Nerve agent 21710 225188657 2008-07-12T10:37:02Z 84.48.202.246 {{otheruses4|the chemical|the band|The Nerve Agents}} {{Chemical warfare vert}} '''Nerve agents''' (also being referred to as '''nerve gases''', though these chemicals are liquid at room temperature) are a class of [[phosphorus]]-containing [[organic chemistry|organic chemicals]] ([[organophosphate]]s) that disrupt the mechanism by which nerves transfer messages to organs. The disruption is caused by blocking [[acetylcholinesterase]], an [[enzyme]] that normally relaxes the activity of [[acetylcholine]], a [[neurotransmitter]]. As [[chemical weapon]]s, they are classified as [[weapon of mass destruction|weapons of mass destruction]] by the [[United Nations]] according to [[UN Resolution 687]], and their production and stockpiling was outlawed by the [[Chemical Weapons Convention]] of [[1993]]; the Chemical Weapons Convention officially took effect on [[April 29]][[1997]]. Poisoning by a nerve agent leads to contraction of pupils, profuse salivation, convulsions, involuntary urination and defecation, and eventual death by asphyxiation as control is lost over respiratory muscles. Some nerve agents are readily vaporized or aerosolized and the primary portal of entry into the body is the respiratory system. 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]]. ==Biological effects== As their name suggests, nerve agents attack the [[nervous system]] of the human body. All such agents function the same way: by interrupting the breakdown of the [[neurotransmitters]] that signal muscles to contract, preventing them from relaxing. Initial symptoms following exposure to [[sarin]] (and other nerve agents) are a runny nose, tightness in the chest and constriction of the pupils. Soon after, the victim will then have difficulty breathing, and will experience nausea and drooling. As the victim continues to lose control of his or her bodily functions, he or she will involuntarily salivate, [[tears|lacrimate]], urinate, defecate, and experience gastrointestinal pain and [[emesis]]. This phase is followed by twitching and jerking, and ultimately the victim will become comatose and suffocate as a consequence of convulsive spasms. The effects of nerve agents are very long lasting and cumulative (increased successive exposures), and survivors of nerve agent poisoning almost invariably suffer chronic neurological damage.{{Dubious|date=March 2008}} ===Mechanism of action=== When a normally functioning [[motor nerve]] is stimulated it releases the [[neurotransmitter]] [[acetylcholine]], which transmits the impulse to a muscle or organ. Once the impulse is sent, the enzyme [[acetylcholinesterase|acetylcholine esterase]] 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 acetylcholinesterase by forming a [[covalent bond]] with the site of the enzyme where acetylcholine normally undergoes [[hydrolysis]] (breaks down). The result is that acetylcholine 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 mucous from the nose ([[rhinorrhea]]). ===Antidotes=== [[Atropine]] and related [[anticholinergic]] drugs act as antidotes to nerve agent poisoning because they block acetylcholine receptors, but they are poisonous in their own right. (Some synthetic anticholinergics, such as [[biperiden]] may counteract the central symptoms of nerve agent poisoning better than [[atropine]], since they pass the blood-brain barrier better than atropine.) While these drugs will save the life of a person affected with nerve agents, that person may be incapacitated briefly or for an extended period, depending on the amount of exposure. The endpoint of atropine administration is the clearing of bronchial secretions. Atropine for field use by military personnel is often loaded in an [[autoinjector]], for ease of use in stressful conditions. [[Pralidoxime chloride]], also known as ''2-PAM chloride'', is also used as an antidote. Rather than counteracting the initial effects of the nerve agent on the nervous system like [[atropine]], ''pralidoxime chloride'' reactivates the poisoned enzyme (acetylcholinesterase) by scavenging the phosphoryl rest attached on the functional hydroxyl group of the enzyme. Though safer to use, it takes longer to act. Recent scientific breakthroughs have seen antidotes being produced in the milk of genetically modified goats.<ref>[http://www.null-hypothesis.co.uk/science/news/item/goat_milk_gas_chemical_attack Goats Can Foil Gas Attack]</ref> ==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-character [[NATO]] identifier (such as GB). === G-Series === The ''G-series'' is thus named because [[Germany|German]] scientists first synthesized them. All of the compounds in this class were discovered and synthesized during or soon after World War II, led by Dr. [[Gerhard Schrader]] (later under the employment of [[I.G. Farben]]). This series is the first and oldest family of nerve agents. The first nerve agent ever synthesised was GA ([[tabun (nerve agent)|tabun]]) in [[1936]]. GB ([[sarin]]) was discovered next in [[1938]], followed by GD ([[soman]]) in [[1944]] and finally the more obscure GF ([[cyclosarin]]) in [[1949]]. GB was the only G agent that was fielded by the USA as a munition, specifically in rockets, aerial bombs, howitzer rounds, and gun rounds.<ref name="FM 3-8">'''FM 3-8 Chemical Reference handbook'''; US Army; 1967</ref> === V-Series === [[Image:VX-S-enantiomer-3D-balls.png|thumb|200px|Chemical form of the nerve agent VX]] Dr. Ranajit Ghosh, a chemist at the Plant Protection Laboratories of [[Imperial Chemical Industries]] was investigating a class of organophosphate compounds (organophosphate esters of substituted aminoethanethiols). Like the earlier investigator of organophosphate, Dr. Schrader, Dr. Ghosh found that they were quite effective pesticides. In 1954, ICI put one of them on the market under the trade name Amiton. It was subsequently withdrawn, as it was too toxic for safe use. The toxicity did not go unnoticed, and some of the more toxic materials had in fact been sent to the British Armed Forces research facility at Porton Down for evaluation. After the evaluation was complete, several members of this class of compounds would become a new group of nerve agents, the V agents (depending on who you talk to, the V stands for Victory, Venomous, or Viscous). The best known of these is probably VX, with the [[VR (nerve agent)|Russian V-gas]] coming a close second (Amiton is largely forgotten as VG). This class of compounds is also sometimes known as Tammelin's esters, after Lars-Erik Tammelin of the Swedish Institute of Defense Research. Dr. Tammelin was also conducting research on this class of compounds in 1952, but for obvious reasons he did not publicize his work widely. The ''V-series'' is the second family of nerve agents, and contains five well known members: [[VE (nerve agent)|VE]], [[VG (nerve agent)|VG]], [[VM (nerve agent)|VM]], [[VR (nerve agent)|VR]] and [[VX (nerve agent)|VX]], along with several more obscure analogues. The most studied agent in this family, [[VX (nerve agent)|VX]], was invented in the [[1950]]s at [[Porton Down]] in the [[United Kingdom]]. The other agents in this series have not been studied extensively, and information about them is limited. It is known, however, that the V-series agents are about 10 times more toxic than the G-agent [[sarin]] (GB). 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 USA as a munition, consisting of rockets, [[artillery shell]]s, airplane spray tanks, and landmines.<ref name="FM 3-8">'''FM 3-8 Chemical Reference handbook'''; US Army; 1967</ref><ref>"U.S. Army Destroys Entire Stockpile of VX Spray Tanks" http://www.cma.army.mil/fndocumentviewer.aspx?docid=003677713, U.S. Army Chemical Materials Agency, December 26, 2007, accessed January 4, 2007</ref> ===Novichok agents=== {{main|Novichok agent}} The Novichok (Russian for "newcomer") agents are a series of organophosphate compounds that were developed in the [[Soviet Union]] from the 1970's to the 1990's. The goal of this program was to develop and manufacture highly deadly chemical weapons that were unknown to the West. These new agents were designed to be undetectable by standard NATO chemical detection equipment, and to defeat chemical protective gear. In addition to the newly developed "third generation" weapons, binary versions of several Soviet agents were developed and are designated as "Novichok" agents. === Insecticides === A number of [[insecticide]]s, the [[phenothiazine]]s, [[organophosphates]] such as [[dichlorvos]], [[malathion]] and [[parathion]], are nerve agents. The metabolism of [[insect]]s is sufficiently different from [[mammal]]s that these compounds have little effect on humans and other mammals at proper doses; but there is considerable concern about the effects of long-term exposure to these chemicals by farm workers and animals alike. At high enough doses, however, [[Acute (medical)|acute]] toxicity and death can occur through the same mechanism as other nerve agents. Organophosphate [[pesticide poisoning]] is a major cause of disability in many developing countries, and is often the preferred method of suicide.<ref>[http://www.bmj.com/cgi/content/full/329/7476/1231?ck=nck "Overcoming apathy in research on organophosphate poisoning"], BMJ (former ''British Medical Journal'') 2004;329:1231-1233 (20 November)</ref> == History == ===The discovery of nerve agents=== This first class of nerve agents, the so-called ''G-Series'', was accidentally discovered in [[Germany]] on [[December 23]], [[1936]] by a research team headed by [[Gerhard Schrader|Dr. Gerhard Schrader]]. Since [[1934]], Schrader had been in charge of a laboratory in [[Leverkusen]] to develop new types of [[insecticide]]s for [[IG Farben]]. While working toward his goal of improved insecticide, Schrader experimented with numerous [[fluorine]]-containing compounds, eventually leading to the preparation of [[tabun (nerve agent)|tabun]]. In experiments, tabun was extremely potent against insects: as little as 5 [[Parts per million|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]] (constriction of the pupils of the eyes), dizziness, and severe shortness of breath. It took them three weeks to recover fully. In [[1935]] the [[Nazism|Nazi]] government had passed a decree that required all inventions of possible military significance to be reported to the [[Ministry of War]], so in May of [[1937]] Schrader sent a sample of tabun to the [[chemical warfare]] (CW) section of the [[Army Weapons Office]] in [[Berlin-Spandau]]. Dr. Schrader was summoned to the Wehrmacht chemical lab in Berlin to give a demonstration, after which Schrader's patent application and all related research was classified. 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-Elberfeld in the Ruhr valley to continue his research in secret throughout [[World War II]]. The compound was initially codenamed Le-100 and later Trilon-83. [[Sarin]] was discovered by Schrader and his team in 1938 and named after their initials: Schrader, Ambrose, Rudriger, and van der Linde. It was codenamed T-144 or Trilon-46. It was found to be more than ten times as potent as tabun. [[Soman]] was discovered by Dr. [[Richard Kuhn]] in 1944 as he worked with the existing compounds, the name is derived from either the Greek 'to sleep' or the Latin 'to bludgeon', it was codenamed T-300. [[Cyclosarin]] was also discovered during WWII but the details were lost and it was 'discovered' again 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.<ref name="sidell">[https://ccc.apgea.army.mil/sarea/products/textbook/Web_Version/chapters/chapter_5.htm#history], Frederick Sidell</ref> Ethyl sarin was tagged GE and cyclosarin as GF. ===During World War II=== In [[1939]], a pilot [[factory|plant]] for tabun production was set up at [[Munster-Lager]], on Luneberg heath near the German Army proving grounds at [[Raubkammer]]. In January [[1940]], construction began on a secret plant, code named "[[Hochwerk]]" (''High factory''), for the production of tabun at [[Dyherrnfurth an der Oder]] (now [[Brzeg Dolny]] in [[Poland]]), on the [[Oder River]] 40 km (24.9 miles) from [[Breslau]] (now [[Wrocław]]) in [[Silesia]]. The plant was large, covering an area of 2.4 by 0.8 km (1.5 by 0.5 miles), 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) in Upper Silesia. The plant was operated by [[Anorgana GmbH]], a subsidiary of [[IG Farben]], as were all other [[chemical weapon agent]] 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. 3,000 German nationals were employed at Hochwerk, all equipped with [[respirators]] and [[clothing]] 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 10 workers died during the 2.5 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; they died before their rubber suits could be removed. * A worker had 2 liters of tabun pour down the neck of his rubber suit; he died within 2 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 heroic [[resuscitation]] measures. The plant produced between 10,000 and 30,000 tons of tabun before its capture by the Soviet Army.<ref name="sidell"/> 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]]. Estimates for total sarin production by Nazi Germany range from 500 kg to 10 tons. During that time, German [[Intelligence (information gathering)|intelligence]] believed that the [[Allies#World War II|Allies]] 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]] shells, the German government ultimately decided not to use nerve agents against Allied targets. The Allies didn't learn of these agents until shells filled with them were captured towards the end of the war. This is detailed in [[Joseph Borkin]]'s book ''The Crime and Punishment of IG Farben'': {{Quotation|[[Albert Speer|Speer]], who was strongly opposed to the introduction of [[tabun (nerve gas)|tabun]], flew [[Otto Ambros]], [[IG Farben|I.G.'s]] authority on poison gas as well as synthetic rubber, to the meeting. Hitler asked Ambros, "What is the other side doing about poison gas?" Ambros explained that the enemy, because of its greater access to [[ethylene]], probably had a greater capacity to produce [[mustard gas]] than Germany did. Hitler interrupted to explain that he was not referring to traditional poison gases: "I understand that the countries with petroleum are in a position to make more [mustard gas], but Germany has a special gas, tabun. In this we have a monopoly in Germany." He specifically wanted to know whether the enemy had access to such a gas and what it was doing in this area. To Hitler's disappointment Ambros replied, "I have justified reasons to assume that tabun, too, is known abroad. I know that tabun was publicized as early as 1902, that Sarin was patented, and that these substances appeared in patents. (...) Ambros was informing Hitler of an extraordinary fact about one of Germany's most secret weapons. The essential nature of tabun and sarin had already been disclosed in the technical journals as far back as [[1902]], and [[IG Farben|I.G.]] had [[patent]]ed both products in [[1937]] and [[1938]]. Ambros then warned Hitler that if Germany used tabun, it must face the possibility that the Allies could produce this gas in much larger quantities. Upon receiving this discouraging report, Hitler abruptly left the meeting. The nerve gases would not be used, for the time being at least, although they would continue to be produced and tested.|Joseph Borkin|The Crime and Punishment of IG Farben}} ===The secret gets out=== Towards the end of World War II and during the occupation of Germany, the Allies recovered weapons containing the three German nerve agents of the day, prompting further research into nerve agents by the former Allies. The Red Army captured a factory producing tabun at [[Dyhernfurth]] in early 1945, they dismantled the entire site and took it back to Russia. Stocks of tabun, sarin and soman were discovered by all the Allies within Germany; the Anglo-American advance seizing around 250,000 tons of chemical weapons, the subset of nerve agents (totaling around 30,000 tons) was split with the British taking 14,000 tons of tabun-filled bombs and the Americans taking the balance of sarin-filled devices. The fourth G-series nerve agent, cyclosarin, although discovered by German scientists studying organophosphates during WWII was seemingly not found by the Allies, but independently rediscovered in 1949. In [[1952]], researchers in [[Porton Down]], [[England]] invented the [[VX (nerve agent)|VX]] nerve agent, inspired by the commercial pesticide [[Amiton]], later reclassified as [[VG (nerve agent)|VG]]. The UK soon unilaterally abandoned the chemical weapons and chemical weapons research. In [[1958]] the British government traded their VX technology with the [[United States of America]] in exchange for information on [[thermonuclear weapons]]; by [[1961]] the US was producing large amounts of VX, and performed its own nerve agent research. The four agents (VE, VG, VM, VX) are collectively known as the "V-Series" class of nerve agents. === Since World War II === [[image:Halabja1.jpg‎|left|thumb|200px|Victims of the Halabja chemical weapons attack.]] Since World War II, Iraq's use of mustard gas against Iranian troops and [[Kurdish people|Kurds]] ([[Iran-Iraq war]] of 1981–1988) has been the only large-scale use of any chemical weapons. On the scale of the single Kurdish village of [[Halabja]] within its own territory, Iraqi forces did expose the populace to some kind of chemical weapons, possibly mustard gas, and most likely nerve agents. In the [[Gulf War]], 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]] 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]]. One of the most widely publicised uses of nerve agents was the [[Sarin gas attack on the Tokyo subway|1995 terrorist attack in which]] operatives of the [[Aum Shinrikyo]] religious group released [[sarin]] into the [[Tokyo]] [[metro|subway]] system. ===Ocean disposal of chemical weapons=== In 1972, The United States Congress banned the practice of disposing chemical weapons into the ocean. However 32,000 tons of nerve and mustard agents had already been dumped into the ocean waters off the United States by the U.S. Army. According to a 1998 report created by William Brankowitz, a deputy project manager in the U.S. Army Chemical Materials Agency, the Army created at least 26 chemical weapons dumpsites in the ocean off at least 11 states on both the west and east coasts. Additionally due to poor records, currently they only know the rough whereabouts of half of them. It is unknown how these dumps of chemical weapons have affected the ocean ecology—it may be responsible for some of the decline in fish populations over the past decades, but no evidence has yet proved a causal relationship between dumping and fish population decline. The steel containers they are contained within face a variable rate of decay and no one is really certain where or how deep they were dumped. If a nerve agent leaks into the ocean, it can last up to six weeks, during which time it will kill every susceptible organism it touches before it breaks down into its nonlethal chemical components. == Footnotes == {{reflist}} ==References== <!-- Citation format is detailed in Wikipedia:Cite_sources --> *Borkin, Joseph (1978). ''The Crime and Punishment of IG Farben''. Nw York: Free Press. 1978. ISBN 0-02-904630-0, available for download in [[Australia]] (as it is out-of-print) see [http://www.soilandhealth.org/copyform.asp?bookcode=030311 this link]. *{{cite book | author=Clarke, Robin | title=We all fall down: the prospects of biological and chemical warfare | publisher=Penguin | year=1969 | id=ISBN 0-14-021121-7}} * E-Medicine. (June 29, 2004). [http://www.emedicine.com/Emerg/topic899.htm CBRNE - Nerve Agents, V-series: Ve, Vg, Vm, Vx]. Retrieved Oct. 23, 2004. * E-Medicine. (June 30, 2004). [http://www.emedicine.com/emerg/topic898.htm CBRNE - Nerve Agents, G-series: Tabun, Sarin, Soman]. Retrieved Oct. 23, 2004. * Mitretek Systems. (May 2004). [http://www.mitretek.org/home.nsf/homelandsecurity/HistoryNerveGases Short History of the Development of Nerve Gases]. Retrieved Oct. 23, 2004. * Paxman, J.; Harris, R. (2002). ''A Higher Form of Killing: The Secret History of Chemical and Biological Warfare'' (2002 Rando edition). Random House Press. ISBN 0-8129-6653-8. * United States Senate, 103d Congress, 2d Session. (May 25, 1994). [http://www.gulfweb.org/bigdoc/report/riegle1.html The Riegle Report]. Retrieved Nov. 6, 2004. * Organisation for the Prohibition of Chemical Weapons - Nerve Agents [http://www.opcw.org/resp/html/nerve.html] * [http://www.fluoride-history.de/p-mfp.htm History of fluorophosphates as related to the development of nerve agents in Germany, Great Britain and the U.S.A.] * {{cite journal|journal= Neurology| volume=42|pages= 946–950|title= Nerve agents: a review| author= C. H. Gunderson, C. R. Lehmann, F. R. Sidell, B. Jabbari |year=1992| url=http://neurology.org/cgi/content/abstract/42/5/946 }} *Buckley NA, Roberts D, Eddleston M. ''Overcoming apathy in research on organophosphate poisoning.'' BMJ. 2004 Nov 20;329(7476):1231–3. Review. PMID 15550429 ==External links== * [http://www.atsdr.cdc.gov/csem/cholinesterase ATSDR Case Studies in Environmental Medicine: Cholinesterase Inhibitors, Including Pesticides and Chemical Warfare Nerve Agents] U.S. [[Department of Health and Human Services]] *Nervegas: America's Fifteen-year Struggle for Modern Chemical Weapons [http://www.wood.army.mil/chmdsd/Army_Chemical_Review/pdfs/Jan-June%202006/Kirby-Nerve%20Gas.pdf Army Chemical Review] *History Note: The CWS Effort to Obtain German Chemical Weapons for Retaliation Against Japan [http://www.cbiac.apgea.army.mil/products/newsletter_pdfs/vol5_num1.pdf CBIAC Newsletter] *[http://www.null-hypothesis.co.uk/science/news/item/goat_milk_gas_chemical_attack Goats' Milk Used in Production of Anti-nerve Gas Agents] *[http://www.youtube.com/watch?v=TWyj5-IKl-k Video footage of nerve gas tests on animals] *[http://www.youtube.com/watch?v=y9B6Nnz9-jg&feature=related Video footage of VX nerve gas test on a rabbit] {{Chemical warfare}} [[Category:Anticholinesterases]] [[Category:Nerve agents| ]] [[de:Nervenkampfstoff]] [[es:Gas nervioso]] [[fr:Gaz innervant]] [[it:Gas nervino]] [[he:גז עצבים]] [[nl:Zenuwgas]] [[ja:神経ガス]] [[no:Nervegass]] [[simple:Nerve agent]] [[sl:Živčni strup]] [[fi:Hermokaasu]] [[sv:Nervgas]] [[tr:Sinir gazı]] [[zh:神經毒素]]