Chemotherapy

Chemotherapy emerged because World War II forced scientists to study chemical weapons—and in doing so, they discovered that the same agents that killed soldiers could kill cancer cells. The transformation of mustard gas from weapon to medicine remains one of medicine's darkest origin stories.

During World War I, mustard gas proved devastatingly effective at destroying rapidly dividing cells in victims' bone marrow and lymphatic systems. The soldiers who survived showed profound suppression of white blood cell production. This observation lingered in medical literature, a grim data point waiting for interpretation.

In 1942, with World War II raging and fears of chemical warfare mounting, Yale School of Medicine's Dean Milton Winternitz signed a secret contract with the Office of Scientific Research and Development. Two young pharmacologists, Louis Goodman and Alfred Gilman, were assigned to study nitrogen mustard—a more stable derivative of sulfur mustard, coded as 'substance X' for secrecy.

Goodman and Gilman made the conceptual leap: if mustard compounds destroyed rapidly dividing cells, they might destroy cancer cells too—tumors being among the fastest-dividing tissues in the body. They consulted Thomas Dougherty, a Yale anatomist who provided them with mice transplanted with lymphosarcoma. When treated with nitrogen mustard, the tumors softened and shrank. After multiple doses, the tumors disappeared entirely.

At 10 a.m. on August 27, 1942, a patient known only as 'J.D.' received the first recorded dose of cancer chemotherapy: 0.1 mg/kg of synthetic lymphocidal chemical. J.D. had advanced lymphoma so severe he could barely swallow or move his head. After ten daily intravenous injections, with symptomatic improvement noted after the fifth treatment, biopsy revealed no tumor tissue. He could eat and move freely again.

The remission didn't last. J.D. relapsed, and subsequent treatments proved less effective. But the principle was established: chemicals could treat cancer. The research remained classified as a military secret until 1946.

Reinforcement came from an unexpected direction. On December 2, 1943, German bombers attacked the Italian port of Bari. Among the ships destroyed was the USS John Harvey, secretly carrying 2,000 chemical bombs containing 60-70 pounds of sulfur mustard each. Dr. Stewart Alexander, investigating the strange deaths among survivors, noted that victims showed profound lymphoid and myeloid suppression. His classified report theorized that mustard gas might suppress cancerous cell division—the same conclusion Goodman and Gilman had reached independently.

Goodman and Gilman published their results in the Journal of the American Medical Association on September 21, 1946. They were immediately hailed as pioneers of cancer chemotherapy. Nitrogen mustard was incorporated into multidrug chemotherapy for Hodgkin's disease and remains part of the anticancer arsenal today. The weapon designed to kill through cell destruction had been repurposed to kill the cells that were killing patients—a transformation from poison to medicine that required only a change in target.