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expert reaction to nerve agent being substance identified in case of Russian ex-spy and his daughter

Police have said the substance responsible for the critical illness of a Russian ex-spy and his daughter in Salisbury was a nerve agent.

 

One comment below specifically addressing the claims made by Dr Vil Mirzayanov that people exposed to tiny traces of Novichok nerve agent could develop long term health problems – 15 March

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

“There is no evidence whatsoever to support Mirzayanov’s claims. Toxicologically it is nonsense.

“In the absence of acute effects from nerve agents, long term effects are not going to be a problem.  If, 10 years down the line some symptom appears, it is much more likely to be due to some other event happening during that decade.  It doesn’t work like (say) diabetes where, as a result of continuing problems with blood sugar, damage occurs to blood vessels.

“I think the comments by Mirzayanov are irresponsible and likely to cause unwarranted fear.”

 

Comments issued on 12 March:

Prof Gary Stephens, pharmacology expert at the University of Reading, said:

“This is a more dangerous and sophisticated agent than sarin or VX and is harder to identify. It causes a slowing of the heart and restriction of the airways, leading to death by asphyxiation.

“One of the main reasons these agents are developed is because their component parts are not on the banned list. It means the chemicals that are mixed to create it are much easier to deliver with no risk to the health of the courier.”

 

Dr Robert Stockman, Associate Professor and Reader of Organic Chemistry, University of Nottingham, said:

“Fluoro phosphate-based nerve agents (such as Sarin, VX) work quickly – so in terms of half-lives within the body, this will not be very long (minutes, maybe hours).  They react in stages however with the nervous system – if an antidote can be administered within the first 24-48 hours, much of the effects can be reversed.  However, the longer the victim goes before the antidote is administered, the agent’s effect on the nervous system ‘ages’ and the effects become irreversible.  This is due to further changes in the nerve agent once it is attached to the receptors in the nervous system, which happen quite slowly.

“Within the environment, these agents react with water to degrade, including moisture in the air, and so in the UK they would have a very limited lifetime.  This is presumably why the street in Salisbury was being hosed down as a precaution – it would effectively destroy the agent.

“In terms of their effect on the body, they interfere with the nervous system, rendering the parts effected inoperable – thus the uncontrollable muscle spasms, the difficulty breathing – the nervous system tells these muscles when and how to move, and interfering in this causes the spasms.  The effects of the nervous agent can only be removed with an antidote given in time, or irreparable damage will be done.”

 

Dr David Caldicott, Clinical Senior Lecturer, Faculty of Medicine, Australian National University, said:

“Nerve agents are possibly some of the most dangerous things that humans have ever made, after the atom bomb.

“All these chemicals work in much the same way by inhibiting an enzyme called acetylcholinesterase at the nerve junction (synapse).  Under normal circumstances, acetylcholinesterase regulates the amount of the neurotransmitter acetylcholine crossing nerve synapses — so it effectively works as an off-switch.  Acetylcholine acts mainly on the body’s autonomic nervous system — the body’s involuntary nervous system — which controls things such as heart rate, respiratory rate, salivation, digestion, pupil dilation, and urination.

“You can imagine that if you block one of the major ‘off-switches’ of the body, and are left with all the lights turned ‘on’ all of the time, the body might run into trouble.  With an extremely rapid build up of acetylcholine in the synapse, things like secretions, respiratory problems, and muscular dysfuntion can go on unattenuated.

“There are some commonly-used chemicals of this type – we use them in agriculture as organophosphate pesticides, but obviously these are designed to attack the nervous system of agricultural pests, not people.  The Germans invented a weaponised version in the form of tabun in the Second World War.  Sarin, in dilute form, was deployed in the Tokyo gas attacks, and VX on Kim Jong Nam in Korea.  That last example showed that with some ingenuity, versions of these chemicals can be used as personalised weapons and not just weapons of mass destruction.”

 

Comments issued on Wednesday 7 March:

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

“Nerve agents are small molecules based on phosphorus that interfere with nerve transmission in an irreversible fashion by mimicking the neurotransmitter acetylcholine and binding to a key enzyme involved its biochemistry.  In essence what they do is to block the mechanism that allows a nerve to reset itself after a signal has been transmitted.  This causes a pretty systemic collapse of many bodily functions.  The symptoms are largely consistent, especially the laboured breathing and the muscular rigidity, and the fact that some of the emergency workers were affected and reported itching and runny noses.  It would have been passed by skin contact and because the materials are quite volatile and would have reached mucous membranes.

“Such nerve agents have been used before most spectacularly reportedly in Korea in the murder of Kim Jon Un’s brother.  It is a very high risk way to attack someone and it shows the sheer audaciousness of the attack.

“Treatment involves supporting breathing and delivering pharmaceuticals that on the one hand moderate the behaviour of the nervous system and that can reverse the action of the agent.  It is likely that there will be long term neurological problems for a person who has been exposed to these agents.

“In spite of the extreme toxicity of these compounds, which would be very dangerous for the person delivering the attack, there would be very little risk to the general population as there is no way of spreading the material around and it would decompose relatively swiftly in damp conditions.  This was a highly targeted attack.

“Nerve agents are not materials that can be made at home.  Their level of toxicity is such that they are only to be manufactured in specialised facilities.  A key forensic issue here is to identify impurities and residues that might provide clues as to the precise chemical process used to manufacture the material.  There is no question that the authorities will be looking for the container used to deliver the material as the chemical contents would be a goldmine.  With this information it might well be possible to trace the origin of the substance, just as has been done for the Khan Sheikhoun attack in Syria.”

 

Dr Hilary Walker, a former radiation scientist and health emergency planner, said:

“In my view, the finding of nerve agent poisoning is not surprising considering the further details we have been reading about the symptoms of the two cases and that others attending them have also been affected.  The latter being due to the agent/gas still lingering in the environment when the emergency services initially arrived.  Nerve agents will act within seconds or minutes if inhaled and slightly slower if exposure is the result of skin contamination.  Nerve agents affect the nerve junctions in the body and acute exposure leads to the symptoms that have been described such as apparent white eyes as the pupils are constricted, convulsions, drooling and in the worse cases – coma, respiratory failure and death.  There are well rehearsed emergency procedures for dealing with such contamination and the emergency services obviously activated these to prevent spread – hence the decontamination activity with hoses.  There are antidotes to help reverse the effect of the gas which the emergency services hold but they need to be administered rapidly and by this time, I expect that the hospitalised patients might only be receiving symptomatic treatment.”

 

Dr Chris Morris, Medical Toxicology Centre, Newcastle University, said:

What are nerve agents, and how do they work?

“Typically ‘nerve agents’ are organophosphorous or carbamate compounds that work by binding to and inhibiting the enzyme acetylcholinesterase which leads to a build up in the neurotransmitter acetylcholine (ACh) ate nerve endings.  This causes activation of the muscles in particular leading to excessive stimulation.

Do the symptoms described match that this was caused by a nerve agent?

“Difficult to say since the symptoms described appeared non-specific.  Some of the disorientation may have been due to the early effects of agents and these are then followed by breathing difficulties and then cramps and seizures.  Some of the early acute effects could have been put down to food poisoning since vomiting, diarrhoea, and urinary incontinence occur (turning on all the taps is a phrase often used).

Have nerve agents been used in such isolated (i.e. only two people) cases before?

“The case of Kim Jong-Nam was an isolated and targeted approach to using nerve agents such as VX, but typically these are used in warfare for mass effects as reportedly seen in Syria recently and Iran (reportedly used by Iraq in the Iran/Iraq war), and on the Tokyo Underground attack in 1995 which used sarin.

Are there any clues here about how and where the nerve agent may have been delivered?

“Not really, could have been delivered in a variety of ways if via covert delivery but contact with the skin might be one route for the V type nerve agents.

How will patients exposed to nerve agents likely be being cared for in hospital?

“Typically this is supportive care to reduce the symptoms associated with exposure.  Atropine and pralidoxime are given to reduce the effects of acetylcholine and then there is administration of anti-seizure medication to reduce any central effects of nerve agents.  Ventilatory support and cardiac support is given to help with breathing since this is affected.

Do we know what the likely outcome for the two people exposed might be?

“It would depend on the severity of exposure but typically if the symptoms can be controlled until the agent is removed then recovery is good.  With the type of supportive care given in these cases, then there may be minimal long term effects if treatment was rapid and effective.  There are some possible long term symptoms such as anxiety and depression but these are relatively non-specific.

Do we know where people access nerve agents?

“Covert production is the likely source since they are controlled by international treaty.

Does information so far suggest this is an isolated incident; does information suggest there is any risk to the wider public?

“If the agent is something like VX, then the agent is viscous and doesn’t spread far and it isn’t very volatile.  Since it’s a direct contact agent, only small amounts are needed.  Public exposure would be minimal since the agent would have to be applied at close range.  Due to this it’s very unlikely to spread and there would be effective decontamination procedures in place to limit exposure.”

 

Comments issued on Tuesday 6 March:

Prof Malcolm Sperrin, medical physics expert, said:

“We need to keep view of reality.  The symptoms may be related to some sort of exposure to common domestic chemicals – I am not saying that is the cause but we could be looking at a coincidence.  Forensic evidence will be collected and managed for the common good and will comprise environmental material, body material and clothes including monitoring carried by the emergency services.  I expect updates to be issued since there is a clear need to know at local, national and international level.  Don’t assume Russian involvement!”

 

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

Do we know what conditions to two people affected will likely be being kept in hospital?

“I’m not sure about this – we can’t know for sure.  I suspect individuals might well be in rooms away from others.  There would sensibly have been some care taken in removing clothing in case this was contaminated.  I’m not sure whether they will be in quarantine as the evidence is unclear – as microbiological agents and radioactive poisoning seem to perhaps be less likely, quarantine may be unnecessary, but they may do so as a precautionary measure until more is known.  The usual precautionary measures would be in place when collecting body fluids as these measures offer a degree of protection.”

 

Anonymous comment from an ex radiation biologist:

“Hospital policies are not to release any specific detail on patients’ conditions or treatments unless with consent and then not if it is prejudicial to any ongoing inquiries.  Hence I think that we are not likely to get further details at present.

“However all hospitals have to plan and exercise procedures for the possibility of such eventualities – e.g. receiving patients either contaminated and/or poisoned.  These would have been implemented.  What those conditions are will depend on the patients’ clinical states and on the possible causes for their symptoms.

“Simply put, there are procedures in place but we won’t know any specific details until we are told!”

 

Prof Malcolm Sperrin, medical physics expert, said:

“The speed at which this has occurred suggests this is probably not radiation – radiation poisoning tends to take tens of hours to several days to show symptoms after exposure.  Some of the symptoms being described in these two people suggest this may have been chemical, but we can’t be sure.  The time delay after exposure to chemical tends to be seconds to minutes.  Using an encapsulated chemical delivered directly could have given a person responsible time to escape.”

 

Anonymous comment from an ex radiation biologist:

“From the media, all we know is that the Russian and his daughter are seriously ill in hospital, having been found collapsed in a shopping centre in Salisbury.  We know nothing more about their symptoms apart from one witness stating that “he appeared out of it”.  We also know that the nearby restaurant and pub have been secured and that the streets nearby have been decontaminated with hoses.  His house is also secured.

“Not much to go on!  A question has been asked by journalists about radioactive substances.  Unless the initial dose is really massive then there is a delay before any symptoms show.  To cause unconsciousness over a short space of time would require an implausible absorbed dose from either ingested or inhaled radioactivity.  Also even if there had been a delay from initial ingestion, it would be most unlikely that there would be synchrony between symptoms with father and daughter.  Frankly I would put radioactive substances to one side.

“If the outcome is not just something like a couple of dodgy kebabs – again less probable with both individuals being symptomatic at the same time and with considerable rapidity if they had just eaten there – then I would look for a chemical source.  Decontamination at the scene would also suggest that possibility.  However we shouldn’t totally ignore biological contamination of food or the environment.  However the latter would have caused a wider response from PHE and the authorities.

“We have no information on symptoms apart from severity so I wouldn’t like to speculate on possible chemicals which can range widely and include the increasing range of designer drugs so that this includes not only those designed for chemical warfare but also those for the new range of artificial highs.  We could be looking at self-inflicted accidental overdoses or a targeted attack.

“Toxicologists would have received samples from the patients of both fluids and tissues as well as being given the symptoms for the patients being treated and their response to particular drug therapies.  From the samples they can investigate possible chemicals and their metabolites produced in the tissues.  This can take a variable amount of time dependent on the knowledge about each chemical.

“I certainly would imagine that all the relevant agencies would be working together to pool expertise and knowledge – certainly from my experience this has indeed been the case.  From the health point of view PHE would be working not only with their own laboratories but also with the relevant expertise in universities and other such institutions such as Porton Down.”

 

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

“The first clue is signs and symptoms in the individual. A second may be the circumstances in which someone is found.  Ideally it would help to question someone about this but if they have collapsed you have to test for substances.  Signs and symptoms will give a clue about candidate agents.

“Standard blood tests will be done to assess electrolyte levels and liver and kidney function. Individuals will be receiving intravenous fluids anyway and it is essential to maintain fluid balance.

“Intensive care facilities in hospitals are best placed to look after poisoned patients as they have the necessary skills and equipment.

“As for tests, a variety of fluids will be investigated. Blood, saliva and urine will all be tested. Urine may provide clues for substances excreted more rapidly.

“Given the apparent rapidity of onset of symptoms a bacterial or viral cause seems less likely but we know nothing at this stage about how the couple were feeling hours earlier. So a microbiology lab may well do a range of screening tests to check for a bacterial cause. But this will depend on what the clinical team feels is appropriate.

“Signs and symptoms give a clue about possible candidate chemicals or drugs and the hospital’s own laboratory may be able to do some of the testing.

“Other labs at Guy’s hospital or in Birmingham are also equipped to screen for a wide range of substances. And finally, there is the government’s Chemical Defence laboratory at Porton Down which has state-of-the -art equipment to look for trace amounts of substances.

“Individuals cannot provide unlimited amounts of blood for testing so investigations will be guided by the clinical team.  Some tests are rapid and some candidates will be looked at quickly But if the cause is more unusual body fluids will require significant clean-up preparation before they can be put in an instrument. So this could take a day or several days.

There will be active co-ordination with a whole range of agencies and hospital departments in a case like this.”

 

Comments issued on Monday 5 March:

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

“It is impossible to speculate at this stage about the substance.  If PHE say there is no wider risk this may suggest some very specific contact with the substance and limited spread.  It would be helpful to know what they used to hose down the area.  In the end it will be signs and symptoms and specific blood, saliva or sputum, urine, and possible faecal testing that will tell us what it was.  It was classed as a major incident.  Part of the investigation now will be working out if it is known for certain where contact with any offending agent occurred.  Was it declared a major incident because of who was affected or because of the rate of onset of symptoms?”

 

Declared interests

Prof Alastair Hay: “No conflicts of interest.  I worked on UK government committees (from 1989 until 2015) and an EU committee (2005-14) that recommended standards for chemical exposure in the workplace.  Over the years I have investigated some 6 allegations of use of chemical weapons.”

None others received.

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