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.
Happy Saturday.
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.
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.
Wilson.
Okay, so true confession on this one. This episode is inspired by one of my cats.
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 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.
Where did this all begin?
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 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 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 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 of thyroid function back up to normal.
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.
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 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 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 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.
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.
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 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 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 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 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 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, and five.
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.
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 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 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, 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 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.
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 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 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 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 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, 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, 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 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 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 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 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 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 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, 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 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, 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 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 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 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.
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 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.
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 Association for review and publication.
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 on writing the paper itself, he didn't get published.
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 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.
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 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 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 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. 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, 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 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. 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 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 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 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, 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 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 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 radio nuclide therapy.
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 only minor changes, it is really pretty much one of the recommended treatments today in both people and animals. Yeah, thank you, Saul Hurtz.
I know people who have had it, and only one cat, which is yours.
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 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 over the course of the show, that could be obsolete. Now. Our current email address.
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