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June 8, 2024 24 mins

This 2019 episode examines thyroid disease through history, and the physics lecture heard by Saul Hertz in the 1930s that changed the treatment of hyperthyroidism forever. 

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Speaker 1 (00:02):
Happy Saturday.

Speaker 2 (00:03):
We just had an episode on the history of iodized
salt and that has some connections to our previous episode
on the invention of radioiodine therapy. So that is today's
Saturday classic.

Speaker 1 (00:16):
This one originally came out on June tenth, twenty nineteen,
So enjoy. Welcome to Stuff you Missed in History Class,
a production of iHeartRadio. Hello, and welcome to the podcast.
I'm Holly Frye and I'm Tracy B.

Speaker 2 (00:38):
Wilson.

Speaker 1 (00:39):
Okay, so true confession on this one. This episode is
inspired by one of my cats.

Speaker 2 (00:44):
Yeah, but simultaneously fascinating and a lot older than I thought. Yes,
it's not about kitties or animals really at all, although
they are mentioned in terms of medical testing. Nothing particularly gruesome,
but just FYI if that's trouble for you. It is
in fact about science because my cat osile was hyper

(01:06):
thyroid and so we opted to have radioiodine therapy treatment
for him. And as my vent was describing this to
me and she's like, Oh, it's just like how they
do it in humans, blah blah blah blah, and I
was like, I have never thought about this one.

Speaker 1 (01:20):
Where did this all begin?

Speaker 2 (01:22):
So It just got me wondering about the origins of
this treatment because it is a very successful treatment and
it's one of those things that both humans and animals
seem to respond well to, which just was fascinating to
me because, as you know, I love a little bit
of science. So that is what we were talking about today,
the advent of radioiodine therapy. So first we're going to

(01:45):
talk just a little bit about your thyroid and how
it works. Your thyroid is a small organ that sits
below your larynx, and in the most basic terms, its
job is to convert the iodine and the food you
eat into hormones that regulate your metabolism. Thyroid cells are
the only ones in the human body that take in iodine,
but all of the other cells in the body are

(02:06):
affected by the work that the thyroid does. So the
hormone known as thyroxine abbreviated as T four and the
hormone triiodithyronine known also as T three are vital to
normal metabolic function. But the thyroid, which makes those again
out of iodine, isn't out there just functioning solo. It
is regulated by the pituitary gland, which is in turn

(02:27):
regulated by the hypothalamus. If your thyroid isn't producing enough hormone,
that's called hypothyroidism, and it doesn't present really obvious symptoms
at the beginning a lot of the time, but it
can lead to other problems, including obesity and heart disease. Normally,
hypothyroidism is treated with synthetic hormones to get the level

(02:49):
of thyroid function back up to normal.

Speaker 1 (02:51):
And if your thyroid is producing too much hormone like
my cats, that is known as hyperthyroidism, And in this
case it's sort of overcla the body's metabolic function. So
in this case, unintentional weight loss and rapid heart rate
and even irregular heartbeat are all symptoms, which obviously can
lead to some pretty serious problems if they're left unchecked.

Speaker 2 (03:12):
The advances in thyroid treatment that we're going to talk
about today took place less than one hundred years ago,
but thyroid disease has been part of recorded history going
all the way back to twenty seven hundred BCE, when
seaweed was prescribed in China to treat goiter. The goiter
is a swelling of the thyroid that's most commonly caused
by low iodine, but the thyroid itself wasn't even recognized

(03:36):
and illustrated until Leonardo da Vinci drew it in fifteen hundred.
The name thyroid didn't exist until sixteen fifty six, when
Thomas Wharton named it using a word for shield because
of the resemblance in shapes to ancient Grecian shields. In
eighteen twenty, Jean Francois Quonda made the connection between iodine

(03:57):
and goiter and began to use iodine as a treatment.
By eighteen thirty one, iodine used as a prophylaxis to
prevent thyroid disease was proposed by a Brazilian doctor, but
even so conclusive scientific literature establishing iodine as a necessity
to thyroid function was not published until nineteen oh seven
in a paper by doctor David Marine, and it was

(04:20):
Marine's work in thyroid research that eventually led to iodized
salt as a standard approach to preventing thyroid disease as
a public health initiative. I like how it was nineteen
oh seven when that happened, but using seaweed to treat goiter.

Speaker 1 (04:36):
From thousands of years before they were onto it, they
just hadn't done all the math on what exactly in
the seaweed was fixing.

Speaker 2 (04:43):
The pro seaweed has lots of iodine in it, That's
what was up with that. In the late eighteen nineties,
knowledge about the thyroid really started to accelerate, as Adolph
Magnus Levy made the connection between thyroid function and metabolic rate.
Radium was used to treat a pay patients goiter in
nineteen oh five by physician Robert Abbey, and the term

(05:04):
hyperthyroidism was coined in nineteen ten by Charles H. Mayo,
but descriptions of that condition actually date back to the
eighteen twenties, and for a long time the only real
treatment for hyperthyroidism was surgery, but it was so risky
that often doctors waited until the patient's illness was pretty
advanced to perform the surgery, and that meant that the

(05:26):
patient by that point was already in a week ined state,
which only reduced the likelihood of a successful outcome. There
was actually a pretty high mortality rate for that surgery.
In nineteen twenty three, Georges to have a seed developed
the idea of radioactive tracers to say metabolic pathways. A
tracer Permiriam Webster as a substance used to trace the
course of a chemical or biological process. He went on

(05:48):
to receive a Nobel Prize for his work, but not
for another two decades, and in the early nineteen hundreds,
research into thyroid function and disease was taking place in
a number of different hospitals and medical research centers, because
it really had, as we said, accelerated in terms of
what we knew about thyroid and thyroid disease in the
decades leading up to that, but it was not until

(06:10):
the nineteen thirties that a breakthrough idea occurred to a
physician to use radioactivity in the treatment of hyperthyroidism. And
to get into that, we have to talk about Sal Hurts.
Sal Hurtz was born on April twentieth, nineteen oh five,
in Cleveland, Ohio. His parents, Aaron and Bertha Hertz, were
Polish immigrants who raised Saul and his six brothers in

(06:31):
an Orthodox Jewish household. After a public school, Saul went
to the University of Michigan and then onto medical school
at Harvard. After he got his medical degree in nineteen
twenty nine, he did his internship and residency in Cleveland
before moving to Boston. Starting in nineteen thirty one, he
was at the thyroid clinic at Boston's Massachusetts General Hospital,

(06:51):
and five.

Speaker 1 (06:51):
Years into his time at that position, in November of
nineteen thirty six, he attended a lunch at Harvard Medical
School in which Carl Compton was giving a lecture and Compton,
who was the president of MIT at the time, had
entitled his talk what Physics Can Do for Biology and Medicine,
and in it he discussed the concept of making radioactive
isotopes of common elements.

Speaker 2 (07:14):
After the lecture was over, Hertz asked Compton a question,
could iodine be made radioactive? He was thinking about a
practical application of the science that Compton had discussed in
the talk, which was using radioactive iodine, which theoretically only
the thyroid could absorb, to address thyroid issues. Compton didn't
really know the answer to the question offhand, so he

(07:35):
noted the question, intending to follow up with Hertz later.
It took a month, and when Compton followed up on it,
he apologized, Yeah. That letter is dated December fifteenth, nineteen
thirty six, and it reads, dear doctor Hertz, to my chagrin,
I have just come across the memorandum which I made
on your question about the radioactivity of iodine. Iodine can

(07:57):
be made artificially radioactive. It has half period of decay
of twenty five minutes in amidst gamma rays and beta
rays electrons is put in parentheses with a maximum energy
of two point one million volts. It is probable that
there are several other periods of decay, but if so,
they correspond to types of radioactivity like the one indicated,

(08:17):
and they are not yet very definitely established. In his
response letter, dated eight days later on December twenty third,
Hertz thanked Professor Compton and wrote, quote, the fact that
iodine is selectively taken up by the thyroid gland when
injected into the body makes that possible to hope that iodine,
which is made radioactive, and which loses its radioactivity as
rapidly as you indicated, would be a useful method of

(08:40):
therapy in cases of overactivity of the thyroid gland. Then
promised Carl Compton that he would relay the results of
any of the tests that they conducted on animals using
radioactive iodine.

Speaker 1 (08:50):
And Saul Hurts was ready to start exploring this idea
in the lab, and we're going to talk about that
after we first pause for a little sponsor break. Saul Hurts,
along with James Howard Means, who was his supervisor at

(09:12):
the hospital and was actually the man who established a
Massachusetts General Hospital's thyroid unit in nineteen thirteen, reached out
to the physics community to put their plan into action.
They joined forces with Robley Evans and Arthur Roberts of
the Massachusetts Institute of Technology to combine the work of
the physicists and physicians to treat hyperthyroidism. The team started

(09:35):
working with the isotope iodine one twenty eight or just
I one twenty eight in rabbits. In nineteen thirty eight.
They used a test group of four dozen animals. The
rabbits thyroids took up the I one twenty eight, which
was of great indicator that Hertz's idea would work. When
the rabbits were tested after the I one twenty eight
was administered, it was found that their thyroid glands had

(09:57):
quote nine times the concentration of radioactive eye iodine as
that found in the liver. Additionally, the rabbits among the
group with hyperplastic thyroid glands, which are glands that had
additional growth from cell proliferation, had an even greater retention
of radioactive iodine in the thyroid tissue than those who
had healthy thyroid glands. Yeah, so the rabbits with abnormalities

(10:17):
in their thyroids actually took up more of this radioactive
isotope than those that were healthy. And at this point
the I one twenty eight was being used as a
tracer to diagnose thyroid issues, it was not yet at
the phase where it was being used as a treatment.
In a write up of this initial success, Hurts and
his team stated, quote, it is therefore logical to suppose that,

(10:39):
when strongly active materials are available, the concentration power of
the hyperplastic and neoplastic thyroid for radioactive iodine may be
of clinical or therapeutic significance. This offered up hope as
well for an alternative to thyroid surgery, one that was
far less invasive and consequently less dangerous. This was, however,

(11:00):
very early on. There was also one fundamental problem that
twenty five minute half life. In very basic terms, the
isotope decayed so quickly that it had to be used
immediately after creation or it would just be useless before
it could actually treat the thyroid tissue. Hertz's Boston group
was sharing their information with another team on the West

(11:20):
coast at the University of California, Berkeley. The California team,
headed by Mayo Soli and Joseph Hamilton, conscripted the help
of two other scientists, Glenn Seborg and Jack Livingood, who
had access to a cyclotron. That's an early particle accelerator
apparatus that accelerates atomic and subatomic particles in a constant
magnetic field, and the cyclotron had only been patented for

(11:44):
four years before this, so it was still a very
new technology. Using the cyclotron, Seaborg and Jack Livingood were
able to create new iodine isotopes. First, I won thirty
for a half life of twelve hours, and eventually I
won thirty one. I won thirty one has an eight
day half life. These longer half lives made these isotopes

(12:04):
good candidates for Hertz's treatment. The longer half life meant
that doctors would have time to treat the problematic thyroid
tissue between the isotopes creation and the point where it
became useless, and as the California team was working with
the cyclotron to create those new isotopes. The Boston team
was working with humans to test whether they're thyroids like
those of the rabbits in the earlier tests, would uptake

(12:27):
the radioactive iodine and they had positive results. The data
collected from those early tests was also used to determine
procedure and dosage guidelines for human patients once they moved
into the treatment phase, and once those new isotopes were
established and could be replicated at the Boston LAMB after
it had acquired its own cyclotron, it was time for

(12:48):
a true clinical trial. In January nineteen forty one, Salhertz
treated his first human patient with hyperthyroid using a combination
of I one thirty and I one thirty one. This
is a patient identified in his notes as Elizabeth D.
Was the birth of nuclear medicine. It is often referred
to as the first and the gold standard in targeted

(13:09):
radio nucleid therapy. Hertz and his team treated additional patients
at the rate of one a month, tracking their progress
after receiving the radioiodine therapy, and most of them had
significant improvement in their conditions. The Cleveland Press ran a
story about Hertz's work under the headline former Clevelander developed
first atomic medical cure. After initial success with the treatment,

(13:30):
Heurtz began to take on more patients as candidates for
radioiodine treatment, and in nineteen forty two he expanded his
work with radioiodine therapy and began clinical trials of treatment
for patients with thyroid cancer. And this was actually something
that he had begun working on, at least in its
theoretical form, as early as nineteen thirty seven, when those
initial rabbit trials for hyperthyroidism were underway. This research had

(13:55):
gotten the attention of the medical community early on. In
nineteen forty two, the Mayo cli Clinic arranged for one
of their physicians, doctor f. Raymond Keating, Junior, to spend
six months in Boston working with the researchers at Massachusetts
General Hospital to learn about their work with radioactive iodine. Later,
the Mayo Clinics doctor Samuel Haynes wrote of this period quote,

(14:15):
when ray Keating finished his fellowship, we asked Howard Means
to let him go to the MGH for six months.
We were especially interested in having him see what means.
Saul Hurtz and Rulan Ralson were doing with radioiodine, a
program which as you know, was carried out with Robley
Evans and Wendell Peacock from mit Ray's day in Boston

(14:35):
was very successful, and when he came back he had
arranged with Evans to have small amounts of I one
thirty one sent to him to be used in some
studies in chicks. Haines also described the Mayo clinics first
use of I one thirty one in thyroid treatment in
the same writing, which was a letter that he was
writing to a colleague at Cornell, and he wrote of
the patient who was a woman who had been quite
ill and for whom surgery would have been a highly

(14:58):
dangerous prospect. He wrote, she had a good outcome with
the I one thirty one treatment. So this treatment developed
through Hurts' work was indeed one spreading to other clinics
and being used by other doctors, and was saving people
from very high risk surgeries. But Hurts had the unfortunate
timing of developing this breakthrough treatment at the same time

(15:18):
that World War II was brewing. Sal Hurts put aside
his medical research temporarily in nineteen forty three and joined
the Navy to fight against Hitler's Nazi regime. But before
he shipped out, Hurts, who did not want work in
this new field to be hampered by his absence, met
with a private practice doctor who worked part time at MGH,
and that was doctor Earl M. Chapman.

Speaker 2 (15:40):
Chapman had continued to make time for medical research even
while running his own practice, and he was ineligible for
military service, so Hertz asked him if he would keep
working with Hurtz's roster of thyroid patients, and Chapman, probably flattered,
agreed and continued the work that Hurts had begun. But
when sal Hurts returned from the war, there were problems

(16:00):
between the two men. Chapman didn't want to give up
the project and give it back to its originator after
his two years of involvement, and of course Hertz wanted
his research project back, but he wasn't given his old
position at MGH. Instead, he took a position at the
Beth Israel Hospital.

Speaker 1 (16:16):
Yeah, there are many stories that are told among their
colleagues about the fights that broke out over this issue.
And then those two former colleagues eventually found themselves just
each running their own trials, and then they both wrote
papers about them, and Chapman actually finished his paper first
and submitted it to the Journal of the American Medical

(16:37):
Association for review and publication.

Speaker 2 (16:40):
This kicked off some drama, and we will get to
that paper and the rivalry between the two of them
and how that was stirred up after we take a
quick break and hear from one of our sponsors. So,
though Chapman had been eaten Hurts to the finish line

(17:01):
on writing the paper itself, he didn't get published.

Speaker 1 (17:04):
First. The Journal of the American Medical Association returned his
paper and said it needed to be edited for length
before it could be published. And in the meantime, the editor,
who knew that Hurts had been the one to spearhead
the work in this field and yet had not even
been mentioned in Chapman's paper, reached out to Saul Hurtz
and encouraged him to do his own write up as

(17:24):
quickly as possible. So Hertz, along with Arthur Roberts, finished
his own paper recounting the methods and results of his
trials treating hyperthyroid patients with I one thirty one.

Speaker 2 (17:35):
The end of all this jockeying was that the Journal
of the American Medical Association published both the Chapman and
Hertz papers, both on the same topic, both researched in
the same hospital, printed in the same issue on May eleventh,
nineteen forty six. Both scientists' findings were made available to
the Journal of the American Medical Association's readership, and if
nothing else, two papers on exactly the same topic with

(17:58):
only minor differences and treatment method achieved one thing. It
made nuclear medicine a really hot topic and established radioiodine
therapy as an effective way to treat thyroid disease. Yeah,
they had been writing other papers leading up to that,
but that was really the paper that was like, we
have figured out how to treat hyperthyroide. Here's how we
do it. Here are the methods. And they both essentially

(18:18):
did the same thing. Depending on whose account you read,
Chapman's approach was a little less careful in terms of
dosage and how he managed patient treatment, but they were
still very, very similar. And interestingly enough, that was not
the end of the squabbling over academic papers and who
got credit for the research that led to this game

(18:40):
changing treatment. In reference to an earlier paper on the
radioiodine work they were doing in MGH. Salhertz wrote the
following letter to a doctor Goldfbe on April twelfth, nineteen
thirty eight. He writes, quote with reference to the article
submitted for publication by doctors Shertz and Arthur Roberts, a
change is desired with the addition of Professor Robley D.

(19:01):
Evans as a third co author. He has shared considerably
in the time devoted to this problem, and we have
decided that full credit to the Massachusetts Institute of Technology
cannot be given without including him as co author. His
title is Assistant Professor of Physics at the Massachusetts Institute
of Technology, and we would appreciate the addition to the
authorship of him on the publication. But many years later,

(19:25):
in nineteen ninety one, doctor Arthur Roberts wrote a scathing
letter to doctor John Stanbury, who wrote a book titled
A Constant Ferment. This was a history of the MGH
Thyroid Clinic and the work that was done there from
nineteen thirteen to nineteen ninety. Apparently Stanbury interviewed Evans and
spoke very highly of him in the book. Roberts, who

(19:47):
had received pre publication manuscripts just tore into Evans in
this letter. Roberts had actually worked for Evans at MIT,
and according to his account, quote Evans made it a
condition of my employment. I wish I still had the
letter that his name was to appear on all publications.
Even at the time, this was unusual and occasioned much comment.

(20:09):
It led to the contretemps concerning the late edition of
his name to our first paper. It was on the
second paper, but after that Saul and I felt sufficiently
secure that we ignored him in our subsequent publications. Had
he actually participated in the work, there would have been
no problem including him. Roberts continued his takedown of Evans

(20:29):
over the course of several pages, calling him, among other things,
quote a thoroughly unprincipled racist manipulator. He also cautioned author Stanbury, quote,
I would believe nothing on this subject from Chapman, whose
self interest is obvious, and who bungled, whether deliberately or not,
the follow up on Hertz's original series when Hurtz joined
the Navy, apparently despite all of Roberts' passioned rhetoric, though

(20:51):
Stanbury did not make changes to his manuscript, this whole
mess of exchanges is a good reminder that even people
who do important and groundbreaking work are often my in
their own personal conflicts that are not necessarily apparent so
the outside, I, yeah, it's such a This sort of
thing does happen in academia with some frequency. If you
have any friends who are maybe professors or researchers, they

(21:14):
probably have similar stories. I should also note that in
the midst of that big shakeup, Evans went with Chapman
while Roberts went with Hertz, so they sort of separated
into two teams, and that's kind of why there is
so much friction between them. But as for Saul Hurts,
he continued his work in radioiodine therapy. In fall of
nineteen forty six, he set up the Radioactive Isotope Research Fund,

(21:38):
and a few years later that fund paid for the
establishment of the Radioactive Isotope Research Institute, with offices in
Boston and New York. Hertz believed that the study of
thyroid cancer and research into its possible treatments could lead
to breakthroughs in the treatment of all cancers, and he
was happy to discuss this work with the media anytime
they asked. Unfortunately, though that work was cut short. Salhurtz

(22:01):
died suddenly at the age of forty five, and he
had a heart attack on July twenty eighth, nineteen fifty.
His daughter, Barbara, who was just three when her father died,
has become the steward of his story and legacy and
has worked with professionals in the medical community to make
sure that his contributions to medical science are documented and remembered.
To that end, she's set up a digital archive online

(22:22):
and has made some of his correspondents and research available. Yeah,
I used a lot of that in any of these
letters that were quoting back and forth often came from
her archive. In twenty sixteen, the Society of Nuclear Medicine
and Molecular Imaging established the Doctor Salhurt's Lifetime Achievement Award
to recognize those who have quote made outstanding contributions to

(22:44):
radio nuclide therapy.

Speaker 1 (22:46):
That's awesome. Yeah, So my personal thanks to doctor Salhurts
because now my cat has benefited directly from his work,
and that is because this process that he came up
with in the nineteen thirties, literally just after hearing a
lecture and going hi, I wonder if I could use
that still works. It is very common treatment with a
really high rate of success, so much so that with

(23:07):
only minor changes, it is really pretty much one of
the recommended treatments today in both people and animals. Yeah,
thank you, Saul Hurtz.

Speaker 2 (23:17):
I know people who have had it, and only one cat,
which is yours.

Speaker 1 (23:20):
Yeah. Yes, he went to what I called radio I
had i'd sleep away camp for a few days because
he was radioactive. Now he's home. We haven't had his
follow up blood work yet, but all signs point to
successful outcome. But it is just fascinating and cool. It's,
like I said, it's one of those things that it
is literally a ninety year old treatment that was come

(23:41):
up with just through like this moment of insight, and
yet it is still like really benefiting people's lives and
is still, as we said, the gold standard of treatment.
Thanks so much for joining us on this Saturday. Since
this episode is out of the archive, if you heard
an email address or a Facebook RL or something similar

(24:04):
over the course of the show, that could be obsolete. Now.
Our current email address.

Speaker 2 (24:09):
Is History Podcast at iHeartRadio dot com. You can find
us all over social media at missed Inhistory, and you
can subscribe to our show on Apple podcasts, Google podcasts,
the iHeartRadio app, and wherever else you.

Speaker 1 (24:23):
Listen to podcasts. Stuff you Missed in History Class is
a production of iHeartRadio.

Speaker 2 (24:31):
For more podcasts from iHeartRadio, visit the iHeartRadio app, Apple podcasts,
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