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Nervous about “nerve agents”

When it comes to synthesizing novel chemicals, human ingenuity seems boundless, ranging from developing medicines that save lives to nerve agents that destroy them.

It was back in 1939, that German chemist Gerhard Schrader was searching for better methods to control insects when he chanced upon a substance that had greater insecticidal activity than anything he had ever seen. He named the new compound "tabun" and envisioned a breakthrough for agriculture. Hitler, however, had something else in mind for the newly developed substance. If it could kill pests, it could also kill people. A terrible new weapon was born.

Tabun was actually a colourless, odourless, relatively volatile liquid. Exposure to a few milligrams was enough to cause death. It penetrated through intact skin without any irritating effect so that a fatal dose could be absorbed with no warning. The term "nerve gas" was used to describe the substance because of its mechanism of action. The chemical interferes with the way information is transmitted from one nerve cell to another. Such transmission involves the release of chemicals called neurotransmitters from a nerve ending followed by the migration of this substance across the tiny gap separating nerve cells, known as the synapse. The neurotransmitter then stimulates an adjacent cell by fitting into a "receptor site" on its surface, very much as a key fits into a lock. This cell then releases a neurotransmitter which stimulates the next cell, and thus the message is propagated. The specific neurotransmitter involved in the nerve gas story is acetylcholine.

Once acetylcholine has carried out its job of triggering a reaction in an adjacent cell, it is decomposed by an enzyme present in the synapse. Overstimulation is therefore prevented.  It is this enzyme, acetylcholinesterase, that is inactivated by nerve gases. The result is overstimulation of the nervous system, eventually leading to convulsions, paralysis and respiratory failure. The first symptoms of exposure generally include constriction of the pupils, dimming of vision, vomiting, sweating, defecation, release of secretions from the nose, eyes, mouth and lungs and twitching of muscles. Inhalation of the gas causes death within minutes but the effects of liquid exposure may be delayed as much as 18 hours.

By the end of the second World War, the Germans had developed sarin, a nerve gas far more potent than tabun. Then everyone else got into the picture, including the Americans and the Soviets, both of whom began to research even more efficient ways to inflict casualties. It was in the 1960s, at the height of the Cold War, that the Soviets came up with the “Novichok agents,” modeled on the German nerve gases. The name means “newcomer” in Russian and this class of chemicals were indeed designed to have new features. Hope was for a novel agent that could negate the effectiveness of NATO protective clothing and would be undetectable by standard testing reagents.

Novichoks had another “advantage.” They were fine powders, making for easier dispersion and for targeting individuals. Any powder released in front of a victim’s face would be readily inhaled. This could be accomplished in many ways including designing a package that would discharge the chemical when opened. Like sarin, these nerve agents are acetylcholinesterase inhibitors and affect the muscles that control breathing as well as the heart muscle. Now we are waiting to see if the criminal behind this poisoning is caught. If indeed it turns out to be the handiwork of Russian agents, the real criminal, someone in the Russian political hierarchy, will remain unscathed.


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