Saul Hertz

Saul Hertz, M.D. (April 20, 1905 – July 28, 1950) was an American physician who discovered the medical uses of radioactive iodine. Hertz pioneered the first targeted cancer therapies. Hertz is called the father of theranostics.

Dr. Saul Hertz

Early life and education

Saul Hertz was born on April 20, 1905, to Aaron Daniel (A.D.) Hertz and Bertha Hertz in Cleveland, Ohio. His parents were Jewish immigrants from what is currently Golub-Dobrzyń in Poland. The father was a successful real estate developer. The Hertzs raised their seven boys according to Orthodox traditions. Saul attended public school, and went on to graduate from the University of Michigan. He received his medical degree from Harvard Medical School in 1929, at a time when there were strict quotas for outsiders. Hertz performed his internship and residency at Cleveland's Mount Sinai Hospital that had been established to serve Cleveland's East side Jewish population.[1]

Early studies with radioactive Iodine

Hertz joined the Thyroid Clinic and Metabolism Laboratories at Massachusetts General Hospital in 1931.[2] He came as a volunteer, since Jews were not paid at that time.

Hertz served as Chief of the Thyroid Clinic from 1931-1943, and in 1936 conceived the idea of making iodine artificially radioactive.[3] Compton responded in a letter to Hertz on December 15, 1936, describing radioactive iodine.

In 1937, a collaboration began with the physicist Arthur Roberts of The Massachusetts Institute of Technology. A condition of Roberts' employment included that the name of Robley Evans, director of the MIT lab, be added to any articles that would be published. The first of the Hertz/Roberts studies in rabbits evaluated the effects of non cyclotron produced I-128 which Roberts produced by neutron bombardment, based on Enrico Fermi's work.[4] The experiment involving 48 rabbits demonstrated the tracer capabilities of radioactive iodine and its effects on the thyroid gland. The studies showed that the hyperplastic thyroid gland absorbed more of the radioactive substance than the normal gland.[5] This proved the tracer qualities of the radioactive substance.[6] The tracer procedure was critical for determining the amount of iodine the human thyroid took up so that a calculation of the dosage of radioactive iodine could be calibrated for treatment.[7]

At the time of the rabbit studies in 1937 Hertz predicted the therapeutic use of radioiodine for treating thyroid carcinoma.[8]

Human treatment with radioactive iodine

Dr. Saul Hertz demonstrates a Multiscaler with colleague Doris Darby

Human studies required a better source of the radioactive Iodine. In 1938, Glenn Seaborg and John Livingood had developed I-131 on the University of California Berkeley's cyclotron. The building of the cyclotron at MIT 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.[9]

In early 1941, Hertz administered cyclotron-produced radioiodine (RAI), as a therapeutic dose to the first human patient at The Massachusetts General Hospital, to a patient with hyperthyroidism, Graves' Disease.[10] This was the first successful treatment of humans with an artificially produced radioactive material.[11]

Gradually a series of 29 patients were treated and documented. The Journal of the American Medical Association published “Radioactive Iodine in the Study of Thyroid Physiology" in the May 1946 issue. This article was a five-year follow up study of the 29 patients and documented the successful treatment and safety of radioactive iodine for the treatment of hyperthyroidism. The follow-up study firmly launched the use of radioactive iodine therapy as a standard treatment for Graves’ Disease.[9]

World War II

In 1943, Hertz joined the Navy Medical Corps. He was an adjunct to The Manhattan Project for biology and medicine in furthering medical uses of atomic energy. Upon his return from serving his country, Hertz learned that MGH's Dr. Earl Chapman (who had taken over Hertz's clinical trials) and MIT's Robley Evans, had submitted a paper to the Journal of American Medicine claiming priority for the discovery of the use of RAI to threat Graves' Disease. Thus two papers appeared side by side in JAMA May, 1946 with the Hertz/Roberts paper being first.[12][13]

Nuclear fission products in cancer treatment

Interest in atomic energy for peaceful purposes was heightened after the explosion of the atomic bomb. 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. Dr Samuel Seidlin of New York City was the associate director. Its purpose was to apply fission products to the treatment of thyroid cancer, goiter, and other malignant growths. After WWII, Hertz joined the newly expanding Boston's Beth Israel Hospital. At Beth Israel Hospital, 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 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, which lowered the cost and increased radioiodine's distribution.[14] He made extensive studies of radioactive iodine in the treatment of thyroid cancer as well as in the production of total thyroidectomy in the treatment of certain cases of heart disease.[4] In 1949, Hertz established the first nuclear medicine 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 and the influences of hormones on cancer as displayed by isotope studies.

Later career and influence

Hertz research established a paradigm change. He influenced the development of the convergence of the sciences in the quest to conquer cancer through his research and instruction at both Harvard and MIT. He was an instructor in medicine at Harvard Medical School and Harvard University from 1946 to 1950. His teaching included an attachment to the Nuclear Physics Department at Massachusetts Institute of Technology from 1939 to 1950.Today there are joint programs offering Ph.D/M.D dual degrees, worldwide.

The development of radioactive iodine in the diagnosis and treatment of thyroid disease is the cornerstone of nuclear medicine.[9]Barbara Bush, 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.” [15]

Currently there is a renaissance in the use of radionuclides to diagnose and treat cancer, called theranostics. Yttrium 90 (Y-90) and Lutetium -177 (Lu-177) are being used to diagnose and treat neuroendocrine tumors. The use of dosimetry has its origin in Hertz's work. Alpha targeted therapy is extending the lives of those with neuroblastomas (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 replacement for leukemia patients.

Hertz died on July 28, 1950 at age forty-five of a heart attack.

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

See also

References

  1. Hay, Ian, ed. (2008). Clinical Endocrine Oncology (2nd ed.). Blackwell. pp. xvi–xx. ISBN 978-1-4051-4584-8.
  2. Hertz, Barbara; Schuller, Kristin "title=Saul Hertz, MD (1905 - 1950): A Pioneer in the Use of Radioactive Iodine (2010). Endocrine Practice. 16 (4): 713–15. Missing or empty |title= (help)<
  3. .Fahey FH, Grant FD, Thrall JH 2017 "Saul Hertz, MD, and the birth of radionuclide therapy". EJNMMI Phys 4(1):15 doi:10.1186/s40658-017-0182-7
  4. Bander, Martin (1987). "Remembering the Early Days of Nuclear Medicine". MGH News. Massachusetts General Hospital. 46 (6): 5–6.
  5. Hertz, S.; Roberts, A. (1940). "Radioactive Iodine as an Indicator in Thyroid Physiology". The American Journal of Physiology. 128 (3): 565–576.
  6. Soley M, Miller E,. "Symposium on Endocrinology: Treatment of Graves’ Disease with Radioactive iodine".Medical Clinics of North America 1948 32;3-17.
  7. Hertz S, Roberts A, Salter WT. "Radioactive iodine as an indicator in thyroid physiology, IV: the metabolism of iodine in Graves’ disease. Hertz and Roberts pioneered the process of dosimetry that is the foundation of precision medicine." Journal of Clinical Investigation 1942;21:25-29.
  8. Hertz, S. "A Plan for Analysis of the Biological Factors Involved in Experimental Carcinogenesis of the Thyroid by Means of Radioactive Isotopes". The Western Journal of Surgery, Obstetrics and Gynecology, Vol.54 (December 1946), p.487-489, Greenwich, CT, accessed January 9th, 2019
  9. Hertz, Barbara, Schuller, Kristin, "Saul Hertz, MD (1905 - 1950) A Pioneer in the Use of Radioactive Iodine", Endocrine Practice 2010 16,4;713-715.
  10. Fragu, Philippe, "How the field of thyroid endocrinology developed in France after World War II", Bulletin of the History of Medicine, 1948 77,2:393-414.
  11. Hertz S, Roberts A, Means JH, Evans RD. "Radioactive iodine as an indicator in thyroid physiology, II: iodine collection by normal and hyperplastic thyroids in rabbits". American Journal of Physiology 1940; 565 - 576.
  12. Hertz S, Roberts A 1946 "Radioactive iodine in the study of thyroid physiology. VII the use of radioactive iodine therapy in hyperthyroidism".JAMA 131:81-86
  13. Fragu, Philippe, "How the field of thyroid endocrinology developed in France after World War II", Bulletin of the History of Medicine, 1948 77,2:393-414.
  14. Vincent, Donald. (1949 May 24). "Hertz to Use Nuclear Fission in Cure for Cancer". The Harvard Crimson, May 24, 1949.
  15. News and Public Affairs Office of MGH. "50th Anniversary of 'atomic cocktail' to treat overactive thyroid gland". MGH Hotline 1991, Jan 31;1-3.
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