August 27: “Substance X” Leads To the Nation’s First Chemotherapy Treatment


Today in 1942, physicians at Yale University made medical history as they administered the first use of intravenous chemotherapy as a cancer treatment in the United States. This medical milestone was the culmination of top-secret experiments aimed at defending against the horrors of mustard gas that a handful of Yale doctors conducted for the U.S. military during World War I and World War II.

In doing their research on mice, scientists realized the mustard gas that had been so devastating in World War I had cytotoxic –- that is, cell-destroying -– effects that could make it a powerful anti-cancer therapy, especially for patients with cancers involving the lymph nodes.

For security reasons and to avoid bad publicity they were not allowed to use words like “mustard gas” when talking about their work, so these experimental drugs were disguised in letters and medical records with vague names like “substance X.”

What they needed was a way to find out if these drugs–– which had at that point only been tested on rabbits – would work for human patients.

New Haven Hospital .jpg
1937 Postcard of Yale New Haven Hospital. (Harvey Cushing/John Hay Whitney Medical Library)

In 1941, a patient known to history only as “J.D.” was admitted to Yale Medical Center in New Haven with a severe case of lymphosarcoma and began undergoing standard cancer treatments, which then consisted of surgical removal and radiation therapy. While the patient initially showed signs of improvement, the cancer quickly staged an aggressive comeback. When J.D. was readmitted in August of the following year, he could barely move his head owing to the size of his tumors.

With a grim prognosis, the 47-year-old J.D. agreed to undergo a new, experimental treatment, that would test the Yale researchers’ new chemical therapy.

On August 27, 1942, Yale physicians began the first chemotherapy regimen for a cancer patient in the United States. J.D. received ten injections of the “lymphocidal chemical” derived from mustard gas, and by the end of the month, he told his doctors that he felt cautiously better –– he had been able to sleep more than usual, and even eat a little. His cancer soon returned, however, and though the chemotherapy treatments helped extend his life by almost three months, J.D. died in December 1942.

Because his medical records were made anonymous and the drugs he was treated with were labeled with vague nicknames, no one knew much about J.D. and his role in creating modern cancer science for years. But in 2011, Yale doctors John Fenn and Robert Udelsman located his chart and uncovered new details about both J.D. and his treatment. An unmarried man in his late forties at the time of treatment, J.D. was born in 1894 in Poland, and immigrated to the United States when he was 18. He settled in Meriden, and worked at a ball bearing factory from 1924 until he became sick in 1940.

“It was all there,” said Fenn, clinical professor of surgery at Yale School of Medicine. “In one patient, there was the revelation that cancer would respond to chemical injections, and that chemotherapy also had potentially lethal implications in the depression of bone marrow.”

Today, chemotherapy is one of the most universally-prescribed treatments for cancer around the world. A life-saving breakthrough that led to the birth of modern medical oncology, hidden under a cloud of secrecy for decades, took place in New Haven today in Connecticut history.

Further Reading

Helen Dodson, “Setting the Record Straight: The Birth of Chemotherapy at Yale,” Yale University News

Panos Christakis, “The Birth of Chemotherapy at Yale [Introduction],” Yale Journal of Biology and Medicine

History and Heritage: Milestones,” Yale-New Haven Hospital