Part III - Historical Survey of the Porton Down Service Volunteer ...

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• changes in EEG readings reflect changes in neuronal function but the physiological significance of GB-induced long term changes in EEG readings remains unknown; • however, long term changes in EEG readings are generally accepted to represent long term changes in brain function. The results obtained in this study thus imply that exposure of individuals to GB "could be hazardous to long term health". By way of a post-script, these three studies were considered to have some grave limitations in terms of the technique available when they were conducted to record EEG measurements from monkeys. EEG probes were fitted to the head of each monkey, which was anaesthetised and kept in a restraint chair. This technique was suspected of affecting EEG measurements. A more recent study [138] with marmosets used the technique of remote radiotelemetry to record EEG measurements. No anaesthesia was required during the study which meant the animals suffered minimal disruption: they could continue to live in their usual environment during the study. This new technique has been widely demonstrated to have considerable advantages over the method used to record EEG in the three studies described above. Moreover, the recent study collected data from more animals than these three studies, thus increasing the sample size and the robustness of the statistical analysis which ensued. The study [138] considered the effect of a single low dose of GB, which induced a ChE inhibition of about 51%, on the EEG and cognitive behaviour of marmosets. Measurements were taken for up to 15 months after the dose of GB had been administered. The observations made by the study were that the low dose of GB produced no significant changes in EEG and no decrement in cognitive behaviour in the task used to measure it. 94
10.1. Background 10.1.1. The nature of V agents Chapter 10. V agents Work started on a new series of nerve agents, called V agents, in 1953 after a commercial firm sent Porton details of a new compound 9 [1]. V agents were found from animal studies to be highly toxic through the skin. By the end of 1955 Porton estimated that the LD50 for man of liquid V agent on the skin was about 6-10 mg [2], compared to the contemporary estimated LD50 for liquid GB of 1500-1700 mg and for GD 300-350 mg. Comparing these estimates indicates why the discovery of V agents was regarded in 1955 as the most outstanding advance in defence science [3]. V agents have a very low vapour pressure [4]; that is to say they evaporate very slowly, much more slowly than the more volatile GB. In practice liquid V agents would persist in the field for a long time after they had been initially delivered. With V agents being much more persistent and much more lethal through the skin, personnel could be killed not just by the initial attack but also by picking up lethal doses from surfaces and objects contaminated with liquid V [5]. This prompted Porton to conduct field trials with V simulants to determine whether troops would pick up lethal doses when moving over contaminated terrain. In 1955 the very high toxicity through the skin of V agents was thought to present such a hazard, even to those merely handling the agents, that no human studies were contemplated [4]. Inhaling V also posed a hazard which came in two forms. As V evaporated so slowly, it could be delivered only in liquid form [4] so the first hazard was from breathing in very small droplets of V disseminated as an aerosol. The second hazard arose from the inhalation of vapour. Although V agents evaporated slowly it was found from animal work that not much vapour was required to produce a toxic concentration [6]. Many V agents were considered in animal work at Porton from 1953 to 1958. By October 1958 VX had emerged as the one requiring further study and agreement had been reached about the nature of human studies to be conducted [8]. Over the next ten years or so, the following classes of human studies were conducted at Porton with VX: liquid VX skin and clothing penetration, VX vapour inhalation and absorption through the skin, and effects of VX vapour on the eyes. 10.1.2. Permission for human studies with V agents The constraints imposed by the Adrian Committee on human studies with nerve agents allowed work only with GB. Proposals to relax the constraints were made by Porton in 1957 [9] and were considered initially by the Biology Committee (BC) in April 1957 [10]. Two proposals were made: to administer GB by IV injection and to conduct human studies with V agents. The BC decided to defer the question of V agent experiments until more information had been obtained on the GB IV proposal [10]. The Adrian Committee limits could be changed only with the agreement of the Minister of Supply [11]. That condition imposed much activity: the Adrian Committee needed to be reconvened to consider the proposals [12] followed by SAC approval and consultation with Service ministries before a proposal was submitted to the Minister [11, 13]. Naturally, that took some time. The BC decision to defer the V proposal effectively added to the delay because the GB IV proposal was regarded as contentious. Deliberations over the GB IV proposal meant that the V proposal was not considered in detail until June 1959 [11]. Permission was sought for human studies in which small drops, up to a maximum dose of 20 µg, of radioactively tagged VX were applied to the skin. The SAC 9 The compound was referred to as C11. In the mid-1950s V agents were, in some official documents referred to as the C11 series or as phosphorus-sulphur compounds. 95
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