Unlikely connection between chemical warfare agents and modern chemotherapy

Modern chemotherapy can be traced back to military chemical agents

Medicine and armed conflict may seem unlikely bedfellows. Especially following the recent use of the nerve gas sarin in a chemical attack that killed 75 people, including 27 children, in Syria’s Idlib province.

Sarin is clear, colourless, tasteless and has no odour in its pure form. It is described as “a human-made chemical warfare agent” by the Centres for Disease Control and Prevention. Because sarin is odourless and tasteless it’s difficult for people to know when they have been exposed to it.

Classified as a nerve agent, sarin is similar to an organophosphate pesticide, albeit much more powerful.

Nerve agents cause their toxic effects by preventing the proper operation of an enzyme that acts as the body’s “off switch” for glands and muscles. Without an “off switch” the glands and muscles are constantly being stimulated. So instead of releasing some water into a dry eye, for example, the tear gland floods the eyes uncontrollably.


Symptoms of sarin poisoning include a runny nose, eye pain, drooling, excessive sweating, rapid breathing, coughing, increased urination and nausea.  More extreme exposure may lead to a loss of consciousness, paralysis, convulsions, respiratory failure and death.

Symptoms appear within a few seconds after exposure to the vapour form of sarin, and within a few minutes to hours after exposure to the liquid version.

The drugs pralidoxime and atropine work as antidotes for sarin, although Syrian doctors treating the recent victims reportedly had little supply of the former, the more effective treatment.

Deadly chemical

There is an unlikely connection between chemical warfare agents and modern chemotherapy. Mustard gas, first produced during the first World War, was a deadly chemical that killed some 10,000 Allied troops at Ypres,


, in 1917.

Yet it was after the second World War, when British research chemist Prof Alexander Haddow was working on compounds that could block the growth of tumours, that nitrogen mustard gas began a second and more benign life as a cancer treatment.

In 1948, Haddow published a ground-breaking piece of research in the journal Nature showing exactly which bits of the nitrogen mustard molecule were needed to kill cancer cells. He also discovered how to make the chemical less toxic, but with more potent cancer-killing activity.

Amazingly, the chemical structure Haddow published is only a few atoms away from the structure of the drug chlorambucil, which is still used to treat chronic lymphocytic leukaemia and another blood cancer called non-Hodgkin lymphoma (NHL). It has helped over 60 per cent of those with NHL to survive for at least 10 years.

Haddow’s research has also triggered the development of more chemotherapy treatments: cisplatin and carboplatin work in a similar way to the nitrogen mustards and are still in use today.

Writing in the Canadian Medical Association Journal this year, Dr Susan Smith of the University of Alberta noted the connection between chemical weapons and cancer treatment may seem surprising, even disturbing.

Wartime research

“However, for the physician-researchers and medical scientists at the time, it was the logical outcome of their wartime research on mustard gas. They learned about the medical effects from toxic exposures of servicemen, both the unintentional from a wartime disaster in Bari,


, and the intentional in the mustard gas experiments conducted at military and civilian facilities, including medical schools. Their interdisciplinary research produced an enormous amount of data on the health effects of mustard agents on animals and humans.”

Medical oncology, which seeks to control cancer through chemotherapy, originated in the science of war. It grew out of medical research for military benefits. Today governments need to support medical research for its own sake, and not to serve other agendas. As the history of chemotherapy reminds us, it was science, not war, that was good for medicine.

And despite decades of evolution away from the trenches of the first World War, undergoing chemotherapy remains a challenging experience for some.