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Nerve agents, sometimes also called nerve gases, are a class of
organic chemicals
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The s ...
that disrupt the mechanisms by which nerves transfer messages to organs. The disruption is caused by the blocking of 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 ...
(AChE), an enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that catalyzes the breakdown of 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 ...
, a 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 ...
. Nerve agents are acetylcholinesterase inhibitor
Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and ...
s used as poison
Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broa ...
.
Poisoning by a nerve agent leads to constriction of pupil
The pupil is a black hole located in the center of the iris of the eye that allows light to strike the retina.Cassin, B. and Solomon, S. (1990) ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishing Company. It appears black ...
s, profuse salivation
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be e ...
, convulsion
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
s, and involuntary urination
Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
and defecation
Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...
, with the first symptoms appearing in seconds after exposure. Death by asphyxiation
Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects primarily the tissues and organs. There are many circumstances that can i ...
or cardiac arrest
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
may follow in minutes due to the loss of the body's control over respiratory
The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...
and other muscles. Some nerve agents are readily vaporized or aerosol
An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be natural or Human impact on the environment, anthropogenic. Examples of natural aerosols are fog o ...
ized, and the primary portal of entry into the body is the respiratory system
The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...
. Nerve agents can also be absorbed through the skin, requiring that those likely to be subjected to such agents wear a full body suit in addition to a respirator
A respirator is a device designed to protect the wearer from inhaling hazardous atmospheres including fumes, vapours, gases and particulate matter such as dusts and airborne pathogens such as viruses. There are two main categories of respir ...
.
Nerve agents are generally colorless, tasteless liquids that may evaporate to a gas
Gas is one of the four fundamental states of matter (the others being solid, liquid, and plasma).
A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or ...
. Agents Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.VX are odorless; Tabun has a slightly fruity odor and
Soman
Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiti ...
has a slight camphor
Camphor () is a waxy, colorless solid with a strong aroma. It is classified as a terpenoid and a cyclic ketone. It is found in the wood of the camphor laurel ('' Cinnamomum camphora''), a large evergreen tree found in East Asia; and in the k ...
odor.
Biological effects
Nerve agents attack thenervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
. All such agents function the same way resulting in cholinergic crisis
A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine.
Symptoms and diagnosis
As a result of ch ...
: they inhibit
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...
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 ...
, which is responsible for the breakdown of 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 ...
(ACh) in the synapse
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.
Synapses are essential to the transmission of nervous impulses from ...
s between nerves that control whether muscle tissues are to relax or contract. If the agent cannot be broken down, muscles are prevented from receiving 'relax' signals and they are effectively paralyzed. It is the compounding of this paralysis throughout the body that quickly leads to more severe complications, including the heart and the muscles used for breathing. Because of this, the first symptoms usually appear within 30 seconds of exposure and death can occur via asphyxia
Asphyxia or asphyxiation is a condition of deficient supply of oxygen to the body which arises from abnormal breathing. Asphyxia causes generalized hypoxia, which affects primarily the tissues and organs. There are many circumstances that can i ...
tion or cardiac arrest
Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
in a few minutes, depending upon the dose received and the agent used.
Initial symptoms following exposure to nerve agents (like Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.constriction of the pupils. Soon after, the victim will have difficulty breathing and will experience nausea and salivation. As the victim continues to lose control of bodily functions, involuntary
The ''G-series'' is thus named because German scientists first synthesized them. G series agents are known as non-persistent, meaning that they evaporate shortly after release, and do not remain active in the dispersal area for very long. All of the compounds in this class were discovered and synthesized during or prior to
The ''V-series'' is the second family of nerve agents and contains five well known members: VE, VG, VM, VR, and VX, along with several more obscure analogues.
The most studied agent in this family, VX (it is thought that the 'X' in its name comes from its overlapping isopropyl radicals), was invented in the 1950s at
salivation
Saliva (commonly referred to as spit) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which DNA can be e ...
, lacrimation
Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all land mammals. Tears are made up of water, electrolytes, proteins, lipids, and mucins that form layers on the surface of eyes. The different types of ...
, urination
Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
, defecation
Defecation (or defaecation) follows digestion, and is a necessary process by which organisms eliminate a solid, semisolid, or liquid waste material known as feces from the digestive tract via the anus. The act has a variety of names ranging f ...
,
gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
pain and vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
will be experienced. Blister
A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled wi ...
s and burning of the eyes and/or lungs may also occur. This phase is followed by initially myoclonic jerks
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
(muscle jerks) followed by status epilepticus
Status epilepticus (SE), or status seizure, is a single seizure lasting more than 5 minutes or 2 or more seizures within a 5-minute period without the person returning to normal between them. Previous definitions used a 30-minute time limit. The s ...
–type epileptic seizure. Death then comes via complete respiratory depression, most likely via the excessive peripheral activity at the neuromuscular junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber.
It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction.
Muscles require innervation to ...
of the diaphragm
Diaphragm may refer to:
Anatomy
* Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen
* Pelvic diaphragm or pelvic floor, a pelvic structure
* Urogenital diaphragm or triangular ligament, a pelvic structure
Other
* Diap ...
.
The effects of nerve agents are long lasting and increase with continued exposure. Survivors of nerve agent poisoning almost invariably develop chronic neurological damage and related psychiatric
Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry.
Initial psychi ...
effects. Possible effects that can last at least up to 2–3 years after exposure include blurred vision, tiredness
Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, declined memory, hoarse voice, palpitations
Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart.
Symptoms include a rapi ...
, sleeplessness
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, shoulder stiffness and eye strain
Eye strain, also known as asthenopia (from Greek ''a-sthen-opia'', grc, ἀσθενωπία, ), is a common eye condition that manifests through non-specific symptoms such as fatigue, pain in or around the eyes, blurred vision, headache, and ...
. In people exposed to nerve agents, serum and erythrocyte
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
acetylcholinesterase in the long-term are noticeably lower than normal and tend to be lower the worse the persisting symptoms are.
Mechanism of action
When a normally functioningmotor nerve
A motor nerve is a nerve that transmits motor signals from the central nervous system (CNS) to the muscles of the body. This is different from the motor neuron, which includes a cell body and branching of dendrites, while the nerve is made up of ...
is stimulated, it releases 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 ...
, which transmits the impulse to a muscle or organ. Once the impulse is sent, 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 ...
immediately breaks down the acetylcholine in order to allow the muscle or organ to relax.
Nerve agents disrupt the nervous system by inhibiting the function of the enzyme acetylcholinesterase by forming 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 ...
with its active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
, where acetylcholine would normally be broken down (undergo hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
). Acetylcholine thus builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. This same action also occurs at the gland and organ levels, resulting in uncontrolled drooling, tearing of the eyes (lacrimation) and excess production of mucus from the nose (rhinorrhea).
The reaction product of the most important nerve agents, including Soman, Sarin, Tabun and VX, with acetylcholinesterase were solved by the U.S. Army using X-ray crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
in the 1990s. The reaction products have been confirmed subsequently using different sources of acetylcholinesterase and the closely related target enzyme, butyrylcholinesterase. The X-ray structures clarify important aspects of the reaction mechanism (e.g., stereochemical inversion) at atomic resolution and provide a key tool for antidote development.
Treatment
Standard treatment for nerve agentpoisoning
A poison can be any substance that is harmful to the body. It can be swallowed, inhaled, injected or absorbed through the skin. Poisoning is the harmful effect that occurs when too much of that substance has been taken. Poisoning is not to ...
is a combination of an anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.
These agents inhibit the parasympathetic nervous system ...
to manage the symptoms, and an oxime
In organic chemistry, an oxime is a organic compound belonging to the imines, with the general formula , where R is an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted ...
as an antidote. Anticholinergics treat the symptoms by reducing the effects of acetylcholine, while oximes displaces phosphate molecules from the active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
of the cholinesterase
The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:
: an acylcholine + H2O = choline + a carboxylate
Several of these serve as neurotransmitters ...
enzymes, allowing the breakdown of acetylcholine. Military personnel are issued the combination in an autoinjector
An autoinjector (or auto-injector) is a medical device designed to deliver a dose of a particular drug. The injectors were initially designed to overcome the hesitation associated with self-administration of the needle-based drug delivery device ...
(e.g. ATNAA
An ATNAA (Antidote Treatment Nerve Agent Autoinjector) is any of a variety of autoinjectors in use with the US Armed Forces. An autoinjector is a medical device designed to deliver a single dose of a particular (typically life-saving) drug.
Mos ...
), for ease of use in stressful conditions.
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 ...
is the standard anticholinergic drug used to manage the symptoms of nerve agent poisoning. It acts as an antagonist to muscarinic acetylcholine receptor
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...
s, blocking the effects of excess acetylcholine. Some synthetic anticholinergics, such as biperiden
Biperiden, sold under the brand name Akineton among others, is a medication used to treat Parkinson disease and certain drug-induced movement disorders. It is not recommended for tardive dyskinesias. It is taken by mouth, injection into a vein, ...
, may counteract the central symptoms of nerve agent poisoning more effectively than atropine, since they pass the blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
better than atropine. While these drugs will save the life of a person affected by nerve agents, that person may be incapacitated briefly or for an extended period, depending on the extent of exposure. The endpoint of atropine administration is the clearing of bronchial secretions.
Pralidoxime chloride
Pralidoxime (2-pyridine aldoxime methyl chloride) or 2-PAM, usually as the chloride or iodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to treat organophosph ...
(also known as ''2-PAMCl'') is the standard oxime used to treat nerve agent poisoning. Rather than counteracting the initial effects of the nerve agent on the nervous system as does atropine, pralidoxime chloride reactivates the poisoned enzyme (acetylcholinesterase) by scavenging the phosphoryl group attached on the functional hydroxyl group of the enzyme, counteracting the nerve agent itself. Revival of acetylcholinesterase with pralidoxime chloride works more effectively on nicotinic receptors
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
while blocking acetylcholine receptors with atropine is more effective on muscarinic receptors
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...
.
Anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s, such as diazepam, may be administered to manage seizures, improving long term prognosis and reducing risk of brain damage. This is not usually self-administered as its use is for actively seizing patients.
Countermeasures
Pyridostigmine bromide
Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth b ...
was used by the US military
The United States Armed Forces are the Military, military forces of the United States. The armed forces consists of six Military branch, service branches: the United States Army, Army, United States Marine Corps, Marine Corps, United States N ...
in the first Gulf War
The Gulf War was a 1990–1991 armed campaign waged by a 35-country military coalition in response to the Iraqi invasion of Kuwait. Spearheaded by the United States, the coalition's efforts against Iraq were carried out in two key phases: ...
as a pretreatment for Soman
Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiti ...
as it increased the median lethal dose
In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the ...
. It is only effective if taken prior to exposure and in conjunction with Atropine and Pralidoxime, issued in the Mark I NAAK
In the United States military, the Mark I NAAK, or MARK I Kit, ("Nerve Agent Antidote Kit") is a dual-chamber autoinjector: Two anti-nerve agent drugs— atropine sulfate and pralidoxime chloride—each in injectable form, constitute the kit. T ...
autoinjector, and is ineffective against other nerve agents. While it reduces fatality rates, there is an increased risk of brain damage; this can be mitigated by administration of an anticonvulsant. Evidence suggests that the use of pyridostigmine may be responsible for some of the symptoms of Gulf War syndrome
Gulf War syndrome or Gulf War illness is a chronic and multi-symptomatic disorder affecting military veterans of both sides of the 1990–1991 Persian Gulf War. A wide range of acute and chronic symptoms have been linked to it, including fatigue ...
.
Butyrylcholinesterase
Butyrylcholinesterase (HGNC symbol BCHE; EC 3.1.1.8), also known as BChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it ...
is under development by the U.S. Department of Defense as a prophylactic
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
countermeasure
A countermeasure is a measure or action taken to counter or offset another one. As a general concept, it implies precision and is any technological or tactical solution or system designed to prevent an undesirable outcome in the process. The fi ...
against 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 ...
nerve agents. It binds nerve agent in the bloodstream before the poison can exert effects in the nervous system.
Both purified 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 ...
and butyrylcholinesterase have demonstrated success in animal studies as "biological scavengers" (and universal targets) to provide stoichiometric
Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions.
Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equal ...
protection against the entire spectrum of organophosphate nerve agents. Butyrylcholinesterase currently is the preferred enzyme for development as a pharmaceutical drug primarily because it is a naturally circulating human plasma protein (superior pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
) and its larger active site compared with acetylcholinesterase may permit greater flexibility for future design and improvement of butyrylcholinesterase to act as a nerve agent scavenger.
Classes
There are two main classes of nerve agents. The members of the two classes share similar properties and are given both a common name (such as ''Sarin'') and a two-characterNATO
The North Atlantic Treaty Organization (NATO, ; french: Organisation du traité de l'Atlantique nord, ), also called the North Atlantic Alliance, is an intergovernmental military alliance between 30 member states – 28 European and two No ...
identifier (such as GB).
G-series
The ''G-series'' is thus named because German scientists first synthesized them. G series agents are known as non-persistent, meaning that they evaporate shortly after release, and do not remain active in the dispersal area for very long. All of the compounds in this class were discovered and synthesized during or prior to World War II
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
, led by Gerhard Schrader
Gerhard Schrader (25 February 1903 – 10 April 1990) was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. Schrader is best known for his accidental discovery of ...
(later under the employment of IG Farben
Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate (company), conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, ...
).
This series is the first and oldest family of nerve agents. The first nerve agent ever synthesized was GA ( Tabun) in 1936. GB (Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.Soman
Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiti ...
) in 1944, and finally the more obscure GF (Cyclosarin
Cyclosarin or GF (cyclohexyl methylphosphonofluoridate) is an extremely toxic substance used as a chemical weapon. It is a member of the '' G-series'' family of nerve agents, a group of chemical weapons discovered and synthesized by a German te ...
) in 1949. GB was the only G agent that was fielded by the US as a munition, in rockets, aerial bombs
An aerial bomb is a type of Explosive weapon, explosive or Incendiary bomb, incendiary weapon intended to travel through the Atmosphere of Earth, air on a predictable trajectory. Engineers usually develop such bombs to be dropped from an aircraft ...
, and artillery shell
A shell, in a military context, is a projectile whose payload contains an explosive, incendiary, or other chemical filling. Originally it was called a bombshell, but "shell" has come to be unambiguous in a military context. Modern usage ...
s.
V-series
The ''V-series'' is the second family of nerve agents and contains five well known members: VE, VG, VM, VR, and VX, along with several more obscure analogues.
The most studied agent in this family, VX (it is thought that the 'X' in its name comes from its overlapping isopropyl radicals), was invented in the 1950s at Porton Down
Porton Down is a science park in Wiltshire, England, just northeast of the village of Porton, near Salisbury. It is home to two British government facilities: a site of the Ministry of Defence's Defence Science and Technology Laboratory (Dstl ...
in the United Kingdom. Ranajit Ghosh, a chemist at the Plant Protection Laboratories of Imperial Chemical Industries
Imperial Chemical Industries (ICI) was a British chemical company. It was, for much of its history, the largest manufacturer in Britain.
It was formed by the merger of four leading British chemical companies in 1926.
Its headquarters were at M ...
(ICI) was investigating a class of organophosphate compounds (organophosphate esters of substituted aminoethanethiols). Like Schrader, Ghosh found that they were quite effective pesticides. In 1954, ICI put one of them on the market under the trade name Amiton
VG (IUPAC name: ''O'',''O''-diethyl ''S''- -(diethylamino)ethylphosphorothioate) (also called Amiton or Tetram) is a "V-series" nerve agent chemically similar to the better-known VX nerve agent. Tetram is the common Russian name for the substance ...
. It was subsequently withdrawn, as it was too toxic for safe use. The toxicity did not escape military notice and some of the more toxic materials had been sent to the British Armed Forces research facility at Porton Down
Porton Down is a science park in Wiltshire, England, just northeast of the village of Porton, near Salisbury. It is home to two British government facilities: a site of the Ministry of Defence's Defence Science and Technology Laboratory (Dstl ...
for evaluation. After the evaluation was complete, several members of this class of compounds became a new group of nerve agents, the V agents (depending on the source, the V stands for Victory, Venomous, or Viscous). The best known of these is probably VX, with VR ("Russian V-gas") coming a close second (Amiton is largely forgotten as VG, with G probably coming from "G"hosh). All of the V-agents are persistent agents, meaning that these agents do not degrade or wash away easily and can therefore remain on clothes and other surfaces for long periods. In use, this allows the V-agents to be used to blanket terrain to guide or curtail the movement of enemy ground forces. The consistency of these agents is similar to oil; as a result, the contact hazard for V-agents is primarily – but not exclusively – dermal. VX was the only V-series agent that was fielded by the US as a munition, in rockets, artillery shell
A shell, in a military context, is a projectile whose payload contains an explosive, incendiary, or other chemical filling. Originally it was called a bombshell, but "shell" has come to be unambiguous in a military context. Modern usage ...
s, airplane spray tanks, and landmine
A land mine is an explosive device concealed under or on the ground and designed to destroy or disable enemy targets, ranging from combatants to vehicles and tanks, as they pass over or near it. Such a device is typically detonated automati ...
s.''FM 3–8 Chemical Reference handbook''; US Army; 1967
Analyzing the structure of thirteen V agents, the standard composition, which makes a compound enter this group, is the absence of halides
In chemistry, a halide (rarely halogenide) is a binary chemical compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative (or more electropositive) than the halogen, to make a fluor ...
. It is clear that many agricultural pesticides can be considered as V agents if they are notoriously toxic. The agent is not required to be a phosphonate and presents a dialkylaminoethyl group. The toxicity requirement is waived as the VT agent and its salts (VT-1 and VT-2) are "non-toxic". Replacing the sulfur atom with selenium increases the toxicity of the agent by orders of magnitude.
Novichok agents
The Novichok (Russian: , "newcomer") agents, a series oforganophosphate
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 ...
compounds, were developed in the Soviet Union
The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen national ...
and in Russia from the mid-1960s to the 1990s. The Novichok program aimed to develop and manufacture highly deadly chemical weapons that were unknown to the West. The new agents were designed to be undetectable by standard NATO chemical-detection equipment and overcome contemporary chemical-protective equipment.
In addition to the newly developed "third generation" weapons, binary versions of several Soviet agents were developed and were designated as "Novichok" agents.
Carbamates
Contrary to some claims, not all nerve agents areorganophosphate
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 ...
s. The starting compound studied by the USA was the carbamate EA-1464, of notorious toxicity.SUMMARY OF MAJOR EVENTS and PROBLEMS. United States Army Chemical Corps (U). FISCAL YEAR 1960. p-116 Compounds typified by EA-1464 formed a large group of them are carbamate
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally o ...
s like EA-3990
EA-3990 is a deadly carbamate nerve agent. It is lethal because it Enzyme inhibitor, inhibits acetylcholinesterase. Inhibition causes an overly high accumulation of acetylcholine between the Neuron, nerve and Myocyte, muscle cells. This paralyzes ...
and EA-4056
EA-4056 is a deadly carbamate nerve agent. It is lethal because it inhibits acetylcholinesterase. Inhibition causes an overly high accumulation of acetylcholine between the nerve and muscle cells. This paralyzes the muscles by preventing the ...
, both of which have been claimed to be about 3 times more toxic than VX. Both the USA and the Soviet Union
developed carbamate nerve agents during the Cold War
The Cold War is a term commonly used to refer to a period of geopolitical tension between the United States and the Soviet Union and their respective allies, the Western Bloc and the Eastern Bloc. The term '' cold war'' is used because the ...
. They are sometimes grouped as "fourth generation" agents along with the Novichok agents due to their falling outside the definitions of controlled substances under the CWC.
Insecticides
Someinsecticide
Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...
s, including carbamates
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally obta ...
and 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 ...
such as dichlorvos
Dichlorvos (2,2-dichlorovinyl dimethyl phosphate, commonly abbreviated as an DDVP) is an organophosphate widely used as an insecticide to control household pests, in public health, and protecting stored products from insects. The compound has bee ...
, malathion
Malathion is an organophosphate insecticide which acts as an acetylcholinesterase inhibitor. In the USSR, it was known as carbophos, in New Zealand and Australia as maldison and in South Africa as mercaptothion.
Pesticide use
Malathion is a pesti ...
and parathion
Parathion, also called parathion-ethyl or diethyl parathion and locally known as "Folidol", is an organophosphate insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, incl ...
, are nerve agents. The metabolism of insect
Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pairs ...
s is sufficiently different from mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s that these compounds have little effect on humans
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
and other mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
at proper doses, but there is considerable concern about the effects of long-term exposure to these chemicals by farm workers
A farmworker, farmhand or agricultural worker is someone employed for labor in agriculture. In labor law, the term "farmworker" is sometimes used more narrowly, applying only to a hired worker involved in agricultural production, including harv ...
and animals
Animals are multicellular, eukaryotic organisms in the biological kingdom Animalia. With few exceptions, animals consume organic material, breathe oxygen, are able to move, can reproduce sexually, and go through an ontogenetic stage in ...
alike. At high enough doses, acute
Acute may refer to:
Science and technology
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf morphology
* Acute (medicine), a disease that it is of short duration and of recent onset.
** Acute toxicity, the adverse eff ...
toxicity and death can occur through the same mechanism as other nerve agents. Some insecticides such as demeton
Demeton, sold as an amber oily liquid with a sulphur like odour under the name Systox™, is an organophosphate derivative causing irritability and shortness of breath to individuals repeatedly exposed. It was used as a phosphorothioate insecticid ...
, dimefox
Dimefox was an organophosphate pesticide. In its pure form it is a colourless liquid with a fishy odour. Dimefox was first produced in 1940 by the group of Gerhard Schrader in Germany. It was historically used as a pesticide, but has been deemed ...
and paraoxon
Paraoxon is a parasympathomimetic which acts as an cholinesterase inhibitor. It is an organophosphate oxon, and the active metabolite of the insecticide parathion. It is also used as an ophthalmological drug against glaucoma. Paraoxon is one o ...
are sufficiently toxic to humans that they have been withdrawn from agricultural use, and were at one stage investigated for potential military applications.
Paraoxon was allegedly used as an assassination
Assassination is the murder of a prominent or important person, such as a head of state, head of government, politician, world leader, member of a royal family or CEO. The murder of a celebrity, activist, or artist, though they may not have ...
weapon by the apartheid
Apartheid (, especially South African English: , ; , "aparthood") was a system of institutionalised racial segregation that existed in South Africa and South West Africa (now Namibia) from 1948 to the early 1990s. Apartheid was ...
South African government as part of Project Coast
Project Coast was a 1980s top-secret chemical and biological weapons (CBW) program instituted by the apartheid-era government of South Africa. Project Coast was the successor to a limited postwar CBW program, which mainly produced the lethal agen ...
. Organophosphate pesticide poisoning
A pesticide poisoning occurs when pesticides, chemicals intended to control a pest, affect non-target organisms such as humans, wildlife, plant, or bees. There are three types of pesticide poisoning. The first of the three is a single and short- ...
is a major cause of disability in many developing countries and is often the preferred method of suicide.
Methods of spreading
Many methods exist for spreading nerve agents such as: *uncontrolledaerosol
An aerosol is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be natural or Human impact on the environment, anthropogenic. Examples of natural aerosols are fog o ...
munitions
*smoke generation
*explosive dissemination
* atomizers, humidifier
A humidifier is a device, primarily an electrical appliance, that increases humidity (moisture) in a single room or an entire building. In the home, point-of-use humidifiers are commonly used to humidify a single room, while whole-house or furnac ...
s and fogger A fogger is any device that creates a fog, typically containing an insecticide for killing insects and other arthropods. Foggers are often used by consumers as a low cost alternative to professional pest control services. The number of foggers nee ...
s
The method chosen will depend on the physical properties of the nerve agent(s) used, the nature of the target, and the achievable level of sophistication.
History
Discovery
This first class of nerve agents, the G-series, was accidentally discovered in Germany on December 23, 1936, by a research team headed byGerhard Schrader
Gerhard Schrader (25 February 1903 – 10 April 1990) was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. Schrader is best known for his accidental discovery of ...
working for IG Farben
Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate (company), conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, ...
. Since 1934, Schrader had been working in a laboratory in Leverkusen
Leverkusen () is a city in North Rhine-Westphalia, Germany, on the eastern bank of the Rhine. To the south, Leverkusen borders the city of Cologne, and to the north the state capital, Düsseldorf.
With about 161,000 inhabitants, Leverkusen is on ...
to develop new types of insecticide
Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...
s for IG Farben
Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate (company), conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, ...
. While working toward his goal of improved insecticide, Schrader experimented with numerous compounds, eventually leading to the preparation of Tabun.
In experiments, Tabun was extremely potent against insects: as little as 5 ppm of Tabun killed all the leaf lice he used in his initial experiment. In January 1937, Schrader observed the effects of nerve agents on human beings first-hand when a drop of Tabun spilled onto a lab bench. Within minutes he and his laboratory assistant began to experience miosis
Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...
(constriction of the pupils of the eyes), dizziness and severe shortness of breath. It took them three weeks to recover fully.
In 1935 the citing: ...
Nazi
Nazism ( ; german: Nazismus), the common name in English for National Socialism (german: Nationalsozialismus, ), is the far-right totalitarian political ideology and practices associated with Adolf Hitler and the Nazi Party (NSDAP) in ...
government had passed a decree that required all inventions of possible military significance to be reported to the Ministry of War Ministry of War may refer to:
* Ministry of War (imperial China) (c.600–1912)
* Chinese Republic Ministry of War (1912–1946)
* Ministry of War (Kingdom of Bavaria) (1808–1919)
* Ministry of War (Brazil) (1815–1999)
* Ministry of Defence (Est ...
, so in May 1937 Schrader sent a sample of Tabun to the chemical warfare
Chemical warfare (CW) involves using the toxic properties of chemical substances as weapons. This type of warfare is distinct from nuclear warfare, biological warfare and radiological warfare, which together make up CBRN, the military acronym ...
(CW) section of the Army Weapons Office in Berlin-Spandau
Spandau () is a locality (''Ortsteil'') of Berlin in the homonymous borough (''Bezirk'') of Spandau. The historic city is situated, for the most part, on the western banks of the Havel river. As of 2020 the estimated population of Spandau was 39, ...
. Schrader was summoned to the Wehrmacht chemical lab in Berlin to give a demonstration, after which Schrader's patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...
application and all related research was classified as secret. Colonel Rüdiger, head of the CW section, ordered the construction of new laboratories for the further investigation of Tabun and other organophosphate compounds and Schrader soon moved to a new laboratory at Wuppertal
Wuppertal (; "''Wupper Dale''") is, with a population of approximately 355,000, the seventh-largest city in North Rhine-Westphalia as well as the 17th-largest city of Germany. It was founded in 1929 by the merger of the cities and to ...
-Elberfeld
Elberfeld is a municipal subdivision of the German city of Wuppertal; it was an independent town until 1929.
History
The first official mentioning of the geographic area on the banks of today's Wupper River as "''elverfelde''" was in a docu ...
in the Ruhr valley
The Ruhr ( ; german: Ruhrgebiet , also ''Ruhrpott'' ), also referred to as the Ruhr area, sometimes Ruhr district, Ruhr region, or Ruhr valley, is a polycentric urban area in North Rhine-Westphalia, Germany. With a population density of 2,800/km ...
to continue his research in secret throughout World War II
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
. The compound was initially codenamed Le-100 and later Trilon-83.
Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.Gerhard Schrader, Otto Ambros, , and Hans-Jürgen von der Linde.
It was codenamed T-144 or Trilon-46. It was found to be more than ten times as potent as Tabun.
Soman
Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiti ...
was discovered by Richard Kuhn
Richard Johann Kuhn (; 3 December 1900 – 1 August 1967) was an Austrian-German biochemist who was awarded the Nobel Prize in Chemistry in 1938 "for his work on carotenoids and vitamins".
Biography
Early life
Kuhn was born in Vienna, Austria ...
in 1944 as he worked with the existing compounds; the name is derived from either the Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
'to sleep' or the Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
'to bludgeon'. It was codenamed T-300.
CycloSarin
Cyclosarin or GF (cyclohexyl methylphosphonofluoridate) is an extremely toxic substance used as a chemical weapon. It is a member of the '' G-series'' family of nerve agents, a group of chemical weapons discovered and synthesized by a German te ...
was also discovered during WWII but the details were lost and it was rediscovered in 1949.
The G-series naming system was created by the United States when it uncovered the German activities, labeling Tabun as GA (German Agent A), Sarin as GB and Soman as GD. Ethyl Sarin was tagged GE and CycloSarin as GF.
During World War II
In 1939, a pilotplant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
for Tabun production was set up at Munster-Lager, on Lüneburg Heath
Lüneburg Heath (german: Lüneburger Heide) is a large area of heath, geest, and woodland in the northeastern part of the state of Lower Saxony in northern Germany. It forms part of the hinterland for the cities of Hamburg, Hanover and Bremen a ...
near the German Army proving grounds at . In January 1940, construction began on a secret plant, code named " Hochwerk" (''High factory''), for the production of Tabun at ''Dyhernfurth an der Oder'' (now Brzeg Dolny
Brzeg Dolny (german: Dyhernfurth) is a town in Wołów County, Lower Silesian Voivodeship in south-western Poland. It is located north-west of Wrocław on the Oder River, and is the site of a large chemical plant complex, PCC Rokita SA. As of ...
in Poland
Poland, officially the Republic of Poland, is a country in Central Europe. It is divided into 16 administrative provinces called voivodeships, covering an area of . Poland has a population of over 38 million and is the fifth-most populous ...
), on the Oder River
The Oder ( , ; Czech, Lower Sorbian and ; ) is a river in Central Europe. It is Poland's second-longest river in total length and third-longest within its borders after the Vistula and Warta. The Oder rises in the Czech Republic and flows thr ...
from Breslau (now Wrocław
Wrocław (; german: Breslau, or . ; Silesian German: ''Brassel'') is a city in southwestern Poland and the largest city in the historical region of Silesia. It lies on the banks of the River Oder in the Silesian Lowlands of Central Europe, rou ...
) in Silesia
Silesia (, also , ) is a historical region of Central Europe that lies mostly within Poland, with small parts in the Czech Republic and Germany. Its area is approximately , and the population is estimated at around 8,000,000. Silesia is split ...
.
The plant was large, covering an area of and was completely self-contained, synthesizing all intermediates as well as the final product, Tabun. The factory even had an underground plant for filling munitions, which were then stored at Krappitz (now Krapkowice
Krapkowice (; german: Krappitz; szl, Krapkowicy) is a town in southern Poland with 16,301 inhabitants (2019), situated in the Opole Voivodeship, straddling both banks of the Oder River at the point where it joins with the Osobłoga. It is the re ...
) in Upper Silesia. The plant was operated by , a subsidiary of IG Farben
Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate (company), conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, ...
, as were all other chemical weapon agent
A chemical weapon (CW) is a specialized munition that uses chemicals formulated to inflict death or harm on humans. According to the Organisation for the Prohibition of Chemical Weapons (OPCW), this can be any chemical compound intended as ...
production plants in Germany at the time.
Because of the plant's deep secrecy and the difficult nature of the production process, it took from January 1940 until June 1942 for the plant to become fully operational. Many of Tabun's chemical precursors were so corrosive that reaction chambers not lined with quartz or silver soon became useless. Tabun itself was so hazardous that the final processes had to be performed while enclosed in double glass-lined chambers with a stream of pressurized air circulating between the walls.
Three thousand German nationals were employed at Hochwerk, all equipped with respirators
A respirator is a device designed to protect the wearer from inhaling hazardous atmospheres including fumes, vapours, gases and particulate matter such as dusts and airborne pathogens such as viruses. There are two main categories of respi ...
and clothing
Clothing (also known as clothes, apparel, and attire) are items worn on the body. Typically, clothing is made of fabrics or textiles, but over time it has included garments made from animal skin and other thin sheets of materials and natural ...
constructed of a poly-layered rubber/cloth/rubber sandwich that was destroyed after the tenth wearing. Despite all precautions, there were over 300 accidents before production even began and at least ten workers died during the two and a half years of operation. Some incidents cited in ''A Higher Form of Killing: The Secret History of Chemical and Biological Warfare'' are as follows:
*Four pipe fitters had liquid Tabun drain onto them and died before their rubber suits could be removed.
*A worker had two liters of Tabun pour down the neck of his rubber suit. He died within two minutes.
*Seven workers were hit in the face with a stream of Tabun of such force that the liquid was forced behind their respirators. Only two survived despite resuscitation
Resuscitation is the process of correcting physiological disorders (such as lack of breathing or heartbeat) in an acutely ill patient. It is an important part of intensive care medicine, anesthesiology, trauma surgery and emergency medicine. W ...
measures.
and moved, probably to Dzerzhinsk, USSR
The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen nationa ...
.
In 1940 the German Army Weapons Office ordered the mass production of Sarin for wartime use. A number of pilot plants were built and a high-production facility was under construction (but was not finished) by the end of World War II
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
. Estimates for total Sarin production by Nazi Germany range from 500 kg to 10 ton
Ton is the name of any one of several units of measure. It has a long history and has acquired several meanings and uses.
Mainly it describes units of weight. Confusion can arise because ''ton'' can mean
* the long ton, which is 2,240 pounds
...
s.
During that time, German intelligence
Intelligence has been defined in many ways: the capacity for abstraction, logic, understanding, self-awareness, learning, emotional knowledge, reasoning, planning, creativity, critical thinking, and problem-solving. More generally, it can b ...
believed that the Allies
An alliance is a relationship among people, groups, or states that have joined together for mutual benefit or to achieve some common purpose, whether or not explicit agreement has been worked out among them. Members of an alliance are called ...
also knew of these compounds, assuming that because these compounds were not discussed in the Allies' scientific journals information about them was being suppressed. Though Sarin, Tabun and Soman were incorporated into artillery
Artillery is a class of heavy military ranged weapons that launch munitions far beyond the range and power of infantry firearms. Early artillery development focused on the ability to breach defensive walls and fortifications during siege ...
shells, the German government ultimately decided not to use nerve agents against Allied targets. The Allies did not learn of these agents until shells filled with them were captured towards the end of the war. German forces used chemical warfare against partisans during the Battle of the Kerch Peninsula
The Battle of the Kerch Peninsula, which commenced with the Soviet Kerch-Feodosia Landing Operation (russian: Керченско-Феодосийская десантная операция, ''Kerchensko-Feodosiyskaya desantnaya operatsiya'') ...
in 1942, but did not use any nerve agent.
This is detailed in Joseph Borkin's book ''The Crime and Punishment of IG Farben'':
Post–World War II
Since World War II, Iraq's use of mustard gas against Iranian troops andKurds ug:كۇردلار
Kurds ( ku, کورد ,Kurd, italic=yes, rtl=yes) or Kurdish people are an Iranian ethnic group native to the mountainous region of Kurdistan in Western Asia, which spans southeastern Turkey, northwestern Iran, northern Ir ...
(Iran–Iraq War
The Iran–Iraq War was an armed conflict between Iran and Iraq that lasted from September 1980 to August 1988. It began with the Iraqi invasion of Iran and lasted for almost eight years, until the acceptance of United Nations Security Council ...
of 1980–1988) has been the only large-scale use of any chemical weapons. On the scale of the single Kurdish village of Halabja
Halabja ( ku, هەڵەبجە, Helebce, ) is a city in the Kurdistan Region of Iraq and the capital of Halabja Governorate, located about northeast of Baghdad and from the Iranian border.
The city lies at the base of what is often referred to ...
within its own territory, Iraqi forces did expose the populace to some kind of chemical weapons, possibly mustard gas and most likely nerve agents.
Operatives of the Aum Shinrikyo
, formerly , is a Japanese doomsday cult founded by Shoko Asahara in 1987. It carried out the deadly Tokyo subway sarin attack in 1995 and was found to have been responsible for the Matsumoto sarin attack the previous year.
The group says tha ...
religious group made and used Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.Tokyo subway sarin attack
The was an act of domestic terrorism perpetrated on 20 March 1995, in Tokyo, Japan, by members of the cult movement Aum Shinrikyo. In five coordinated attacks, the perpetrators released sarin on three lines of the Tokyo Metro (then ''Teito Rapi ...
.
In the Gulf War
The Gulf War was a 1990–1991 armed campaign waged by a 35-country military coalition in response to the Iraqi invasion of Kuwait. Spearheaded by the United States, the coalition's efforts against Iraq were carried out in two key phases: ...
, no nerve agents (nor other chemical weapons) were used, but a number of U.S. and UK personnel were exposed to them when the Khamisiyah Khamisiyah ( ar, الخميسية ') is an area in southern Iraq located approximately 350 km (217 mi) south-east of Baghdad, 200 km (124 mi) north-west of Kuwait City and 270 km (168 mi) north of Al Qaysumah. Khamisiyah is under th ...
chemical depot was destroyed. This and the widespread use of anticholinergic drugs as a protective treatment against any possible nerve gas attack have been proposed as a possible cause of Gulf War syndrome
Gulf War syndrome or Gulf War illness is a chronic and multi-symptomatic disorder affecting military veterans of both sides of the 1990–1991 Persian Gulf War. A wide range of acute and chronic symptoms have been linked to it, including fatigue ...
.
Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.a 2013 attack on
Ghouta
Ghouta ( ar, غُوطَةُ دِمَشْقَ / ALA-LC: ''Ḡūṭat Dimašq'') is a countryside and suburban area in southwestern Syria that surrounds the city of Damascus along its eastern and southern rim.
Name
Ghouta is the Arabic term (''gh ...
during the Syrian Civil War, killing several hundred people. Most governments contend that forces loyal to President Bashar al-Assad
Bashar Hafez al-Assad, ', Levantine pronunciation: ; (, born 11 September 1965) is a Syrian politician who is the 19th president of Syria, since 17 July 2000. In addition, he is the commander-in-chief of the Syrian Armed Forces and the ...
deployed the gas; however, the Syrian Government
Government of the Syrian Arab Republic is the union government created by the constitution of Syria where by the president is the head of state and the prime minister is the head of government. Executive power is exercised by the government. Syr ...
has denied responsibility.
On 13 February 2017, the nerve agent VX was used in the assassination of Kim Jong-nam
On 13 February 2017, the eldest son of Kim Jong-il and half-brother of Kim Jong-un, Kim Jong-nam, was attacked with the nerve agent VX at Kuala Lumpur International Airport in Malaysia. He had been exiled from North Korea in 2003 and had been ...
, half-brother of the North Korean leader Kim Jong-un
Kim Jong-un (; , ; born 8 January 1982) is a North Korean politician who has been Supreme Leader of North Korea since 2011 and the leader of the Workers' Party of Korea (WPK) since 2012. He is a son of Kim Jong-il, who was North Korea's sec ...
, at Kuala Lumpur International Airport
Kuala Lumpur International Airport (KLIA) is Malaysia's main international airport. It is located in the Sepang District of Selangor, approximately south of Kuala Lumpur and serves the city's greater conurbation.
KLIA is the largest and b ...
in Malaysia
Malaysia ( ; ) is a country in Southeast Asia. The federation, federal constitutional monarchy consists of States and federal territories of Malaysia, thirteen states and three federal territories, separated by the South China Sea into two r ...
.
On 4 March 2018, a former Russian agent (who was convicted of high treason but allowed to live in the United Kingdom
The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...
via a spy swap
A prisoner exchange or prisoner swap is a deal between opposing sides in a conflict to release prisoners: prisoner of war, prisoners of war, spy, spies, hostages, etc. Sometimes, dead bodies are involved in an exchange.
Geneva Conventions
Un ...
agreement), Sergei Skripal
Sergei Viktorovich Skripal ( rus, Серге́й Ви́кторович Скрипáль, p=sʲɪrˈɡʲej ˈvʲiktərəvʲɪtɕ skrʲɪˈpalʲ; born 23 June 1951) is a former Russian military intelligence officer who acted as a double agent f ...
, and his daughter, who was visiting from Moscow, were both poisoned by a Novichok nerve agent in the English city of Salisbury
Salisbury ( ) is a cathedral city in Wiltshire, England with a population of 41,820, at the confluence of the rivers Avon, Nadder and Bourne. The city is approximately from Southampton and from Bath.
Salisbury is in the southeast of Wil ...
. They survived, and were subsequently released from hospital. In addition, a Wiltshire Police
Wiltshire Police, formerly known as Wiltshire Constabulary, is the territorial police force responsible for policing the county of Wiltshire (including the Borough of Swindon) in South West England.
The force serves 722,000 people over an area ...
officer, Nick Bailey, was exposed to the substance. He was one of the first to respond to the incident. Twenty-one members of the public received medical treatment following exposure to the nerve agent. Despite this, only Bailey and the Skripals remained in critical condition. On 11 March 2018, Public Health England
Public Health England (PHE) was an executive agency of the Department of Health and Social Care in England which began operating on 1 April 2013 to protect and improve health and wellbeing and reduce health inequalities. Its formation came as a ...
issued advice for the other people believed to have been in the Mill pub (the location where the attack is believed to have been carried out) or the nearby Zizzi
Zizzi is a chain of Italian-inspired restaurants in the United Kingdom and Ireland. In February 2015, Bridgepoint Capital completed a £250 million acquisition of ''ASK Italian'' and ''Zizzi'', and subsequently bought by TowerBrook Capital Partne ...
Restaurant. On 12 March 2018, British Prime Minister Theresa May
Theresa Mary May, Lady May (; née Brasier; born 1 October 1956) is a British politician who served as Prime Minister of the United Kingdom and Leader of the Conservative Party from 2016 to 2019. She previously served in David Cameron's cab ...
stated that the substance used was a Novichok nerve agent.
On 30 June 2018, two British nationals, Charlie Rowley and Dawn Sturgess, were poisoned by a Novichok nerve agent of the same kind that was used in the Skripal poisoning, which Rowley had found in a discarded perfume bottle and gifted to Sturgess. Whilst Rowley survived, Sturgess died on 8 July. Metropolitan Police
The Metropolitan Police Service (MPS), formerly and still commonly known as the Metropolitan Police (and informally as the Met Police, the Met, Scotland Yard, or the Yard), is the territorial police force responsible for law enforcement and ...
believe that the poisoning was not a targeted attack, but a result of the way the nerve agent was disposed of after the poisoning in Salisbury.
Ocean disposal
In 1972, the United States Congress banned the practice of disposing chemical weapons into the ocean. Thirty-two thousandton
Ton is the name of any one of several units of measure. It has a long history and has acquired several meanings and uses.
Mainly it describes units of weight. Confusion can arise because ''ton'' can mean
* the long ton, which is 2,240 pounds
...
s of nerve and mustard agents had already been dumped into the ocean waters off the United States by the U.S. Army, primarily as part of Operation CHASE Operation CHASE (an acronym for "Cut Holes And Sink 'Em") was a United States Department of Defense program for the disposal of unwanted munitions at sea from May 1964 until the early 1970s.Kurak, Steve "Operation Chase" ''United States Naval Instit ...
. According to a 1998 report by William Brankowitz, a deputy project manager in the U.S. Army Chemical Materials Agency, the Army created at least 26 chemical weapons dump sites in the ocean off at least 11 states on both the west and east coasts. Due to poor records, they currently only know the rough whereabouts of half of them.
There is currently a lack of scientific data regarding the ecological and health effects of this dumping. In the event of leakage, many nerve agents are soluble in water and would dissolve in a few days, while other substances like sulfur mustard
Mustard gas or sulfur mustard is a chemical compound belonging to a family of cytotoxic and blister agents known as mustard agents. The name ''mustard gas'' is technically incorrect: the substance, when dispersed, is often not actually a gas, b ...
could last longer. There have also been a few incidents of chemical weapons washing ashore or being accidentally retrieved, for example during dredging or trawl fishing
Trawling is a method of fishing that involves pulling a fishing net through the water behind one or more boats. The net used for trawling is called a trawl. This principle requires netting bags which are towed through water to catch different speci ...
operations.
Detection
Detection of gaseous nerve agents
The methods of detecting gaseous nerve agents include but are not limited to the following.Laser photoacoustic spectroscopy
Laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word "laser" is an acronym for "light amplification by stimulated emission of radiation". The fir ...
photoacoustic spectroscopy
Photoacoustic spectroscopy is the measurement of the effect of absorbed electromagnetic energy (particularly of light) on matter by means of acoustic detection. The discovery of the photoacoustic effect dates to 1880 when Alexander Graham Bell sho ...
(LPAS) is a method that has been used to detect nerve agents in the air. In this method, laser light is absorbed by gaseous
Gas is one of the four fundamental states of matter (the others being solid, liquid, and plasma).
A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or ...
matter
In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ultimately composed of atoms, which are made up of interacting subatomic partic ...
. This causes a heating/cooling cycle and changes in pressure
Pressure (symbol: ''p'' or ''P'') is the force applied perpendicular to the surface of an object per unit area over which that force is distributed. Gauge pressure (also spelled ''gage'' pressure)The preferred spelling varies by country and e ...
. Sensitive microphones
A microphone, colloquially called a mic or mike (), is a transducer that converts sound into an electrical signal. Microphones are used in many applications such as telephones, hearing aids, public address systems for concert halls and public ...
convey sound waves
In physics, sound is a vibration that propagates as an acoustic wave, through a transmission medium such as a gas, liquid or solid.
In human physiology and psychology, sound is the ''reception'' of such waves and their ''perception'' by the ...
that result from the pressure changes. Scientists at the U.S. Army Research Laboratory
The U.S. Army Combat Capabilities Development Command Army Research Laboratory (DEVCOM ARL) is the U.S. Army's foundational research laboratory. ARL is headquartered at the Adelphi Laboratory Center (ALC) in Adelphi, Maryland. Its largest singl ...
engineered an LPAS system that can detect multiple trace amounts of toxic gases in one air sample.
This technology
Technology is the application of knowledge to reach practical goals in a specifiable and reproducible way. The word ''technology'' may also mean the product of such an endeavor. The use of technology is widely prevalent in medicine, science, ...
contained three lasers modulated
In electronics and telecommunications, modulation is the process of varying one or more properties of a periodic waveform, called the ''carrier signal'', with a separate signal called the ''modulation signal'' that typically contains informatio ...
to different frequency
Frequency is the number of occurrences of a repeating event per unit of time. It is also occasionally referred to as ''temporal frequency'' for clarity, and is distinct from ''angular frequency''. Frequency is measured in hertz (Hz) which is eq ...
, each producing a different sound wave tone. The different wavelengths of light were directed into a sensor referred to as the photoacoustic cell. Within the cell were the vapors of different nerve agents. The traces of each nerve agent had a signature effect on the "loudness" of the lasers' sound wave tones. Some overlap of nerve agents' effects did occur in the acoustic results. However, it was predicted that specificity would increase as additional lasers with unique wavelengths were added. Yet, too many lasers set to different wavelengths
In physics, the wavelength is the spatial period of a periodic wave—the distance over which the wave's shape repeats.
It is the distance between consecutive corresponding points of the same phase on the wave, such as two adjacent crests, tro ...
could result in overlap of absorption spectra
Absorption spectroscopy refers to spectroscopic techniques that measure the absorption of radiation, as a function of frequency or wavelength, due to its interaction with a sample. The sample absorbs energy, i.e., photons, from the radiating ...
. Citation LPAS technology can identify gases
Gas is one of the four fundamental states of matter (the others being solid, liquid, and plasma).
A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or ...
in parts per billion
In science and engineering, the parts-per notation is a set of pseudo-units to describe small values of miscellaneous dimensionless quantities, e.g. mole fraction or mass fraction. Since these fractions are quantity-per-quantity measures, they ...
(ppb) concentrations.
The following nerve agent simulants have been identified with this multiwavelength LPAS:
* dimethyl methyl phosphonate (DMMP)
* diethyl methyl phosphonate (DEMP)
* diisopropyl methyl phosphonate (DIMP)
* dimethylpolysiloxane (DIME), triethyl phosphate (TEP)
* tributyl phosphate
Tributyl phosphate, known commonly as TBP, is an organophosphorus compound with the chemical formula (CH3CH2CH2CH2O)3PO. This colourless, odorless liquid finds some applications as an extractant and a plasticizer. It is an ester of phosphoric aci ...
(TBP)
* two volatile organic compounds (VOCs)
* acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
(ACE)
* isopropanol
Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group (chemical formula ) it is the simple ...
(ISO), used to construct Sarin
Sarin (NATO designation GB G-series, "B"">Nerve_agent#G-series.html" ;"title="hort for Nerve agent#G-series">G-series, "B" is an extremely toxic synthetic organophosphorus compound.
* CO2
ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents
U.S.
Army Chemical Review
* History Note: The CWS Effort to Obtain German Chemical Weapons for Retaliation Against Japa
CBIAC Newsletter
AChE inhibitors and substrates
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in
Carbon dioxide
Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...
* Benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...
* Formaldehyde
Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
* Acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
* Ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...
* NOx Nitrogen oxide Nitrogen oxide may refer to a binary compound of oxygen and nitrogen, or a mixture of such compounds:
Charge-neutral
*Nitric oxide (NO), nitrogen(II) oxide, or nitrogen monoxide
*Nitrogen dioxide (), nitrogen(IV) oxide
* Nitrogen trioxide (), or n ...
* SO2 Sulphur oxide
Sulfur oxide refers to many types of sulfur and oxygen containing compounds such as SO, SO2, SO3, S7O2, S6O2, S2O2, etc.
Sulfur oxide (SO''x'') refers to one or more of the following:
* Lower sulfur oxides (S''n''O, S7O2 and S6O2)
* Sulfur mono ...
* Ethylene Glycol
Ethylene glycol (IUPAC name: ethane-1,2-diol) is an organic compound (a vicinal diol) with the formula . It is mainly used for two purposes, as a raw material in the manufacture of polyester fibers and for antifreeze formulations. It is an odo ...
* TATP
* TNT
Trinitrotoluene (), more commonly known as TNT, more specifically 2,4,6-trinitrotoluene, and by its preferred IUPAC name 2-methyl-1,3,5-trinitrobenzene, is a chemical compound with the formula C6H2(NO2)3CH3. TNT is occasionally used as a reagen ...
Non-dispersive infrared
Non-dispersive infrared techniques have been reported to be used for gaseous nerve agent detection.IR absorption
Traditional IR absorption has been reported to detect gaseous nerve agents.Fourier transform infrared spectroscopy
Fourier transform infrared (FTIR) spectroscopy has been reported to detect gaseous nerve agents.References
External links
ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents
U.S.
Department of Health and Human Services
The United States Department of Health and Human Services (HHS) is a cabinet-level executive branch department of the U.S. federal government created to protect the health of all Americans and providing essential human services. Its motto is " ...
* Nervegas: America's Fifteen-year Struggle for Modern Chemical WeaponArmy Chemical Review
* History Note: The CWS Effort to Obtain German Chemical Weapons for Retaliation Against Japa
CBIAC Newsletter
AChE inhibitors and substrates
2wfz
in
Proteopedia
Proteopedia is a wiki, 3D encyclopedia of proteins and other molecules.
The site contains a page for every entry in the Protein Data Bank (>130,000 pages), as well as pages that are more descriptive of protein structures in general such as acetylch ...
{{Acetylcholine metabolism and transport modulators
Acetylcholinesterase inhibitors