nitrogen mustard as a cancer chemotherapy agent (Gilman, 1946, 1963; Gilman and Philips, 1946; Rhoads, 1947).
Although the concept of chemotherapy does not seem radical today, in 1942 the idea of injecting poisons into cancer patients, especially poisons marked ''compound X" due to their classified status, would have been viewed by most physicians as "the act of a charlatan" (Gilman, 1963). With the help of Gustav Lindskog however, clinical trials were begun in December 1942 with a patient dying of lymphosar-coma for whom all other treatments had failed. The patient's tumors regressed, the outlook brightened, and another patient was begun on the nitrogen mustard therapy. In all, six patients made up this first trial. However, as had happened in the animal studies, the tumors reappeared as the bone marrow recovered, and no long-lasting cure was attained. The challenge remained to establish the regimen of therapy that would kill the cancer cells completely, yet preserve enough of the bone marrow to regenerate needed healthy cells. In addition, there was no reason to assume that all types of cancer cells would be equally affected by nitrogen mustard therapy.
The Yale group dispersed in June 1943, but clinical trials with nitrogen mustard continued in several other locations. By 1948, close to 150 patients in the terminal stages of Hodgkin's disease, lymphosarcoma, or certain leukemias had been treated with this agent (Gilman and Cattell, 1948). The best results were obtained in cases of Hodgkin's disease. Derivatives of nitrogen mustard (hydrochloride forms) are still used today, particularly for treatment of lymphoma, in a regimen that includes an array of other drugs and chemicals administered with the nitrogen mustard (see also Chapter 6).
The vast majority of the post-WWII research concerning mustard agents and Lewisite has been done in animal studies or in model systems, such as skin tissue culture. This research has been aimed toward the development of pretreatments to prevent mustard toxicity or toward improved treatments against acute poisoning. Emphasizing these issues, Papirmeister and colleagues reviewed the literature on sulfur mustard in 1991, including consideration of all such work published up to 1990. For the purposes of the present report, discussion is confined to only those research programs that used human subjects.
Once WWII was over, all of the research programs of the Chemical Warfare Service were scaled down. Very little research was done during