Saul Hertz, M.D. (April 20, 1905 – July 28, 1950) was an American

physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...

who devised the medical uses of

radioactive iodine There are 37 known isotopes of iodine (53I) from 108I to 144I; all undergo radioactive decay except 127I, which is stable. Iodine is thus a monoisotopic element. Its longest-lived radioactive isotope, 129I, has a half-life of 15.7 million year ...

. Hertz pioneered the first targeted cancer therapies. Hertz is called the father of the field of theranostics, combining diagnostic imaging with therapy in a single or paired chemical substance(s).

Early life and education

Saul Hertz was born on April 20, 1905, to father Aaron Daniel (A.D.) Hertz and mother Bertha Hertz in

Cleveland, Ohio Cleveland ( ), officially the City of Cleveland, is a city in the U.S. state of Ohio and the county seat of Cuyahoga County. Located in the northeastern part of the state, it is situated along the southern shore of Lake Erie, across the U.S. ...

. His parents were Jewish immigrants from what is currently

Golub-Dobrzyń Golub-Dobrzyń () is a town in northern Poland, located on the Drwęca. Situated in the Kuyavian-Pomeranian Voivodeship (since 1999), it was previously in the Torun Voivodeship (1975–1998). It is the capital of Golub-Dobrzyń County and has a po ...

in Poland. A.D. Hertz was a successful real estate developer. The Hertz's raised their seven sons according to Orthodox traditions. Saul Hertz attended public school and went on to graduate from the

University of Michigan , mottoeng = "Arts, Knowledge, Truth" , former_names = Catholepistemiad, or University of Michigania (1817–1821) , budget = $10.3 billion (2021) , endowment = $17 billion (2021)As o ...

with Phi Betta Kappa honors in 1924. He received his medical degree from

Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...

in 1929, at a time when there were strict quotas for outsiders (particularly Jews and Catholics – there were no women). Hertz completed his internship and residency at Cleveland's Mount Sinai Hospital, which had been established to serve Cleveland's East side Jewish population.

Early studies with radioactive iodine

Hertz joined the Thyroid Clinic and Metabolism Laboratories at

Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is the original and largest teaching hospital of Harvard Medical School located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United Stat ...

in 1931. Although initially a volunteer, shortly thereafter, Hertz became Chief of the Thyroid Clinic, serving in this capacity from 1931-1943. On November 12, 1936,

Karl Compton Karl Taylor Compton (September 14, 1887 – June 22, 1954) was a prominent American physicist and president of the Massachusetts Institute of Technology (MIT) from 1930 to 1948. The early years (1887–1912) Karl Taylor Compton was born in ...

, then president of the

Massachusetts Institute of Technology The Massachusetts Institute of Technology (MIT) is a private land-grant research university in Cambridge, Massachusetts. Established in 1861, MIT has played a key role in the development of modern technology and science, and is one of the ...

, gave a presentation, entitled "What Physics Can Do For Biology and Medicine" in Harvard Medical School's Vanderbilt Hall. Hertz spontaneously asked President Compton, "Could iodine be made radioactive artificially?" on possible applications of physics to medicine. Compton responded in a letter to Hertz on December 15, 1936, writing, "Iodine could be made artificially radioactive" and "emits gamma rays and beta rays." On December 23, 1936, Hertz replied, “that iodine is selectively taken up by the thyroid” and “that he hopes that it will be a useful method of therapy.” In 1937, Hertz began a

collaboration Collaboration (from Latin ''com-'' "with" + ''laborare'' "to labor", "to work") is the process of two or more people, entities or organizations working together to complete a task or achieve a goal. Collaboration is similar to cooperation. Most ...

with the physicist Arthur Roberts of the Massachusetts Institute of Technology (MIT). The purpose of the collaboration was to explore possible applications of iodine radioisotopes for diagnosis and treatment of thyroid diseases. Robley D. Evans, Director of the Radiation lab of MIT hired Arthur Roberts. As a condition of his employment, any papers forthcoming would include Robley Evans as an author. The Harvard Milton Fund sponsored the first preclinical studies of

isotope Isotopes are two or more types of atoms that have the same atomic number (number of protons in their nuclei) and position in the periodic table (and hence belong to the same chemical element), and that differ in nucleon numbers (mass numbers) ...

iodine-128 on thyroid function in 48 rabbits, which Roberts produced without a cyclotron. Roberts produced the iodine-128 by means of neutron bombardment, building on previous studies by physicist

Enrico Fermi Enrico Fermi (; 29 September 1901 – 28 November 1954) was an Italian (later naturalized American) physicist and the creator of the world's first nuclear reactor, the Chicago Pile-1. He has been called the "architect of the nuclear age" and ...

. Roberts also devised a Geiger-Müller detector for quantifying the amount of the radioisotope of iodine present in the biological specimens produced in the experiment. Hertz's experiment with Roberts involved studies of 48 rabbits. They determined in the study that the

hyperplastic Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferatio ...

thyroid gland absorbed more of the radioactive substance than the normal gland. This proved that radioactive iodine could serve as a

radioactive tracer A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by ...

in thyroid function. The tracer procedure was critical for determining the amount of iodine the human thyroid took up so that the dosage of radioactive iodine could be established for therapeutic purposes. The original manuscript describing their rabbit study findings had Hertz and Roberts as the coauthors as they had done the work and written the paper. Primary sources document Roberts' production of I-128 at the MIT laboratory, while Hertz and Roberts solely administered and analyzed the biodistribution of the radioisotope in the rabbits. Robley Evans insisted that his name be added to the author list at the time the Hertz/Roberts study paper was published. Evans had taken no part in the research or writing of the paper. At the time of the 1937 rabbit studies, Hertz predicted the therapeutic use of radioactive iodine for treating thyroid carcinoma in a medical journal.

Therapy with radioactive iodine

Hertz's initial studies were conducted with iodine-128. However, this isotope has a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

of only 25 minutes, rendering it impractical as a therapeutic or diagnostic agent. Human application of the iodine radioisotopes required a more suitable radioisotope of iodine. Dr. Joseph Hamilton, a neurologist in a medical practice near Berkeley, became interested in the Hertz-Roberts research. Hamilton measured the differential absorption ratio of various radionuclides produced by the Berkeley cyclotron. Dr. Mayo Soley, a former colleague of Hertz at MGH, wrote to Hertz congratulating him on his RAI work. Dr. Soley was then at University of California Berkeley, where Ernest Lawrence had built a cyclotron. Hamilton and Soley were motivated by the animal work of Hertz and Roberts and sent Hamilton to Boston. Hamilton went to California to join Soley in the thyroid clinic. Hamilton Complained to Berkeley's Glenn Seaborg about the short half-life of I-128. In 1938,

Glenn Seaborg Glenn Theodore Seaborg (; April 19, 1912February 25, 1999) was an American chemist whose involvement in the synthesis, discovery and investigation of ten transuranium elements earned him a share of the 1951 Nobel Prize in Chemistry. His work i ...

and John Livingood had artificially prepared

I-131 Iodine-131 (131I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nu ...

using the

University of California Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant univ ...

cyclotron A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Janu ...

. With a half-life of 8 days, this isotope was better suited to practical medical applications than I-128. The building of the cyclotron at MIT for producing suitable isotopes was funded for $30,000 by the Mary Markle Foundation of New York City in 1938. The construction project was completed two years later in 1940. During those two years, the experiments with rabbits continued. In early 1941, Hertz administered to the first human patient a therapeutic dose of cyclotron-produced radioiodine (RAI), the patient suffering from

Graves' disease Graves' disease (german: Morbus Basedow), also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyr ...

, a form of hyperthyroidism. This clinical trial was at the Massachusetts General Hospital. This administration was the first successful treatment of humans with an artificially produced radioactive material. Subsequently, a series of 29 patients were treated in this way, and their outcomes were documented. The ''

Journal of the American Medical Association ''The Journal of the American Medical Association'' (''JAMA'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of bio ...

'' published “Radioactive Iodine in the Study of Thyroid Physiology" with Hertz as lead author in its May 1946 issue. This article was a five-year follow-up study of the 29 patients, and it documented the successful treatment and safety of radioactive iodine for the treatment of

hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...

. The follow-up study established the use of radioactive iodine therapy as a standard treatment for Graves’ disease.Hertz, Barbara, Schuller, Kristin, "Saul Hertz, MD (1905–1950) A Pioneer in the Use of Radioactive Iodine", ''Endocrine Practice'' 2010 16,4;713–715.

World War II interval

In 1943, Hertz joined the

United States Navy Medical Corps The Medical Corps of the United States Navy is a staff corps consisting of military physicians in a variety of specialties. It is the senior corps among all staff corps, second in precedence only to line officers. The corps of commissioned offic ...

. He served as an adjunct to the

Manhattan Project The Manhattan Project was a research and development undertaking during World War II that produced the first nuclear weapons. It was led by the United States with the support of the United Kingdom and Canada. From 1942 to 1946, the project w ...

, working in an aspect of the project related to biology and medicine for furthering medical uses of atomic energy. After his return from military duty, Hertz learned that MGH's Earl Chapman (who had taken over Hertz's clinical trials) and MIT's Robley Evans, had submitted a scientific publication to the ''Journal of American Medicine (JAMA)'' claiming priority for the development of the use of RAI to treat Graves' Disease. Morris Fishbein, editor of JAMA, requested that Hertz and Roberts, submit their seventh article on the subject, describing their successful use of RAI in the first clinical trials. As a result, two scientific publications appeared side by side in the May 1946, issue of the ''Journal of the American Medical Association'', with the Hertz publication with Roberts appearing first in the issue of the journal.

Stolen intellectual property

Current historians have documented the reason for two articles from the same institution appearing side by side in the Journal of the American Medical Association (JAMA) May 11, 1946 issue. The first by Hertz and Roberts, and the second by MGH's Earle Chapman and MIT's Robley Evans. Chapman, who took over Hertz's established cases during the war, teamed up with Evans to treat 22 new cases of their own. Chapman and Evans used Hertz's data to do their own human trials with minor tweaks and were the first to submit an article to JAMA, without consulting or acknowledging Hertz. They claimed propriety of the RAI therapy in treating Graves' disease. Hertz was informed about the Chapman-Evans Paper submission after the Chapman–Evans paper was sent back for revisions. Roberts insists that neither Chapman nor Evans have any propriety for the development of RAI treatment stating, "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 Hertz joined the Navy."

Nuclear fission products in cancer treatment

Interest in atomic energy for peaceful purposes was heightened as the

Atomic Age The Atomic Age, also known as the Atomic Era, is the period of history following the detonation of the first nuclear weapon, The Gadget at the ''Trinity'' test in New Mexico, on July 16, 1945, during World War II. Although nuclear chain reactio ...

commenced following the

atomic bombings of Hiroshima and Nagasaki The United States detonated two atomic bombs over the Japanese cities of Hiroshima and Nagasaki on 6 and 9 August 1945, respectively. The two bombings killed between 129,000 and 226,000 people, most of whom were civilians, and remain the onl ...

. Hertz envisioned broader applications of radioisotopes in cancer treatment stating, “My new research project is in cancer of the thyroid which I believe holds the key to the larger problem of cancer in general". Hertz established the Radioactive Isotope Research Institute in Boston, Massachusetts, in September 1946, with Samuel Seidlin of New York City as the associate director. Its purpose was to develop the applications of

nuclear fission products Nuclear fission products are the atomic fragments left after a large atomic nucleus undergoes nuclear fission. Typically, a large nucleus like that of uranium fissions by splitting into two smaller nuclei, along with a few neutrons, the release ...

to the treatment of

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

goiter A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...

, and other malignant growths. After WWII, Hertz joined the newly expanding Boston's Beth Israel Hospital. There, Hertz directed the successful use of RAI in the diagnosis and treatment of thyroid carcinoma. Hertz worked with the government to centralize an agency to handle the distribution of

radioactive isotopes A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...

for use by private enterprises working on approved projects. He advocated for the Atomic Energy Commission to produce iodine-131 in the government’s atomic piles (nuclear reactors) at

Oak Ridge National Laboratory Oak Ridge National Laboratory (ORNL) is a U.S. multiprogram science and technology national laboratory sponsored by the U.S. Department of Energy (DOE) and administered, managed, and operated by UT–Battelle as a federally funded research and ...

, which lowered the cost and increased radioiodine's distribution.Vincent, Donald. (1949 May 24). "Hertz to Use Nuclear Fission in Cure for Cancer". ''The

Harvard Crimson The Harvard Crimson are the intercollegiate athletic teams of Harvard College. The school's teams compete in NCAA Division I. As of 2013, there were 42 Division I intercollegiate varsity sports teams for women and men at Harvard, more than at ...

'', May 24, 1949. He made extensive studies of radioactive iodine in the treatment of thyroid cancer as well as in the production of total

thyroidectomy A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other conditi ...

in the treatment of certain cases of

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

. In 1949, Hertz established the first

nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...

department at the Massachusetts Women's Hospital where he expanded his research to use radionuclides to diagnose and treat other forms of cancer. Hertz studied the application of radioactive

phosphorus Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ear ...

and the influences of hormones on cancer as displayed by isotope studies.

Later career and influence

Hertz's research was seminal in the emergence of the field of nuclear medicine. His research continued with his appointments as instructor at Harvard Medical School from 1946 to 1950 and as an attachment to the Nuclear Physics Department at the Massachusetts Institute of Technology from 1939 to 1950. The application of radioactive iodine in the diagnosis and treatment of thyroid disease is the cornerstone of nuclear medicine.

Barbara Bush Barbara Pierce Bush (June 8, 1925 – April 17, 2018) was First Lady of the United States from 1989 to 1993, as the wife of President George H. W. Bush, and the founder of the Barbara Bush Foundation for Family Literacy. She previously was ...

, who was successfully treated with radioiodine, wrote to Vitta Hertz, his widow, “It is comforting to know that so many people are well because of the scientific expertise of people like Dr. Hertz.” In the early 21st century, there is a significant rise in the use of radioisotopes to diagnose and treat cancer, in a field of nuclear medicine referred to as theranostics.

Yttrium-90 Yttrium-90 () is an isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer. Decay undergoes β− decay to zirconium-90 with a half-life of 64.1 hours and a decay energy of 2.28 M ...

(Y-90) and

Lutetium-177 Naturally occurring lutetium (71Lu) is composed of one stable isotope 175Lu (97.41% natural abundance) and one long-lived radioisotope, 176Lu with a half-life of 3.78 × 1010 years (2.59% natural abundance). Thirty-five radioisotopes have been ch ...

are being used to diagnose and treat neuroendocrine tumors. The use of

dosimetry Radiation dosimetry in the fields of health physics and radiation protection is the measurement, calculation and assessment of the ionizing radiation dose absorbed by an object, usually the human body. This applies both internally, due to ingested o ...

has its origin in Hertz's work. Alpha targeted therapy is a therapy for patients with

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...

s (brain tumors). The use of the protein called NIS, that is needed for the thyroid to take up the RAI in the treatment of thyroid carcinoma, is being explored to treat breast cancer. Additionally I-131 is being utilized in the treatment of

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

replacement for

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

patients. These are all modern applications of nuclear medicine. Hertz died on July 28, 1950, at age 45 of a

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...

Selected honors

*Dalton Scholar - Massachusetts General Hospital - 1931 - 1933 *Henry Pickering Wolcott Fellow - Harvard Medical School - 1935 - 1937 *Key to Science/Sigma XI - Massachusetts Institute of Technology (Scientific Society) - 1940

Enduring memorials

The Society for Nuclear Medicine and Molecular Engineering administers the Saul Hertz, MD, Award in honor of Saul Hertz. The award recognizes individuals who have made outstanding contributions to the field of radionuclide therapy. Connecticut Senator

Richard Blumenthal Richard Blumenthal (; born February 13, 1946) is an American lawyer and politician who is the senior United States senator from Connecticut, a seat he has held since 2011. A member of the Democratic Party, he is one of the wealthiest members of ...

entered into the congressional record on May 11, 2021 "''Senate'' Remembering Dr. Saul Hertz." He stated "Mr. President, today I rise to recognize Dr Saul Hertz, a pioneer for medical uses of radioiodine, RAI... On March 31b, 1941... Hertz administered the first therapeutic use of radioiodine... Today, medical uses of RAI remain the g©old standard of targeted precision oncology." Beginning in 2000, Hertz's daughter Barbara Hertz has led an effort to more thoroughly document the contributions of Hertz to medicine. This has included a website with his major publications. Barbara Hertz also co-authored with Kristin Schuller a 2010 publication in the journal

Endocrine Practice ''Endocrine Practice'' is a bimonthly peer-reviewed medical journal covering endocrinology. It was established in 1995, and is the official journal of the American Association of Clinical Endocrinologists (AACE) and the American College of Endocr ...

on her father's major contributions to human health. In 2014, the National Museum of Nuclear Science and History, a Smithsonian affiliate, displayed the, "Dr. Saul Hertz and the Origin of Nuclear Medicine" exhibit. In 2021, the American Chemical Society (ACS) designated the Mass General Hospital as the "Saul Hertz and the Medical Uses of Radioiodine" National Historic Chemical Landmark. ACS Landmark commemorates this seminal achievement in the history of chemical sciences and provides a record of Dr. Hertz's contributions to chemistry and society that have profoundly transformed our lives.

References

External links

{{DEFAULTSORT:Hertz, Saul 1905 births 1950 deaths American nuclear medicine physicians Physicians from Cleveland University of Michigan alumni Harvard Medical School alumni 20th-century American Jews