Sun. Oct 2nd, 2022
The Novichok agent A-234 molecule - a proposed structure.
enlarge The Novichok agent A-234 molecule – a proposed structure.

Molecule/Getty Images

According to the hospital treating him, Russian opposition leader Alexei Navalny is likely to survive a suspected poisoning with the nerve agent Novichok. At least six cases of serious Novichok poisoning have been reported in the past two years. But only one victim died tragically from it.

Why is that? Is the substance less deadly than previously thought? Or could it be that the nerve gas supply is degrading?

Nerve drugs were discovered through research on pesticides. They belong to a group of substances known as organophosphorus chemicals, or “OPs” for short. There are literally thousands of OP substances, many of which can damage the body by inhibiting a family of enzymes known as “cholinesterases” that are essential for regulating central nervous system activity in animals.

OP pesticides are much less toxic to humans than nerve agents because they are designed to specifically inhibit the cholinesterases of insects. In contrast, nerve agents target human cholinesterases.

By interfering with the nervous system, Novichok and other nerve agents can kill people through suffocation or cardiac arrest. We know they are deadly. The nerve agent Sarin caused several victims in 1995 when it was released on the Tokyo subway.

The nerve agent VX is said to have killed Kim Jong-nam, the half-brother of North Korean leader Kim Jong-un, in just 20 minutes after it was reportedly smeared over his face. But all types of nerve poisoning can be treated with standard antidotes such as atropine and diazepam.

Little is known about the types of Novichok synthesized or used in assassination attempts, except that they are usually liquids or powders.

The dose makes the poison

One of the fundamental principles of toxicology was first proposed by a 16th century alchemist known as Paracelsus, to whom the statement is often attributed:sola dose of facit venenum”, or “the dose makes the poison”. It means that all substances can be toxic if administered in a sufficient dose. This applies to normally harmless chemicals such as water, but also to highly toxic materials such as nerve agents.

So have the recent Novichok victims somehow been given smaller doses than intended? In the case of the poisoning of Sergei and Yulia Skripal in Salisbury, UK, in 2018, it appears that the poison was initially applied to a doorknob.

While the dose administered may have been quite large, possibly equivalent to several thousand lethal doses, the amount transferred to their skin would have been a fraction of that. The palm is also one of the least permeable parts of the human body, which is said to reduce the absorption rate in the body.

Subsequent contact with other surfaces through normal daily activities would be expected to further reduce the dose on victims’ hands. This means that the net dose absorbed through the skin would have been relatively small compared to the original amount.

In the case of the Skripals, after a delay of several hours, this was still enough to cause life-threatening toxicity. The fact that they were promptly given the appropriate antidotes and supportive therapies was essential to their survival.

Emergency services outside the Prezzo restaurant in Salisbury respond to the Novichok poisonings there.
enlarge Emergency services outside the Prezzo restaurant in Salisbury respond to the Novichok poisonings there.

Jonathan Brady/PA Images/Getty

Police officers were also subsequently poisoned with the substance when searching Skripals’ home – and both survived. It is possible that they were given an even lower dose of Novichok than the Skripals.

Shortly after the incident, two more people were poisoned in nearby Amesbury. Tragically, one victim, Dawn Sturgess, died. She had unknowingly sprayed Novichok directly onto her wrist from a perfume bottle her partner had found nearby.

This would no doubt have resulted in a much higher dose than the Skripals were given and applied to a thinner, more permeable area of ​​skin. The fact that the onset of the poisoning was much faster (minutes) than in the case of the Skripals seems to support this idea.

Unfortunately, prompt medical treatment could not prevent her death. Antidotes can be effective against multiples of a lethal dose. Military antidotes, for example, are generally designed to survive from at least five lethal doses of a nerve agent. However, no antidote will be effective against a massive dose.

Sturgess’ partner, Charlie Rowley, reportedly spilled some of the contents of the perfume bottle on his hands, but immediately washed off the oily residue. Immediate decontamination is known as a highly effective method against nerve agents and is the recommended initial treatment strategy for chemically contaminated victims in the UK and US. It is likely that this action saved Rowley’s life.

In the case of Navalny, he has been reported to have been poisoned by a contaminated cup of tea. How did he survive, since the amount added to the drink was probably a multiple of a lethal dose?

The exact details of the incident are not available, but several factors may have influenced the dose he absorbed. For example, he may have only had a few sips instead of the entire cup. Early reports indicate that Navalny has also vomited. We also do not know whether the Novichok is sufficiently dissolved in the tea. These factors may all have contributed to lowering the dose.

Alexey Navalny, Russian opposition leader, walks with protesters during a rally in Moscow, Russia, on Saturday, February 29, 2019.
enlarge Alexey Navalny, Russian opposition leader, walks with protesters during a rally in Moscow, Russia, on Saturday, February 29, 2019.

Andrey Rudakov/Bloomberg/Getty

The inherent toxicity of nerve agents is an obvious attraction to would-be assassins, as are other poisons such as arsenic, cyanide, and ricin. However, the practical difficulties of distributing any type of poison will introduce a large margin of error in dosing.

Current information suggests that Novichok agents are chemically stable and manufactured with high purity in specialized production facilities. Therefore, survival of exposure is unlikely to be due to “poor quality” Novichok. The substance is undoubtedly deadly and has resulted in the deaths of both innocent people and the intended victims.

The conversation

Robert Chilcott is a professor at the Center for Research into Topical Drug Delivery and Toxicology, University of Hertfordshire. This article is republished from The Conversation under a Creative Commons license. Read the original article.

By akfire1

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