Nitrogen Mustard Chemotherapy

The lead came from poison gas. Gases used in the First World War caused 1,205,655 non-fatal casualties and 91,198 deaths, and in 1919 Edward Krumbhaar, who had treated exposed soldiers at a hospital in France, reported what mustard gas did to their blood and bone marrow, including a fall in white cells.

When war came again, the US Office of Scientific Research and Development contracted with Yale School of Medicine to study the gases and possible antidotes. The pharmacologist Alfred Gilman and the physician and pharmacologist Louis Goodman gave nitrogen mustard to rabbits and saw their lymphocytes and granulocytes fall. That suggested a use against cancers of lymphoid tissue. With the anatomist Thomas Dougherty they treated mice carrying transplanted lymphomas; the tumors shrank and the mice lived longer. They took the results to Gustaf Lindskog, then an assistant professor of surgery at Yale.

The patient, known in the records only as JD, was an immigrant who worked in a ball bearing factory in Connecticut. His illness began in August 1940 with an enlarged tonsil and pain under the jaw, and was diagnosed as lymphosarcoma. Surgery and repeated radiation failed, and by August 1942 he had trouble breathing and swallowing and was losing weight. At 10 a.m. on 27 August 1942 he received 0.1 mg per kilogram of what the chart called a synthetic lymphocidal chemical, the first of 10 daily intravenous doses. His tumors regressed.

The response did not last. His white cell and platelet counts fell, his gums bled and he needed transfusions, and by day 49 the tumors had returned. Further courses helped only briefly, and he died on 1 December 1942, 96 days after the first dose. The work stayed secret during the war. In 1946 Goodman, Wintrobe and colleagues reported nitrogen mustard treatment of Hodgkin's disease, lymphosarcoma and leukemia in JAMA. JD's chart was found in an off-site storage facility in May 2010, and his story was first told at Yale in January 2011.