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Surgeons find new twists to an old story

Yale Medicine Magazine, 2011 - Autumn


A search for 70-year-old records unearths new details about the first use of chemotherapy for cancer.

In 1942 he was 47 years old and living alone, working day shifts at a ball-bearing factory in central Connecticut. He tried for years to speak English but his native Polish stuck stubbornly to his tongue. After treatment at another hospital, he came to Yale with neck and throat pain. He couldn’t turn his head, he couldn’t eat. Surgeons elsewhere had removed his tonsils; months later, when the pain returned, and believing that a bad tooth was the source of the problem, he had a right lower molar pulled. When doctors found a tumor—11 by 5 centimeters—growing in the lymph nodes lining his neck, he was referred to Yale. The tumor initially responded to rounds of radiation therapy—it turned his skin brown but the tumor became progressively resistant to radiation. The swelling and painin his face returned. During a visit to his doctor at Yale, Gustaf E. Lindskog, M.D., he learned that a new treatment might help him. Recognizing his desperate situation, he agreed to try it. “The patient’s outlook is utterly hopeless,” it was noted in the chart.

This is the story of J.D. (which does not stand for John Doe), the HIPAA-protected initials of the first recipient of intravenous chemotherapy for cancer. For years his story was overshadowed by the larger tale of chemotherapy’s discovery by Louis Goodman, M.D., and Alfred Gilman, M.D., Ph.D., who, as World War II approached, were working under a secret contract with the U.S. government to develop an antidote to mustard gas, a lethal form of chemical warfare that had beenused against the Allieson the Western Front from 1916 through 1918. Goodman and Gilman found that when injected into mice and rabbits, nitrogen mustard, a chemical relative of the mustard gas, slowed the growth of tumors—but in the prelude to World War II, their discovery was classified as highly secret by the War Department, which did not want the enemy to be aware of their work.

As Lindskog looked at J.D., he had an idea: Take the work that Goodman, Gilman, and their colleague Thomas Dougherty Ph.D., had done on rabbits andmice and apply it to this man.

At grand rounds on June 30, the last day of the School of Medicine’s bicentennial, Robert Udelsman, M.D., M.B.A., chair and William H. Carmalt Professor of Surgery; and John E. Fenn, M.D., clinical professor of surgery, described how they discovered J.D.'s identity; and how a team of nurses, medical students, and pharmacists administered nitrogen mustard to treat what was likely an aggressive case of large B-cell lymphoma.

J.D. was mentioned in the literature only once, in a 1946 issue of JAMA: The Journal of the American Medical Association, which described his case and treatment in spotty fashion based on recollections. The article misdated J.D.’s treatment and contained few biographical details. Two years ago, Fenn and Udelsman decided that J.D.’s whole story should be told.

Fenn and Udelsman described their hunt for J.D.’s medical records, which would not only document the novel treatment but also prove that Yale doctors sought patient approval before administering chemotherapy. A mix-up of the medical records numbering system stalled their search. When Fenn found a record, complete with detailed drawings of lymph nodes and a medical narrative that fit the pioneer patient, he sent a one-word e-mail to Udelsman that read “FOUND.”

Among their findings were pages from J.D.’s chart, and the dosage of “substance X,” the code name for nitrogen mustard. J.D. began receiving daily injections on August 27, 1942. The formula for the dosage was based on a rough calculation that scaled the rabbit’s weight up to J.D.’s size. A month later, his cancer was gone. His tumors had shrunk, he could eat and move his head, and the edema that had marred his face had disappeared. But the medical chart shows that his white blood cells had been obliterated weeks later. By December he was dead—but modern medicaloncology was born. Until then, cancer had been treated exclusively by surgeons.

Fenn and Udelsman wrote about their discovery of J.D.'s medical chart in the March 2011 issue of the Journal of the American College of Surgeons. J.D.’s story touched both doctors, as did the care and attention provided to the patient by the entire staff of doctors, nurses, and students. A Yale medical student, according to Fenn, providedthe most thorough and complete patient history notes in the entire medical record.

“Everyone in this room shares the legacy of this story,” said Udelsman. “It happened here.”

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