Novichok (russian: Новичо́к, lit=newcomer, novice, newbie) is a group of
nerve agents, some of which are
binary chemical weapon
__NOTOC__
Binary chemical weapons or munitions are chemical weapons which contain the toxic agent in its active state as chemical precursors that are significantly less toxic than the agent. This improves the safety of storing, transporting, and di ...
s. The agents were developed at the
GosNIIOKhT
The State Research Institute of Organic Chemistry and Technology () (GosNIIOKhT) is a Russian research institute engaged in the development of chemical technologies for use in the national economy and the production of relevant goods and prod ...
state chemical research institute by the
Soviet Union and Russia between 1971 and 1993.
Some Novichok agents are solids at standard temperature and pressure
Standard temperature and pressure (STP) are standard sets of conditions for experimental measurements to be established to allow comparisons to be made between different sets of data. The most used standards are those of the International Union o ...
, while others are liquids. Dispersal of solid form agents is thought possible if in ultrafine powder state.
Russian scientists who developed the nerve agents claim they are the deadliest ever made, with some variants possibly five to eight times more potent than VX, and others up to ten times more potent than soman. As well as Russia, Novichok agents have been known to be produced in Iran.
In the 21st century, Novichok agents came to public attention after they were used to poison opponents of the Russian government, including the Skripals and two others in Amesbury, UK (2018), and Alexei Navalny
Alexei Anatolievich Navalny ( rus, links=no, Алексей Анатольевич Навальный, , ɐlʲɪkˈsʲej ɐnɐˈtolʲjɪvʲɪtɕ nɐˈvalʲnɨj; born 4 June 1976) is a Opposition to Vladimir Putin in Russia, Russian opposition ...
(2020), but civil poisonings with this substance have been known since at least 1995.
In November 2019, the Organisation for the Prohibition of Chemical Weapons (OPCW), which is the executive body for the Chemical Weapons Convention
The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
(CWC), added the Novichok agents to "list of controlled substances" of the CWC "in one of the first major changes to the treaty since it was agreed in the 1990s" in response to the 2018 poisonings in the UK.
Design objectives
Novichok agents were designed to achieve four objectives:
* to be undetectable using standard 1970s and 1980s NATO chemical detection equipment;
* to defeat NATO chemical protective gear;
* to be safer to handle; and
* to circumvent the Chemical Weapons Convention
The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
list of controlled precursors, classes of chemical and physical form.
Some of these agents are binary weapons, in which precursors for the nerve agents are mixed in a munition to produce the agent just prior to its use. The precursors are generally significantly less hazardous than the agents themselves, so this technique makes handling and transporting the munitions a great deal simpler. Additionally, precursors to the agents are usually much easier to stabilise than the agents themselves, so this technique also makes it possible to increase the shelf life of the agents. This has the disadvantage that careless preparation may produce a non-optimal agent. During the 1980s and 1990s, binary versions of several Soviet agents were developed and are designated as "Novichok" agents.
History and disclosure
Novichok agents were designed as part of a Soviet program codenamed Foliant. Five Novichok variants are believed to have been adapted for military use. The most versatile is A-232 (Novichok-5). Novichok agents have never been used on the battlefield. The UK government determined that a novichok agent was used in the poisoning of Sergei and Yulia Skripal in Salisbury, Wiltshire, England in March 2018. It was unanimously confirmed by four laboratories around the world, according to the OPCW. Novichok was also involved in the poisoning of a British couple in Amesbury, Wiltshire, four months later, believed to have been caused by nerve agent discarded after the Salisbury attack.[ The attacks led to the death of one person, left three others in a critical condition from which they recovered, and briefly hospitalised a police officer. The Russian government denies producing or researching agents "under the title Novichok".] In September 2020, the German
German(s) may refer to:
* Germany (of or related to)
**Germania (historical use)
* Germans, citizens of Germany, people of German ancestry, or native speakers of the German language
** For citizens of Germany, see also German nationality law
**Ger ...
government said that opposition figure and anti-corruption activist Alexei Navalny
Alexei Anatolievich Navalny ( rus, links=no, Алексей Анатольевич Навальный, , ɐlʲɪkˈsʲej ɐnɐˈtolʲjɪvʲɪtɕ nɐˈvalʲnɨj; born 4 June 1976) is a Opposition to Vladimir Putin in Russia, Russian opposition ...
, who was evacuated from Omsk
Omsk (; rus, Омск, p=omsk) is the administrative center and largest city of Omsk Oblast, Russia. It is situated in southwestern Siberia, and has a population of over 1.1 million. Omsk is the third largest city in Siberia after Novosibirsk ...
to Berlin for treatment in late August after becoming ill during his flight, was poisoned by a Novichok agent.
Novichok has been known to most western intelligence services since the 1990s, and in 2016 Iranian chemists working at a university in Tehran synthesised five of the seven Novichok agents for analysis and produced detailed mass spectral data which was added to the OPCW's Central Analytical Database. Previously, there had been no detailed descriptions of their spectral properties in open scientific literature. A small amount of agent A-230 was also claimed to have been synthesised in the Czech Republic in 2017 for the purpose of obtaining analytical data to help defend against these novel toxic compounds.
The Soviet Union and Russia reportedly developed extremely potent fourth-generation chemical weapons from the 1970s until the early 1990s, according to a publication by two chemists, Lev Fyodorov
Lev may refer to:
Common uses
*Bulgarian lev, the currency of Bulgaria
*an abbreviation for Leviticus, the third book of the Hebrew Bible and the Torah
People and fictional characters
*Lev (given name)
*Lev (surname)
Places
* Lev, Azerbaijan, ...
and Vil Mirzayanov in ''Moskovskiye Novosti
''Moskovskiye Novosti'' (russian: Московские новости, ''Moscow News'') was a Russian-language daily newspaper in Russia relaunched in 2011. The paper - by then a 'youth-oriented' free sheet handed out at more than 850 places aro ...
'' weekly in 1992. The publication appeared just on the eve of Russia's signing of the Chemical Weapons Convention
The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
. According to Mirzayanov, the Russian Military Chemical Complex (MCC) was using defence conversion money received from the West for development of a chemical warfare facility. Mirzayanov made his disclosure out of environmental concerns. He was the head of a counter-intelligence department and performed measurements outside the chemical weapons facilities to make sure that foreign spies could not detect any traces of production. To his horror, the levels of deadly substances were eighty times greater than the maximum safe concentration.
The Prosecutor-General of Russia
The Prosecutor General of Russia (also Attorney General of Russia, russian: Генеральный прокурор Российской Федерации, Generalʹnyy prokuror Rossiyskoy Federatsii) heads the system of official prosecution i ...
effectively admitted the existence of Novichok agents when he brought a treason case against Mirzayanov. According to expert witness testimonies that three scientists prepared for the KGB, Novichok and other related chemical agents had indeed been produced and therefore Mirzayanov's disclosure represented high treason.
Mirzayanov was arrested on 22 October 1992 and sent to Lefortovo prison for divulging state secrets. He was released later because "not one of the formulas or names of poisonous substances in the ''Moscow News'' article was new to the Soviet press, nor were locations ... of testing sites revealed." According to Yevgenia Albats, "the real state secret revealed by Fyodorov and Mirzayanov was that generals had lied—and were still lying—to both the international community and their fellow citizens." Mirzayanov now lives in the U.S.
Further disclosures followed when Vladimir Uglev, one of Russia's leading binary weapons scientists, revealed the existence of A-232/Novichok-5 in an interview with the magazine ''Novoye Vremya
''The New Times'' (russian: Новое Время) is a Russian language magazine in Russia. The magazine was founded in 1943. The current version, established in 1988, is a liberal, independent Russian weekly news magazine, publishing for Russi ...
'' in early 1994. In his 1998 interview with David E. Hoffman
David Emanuel Hoffman (born August 5, 1953) is an American writer and journalist, a contributing editor to ''The Washington Post''. He won a Pulitzer Prize in 2010 for a book about the legacy of the nuclear arms race.
Journalism
Hoffman was born ...
for '' The Washington Post'' the chemist claimed that he helped invent the A-232 agent, that it was more frostproof, and confirmed that a binary version has been developed from it. Uglev revealed more details in 2018, following the poisoning of the Skripals, stating that "several hundred" compounds were synthesised during the Foliant research but only four agents were weaponised (presumably the Novichok-5, −7, −8 and −9 mentioned by other sources): the first three were liquids and only the last, which was not developed until 1980, could be made into a powder. Unlike the interview twenty years earlier, he denied any binary agents were developed successfully, at least up until his involvement in the research ceased in 1994.
In the 1990s, the German Federal Intelligence Service (BND) obtained a sample of one Novichok agent from a Russian scientist, and the sample was analysed in Sweden, according to a 2018 '' Reuters'' report. The chemical formula was given to Western NATO countries, who synthesized it, then used small amounts to test protective equipment, detection of it, and antidotes to it.
Novichok was referred to in a patent filed in 2008 for an organophosphorus poisoning treatment. The University of Maryland, Baltimore research was part-funded by the U.S. Army.[
Professor ]Leonid Rink
Leonid (russian: Леонид ; uk, Леонід ; be, Леанід, Ljeaníd ) is a Slavic version of the given name Leonidas. The French version is Leonide.
People with the name include:
* Leonid Andreyev (1871–1919), Russian playwright a ...
, who said he had participated in the creation of Novichok agents, confirmed that the structures leaked by Mirzayanov were the correct ones. Rink was himself convicted in Russia for illegally selling a Novichok agent used to assassinate in 1995 a banker Ivan Kivelidi
Ivan () is a Slavic male given name, connected with the variant of the Greek name (English: John) from Hebrew meaning 'God is gracious'. It is associated worldwide with Slavic countries. The earliest person known to bear the name was Bulgar ...
and his secretary.
David Wise, in his book ''Cassidy's Run'', implies that the Soviet program may have been the unintended result of misleading information, involving a discontinued American program to develop a nerve agent code named " GJ", that was fed by a double agent to the Soviets as part of Operation Shocker Operation Shocker was a 23-year counterintelligence operation run by the US Federal Bureau of Investigation against the Soviet Union. The operation involved the fake defection in place of a US Army sergeant based in Washington, D.C. who, in return f ...
.
Development and test sites
Stephanie Fitzpatrick, an American geopolitical consultant, has claimed that the Chemical Research Institute in Nukus, Soviet Uzbekistan produced Novichok agents and '' The New York Times'' has reported that U.S. officials said the site was the major research and testing site for Novichok agents.[ Small, experimental batches of the weapons may have been tested on the nearby Ustyurt Plateau.] Fitzpatrick also writes that the agents may have been tested in a research centre in Krasnoarmeysk near Moscow. Precursor chemicals were made at the Pavlodar Chemical Plant in Soviet Kazakhstan, which was also thought to be the intended Novichok weapons production site, until its still-under-construction chemical warfare agent production building was demolished in 1987 in view of the forthcoming 1990 Chemical Weapons Accord
On June 1, 1990, Presidents George H. W. Bush and Mikhail Gorbachev signed the bilateral U.S.–Soviet Chemical Weapons Accord; officially known as the "Agreement on Destruction and Non-production of Chemical Weapons and on Measures to Facilita ...
and the Chemical Weapons Convention
The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
.
Since its independence in 1991, Uzbekistan has been working with the government of the United States to dismantle and decontaminate the sites where the Novichok agents and other chemical weapons were tested and developed. Between 1999 and 2002 the United States Department of Defense dismantled the major research and testing site for Novichok at the Chemical Research Institute in Nukus, under a $6 million Cooperative Threat Reduction
A cooperative (also known as co-operative, co-op, or coop) is "an autonomous association of persons united voluntarily to meet their common economic, social and cultural needs and aspirations through a jointly owned and democratically-control ...
programme.
Hamish de Bretton-Gordon
Colonel Hamish Stephen de Bretton-Gordon (born September 1963) is a chemical weapons expert and was a director of SecureBio Limited until its dissolution on 17 August 2017. He was formerly a British Army officer for 23 years and commanding officer ...
, a British chemical weapons expert and former commanding officer of the UK's Joint Chemical, Biological, Radiation and Nuclear Regiment and its NATO equivalent, "dismissed" suggestions that Novichok agents could be found in other places in the former Soviet Union such as Uzbekistan and has asserted that Novichok agents were produced only at Shikhany
Shikhany (russian: Шиханы) is a town in Saratov Oblast, Russia, located north of Saratov on the right bank of the Volga River Population: . It has been a closed town since 1997, but lost this status on 1 January 2019. The town is located 2 ...
in Saratov Oblast
Saratov Oblast (russian: Сара́товская о́бласть, ''Saratovskaya oblast'') is a federal subjects of Russia, federal subject of Russia (an oblast), located in the Volga Federal District. Its administrative center is the types of ...
, Russia. Mirzayanov also says that it was at Shikhany, in 1973, that scientist Pyotr Petrovich Kirpichev first produced Novichok agents; Vladimir Uglev joined him on the project in 1975. According to Mirzayanov, while production took place in Shikhany, the weapon was ''tested'' at Nukus between 1986 and 1989.
Following the poisoning of the Skripals, former head of the GosNIIOKhT security department Nikolay Volodin confirmed in an interview to ''Novaya Gazeta
''Novaya Gazeta'' ( rus, Новая газета, t=New Gazette, p=ˈnovəjə ɡɐˈzʲetə) is an independent Russian newspaper known for its critical and investigative coverage of Russian political and social affairs. It is published in Mo ...
'' that there have been tests at Nukus, and said that dogs were used.
In May 2018, the ''Irish Independent'' reported that "Germany's foreign intelligence service secured a sample of the Soviet-developed nerve agent Novichok in the 1990s and passed on its knowledge to partners including Britain and the US, according to German media reports." The sample was analysed in Sweden. Small amounts of the Novichok nerve agent were subsequently produced in some NATO countries for test purposes.
Description of Novichok agents
Mirzayanov provided the first description of these agents. Dispersed in an ultra-fine powder instead of a gas or a vapour, they have unique qualities. A binary agent was then created that would mimic the same properties but would either be manufactured using materials which are not controlled substances under the CWC
CWC may refer to:
Arts and entertainment
* California Writers Club
* Crime Writers of Canada
Businesses and organizations Businesses
* Central Warehousing Corporation, an Indian government-owned corporation
* Cable & Wireless Communications, a ...
, or be undetectable by treaty regime inspections. The most potent compounds from this family, Novichok-5 and Novichok-7, are supposedly around five to eight times more potent than VX.[ The "Novichok" designation refers to the binary form of the agent, with the final compound being referred to by its code number (e.g. A-232). The first Novichok series compound was in fact the binary form of a known V-series nerve agent, VR,] while the later Novichok agents are the binary forms of compounds such as A-232 and A-234.[
According to a classified (secret) report by the US Army National Ground Intelligence Center in '']Military Intelligence Digest
A military, also known collectively as armed forces, is a heavily armed, highly organized force primarily intended for warfare. It is typically authorized and maintained by a sovereign state, with its members identifiable by their distinct ...
'' dated 24 January 1997, agent designated A-232 and its ethyl analogue A-234 developed under the Foliant programme "are as toxic as VX, as resistant to treatment as soman, and more difficult to detect and easier to manufacture than VX". The binary versions of the agents reportedly use acetonitrile
Acetonitrile, often abbreviated MeCN (methyl cyanide), is the chemical compound with the formula and structure . This colourless liquid is the simplest organic nitrile (hydrogen cyanide is a simpler nitrile, but the cyanide anion is not clas ...
and an organic phosphate "that can be disguised as a pesticide precursor."
The agent A-234 is also supposedly around five to eight times more potent than VX.[
The median lethal dose for inhaled A-234 has been estimated as 7 mg/m3 for two minute exposure (minute volume of 15 L, slight activity). The median lethal dose for inhaled A-230, likely the most toxic liquid Novichok, has been estimated as between 1.9 and 3 mg/m3 for two minute exposure. Thus the median lethal dose for inhaled A-234 is 0.2 mg (5000 lethal doses in a gram) and is below 0.1 mg for A-230 (10 000 lethal doses in a gram).
The agents are reportedly capable of being delivered as a liquid, aerosol or gas via a variety of systems, including artillery shells, bombs, missiles and spraying devices.]
Controversy over formulation
Mirzayanov gives somewhat different structures for Novichok agents in his autobiography than those which have been identified by Western experts. The Western formulations suffered from imperfect information,[ as can be seen in Fig. 1 of Chai ''et al'' in which Mirzayanov describes a family of compounds whereas Western scientists instantiate a particular salt.][
Mirzyanov makes clear that a large number of compounds were made, and many of the less potent derivatives were reported in the open literature as new organophosphate insecticides, so that the secret chemical weapons program could be disguised as legitimate pesticide research.
]
Chemistry
According to chemical weapons expert Jonathan Tucker, the first binary formulation developed under the Foliant programme was used to make Substance 33 ( VR), very similar to the more widely known VX, differing only in the alkyl substituents on its nitrogen and oxygen atoms. "This weapon was given the code name Novichok."
A wide range of potential structures have been reported. These all feature the classical organophosphorus core (sometimes with the P=O replaced with P=S or P=Se), which is most commonly depicted as being a phosphoramidate or phosphonate, usually fluorinated (cf. monofluorophosphate
Monofluorophosphate is an anion with the formula PO3F2−, which is a phosphate group with one oxygen atom substituted with a fluoride atom. The charge of the ion is −2. The ion resembles sulfate in size, shape and charge, and can thus form comp ...
). The organic groups are subject to more variety; however, a common substituent is phosgene oxime
Phosgene oxime, or CX, is an organic compound with the formula Cl2CNOH. It is a potent chemical weapon, specifically a nettle agent. The compound itself is a colorless solid, but impure samples are often yellowish liquids. It has a strong, disag ...
or analogues thereof. This is a potent chemical weapon in its own right, specifically as a nettle agent, and would be expected to increase the harm done by the Novichok agent. Many claimed structures from this group also contain cross-linking agent
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...
motifs which may covalently bind to the acetylcholinesterase
Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme
Enzymes () are proteins that a ...
enzyme's active site in several places, perhaps explaining the rapid denaturing of the enzyme that is claimed to be characteristic of the Novichok agents.
Zoran Radić, a chemist at the University of California, San Diego, performed an ''in silico'' docking study with Mirzayanov's version of the A-232 structure against the active site of the acetylcholinesterase enzyme. The model predicted a tight fit with high binding affinity and formation of a covalent bond
A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...
to a serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
residue in the active site, with a similar binding mode to established nerve agents such as sarin and soman.
Detection
A procedure of retrospective detection of Novichok type poisons in victim's tissues has been proposed recently[ Daan Noort,* Alex Fidder, Debora van der Riet-van Oeveren, Ruud Busker, and Marcel J. van der Schans. Verification of Exposure to Novichok Nerve Agents Utilizing a Semitargeted Human Butyrylcholinesterase Nonapeptide Assay. ''Chem. Res. Toxicol.'' 2021, 34, 1926−1932] This method is a modification of the procedure that was developed earlier for identification of sarin poisoning.[Fidder, A., Noort, D., Hulst, A. G., De Ruiter, R., Van der Schans, M. J., Benschop, H. P., and Langenberg, J. P. (2002) Retrospective detection of exposure to organophosphorus anti-cholinesterases: mass spectrometric analysis of phosphylated human butyrylcholinesterase. ''Chem. Res. Toxicol.'' 15, 582−590.] This method capitalizes on the fact that poisoning by organic phosphonates occurs via phosphonylation of the hydorxy group of serine in the active site of cholinesterases,[ and that severe poisoning occurs when a major part of these enzymes are inactivated. The concentration of butyryl cholinesterase (HuBuChE) in human plasma is normally about 80 nM.][ That makes it a good source of adducts that can be subjected to analysis.
The procedure consists in three steps (see the Figure A). First, HuBuChE is obtained from the victim's plasma. Second, the enzyme is subjected to pepsin proteolysis. Third, the peptide mixture obtained is subjected to LC-MSMS analysis.][ If no poisoning took place, the peptide mixture contains a non-modified nonapeptide FGESAGAAS. However, cholinesterases are inactivated due to a chemical reaction with Novichok type nerve agent, the modified nonapeptide is be detected, and its exact (high resolution) mass (along with the mass of the secondary ion produced during collision induced dissociation) allows inambiguous identification of the fact of poisoning and the exact structure of the poison.][ Thus, the example at Figure A shows the masses of the primary and secondary ions obtained from the plasma of the victim poisoned by A-230. If a victim is poisoned by other Novichok type agents, the masses are different.][
This method allows identification of poisons at few ppb ratio, but that may be insufficient for reliable detection of the isotopic signature of the adducts, and, therefore an unambiguous identification of the geographic origin of the poison.
]
Lifetime
According to Vladimir Uglev, who headed a group that worked on the development of the Novichok agents,[ at least one liquid form of Novichok is very stable with a slow evaporation rate and can remain potent for possibly up to 50 years. Insufficient research has been conducted to fully understand its persistence in various situations in the environment.
]
Effects and countermeasures
As nerve agents, the Novichok agents belong to the class of organophosphate
In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered a ...
acetylcholinesterase inhibitors. These chemical compounds inhibit the enzyme acetylcholinesterase
Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme
Enzymes () are proteins that a ...
, preventing the normal breakdown of the neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
. Acetylcholine concentrations then increase at neuromuscular junctions to cause involuntary contraction of all skeletal muscles ( cholinergic crisis). This then leads to respiratory and cardiac arrest (as the victim's heart and diaphragm muscles no longer function normally) and finally death from heart failure or suffocation as copious fluid secretions fill the victim's lungs.
As can be seen with other organophosphate poisonings, Novichok agents may cause lasting nerve damage, resulting in permanent disablement of victims, according to Russian scientists. Their effect on humans was demonstrated by the accidental exposure of Andrei Zheleznyakov, one of the scientists involved in their development, to the residue of an unspecified Novichok agent while working in a Moscow laboratory in May 1987. He was critically injured and took ten days to recover consciousness after the incident. He lost the ability to walk and was treated at a secret clinic in Leningrad for three months afterwards. The agent caused permanent harm, with effects that included "chronic weakness in his arms, a toxic hepatitis that gave rise to cirrhosis of the liver, epilepsy, spells of severe depression, and an inability to read or concentrate that left him totally disabled and unable to work." He never recovered and, after five years of deteriorating health, died in July 1992.
The use of a fast-acting peripheral anticholinergic drug such as atropine
Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...
can block the receptors where acetylcholine acts to prevent poisoning (as in the treatment for poisoning by other acetylcholinesterase inhibitors). Atropine, however, is difficult to administer safely, because its effective dose for nerve agent poisoning is close to the dose at which patients suffer severe side effects, such as changes in heart rate and thickening of the bronchial secretions, which fill the lungs of someone suffering nerve agent poisoning so that suctioning of these secretions, and other advanced life support techniques, may be necessary in addition to administration of atropine to treat nerve agent poisoning.
In the treatment of nerve agent poisoning, atropine is most often administered along with a Hagedorn oxime
Hagedorn is a surname of German language origin, meaning "hawthorn". Notable people with the surname include:
* Bettina Hagedorn (born 1955), German politician
* Bob Hagedorn, US Democratic legislator from Colorado
* Brian Hagedorn, Wisconsin Jud ...
such as pralidoxime, obidoxime
Obidoxime is a member of the oxime family used to treat nerve gas poisoning. Oximes are drugs known for their ability to reverse the binding of organophosphorus compounds to the enzyme acetylcholinesterase (AChE).
AChE is an enzyme that removes ...
, TMB-4
Trimedoxime bromide (INN), also known as dipyroxime or TMB-4, is an oxime used in the treatment of organophosphate poisoning It is chemically related to pralidoxime
Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM, usually as the chl ...
, or HI-6, which reactivates acetylcholinesterase which has been inactivated by phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
by an organophosphorus nerve agent and relieves the respiratory muscle paralysis caused by some nerve agents. Pralidoxime is not effective in reactivating acetylcholinesterase inhibited by some older nerve agents such as soman[ or the Novichok nerve agents, described in the literature as being up to eight times more toxic than nerve agent VX.]
The US Army has funded studies of the use of galantamine along with atropine in the treatment of a number of nerve agents, including soman and the Novichok agents. An unexpected synergistic interaction was seen to occur between galantamine (given between five hours before to thirty minutes after exposure) and atropine in an amount of 6 mg/kg or higher. Increasing the dose of galantamine from 5 to 8 mg/kg decreased the dose of atropine needed to protect experimental animals from the toxicity of soman in dosages 1.5 times the LD50 (lethal dose in half the animals studied).
There have been differing claims about the persistence of Novichok and binary precursors in the environment. One view is that it is not affected by normal weather conditions, and may not decompose as quickly as other organophosphates
In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...
. However, Mirzayanov states that Novichok decomposes within four months.
Instances of usage
Poisoning of Ivan Kivelidi and Zara Ismailova
A Novichok agent was used in 1995 to poison Russian banker , who died three days later in a hospital at the age of 46. The poison was believed to have been applied to Kivelidi's office phone in Moscow. His secretary Zara Ismailova also developed symptoms one month later and then died a day later in a hospital at the age of 35.
Kivelidi was the head of the Russian Business Round Table, and had close ties to Viktor Chernomyrdin, who was at that time Prime Minister of Russia
The chairman of the government of the Russian Federation, also informally known as the prime minister, is the nominal head of government of Russia. Although the post dates back to 1905, its current form was established on 12 December 1993 fo ...
. Russian opposition
Opposition to the government of President Vladimir Putin in Russia can be divided between the parliamentary opposition parties in the State Duma and the various non-systemic opposition organizations. While the former are largely viewed as bei ...
–linked historians Yuri Felshtinsky and Vladimir Pribylovsky speculated that the murder became "one of the first in the series of poisonings organised by Russia's security services".
The Russian Ministry of Internal Affairs analysed the substance and announced that it was "a phosphorus-based military-grade nerve agent" "whose formula was strictly classified". According to Nesterov, the administrative head of Shikhany, he did not know of "a single case of such poison being sold illegally" and noted that the poison "is used by professional spies".
Vladimir Khutsishvili, a former business partner of Kivelidi's, was subsequently convicted of the killings. According to ''The Independent'', "A closed trial found that his business partner had obtained the substance via intermediaries from an employee of the State Research Institute of Organic Chemistry and Technology (ГосНИИОХТ / GosNIIOKhT), which was involved in the development of Novichok agents. However, Khutsishvili, who claimed that he was innocent, had not been detained at the time of the trial and freely left the country. He was only arrested in 2006 after he returned to Russia, believing that the ten-year old case was closed. Felshtinsky and Pribylovsky claimed that Russia's security services, which had access to the chemical agent, had framed Khutsishvili for the murder, and that the security services had organised the murder on the orders of a senior Russian state official. Boris Kuznetsov, who represented Khutsishvili and believed in his innocence, blames "rogue intelligence officers".[
Leonid Rink, an employee of GosNIIOKhT, received a one-year suspended sentence for selling Novichok agents to unnamed buyers "of Chechen ethnicity" soon after the poisoning of Kivelidi and Izmailova.
]
Poisoning of Sergei and Yulia Skripal
On 12 March 2018, the UK government said that a Novichok agent had been used in an attack in the English city of Salisbury on 4 March 2018 in an attempt to kill former GRU officer Sergei Skripal and his daughter Yulia. British Prime Minister Theresa May said in Parliament: "Either this was a direct action by the Russian state against our country, or the Russian government lost control of its potentially catastrophically damaging nerve agent and allowed it to get into the hands of others." On 13 March the BBC asked Vladimir Putin if Russia was "behind the poisoning of" Skripal and he answered "Get to the bottom of it first then we can discuss it" while he delegated a spokesperson to claim that "a circus show in the British parliament" was the upshot. Boris Johnson, the Foreign Secretary
The secretary of state for foreign, Commonwealth and development affairs, known as the foreign secretary, is a minister of the Crown of the Government of the United Kingdom and head of the Foreign, Commonwealth and Development Office. Seen as ...
, refused to shake hands with Russian ambassador Alexander Yakovenko as he expressed "outrage" over the attack. On the next day, the UK expelled 23 Russian diplomats after the Russian government refused to meet the UK's deadline of midnight on 13 March 2018 to give an explanation for the use of the substance. Addressing the United Nations Security Council on 15 March, Vassily Nebenzia
Vasily Alekseyevich Nebenzya ( rus, Василий Алексеевич Небензя; born 26 February, 1962) is a Russian diplomat and the current Permanent Representative of Russia to the United Nations. His official title is Ambassador Extra ...
, the Russian envoy to the UN, responded to the British allegations by denying that Russia had ever produced or researched the agents, stating: "No scientific research or development under the title novichok were carried out."[
After the attack, 21 members of the emergency services and public were checked for possible exposure, and three were hospitalised. As of 12 March, one police officer remained in hospital.][ Five hundred members of the public were advised to decontaminate their possessions to prevent possible long-term exposure, and 180 members of the military and 18 vehicles were deployed to assist with decontamination at locations in and around Salisbury. Up to 38 people in Salisbury have been affected by the agent to an undetermined extent.
Daniel Gerstein, a former senior official at the U.S. Department of Homeland Security, said it was possible that Novichok nerve agents had been used before in Britain to assassinate Kremlin targets, but had not been detected: "It's entirely likely that we have seen someone expire from this and not realised it. We realised in this case because they were found unresponsive on a park bench. Had it been a higher dose, maybe they would have died and we would have thought it was natural causes."
On 20 March 2018, Ahmet Üzümcü, Director-General of the OPCW, said that it would take "another two to three weeks to finalise the analysis" of samples taken from the poisoning of Skripal. On 3 April 2018, the Defence Science and Technology Laboratory announced that it was "completely confident" that the agent used was Novichok, although they still did not know the "precise source" of the agent. Experts said that their findings did not challenge the conclusions by UK government: "We provided that information to the Government who have then used a number of other sources to come to the conclusions that they have." On 12 April 2018 the OPCW announced that their investigations agreed with the conclusions made by the UK about the identity of the chemical used.]
By September 2018 two Russian "tourists", " Alexander Petrov" and "Ruslan Boshirov
Anatoly Vladimirovich Chepiga (russian: Анатолий Владимирович Чепига, born 5 April 1979) is a colonel in the Russian General Staff's Main Directorate (also known as GRU), the military intelligence service of the Russ ...
", had been identified as suspects. They told Margarita Simonyan, the chief editor of RT television, in an interview that they both worked in the sports nutrition business and that "Those are our real names.. We're afraid to go out, we fear for ourselves, our lives and lives of our loved ones." The Crown Prosecution Service announced enough evidence was obtained by that date "to convict the two men" of the attack, although it did not apply to Russia "for their extradition because Russia does not extradite its own nationals... A European Arrest Warrant has been obtained in case they travel to the EU."
In February 2019, the Bellingcat website published precise allegations that identified GRU Major Denis Vyacheslavovich Sergeev
Denis Vyacheslavovich Sergeev, in Europe alias Sergej Fedotov (born 1973 in Usharal, Kazakhstan) is a Russian officer of military intelligence service GRU (G.U.), GRU. He is suspected to be the local coordinator of the poisoning of Sergei and Yul ...
as a man who travelled in March 2018 to London under the false identity of Sergei Fedotov. It is claimed with detailed photograph evidence, and phone, travel, passport, and motoring database records that GRU Colonels Alexander Mishkin
Alexander Yevgenyevich Mishkin (russian: Алекса́ндр Евге́ньевич Ми́шкин) is a doctor in the Russian General Staff's Main Directorate (also known as GRU), the military intelligence service of the Russian Federation.
O ...
and Anatoly Chepiga assumed the identities of Petrov and Boshirov, placed the poison on Skripal's doorknob. On 28 June 2019 it was reported that Sergeyev received instructions from his GRU superior by cell phone on more than ten occasions during his UK visits.
Poisoning of Charlie Rowley and Dawn Sturgess
On 30 June 2018, Charlie Rowley and Dawn Sturgess were found unconscious at a house in Amesbury
Amesbury () is a town and civil parish in Wiltshire, England. It is known for the prehistoric monument of Stonehenge which is within the parish. The town is claimed to be the oldest occupied settlement in Great Britain, having been first settle ...
, Wiltshire, about eight miles from the Salisbury poisoning site. On 4 July 2018, police said that the pair had been poisoned with the same nerve agent as ex-Russian spy Sergei Skripal.[
On 8 July 2018, Sturgess died as a result of the poisoning. Rowley regained consciousness and began recovering in hospital. He told his brother Matthew the nerve agent had been in a small perfume or aftershave bottle, which they had found in a park about nine days before spraying themselves with it. The police later closed and fingertip-searched Queen Elizabeth Gardens in Salisbury.
]
Poisoning of Emilian Gebrev
In the aftermath of the Skripal poisoning, investigative journalists were able to track some of the people involved also in Bulgaria. This is how another suspected poisoning case dating back to April 2015 during their stay in the country was linked to the Novichok nerve agent. The victim was the Bulgarian arms dealer Emilian Gebrev, who shares two hypotheses why he might have been attacked: The first one links to the fact that his arms manufacturing company Dunarit exports defense equipment to Ukraine. The other one relates to an attempt by an offshore company to take over Dunarit. The takeover attempt was ultimately linked to the influential Bulgarian politician and oligarch Delyan Peevski
Delyan Slavchev Peevski ( bg, Делян Славчев Пеевски ) (born 27 July 1980) is a Bulgarian politician, oligarch, entrepreneur and media mogul. He served as MP from the parliamentary group of the DPS in the 41st, 42nd, 43rd an ...
who has historically been funded by Russia's state-owned VTB Bank.
Poisoning of Alexei Navalny
On 20 August 2020, Russian opposition leader Alexei Navalny
Alexei Anatolievich Navalny ( rus, links=no, Алексей Анатольевич Навальный, , ɐlʲɪkˈsʲej ɐnɐˈtolʲjɪvʲɪtɕ nɐˈvalʲnɨj; born 4 June 1976) is a Opposition to Vladimir Putin in Russia, Russian opposition ...
fell ill during a flight from Tomsk
Tomsk ( rus, Томск, p=tomsk, sty, Түң-тора) is a city and the administrative center of Tomsk Oblast in Russia, located on the Tom River. Population:
Founded in 1604, Tomsk is one of the oldest cities in Siberia. The city is a not ...
to Moscow. The plane made an emergency landing in Omsk
Omsk (; rus, Омск, p=omsk) is the administrative center and largest city of Omsk Oblast, Russia. It is situated in southwestern Siberia, and has a population of over 1.1 million. Omsk is the third largest city in Siberia after Novosibirsk ...
, where Navalny was hospitalized and put in a medically induced coma
An induced comaalso known as a medically induced coma (MIC), barbiturate-induced coma, or drug-induced comais a temporary coma (a deep state of unconsciousness) brought on by a controlled dose of an anesthetic drug, often a barbiturate such as pe ...
. His family suspected his illness was caused by a poison put into a cup of tea he drank before the flight. He was evacuated to the Charité
The Charité – Universitätsmedizin Berlin (Charité – Berlin University of Medicine) is one of Europe's largest university hospitals, affiliated with Humboldt University and Free University Berlin. With numerous Collaborative Research Cen ...
hospital in Berlin, Germany, the following day. On 2 September, the German government said that it had "unequivocal evidence" that Navalny was poisoned by a Novichok agent after tests at a German military lab and had called on the Russian government for an explanation, with labs in France and Sweden corroborating the findings.
On 4 September, the North Atlantic Council was briefed by the German representative on the "appalling assassination attempt on" Navalny. In a post-meeting press conference, Secretary-General Jens Stoltenberg
Jens Stoltenberg (born 16 March 1959) is a Norwegian politician who has been serving as the 13th secretary general of NATO since 2014. A member of the Norwegian Labour Party, he previously served as the 34th prime minister of Norway from 2000 to ...
said that NATO allies "agree that Russia has serious questions it must answer", that the OPCW needed to conduct an impartial investigation, that "those responsible for this attack must be brought to justice" and called on Russia to "provide complete disclosure of the Novichok programme to the OPCW."
Navalny has been out of his coma since 7 September.
On 6 October, the OPCW confirmed the presence of a cholinesterase inhibitor
Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the syn ...
from the Novichok group in Navalny's blood and urine samples. At the same time, the OPCW report clarified that Navalny was poisoned with a new type of Novichok, which was not included in the list of controlled chemicals of the Chemical Weapons Convention
The Chemical Weapons Convention (CWC), officially the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, is an arms control treaty administered by the Organisation for ...
.
See also
* Poison laboratory of the Soviet secret services
The poison laboratory of the Soviet secret services, alternatively known as Laboratory 1, Laboratory 12, and Kamera (which means "The Cell" in Russian), was a covert research-and-development facility of the Soviet secret police agencies. Th ...
* Russia and weapons of mass destruction
List of Novichok agents
* A-230
* A-232
* A-234
* A-242
* A-262
A-262 is an organophosphate nerve agent. It was developed in the Soviet Union under the FOLIANT program and is one of the group of compounds referred to as Novichok agents that were revealed by Vil Mirzayanov. Mirzayanov gives little specific infor ...
(Novichok-7)
* C01-A035
* C01-A039
C01-A039 is a Novichok agent. It is the ethyl phosphorofluoridate ester of phosgene oxime.
See also
*C01-A035
C01-A035 is a Novichok agent. It is the methyl phosphorofluoridate ester of phosgene oxime
Phosgene oxime, or CX, is an organic ...
* C01-A042
C01-A042 is a Novichok agent.
See also
*Novichok agent
*C01-A035
*C01-A039
C01-A039 is a Novichok agent. It is the ethyl phosphorofluoridate ester of phosgene oxime.
See also
*C01-A035
C01-A035 is a Novichok agent. It is the methyl phos ...
References
Notes
Citations
Bibliography
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External links
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{{Neurotoxins
Acetylcholinesterase inhibitors
Cold War weapons of the Soviet Union
Nerve agents
Organophosphates
Science and technology in the Soviet Union
Soviet chemical weapons program
Soviet inventions