How to defeat a nerve agent

Even 3 decades later, Seyed Naser Emadi's first encounter with nerve agents haunts him. In 1987, as a soldier fighting for Iran in its war with Iraq, he came across a hillside strewn with comrades killed by an Iraqi nerve agent, perhaps tabun or sarin. Unable to breathe, the victims had clawed at their necks to try to open a hole in their throats, recalls Emadi, now a dermatologist in Tehran. In fact, their windpipes were clear; the nerve agent had shut down control of breathing in the central nervous system. They "had no choice except death," he says.

The long-term effects of nerve agents remain uncertain, but with the right antidotes, these poisons need not be an immediate death sentence. A few years after Emadi's experience, U.S. soldiers in 1991's Gulf War carried autoinjectors filled with drugs that—in principle—would keep them breathing and protect them from seizures if Iraqi forces again unleashed nerve agents. They never did, most historians agree, but the threat remains real today, as chemical attacks in Syria's ongoing civil war make clear. It is spurring urgent efforts to find better countermeasures, with several promising compounds in the pipeline.

First synthesized by German chemists on the eve of World War II, nerve agents kill by binding to acetylcholinesterase (AChE), an enzyme that dismantles the neurotransmitter acetylcholine when it is released into synapses. One of the most efficient enzymes known, a single AChE molecule can hydrolyze 600,000 acetylcholine molecules per minute, says Palmer Taylor, a pharmacologist at the University of California, San Diego.

Nerve agents slot right into AChE's active center, a narrow gorge. Once one nestles there and forms a covalent bond with a serine group, AChE "can't spit it out," says James Madsen of the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD) in Edgewood, Maryland. As acetylcholine builds up in the synapses, victims may develop chorea and dance ghoulishly before collapsing and writhing in seizures. Without medical intervention, the brain stops sending signals to the muscles that control respiration and maintain blood pressure: Victims drift into a coma and will probably stop breathing. Milligram amounts of nerve agents are enough to kill.

A deadly grasp Nerve agents bind to acetylcholinesterase (AChE), an enzyme that controls levels of the neurotrans-mitter acetylcholine. Each agent's “aging time,” listed here, indicates how long it takes for the bond to become irreversible. Taking an AChE-blocking drug before exposure ups the odds of surviving soman and its lightning- fast aging time. Leaving groupMolecular fragment detaches during aging. SOMAN2minutes A German chemist discovered tabun's lethality in humans by accident in 1936. The first nerve agent saw extensive use during the Iran-Iraq War. Responders would have a brief window after exposure to treat sarin victims with oxime, which pries the nerve agent off AChE before aging is complete. TABUN46hours SARIN5hours Reputedly short for “venomous agent X,” VX is the most toxic nerve agent: Several milligrams absorbed through the skin is a lethal dose. VX36.5hours C H N F O P S