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A historic review of the discovery of the
medical uses of radioiodine
Barbara Hertz1*, Pushan Bharadwaj2, Bennett Greenspan3
Pakistan Journal of Nuclear Medicine
Volume 10(1):1–4
© Pakistan Society of Nuclear Medicine
Reprints and permissions:
contact@psnmed.com
https://pjnmed.com
Received: 01 March 2020 Accepted: 23 April 2020
Type of Arcle: REVIEW
hps://doi.org/10.24911/PJNMed.175-1582813482
Correspondence to: Barbara Hertz
*Dr. Saul Hertz Archives Greenwich, CT.
Email: htziev@aol.com
Full list of author informaon is available at the end of the arcle.
Dr. Saul Hertz (1905–1950) discovers the medical
uses of radioiodine.
How many times have you prescribed Iodine-131 for
thyrotoxicosis or differentiated thyroid cancer? Probably
too many to count. For nearly 80 years, radioiodine
(RAI) has been the mainstay of nuclear medicine ther-
apy. One pivotal question began it all. This enduring
paradigm change was sparked on November 12, 1936,
when Dr. Saul Hertz, director of the Massachusetts
General Hospital's (MGH) Thyroid Unit went to a lec-
ture presented by the president of the Massachusetts
Institute of Technology (MIT), Karl Compton, Ph.D.
Dr. Hertz conceived and spontaneously asked the ques-
tion to President Compton, “Could iodine be made radi-
oactive articially?”[1]
MIT's President Compton responded and wrote about
the qualities of radioactive iodine. Hertz replied, “that
iodine is selectively taken up by the thyroid” and “that
he hopes that it will be a useful method of therapy.”[1]
Quickly thereafter, a unique collaboration was established
between MGH and MIT, when physicist Arthur Roberts
was hired by MIT's lab's director, Robley Evans.
Hertz and Roberts-Animal Studies 1937: 1st
Therapeutic Use 1941
In 1937, Harvard Medical School funded the Hertz/
Roberts rst series of experiments with 48 rabbits and
Iodine-128. MIT physicist Arthur Roberts, Ph.D. made
I-128 without a cyclotron. I-128, with a half-life of only
25 minutes, was given to the rabbits with altered thyroid
gland function. The data showed that hyperplastic glands
held more I-128 than normal glands. These studies con-
firmed the tracer quality of a radioactive substance, bring-
ing to light the tracer principle that RAI could be used
to study thyroid physiology; a giant step for what was to
become Nuclear Medicine.
MIT's Robley Evans, the lab director, insisted that his
name be added to the author list at the time the Hertz/
Roberts rabbit study paper was accepted for publication.
Evans had taken no part in the research or writing of the
paper. This event foreshadowed other unethical practices
that Dr. Hertz needed to overcome to bring his lifesaving
research to fruition.
After the publication of the Hertz/Roberts rabbit stud-
ies, Dr. Joseph Hamilton, a neurologist in a medical prac-
tice near Berkeley, CA, became interested in their research.
Hamilton measured the differential absorption ratio of
various radionuclides produced by the Berkeley cyclo-
tron. Hertz's former Boston colleague, Dr. Mayo Soley,
wrote to Hertz about copying the Hertz/Roberts rabbit
study. Hertz wrote back, “Welcome aboard!” The Soley/
Hamilton group in Berkeley was motivated by the animal
work of Hertz and Roberts and sent Hamilton to Boston.
Hamilton went back to California to join Mayo Soley in
the thyroid clinic. Hamilton complained to Berkeley’s
Glenn Seaborg about the short half-life of I-128. In June,
1938, Glenn Seaborg and John Livingood made a cyclo-
tron mixture of I-130 (t1/2 12 hours) and I-131, with a
physical half-life of about 8 days.
Hertz and Roberts needed a cyclotron to produce
RAI to start clinical trials. MGH's Chief of Medicine
and founder of MGH's Thyroid Unit, Dr. James Means,
received $30,000 from the Markle Foundation to estab-
lish MIT's rst cyclotron. Means reported to the Markle
Foundation, “My former house ofcer, Mayo Soley, is
working on radioactive iodine. Hertz and Roberts deserve
a great deal of credit in getting the pioneering work done
without a cyclotron, as soon as the cyclotron here is avail-
able, we can progress rapidly.”
On March 31,1941, Dr. Hertz gave 2.1 mCi of MIT
cyclotron-produced RAI, the rst therapeutic treatment
of radioiodine to a patient, Elizabeth D, with a chas-
ing dose of stable iodine in the form of Lugol Solution
to prevent a possible thyroid storm. Gradually, the rst
series of 29 patients was developed. Hertz and Roberts
continued to treat hyperthyroid patients in 1942.
Of importance, also in 1942, are the rst limited clinical
trials to treat thyroid cancer patients with RAI that Hertz
administered and reported to the Markle Foundation.
(Figure 1)
In early 1943, Dr. Hertz joined the Navy during World
War II. Hertz felt that his cases had been well established
and that the protocol was in place, having used uptake
testing and dosimetry in making an effective therapy. Dr.
Earle Chapman, who treated wealthy patients, worked
part time at MGH. Hertz asked Chapman to take over his
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Hertz B, et al. PJNM. 10(1), 1-4
cases during his absence. Hertz had rmly established the
work. Arthur Roberts, wrote, “I would believe nothing on
this subject from Chapman, who bungled the follow-up
on Hertz’s original series when Hertz joined the Navy.”[2]
Yes, Chapman changed the protocol, making little use of
dosimetry, used a standard large dose and stopped giving
the chasing dose of stable iodine.
Stolen Intellectual Property
Chapman together with MIT's Robley Evans went to
publish the work as their own in JAMA without Dr. Hertz's
name and before Dr. Hertz returned from WWII. The edi-
tor of JAMA asked Hertz and Roberts for their paper on
the topic, so two papers from the same institutions were
published side by side in JAMA on May 11, 1946.
During the war many professional meetings were post-
poned. Chapman and Evans state in their paper, “Although
Hertz and Roberts were encouraged by their therapeutic
trials, the details of their ndings have not been pub-
lished.” They also used the follow up Lugol solution to
justify their ownership of the RAI discovery.
The truth was revealed and explained in April, 2016
by MGH's Chairman Emeritus of the Department of
Radiology, Dr. James Thrall, who stated, “Chapman and
Evans had basically stolen Hertz's work...the most a-
grant, unethical, academically reprehensible behavior,
worst yet, ...Chapman and Evans spent a great deal of time
and effort rewriting history.”
Use of Radionuclides to Diagnose and Treat Can-
cer: Precision Targeted Oncology
With courage and tenacity, Saul Hertz moved for-
ward. He used newspapers and magazines. There was a
great interest in using atoms for peace. Hertz stated in the
June 2, 1946 American Weekly Magazine, “...demand is
expected for radioactive iodine and as research develops
in the eld of cancer and leukemia, for other radioactive
medicines.” [2]
To be noted, a limited number of outsiders were being
trained at medical schools however, they were not allowed
on the staffs of most hospitals. At that time, there was a
signicant lack of diversity at medical schools and on the
staff of most hospitals. In fact, Hertz had come to MGH in
1931 as a volunteer and was not paid. Catholics and Jews
built their own hospitals. After World War II, Hertz joined
Boston's newly expanded Beth Israel Hospital.
It's at the Beth Israel Hospital that Dr. Hertz contin-
ued to develop and rene the use of RAI to diagnose and
Figure 1. Mallinckrodt Commemorative Poster. Courtesy: Dr. Saul Hertz Archives Greenwich, CT USA..
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treat thyroid cancer. He had funding from the Navy to use
radioiodine for the treatment of thyroid carcinoma and to
research disabling the thyroid to explore its possible benets
for patients with angina. Hertz used radionuclides with the
tracer targeted method. This upset Dr. Hermann Blumgart,
a cardiologist and the director of the hospital, who used
Radium-C (Bismuth-214) to determine the velocity of blood
ow in the 1920’s. Blumgart blocked Hertz and his research.
Hertz's work was an economic threat. The cost of the RAI
treatment was $3.40. Surgery to remove the thyroid was
much more expensive, costing hundreds of dollars. Many
patients wrote to Dr. Hertz with the same themes, “How can
we get it?” and “I can't afford an operation.” There was no
medical insurance and patients were desperate to have the
RAI treatment. Additionally, Blumgart resented Hertz’s suc-
cess and his international reputation.
Hertz wrote, “..my new research project is in Cancer
of the Thyroid which I believe holds the key to the larger
problem of Cancer in general.”[2] In September, 1946,
The Radioactive Isotope Research Institute was estab-
lished with the mission of applying nuclear physics to
medical investigation, diagnosis, and treatment. There
were clinical and laboratory facilities in Boston and New
York. Dr. Hertz was the founder and director. New York
Monteore Hospital's Dr. Samuel Seidlin was the associ-
ate director who managed the New York ofces.
By happenstance, Dr. Seidlin used RAI to treat can-
cer, when a patient known as “BB” came to Monteore
Hospital with thyrotoxicosis due to metastasized thyroid
cancer. Years earlier, patient BB's thyroid had been sur-
gically removed. After consulting with Hertz, Seidlin
treated the cancer patient with RAI, in 1943. BB's metas-
tases responded to the RAI. No new lesions appeared and
some had completely disappeared. However, in 1952, BB
died from anaplastic carcinoma.
Dosimetry became essential in preparing a personal-
ized treatment plan. Dosimetry expert Glenn Flux writes,
“To calculate patient-specic dosimetry showed an early
understanding of the medical use of radionuclides that
is now being investigated on a large scale to personalize
treatments. Hertz and Roberts were truly visionaries.”[1]
Dr. Hertz developed a Multiscaler, equipment that facili-
tated uptake testing, to determine with precision an effec-
tive dose of RAI for each patient.
Hertz wrote, “I have certain ideas in the eld of
Cancer. Only recently a group of workers in England
have reported the regular production of cancer of the thy-
roid in animals by a series of steps which are subject to
analysis and close study by means of Radioactive Iodine
as a tracer.”[3] Hertz thought of using RAI to treat thy-
roid cancer in 1937, at the time of the pre-human studies,
as well as conducting limited clinical trials in 1942 that
were reported to The Markle Foundation. [4]
The headline from The Harvard Crimson, read, “Hertz
to Use Nuclear Fission in Cure for Cancer.” He supported
the production of I-131 off the atomic piles that lowered
the cost and increased the RAI distribution. Hertz stated,
“The goiter treatment by means of radioactive iodine rep-
resents a 'rst' in hopefully a long series of denitive treat-
ments.” [3]
Dr. Hertz established the rst Nuclear Medicine
Department in 1949 at The Massachusetts Women's
Hospital. It was reported as, “Opening a new division
where radioactive isotopes will be used to study and treat
disease.” (Figure 2)
In the 1980's, building on Dr. Hertz's work, the rst
radioimmunotherapy using monoclonal antibodies was
developed. Hertz's teaching at both Harvard Medical
School and MIT was the beginning of today's dual degree
programs. Currently, we are internally targeting other
tumors with radionuclides, such as, Yttrium-90 and
Lutetium-177. In addition to thyroid, targeted therapies
are being used for neuroendocrine tumors, lymphoma,
prostate cancer, metastatic bone cancers, and neuroblas-
toma in children and there are many more to follow.
Saul Hertz's prediction that radionuclides, “...would
hold the key to the larger problem of Cancer in general,”
may just be the best hope for diagnosing and treating can-
cer. Using the power of radionuclides as a weapon to ght
cancer has extended the lives of countless generations of
patients. A cancer survivor wrote, “Treatment with radi-
oactive iodine knocked the thyroid cancer (metastatic to
a little bit of bone and lung) right out of me, I am now
81. We have a large family. Many were praying for me.
The cure delivered on the wings of prayer was Dr. Saul
Hertz's discovery, the miracle of radioactive iodine. Few
can equal such a powerful and precious gift.” [3]
Figure 2. Dr. Saul Hertz (circa 1940's) Multiscaler-Uptake
Testing-Dosimetry-PrecisionOncology. Courtesy: Dr. Saul Hertz
Archives Greenwich, CT USA.
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Hertz B, et al. PJNM. 10(1), 1-4
Conflict of interest
The authors declare that there is no conflict of interest regard-
ing the publication of this article.
Funding
None.
Consent for publication
Not applicable.
Ethical approval
Not applicable.
Author details
Barbara Hertz1, Pushan Bharadwaj2, Bennett Greenspan3
1. Dr. Saul Hertz Archives Greenwich, CT
2. Consultant in Nuclear Medicine and PET, Singapore General
Hospital, Singapore
3. B.G. Consulting North Augusta, SC
References
1. Fahey FH, Grant FD, Thrall JH. Saul Hertz, MD, and The Birth
of Radionuclide Therapy. EJNMMI Phys. 2017;4(1):15.
https://doi.org/10.1186/s40658-017-0182-7
2. Braverman L. I-131 Iodine therapy: a brief history.
Presented at the AACE 2016 annual meeting Orlando, FL,
May, 2016
3. Hertz B. A tribute to Dr. Saul Hertz: the discovery of the
medical uses of radioiodine. World J Nucl Med. 2019;18:8–
12. https://doi.org/10.4103/wjnm.WJNM_107_18
4. Hertz S. A plan for analysis of the biological factors
involved in experimental carcinogenesis of the thyroid
by means of radioactive isotopes. West J Surg Obstet
Gynecol. 1946;54(12):487–9.
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