On Aug. 27, 1942, Yale physicians administered the world’s first intravenous chemotherapy to a patient with advanced lymphoma. J.D. became the first person in the world to receive intravenous chemotherapy.

During World War II, naval personnel who were exposed to mustard gas during military action were found to have toxic changes in the bone marrow cells that develop into blood cells. During that same period, the US Army was studying a number of chemicals related to mustard gas to develop more effective agents for war and also develop protective measures.

The origins of chemotherapy can be traced to World War I. Physicians treating soldiers exposed to mustard gas observed that the chemical severely damaged bone marrow and lymphatic tissue. White blood cell counts dropped sharply, and lymph nodes shrank.

Those effects were devastating in war—but they suggested a scientific possibility. If mustard compounds destroyed rapidly dividing white blood cells, might a related compound also affect cancers of the lymphatic system?

In the early 1940s, after the United States entered World War II, the federal government launched a classified program to study chemical warfare agents. At Yale School of Medicine, pharmacologists Louis S. Goodman, MD, and Alfred Gilman, PhD, were assigned to investigate sulfur and nitrogen mustards. In laboratory studies, nitrogen mustard caused lymphoma tumors in mice and rabbits to shrink dramatically. Because the research was classified, the compound was referred to only as “Substance X.” But its potential was becoming clear.

Working with surgeon Gustaf Lindskog, MD, the team identified a patient with advanced lymphosarcoma (a cancer of the lymph nodes) who had exhausted all available treatments. The patient—a 47-year-old factory worker from Meriden, Connecticut known only as “J.D.”—had tumors so extensive he could barely move his head. Radiation had failed. Understanding the risks, he agreed to receive the experimental drug.

Shortly after the discovery of nitrogen mustard, Sidney Farber in Boston demonstrated that aminopterin, a compound related to the vitamin folic acid, produced remissions in children with acute leukemia. That drug was the predecessor of methotrexate, a cancer treatment drug used commonly today. The era of chemotherapy had begun.