Methods of Treatment:
Alkylating Agents: The Janus Effect

Cornelius P. Rhoads

In looking back across the history of the chemical causes and cures of cancer, some scientists have compared these chemical substances to an ancient Roman god called Janus. Janus was a deity associated with beginnings, and symbolically with doorways and arches. His most distinguishing characteristic was the two faces attached to his single head. His faces pointed in opposite directions, one looking ahead and the other looking behind. Like Janus' dual nature, chemical substances—like those used to cure diseases such as cancer—are capable both of great destruction and of great healing. One of the most striking examples of this dual nature of chemical compounds is the story of mustard gas and Dr. Cornelius Packard Rhoads.

During World War II, Rhoads was stationed at the southeastern Italian seaport of Bari. Allied ships were using the port of Bari to make deliveries of supplies and munitions. On the night of December 3, 1943, German bombers raided the harbor and sixteen ships were sunk. Among them was the ship Liberty, that had been carrying explosives as well as a top-secret cargo of 100 tons of mustard gas. The mustard gas, a poisonous gas used as a weapon during World War I, had been loaded into warheads of airplane bombs, ready for use. Later, officials claimed that they were intended only for defensive purposes.

Rhoads treated many of the more than 600 survivors of the Liberty attack. Survivors had been pulled from the bay with stinging eyes, burns on their skin, and a host of internal problems. Many had reported the smell of garlic immediately after the attack. Rhoads noticed a dramatic drop in the number of white blood cells in the survivors and that other tissue was seemingly unaffected. It was at this point that Rhoads posed the possible connection between ingredients of the poisonous gas and cancers, especially leukemia. If these “nitrogen mustards,” specifically mechlorethamine hydrochloride, could destroy white blood cells in the survivors of the Liberty, then these same compounds might be used to treat cancer.

At the same time, many other scientists were realizing that cancer could be treated chemically. For example, two pharmacologists from Yale University—Louis Goodman and Alfred Gilman—found that the nitrogen mustards affect rapidly dividing cells. From their work, researchers developed the drug mechlorethamine, that is still used today to treat leukemia. Work in Russia and England also produced new anti-cancer compounds.

mechlorethamine