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The poisons were so fearsome that U.S. government scientists were forbidden from publicly uttering their name. Then, in 2018, one of the Novichok compounds was used in an attempt to assassinate a former Russian spy on U.K. soil—spurring the United States and allies to lift the veil of secrecy and mount a drive to outlaw the obscure class of nerve agents, concocted in a Soviet weapons lab during the height of the Cold War. Now, their effort to amend the Chemical Weapons Convention (CWC) is about to pay off.
On 9 October, the Executive Council of the Organisation for the Prohibition of Chemical Weapons (OPCW), the body that administers the treaty, reviewed a revised proposal from Russia that would bring Novichoks under the treaty’s verification regime, along with a class of potential weapons known as carbamates. If the Russian proposal and a similar one from the United States, Canada, and the Netherlands are approved at a treaty review meeting next month, as expected, they would be the first update to the list of banned chemical weapons since the CWC came into force in 1997. “This is a historic milestone for the treaty,” says Gregory Koblentz, a chemical and biological weapons expert at George Mason University in Fairfax, Virginia.
The newfound glasnost on Novichoks, also known as fourth-generation nerve agents, should spur research on their mechanism of action and on countermeasures and treatments. “Fourth-generation agents are now on the list of compounds we can study,” says David Jett, director of the Countermeasures Against Chemical Threats Program at the U.S. National Institutes of Health. The U.S. government limits work on Novichoks to a handful of defense labs, but academic researchers may now partner with these labs and conduct computer modeling or other studies that don’t require the chemicals. Such research, Jett hopes, will “provide more information on the toxicity of these threat agents.”
Like other nerve agents, the known Novichok agents bind to acetylcholinesterase, an enzyme that dismantles the neurotransmitter acetylcholine after it’s released into synapses. Without rapid medical intervention, the buildup of acetylcholine blocks brain signals from reaching muscles that control respiration and maintain blood pressure. Distinctive chemical groups jutting from the Novichok molecules may allow them to bind to other enzymes—and perhaps trigger a long-lasting syndrome in victims who survive an attack.
Chemical weapons experts had been whispering about Novichoks for decades. The first public clues came from Vil Mirzayanov, a Soviet military chemist who divulged the Novichok program in 1992. In a 2008 memoir, he revealed details about the chemicals’ structures and claimed that some Novichok agents are several times more toxic than VX, the deadliest known nerve agent developed for warfare, which North Korean operatives used to assassinate Kim Jong-un’s half-brother at the Kuala Lumpur airport in 2017. However, Mirzayanov did not publish toxicity data on A-234, the compound believed to have been used in last year’s U.K. attack. A modeling study published in February in Royal Society Open Science by Ponnadurai Ramasami, a chemist at the University of Mauritius in Moka, and colleagues suggests that A-234 may not be more potent than VX.
Treaty nations have long resisted adding Novichoks to the CWC’s so-called Schedule 1 list of chemical weapons, which compels signatories to declare and destroy any stockpiles. “People were worried about a Pandora’s box,” fearing such a listing would force them to regulate ingredients of the weapons, Koblentz says. That could hamper the chemical industry and might clue in enemies on how to cook them up. (Who has the agents now is anyone’s guess.) Indeed, the U.S. government for years classified the Novichok agents as top secret. “There was a desire among Western countries to keep the information as limited as possible to avoid proliferation issues,” Koblentz says.
Last year’s assassination attempt against former Russian spy Sergei Skripal in Salisbury, U.K., thrust the Novichok agents into the spotlight. The botched attack gravely sickened Skripal, his daughter Yulia, two police officers who investigated the crime scene, and a couple—Charlie Rowley and Dawn Sturgess—who a few months later happened on a perfume bottle containing the agent. After long hospitalizations, the Skripals, the officers, and Rowley recovered; Sturgess died. The United Kingdom charged two Russian men, reportedly military intelligence officers, as the alleged assailants, and obtained a European warrant for their arrest; they remain at large in Russia.
Now, Novichok agents are shaping up as a potential area of comity. The Canadian-Dutch-U.S. proposal targets two broad groups of Novichoks, one of which includes A-234. The Russian proposal covers the same compounds and adds a third group of Novichoks and two families of carbamates. The United States studied carbamates, which also inhibit acetlycholinesterase, as potential weapons during the Cold War; some carbamates are reportedly twice as toxic as VX, note Koblentz and Stefano Costanzi, a nonproliferation expert at American University in Washington, D.C., in a review in the current issue of The Nonproliferation Review. (There are many less toxic carbamates as well, some of them in use as insecticides or drugs.)
Russia initially opposed the three-nation proposal to bring the Novichoks under the CWC, arguing it was scientifically “substandard” and politically motivated. But after months of wrangling, the sides have resolved their differences. In a sign of the new openness, the U.S. Department of Commerce in August published a description of both the Novichok agents and the carbamates that the two proposals would cover in the Federal Register—including structural information.
If nations approve the Schedule 1 listings next month, CWC negotiators could then choose to puzzle out which precursor ingredients to cite on other treaty schedules. “It’s complicated,” Costanzi says. “There could be many precursors, and it will be difficult to find an optimal solution that minimizes the risk of chemical proliferation without hindering legitimate industrial uses or revealing synthetic pathways for the preparation of Novichoks.” But that task will be well worth the trouble. “It’s not like Novichoks are relics of the past,” Koblentz says. “These are weapons that are still killing people.”
Other agenda items at next month’s treaty meeting are far more contentious. Russia and Syria are expected to denounce the work of an OPCW panel tracing the origins of chemical weapons used in Syria’s civil war and identifying the parties that used them. And Russia and its allies are likely to continue to resist efforts to eliminate a treaty provision permitting use of aerosolized incapacitants for domestic law enforcement. Russia exploited that loophole in 2002, when it pumped two powerful opioids, remifentanil and carfentanil, into a theater in Moscow to subdue armed terrorists—killing scores of hostages along with the terrorists.
Source: Science Mag