On pages 58-62 of the October 2020 issue of CBRNeWorld you will find an article from me on the existing analytical methods that allowed to identify a nerve agent from the so-called Novichok-group as the cause for Alexei Navalny’s poisoning. The article also touches upon the question why so many people have survived exposure to such high toxic nerve agents and that a further amendment of the schedules of chemicals in the Chemical Weapons Convention is vital.
German news Magazin DER SPIEGEL published an article on the recovery process of Mr Navalny where I was able to contribute with some commentary.
While it might appear like a fast recovery Mr Navalny spent almost the same time in hospital as Yulia Skripal, the daughter of Sergey Skripal, who was poisoned in March 2018 together with her father. Key aspects for recovery (apart from a good general intensive care) are the elimination of potentially remaining poison from the body and the time the body requires to synthesize new cholinesterases to restore functionality to nerve impulse transmission.
As the result of a scientific collaboration with the Bundeswehr Institut of Pharmacology and Toxicology we have jointly published a research article in the journal Analytical and Bioanalytical Chemistry, which was selected by the editors to become a “Paper in Forefront” (according to the journal Papers in Forefront are exceptional papers that the Editors selected guided by peer review).
In this paper we report on the adduct of the blistering agent Sesquimustard with Human Serum Albumin (HSA) and its mass spectrometric identification for biomedical verification of exposure. Why is this important?
In addition to the well known chemical warfare agent sulfur mustard (SM) a range of higher sulfur mustards exist that are also listed in Schedule 1 of the Chemical Weapons Convention and show stronger blistering properties than SM. Sesquimustard is regularly found as a common impurity in mustard mixtures and in old munitions but can also be used in pure form.
Victims of an exposure to Sesquimustard would show the same symptoms as those exposed to regular sulfur mustard but a bioanalytical investigation would come back negative as the typical biomarkers (including protein biomarkers) of sulfur mustard would be missing.
We report for the first time the adduct of Q with the nucleophilic Cys34 residue of human serum albumin (HSA) formed in vitro and introduce two novel bioanalytical procedures for detection. After proteolysis of this HSA adduct catalyzed either by pronase or by proteinase K, two biomarkers were identified by high-resolution tandem mass spectrometry (MS/HR MS), namely a dipeptide and a tripeptide, both alkylated at their Cys residue, which we refer to as HETETE-CP and HETETE-CPF. HETETE represents the Q-derived thio- alkyl moiety bearing a terminal hydroxyl group: “hydroxyethylthioethylthioethyl.” Targeting both peptide markers from plasma, a micro liquid chromatography–electrospray ionization tandem mass spectrometry method working in the selected reaction monitoring mode (μLC-ESI MS/MS SRM) was developed and validated as well suited for the verification of exposure to Q. Fulfilling the quality criteria defined by the Organisation for the Prohibition of Chemical Weapons, the novel methods enable the detection of exposure to Q alone or in mixtures with SM. We further report on the relative reactivity of Q compared to SM.
Based on experiments making use of partially deuterated Q as the alkylating agent, we rule out a major role for six-membered ring sulfonium ions as relevant reactive species in the alkylation of Cys34 .
Furthermore, the results of molecular dynamics simulations are indicative that the protein environment around Cys34 allows adduct formation with elongated but not bulky molecules such as Q, and identify important hydrogen bonding interactions and hydrophobic contacts.
The paper is available open-access on the journal’s homepage.
Adduct of the blistering warfare agent sesquimustard with human serum albumin and its mass spectrometric identification for biomedical verification of exposure
Marc-Michael Blum, Annika Richter, Markus Siegert, Horst Thiermann & Harald John
Analytical and Bioanalytical Chemistry (2020), 412:7723-7737.
In June 2020 the addition of a number of new chemicals and family of chemicals to Schedule 1 of the Chemical Weapons Convention entered into force. According to Member States these additions include agents from the so-called “Novichok” group of agents.
Written totally unrelated to the recent poisoning of Mr Navalny by a Novichok agent, but certainly well timed, my article “Ein unbekanntes Nervengift” covering these nerve agents appeared in the September issue of “Nachrichten aus der Chemie”, the monthly publication of the German Chemical Society. Due to the Navalny case and general interest the GDCh made the article open-access so please follow the above link (Article in German).
I gave an interview to the Riga based Russian online newspaper meduza.io on the Navalny case. I gave the interview just before Germany announced that they identified a nerve agent from the Novichok family as the chemical responsible for Mr Navalny’s poisoning.
Me an interview partner Alexander Ershov went into quite some detail on how such substances act a poisons, how analytical chemistry is able to identify them and how the outlook is for a total recovery.
I have to mention Medusa’s managing editor Kevin Rothrock who announced me on Twitter as “basically the real-life Nicholas Cage character from “The Rock” “. Well one important takeaway message from that movie is that VX nerve agent is not green (as depicted there).
I gave an interview to the German magazine DER SPIEGEL on the Navalny case. Asking “Waren Sie wirklich so dumm” (“Were they really so stupid”) relates to the question if Russia wants to be associated with an assassination attempt using a potential organophosphorus agent again. While this is an import question the article (given to their science section) focuses on how a cholinesterase inhibitor (as generically identified by the Berlin university hospital Charité) can be identified by name and structure.
One of the core problems: The concentrations of relevant analyze chemical in biomedical samples is so low that you have to conduct so called targeted analysis – you have to search for specific compounds. A wide screening (let’s just look for everything) is not possible.
Nevertheless, I remain confident that the compound that is responsible for Mr Navalny’s current condition will be identified shortly.
….and I am actually quite proud of the fact that the interview for some time was second most read article on the SPIEGEL website.
The Washington Post published an article on the risks, dangers and properties of ammonium nitrate – the chemical that was in all likelihood responsible for the catastrophic explosion in Beirut. It was a pleasure to be able to contribute some insights. Read the article here.
It is probably a natural thing that explosions of this size trigger conspiracy theories. From a nuclear detonation to the infamous “red mercury” – numerous “theories” float our social media channels.
This is interesting also from a historical perspective: When an explosion of ammonium nitrate for fertilizers of similar size blew up the BASF plant in Oppau in 1921 – just a few years after the end of World War 1 – there were theories floating in international media that secret weapon experiments were carried out with the possible involvement of Fritz Haber – the father of German gas warfare in the war but also Nobel Prize winner for inventing the Haber process to produce ammonia from nitrogen from the air. This ammonia was the precursor for the ammonium nitrate. It also shows the dual use dilemma of many chemicals.
The Stanton Foundation (well known for their work on nuclear security and other field) currently runs a size contest “Applying History to Clarify the COVID-19” and selects winning articles and Op-Eds through an advisory panel from the Applied History Project at Harvard Kennedy School’s Belfer Center.
The article “Corona and Bioterrorism: How serious is the Threat?” I published together with Prof Peter Neumann of King’s College on War on The Rocks, was awarded a prize in this contest. The Selection Committee described the article as “an illuminating analysis of the risk of bioterrorism in light of coronavirus, informed by history and technical expertise.”
Together with Prof. Peter Neumann from King’s College London I have published an article on Corona and Bioterrorism on the online platform “War On The Rocks”.
We argue that the challenges for a sophisticated large scale bioterrist attack remain significant unless the attackers receive major help from a state or can use a states infrastructure as an insider. The likelihood that a terrorist group will come up with a virus similar to SARS-CoV-2 by themselves having a „zero-day-exploit“ on the human immune sytem is very low. However more crude types of attack remain a viable possibility.
Chemical & Engineering News published an article on the use of riot control agents and how to neutralize their effects. I was asked to comment on some aspects including why riot control agents are banned by the Chemical Weapons Convention for use in warfare but not for law enforcement and riot control purposes. Read the article here.