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

Incapacitating AgentsSafety of the GlycolatesAs with most drugs, the per kilogram lethality ofBZ (for example) is progressively less in larger species.This relationship provides an extrapolated LD 50of 3 to5 mg/kg, which would suggest a very high therapeuticratio (more than 200). Such a safety margin is probablytoo optimistic, however, and a ratio of 40 has been acceptedas a conservative, but more likely, estimate. Thelatter figure was calculated by noting that preferentialaffinity for peripheral (such as cardiac) rather than centralmuscarinic receptors seems to predict the lethalityof the various belladonnoids. Before the Edgewoodstudies, central toxicity was usually considered thecause of death from atropine-like drugs, but it is morelikely that cardiotoxicity rather than central respiratoryfailure is the usual cause of death.Goodman collected data from hundreds of reportsof lethality and survival following high doses of atropine(most of them published in the 19th century) toestimate its LD 50. 134 Abood reports survival of at leastone individual who ingested more than 1,000 mgof atropine. 98 Recovery took 7 days. This case alonesuggests that the LD 50is much higher than the valuesgiven in textbooks. The LD 50values for the variousother belladonnoids were calculated by extrapolatingfrom Goodman’s estimate from atropine, taking intoaccount the other drugs’ relative central potency. 96The therapeutic ratio for BZ obtained by this methodis approximately 40. For scopolamine and other belladonnoidswith high relative central potency, thetherapeutic index is probably at least 100.In actual use, inhalation doses would be highlyvariable, depending to a degree on weather conditionsand methods of dissemination. The OperationsResearch Branch at Edgewood Arsenal computeddose distribution from a point source, ignoring windand other factors. Although difficult to apply withconfidence to a real-life situation, their results showedthat airborne concentration would taper rapidly fromany single source, causing a gradient of dosage.A 1964 feasibility study (Project Dork) involved 10volunteers and a team of medical personnel at DugwayProving Ground, Utah. 94 The subjects, standingon a flatbed trailer that moved to track the cloud, inhaledsmall particles of BZ disseminated from a pointsource. Breath samples from their modified maskswere fed to spectrophotometric devices, monitored bytechnicians and the physician, who watched the menand gave them telephonic directions from an airtightbooth mounted just behind them. Cumulative dosemeasurements in real time allowed the physician toterminate the exposure when the putative medianincapacitating exposure was reached. At 1,000 yards,50 pounds of BZ, floated downwind under idealatmospheric conditions, was required to reach thedesired dose.The volunteers actually had to jog in place for mostof 40 minutes to inhale the required dose. Consideringthat the arc subtended by the cloud of BZ was probablyno more than a few degrees, it would presumably takethousands of kilograms of BZ to produce incapacitatingconcentrations throughout 360° at a distance of1,000 yards. Under less than ideal weather conditionsit would take much more. This study provides someidea of the limitations of point source disseminationof agents possessing potency similar to that of BZ. Italso underlines the importance of accurate logisticalcalculations.The operations analysis group at Edgewooddeveloped idealized models for the disseminationof aerosolized BZ. Realistic projections, however,would require giving appropriate weights to all thegeographic, terrain, and atmospheric conditions in agiven tactical situation. Evasive action and protectivemeasures taken by the target population would addfurther variance. Aiming at a lower target dose wouldbe one way to minimize lethality while attaining thedesired goal of disrupting a group’s ability to function.Taking care of those who were completely nonfunctionalwould divert those who were unaffected. Itwould then be necessary to rely on partly incapacitatedpersonnel whose dependability would be uncertain.A military commander, even if personally protectedfrom the agent, would undoubtedly find it difficultto contend with such a complicated situation, even ifthe median dose absorbed by his troops were only afraction of the ID 50.Another theoretical possibility is the use of combinations.For example, a rapidly acting but short-lastingbelladonnoid could be mixed with a longer-actingagent that would take effect later and last from 1 to 3days (depending on the choice). A more problematicbut possibly effective mixture would be a fast-acting,potent opioid combined with a slower-acting belladonnoid.Opium was used to manage the agitation of belladonnadelirium for centuries before physostigminereplaced it. Whether such a mixture would increasethe danger of lethal overdose more than either agentused singly could only be learned from dose-responseanimal studies using various combinations of candidateopioids and belladonnoids.427