Medical Aspects of Chemical Warfare (2008) - The Black Vault

History of Chemical WarfareExhibit 2-10ORGANOPHOSPHORUSCATEGORIZATIONAltogether, there are five organophosphorus compoundsrecognized as nerve agents, designated GA(tabun), GB (sarin), GD (soman), GF (cyclosarin),and VX by their North Atlantic Treaty Organizationmilitary abbreviation. The “G” series is so named becausethese compounds originated in Germany. The Athrough F designation was based on the chronologicalorder of synthesis of each agent. Soman was termedGD rather than GC because the latter acronym hadalready been established in the medical literature, possiblyreserved for gonococcus. GF was the fourth agentsynthesized, but interest in this nerve agent declinedin favor of the other organophosphorus compounds.The fifth agent (VX) was named for being venomousand was synthesized many years later at Porton Down,England, in 1952. Only tabun, sarin, and soman werecategorized as the “Trilon group.” The toxicity andlethality of these three nerve agents on the civilianpopulation can be approximated based on their lethaldoses. The lethal dose for oral ingestion of tabun isroughly 100 to 200 mg min/m 3 , and 50 to 100 mg min/m 3 for sarin. Only 200 to 1000 mg of tabun applied tothe skin is sufficient to kill an adult human. The 12,000tons of tabun stocks alone that were reported at the endof the war could kill 60 billion individuals.Data source: German Munition Plants and Depots During WorldWar II. Aberdeen Proving Ground, Md: US Army Chemicaland Biological Defense Command; 1996.carbamate-type (eg, physostigmine-type, reversible)and OP-type (irreversible) cholinesterase inhibitorsled to a series of monumental discoveries by Germanscientists (Exhibit 2-10).The earliest reported incident of OP toxicity frominhalation came from the laboratory of Willy Langeat Friedrich Wilhelms University. In 1932 Lange andhis student, Gerde von Krueger, prepared dialkylmonofluorophosphates and noted their toxic fumes. 84,86They described the effects of the vapors on themselves,reporting breathing difficulties and blurred visionthat lasted many hours before subsiding. Towardthe close of 1936, at the chemical and pharmaceuticalconglomerate IG Farbenindustrie, Gerhard Schraderaccidentally discovered powerful OP compoundsduring his investigation into new insecticides. Afterpreparing them, Schrader’s biologist colleague, HansKukenthal, tested them for insecticidal activity. On De-cember 23, 1936, Kukenthal tested the new compoundson leaf lice and noted one to be particularly potent.All of the insects died after being sprayed with a concentrationof only one part in 200,000 of the deadlysubstance. 20,84 During preliminary manufacture of thecompound, Kukenthal noticed its equally impressiveeffects in humans. A spilled droplet from a solutioncould constrict the pupils and cause labored breathingimmediately. Even Schrader and his colleague felt theeffects upon themselves, requiring several weeks torecover. This was the first of the nerve agents or gases,called “tabun.”In 1936 tabun was reported to the chemical weaponssection of the German military prior to patenting. As acolorless, odorless poison, tabun was an ideal chemicalweapon. In May 1937 Schrader demonstrated itsdeadly effects to Colonel Rüdiger, a German ordnanceofficer and director of the Heereswaffenamt (HWA[German army weapons agency]). The military wasimpressed with the effects of the compound on thenervous system and classified the project for furtherresearch. The military assigned various names to thenew substance, including “Trilon-83,” “Le100,” “Präparat9/91,” “Nr 100,” “Gelan,” “Grünring 3,” “Stoff83,” and “Stoff 100,” but tabun was the name thatstuck. 20,91 After World War II, the CWS designated it“GA,” for “German agent A.”During a 2-year period between 1937 and 1939, theHWA assigned a large number of chemists to evaluatetabun and work on developing new nerve agents. 4,92,93The next step was mass production by the military, sothe HWA built a test plant in Münsterlager. Schraderfiled a patent on August 2, 1938, but it was kept secretuntil September 1951. 94 Schrader continued to synthesizeesters of fluorophosphoric acid, including diisopropylfluorophosphate, which Lange and Kruegerhad synthesized in 1932 and 1933.On December 10, 1938, 2 years after the discoveryof tabun, Schrader discovered a second lethal agent.This nerve agent was initially designated “T-144,” thebuilding number at the Dyhernfurth plant responsiblefor its pilot production. 20 It also went by the codenames“Le 213,” “Trilon-46,” and “Grünring 4.” 20,91,95 The compoundwas eventually dubbed “sarin” after the fourindividuals involved in the initial production process(Gerhard Schrader, Otto Ambros [IG Farben boardmember], Colonel Rüdiger [HWA], and Hans-Jürgenvon der Linde [HWA]). Some believe the “R” is namedfor fellow German chemist Franz Ritter. 95,96 Animaltesting showed sarin to be five to ten times as lethalas tabun. As the second nerve agent to be synthesized,sarin was later designated “GB,” for “German agentB,” by the United States.47