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Tessa Fiorini Cohen
Tessa Fiorini Cohen

On April 22nd, 1915, Allied troops crouched in battlefield trenches in Ypres, Belgium. As a cloud of greenish smoke started drifting down towards them from the Axis frontline, they assumed it masked a German advance. An order was given to line the trenches and the soldiers prepared their rifles, readying to fire through the smoke. They had no idea what actually lay in store.

Soon they were flailing about, blinded and choking for air. The smoke was chlorine gas, which formed acid on reaction with water in their lungs and eyes; destroying both organs. The soldiers literally drowned on dry land. Ypres marked the first time that poison gas was used in World War I and the start of a chemical arms race to develop more. The most feared of these was soon mustard gas, as it could penetrate through protective clothing, leaving no chance of escape. Mustard gas worked more slowly and quite differently to chlorine; it bound irreversibly to DNA and proteins, killing cells and causing disfiguring burns and breathing problems. Effects continued to worsen after exposure, with some victims taking agonizing weeks to die.

After World War I, the use of poison gas in war was banned by the Geneva Protocol, but no such ban was enforced on its development or stockpiling. So, with the advent of World War II, research programs were instigated on both sides in preparation for retaliation. As mustard gas stockpiles were being created as armaments, two researchers at Yale focused on a wholly different use for the poison; anticancer therapy.

alfred louis

Alfred Gilman and Louis Goodman were originally searching for antidotes to mustard gas poisoning. But they were inspired by medical notes written on the battlefields of World War I, which showed that the chemical markedly decreased white blood cell counts. If they could get it to do the same to cancerous white blood cells, patients with lymphoma might stand a chance of survival. Animal trials were initiated, followed by the first human trial in a patient known only as JD in 1942. The trial showed promise; JD’s tumor shrunk considerably but treatment had to be stopped due to the drug’s harsh side effects. He died soon afterwards.

As part of wartime research, the trial was shrouded in secrecy – JD’s medical records only documented treatment with ‘substance X’. But a military disaster in Bari in 1943 soon brought worldwide attention to mustard gas’ anti-lymphoma capabilities. An American ship carrying a two thousand bomb stockpile of the gas was docked in Bari’s port when German forces attacked. The ship exploded and sixteen neighboring vessels sunk. Hundreds of survivors swam to shore in a sea contaminated with mustard gas.

Their exposure was different to the usual World War I experience. Instead of breathing in a highly concentrated, short burst, they were exposed to diluted amounts for a prolonged period of time. The symptoms that soon started appearing were a mystery as the ship’s cargo was a closely guarded secret that died with its crew. Pathologists were flown in to investigate and soon diagnosed mustard gas. Victims were thoroughly studied and a profound decrease in their white blood cells was noted.

After the war ended, the veil of secrecy was lifted off JD’s trial. Coupled with observations noted in Bari, the great potential of mustard gas was evident. Up till then cancer had only been treated through surgery or radiotherapy.

Mustard gas gave rise to the field of chemotherapy.

Studies homed in on the exact part of the molecule that affected white blood cells, which allowed similar molecules with less harsh side effects to be designed. A new poison race was on, which continues to this day; killing the cancer before killing its host. The first drug thus developed was mustine and related drugs are now used to treat a variety of cancers.

Chlorine, the mother of all poison gases, has had its own rehabilitation. The gas is now used to disinfect drinking water and wastewater around the world, removing life-threatening waterborne diseases. The American Water Works Association credits it with increasing life expectancy by half over the last century. Quite a turn for a gas which claimed over a thousand lives in its first outing at Ypres.