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Russian opposition politician Alexei Navalny fell ill on August 20 after drinking a cup of tea at a Siberian airport. The German government says he was poisoned with a Novichok.
Valeriy Melnikov / Sputnik via AP
By Richard Stone
On September 2, German Chancellor Angela Merkel revealed that Alexei Navalny, a Russian opposition politician, had been poisoned with a nerve agent “unequivocally identified in tests” as a Novichok, one of a family of exotic chemical weapons from the it was soviet. Merkel, a chemist by training, did not reveal the nature of the tests, carried out in a military laboratory in Munich. But scientists familiar with the Novichoks have a good idea how the toxicology detectives did it, and they are shocked at how quickly the culprit was unmasked.
Navalny fell ill on August 20 after drinking a cup of tea at a Siberian airport. He fell into a coma and was flown to Berlin two days later; In a statement yesterday, the hospital that treats him said that he is out of a coma and “responding to verbal stimuli.” Navalny supporters have accused Russian agents of pouring poison into tea, an accusation that seems credible in light of Russia’s recent record of using toxic substances to silence critics.
The Salisbury scandal brought Novichoks out of the shadows. After a Russian chemist in 1992 disclosed some details about exquisitely toxic nerve agents (there are at least seven of them), the US government and its allies stifled open discussion; The novichoks were classified as secrets. The blatant use of A234 in England led to a public reckoning. Last October, parties to the Chemical Weapons Convention agreed to add Novichoks to the treaty’s list of toxic chemicals, placing them under the convention’s verification regime and paving the way for investigation into the mechanism of action of these nerve agents from “Fourth generation”. as in countermeasures and treatments.
Diplomatic progress hardly deterred Navalny’s unknown attackers. As doctors in Berlin struggled to save him, scientists at the Bundeswehr Institute for Pharmacology and Toxicology in Munich set out to unravel the mysterious cause of his symptoms.
They had clear goals to pursue. Like other nerve agents, Novichoks bind to acetylcholinesterase (AChE), an enzyme that breaks down the neurotransmitter acetylcholine when it is released at synapses. Common symptoms of Novichok poisoning include nausea, shortness of breath, and seizures; without medical intervention, victims can go into a coma. Red blood cells have AChE anchored to their membranes, so a blood sample could produce a conjugate formed when a Novichok attaches to AChE, which scientists could detect using mass spectrometry, says Palmer Taylor, a pharmacologist at the University of California in San Diego (UCSD). ).
Another possibility is a Novichok conjugate of serum albumin, the most abundant protein in the blood. Conjugates of nerve agents with serum albumin “are very useful markers” that can be detected for at least a couple of weeks after poisoning, says Stefano Costanzi, a chemist and non-proliferation analyst at the American University in Washington, DC.
A third candidate is a butyrylcholinesterase (BChE) conjugate, an enzyme that removes nerve agent molecules from the bloodstream. It would be simple to use an anti-BChE antibody to adhere to the conjugate and then digest the protein. Most of the Novichok molecule would remain bound to one of the fragments and would be easy to detect using mass spectrometry, says Oksana Lockridge, a toxicologist at the University of Nebraska Medical Center. “I have no doubt that the Bundeswehr group used this method,” he says. “The part of the Novichok that remains attached to the enzyme is much larger than that of any other nerve agent,” says Zoran Radić, a UCSD chemist. Detection of such a conjugate would make the identification of a Novichok “100% safe,” says Lockridge, who is developing BChE as a prophylactic for exposure to nerve agents.
The Salisbury investigation presumably yielded detailed information on the Novichoks. UK authorities now “know much more about the toxicity, detection and general behavior of Novichoks,” says Kamil Kuča, a toxicologist at the University of Hradec Králové in the Czech Republic. “They could share their results with ‘friends,'” like Germany says. And chemical detective work by researchers at the UK defense lab Porton Down may have sped up the analyzes at the Munich lab, says Radić, by “providing an appropriate set of protocols to follow.”
Novichok’s structures are unique. Really different from other nerve agents.
It is also possible to directly detect the original compound, Novichok himself, in Navalny’s body. “One could easily assume that they accumulate in lipids,” says Radić. In an article earlier this year in the magazine Propeller, a team from the Biological Chemical Center of the US Army Combat Capabilities and Development Command showed that three Novichok compounds are much more stable than other nerve agents, the most durable, A234, being about a thousand times more stable. than the nerve agent sarin.
That stability may be a major factor in why the handful of known Novichok victims respond so poorly to treatment: It could take weeks for the lipids in fat cells to give up their Novichok stores. Another insidious characteristic of the Novichoks is their deadly control over AChE: they bind together and do not block one site in the active center, as other nerve agents do, but two. “Novichok structures are unique. Really different from other nerve agents, ”says Radić. For that reason, oximes, an antidote that separates nerve agents from AChE and leads to reactivation of the enzyme, may be much less effective against Novichoks than against classical nerve agents such as sarin. “There is no declassified information on reactivation” on Novichok’s victims, Radić says. One researcher says that pralidoxime, an antidote carried by US soldiers at risk of exposure to nerve agents, helped the Salisbury victims, but not by reactivating AChE.
Regardless of who perpetrated the attack on Navalny, the blatant incident and revelations about the durability of the Novichok raise concerns about the threat they pose. And although most nerve agents are stored in liquid form, some Novichoks are stable as an ultrafine powder. “They can be hidden and stored much more easily than classic nerve agents,” says Radić, who says that makes them more likely to end up on the black market.
