Chemotherapy's effectiveness against cancer was discovered from mustard gas, a lethal weapon used in the World War I trenches. Autopsy observations of soldiers exposed to the gas revealed destruction of lymphatic tissue and bone marrow. Scientists at the time reasoned that mustard gas might destroy cancer cells in lymph nodes, but nothing was done.
Early in 1942 Alfred Gilman (1908-1984) and Louis S. Goodman (1906-2000), two pharmacologists at Yale University, were recruited by the U.S. Department of Defense to investigate potential therapeutic applications of nitrogen mustard (a derivative of mustard gas) on lymphoma. After establishing lymphomas in mice and rabbits, they went on to show that they could treat them with mustard agents.
The- next step was to inject mustine (the prototype anticancer agent) into a patient with non-Hodgkin's lymphoma, whose cancer had become resistant to radiation. Initially the patient responded well, with doctors noting a softening of the tumor masses within two days, but unfortunately the beneficial effect lasted only a few weeks. In 1946 the government gave the team permission to publish the first paper on the use of nitrogen mustard in cancer treatment, providing the first "proof" that cancer could be treated by pharmacological agents.
Nitrogen mustard became a model for the discovery of further classes of chemotherapy, drugs that damage the cell control centers that make cells divide, thereby preventing further division. Chemotherapy gradually became a standard treatment for many cancers, often in combination with surgery and radiation, and nitrogen mustard was incorporated into today's multidrug chemotherapy for Hodgkin's disease.
