, if you wanted to, you could strip the lead off the column with ammonium
carbonate, and use it in that form. We haven't done that. |
| FISHER: |
Bismuth-212 has a short half-life? |
| HARPER: |
One hour. |
| FISHER: |
That makes it difficult to work with in some applications. |
| HARPER: |
Well, we took that into consideration as a possible advantage. We didn't
know whether the bismuth would form clumps or not, but we thought that,
possibly, it took a while for the clumps to form if you put it in the peritoneal
cavity. That short–half-life material would float around more-or-less
uniformly; and if clumps formed later on, it wouldn't matter, because the
radioactivity would be gone. |
| FISHER: |
Perhaps for that application it's ideal. |
| HARPER: |
That's what we thought might be the case. |
| FISHER: |
If you can get it into the cells or in close proximity to cells that you
want to irradiate— |
| HARPER: |
Well, we tried this in animals, in rabbits, putting in ionic bismuth, not
colloidal material, and 80 to 90 percent [of] it had apparently stayed in the
peritoneal cavity in the two-hour period during which most of [the radiation
dose] takes place.
We were able to recover [injected activity] by
washing out the peritoneal cavity, measuring the activity which was still
[present] there.
So it looked as though it would be the ideal agent
for killing cells floating around in the peritoneal fluid or just sitting on the
peritoneal surfaces. This, of course, we will have to confirm [later].
Some studies had been done out at Argonne by Rotmensch some years ago, using
bismuth to kill tumor cells in mice. He was able, without killing the mice, to
get some permanent survivors, so there is reason to suspect that this will be
efficacious. |
| FISHER: |
Roger Maeklis,191 when he was at Harvard, also did something
like this with tumor mice and found effective irradiation of those tumors. |
| HARPER: |
With what? |
| FISHER: |
With bismuth-212. |
| HARPER: |
He did? |
| FISHER: |
I think. Or was it astatine-211?192 |
| HARPER: |
I think it was astatine.193 |
| FISHER: |
It must have been. |
| HARPER: |
Astatine is the ideal agent, but it's too hard to get hold of. |
| FISHER: |
It must have been astatine-211. |
| HARPER: |
I think it was astatine. That was done at the Brigham [and Women's
Hospital, Boston]? |
| FISHER: |
Yes. |
| HARPER: |
Yeah, I think they were working on that there. |
| FISHER: |
I think he had that flown over from England on the Concorde [(supersonic
jet airliner)]. |
| HARPER: |
Might be. Twelve-hour half-life on that [(astatine-211)]. |
| FISHER: |
Seven hours. |
| HARPER: |
Seven hours, you're right. |
| FISHER: |
You're close. |
| HARPER: |
Not that close. |
| FISHER: |
That's really interesting. But, as far as you know, the bismuth-212 hasn't
been used in any humans so far in this country? |
| HARPER: |
I don't think so. |
| FISHER: |
I think astatine-211 has been used in England. |
| HARPER: |
It may well have been. |
| FISHER: |
On one or two humans. |
| HARPER: |
Well, that's hard to make; you have to bombard bismuth with just the right
energy, or you get a lot of polonium.
Yeah, well, [about] 27 MeV.194 |
| FISHER: |
Something like that. |
| HARPER: |
One of the things that impresses me about this account of what our
accomplishments is the fact of how frequently we're presented with a problem,
and it isn't for a long interval, maybe years, before, suddenly, the solution
leaps out. |
|
Difficulties Involved With Using Human
Volunteers |
| FISHER: |
What have you found to be the most difficult aspect of working with
radioactive materials in human subjects; first of all normal human subjects and
then, patients with cancer? |
| HARPER: |
No real problems, short of the regulations, which we didn't have to face
at first. |
| FISHER: |
Did you develop your own techniques for radiation protection and handling
of isotopes [and] waste disposal? |
| HARPER: |
No, we did what was conventional at the time. |
| LATHROP: |
Well, to some extent, we did develop techniques. |
| HARPER: |
We made one horrible mistake once: we disposed of our excess radioiodine
into a big carboy [(plastic jug)] under the hood, overlooking the fact that it
was full of acid. |
| FISHER: |
And it vaporized. |
| HARPER: |
And, after a while, anything we touched— |
| LATHROP: |
After a while, it [(the evaporated acid)] was a big [radioactive]
background that kept bothering when we were counting. |
| HARPER: |
Yeah. Anything you touched came up hot. |
| FISHER: |
[The acid] volatized the iodine. |
| HARPER: |
Right. Well, that's the sort of mistake you shouldn't make, but there
wasn't anybody around to point it out to us at the time. |
| LATHROP: |
But at least we were— |
| HARPER: |
—we recognized it when it happened. |
| LATHROP: |
Yes. |
| FISHER: |
Did you go to the next step and do any thyroid counting195 on
yourselves to see if you had iodine uptakes? |
| HARPER: |
No. |
| LATHROP: |
We were pretty sure we did have some, but it wasn't [a large amount.] |
| HARPER: |
We were aware that it takes 100 millicuries to ablate196 a
thyroid, and we weren't anywhere near that. |
| FISHER: |
That's true. |
| LATHROP: |
Rather early in my career in working with radioactivity, I developed a
thyroid nodule,197 and the physician wanted to [do a thyroid scan];
[it turned out that] it had nothing to do with my working with radioactivity. I
come from a family that has thyroid disease. My grandmother had a beautiful,
great big tumor down here (points to her neck) on her thyroid; at one
time, this was thought to be [a tumor.] |
| HARPER: |
You've got the Oak Ridge paper, with the figures in it [of this]? |
| LATHROP: |
At one time, this protuberance in the neck was thought to be a sign of
beauty, that was back, several centuries ago. But anyway, I developed a thyroid
tumor— |
| HARPER: |
—upper right-hand corner. |
| LATHROP: |
This was discovered on a routine health examination at the Argonne
National Laboratory, and they urged me to see a physician. I did, and the first
thing they wanted to do was to give me [a thyroid scan using 131I]. |
| HARPER: |
A millicurie? |
| LATHROP: |
Oh, a millicurie of 131I, for a scan?
(laughter) |
| LATHROP: |
This seemed to me like it was something that I really didn't want to do;
so, anyway, the nodule was removed. Another thing— |
| FISHER: |
Was it removed surgically? |
| LATHROP: |
Yes. |
| FISHER: |
Rather than with iodine-131? |
| HARPER: |
It was a "cold" nodule [(not actively producing hormone)]. |
| FISHER: |
A cold nodule? |
| LATHROP: |
Yes. [So it wouldn't have taken up activity.] But also, in addition to
that—talking about the use of radioactivity—when I first came to
Chicago, my two oldest children, the only ones we had at that time, were four
and six years old, I think, something like that.
We had been, as I
told you, living in Wyoming. We came to Chicago, where there were all sorts of
diseases that we hadn't been exposed to, and all of us were having frequent
respiratory diseases. The doctor that was seeing the children wanted to give
them radiation, and I had learned enough by that time that I was a little scared
about this.
I consulted Dr. Lisco, who was an M.D., in the Biology
Division. He said "No," he thought it would be better not [to do it].
And I've never regretted that we didn't have it done. |
| FISHER: |
It sounds like— |
| HARPER: |
I have an experience, an anecdote about that. I was on a panel once; we
were discussing this sort of thing, and I brought up the question of radiation
of the neck leading to thyroid disease, thyroid carcinoma.
The
[person] sitting next to me was a therapist, and he jumped up and said, "This
is absolutely ridiculous! There is not a possibility! We do this all the time!"
Six months later, his son turned up with carcinoma of the thyroid [following x
ray to the neck.] |
| FISHER: |
His own son? |
| HARPER: |
His own son, whom he had treated. |
| YUFFEE: |
Tough way to learn your lesson. |
| FISHER: |
It sounds like each of you have, although you've worked extensively with
isotopes, tracers, [and] radioactive materials, that you've developed a cautious
respect for the hazards associated with radiation, and you've treated these with
some care to protect not only yourselves, but others, from radiation,
unnecessary exposures to radiation. |
| HARPER: |
But we're not paranoid. |
| FISHER: |
Not paranoid to work with them. |
| HARPER: |
No. |
| FISHER: |
And not paranoid to use them— |
| HARPER: |
—to accept modest amounts of radiation. |
| FISHER: |
—where they can be used as tools for diagnosis of disease— |
| HARPER: |
Right. |
| FISHER: |
—for therapy of otherwise untreatable cancer and other applications.
I was impressed with both of you and your scientific curiosity and your
willingness to explore new options for solving problems in medicine using
isotopes. |
| HARPER: |
One of the things that one hears from time to time is that some young man
makes a great discovery and then will waste the rest of his life working out the
details of his great discovery.
The opposite principle is, when
you've made a great discovery, abandon it and go on to something else.
(laughter) |
| HARPER: |
We've conformed to this last idea more than the former, I think. |
| FISHER: |
Perhaps that is one reason why anyone reading your résumé
cannot help to be impressed by the breadth of your knowledge and experience. |
| HARPER: |
Yeah. And that's why I've been called a phenomenologist.198 |
| FISHER: |
And not just a surgeon, but an interesting scientist. I've also been
impressed with this more-than-40–year collaboration between you and
Katherine Lathrop. |
| HARPER: |
I told you earlier how I phrased that. ["I provided the ingenuity and
Katherine provided the scholarship."] |
| LATHROP: |
Well, it just worked. |
| FISHER: |
(to Yuffee) Michael, can I ask you if you have any more concluding
questions before we finish? |
| YUFFEE: |
I don't. I basically wanted to close out with a few more personal
comments, which we have. So I guess that's it.
Thank you for agreeing
to speak with us, and we appreciate your time. |
| HARPER: |
I've been doing some historical reading recently about the problems of
science—physics and astronomy and so forth—and it has been absolutely
amazing how the great people in the past have had absolute blind spots toward
future developments.
[Sir Arthur Stanley] Eddington199
refused to accept anything about black holes, even though [astrophysicist
Subrahmanyan] Chandrasekhar200 [at the University of Chicago] was
working in his laboratory. This pattern is repeated and repeated and repeated,
all through physics and chemistry, over the centuries.
Well, we
really can't make a judgment about that. It's going to take more years than we
have. |
| HARPER: |
Well, we've done it ourselves. |
| LATHROP: |
Well, we've overlooked a few things. |
| HARPER: |
The brain scan that we didn't recognize as a brain scan. The technetium we
didn't recognize as the way of the future. |
| FISHER: |
Who would have guessed that technetium-99m would become the most used
radionuclide in the world? |
| HARPER: |
Dr. Gottschalk had an interesting comment about that once when he was
making an introductory speech somewhere for the Society [of Nuclear Medicine,]
(I think that's when he was president,) that if somebody came to a funding
agency with a new isotope that nobody had ever heard of with a mode of decay
that nobody had ever heard of before and a half-life that was only a few hours,
no way would he have gotten funding.
(laughter) |
| FISHER: |
Yes, I can relate to that, Dr. Harper, because of my interest in
radium-223. |
| HARPER: |
Of course. |
| FISHER: |
Which no one is using yet, and has had not clinical or animal applications
since the 1950s. |
| HARPER: |
Well, you'll have to cure some mouse cancers with it before [it flies]. |
| FISHER: |
Well, certainly, the alpha emitters have great promise for therapy of
cancer.
I think, with that, we'll thank you and Katherine Lathrop.
May I first, before we turn off the tape, ask what your age is, Katherine? |
| LATHROP: |
Same as his. |
| FISHER: |
Seventy-nine? |
| HARPER: |
Seventy-nine in July. |
| FISHER: |
Seventy-nine in July. |
| LATHROP: |
He's in July and I'm in June. |
| FISHER: |
So you're both the same age, still collaborating at the University of
Chicago Hospital, both of you at the age of 79, and still doing very productive
work. Katherine a member of the MIRD Committee, Paul still active in the Society
of Nuclear Medicine.
Thank you very much. |
| HARPER: |
Not active in the Society, but active in— |
| FISHER: |
In the field? |
| HARPER: |
In the field. |
| HARPER: |
Well, we've done it ourselves. |
| LATHROP: |
Well, we've overlooked a few things. |
| HARPER: |
The brain scan that we didn't recognize as a brain scan. The technetium we
didn't recognize as the way of the future. |
| FISHER: |
Who would have guessed that technetium-99m would become the most used
radionuclide in the world? |
| HARPER: |
Dr. Gottschalk had an interesting comment about that once when he was
making an introductory speech somewhere for the Society [of Nuclear Medicine,]
(I think that's when he was president) that if somebody came to a funding agency
with a new isotope that nobody had ever heard of with a mode of decay that
nobody had ever heard of before and a half-life that was only a few hours, no
way would he have gotten funding.
(laughter) |
| FISHER: |
Yes, I can relate to that, Dr. Harper, because of my interest in
radium-223. |
| HARPER: |
Of course. |
| FISHER: |
Which no one is using yet, and has had not clinical or animal applications
since the 1950s. |
| HARPER: |
Well, you'll have to cure some mouse cancers with it before [it flies]. |
| FISHER: |
Well, certainly, the alpha emitters have great promise for therapy of
cancer.
I think, with that, we'll thank you and Katherine Lathrop.
May I first, before we turn off the tape, ask what your age is, Katherine? |
| LATHROP: |
Same as his. |
| FISHER: |
Seventy-nine? |
| HARPER: |
Seventy-nine in July. |
| FISHER: |
Seventy-nine in July. |
| LATHROP: |
He's in July and I'm in June. |
| FISHER: |
So you're both the same age, still collaborating at the University of
Chicago Hospital, both of you at the age of 79, and still doing very productive
work. Katherine a member of the MIRD Committee, Paul still active in the Society
of Nuclear Medicine.
Thank you very much. |
| HARPER: |
Not active in the Society, but active in— |
| FISHER: |
In the field? |
| HARPER: |
In the field. |
| HARPER: |
Well, we've done it ourselves. |
| LATHROP: |
Well, we've overlooked a few things. |
| HARPER: |
The brain scan that we didn't recognize as a brain scan. The technetium we
didn't recognize as the way of the future. |
| FISHER: |
Who would have guessed that technetium-99m would become the most used
radionuclide in the world? |
| HARPER: |
Dr. Gottschalk had an interesting comment about that once when he was
making an introductory speech somewhere for the Society [of Nuclear Medicine,]
(I think that's when he was president) that if somebody came to a funding agency
with a new isotope that nobody had ever heard of with a mode of decay that
nobody had ever heard of before and a half-life that was only a few hours, no
way would he have gotten funding.
(laughter) |
| FISHER: |
Yes, I can relate to that, Dr. Harper, because of my interest in
radium-223. |
| HARPER: |
Of course. |
| FISHER: |
Which no one is using yet, and has had not clinical or animal applications
since the 1950s. |
| HARPER: |
Well, you'll have to cure some mouse cancers with it before [it flies]. |
| FISHER: |
Well, certainly, the alpha emitters have great promise for therapy of
cancer.
I think, with that, we'll thank you and Katherine Lathrop.
May I first, before we turn off the tape, ask what your age is, Katherine? |
| LATHROP: |
Same as his. |
| FISHER: |
Seventy-nine? |
| HARPER: |
Seventy-nine in July. |
| FISHER: |
Seventy-nine in July. |
| LATHROP: |
He's in July and I'm in June. |
| FISHER: |
So you're both the same age, still collaborating at the University of
Chicago Hospital, both of you at the age of 79, and still doing very productive
work. Katherine a member of the MIRD Committee, Paul still active in the Society
of Nuclear Medicine.
Thank you very much. |
| HARPER: |
Not active in the Society, but active in— |
| FISHER: |
In the field? |
| HARPER: |
In the field.
|
