Were the Skripals attacked by use of Novichok?

Question

According to Wikipedia quoting The Guardian, Sergei and Yulia Skripal were poisoned with Novichok, an organophosphate nerve agent in March 2018.

For me, there is a problem : the Skripals showed stiffness, and the organophosphate nerve agents cause muscular flaccidity.

Jamie Paine, an eyewitness who gave first aid to Yulia Skripal and also observed Sergei, gave an interview to the BBC:

The lady was sort of passed out. Her eyes were completely white, they were wide open but just white, and she was frothing at the mouth and then the man went stiff, his arms stopped moving. He was still looking dead straight.

He also gave an interview to Euronews:

"It was like her body was dead," he said, of the woman, who police says was known to Skripal.

"Her legs were really stiff... you know when animals die, they have rigor mortis. Both her legs came together when people pulled (her), and when she was on the floor her eyes were just completely white. They were wide open but just white and frothing at the mouth. Then the man went stiff: his arms stopped moving, but he's still looking dead straight."

He was also quoted in ITV News and interviewed to camera with similar accounts. (In both interviews, Jamie Paine said that both Yulia and Sergei Skripal became stiff.)

In this Daily Mail article (March 6, 2018), two other persons, in the first days of the affair, testify that the man showed rigidity.

Later, in this Guardian article (December 14, 2018), a policewoman also attested to the father's rigidity.

Fentanyl can cause muscle stiffness, as shown by this article.

Nerve agents, on the contrary, cause muscular flaccidity, as shown in this passage (about nerve agents):

A large amount of liquid on the skin causes effects within minutes. Commonly there is an asymptomatic period of one to 30 minutes, and then the sudden onset of an overwhelming cascade of events, including loss of consciousness, seizure activity, apnea, and muscular flaccidity.

Note that "shoulder stiffness" is mentioned in this article as being an effect of sarin, but among the late sequelae. The Skripals were not at the stage of late sequelae.

At Salisbury Hospital, where surely it was known that nerve agents cause flaccidity, not stiffness, an overdose of Fentanyl was diagnosed. The hospital was sure of its diagnosis, as seen by the initial form of its announcement of a "major incident":

Salisbury District Hospital declared a "major incident" on Monday 5 March after two patients were exposed to an opioid. (...) It followed an incident hours earlier in which a man and a woman were exposed to the drug Fentanyl in the city. The opioid is 10,000 times stronger than heroin.

The initial form of the announcement was reproduced on April 26, 2018 in a tweet from Dilyana Gaytandzhieva.

On the day of the publication of D. Gaytandzhieva's tweet, the hospital changed its announcement (recognizing this change). The announcement now said:

Salisbury District Hospital declared a “major incident” on Monday March 5, after two patients were exposed to what is believed to be an opioid. The fire service was called to decontaminate the hospital's Accident & Emergency unit, as paramedics treated the casualties. Emergency personnel arrived to the scene, wearing full-body hazardous materials protective and an incident response unit was on site. It followed an incident hours earlier in which a man and a woman were exposed to a substance in the city center.

And there was this note:

Note: This story was updated on April 26, 2018 to remove suggestion (which was widely speculated and reported at the time of writing) that the substance found was fentanyl.

If this BBC article is to be believed, the hospital changed the diagnosis at the initiative of the police.

By the way, the rigidity attested by several witnesses seems embarrassing for some. Not only made Mark Urban, a BBC journalist, a BBC broadcast aired in November 2018, where none of the witnesses of the bench scene named by the press at the material time appeared, but he published (first edition in October 2018) a book, ''The Skripal Files'', where, supposedly describing the symptoms that the Skripals showed during the bench scene, he obviously aims only to persuade the reader that all of these "nerve agent" symptoms could be mistaken for opioid symptoms, which appears to explain the hospital's "error". It is likely for that reason that he does not say a word of the rigidity attested by several witnesses. He also alleges the contraction of the pupils, which is a symptom common to nerve agents and certain opioids (among which fentanyl), but which was not attested by the witnesses of the scene of the bench named by the press at the time of the facts. The passage from his book can be viewed on Google Books, from page 193.

The conclusion seems inevitable: the nerve agents cause flaccidity and not rigidity, the Skripals presented rigidity, therefore they were not under the influence of an nerve agent. However, I'm not a toxicologist, so I could be wrong. In this case, I would gratefully be corrected.

Are there any toxicological sources demonstrating that organophosphates like Novichok can cause rigidity?

Edit 1: Lag answered that, yes, the Skripals were attacked by use of Novichok, because the UK government and the OPCW said it. But I'm not sure that the OPCW is independent and credible. Read this Wikipedia article:

https://en.wikipedia.org/wiki/Jos%C3%A9_Bustani

Edit 2: As I said in a reply to a comment, this article:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890077/

doesn't prove that organophosphates can cause stiffness, since it says : "Firstly, farmers were exposed to other pesticides in addition to OPs and carbamates, such as fungicides and pyrethroids. Consequently, it is difficult to determine which types of pesticides caused the health symptoms described herein."

Edit 3: I'm astonished that my question got three bad appreciations and that irrelevant answers got good appreciations. These answers are irrelevant, because they don't indicate a single toxicological source (I don't speak of Wikipedia) saying that organophosphates can cause stiffness.

Edit 4: Lag gave the two following links :

https://jnnp.bmj.com/content/66/2/253.full

https://n.neurology.org/content/52/7/1467.short

These links confirm that poisoning by organophosphate pesticides can cause rigidity. It is thus a little surprising that many toxicological sites mention muscular flaccidity as a symptom of poisoning by a nerve agent, but don't mention rigidity. In any case, I believe my question has been answered.

Answer 1

Yes, the Skripals were attacked by use of Novichok

The UK found that was the case and the Organisation for the Prohibition of Chemical Weapons (OPCW) agreed.

OCPW press release:

THE HAGUE, Netherlands—4 September 2018— The Organisation for the Prohibition of Chemical Weapons (OPCW) transmitted today to the United Kingdom of Great Britain and Northern Ireland (UK) the report of the OPCW’s mission to provide requested technical assistance in regard to an incident in Amesbury on 30 June 2018.

The results of the analysis by the OPCW designated laboratories of environmental and biomedical samples collected by the OPCW team confirm the findings of the United Kingdom relating to the identity of the toxic chemical that intoxicated two individuals in Amesbury and resulted in one fatality.

The toxic chemical compound displays the same toxic properties of a nerve agent. It is also the same toxic chemical that was found in the biomedical and environmental samples relating to the poisoning of Mr Sergei Skripal, Ms Yulia Skripal, and Mr Nicholas Bailey on 4 March 2018 in Salisbury. ...

Executive Summary of OPCW report.

[edit]

"But I'm not sure that the OPCW is independent and credible."

An obstacle to answering your question to your satisfaction is that, so far as I'm aware, no-one other than the workers at Porton Down and the four labs employed by OPCW examined the substance. Therefore, other than those entities and the producer/supplier of the substance, no-one is in a position to know.

You know the official conclusion, which doesn't seem seriously disputed by any authority - except by the alleged sponsor/perpetrator Russia - I doubt anyone else is a position to overturn it.

[edit]

Can organophosphate poisoning cause rigidity? Yes.

The OP has asked for evidence from the literature that organophosphate poisoning can lead to "rigidity" or "stiffness".

Here are links to some papers - there are more - that explicitly mention rigidity in association with organophosphate poisoning:

jnnp.bmj.com/content/66/2/253.full

link.springer.com/article/10.1007/BF03011077

sciencedirect.com/science/article/abs/pii/S0161813X01000444

tandfonline.com/doi/abs/10.3109/15563650.2015.1126841

casereports.bmj.com/content/2009/bcr.04.2009.1766.short

n.neurology.org/content/52/7/1467.short

There are other papers about organophosphate poisoning that talk about Parkinsonism but do not mention "rigidity" or stiffness". Parkinsonism is an umbrella term covering several conditions including Parkinson's disease that have similar symptoms. These symptoms include rigidity - one of the main motor symptoms of Parkinson's.

Answer 2

So, the actual claim here (the OP's) is that Novichok doesn't cause muscle stiffness/rigidity. I think there are not much in the way of experiments with Novichok itself, but if we assume (following Wikipedia) that it's of the organophosphate family, such poisonings with more commonly available compounds have displayed various symptoms including both stiffness and flaccidity:

A study in 214 Indonesian farmers reported symptoms after the spraying of pesticides, with the most frequent symptoms being fatigue (60 %), muscle stiffness (54 %), dry throat (30 %), muscle weakness (23 %), dizziness (21 %), difficulty in breathing (18.5 %), and chest pain (13.6 %)

Some of the survivors of the Tokyo subway Sarin attack also reported muscle stiffness, among the long term effects:

Symptom frequency (Table I) was highest for "tiredness of eyes," followed by "tiredness," "dim vision," and "difficulty focusing." Eye symptoms had higher rates of occurrence than other physical symptoms at all three time points. Other frequent physical symptoms (>10%) were "fatigue," "muscle stiffness," and "headache."

The exact biological effects of the Novichok agents have yet to be published in the usual peer-reviewed science publications, but a recent one highlighted some differences from other nerve agents, in terms of stability in the environment and (speed of) degradation by enzymes:

Hydrolysis and Enzymatic Degradation of Novichok Nerve Agents [...]

Hydrolysis of the Novichok agents at 25 C was two to three orders of magnitude slower than the G-series agents and zero to two orders of magnitude slower than the V-series agents. The hydrolysis data should be relevant to the effort to determine the persistence of Novichok agents in the environment or in the body although other factors such as binding to inorganic materials or proteins may play a role.

The catalytic activity of OPAA on the Novichok compounds was approximately two to three orders of magnitude less than its activity on G-type agents and two orders of magnitude greater than its activity on V-type agents (Bae et al., 2018) (Li et al., 2016) (Daczkowski et al., 2015). The stereochemistry of these catalytic reactions still needs to be explored because other nerve agents have been shown to exhibit stereospecific toxicity and the OPAA enzyme has been shown to exhibit stereospecificity in its interaction with other nerve agents.

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N.B.: the fact the Skripals were initially suspected of suffering from opioid poisoning upon hospital admission, only later revised to organophosphate (nerve agent) poisoning (OPP) is also not incredibly uncommon. There are some similar case reports in the literature. It seems that in general OPP is differentially diagnosed in such cases by non-response to naloxone (the first line counter-drug given in opioid poisonings/overdoses.)

Finally, regarding the eyewitness accounts published by the media; it's not clear to me that these people were trained enough to able to distinguish between "rigidity" (or "legs were really stiff" in actual statement) and status epilepticus for instance. Other reports, e.g. the NYT says

Skripal, a former Russian spy was found twitching beside his unconscious daughter on a park bench in Salisbury, England, both poisoned

Twitching would be consistent with status epilepticus, which is seen in the acute phase of severe OPP.

But even alone that is not enough to establish even the class of compounds involved. Pyrethroids, which are generally much safer to humans, have been known to cause poisoning symptoms that progress from status epilepticus in the acute phase to muscle weakness later on, i.e. very similar presentation to OPP. So, at some point you have to trust the laboratory analysis of the compounds found at the scene i.e. that done by the UK's authorities' and that of the OPCW.