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Paradise Lost-The Psycho Agents Reid Kirby

Paradise Lost-The Psycho Agents Reid Kirby

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May 2006 page 1 CBWCB 71
THE CBW CONVENTIONS BULLETIN
News, Background and Comment on Chemical and Biological Weapons Issues
ISSUE NO. 71 MAY 2006
Quarterly Journal of the Harvard Sussex Program on CBW Armament and Arms Limitation
Invited Article, by Reid Kirby 1-5 Comment: The Summer of ‘76, by Ian Kenyon 5-6 Report from Geneva, by Graham Pearson 6-15 News Chronology November 05 - January 06 5-31Book Reviews, by Ian Kenyon 32 Forthcoming Events 32 Recent Publications 33-36 
After the First World War, advocates of chemical warfareput forth the notion of its humanitarian aspects. They definedhumanitarian as an avoidance of death, followed by practicalcomplete recovery. There was some merit to the claimscomparing the plight of chemical casualties with those frommechanical injuries of bullets, shrapnel, and explosives. ErnstFriedrich’s pictorial classic
War Against War!
(1924) is pivotalto reaching an understanding of this point. Unfortunately, theplight of chemical casualties at the time relied on questionablestatistical evidence. Pacifists and humanitarians did notembrace war by any means, even if it had no permanentlydebilitating consequences.The soldiers that molded the character of the United StatesArmy Chemical Warfare Service believed they wereproprietors of an awesome weapon with yet unrealizedpotentials. The problem was technical. It was not until afterthe Second World War, with a revolution in the pharmaceuticalindustry, that a realistic potential of chemical warfare withoutfatalities seemed to become a possibility.Prior to this point there were only two classes of chemicalwarfare agents: those safe enough for training and riot controluse (harassing agents), and the mass casualty agents forgeneral war that were likely to result in death or permanentinjury (lethal agents). A new class of chemical agents neededto be invented – the incapacitating agents.The harassing agents did not require medical intervention,and had fleeting effects lasting only minutes or hours. Lethalagents necessitated medical intervention, and hospitalizationin excess of a few days. The emerging incapacitating agentscould, it was thought, assure casualties for a day or moreand medical intervention was not needed in order to avoiddeath or permanent injury. A division in incapacitating agentssoon became apparent between those affecting the mentalfaculties (psycho agents), and those that affected thephysiological processes of the body, e.g. temporary paralysis.Only the psycho agents seemed sufficiently safe andlogistically feasible to warrant standardization by the UnitedStates Army Chemical Corps.
Psycho agents 
The psycho agents consisted of central nervous system (CNS)stimulants, such as Lysergic Acid Diethylamide (LSD), andCNS depressants, such as Agents SN, BZ, and EA3834. Ina publicity effort, the Chemical Corps showed the potentialof incapacitants (K Agents)
2
with animal experiments thatproclaimed the new agents as ‘fear gas’ or ‘war withoutdeath’. Infamous at the time, and a celebrity within theChemical Corps, was the cat exposed to an aerosol of LSDthat became frightened of a mouse (figures 1 and 2). Thecat later had a healthy litter of kittens.The psycho agents incapacitated primarily by interferingwith cognitive mental abilities and produced delirium orhallucinations. The produced spectrum of mental aberrationsranged from colourful mental sensation-confusing states (CNSstimulants - hallucinations) to black and white dream-likescurrility (CNS depressants - deliriums).The CNS depressants dominated the Chemical Corps’psychochemical programme into its weaponization phase. Thefirst agent to be standardized was Agent SN, followed bythe preferred Agent BZ. Then later, EA3834 became BZ’sprime replacement candidate. Interest in the incapacitatingagents remains throughout the world in the current searchfor ‘nonlethals’ for purposes such as law enforcement.For a lung effect, the principle anatomic barrier is thelung-blood barrier. Psycho agents have an additional blood-brain barrier to circumvent. The CNS depressants, thoughchemically different, typically relied on a tertiary amine to
P
ARADISE
L
OST
: T
HE
P
SYCHO
A
GENTS
Reid Kirby 
Project Manager, TALX Corporation 
 In the third Chapter of Sun-Tzu’s military classic
The Art of War
1
is conveyed the wisdom that preserving a nation,army, battalion, company, or squad is best, and destruction is second best. Later in his fifth Chapter it is stated that a commander engages with the orthodox and garners victory through the unorthodox. To these ends the utility of chemical warfare led to the invention of the psycho agents.
 
CBWCB 71 page 2 May 2006 
penetrate the blood-brain barrier and depress the synapticactivities of the brain. Furthermore, the psycho agents aregenerally anticholinergic, having a pharmacological actionsimilar to the nerve agent antidote Atropine.With such a specific site of action, the dose-response curvefor these agents is steep. The degree of incapacitation andhence the requisite dose was always a matter of debate.Disruption of cognitive abilities could be produced at relativelylow doses, comparable to the incapacitating doses of the G-series nerve agents. Rendering a person incapable of function-ing within their environment often required doses around thoseof the lethal index for the G-series nerve agents, andincapacitation from ataxia or a coma-like state required quant-ities approaching those of the lethal index of First World Warchemical agents.Also, like designer drugs, modifying the chemical structureof the psycho agents - by changing functional groups, length-ening hydrocarbon chains, or replacing phenyl with thienylrings - greatly modified the duration, degree, and type of in-capacitation. For example, a lengthened hydrocarbon chainon the quinuclidine group of Agent BZ displaces its incapacit-ation budget into increased ataxia.
3
Agent SN (Sernyl) 
First synthesized in 1926, it was not until the 1950s that thechemical phencyclidine attracted medical interest. The Parke-Davis Company hoped that its candidate Sernyl, named forits intended somnolent effect, would be highly valued amongthe surgical anesthetics because of its uncommon cardio-vascular and respiratory stimulation. However, clinical trialsin 1957 demonstrated a disturbing dissociative effect, withpost-operative thought disturbances and agitation. By 1965,Parke-Davis had discontinued its interest in Sernyl, thoughthey later promoted it in a salt formulation for use as aveterinary immobilizing agent (Sernylan).The Chemical Corps was alerted to the potential of Sernylas an incapacitant in 1959, and investigated its potential atEdgewood Arsenal, renaming it EA 2148. A limited numberof 
 per oral
and aerosol laboratory studies using humansubjects before 1960 demonstrated a high degree of variabilityin its effects.
4
Nonetheless, the manufacturing process forSernyl was well established and the United States approvedits adoption for chemical weapons as Agent SN under ProjectNEWYEAR, a program that sought to deliver incapacitatingmunitions by 1960.
5
The British were unimpressed with thedecision, believing that the dosage requirements were unattain-able in the field.The envelope-of-action for SN is a 30 minute to one houronset, with duration-of-effect lasting 8 to 24 hours. At 25 –50 mg
.
min/m
3
SN is anesthetic, and dosages over 100 mg
.
min/ m
3
begin to be incapacitating with mental disturbances. TheUnited States and British believed that the ICt
50
 
for employ-ment needed to be around 1,000 mg.min/m
3
, a dosage pro-ducing marked ataxia and verging on a coma-like state.Dosages approaching 3,000 mg.min/m
3
had been survivedwithout convulsions or adverse sequelea, resulting in aduration-of-action of 1 – 2 days.Agent SN had a reasonable margin of safety, with
 per oral
ID
50
and LD
50
estimates being 10-20 mg/man and 100mg/man respectively. Death, if it ensued, followed a coma-like state and resulted from cardiovascular and respiratoryfailure.Sernyl is more commonly known as PCP, or the illicitdrug ‘Angel Dust’. As such, Sernyl has the distinction of beingthe only drug that non-human primates will self-inject. Its illicitrecreational use in US ‘markets’ started in the mid-1960s,peaked about 1980, and was replaced by other drugs in themid-1980s. The erratic and violent behavior produced by PCPis well known today: it makes criminals seemingly invulnerablebecause of their inability to sense pain while remaining fullymobile. If Agent SN had been used under combat conditions,the results may well have not been the ‘somnolence’ en-visioned, but more like something out of the movie
 Night of the Living Dead 
. Though approved, Agent SN munitions werenever produced.
Agent BZ (Buzz) 
Hoffmann-La Roche Inc invented 3-quinuclidinyl benzilate in1951, while they were investigating antispasmodic agentsresembling Tropine for the treatment of gastrointestinalconditions.
6
Interest in the drug as a potential chemical war-fare agent followed a screening program that took place inabout 1959 at the University of Chicago College of Medicine,in cooperation with an outside commercial firm.
7
EdgewoodArsenal soon investigated it under the name EA 2277, and itbecame the single most important agent under consideration.Originally given the military symbol TK, it was standardizedfor use in chemical munitions in 1961 under the name of AgentBZ. But the unofficial name for the agent emerged as ‘Buzz’,because of the mental aberrations it purportedly caused.Millmaster Chemical manufactured 100,000 lbs of BZ for
Fig 2: Cat on LSD terrified of mouseFig 1: Cat not on LSD treating a mouse as cats do
 
May 2006 page 3 CBWCB 71
the US Army in 1963 – 1964, and shipped it by rail in 16-gallon drums to Pine Bluff Arsenal for filling into munitions.
8
Given the Q
50
for BZ, this signified a quantity adequate for asingle action on a Brigade or town-sized target (15 km
2
).10,000 lbs of BZ would be used through the 1960s for weaponsdevelopment and field trials. There was consideration of numerous weapon systems, ranging from small-arm grenadesand MARS smoke generators to aerial spray tanks and ballisticmissile warheads (notably the Padeye and CBU-16A/Adispensers). However, only two weapon systems attainedsignificant standardization:
9
BZ was a complex agent to synthesize, and ratherexpensive. At $40/kg at the time of its manufacture, it wasprobably the single most expensive chemical agent standard-ized by the US.
12
The quantity purchased by the US indicatesthat large-area employment of BZ was not practical, and thatit was reserved for more-or-less critical point situations (i.e.landing zones, special operations, and fortified positions).Its weaponization also presented a manufacturing problem.BZ was to be disseminated by thermal munitions in a 50:50pyrotechnic mixture. Prior to the adoption of BZ, thermalmunitions were ‘dry-pressed’. Accidental ignition wouldoccasionally occur in production lines, but as with signalsmokes or tear agents, such accidents had only a transientimpact on productivity. With BZ, the potential casualty effectnecessitated the use of a ‘wet-pressed’ method to avoid thesesorts of mishaps. The solvent used (acetone) had a deleteriouseffect on many of the plastics used in standard weaponsystems.
13
The eventual doses for BZ were somewhat higher thanoriginally anticipated, after it was discerned that the lungsonly retained 45% of the inspired agent instead of the 50%originally believed.
14
For a person at rest, the ICt
50
is 170mg
.
min/m
3
. For mild activity this dosage drops to 110 mg
.
min/ m
3
. In either case, the incapacitating doses are comparableto the lethal index of the G-series nerve agents. The LCt
50
isbelieved to be 200,000 mg
.
min/m
3
based on animal studies.Agent BZ was far superior to Agent SN in terms of casualtyeffect and safety margin.But the operational problems that BZ presented werenumerous. Its visible white agent cloud warned of its presence.Improvised masks, such as several layers of folded cloth overthe nose and mouth could defeat it.
15
Its envelope-of-actionwas less than ideal. The rate-of-action was delayed (5% within2 hours, 50% within 4.5 hours, and 95% within 9.5 hours),and the duration-of-action was variable from 36 to 96 hours.
16
Additionally, 50% to 80% of the casualties required restraintto prevent self-injury, and paranoia and mania were commonpersonality traits during recovery. These uncertainties madeBZ unattractive to military planners.
EA 3834 
Doubling the dosage of BZ increased the duration-of-actionby an additional 40 hours. This meant burdening exploitationforces with restraining casualties well after employment.Towards the end of the 1960s Edgewood Arsenal startedconsidering 1-methyl-4-piperidyl isopropylphenylglycolate, orEA 3834, as a replacement for BZ.EA 3834A, a hydrochloride salt, had greater absorptionfor a lung effect than the base, with an ICt
50
of 73.4 mg
.
min/ m
3
(mild activity). This was somewhat better than that forBZ. The envelope-of-action was also more predictable. Atthe ICt
50
the rate-of-action was 35 minutes, with duration-of-action of 10 to 15 hours. At three-times the ICt
50
, the rate-of-action dropped to 10 minutes, with a duration-of-action thatwas still under 24 hours. The superior envelope-of-action tothat of BZ meant that it would not be necessary for victims tobe interned for a week after a 1-day combat action.Concerns that EA3834 could produce hematuria delayedits adoption.
17
A human subject developed hematuria thatpersisted intermittently over a year. Subsequent animal studieswere conducted and concluded that hematuria was possiblefrom EA 3834, BZ, and atropine. The results were disputed
·
The 175-lb generator cluster (M44 or E154) - for deliveryby light aircraft used for observation and spotting in tacticalcombat. It was composed of three 50-lb thermal generators(M16) that resembled the standard US floating smoke potfilled with thermal canisters and a chute attachmentdropped from a hard-back assembly (figure 3).
10
Fig 3: 175-lb generator cluster (M44 or E154)Fig 4: 750-lb bomb cluster (M43 or E153)
·
The 750-lb bomb cluster (M43 or E153) - also for subsonicaircraft delivery, using a standard cluster adapter that couldbe adapted for high-speed delivery by adding aerodynamictail fairing. It was composed of 57 M138 thermal bombletsthat resembled the standard US 10-lb smoke bomblet(figure 4).These weapon systems were intended only to cover targetsof about 0.11 to 0.88 hectares respectively – used againstsquad- to company-sized targets; they were to be used forspecial operations against hard targets of intelligence value,hostage/prisoner rescue, or in cases where friendly and threatforces were intermingled.
11
Only about 1,500 of these munit-ions were stockpiled. There were also other employmentconcepts envisioned, based on the low-intensity conflictexperiences in Algeria and Berlin. But the Chemical Corpsformulated its employment doctrine in a vacuum; other militarybranches never furnished end-user requirements.

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