1943

Bari Raid

Louis Sanford Goodman (1906–2000), Alfred Gilman Sr. (1908–1984), Stewart Francis Alexander (1914–1991)

Chemotherapy, in its classic form, is an easy concept to understand. Cancer cells divide more quickly than normal ones, so if you can find something that kills cells when they divide, you’ll have an anticancer agent. That’s a crude summary of the process, but the idea can be an effective one.

Its origins are even cruder. In 1943, a German air raid on the southern Italian port of Bari had the inadvertent and hideous side effect of releasing large quantities of mustard gas. This chemical warfare agent was (in theory) banned by international treaty, but the Allies wanted to have it on hand as a countermeasure in case Germany deployed a chemical weapon of its own. The U.S. cargo ship S.S. John Harvey, destroyed in the raid, was secretly carrying mustard gas bombs, and treatment of the victims of the raid was severely impaired because no one was told that the chemical could have been involved. In the aftermath of the bombing, the Army sent Lieutenant Colonel Stewart Francis Alexander, a doctor specializing in chemical warfare, to investigate its effects on the victims. He noted that they showed signs of having had populations of fast-dividing cells in their bodies selectively destroyed and proposed that this might be used as a type of cancer therapy.

Pharmacologists Louis Sanford Goodman and Alfred Gilman Sr. were already working for the military, investigating possible medical applications of such chemical warfare agents, and they quickly took up Alexander’s suggestion. Analogs of mustard gas with a nitrogen, instead of a sulfur, atom in the center turned out to shrink lymphomas in both mice and humans, which was the first evidence that there could be such a thing as a drug against cancer. Oncology has always been an any-weapon-to-hand endeavor, and “nitrogen mustards” are still used today in some cases, prolonging lives in a strange echo of two world wars.

An ammunition ship explodes in the harbor of Bari, Italy, in this photo from a German news agency, 1943.