THE BIRTH OF NUCLEAR MEDICINE:
RADIOIODINE
The decade of the 1930s was a heady time in the world of physics. Among other achievements, including atom splitting, Irene Curie and her husband Frederick Joliot, in 1934, used polonium (discovered by Irene’s mother, Marie Curie, as a source of alpha particles, or helium nuclei) to bombard a strip of aluminum foil. They discovered small amounts of a radioactive byproduct: an isotope of phosphorous. Hearing of this, Enrico Fermi, in Rome, used neutron bombardment to create, in a burst of modern alchemy,
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| Ernest Lawrence (Wikipedia) |
fourteen isotopes in one year. Meanwhile, Ernest Lawrence and several colleagues were building particle-hurling cyclotrons at the University of California in Berkeley, enabling them to create isotopes almost at will.
One of the first isotopes to emerge from Lawrence’s lab was radioactive sodium: Na24. He used it as a “tracer” element, given in quantities small enough to produce negligible radiation but sufficient to be traced to various tissues. The principle of radioactive tracers was first described by George de Hevesy, a Hungarian scientist, in 1913, a technique that revolutionized the study of physiology and biologic chemistry. Lawrence’s brother, John, a physician interested in medical possibilities for the new isotopes, and Joseph Hamilton, a chemist with a medical degree from San Francisco,
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| John Lawrence (Wikipedia) |
teamed up to investigate medical uses of the new isotopes. In addition to Na24, they studied radioactive phosphorous, P32. Phosphorous concentrates in bone and, reasoning that lying in bone it could radiate bone marrow, they tried large doses as a treatment for leukemias, though to no avail. Radioactive phosphorous served well, however, as a “tracer”.
Iodine isotopes found the greatest medical use. Ingested iodine travels almost exclusively to the thyroid gland. Thus, radiation from an isotope would be limited primarily to the gland itself. The idea of thyroid radiation by isotopes originated at a luncheon conference at the Massachusetts General Hospital (MGH) in 1936. Karl Compton, President of MIT, was speaking on applications of physics in
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| Saul hertz (Wikipedia) |
medicine and biology. Dr. Saul Hertz, in charge of a thyroid unit at the hospital, had seen efforts at direct radiation treatment of “toxic goiter,” an old name for thyrotoxicosis, a disorder due to abnormally high production of thyroid hormone by the gland. The usual treatment at that time was surgery to remove most of the gland, leaving just enough to produce a more normal level of hormone. It was a difficult operation and Hertz was looking for a less invasive therapy.
He asked if radioactive iodine could be made artificially. The answer was yes, and the MIT laboratory produced Iodine128, whose half-life, however, is only 25 minutes. The short half-life forced Hertz and a young physicist, Arthur Roberts, to bring their test rabbits to MIT and feed the isotope quickly before the radioactivity ran out in two or three hours. They established that I128
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| Joseph Hamilton (Wikipedia) |
Meanwhile, in Berkeley, Joseph Hamilton, thinking along the same lines, asked a chemist at Lawrence’s “rad lab,” Glenn Seaborg, if he might produce an iodine isotope with a longer half-life. In short order, Seaborg, using the cyclotron, bombarded tellurium with deuterons to produce I131, an isotope with a half-life of 8 days. Seaborg, in a brilliant career,
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| Glenn Seaborg (Wikipedia) |
Hamilton recruited Mayo Soley from the thyroid service at the U C San Francisco Medical Center, who had trained at the MGH and knew Hertz. They investigated I131 in patients with various thyroid problems, mainly to work out how iodine was processed and excreted, much as Hertz had done earlier with rabbits, and published their similar results in 1939.
Back in Massachusetts, scientists at MIT, to catch up, quickly assembled a cyclotron, and produced a mixture of predominantly I130 (1/2 life 12 hours) and traces of I131. With that mixture, Hertz and Roberts began to treat patients with hyperthyroidism, sending the radioactive iodine to the overactive gland. The radiated gland released less hormone, resulting in reduced tremor, palpitations, and anxiety in patients. In San Francisco, Lawrence and Soley, using predominantly I131, obtained similar results, both teams reporting favorable results in 1942.
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| Scintillation scan of radioactive iodine in thyroid gland (Wikipedia) |
The following year, having treated twenty-seven hyperthyroid patients without surgery, Hertz joined the Navy. He postponed a report on the full series to be sure the treatment was successful. His vacancy at the thyroid service was filled by Earle Chapman, an internist who regularly attended the thyroid conferences. Chapman continued treating hyperthyroid patients, experimenting with various dose regimens.
With the war over, Hertz returned to Boston to find that Chapman had submitted his new series of cases to the Journal of the American Medical Association for publication. Angry that he had not been notified, Hertz rushed his own series to the same journal. Perplexed at receiving two similar studies from the same institution, the editor, Morris Fishbein, wrote secretly to the chief of the medical service at the MGH, Howard Means, asking what was going on. Means satisfied him that the papers represented two distinct, reliable studies and Fishbein published them back-to-back in the same 1946 issue. Bad blood between Hertz and Chapman was never resolved, however, another unfortunate instance of wrangling over scientific recognition.
Radioactive Iodine has become the therapy of choice for most patients with overactive thyroids and for some forms of thyroid cancer that preferentially take up iodine. Other radioactive isotopes have enjoyed widespread use as well, utilized in bone scans, PET scans, and others. The ancient art of alchemy, transmuting elements, has made a comeback.
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| The Polish alchemist and physician, Michael Sendivogius (1566-1636), demonstrating alchemy to Polish King Sigismund III. Painting by Jan Matejko, 1867 (Wikipedia) |
SOURCES:
Creager, ANH, Life Atomic: A History of Isotopes in Science and Medicine. 2013; Univ of Chicago Press.
Anon, “Donner Laboratory: Fifty Years of Nuclear Medicine Innovation.” J Nuclear Med 1968; 29 (4): 431-37.
Sawin, CT, and Becker, DV, “Radioiodine and the Treatment of Hyperthyroidism: The Early History.” Thyroid 1997; 7 (2): 163-176.
Anon, editorial, “Celebrating Eighty Years of Radionuclide Therapy and the Work of Saul Hertz.” J Appl Clin Med Physiol 2021; 22 (1): 4-10.
Hertz, S and Roberts, A, “Radioactive Iodine in the Study of Thyroid Physiology.” JAMA 1946; 131 (2): 81-86.
Chapman, EM and Evans, RD, “The Treatment of Hyperthyroidism with Radioactive Iodine.” JAMA1946; 131 (2): 86-91.
Daniels, DH and Ross, DS, “Radioactive Iodine: A Living History.” Thyroid 2023; 33 (6): 666-673.
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