Chemotherapy: From the Trenches of Warfare A Weapon to Fight Cancer

When medical researchers noticed that mustard gas destroyed lymphatic tissue and bone marrow after World War I, they thought it might also be able to kill cancer cells in the lymph nodes. Experiments in mice later showed that topically applying nitrogen mustard, which was derived from mustard gas, caused tumors to shrink. No further progress was made, however, until 1942. The United States had just entered World War II and, fearing that nitrogen mustard might again be used in battle, the government's Office of Scientific Research and Development asked institutions around the country to study chemical warfare agents.

Among these was Yale, where two young assistant professors in Yale's new Department of Pharmacology, Louis S. Goodman, MD and Alfred Gilman, PhD, began to study the effects of nitrogen mustard on lymphoma. Early studies in mice showed dramatic regression of the disease, which was confirmed in further studies in rabbits. The next step was a clinical trial. The first patient in the world to be treated by chemotherapy was a 48-year-old man in the terminal stages of lymphosarcoma. Radiation no longer had any effect on his tumors and he had run out of treatment options. He was given 10 doses of nitrogen mustard at a dosage that was roughly 2.5 times what became the standard, because nobody had any idea how much to give him. Within two days, doctors noticed that his tumors were softer and by the end of treatment, they had disappeared.

Although he relapsed a short time later and subsequent courses of treatment were less effective, scientists had proof that chemicals could treat cancer. Further clinical trials followed at Yale and around the country, but the results – including the results of the first trial – remained a military secret until 1946, when they were published in The Journal of the American Medical Association.

Thanks to the patients who were willing to undergo an experimental treatment, nitrogen mustard was incorporated into multidrug chemotherapy for Hodgkin's disease and remains a potent agent against cancer today. It has also paved the way for similar chemotherapeutic agents that attack cancer cells.