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,

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, 

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 

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 

Joseph Hamilton (Wikipedia)

indeed concentrated in the thyroid gland, publishing the results in May 1938.

         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,

Glenn Seaborg (Wikipedia)

 discovered (or co-discovered) ten new elements, for which he won a Nobel Prize. He produced an iron isotope allowing George Whipple and colleagues to flesh out the metabolism of iron in humans. And he was instrumental in the Manhattan Project and served as chairman of the U.S. Atomic Energy Commission for a decade.

         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. 

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.

         

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.

 

A full index of past essays is available at: https://museumofmedicalhistory.org/j-gordon-frierson%2C-md

 

 

 THE NÉLATON PROBE: GARIBALDI’S 

ANKLE AND OTHER TALES

 

           In 1862, Guiseppi Garibaldi, the Italian patriot intent on uniting Italy, crossed from Sicily to Italy’s boot, beginning a march toward Rome. In the town of Aspromonte, Garibaldi met soldiers sent to

Giuseppe Garibaldi (Wikipedia)

oppose him. Recognizing them as fellow Italians and reluctant to fire, he ventured forward to arrange a truce. Three bullets caught him, two of no consequence and one that ricocheted off a rock into his right ankle. After his capture, at least six doctors examined him and all but one felt that the bullet was no longer in his ankle. Before the
availability of X-rays, locating a bullet in a wound was a challenge for military surgeons. The stakes were high as a retained missile could lead to infection and death.

         In faraway England, Garibaldi’s campaign was highly popular and his backers raised money to send a surgeon, Richard Partridge, to assist. Partridge agreed that the bullet was no longer present. Inflammation increased substantially, however, and the Italian doctors invited a French surgeon, Auguste Nélaton, to see Garibaldi. After probing the

Auguste Nélaton (Wikipedia)

 wound, Nélaton opined that the bullet was    still in place. But, he wondered, was it bone, and not bullet, that halted his probe? On return to France, he developed a porcelain probe that was unglazed at the tip, which, if rubbed against a bullet, would show traces of lead. He sent the probe to one of Garibaldi’s surgeons, Zanetti, who confirmed that the bullet was still in place. 

         Partridge heard of this and returned to Italy, this time accompanied by Nicolai Pirogov, the famous Russian surgeon (see essay of Dec. 2016). Partridge reversed his opinion, agreeing with Pirogov that the bullet was present. Zanetti enlarged the wound and extracted the bullet fragment (fragmented because of the ricochet), allowing the wound to slowly heal. 

Nélaton probe with unglazed porcelain tip
(National Museum of American History)

      On return to England, Partridge’s reputation fell. The medical

Richard Partridge (Wikipedia)

profession accused him of “stealing a patient,” since he saw Garibaldi without an invitation, and the public disparaged him for his error in diagnosis. His practice dwindled and he died poor.

         Auguste Nélaton, conversely, enjoyed increased renown. Aged 56 at the time, he had spent six years as an intern and extern under the famous surgeon Guillaume Dupuytren at the Saint Louis Hospital in Paris, rising later to a surgical professorship. In 1867, Emperor Napoleon III appointed him as his personal surgeon, and he attained membership in the French Academy of Sciences. He made contributions to pelvic surgery, lithotomy, and especially to surgery on the maxilla and mandible. He invented the flexible urinary catheter still in use today, a much-appreciated advance over the stiff ones in use at the time. He wrote a large text on surgical pathology and several other works. He accumulated a large fortune but lived modestly.

         The prominent Harvard professor of surgery, J. Collins Warren, during study in Europe in 1866 had met both men and wrote that Partridge “was never regarded by his colleagues as an exceptionally brilliant exponent of surgical art.” Nélaton, by contrast, he found refined and highly regarded in surgical circles. Nélaton probes became standard equipment in the military surgeon’s tool kit. Parenthetically, Warren, on his trip  had also watched Joseph Lister apply his new antibacterial techniques for preventing wound infections, work as yet unpublished.

         The Nélaton probe later found a use on two American presidents. Three years after Garibaldi’s episode, John Wilkes Booth shot Abraham Lincoln in the back of the head in Ford’s Theater, Washington. Dr. Charles Leale, in a nearby box, heard the fatal shot and rushed to help. Leale, a recent graduate of the Bellevue Hospital Medical College in New York, was a young surgeon in the U.S. Army

Dr. Charles Leale (Wikipedia)

Hospital in Washington. He found Lincoln slumped forward, unconscious. A clot over part of the occiput showed the wound, which Dr. Leale probed with his finger. Volunteers carried Lincoln across the road to a private home where Dr. R.K. Stone, Lincoln’s personal physician, the Surgeon General, Dr. Joseph K. Barnes, and other volunteer physicians arrived to help. Barnes sent for a Nélaton probe while keeping the wound open with a silver probe (to reduce intracranial pressure). At about 2 AM, as the President was dying, Barnes inserted the Nélaton probe into the wound, twice, and on the second try he claimed to have encountered the bullet, though it was of no help. Five hours later, after a period of loud and “stertorous” breathing, the President expired at 7:20 AM.

On July 2, 1881, the mentally deranged Charles J. Guiteau shot President Garfield in the back while in a railroad station. Dr. Doctor Willard Bliss (Doctor was his first name), one of the first physicians to examine Garfield, in addition to inserting his unwashed finger into the bullet wound,

Doctor Willard Bliss (Wikipedia)

inserted a Nélaton probe. The probe encountered only a fractured rib and the bulb on the end, entrapped in the bone fragments, could only be released by pressing on the President’s chest, a painful maneuver. A rib had deflected the bullet so that a straight, rigid probe, such as the Nélaton probe, would not reach the bullet in any case. 

Another attempt to find the bullet was made by Alexander Graham Bell. He created a device based on magnetic induction that would produce sound when metal entered the circuit. It failed in Garfield's case, Bell surmising that the metal bedsprings interfered with the detection.

Alexander Graham Bell applying his metal detector to President Garfield. Man on the right is 
listening for sounds if metal found. (From Frank Leslie's Illustrated Newspaper, courtesy Library 
of Congress)

Garfield lingered on for three months, undergoing repeated probes with unclean fingers, until he expired from secondary infection. By this time, the role of germs in wound infections was well known to many in the medical profession, though most of those caring for President Garfield were not believers. 

The advent of X-rays, discovered in 1895, soon made the Nélaton probe obsolete. Until then, it was a standard instrument in a military surgeon’s kit.

 

SOURCES:

Rutkow, Ira, James A. Garfield. 2006; Times Books, Henry Holt & Co.

Dobson, J, “A Surgical Problem of the Last Century.” Ann Roy Coll Surg Engl, 1953; 13: 266-69.

Moscucci, O, “Garibaldi and the Surgeons.” J Roy Soc Med 2002; 94: 248-52.

Sabbatani, S, “Garibaldi’s Wounds.” Le Infezioni nella storia della Medicina. 2010; 18(4): 274-87. (Translated by Google)

 

Curca, F P and Patrascu, T, “Historical Landmarks of the Use of Nélaton’s Probe in the Surgical Diagnosis of Gunshot Wounds and Two Famous Applications: Garibaldi’s and Lincoln’s Cases.” Roman J Legal Med, 2019; 27: 388-94.

 

Warren, J Collins, “The Nélaton Probe.” Boston Med Surg J  1919; 181 (8): 235-6.

Dunea, G, "The Bullet in Garibaldi's Ankle." Hektoen International 2021; 13 (3).

 

Mylonis, A I, “Glances in the History of Medicine: Auguste Nélaton.” Hellenic Arch Oral Maxillofacial Surg 2021; 3: 207-12.

 

Papaioannou, H I and Stowell, D W, “Dr. Charles A. Leale’s Report on the Assassination of Abraham Lincoln.” Accessed at: https://quod.lib.umich.edu/j/jala/2629860.0034.105/--dr-charles-a-leales-report-on-the-assassination-of-abraham?rgn=main;view=fulltext

A full index of past essays is available at: https://museumofmedicalhistory.org/j-gordon-frierson%2C-md