September 3, 2020

expert reaction to reports that Russian opposition leader Alexi Navalny was poisoned with the nerve agent Novichok

There have been reports from Germany that the Russian opposition leader Alexi Navalny, who is currently hospitalised in Germany, was poisoned with the nerve agent Novichok.

Prof Andrea Sella, Professor of Inorganic Chemistry, UCL, said:

“The term Novichok refers to a family of nerve-agents which were developed in the then Soviet Union as part of the secret Cold War “FOLIANT” programme of chemical weapons. Because international attention was focused on the major nerve agents like V, VX and so on, these compounds slipped partially under the radar. They are known to act very similarly to “conventional” nerve agents, but were designed to be more robust and persistent in the environment, and in some cases to be more resistant to treatment. The mode of delivery is an interesting question. It is possible that the substance was ingested but the fact that it took time to act may point towards a time-release formulation of the kind that is routinely used for pharmaceuticals. Again this is an indication that this was no amateur attack.

“It is very hard to predict what the prognosis will be for Mr Navalny. In cases of poisoning, very swift action is required in order to stabilise the patient and for the drugs that are known to reverse the action of the agent to do their work. We know that there was a significant delay during which Mr Navalny lay in the hospital in Omsk with a team that stated they had no idea of what the poison might be. The problem is that even if Mr Navalny were to survive there may be lingering long-term neurological issues. Although the Novichok compounds/agents act similarly to other nerve agents, very little is known about their detailed  pharmacology  and each one will be subtly different. There are also parallels with the attack on Pyotr Versilov the nature of which was never established with certainty. Mr Verzilov was also treated at Charité.

“Much was learned from the Skripal attack in 2018 and there is no doubt that significant lessons will have been learned in Salisbury, and that will be being shared with the team at Charité in Berlin.”

Prof Alastair Hay, Professor (Emeritus) of Environmental Toxicology, University of Leeds, said:

What are the Novichok group of nerve agents?

“They comprise some 20 known chemicals which vary in structure and toxicity. Last year the Organisation for the Prohibition of Chemical Weapons agreed that the Novichoks would be proscribed and countries would declare any stocks they possessed. Russia supported that decision.”

What do we know about their manufacture and distribution – can we deduce anything about who may have been behind the attack on Alexei Navalny now that we know a Novichok agent was used?

“We know very little about their manufacture and distribution. What is in the public domain indicates that Russia had an interest in these chemicals and tested some. In view of this, numerous countries would have synthesised small quantities to calibrate equipment to enable detection of the chemical in assay systems. This is almost certainly why the West German military laboratory was able to identify the chemical.”

How do these agents affect people?

“Novichoks work like all nerve agents and block the message from nerves to muscle. They do this by inhibiting a specific enzyme acetylcholinesterase. The enzyme is crucial for regulating messages from nerve to muscle – and its inhibition leaves muscles in a sort of spasm. Muscle cannot contract and relax as they do normally. All muscles are affected with the most crucial being those which control breathing. The nerve agents are extremely potent with very tiny quantities sufficient to kill.”

Do you think the events in Salisbury in 2018 (the attack on the Skripals) and what was learned from that incident will be helping to inform the treatment of Mr Navalny?

“Almost certainly. What worked for the Skripals will be of great help for the German doctors. The exact Novichok chemical which poisoned Mr Navalny is not known. If it is the same as used against the Skripals then their treatment will be of crucial help for the doctors looking after Mr Navalny.”

Prof Rob Chilcott, Professor of Toxicology, University of Hertfordshire, said:

“Specialist laboratory testing can be performed to identify nerve agents in the blood and urine of victims. These are highly sensitive assays which use mass spectrometers to detect miniscule quantities of breakdown products (metabolites) or chemical which has become bound to proteins or other biomolecules.

“Nerve agents such as Novichoks are likely to be absorbed via the skin or following ingestion. The onset of signs and symptoms after skin exposure would be expected to be much slower than poisoning via food or drink. The risk to people other than the intended victim will depend on how the chemical was administered.

“The signs and symptoms of poisoning will likely be the same as other nerve agents. These include nausea, vomiting, incontinence, excessive airway secretions, impaired vision, loss of coordination, confusion and paralysis.

“The first course of action should be thorough decontamination of any exposed skin and hair surfaces, with administration of atropine and diazepam.”

Dr Wayne Carter, Associate Professor, University of Nottingham, said:

“Novichok belongs to a group of chemicals called organophosphates, that includes some pesticides and nerve agents.  Novichok’s primary target is acetylcholinesterase, an enzyme involved in stopping nerve signals as well as switching off muscle contractions. To help confirm exposure to Novichok, a sample of blood from an individual thought to have been exposed to Novichok can be analysed in a lab.  This provides a means to identify Novichok.

“Individuals could be exposed to Novichok through skin absorption or from inhaling or ingesting it.

“Risks to others would depend upon how localized the poisoning was.  There is the potential to spread droplets of the agent, for example from fingertips, from one place (or one person) to another. It will be important to identify the time and location of the proposed poisoning to ensure that the agent is not still present, or has been spread.

“Nerve agents, such as Novichok, affect the nervous system, the result depends upon the individual’s response and the dose encountered.  Hence symptoms can be mild, but in sufficient dose, they can be fatal. Treatment is usually with a drug, atropine, and also a chemical agent that can reactivate the acetylcholinesterase damaged by Novichok.”

Dr Richard Parsons, Senior Lecturer in Biochemical Toxicology, King’s College London, said:

“Novichok are a class of nerve agents called Binary Agents. To make the active toxin, they are transported separately (in forms which are safe) and are then mixed together to form the active poison. They are extremely toxic. We have seen them used against the Skripals in Salisbury a few years ago. They were administered via a spray to the door handle of Mr Skripal’s house. Once in the body, they attach to the cholinesterase enzyme which stops it from breaking down a chemical messenger called acetylcholine. This is released by nerves onto muscles which activates them. If you prevent the breakdown of acetylcholine, then this prevents them being switched off, overactivating the muscles and causing symptoms such as intense stomach pain, difficulties in breathing, cognitive problems and ultimately death.

“Initial suspicion is raised by measuring the level of cholinesterase activity in the blood. Once this is confirmed to be reduced, then scientists look for the specific “fingerprint” the Novichok agent has. This is done in several independent laboratories around the world. Treatment tends to be mechanical ventilation using a tracheotomy and atropine to prevent the effects of the elevated acetylcholine, but in the main it is a wait and see – you have to wait for the body to break down the non-functioning cholinesterase enzyme and produce more, and this can take a long time.

“As we saw in Salisbury, the risk to others can be very significant. Because the Novichok was sprayed onto the door handle of the house, the first responding officer was also poisoned. Also, as it was thrown away in the bin, the couple who found it were also injured, with one dying. in the case of Navalny, if it was administered via a cup of tea, then the risk to others may be significantly reduced, but you cannot rule out contamination of other areas, in particular the hospital and the airplane.

“Unless you are working for the military, it is impossible to be accidently exposed. It is only dangerous when it is about to be used, i.e. mixed together. It is unavailable from anywhere except the Russian military as far as I am aware.”

All our previous output on this subject can be seen at this weblink:

https://www.sciencemediacentre.org/?s=novichok&cat=

Declared interests

None received.