US Air Force officers administer a nerve agent autoinjector during a readiness exercise.{credit}US Air Force photo/Staff Sgt. Chrissy FitzGerald{/credit}

In the early hours of 21 August, doctors in Damascus area hospitals scrambled—often in vain—to save the lives of Syrian civilians brought to the hospital with foaming mouths and convulsions. Today, a report released by a United Nations inspection team confirms, as many have suspected, that the chemical weapon used in the attack was the deadly nerve gas sarin.

There are medical countermeasures proven to help counteract the poisoning of sarin and other organophosphate-based nerve agents such as soman and VX—some of which were available last month to Syrian victims. But “they have their limitations,” notes David Jett, director of the Countermeasures Against Chemical Threats (CounterACT) program at the US National Institutes of Health (NIH) in Bethesda, Maryland. Certain drug therapies don’t enter the brain well and none offers protection from the long-term effects of sarin exposure. So scientists have ratcheted up their efforts to improve the arsenal of antidotes against this particular chemical weapon and its lasting impact on the nervous system.

Sarin proves so fatal because it inhibits an enzyme called acetylcholinesterase (AChE). This enzyme normally degrades the neurotransmitter acetylcholine, a key signaling molecule that has numerous functions in the body, including facilitating cognitive function and triggering muscle contraction. Without functioning AChE, muscle fibers twitch uncontrollably and neurons in the brain become hyperactive, leading to seizures. If untreated, people exposed to sarin typically die of asphyxiation, as the muscles involved with breathing proceed to fire nonstop.

More than 1,400 people, including an estimated 426 children, died in the August gas attack, according to US intelligence estimates. Syrian doctors had only limited amounts of antidotes against the nerve gas, according to Sawsan Jabri, a trained physician who teaches biology courses at Oakland Community College in Eastern Michigan and serves as a spokeswoman for the US-based Syrian Expatriates Organization. She says that medical staff around Damascus (with whom she is in contact) had a total of some 50,000 ampoules of atropine, a drug that blocks the receptor responsible for binding acetylcholine, thereby preventing nerve and muscle cells from responding to the neurotransmitter. She adds that they also had “very limited amounts” of both pralidoxime (2-PAM)—a compound that reactivates sarin-inhibited AChE—and the anti-anxiety drug diazepam (better known as Valium), which prevents and treats seizures.

These three medicines—atropine, 2-PAM and diazepam—together constitute the ‘gold standard’ of anti-sarin therapies. As a matter of precaution, US military personnel are equipped with kits that contain spring-loaded syringes full of these antidotes, known as autoinjectors, which allow them to self-administer drugs through the muscle soon after, or better yet, before a chemical attack. But the therapeutic window is small, and prophylactic treatment is typically only feasible for military personnel, not civilians. So government defense agencies have long sought more robust and widely applicable alternatives to limit the death toll and mitigate permanent disability among survivors.

“There is a very vibrant research and development program in this area,” Jett says. He notes that the US government has been funding work in this area since “long before the chemical attacks in Syria, and even before the civilian attacks in Tokyo,” referring to the domestic terrorist attack on the Tokyo subway system in 1995, one of the first-ever uses of sarin as a chemical weapon. “We’re on this.”

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