History of cancer chemotherapy

The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply. The beginnings of the modern era of cancer chemotherapy can be traced directly to the German introduction of chemical warfare during World War I. Among the chemical agents used, mustard gas was particularly devastating. Although banned by the Geneva Protocol in 1925, the advent of World War II caused concerns over the possible re-introduction of chemical warfare. Such concerns led to the discovery of nitrogen mustard, a chemical warfare agent, as an effective treatment for cancer. Two pharmacologists from the Yale School of Medicine, Louis S. Goodman and Alfred Gilman, were recruited by the US Department of Defense to investigate potential therapeutic applications of chemical warfare agents. Goodman and Gilman observed that mustard gas was too volatile an agent to be suitable for laboratory experiments. They exchanged a nitrogen molecule for sulfur and had a more stable compound in nitrogen mustard. A year into the start of their research, a German air raid in Bari, Italy led to the exposure of more than 1000 people to the SS John Harvey's secret cargo composed of mustard gas bombs. Dr. Stewart Francis Alexander, a lieutenant colonel who was an expert in chemical warfare, was subsequently deployed to investigate the aftermath. Autopsies of the victims suggested that profound lymphoid and myeloid suppression had occurred after exposure. In his report, Dr. Alexander theorized that since mustard gas all but ceased the division of certain types of somatic cells whose nature was to divide fast, it could also potentially be put to use in helping to suppress the division of certain types of cancerous cells. Using that information, Goodman and Gilman reasoned that this agent could be used to treat lymphoma, a tumor of lymphoid cells.