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

Part III. Human studies with nerve agents
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Overview
Human studies with nerve agents were conducted initially with G agents (GA, GB, GD, GE
and GF). Later, a new series of nerve agents was discovered, the V series, and human
studies were conducted with one of them, called VX. Studies were usually of three types:
vapour inhalation, the effect of vapour on the eyes, and penetration of the skin and clothing
by liquid. Each of these types of studies was conducted with G agents from 1945 to 1953.
They sought mainly to understand the effects of G agents on man, to estimate threshold and
harassing dose levels, and to provide results from which lethal doses could be extrapolated.
From 1954 less effort was devoted to G agent work, partly because of the discovery of the V
series and partly because more attention was being paid to incapacitating agents. Also,
studies before 1954 had yielded answers which allowed work to be carried out to develop
treatments. Indeed, the period after 1954 was dominated by human studies of various
therapies and prophylactics for nerve agent poisoning. Those studies are described in Part
VII.
Human studies that were conducted with G agents after 1954 were confined to vapour work.
Most of the studies sought to understand the impact on military efficiency of G agent
poisoning. Many of the studies concentrated on eye effects. VX studies ran from 1958 to
1969. Those involving Service volunteers considered the skin penetration of liquid VX and
the effect of VX vapour on the eyes. Studies of the inhalation of VX vapour were conducted
only with volunteers from the Porton medical staff.
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G Vapour
G Liquid
VX
GA
GA, GB, GD, GE, GF GB,GF
Effects on man and dose estimates
GA
GB, GD, GF
Military performance
Liquid penetration
Eye effects
Eye effects
1945 1950 1955 1960 1970 1989

8.1. Discovery of the "Ideal War Gas"
Chapter 8. G agents 1945-1953
In early April 1945, as Allied Forces moved across Germany, 21 Army Group captured
German artillery shells at the railway marshalling yard at Osnabruck [1]. Two types of 105
mm shells, one marked with a white ring and the other with green and yellow rings, were new
and thought to be worth analysis at Porton and in US laboratories [1]. Four shells, two of
each type, arrived at Porton on 8 April 1945 [2]. The shells marked with the white ring were
quickly found to contain a tear gas. The contents of the other shells eluded identification.
The contents were thought, at first, to be considerably less toxic than mustard gas when
breathed in as a vapour [1] but, by 12 April, were found to be highly toxic when inhaled by
animals, causing rapid death [3]. The new gas, found to be about 80% of the content of these
shells, was given the code T2104 and referred to as Tabun, or GA.
GA was regarded by the Germans as being close to the "ideal war gas". It was effective in
small quantities, colourless and odourless. It acted much more quickly [4] and was much
more lethal than the "traditional" mustard and phosgene war gases. GA was developed as
an insecticide by a German company, IG Farben. The German Army Ordnance Department
took over the manufacturing process, starting in February 1942. Two other toxic substances
of similar chemical composition were discovered, Sarin (GB) and Soman (GD). Work on GB
lagged behind the work on GA and production for the German Army did not start until 1944
[4].
In mammals, impulses between adjacent nerve cells, and from nerve cells to muscles, are
transmitted as messages. Between a nerve cell and a muscle (called the neuromuscular
junction) these messages are passed by a chemical called acetyl choline (ACh). Having
delivered the message, ACh is destroyed by an enzyme called cholinesterase (ChE) which is
present in large quantities in body tissues. If ACh is not destroyed by ChE after transmitting
the message, it will cause cumulative effects: the stimulation of the nervous system, then
over-stimulation, eventually leading to spasms, convulsions and partial paralysis [6].
The basic mode of action of nerve gases is to inhibit the activity of ChE and thereby prevent
the destruction of ACh [6]. Thus, a victim of nerve agent poisoning may not be able to relax
muscles. Nerve gases may have a local effect or a systemic effect. An example of a local
effect is the constriction of the pupil when nerve gas vapour inhibits the activity of ChE in the
eye. Systemic effects may affect muscles (such as those responsible for breathing [7]) in the
peripheral nervous system or elements of the central nervous system.
A compound which inhibited ChE (called PF-3) had been studied at Porton during the war. It
was rejected as a lethal agent, partly because the vapour dose required to induce casualties
was much higher than the casualty dose of mustard gas [8]. This difference in view between
Porton and the Germans, of the value of the organophosphorus nerve agents, arose because
the chemical composition of PF-3 is different from the chemical composition of the G agents
[9].
8.2. Wartime work with GA
8.2.1. Human studies
The first human study with GA was conducted on 10 April 1945, before the substance in the
captured artillery shells had been identified, to ascertain whether or not it was a vesicant [10].
A drop of 1.1 mm diameter was placed on the skin of the arms and a drop of 2 mm was
placed on top of layers of serge and flannel attached to the arms. Eight Service volunteers
received each of these doses [11]. At the same time, drops were placed in the eyes of
rabbits. Men and rabbits then waited together for the substance to have an effect. Five
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minutes later one of the rabbits died. The experiment was brought to an abrupt end and the
men quickly washed off the substance from their arms.
On 14 April 1945, a meeting of the three UK Services was convened at which it was decided
that defensive measures against the new gas were to be developed urgently [12]. The
foundation of the Services' concern was that Germany might yet use the artillery shells
against the Allies as more shells had been found at Espelkamp [13]. Telegrams [14] from the
War Office to the Headquarters of Allied Commands were sent on 16 April, containing
preliminary information about GA [15], including:
GA "is not a vesicant but is rapidly toxic if the eye or skin absorbs liquid - lethal dose
for man of the order of 5 grams absorbed through skin. Vapour in low concentrations
strongly constricts pupils and causes tightness of chest. Mainly dangerous in the
field to eyes and lungs as an initial cloud".
The assessment of GA continued after these telegrams were sent. Studies with animals and
humans were conducted: on 18 April 1945 fifteen men, including Porton staff, were exposed
to GA at levels of 3.2 mg.min/m 3 and 14 mg.min/m 3 (t = 2 mins) [15, 16]. The main results
were:
• pupils were constricted (miosis) by the lower dose, and this persisted for 48
hours;
• although all observers detected a faint smell at the higher dose, it was thought
that the concentration (7mg/m 3 ) could not be reliably detected on the battlefield.
At the higher dose all human subjects had "markedly constricted pupils" followed
by a severe headache. These symptoms lasted for 2 days.
PF-3 was known to cause miosis but exposures of between 40 and 80 mg.min/m 3 of PF-3
were required to induce the same effects as the much lower doses of GA used here. It was
thought important, therefore, to explore miosis further and find out if it affected military
efficiency [15].
The study in July 1945 involved 42 Service volunteers. Seven men were exposed twice.
Some men wore no protection during the study and were exposed to GA at 0.7-21 mg.min/m 3
(t = 10 mins). Some men had their lungs protected by an oro-nasal respirator and were
exposed to 30 mg.min/m 3 (t = 10 mins). The main results were as follows [17]:
• the exposure to 0.7 mg.min/m 3 induced coughing and the feeling of constriction
of the chest;
• exposures to 14, 18 and 21 mg.min/m 3 had a "severe harassing effect"
characterised by some or all of the following symptoms: severe headache,
pinpoint constriction of the pupils, pain when focusing on objects close to the eye,
slight blurring in vision, tightness in the chest and coughing, nausea and
vomiting. Without treatment, these symptoms became most debilitating 24-48
hours after exposure;
• 30 mg.min/m 3 exposed only to one eye decreased visual acuity markedly, and
recovery was not complete until at least 17 days later.
This work suggested that exposures to GA of greater than 14 mg.min/m 3 would impair military
efficiency and, therefore, might be regarded as harassing doses [18] but no studies had
explicitly assessed the ability of the men exposed to GA to conduct military tasks. The next
study [18] sought to remedy that.
Later in July 1945, infantrymen and civilian staff working at Porton were exposed to GA at
28 mg.min/m 3 (t = 10 mins) and then asked to perform tasks that were part of their normal
duties. Twenty nine people participated in this trial. For the infantrymen, the tasks included
standard tests of elementary infantry training (rifle firing on the range and the operation of a
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Bren gun), map reading and visual identification of targets. Porton staff performed simple
tasks in the laboratory and with pen and paper. The main results were [18]:
• Although the symptoms observed were similar to those seen in trials conducted
earlier in July, the effect on performance was "very much less" than those
symptoms might suggest.
• Nonetheless, the 30% loss in vision, combined with the other effects (nausea,
tightness in the chest) observed, was thought likely to render well trained troops
unable to perform military tasks if sustained effort was required.
• GA was "easily detected" by the combination of smell, and initial effects on the
eyes and chest, from about 3 minutes after the start of the exposure.
This trial marked the end of wartime work with humans. The conclusions about the degree of
miosis induced and the difficulty of detecting GA by smell were taken forward. The
provisional appreciation of the value of nerve gases produced in December 1946 [9] noted
that low vapour levels "over about 5 mg.min/m 3 " induced marked and persistent miosis.
8.2.2. Annulus trials
Annulus trials which did not involve human volunteers are not covered by the survey but one
set of trials is worth mentioning as it produced estimates of harassing and lethal doses of GA.
In May 1945 a small team from Porton was sent to Raubkammer, the German Army chemical
warfare experimental station, to examine GA when dispersed from German artillery shells or
from British munitions. Over three months, 26 annulus trials were completed and the effects
of GA vapour on animals assessed [5].
The trials suggested that 120-150 mg.min/m 3 would "present a serious hazard to man" [5].
Lethal doses for GA against man, established by the Germans in 1944, varied from 274
mg.min/m 3 to 400 mg.min/m 3 [19].
During the trials at Raubkammer, Porton staff interviewed German personnel responsible for
chemical warfare work. Details of other types of nerve gas emerged from these discussions.
GB was regarded by the Germans as "three times more toxic than GA in the laboratory and
six times more effective in the field" [5]. GD also came to light in talks with the Germans [20].
The main conclusion of the Raubkammer trials and Porton work with animals was that GA
produced rapid death in very low dosages and Sarin was likely to be even more effective [5].
8.3. Immediate post-war activities
8.3.1. Background
In the immediate aftermath of the war in Europe, the Soviet Union was known [21] to
"physically possess" the German GA and GB production plant at Dyhernfurth, and had
captured German personnel working at the two plants. In October 1945 British intelligence
believed that if the Soviet Union was not already producing compounds similar to GA and GB,
they have "probably learnt enough about them in Germany, to be able to produce them in the
near future" [21]. Subsequent Intelligence assessments in 1949 and 1950 [22] suggested
that the Soviet Union would be producing nerve gases in large quantities by the first half of
1951.
The decision in the spring of 1947 to develop nerve agent weapons for use by the UK Armed
Forces [23] meant that one of the members of the G series had to be chosen for UK offensive
weapons. The studies conducted by Porton informed this choice, which was eventually made
in favour of GB. The studies involving volunteers are described in later sections but the
decisions en route to choosing GB are outlined below because they helped to shape the
nature of human studies with nerve agents: as will be seen, the majority of human studies
considered GB.
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a. Based on Porton work reported in June 1949 [24], it was decided in October
1949 [25, 26] that GA was of little value. GD was found to be the most toxic of
the G series but was ruled out because the raw material (pinacolyl alcohol)
necessary for its production was not available in any quantity. GB was generally
preferable to GE but GF showed some promise as a persistent agent that
attacked through the skin and it was decided that it should be examined further.
b. A further assessment of nerve gases published by Porton in August 1950 [27]
concluded that, from a toxicological aspect, GB is "in every way superior to" GE
as a chemical warfare agent. GD and GF were found to be highly toxic through
the skin but were thought to be of too low a volatility to be used in HE/chemical
munitions. The possibility of using GD and GF as an anti-personnel spray was
considered.
c. In December 1950 the War Office was noted to have "a definite aversion to
persistence" [28]. This ruled out GD and GF which evaporated much more
slowly than GB. In May 1951 it was decided that GB would be the agent used in
UK offensive weapons and would be produced on a large scale [29].
8.3.2. Preparatory work at Porton
Plans for a systematic physiological investigation of the G agents were produced by Porton
[30, 31]. From 1946 to 1948 assessments of nerve agents with animals were undertaken,
which allowed the members of the G series to be compared and paved the way for human
studies.
The remaining preparatory work immediately after the war saw the development of new
experimental techniques and equipment. Nerve agent studies required a supply of samples
of the G agents and the decision to develop weapons meant larger quantities of nerve agents
needed to be produced. Porton, therefore, studied ways of manufacturing G agents.
Existing experimental techniques and equipment at Porton had been developed largely for
mustard gas work. Some were unsuitable or inadequate for studies with nerve agents.
Apparatus for eye studies and techniques for chamber tests were needed [31]. Various
techniques and equipment were developed immediately after the war: new gas chambers
were fitted and calibrated, techniques for measuring the concentration of G agents were
developed, and simulants for G agents were sought.
A technique was developed to measure and compare the effects of G agents. It was thought
in 1946 that measuring ChE activity, and the degree to which it was inhibited by G agents,
would be a useful means of comparing nerve gases [31]. Measurement was a complicated
process and several methods were available at the time. Apparatus was set up to measure
ChE activity by the Warburg method [32] in 1946.
The role of ChE as a detector of nerve gases, an aid to detecting nerve agent poisoning and
a means of predicting lethal doses in man is described at Annex C.
8.4. Human studies with vapour
8.4.1. Detection: chamber studies
The possibility of recognising the presence of nerve gas vapour by a combination of smell,
chest and eye effects was recognised in the plans for nerve agent work produced for CDAB
by Porton in December 1946 [30]. The concern was whether men would recognise these
effects before a dangerous dose was inhaled.
A series of studies was conducted in late April 1948 [16, 33] in which sixteen volunteers from
among Porton staff [16] were exposed, with eyes protected by goggles, to GB, GD and GE.
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Fifteen of the sixteen men were exposed to each agent. Very low exposure levels were used
in each case, less than 1.5 mg.min/m 3 for 30 seconds. The main results were as follows:
• although the men were able to smell the gases (GB having the faintest odour of
the three) it was doubtful that detection by smell in war would enable protective
measures to be taken in time;
• however, in areas of the battlefield contaminated with such low doses of vapour it
"seems certain" [33] that the mildly unpleasant effects (tightness of chest and a
running nose) would induce people to seek protection and thereby eliminate the
risk of inhaling a dangerous dose.
The second point was deemed encouraging. Nonetheless some men might detect a nerve
agent from the symptoms they had but not be able to gain protection in time to prevent
poisoning. Further, very high doses might poison if they were inhaled for only a short time.
Attention turned to measuring the inhibition of ChE as a means of detecting nerve gas
poisoning caused by the inhalation of vapour. For this to be feasible, doses which induced
mild effects must inhibit ChE.
A human study was conducted in August 1949 to explore this [34]. Exposures to GB of
3.4 mg.min/m 3 and 6.4 mg.min/m 3 were used to induce symptoms of mild poisoning. The
plasma 1 ChE of the men who took part was measured before and at various points after
exposure. Ten men participated in the study. Five men were exposed once to the higher
dose and the other 5 men were exposed three times to the lower dose to find out if
cumulative doses induced a fall in ChE. The first and second exposures were separated by a
day; the second and third exposures separated by 3 days [16].
The conclusions drawn were that:
• at these doses, ChE was found to be inhibited but remained within normal limits;
• ChE fell about one hour after exposure, long after clinical symptoms (miosis and
tightness of the chest) were experienced.
These conclusions were found to accord with US work which suggested that the sensitivity of
the eyes meant severe miosis could be induced without a significant fall in blood ChE.
According to initial results from the US, chest symptoms might also be induced without
affecting blood ChE activity.
The lessons drawn from these two studies were that the symptoms induced by nerve agent
vapour would serve as a means of detection and prompt soldiers to don respirators before
lethal doses were inhaled. Further, "there was no point" in using ChE as a means of
detecting poisoning by nerve gas vapour, as the symptoms would serve as a better and
earlier indicator [35, 36]. Despite the clear result that ChE was of little value for diagnosing
vapour poisoning there was agreement in 1950 [27, 34, 35, 36] that ChE activity might be
useful when GB entered the body by other routes.
8.4.2. Detection: field trials
After the decision in May 1951 to use GB in offensive weapons, field trials were conducted to
find out if GB discharged by artillery shells could be detected by smell. The chamber studies
had shown that pure GB had no readily perceptible smell. However, when GB was used in
shells a substance had to be added to keep the GB stable [37]. Two field trials were carried
out in December 1951 with 25 pound shells [37]. In each trial, volunteers were kept under
cover while a shell was exploded. As soon as there was no danger from shell fragments,
volunteers wearing goggles and carrying caged rabbits were brought out of cover by a Porton
1 Blood is made up of plasma and cells. Cells and plasma can be separated and ChE is present in
each. At various times at Porton ChE inhibition was estimated by measuring red blood cell ChE, plasma
ChE and whole blood ChE.
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staff member and moved to sampling positions. Volunteers stood in a line, 5 yards apart, and
remained there until the cloud generated by the shell had passed over them. The distance
from the sampling positions to the point at which the shell was burst was chosen, based on
measurements of temperature and wind speed, so that the maximum accumulated exposure
experienced by volunteers would not exceed 12 mg.min/m 3 .
Trial 1. Ten volunteers took part. Three shells were exploded one at a time: one
shell with GB stabilised with triethylamine, one with GB alone, and one with water.
GB (from the first two shells) at the sampling points varied from 0.35 - 1.6 mg.min/m 3 .
Trial 2. Eight volunteers took part. Four shells were exploded one at a time: three
had the same fillings as Trial 1, the fourth contained GB stabilised with ammonia. GB
at seven of the sampling points varied from less than 0.35 mg.min/m 3 to
1.4 mg.min/m 3 . The volunteer at the remaining sampling position was exposed to
10.5 mg.min/m 3 .
The volunteers who participated in the trials were able to distinguish by smell the shells
containing GB from those containing water. The stabilisers seemed to make the smell
appreciably stronger. Another set of field trials was conducted in February 1952 [38] and the
procedure adopted in the December 1951 field trials was used again. Four trials were carried
out, with a wider variety of stabilisers.
Trial 1. Twelve volunteers took part. Four shells were used: one with water, one
with GB alone, one with GB stabilised by triethylamine and one with GB stabilised by
diethylamine. The exposure levels in this trial were 0.4 - 1 mg.min/m 3 .
Trial 2. Ten volunteers participated. Four shells with the same fillings as Trial 1
were used. Exposure levels were 0.4 - 1.7 mg.min/m 3 .
Trial 3. Fifteen volunteers participated. Three shells were used, one with water, one
with GB alone and one with GB stabilised by methyl-N-morpholine. Exposures were
0.4 - 1.1 mg.min/m 3 .
Trial 4. Fifteen volunteers took part. Three shells with the same filling as Trial 3
were used. Exposure levels were 0.5 - 3.2 mg.min/m 3 .
As in the December trials, volunteers were able to detect GB by smell. The volunteers found
little difference between the smell of GB alone and of stabilised GB. This was thought by
Porton to be somewhat suspicious as it "suggested the possibility of collusion having
occurred between observers" [39]. Therefore a further set of trials was carried out March
1952 but in this trial each volunteer was accompanied at his sampling point by a "responsible
scientist", thus eliminating the possibility of collusion. Apart from this pairing arrangement,
the procedure adopted for the trials was the same as before.
• Two shells were used: one with GB alone and one with GB stabilised by
triethylamine.
• Nineteen sampling positions were used. At 18 of them a volunteer was
accompanied by a member of Porton staff. At the nineteenth, two volunteers and
one member of staff were used. Exposures experienced were 0.4 - 1.7
mg.min/m 3 .
No significant difference was found between the smell of GB alone and stabilised GB. The
trial confirmed that GB dispersed explosively by a shell could be detected by smell at
concentrations of 0.5 - 0.8 mg/m 3 [39]. Trials were held later in March to find out if GB
dispersed as a spray, rather than in an explosion, could be smelled [40]. Ten volunteers
participated. GB alone and stabilised GB were released as spray individually. The duration
of each exposure was about 50 seconds and the levels varied from 0.4 to 3.1 mg.min/m 3 .
Volunteers were unable to detect any difference in smell between the two sprays. However,
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the nature of the smell differed from previous trials. Here the smell was reported as being like
ether; in earlier trials "carbide" was the smell most commonly reported [41].
A final field trial was conducted in June 1952 [41]. Porton were unsure if GB falling on wet
ground might have produced the odours experienced in the previous trials. This trial saw GB
sprayed on surfaces of sand whose moisture content was measured. Four areas of sand
were used, each 1 x 2 m in area, 20 yards apart. GB was applied to the sand by a small
sprayer in 1-2 mm drops. Two of the sand areas were dry.
• Four volunteers took part. After each of the areas of sand had been
contaminated with GB, the volunteers approached the areas from downwind and
across wind. The downwind sampling position for each sand area was marked
by a flag and chosen so that a 1 minute exposure would result in a maximum
exposure of 2 mg.min/m 3 .
• One of the volunteers reported a very faint smell, akin to ether, but none could
distinguish any difference in smell between the sand areas.
• The trial concluded that the moisture content of the surface from which GB
evaporated had no influence on the odour produced.
8.4.3. Threshold and harassment dose assessments
After the two chamber studies on detection, work began on assessing threshold and casualty
doses. A study was conducted from March to July 1949 to identify the threshold dose for
miosis 2 [42]. Forty three unprotected men were exposed to 1.65 mg.min/m 3 , 3.3 mg.min/m 3
and 6.4 mg.min/m 3 of GB for about 20 minutes. Some of the men were exposed twice or
three times. Rabbits were also exposed. Another thirteen men were exposed several times
to the two lower doses over several days to find out if repeated doses increased susceptibility
and therefore lowered the threshold dose.
The following results were obtained:
• For the single exposures, 3.3 mg.min/m 3 seemed to be the threshold. At this
level miosis was suffered, but other symptoms were negligible;
• 6.6 mg.min/m 3 induced effects "approaching the stage of mild harassment";
• The cumulative effect of exposures at 3.3 mg.min/m 3 may amount to mild
harassment after 3 to 4 exposures but the effect could be checked by breaks of a
day or so between exposures.
This work had estimated an approximate threshold dose for miosis. A study was conducted
from March to December 1950 to refine this estimate and to identify harassment doses with
GB [43]. This study is referred to in Porton progress reports [44, 45, 46] as "trials to assess
the relative aggressiveness" of nerve agent vapour, and involved exposures to GA, GB, GD,
GE, GF [45, 47].
No reports have been found summarising the results of this study for GA, GD, GE and GF,
although it was noted in December 1950 [45] that GD had the "most aggressive effects in
humans, at a comparatively low level (5 mg.min/m 3 ) producing eye symptoms of great
severity, consequent marked effect on morale with emotional disturbance".
A summary of the exposures used in the aggressiveness study for GA, GD, GE and GF
appear in Table 8.1 [47, 48]. Exposure times were about two minutes.
2 The experiment log [73] includes details of two exposures to GA and one to GE, among the
exposures to GB reported here.
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G Agent Exposure Range mg.min/m 3
GA 1.8 - 9
GD 1 - 5.1
6.6 - 10.1*
GE 5 - 14
GF 2.25 - 14
* Men exposed to these levels wore oro-nasal respirators.
Table 8.1. Agents other than GB in "Aggressiveness study"
The GB work in the aggressiveness study was split into two [43]. The first part involved
exposures of 1.4 to 13.9 mg.min/m 3 and involved 48 men. Most of the men were exposed
without protection, while some wore oro-nasal respirators to prevent inhalation. The second
part considered only the eye effects of GB vapour. Fifty seven men wearing oro-nasal
respirators were exposed to 7.3 - 36.7 mg.min/m 3 .
The important result of the second part of the study with GB was that the effects induced
showed little variation over 14-36.7 mg.min/m 3 , suggesting that the lowest point in this range
was sufficient to inhibit completely local ChE in the eye. Together with results from the first
part of the GB study and the earlier 1949 study, the conclusions drawn were that [27, 43]:
• the threshold dose for inducing miosis by GB vapour was 1.4 - 4.5 mg.min/m 3 ;
• GB vapour at 6.5 -11.5 mg.min/m 3 would harass, but not cause casualties;
• larger doses would not induce greater effects on the eye and, therefore, that
casualties would not arise solely from eye effects.
The first part of the GB element of the aggressiveness study produced an important indication
about the maximum safe vapour dose. Three men were exposed with no protection to a GB
vapour at 13.9 mg.min/m 3 (t = 1.5 mins). All three suffered severe eye symptoms, and also
suffered persistent tightness of the chest, with nausea and vomiting (these symptoms were
deemed be early signs of systemic poisoning):
• One of the three men, aged 37, was confined to bed under supervision. Red
Blood Cell (RBC) and plasma ChE measurements were taken and compared to
normal values for the general population. The comparison showed a "marked
ChE inhibition". The minimum level of RBC ChE, six days after exposure, was 60
Warburg units 3 compared to a normal lower limit of 90 Warburg units.
• RBC ChE was measured in the other two men exposed to this dose. The
minimum levels in these two cases were 71 units and 74 units.
The conclusion drawn in the report on these experiments was that a GB vapour dose of
"14 mg.min/m 3 may be near to the maximum which men, even breathing quietly, may be
safely exposed to without protection" [43]. The results of the first part of the work were
available for the report published in August 1950 [27], which noted that a marked fall in ChE
levels was observed at 13.9 mg.min/m 3 and concluded that GB vapour at 15 mg.min/m 3
cannot "be far removed from the lower limit of the zone of incapacitation" [27].
8.4.4. Lethal dose estimation
The possibility of linking blood ChE inhibition and symptoms raised by this research
suggested further work to link the degree of ChE inhibition and the GB vapour dose inhaled.
3 As explained in Annex C, ChE was measured by various methods. The units used cited the method:
here, the Warburg method was used. Further references to ChE will include merely "units".
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Scientists hoped that, from these studies, it might be possible to associate different levels of
ChE inhibition with threshold, harassment and casualty doses, and thereby estimate the
lethal doses for man.
Exploring this possibility demanded that the dose inhaled by a man be measured precisely.
Exposing a group of men to a given concentration of vapour for a certain amount of time in
the chamber was inadequate as the precise dose to which each man was subjected was not
accurately measured. That dose depended on the rate at which a man breathed and on the
amount of the vapour inhaled that was retained (i.e. not breathed out).
A study was carried out in 1951 to find out how much of GB vapour inhaled by a man was
retained [49]. Eight men participated. Two features of this study were new:
• an oro-nasal respirator was modified, and the men inhaled GB vapour through
the nose and exhaled through the mouth into a mechanism that sampled the
exhaled air;
• the vapour inhaled was not measured as a product of concentration and time, but
as a precise amount of GB, measured in micrograms (µg). Doses of 107-113 µg
were given. (Annex D contains a comparison of this new method of measuring a
vapour dose with the method of measuring concentration and time).
The study concluded that men retained 96% of the dose inhaled through the nose. US work
[50] suggested that men retained 85% of a dose inhaled through the mouth. The new
apparatus for inhaling vapour used in this study was modified for later work. It was adapted
so that a measured dose could be inhaled in a single breath.
This new and more precise technique for exposing men to GB vapour was used in 1952 in an
attempt to link RBC ChE inhibition to dose [51]. This study, in which 105 men participated,
used doses equivalent to vapour exposures of 2 to about 20 mg.min/m 3 . ChE was measured
before and after exposure. The study therefore produced the average RBC ChE depressions
at particular doses within this range. The variation in the individual (as opposed to average)
ChE depressions was quite wide. It was concluded that the lethal dose of GB vapour could
not be reliably predicted by extrapolating from the ChE depressions observed after exposure
to sub-lethal doses. However, it was noted that more studies might allow a more reliable
prediction to be made.
Further work examining the importance of ChE depression was already being considered in
1951 as a possible technique for estimating the lethal dose of GB vapour to man [52]. The
building blocks of the technique were as follows:
a. Work with animals exposed to various GB vapour doses (up to the lethal dose)
had shown that it was possible to represent "reasonably accurately" with a
straight line the relationship between dose (measured in µg/Kg) and the logarithm
(just another way of measuring) of percentage ChE inhibition.
b. Human studies with sub-lethal doses of GB vapour suggested that a similar linear
relationship between dose and ChE inhibition was reasonable.
c. If it was then assumed that 90% ChE inhibition equates to the lethal dose, and
the report notes that from animal work "this does not seem unreasonable" [52],
then the linear relationship between dose and ChE inhibition in man can be
extrapolated to derive an estimate of the lethal dose to man.
The report concluded that it seemed possible to predict the lethal dose of GB vapour to man
by this method. The preliminary prediction produced by the report [52] based on previous
human studies was a L(Ct)50 of 112 mg.min/m 3 , with a range of 80-200 mg.min/m 3 . The
fundamental idea, that lethal doses could be estimated from the ChE inhibition induced by
exposure to low doses, was pursued in later work.
67

8.4.5. Bronchial constriction.
The study conducted in 1952 [51] to link ChE inhibition with vapour dose also looked at the
effect of those doses on respiratory functions. Breathing rates, maximum breathing capacity
and air velocity index (among others) were measured as indicators of bronchial constriction.
But the report concluded that none of these functions showed any "marked and consistent
variation" after GB vapour exposures of up to the equivalent of about 20 mg.min/m 3 were
administered.
These results were considered to be "somewhat vague" and so further work was conducted
in 1953 to explore bronchial constriction [50]. Features of GB poisoning included impaired
functioning of the muscles controlling breathing, a narrowing of the airways and an increase
in the secretion of mucus into the airways. The last two effects obstruct the flow of air to the
lungs (equivalent to increasing airway resistance) and can impede artificial respiration [50]. A
single breath study was carried out in which 18 men breathed in doses between 0.78 and
2.87 µg/kg to establish if airway resistance was increased by low doses of GB vapour.
The main conclusions were as follows:
• 10 mg.min/m 3 produces a measurable increase in airway resistance;
• with this exposure level, resistance was 3 to 4 times higher than normal in some
men. But this increase did not cause any significant "respiratory embarrassment"
(or breathing difficulty). This was because in healthy humans the respiratory
reserve is large and substantial airflow resistance can be tolerated;
• however, it might be inferred that with larger doses "other factors reducing
available respiratory effort" would make airway resistance or bronchial
constriction less tolerable.
8.4.6. Psychological effects of GB vapour
The 1945 trial assessing the ability of infantrymen and Porton civilian staff to perform tasks
after being exposed to GA suggested some impairment in function [18], but the results were
uncertain because not much was known about the intelligence of the participants.
Two studies were carried out in 1952 and 1953 each using tests to measure intellectual and
visual performance, rate of learning and weariness/boredom. These tests were conducted by
the participants before and after exposure to GB vapour. The intelligence of the men taking
part was assessed before exposure. The first study [53] exposed 20 men to GB at
10 mg.min/m 3 (t = 2 mins), while 8 other men who performed the same tests underwent no
exposure and served as a control group. The main results were as follows:
• normal physiological symptoms (miosis, headache, tightness of chest) developed
as expected. The men exposed to vapour felt lethargic and "couldn't be
bothered", even though they were not feeling bored or resentful. No deterioration
was observed in intelligence. Efficiency in visual tasks was impaired and
learning was slower;
• general anxiety dreams were reported by several men;
• the average ChE inhibition induced by the dose of GB vapour was 31.4% but it
was not possible to link personal ChE inhibition with scores obtained in the
performance tests.
The second study [54] followed similar lines. The GB exposure was higher, 14.7 mg.min/m 3
(t = 2 mins); 12 men experienced this exposure. A control group of 12 men was exposed to a
tear gas (CN). Intelligence ratings of the men involved were obtained from the Services. The
report concluded:
68

• even though the vapour exposure was higher, the men in this second study were
less disturbed than those in the first. This was probably because the men in this
study were "educationally and intellectually a cut above" those in the previous
one;
• the feeling of lassitude observed was again evident here. Again, there was no
real change in intellectual ability;
• a sharp depression in self-confidence was observed;
• average ChE inhibition was 48%. As before, it was not possible to link personal
inhibition with performance test scores.
The conclusion drawn from these experiments was that GB vapour induced no psychological
changes. Feelings of lassitude and loss of self-confidence might have an effect on military
performance but, if these were expected, officers could act to mitigate their effects.
8.4.7. A GD demonstration
As the raw material required to produce it was scarce, GD was not chosen for use in
offensive weapons. A demonstration with GD vapour was performed in December 1951 but
was reported only in 1961 [55]. By that time, interest in GD had revived partly because a
more convenient way of producing it had been developed.
It is not clear why the GD demonstration was carried out in December 1951, but it is
recounted here for completeness. The demonstration was laid on for senior War Office
officials and held at "Mytchett" [55], presumably in Surrey close to Farnborough. Six
volunteers took part in the demonstration; they were exposed to GD at Porton and later driven
to Mytchett. All were exposed to GD at 5.5 mg.min/m 3 (t = 1 min 40 seconds): three wearing
oro-nasal respirators and three with no protection. The L(Ct)50 of GD vapour for man had
been estimated in 1949 to be 180-270 mg.min/m 3 [24].
The symptoms suffered were much more severe than had been imagined from a dose that
was expected to inhibit ChE by 50%. One man collapsed. The maximum ChE depressions
observed in the unprotected men, in each case one day after exposure, were 62, 41 and
74%.
8.4.8. Respirator and protective clothing tests
In August and September 1948, and February and March 1949, human studies were
conducted with GA and GB to assess the efficacy of existing equipment [16]. Various US and
British respirators were tested and respirator face-pieces with spectacles were also evaluated
[16]. American and British respirators were tested by fully protected men in experiments in
December 1950 and January 1951. GA vapour was used in these tests [48].
Other work from October 1948 to 1949 examined whether GA and GB vapour remained in
clothing and thereby posed a hazard. In these experiments clothing was hung up in the
chamber and exposed to vapour, then stored in a "cold bin" for some time. Men would then
wear the clothing in the open air or indoors and their symptoms would be recorded [16].
8.5 Human studies with liquid nerve agents
8.5.1 LD50 estimations for liquid nerve agent on bare skin
Human studies with liquid nerve agents were conducted from 1951 to 1953. The delay in
starting these studies was due to the fact that work with animals to estimate the lethal dose in
man had taken some time to complete. Animal studies were conducted with liquid nerve
agents from 1945 [10]. Initially, the work used animals whose fur was clipped closely to their
skin. Liquid nerve agent was then placed on the clipped fur. By December 1946 this work
69

had produced estimates for the percutaneous LD50 for man [9]. These are shown in Table
8.2.
G Agent mg/kg body weight for the average 70kg man
GA 40-50 2800 - 3500 mg
GB 50-60 3500 - 4200 mg
GE 50 3500 mg
Table 8.2. LD50 for man (agent on bare skin): December 1946
The next phase of animal work continued until 1949 but used a different method of clearing
fur. Clipping, which left short bristles, was thought in 1948 to be inadequate so a depilation
technique was introduced [56]. The technique, similar to commercial cosmetic hair removing
lotions, involved applying a barium sulphate paste after clipping removed the residual bristles.
Studies with depilated fur produced very different results to those with clipped fur. Table 8.3
shows the LD50 estimates for rats with clipped skin from work to December 1946 [9] and for
rats with depilated skin [56, 57] from studies in 1948/49. The effect of depilation is stark.
Liquid nerve agent is more effective against depilated skin: much lower doses can kill.
G Agent Clipped Skin Depilated Skin
GA 20 4
GB 70 11
GE 15 4.9
Table 8.3. LD50 for rats (mg/kg): clipped vs. depilated skin
A new assessment of the hazard of liquid nerve agents seems to have arisen from the
depilation work in June 1949 [24] and August 1950 [27], in which it was stated that with GB
"any contamination greater than 0.2 g [200 mg] on the bare skin would present a serious
hazard, and possibly prove fatal to man".
Whether to base human LD50 estimates on results from clipped animal skin or depilated
animal skin was discussed in 1950. Depilation removed a layer of skin as well as bristles of
fur [58], and it was thought that human LD50 estimates should not be based on results with
depilated animal skin so, in subsequent animal studies in 1950, Porton reverted to clipping fur
[59]. More efficient clippers were used, called Horstman clippers, which enabled animal hair
to be removed "very completely, leaving a smooth surface resembling the skin of man much
more closely than the depilated skin" [58].
The LD50 estimates for animals with Horstman-clipped skin fell between the LD50 estimates
for animals with coarsely-clipped skin (from 1946) and for animals with depilated skin [58, 59].
Naturally, this had an effect on the assessment of LD50 for man. No statement seems to
have been published in 1950 or 1951 on this new human LD50 but a progress report in
September 1953 [60] mentioned a human LD50 estimate of 1200 - 1300 mg (bare skin and
clothed). As expected, this estimate is lower than the original 1946 estimate (Table 8.2) but
higher than the dose derived from depilation work.
8.5.2 LD50 estimations for liquid nerve agent on clothing
Drops of liquid nerve agent might fall on bare skin or onto clothed skin. Experiments were
conducted in early 1950 [61] with rabbits to assess the protection afforded against liquid GB
by normal British battledress. Drops of 0.22 mg of GB were applied, 1.5 cm apart, along up
to five lines depending on the total dose considered. Drops were applied onto a piece of
British Army khaki serge battledress, which had been attached with an underlay of a piece of
British Army flannel shirting to depilated rabbit skin. For comparison, the study also applied
drops directly to depilated skin. The study also used drops of GF. For both GB and GF this
yielded estimates of LD50 for bare skin and clothed skin. These estimates are shown in
Table 8.4.
70

G Agent Bare skin Clothed skin
GB 4.9 3.5
GF 0.35 2.5-4.5
Table 8.4. Rabbit LD50 estimates (mg/kg): 1950 bare and clothed skin
The surprising result was that GB seemed to be more toxic through clothing than on bare
skin. GB is volatile; it evaporates very quickly. Further investigation of this surprising result
revealed:
• a 0.22 mg drop of GB placed on animal skin had evaporated completely within 2
minutes. When drops of GB are placed on clothing, the drops penetrate into the
cloth and evaporation into the atmosphere is retarded;
• the GB evaporates more slowly and produces a high concentration of vapour
against the skin surface. That vapour was found to remain for more than 10
minutes;
• the vapour was found to be more effective against depilated skin than drops of
GB placed directly on skin (here a large proportion, about 90%, of GB evaporated
into the atmosphere anyway).
This work was conducted with depilated skin. Work carried out later in 1950 [62] showed that
"depilation changed the skin surface so as to increase very considerably (some 5-10 fold) the
rate of absorption of GB vapour" compared to clipped skin [27]. Once again this raised the
question of whether depilated or clipped skin should be used.
US work, with clipped animal fur, showed that one layer of clothing gave some protection
against GB droplets [63]. Porton repeated their experiments with clothed skin in 1951 using
Horstman-clipped skin. This new work showed that clothing did not increase the hazard from
GB droplets [64]. The estimate of LD50 for man cited in the September 1953 report [60], of
1200 - 1300 mg, applied to clothed skin as well as bare skin.
8.5.3. Initial human studies
Human studies in which GB drops were placed on the forearm of volunteers began in
October 1951 [48, 65]. The first study, carried out in October and early November 1951 [48],
does not appear to have been reported formally. Details of the work are drawn from
experimental logs and the volunteer records [48, 65].
The study involved drops of GB placed on bare skin. The ChE inhibition experienced by each
volunteer is recorded in the logs. The work may, therefore, have had the same aim as the
main study which was conducted later. For that study the intention was to estimate lethal
doses for man from the relationship between lower doses and ChE inhibition. The method of
estimation to be used was recorded as [66]:
• establish the LD50 dose and the dose that inhibited ChE by 50% (ChE50) for
animals by conducting experiments with animals at sub-lethal and lethal doses;
• establish the ChE50 dose for man from exposure to lower, sub-lethal doses;
• then estimate the lethal dose for man by multiplying the human ChE50 dose by
the ratio between the animal LD50 and the animal ChE50 dose.
Forty four volunteers took part in the study carried out in October and November 1951. Table
8.5 shows the doses used [48].
71

GB drops on bare skin (mg) No. of volunteers
0.5 5
1 4
2 4
4 4
8 4
10 3
15 8
20 3
25 2
30 1
40 6
Table 8.5. GB doses used in October/November 1951
The degree of ChE inhibition varied considerably between the individuals participating in this
study, which prompted the next human study that sought to understand better the factors
affecting the penetration of liquid GB through skin [67]. The report of the study was published
in 1954 [67] but entries in the experimental records show that the exposures were carried out
in late 1951 and in 1952 [48, 65]. In this study the liquid GB placed on the arms of volunteers
was tagged so that it could be tracked. Some liquid GB was dyed and its activity on the skin
watched under magnification. Other drops were tagged with radioactive phosphorus
(called 32 P) and the activity of the GB was tracked with a Geiger counter. The degree of
radioactivity could be controlled. Thirty five volunteers took part in this study [67].
• Twenty men received a 2 mg drop of GB on each forearm. The drop on one of
the forearms was covered in nylon film to prevent the GB evaporating. The arm
with the uncovered drop was held still inside a fume cupboard.
• Fifteen men had a drop of GB placed on their arm, and in each case the drop
was covered by nylon film. Five men received a 0.6 mg drop; five a 2 mg drop
and five a 3.5 mg drop.
The GB drops were monitored to find out how long it took them to clear the skin either from
penetration or evaporation. Similar investigations were conducted with rabbits. The main
conclusion of the work [67] was that the fat in skin (sometimes referred to as "lipid") played
some part in the penetration of GB and might absorb GB to prevent its penetrating further
through the skin to the blood capillaries beneath.
The study was extended to explore the influence of skin fat on liquid GB penetration. Fat is
present on the skin and below the skin surface. Surface skin fat was removed from clipped
rabbit skin by soaking in acetone, with liquid GB then placed on the skin. A marked
difference in penetration rate was found in rabbits with surface skin fat removed, compared to
the rate in rabbits with skin fat intact. The work was repeated with humans.
• The amount of fat normally present on the forearm skin of man was sampled from
100 men. The mean amount was found to be 81.6 µg/cm 2 .
• Fourteen men took part in a study to compare the rate of penetration of liquid GB
through normal skin and "de-fatted" skin. An area of the left arm was "de-fatted"
by soaking with acetone to remove surface skin fat. The 14 men then had a 2 mg
drop of GB placed on each arm. The activity of the GB on each arm was
monitored to compare the penetration rate through normal skin and de-fatted
skin.
The conclusion from this work was that the amount of surface and sub-surface skin fat affects
the degree of penetration of liquid GB. The less fat that is present, the more deeply through
the skin GB will penetrate and the larger the proportion that would be expected to reach the
72

lood supply. Nine of the 14 men who took part in this study showed symptoms of GB
poisoning. The average amount of skin fat removed from these men was 63.7 µg/cm 2 (lower
than the norm).
8.5.4. Main human study
The main human study with liquid G agents was conducted from August 1952 [48] to May
1953 and involved 396 men [66]. Liquid GA, GB, GD or GF was placed on the bare skin of
arms of men, or onto layers of material attached to the bare skin of arms [48, 66, 68]. The
aim of the study was to estimate lethal doses for man from the relationship between lower
doses and ChE inhibition (by the method outlined above).
The doses used in this large human study were administered as a single drop or as a series
of drops: 5mg or 10mg drops for GB, 0.5mg drops for GD and GF. Some men received the
dose directly on their bare skin, others received the dose on material which had been
attached to their bare skin. In every case the drops remained in place for 30 minutes. Doses
of liquid GB ranged from 30mg to 300mg on bare skin and from 100mg to 300mg on one
layer of serge. A single dose of 200mg was used in experiments where the dose was placed
on a layer of serge underlaid by a layer of flannel. Doses of GF on bare skin varied between
5mg and 30mg. Doses of GD on bare skin varied from 10mg to 40mg. None of the doses
were covered. All the men wore respiratory protection.
As with the initial study, ChE inhibition varied. An example of this variation is shown in Figure
8.1. (published in 1954) which gives the percentage ChE inhibition for each man who had GB
placed on his bare skin. Despite this variation, the method of estimating the lethal dose in
man was applied to the results of this main human study. The estimates, reported in January
1954 [66], are shown in Table 8.6. The report notes that although liquid GB penetration
differs across species, the ratio between the lethal dose (LD50) and ChE50 may be
"reasonably constant for various species".
Agent ChE50 for man (from the
large study)
Ratio of
LD50:ChE50 in
rabbits
Estimate of
LD50 man
GB 350 - 400 mg 4.25 1500 - 1700 mg
GD 60 - 70 mg 5 300 - 350 mg
GF 30 mg 18 540 mg
Table 8.6. Estimates of LD50 (bare skin) in man from results of the main study.
73

Figure 8.1. Variation of ChE Inhibition induced by GB on bare skin [66]
Estimates of LD50 (clothed skin) for man were made in the same report. For GB, the
evidence of the main study suggested it "cannot be greater and may be less" than the bare
skin estimate. Liquid GD and GF had only been placed on the bare skin of man in the large
study but work had been conducted with liquid GD and GF on clothed animal skin. If the
clothing protected man in the same way as it protected animals, the LD50 (clothed skin) for
man could be estimated at 1200-1400 mg for GD and 1080 mg for GF [66].
8.5.5. A case of severe poisoning and a fatality
On the 27 th April 1953 one of the six men who received a 300mg dose of GB in the main
human study suffered severe poisoning [69]. The dose was administered in 30 drops of
10mg on a layer of serge fixed to the upper forearm. The man was subsequently
hospitalised, his breathing temporarily ceased and he suffered convulsions; but he recovered
some days later. The points observed from the incident in Porton reports published
afterwards [67, 69] were:
• Three of the 26 men who had received this dose on serge had shown "mild and
temporary systemic responses (nausea and vomiting)".
• The man's pre-exposure RBC ChE activity was 82 Warburg units. This was
described [69] as "low" and "may have been an important contributory factor" 4 .
4 Lower normal limits cited in earlier Porton reports [43, 70] for RBC ChE varied between 84 and 92
Warburg units; a value of 92 was cited in the report published in September 1953 [68].
74

• After the incident the man's surface skin fat was measured and found to be
28.8µg/cm 2 [67], much lower than the norm.
• The first aid treatment for nerve gas poisoning, published in the Lancet and
British Medical Journal in 1952, was used and found wanting:
a. the convulsions suffered by the man meant that an intravenous (IV)
injection of atropine could not be given [69].
b. the Holger-Neilson method of artificial respiration could not be "applied
successfully" because of spasms of the arms, the Schafer method was
used instead in this case. Copious mucus secretions blocked the
airways, complicating artificial respiration, which indicated that an
"efficient suction apparatus" was needed [69].
As a result of this incident, the maximum dose of GB to be used subsequently in the main
study was reduced from 300 mg to 200 mg and a second layer of clothing was interposed
between the liquid GB and the skin.
On the 6 th May 1953, a man died after being exposed during the main human study to 200mg
of GB [68]. The GB was applied, in 20 drops of 10mg, on top of two layers of clothing (one
layer of serge underlain by flannel) fixed to the man's skin. Eighteen men were contaminated
in this fashion; the other seventeen showed no signs or symptoms of GB intoxication. Points
made in Porton reports of the incident were [67, 68]:
• The man's RBC ChE activity before the experiment was measured as 116
Warburg units (normal limits cited as 92-132 units) and 79 units by the
electrometric method (normal limits cited as 63-97 units) [68];
• "The estimated IV LD50 for man is 20µg/kg ". The dose of 200mg used in this
experiment represents 140 IV LD50 doses. "Comparatively small variations in
absorption might therefore encompass the lethal dose" [68]. The Porton report
goes on to say that "this fatal incident is an extreme example of the possible wide
variation in individual response to cutaneous liquid contamination with GB". Up to
and including the study, a total of 396 men had been contaminated with varying
doses of liquid GB, 182 having received contaminations equal to or greater than
that of the man who died. The report concludes that why this man "should have
died with typical clinical and pathological signs of G poisoning and the others
should have been unaffected is not known". The deceased "had no clinical skin
abnormality and no abrasions at the site of contamination. The pieces of serge
and flannel placed on his forearm were cut from the same rolls of cloth as the
pieces used for the other volunteers and were not detectably different from them.
He showed no evidence of pre-existing disease and his pre-exposure blood
cholinesterase content was within normal limits".
• After death, the surface skin fat of the man was found to be 66 µg/cm 2 and
subcutaneous skin fat of the forearm where GB was applied through clothing was
found to be "practically absent" [67].
The fatality "naturally led to the complete banning, by the Minister [of Supply] of further trials
with GB on human observers" [71]. In fact all nerve agent studies with humans were banned.
The decision as to when and how trials should continue was deemed urgent but "there is a
grave responsibility to make certain that we [the Ministry of Supply] take no foreseeable risks
of further serious casualties" [71]. The Minister of Supply agreed that independent and expert
advice was essential, and a committee was appointed on 15 July 1953 chaired by Dr Adrian,
President of the Royal Society [72]. A Court of Inquiry was set up to investigate the
circumstances of the fatality [71].
75

The Biology Committee met in June 1953 to discuss the lessons that should be drawn from
the severe case of poisoning and the fatality [73]:
• first aid treatment needs to be revised urgently, as the Holger-Neilson method of
artificial respiration cannot be given to men suffering from nerve gas poisoning,
and administering atropine by IV injection is not practicable; the secretion of
mucus in the airways needs to be studied, as it complicates the use of artificial
respiration;
• the cough reflex in humans normally clears mucus from the airways, but the
reflex appears to be abolished by nerve gas action. A means should be found of
restoring the cough reflex.
The CDAB accepted these conclusions later in the year [74]. In making suggestions for first
aid treatment for nerve gas poisoning in 1952, it was admitted that no-one had anticipated
convulsions being so great as to make atropine injections and artificial respiration "extremely
difficult to perform".
The report of the main human study [66] during which the severe case of poisoning and the
fatality occurred notes that no-one whose ChE inhibition was less than 80% showed any
signs or symptoms of systemic GB poisoning. It therefore includes a table giving details of
the exposures after which a ChE inhibition of greater than 80% was observed. Of the 14 men
who had a ChE inhibition of over 80%, 7 did not present symptoms that required treatment.
The 14 cases where inhibition exceeded 80% are reproduced below (Table 8.7.) and are all
from 1953.
76
ChE inhibition (%) Dose Details Date of Exposure
83 300 mg on bare skin 29 January
94 300 mg on one layer of serge 10 February
90 250 mg on one layer of serge 16 February
83 250 mg on bare skin 9 March
87 250 mg on bare skin 16 March
81 300 mg on bare skin 23 March
87 200 mg on one layer of serge 30 March
87 200 mg on one layer of serge 30 March
93 300 mg on one layer of serge 22 April
85 300 mg on one layer of serge 27 April
94 300 mg on one layer of serge 27 April
87 200 mg on layer of serge and layer of flannel 4 May
82 200 mg on layer of serge and layer of flannel 6 May
96 200 mg on layer of serge and layer of flannel 6 May
Table 8.7. Occurrences of ChE inhibition of more than 80%.

9.1 Adrian Committee
Chapter 9. G Agents: 1954 to 1989
The Adrian Committee reported in August 1953 [1], recommending the conditions under
which human experiments with nerve agents could resume. The recommendations were
accepted by the Service ministries: the Royal Navy in November 53 [2], the Army in
December 53 [3] and the RAF in January 54 [4]. Porton was notified of the agreement to
resume tests and the conditions imposed [5]:
• tests to be confined to GB (the reasons for this restriction are not given);
• experiments with vapour not to exceed 15 mg/min/m 3 ;
• application to skin or to clothing on skin not to exceed 5 mg per man;
• tests to be conducted in normal (non-tropical) temperatures;
• tests to be conducted in the absence of arduous exercise.
The Adrian Committee report made few detailed comments on the conditions it
recommended [1].
• "Without experiments with GB vapour it would be impossible" to evaluate
therapies against nerve agents. The report does not say why the maximum dose
of 15 mg.min/m 3 was chosen. Perhaps it reflected the 1950/51 assessment that
a GB vapour dose of "14 mg.min/m 3 may be near the maximum to which men,
even when breathing quietly, may safely be exposed without protection" [6] and
dosages of GB vapour of 15 mg.min/m 3 cannot "be far removed from the lower
limit of the zone of incapacitation" [7].
• The wide variation in response to the same dose of liquid GB placed on the skin
or on clothed skin was recognised in the report. The report noted that a dose of
100 mg was safe but far more could be learned by using small doses of up to
5mg of radioactive GB liquid.
The committee felt that it "should be possible to use small doses (outside the toxic range) to
induce minor reductions in ChE and then extrapolate to infer doses which give dangerous
reductions". Human studies with nerve agents were resumed on 21 May 1954.
9.2. G Studies after 1954: "New Terror"
The defence budget was reduced in 1956 and the Services withdrew their requirements for
nerve agent weapons [9]. CDAB inferred in February 1957 [10] that research would
concentrate on CW defensive equipment. The review of the CW field in the early 1960s [11],
which Chiefs of Staff approved [13], recommended that the Services be fully protected
against CW attacks, and also prompted interest in incapacitating agents.
The defensive recommendation meant that work on nerve agent therapy was important [14,
15]. Indeed, a higher priority had been placed on this work in 1954 when nerve agent tests
with GB resumed [16, 17], but the interest in incapacitating agents and the emergence of a
new nerve agent inevitably diverted effort from GB work.
In 1953 a new series of nerve agents, called V agents, was discovered. By November 1955,
V agents were known to be highly toxic in vapour form and when penetrating skin [18]. The
discovery of V agents was hailed as "probably the most outstanding advance of the year
[1955]" across all the fields of defence science [19], and there was a tendency to regard GB
as "old fashioned" [18]. CDAB commented in June 1956 that "the G nerve gases had been
the major terror a few years ago, now V agents were the new terror" [20].
77

9.3 Human studies of the penetration of liquid GB
No human studies involving Service volunteers having liquid GB placed on their skin (or on
clothing on their skin) were carried out between 1954 and 1989. However, much effort was
devoted to understanding better skin and clothing penetration. Excised or resected human
skin was used in studies in 1954 [21, 22] with radioactively-labelled GB. Human skin
samples from the back, forehead and hand were used in the first half of 1960 to measure the
rate of penetration of liquid GF [23].
The part played by skin fat was studied in animals in 1956 and 1957 [24]. This work
continued with excised human and animal skin in 1960 [25]. The results prompted volunteers
to contribute to studies of skin penetrability, as described below:
• One of the conclusions of the work in 1960 was that dead skin cells (called
keratin) seemed to be a barrier to the penetration into the skin of liquid GB.
However, it was not known how much keratin was normally present on human
skin.
• A method was found in 1960 to measure the weight of keratin stripped from
human skin [23] and a mathematical model was produced which related the
penetration rate of GB to the amount of keratin and the electrical conductivity of
the skin.
• As a consequence, during 1960 and 1961, Service volunteers had keratin
stripped from their skin [26] so it could be weighed. Typically, the keratin was
removed by placing a piece of adhesive tape on the skin and then peeling off the
tape to remove dead skin cells. Sometimes "massive keratin-stripping" was
carried out. Here, the forearm was often used. A site was shaved, and then
pieces of adhesive tape were applied and removed from the same site several
times. Keratin was removed also from the shoulder blade region of the back [27].
Seven women volunteers from the Porton staff contributed keratin in this manner
[27] and it was found that the amount removed from them differed only slightly
from the amount of keratin stripped from men.
• In 1961 [26], after keratin had been stripped by adhesive tape from parts of the
skin of human volunteers, the electrical conductivity of the keratin-stripped skin
was measured. Typically, that was carried out by placing electrodes on the skin.
This contribution of Service volunteers in skin penetration work did not involve their being
exposed to nerve agents. Volunteers took part in further studies of skin penetration, none of
which involved nerve agents:
78
• In 1960/61 [28] volunteers took part in studies with radioactively-labelled tri-npropyl
phosphate (TPP). TPP was at that time a simulant for GF, that is to say it
had the physical properties of GD but did not induce the effects of it. Typically, a
volunteer would have a small drop of one of these liquids placed on the bare skin
of the forearm. The drop was covered and the penetration into the skin
measured by a Geiger counter. Work was conducted on normal skin and on a
patch of skin from which keratin had been stripped [28].
• From the work with keratin and by measuring the electrical conductivity of skin,
Porton built up a picture of how liquid penetrated the skin. It became apparent
that penetration might depend on the electrical charge of ions in the liquid placed
on the skin. In 1961/62 [29] volunteers took part in studies of the penetration of
sodium, potassium, phosphate and bromide ions through the skin. No report
specifically on this work has been found but it appears that drops of water
containing these ions were placed on the arms of volunteers [29]. This type of
study was conducted periodically up to June 1965 [30]. The electrical charge of
the ions was not found to influence the penetration rate [29].

Service volunteers took part in studies of simulants for G agents some of which considered
skin penetration. One of the simulants tested by volunteers was called Dimethyl Sulpoxide
(DMSO). DMSO was not toxic but human studies were conducted to determine if it irritated
skin. The human studies with DMSO and other simulants over the period of the survey are
described in Annex B.
9.4 Human studies of the Inhalation of G agent vapour
9.4.1. Techniques and themes
New techniques appear to have been developed and used in the period up to 1960, which
gave a better understanding of the effects of GB vapour. Interest seems to have developed
in 1956 in studying how the clinical symptoms of GB were related to human body
composition, in particular body water, muscle mass and "fatness" [31, 32]. This work saw
men being weighed under water. A technique to measure body volume using air
displacement (rather than water displacement) was developed in 1958 [33]. However, men
continued to be partly immersed in water because measurements could be taken from which
lung volume could be estimated.
Body water was estimated by injecting dye into the human body at different points and, later,
by taking blood samples to measure the concentration of dye in the blood. This work also
investigated "somatotyping" which, at the time, suggested that physical build was related to
personality. Typically, photographs were taken of men for somatotyping.
Experimental techniques were developed to continuously measure pulse and blood pressure,
and these were tested on men in 1958 [33]. Plethysmographs were developed to measure
peripheral blood flow after the inhalation of GB. A plethysmograph measures variations in the
size of parts of the body. These variations can be due to changes in the amount of blood
flow. As an example, a water plethysmograph was used in 1960 to measure the blood
circulation through the hand [23]. Here the hand was submerged in water and water
displacements and changes in water pressure were used to measure the change in hand
size.
These are some examples of the techniques developed in the second half of the 1950s. The
themes explored in human studies involving the inhalation of G agent vapour from 21 May
1954 were:
• the effect of exercise on the symptoms induced by GB;
• investigations into respiratory function, cardiac function and the movement of GB
in the blood;
• the effect of GB vapour on military efficiency.
9.4.2. Human studies with exercise
The Adrian conditions precluded "arduous" exercise when men were exposed to GB vapour.
Clearly, soldiers on the battlefield were unlikely to be sitting quietly when the enemy attacked
with chemicals. Studies with animals [34] showed that exercise increased the effects of
nerve gas. Work with radioactive GB vapour earlier in the 1950s, to study retention and the
effects of respiration and blood circulation in animals [31, 35], revealed the facets of exercise
that influenced the effects of nerve agents [36]:
• increased breathing rate (more vapour inhaled);
• increased air flow in respiratory system (less complete retention of vapour);
• higher blood circulation rate (transports retained nerve agent from the lungs more
quickly to vital organs);
79

• increased muscle activity;
• the effects of stress, such as the release of adrenalin, might affect susceptibility
to nerve agent poisoning.
Proposals were made in February 1958 [36] to change the Adrian conditions to permit studies
with exercise. They were approved by the Biology Committee in March [37], which defined
the level of exercise more precisely. Fully equipped men marching at 4 mph had a metabolic
rate about 4 times the resting metabolic rate. Men digging have a metabolic rate 6 times their
resting value. The committee confined initial studies to exercise which induced an increase in
metabolic rate of 4 times rest and stipulated that the first studies should use exposures to GB
vapour of less than 5 mg.min/m 3 [37]. In making the proposal, Porton suggested RBC and
plasma ChE would be measured before and after and, if any rate of exercise was found to
depress either by 75%, that rate of exercise would not be exceeded in subsequent work.
From June 1964 studies involved men walking at 3 mph while being exposed to a GB vapour
dose of 15 mg.min/m 3 [38]. Some men under these conditions were expected to have their
ChE depressed by over 60% [38]. Although the Biology Committee permitted depressions of
up to 75%, Porton applied a "local safety margin" [39, 40] which aimed to keep ChE
depressions below 55% [40].
By August 1964 ChE depressions of over 50% (but less than 75%) had been observed [39]
with a walking rate of 3 mph. This was reported to the Biology Committee [41] and Porton
reduced the walking rate to 2.5 mph [42]. Studies with men walking at this rate were
conducted from late summer 1965 to spring 1967 involving 68 men [42]. Of the first 5 men
who participated, 4 had severe headaches [43].
No more studies specifically to explore the effect of exercise were conducted. The walking
rate (2.5 mph) determined to inhibit ChE within the Porton safety margin was used in other
work. It become usual for men exposed to GB vapour in the chamber to walk at this rate [44].
Their speed of walking was often paced by a metronome [45].
9.4.3. Effects of GB on human physiological function
A fairly constant symptom observed before 1954 was that men who inhaled small doses of
GB vapour felt a tightness of the chest [46]. It was thought possible that the muscles
between the ribs that play a part in breathing (called the intercostal muscles) might be related
to that feeling. If that were the case, they could prove to be an impediment to artificial
respiration in cases of severe nerve gas intoxication [46].
The activity of the intercostals could be assessed by an electromyograph (EMG), which
measured electrical currents present in muscles. Before 1958 EMG was thought by Porton to
be too unpleasant and hazardous for recording intercostal muscle activity in man [46]. EMG
called for needles to be inserted through the chest and into the intercostal muscle layers. If
the needles were inserted too far, penetrating the delicate membrane that lines the lungs,
they could cause serious injuries. Porton called on an external Consultant Anaesthetist who
advised on a safe way to use EMG.
Little was known about the part played by the intercostals in breathing so EMG was used on
80 men [46] in 1958 [33, 34] to assess their normal activity. EMG measurements were taken
for different conditions: quiet and forced breathing, speech, coughing, and (using a tilt table)
some men were moved from a supine position to a near erect position. It was found that
intercostals play only a small part in quiet breathing, only seeming to be required for more
vigorous respiration [46]. In a later part of this work, 10 men were exposed to GB vapour,
some by single breath. Eight suffered a tightness in the chest but this was not in any way
found to be associated with the intercostals. It was concluded that intercostal muscles did not
contribute to a feeling of tightness.
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Animal work in 1958 suggested that GB vapour had a marked effect on the cardiovascular
system. A study with men was conducted in 1959 [47]; the experiment was organised in the
following way:
• GB was administered as single breath and inhaled by the men by putting their
mouth round a tube. However, the first time each man did so, no GB was
administered. It was found, as expected, that the "anticipation" of inhaling GB
induced an increase in pulse rate. Having established how the pulse rate was
affected solely by anticipation, each man inhaled from the tube a second time;
this time GB was inhaled. Pulse rates were raised and the higher rate persisted
for 15-30 minutes.
• Other men, believing they were to inhale GB, were exposed to amyl nitrate (used
medicinally as a vasodilator). Others acting as a control group received an
injection of adrenalin.
• Overall, it was concluded that the prolonged but small elevation of pulse rate
observed in the men inhaling GB might be an emotional response rather than an
effect of GB [47].
The effect of "anticipation" (and the accompanying emotional response of fear) was observed
again in another study, in 1959 [48], which sought to assess the effect of GB on breathing
rate. Here some men were led to believe they would be inhaling GB when in fact they
breathed in only air. Their breathing rate increased markedly. The studies highlighted the
difficulty in distinguishing real effects of GB from responses induced by emotional change.
The result that GB had no significant effect on pulse rate was re-visited in 1966, when it was
thought GB might induce a drop in pulse rate [49]. Studies underway at the time
(investigating atropine therapy) were used to link pulse rate with ChE depression after
exposure to GB [50]. The conclusion repeated the 1959 result: that GB has no significant
effect on pulse rate.
An investigation was carried out in 1960 into the effect of GB on blood circulation. It had
been suggested that GB might induce the pooling of blood in leg veins. Such pooling could
induce a collapse of the circulation. One way of checking if pooling occurred was to measure
"venous tone" (equivalently, the pressure within veins). However, standard techniques to
record pressure in an isolated segment of a vein "require more co-operation than can be
expected of many subjects. There is a need for a simple procedure which can be readily
applied with the minimum of discomfort and disturbance" [51]. Porton developed a simple
procedure, involving the leg segments of the standard aircrew g-suit. The investigation was
as follows.
• Fifty nine volunteers took part in a study to test the procedure [52]. Inflating the
leg segments of the g-suit forced blood from the legs to the lung which in turn
causes a proportionate amount of air to be expelled. Measuring the volume of air
exhaled after rapidly inflating the g-suit therefore gave an index of "venous tone"
[51]. The 59 volunteers underwent this procedure, which was repeated with them
in different positions on a tilt table (supine, vertical, at an angle of 45 o with the
head up, and at an angle of 25 o with the head down). The work showed that the
procedure was reliable and gave a simple measure of venous tone.
• Twenty three volunteers took part in the study of the effect of GB on venous tone.
They were strapped to a tilt table in a vertical position. Having established their
normal venous tone values, 8 men each received a GB single breath dose of 3 -
3.5 µg/kg [51]. The other 15 men were not exposed to GB but injected with 5 mg
or 10 mg of 1/1000 solution of aramine bitartrate (a medicine to treat cases of
circulatory collapse [51]). The study found no evidence to suggest GB caused
the pooling of blood in the veins [25, 51].
81

Work to understand the effects of GB on the human brain and to associate the effects with
ChE depression started in the late 1970s. Electroencephalography (EEG) was used to
monitor the electrical activity of the brain:
• Porton received reports from the US in 1974/75 suggesting that anti-ChE
compounds might induce changes in brain activity, as measured by EEG. In
response it was decided "most human exposures to GB will in future include EEG
monitoring" [53]. Porton sought expert advice on EEG recordings.
• By mid-1976, apparatus had been constructed for Porton to analyse EEG
recordings on computer [54] and it was intended to use EEG in future human
studies of GB [54]
• Work to explore any link between electrical activity in the brain and the degree of
ChE inhibition started in late 1979 [55, 56].
• By 1980 EEG seems to have been a standard measurement made in human
studies involving GB.
Investigations to associate muscle activity with GB exposure and ChE depression, using
EMG, were started in October 1983 [57]:
• In 1977 Porton staff became aware of open source reports of the long-term
consequences of acute and chronic exposure to chemicals, such as
organophosphorus insecticides, which inhibited ChE [58]. The reports suggested
that the electrical activity associated with muscles could be affected. Porton
started investigating this suggestion in 1977 [58].
• By 1983 facilities and techniques were available at Porton to investigate muscle
activity in detail by using EMG [59]. This was EMG in a different guise to the one
used in the intercostal muscle work in 1959. By 1983 Single Fibre EMG
(SFEMG) had been developed, which was capable of detecting differences at the
neuromuscular junction between pairs of muscle fibres.
Work with EEG and SFEMG are covered in more detail later in Section 9.6.
9.4.4. ChE depression
A study to relate ChE inhibition with inhaled GB vapour was conducted in 1959 [60]. Men
participating in the study were to inhale vapour by the single breath technique. The limit
stipulated by the Adrian Committee on the GB vapour dose was, however, expressed in
mg.min/m 3 . So the study was prefaced by a calculation that the Adrian limit of 15 mg/min/m 3
translated 5 into a single breath dose of a little more than 6 µg/kg.
The study used a maximum dose of 5 µg/kg. Initial exposures were with doses of 0.5 µg/kg,
gradually increasing to the maximum dose. The experiment found that the relationship
between dose and ChE depression was "reasonably linear". The maximum dose of 5 µg/kg
dose induced a depression of about 40%.
The relationship between symptoms and ChE depression remained uncertain. Experiments
in 1957 and 1958, in which 253 men were exposed to GB vapour, concluded that it was not
possible to deduce this relationship [61]. Nonetheless, as observed in a Porton paper written
in 1960, "the only practical quantitative measure of the effect on humans of low doses of anti-
ChE materials, such as GB, is the extent of depression of blood ChE activity" [62].
A later paper, written in 1965 [63], explained why a relationship between blood ChE inhibition
and symptoms was difficult to pin down. The symptoms of nerve agent poisoning are
5 The translation used the equation shown in Annex D, assumed a breathing rate of 29.4 litres/minute
and that all vapour inhaled was retained (to be on the safe side).
82

induced by the inhibition of ChE in the nervous system and muscles. They are not caused by
the inhibition of ChE in blood. However, in 1965, no convenient method of estimating ChE in
the nervous system and muscles was available. So, blood ChE activity was a "guide of some
value in detecting systemic absorption of an anti-ChE compound and the persistence of its
effects" [63]. The paper concluded:
• mild symptoms can occur without any blood ChE inhibition (or only a negligible
inhibition), but these symptoms invariably would be local and not incapacitating;
• any depression of ChE (with or without mild symptoms) indicates systemic
absorption - depressions of 50-60% are not usually associated with the
development of any further symptoms (these being observed when depression
reaches 70%).
9.4.5. Military efficiency
Various human studies were conducted with inhaled GB vapour to understand the impact on
military effectiveness. Most were carried out from 1954 to 1967.
Exercise Hangover, August 1954 [64]. Men from the demonstration battalion at the School of
Infantry were exposed to GB vapour doses of between 11.8 and 13.8 mg.min/m 3 (t = 2
minutes) and then performed infantry duties in field trials. The most obvious effect was the
impairment of vision, although fatigue set in rather quickly and the commanders became
"rather irritable and unduly flustered". The impairment of vision, because of miosis and
physical effects, did not impede military tasks during daylight. However, it was judged that
infantrymen would be vulnerable during night operations.
Cognitive and emotional changes [65], were explored again in 1955, this time with postexposure
tests being carried out over a longer period. Some fall in intellectual capability was
observed, thought to be due to the stress of being exposed rather than the action of GB. A
marked mood change towards depression and anxiety was noted, but not amounting to the
extent of the psychological effects reported by the US [66].
Psychomotor and physical performance. Two studies, conducted in 1962 and 1963,
concerned the effect of exercising after an exposure to GB 6 . Both studies administered
5 µg/kg per man by the single breath method.
• The psychomotor study [67] involved 30 men: 10 inhaled GB, 10 inhaled
isopropanol vapour and 10 inhaled only air. After exposure the men performed
various tasks. No evidence was found that GB at a dose of 5 µg/kg affected
psychomotor behaviour, or that these moderate doses of GB influenced physical
performance.
• In the physical performance study [68], 10 men inhaled GB and 10 inhaled
isopropanol vapour. They rode a bicycle ergometer after exposure, having
ridden the bicycle on previous days to establish their normal performance. The
dose of GB was found to have little influence on the men's performance.
A third study, carried out in 1974 [69], saw men perform the Harvard Pack Test 7 before and
after being exposed to a GB dose of 14.7 mg.min/m 3 . Twenty men were exposed to this GB
dose and performed the test. Another 17 were exposed to GB but did not do the test. The
study found that the GB dose did not affect performance in the test. The difference between
the RBC ChE inhibitions observed in the 20 men who exercised and the 17 who did not was
small.
6 The Adrian condition, that no "arduous" exercise should be undertaken, applied during the exposure,
when such exercise would increase the rate and depth of breathing and, hence, the dose retained.
7 The test involves wearing a pack on the back, the weight of which is one-third of the body weight of
the subject. While wearing the pack, the subject steps on and off a 40.5 cm step thirty times a minute.
83

9.4.6. GF human studies
The Adrian conditions explicitly limited human studies with nerve agents to GB, yet GF was
used in human studies which started in the summer of 1963. It is not clear how these studies
came to be carried out. In June 1963 Porton hosted a meeting of a working party set up by
the 16 th Annual Tripartite (UK, US and Canada) Conference to consider nerve agents other
than GB [71]. The working party concluded that GF (among others) was worth studying in
more detail but no agreement is recorded that the UK should carry out the work. The GF
studies were a breach of the Adrian conditions. Yet, Porton reported them widely in annual
reports [72, 73], from which it might be inferred that permission to conduct the work had been
obtained. The survey has found no reference which confirms this inference.
Before the studies began an estimate was made, from mathematical formula, of the GF LD50
in man: a figure of 24 µg/kg emerged. The dose expected to induce a mean ChE depression
of 50% was estimated to be 2.8 µg/kg. Fifty six men inhaled doses of GF by single breath.
Initially, the doses used were 0.16 µg/kg, gradually being increased as the safety of each
dose was established to a maximum of 2.84 µg/kg.
The maximum ChE depression observed was 70%, in one man who received the maximum
dose. In October 1963 the initial results were reviewed at Porton and a maximum dose of
2 µg/kg was imposed for the remaining work [74]. Thirty men participated in this work which
used doses of 1.24 µg/kg, 1.56 µg/kg or 1.89 µg/kg [70].
The results of this work were noted to be "unduly variable" [74] and further human studies
were stopped in early 1964. The Director of Porton stopped any further work with GF but did
not cite the Adrian conditions in doing so. Instead he noted that "the present interest in GF
does not justify any further testing on humans" [75]. No references to later GF human studies
have been found.
9.5. Human studies to investigate miosis
9.5.1. Predictability of miosis
Work before 1954 had established that GB induced miosis. Initially, work after 1954 sought
to identify if the degree and onset of miosis could be predicted. The first human study
involved 240 men being exposed to GB at 5 mg.min/m 3 , 10 mg.min/m 3 or 15 mg.min/m 3 (t = 1
minute or 2 minutes) [76]. Pupil size was measured before exposure and every 30 seconds
during and after exposure. All men wore respirators, so only the eyes were exposed. Some
men had their eyes bandaged; others received atropine before the exposure. Pupils became
constricted much more slowly with the lowest of the three doses, although no great difference
was observed between the two higher doses.
The second study was carried out in September and October 1957 [77] involving drops of
dilute GB being instilled directly onto the eye. A 0.01 ml drop of 0.01% solution of GB,
equivalent to 1 µg of GB, may have been used [78], this being the approved drop used in later
studies. Forty-eight men took part in this study [79], which again aimed to understand if the
response of the eye to GB could be predicted. No report of this study has been found. The
only other reference found to this study is that 2 volunteers who participated were admitted to
the medical treatment room complaining of sleeplessness and gastric trouble [80].
The third study sought to determine the doses of GB required to reduce the pupil to 50% and
10% of its pre-exposed size [81]. This study was carried out in 1968 [82, 83]. The study
used goggles to expose the eye to GB vapour. The goggle method, developed in 1967,
allowed a measured amount of GB vapour, usually 1 µg, to be passed over the eye [84]. The
goggle method appears to have been calibrated from July to November 1967 [84, 85, 86] with
the help of volunteers. In the 1968 study which followed, 26 volunteers participated. Some
had the same eye exposed 2 or 3 times: in total 62 exposures were conducted. The results
of the study were [81]:
84

• the GB dose to halve the pupil size was found to be 3.13 mg.min/m 3 and
13.85 mg.min/m 3 to reduce the pupil to 10% of its pre-exposure size;
• the goggle method allowed the speed with which the vapour flowed over the eye
to be controlled. This study suggested that vapour passing slowly over the eye
induced a lesser degree of miosis than vapour passing quickly over the eye. This
effect was explored in the next study.
Twelve volunteers participated in the study of the effect of the speed of passage of vapour
(referred to as airflow) over the eye [87]. The airflow speeds used were higher in this study
than in the one outlined above [81]. In this study, airflows of 0.07 m/s and 2.2 m/s were used,
whereas an airflow speed of 0.002 m/s was used in the previous study.
• Seven volunteers were exposed a total of 28 times (each eye twice) to GB at the
lower airflow; 5 were exposed 21 times at the higher airflow. At each airflow rate,
three different GB concentrations were used: 0.68-5.5 mg/m 3 .
• The GB dose required to reduce the pupil to 10% decreased as airflow rate
increased. At an airflow of 0.07 m/s a dose of 7.29 mg.min/m 3 was required; at
an airflow of 2.2 m/s a dose of 3.83 mg.min/m 3 would suffice.
During exposures to GB vapour in which miosis was induced, many participants complained
of not being able to see out of the corner of their eyes. This dimness in peripheral vision
might be a consequence of miosis or it might arise if GB affected the sensitivity of the retina
(or, visual thresholds) [88]. A study was conducted to assess visual thresholds when miosis
had been induced by GB and when a similar degree of miosis had been induced by
physostigmine salicylate eye-drops [89]. Approval for the study was given in November 1970
[90].
• Seven volunteers served as controls and received one 0.03ml drop of a 0.5%
solution of physostigmine salicylate in one eye. Visual thresholds were
measured before and after application of the drop.
• Five other volunteers had one 0.03ml drop of a 0.5% solution of physostigmine
salicylate instilled in each eye, and measurements of visual thresholds were
taken. One week later, the five men were exposed to GB vapour in the gas
chamber, and the measurements were repeated.
• The men were each left alone in a dark room and their eyesight allowed to adapt
before having their visual thresholds assessed (typically, by shining different
intensities of light at them).
• The study concluded that GB affected the visual threshold and that the effect was
independent of miosis, possibly because GB interrupted neurotransmission in the
retina.
9.5.2. Miosis and military performance
A second tranche of studies was concerned with the effect of miosis on military performance.
The Armed Forces expressed great concern about the effects of miosis [91]. A large study
involving 119 men was carried out in 1966 and 1967 [92]. Nine men were not exposed to GB
and acted as controls. The exposures of the remaining men are shown in Table 9.1 [93].
Eighteen of the men were part of a special intake.
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GB exposure Number of men
2 mg.min/m 3 5
3 mg.min/m 3
9
7.5 mg.min/m 3
15
15 mg.min/m 3
35
15 mg.min/m 3
30 (see note)
One drop in each eye of a 0.01% solution
of GB (0.88 µg of GB per drop)
16
Note: these men also received medicinal eye-drops.
Table 9.1. GB exposures in the large miosis study.
After the men had been exposed, various tasks were performed indoors and outdoors.
• Shooting trials were held at dusk and on moonless nights by some of the men
exposed to 15 mg.min/m 3 and by the men exposed to eye drops. A fall in
performance was observed [94], but not as much as was expected [93].
• The eighteen men from a special intake, exposed to 15 mg.min/m 3 completed a
march on a moonless night using a compass only. They managed to take
compass bearings remarkably well [93].
• Three men exposed to 7.5 mg.min/m 3 and three controls performed driving tests
in the afternoon and night [93, 95]. The report of the study concluded that night
driving was affected.
The main conclusions drawn from the study were:
• tests involving colour vision were performed badly after an exposure to GB of
only 3 mg.min/m 3 (care was taken not to involve colour-blind men in the study).
• the performance in other tests was impaired significantly by a GB exposure of
7.5 mg.min/m 3 when the tests were carried out in low light.
• "important" tests, like shooting, driving and taking compass bearings were little
affected even after an exposure to 15 mg.min/m 3 .
• treatment with commercial medicinal eye drops did not improve performance.
• the idea (postulated in pre-1954 work) that there was a GB threshold dose for
inducing miosis was refuted. Here a dose of 2 mg.min/m 3 had reduced pupil area
to about 25% of its original size: lower doses would be expected to induce some
degree of miosis.
Shooting targets while suffering miosis is a task of a certain level of complexity, flying fast-jet
aircraft at low level entirely another. In April 1972 a study was begun to investigate the effect
of miosis on aircrew who might be affected while flying [96, 97]. Twenty seven volunteers
recruited specially from RAF units took part. An RAF ophthalmist helped Porton arrange the
trial. He volunteered to be exposed to 15 mg.min/m 3 (t = 30 minutes) in order to understand
the effects and devise tasks appropriate to aircrew 8 . The exposures received by the 27 men
are shown in Table 9.2.
8 The study was not arranged so that aircrew flew after being exposed to GB. Instead they performed
tasks designed to mimic the skills they used to fly aircraft.
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GB exposure (mg.min/m 3 ) Number of men
1.88 9
3.76 4
7.5 4
14.9 10
The conclusions drawn were as follows [97]:
Table 9.2. GB doses in aircrew miosis study.
• in practical terms, eyesight returned to an acceptable level of performance within
2 days and 5 days for exposures of 3.76 mg.min/m 3 and 7.5 mg.min/m 3
respectively;
• after 15 mg.min/m 3 recovery to an acceptable performance took more than 10
days;
• however, for daytime operations well-motivated aircrew could still function, even
after an exposure to 15 mg.min/m 3 ;
• but 2 mg.min/m 3 was considered the maximum compatible with safe and efficient
flying at night.
Another study of the effect of miosis on aircrew was carried out in late 1981 and early 1982.
This study concerned contrast discrimination, and was held jointly with the US Air Force [99].
Exposures to 15 mg.min/m 3 were used. No report of this work has been found, nor any
reference in the ward diaries which cover 1981 and 1982.
More work was conducted to study the effect of miosis on driving. Trials were carried out in
May and June 1975 to test the night driving skills of tank drivers [100]. The trials were
conducted at Tidworth. A GB simulant, physostigmine sulphate, was used to induce miosis
[54, 100]. It was chosen because its effects wore off quickly [101], compared to GB which
had been observed in the driving trials (detailed above) conducted in 1967 [95] where miosis
that lasted for up to 5 days. The choice of physostigmine sulphate, a commercially available
medicine in clinical use as a simulant, is outlined at Annex B.
Further studies, using a GB vapour exposure of 15 mg.min/m 3 , were conducted in 1979 to
test driving ability [102]. However, the long-lasting effects of GB proved a problem. The
Institute of Aviation Medicine (IAM), which conducted eye tests for Porton, believed that 2
men exposed to the GB dose were unfit to drive over the subsequent four days. This
contrasted with advice given to Porton by an external consultant that, at this dose, men
should be able to drive in daylight the day after exposure and at night 3 days after. Porton
decided to let the IAM and the consultant resolve the issue, but decided to keep men
exposed to 15 mg.min/m 3 at Porton for at least a week after the exposure.
9.5.3. Miosis and vision in dim light
Two studies were conducted to assess how miosis affected vision in dim light which used
ophthalmic examinations rather than performance in military tasks to gather data on the topic.
The first study in 1969 [82, 83] involved 2 volunteers [103]. Each received a drop of GB
solution (1 µg in 15 µl of 0.9% saline) in one eye; the other eye serving as a control. After the
drop was instilled each man sat in a dark room. When he had adapted to the dark, he turned
a control knob which gradually increased the illumination until he could discern details on a
test card on a table in front of him. At that point the level of illumination was recorded.
The report of the study made the following points [103]:
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• mild miosis, defined as a reduction in pupil size of less than 70%, had no effect
on visual acuity in dim light;
• for miosis in which pupil size had been reduced by 90%, visual acuity decreases
rapidly;
• the results were put in a military context: a soldier suffering from miosis would, in
dim light, be able to detect a target but would have difficulty identifying it (he
would discern a shape and might be able to say it was a tank - but he would be
hard pressed to say if it was a Russian or a British tank).
The second study in 1969 assessed how quickly the miotic eye re-adapted to dim light after a
sudden exposure to bright light [104]; even with normal vision, recovery takes some time. Six
men were exposed to GB at 15 mg.min/m 3 in this study. The conclusions drawn were as
follows [104]:
• for one of the tests used to measure recovery, the miotic eye took 40 seconds to
re-adapt to dim light whereas the normal eye took 8 seconds;
• the miotic eye was unable to perform the more stringent visual tests even after a
long recovery period;
• in military terms, a miotic soldier would find it difficult to scan dark terrain at dusk
or dawn against a comparatively light sky, and would be handicapped if flares
were used in combat.
9.6 Permanent and long-term effects
9.6.1. Demyelination
Studies of demyelination ran intermittently over almost the entire period of the survey. Some
nerve fibres are insulated with a myelin sheath. The sheath affects a nerve's ability to
transmit messages of different sizes at different speeds. The essential point is that
destroying myelin sheaths can have grave consequences. Multiple Sclerosis destroys myelin
sheaths of nerve fibres in the brain and the spinal cord. This temporarily interrupts or disrupts
the passage of nerve impulses (or messages) commonly affecting the senses and control of
limbs. If the destruction of myelin sheaths continues, permanent paralysis can result.
Damage to myelin sheaths is one form of neurotoxicity; another is damage to nerve cells.
In 1952 one of the non-government members of CDAB reported his work which suggested
that some insecticides attacked the myelin sheath of nerve fibres [105], causing delayed
effects of a serious nature, including paralysis. The Medical Research Council had
reproduced the effects in experiments with fowl. The insecticides covered by this work
inhibited ChE. CDAB agreed that investigations into the action of anti-ChE agents on nerve
fibres should be carried out, and these had started by November 1952 [106]. It was noted
that no evidence of demyelination had been observed in patients treated with DFP (an anti-
ChE substance) in 1952 [107].
Two studies began in 1952: external work explored the effect of organic phosphorus
compounds in fowl and Porton examined the action of GB on myelin sheaths in animals [107].
The external work was reported in 1955 [108]. PF-3 was found to damage myelin sheaths
and to damage irreparably nerve cells and nerve fibre. However, these effects did not occur
with GB. The extrapolation of these results to man was discussed. Compounds which
induced paralysis in man also produced paralysis in chickens but the converse did not
necessarily follow [18]. It was difficult, therefore, to appreciate the implications for man of the
work conducted with fowl. Results from the Porton work in 1955 [108] suggested that
delayed paralysis sometimes occurs in animals but there was no evidence that GB induced it.
88

Animal work continued at Porton. In 1960 [109] the variability between animal species was
noted and more work was conducted. The issue was clarified by a report produced in 1962
[110]. The main points were that some organic phosphorus compounds can induce
neurotoxic effects, including damage to myelin sheaths and nerve cells, and, in man, chronic
exposure to successive sub-lethal doses of G agents may result in paralysis and ataxia (an
inability to control voluntary muscle movements).
A report in 1980 [111] discussed the delayed neurotoxicity of organophosphorus (OP)
compounds. Many OP compounds produce delayed neurotoxicity in man which develops 8
to 14 days after poisoning. Weakness and ataxia develop in the lower limbs and can
progress to paralysis. In severe cases the upper limbs are affected. The severity depends
on the compound and the dose absorbed. Recovery is slow and "seldom complete". The
report noted the following:
• external studies in academia in 1969 to 1975 discovered that the ability of OP
compounds to produce delayed neurotoxicity is related to their ability to inhibit a
particular enzyme called the neurotoxic esterase (NTE);
• according to these studies, delayed neurotoxicity does not develop if NTE is
inhibited by less than 70%;
• work conducted at Porton exploring the NTE inhibition induced by G agents in
hens reaffirmed previous work in that the dose of G agent required to produce
neurotoxicity was considerably greater than the lethal dose.
9.6.2. Follow-up of GB exposures
In the early 1970s Porton followed-up some of the volunteers who had been exposed to GB.
The first follow-up [112] examined the medical history of 35 volunteers who had been
exposed to a GB dose of 15 mg.min/m 3 during their visits to Porton between October 1964
and March 1969. The medical records of these 35 men were compared with those of a
similar number of men attending Porton at the same time but who had not been exposed to
GB. All the volunteers were from the RAF. The study was carried out, on average, 51.8
months after men had been exposed to GB and noted that:
• no significant differences were found between the number of hospital admissions,
out-patient appointments, incidents of reporting sick or days lost through illness
before or after the men's visit to Porton;
• no significant differences were found between the measures of those exposed to
GB and those who were not.
No significant difference was found in the instances of illnesses among the men exposed to
GB and those who were not. Psychiatric diagnoses had been made in 5 of the 35 men
exposed to GB; 3 had been invalided out of the RAF. Psychiatric diagnoses had been made
in 4 of the 35 men not exposed to GB, leading to the invaliding of one. This higher rate of
invaliding because of psychiatric disorders was the "only striking feature of the breakdown of
diagnoses causing instances of illness". At the time the men attended Porton, psychological
incapacitating agents were being investigated although any men thought to have a tendency
to psychological instability were excluded from the investigations. The report noted this had
the effect of "diverting any volunteer whose complete stability was in question to the
programme of work on GB". The report concluded that exposure to GB at a dose of 15
mg.min/m 3 did not have any adverse effect on the physical or mental health of volunteers.
In a second follow-up study [113] the medical histories of 37 soldiers and airmen "who had
volunteered to be exposed to Sarin (GB)" were compared with those of 37 other volunteers
who had not been exposed. The volunteers had attended Porton between June 1952 and
May 1953. The majority of volunteers followed-up in this study were young National
Servicemen 18-20 years old. This is an important point, recognised by the report, as the
study examined only Service medical records, not necessarily medical history up to the time
89

the study was carried out in 1973. If a National Serviceman had left the Services in, for
example, 1955, only his medical history to that date was considered in this follow-up study.
Indeed, the average length of Service after the volunteers had visited Porton was about 4
years, and varied between 4 months and 10 years.
The points made were as follows [113]:
• no significant difference was found in the instances of illness experienced by the
men exposed to GB and those not exposed, after they had been to Porton;
• there was no significant difference in the sicknesses experienced by men
exposed to GB before and after their visit to Porton;
• no incidents of psychiatric illness were recorded among the 37 men who had
been exposed to GB. One man was invalided for psychiatric reasons from the
group who had not been exposed.
The conclusion drawn was that there was no evidence that exposure to GB at Porton had any
adverse effect upon health, psychiatric or otherwise, of the volunteers exposed to GB
considered by this follow-up study.
A third follow-up study was conducted which analysed medical records of volunteers who
attended Porton between March 1975 and Feb 1980 [114]. Sixty volunteers were chosen for
the study: 30 who had not been exposed to GB during their stay and 30 who had (some of
these took part in studies of nerve agent treatments during which they were exposed to GB,
and some were partially protected when they were exposed). Medical records for three of the
men could not be traced from Service sources and therefore 57 volunteers' medical records
were analysed (29 had been exposed to GB). Service medical records were used, covering
the period up to the end of October 1988, when the study was conducted, or up to the
volunteer's discharge from service. The average length of service since a volunteer had
attended Porton was around 80 months; 24 of the 57 volunteers considered were still serving
at the time of the study.
The medical incidences (measured per 1000 man months) for the two groups were compared
and the observations are summarised in Table 9.3.
Medical Incident Group exposed to GB Group not exposed to GB
Pre-Porton Post-Porton Pre-Porton Post-Porton
Admission to hospital, sick
bay, station sick quarters
17.4 9.5 9.1 8.2
Out patient referrals for
specialist consultation
8.7 4.7 7.3 6.1
Days lost through sickness
133.3 109.6 147.7 73.5
Table 9.3. Medical incidences in third follow-up study
The incidences were not significantly different between groups, nor within groups before or
after the men had attended Porton. The causes of illness were also analysed and no
significant differences were found. There were no cases, in the records used in this study, of
psychiatric invaliding. The conclusion made was that there was "no evidence from this study
that the exposure of volunteers to low doses of nerve agents results in any adverse medical
sequelae" [114].
9.6.3. Detachment of the retina
In January 1982 [99] the Institute of Aviation Medicine (IAM) suggested Porton should adopt
more stringent standards for volunteers used in miosis studies. IAM was concerned that
short-sighted people (myopes) might suffer a detachment of the retina if they were exposed
to GB. GB could induce spasms in the ciliary muscles of the eye (the ciliary muscles form a
90

ing which is attached to the lens of the eye). High myopes (very short-sighted people) were
thought by IAM to be liable to retinal detachment if they suffered ciliary muscle spasms [115].
Porton conducted a review of past miosis work [115] which was hampered because visual
acuity had not always been measured. Nonetheless, it was revealed that 16 short-sighted
people had been exposed to nerve agent at various times (15 to GA in 1945 and one to GB in
1971). In none of these cases did detachment of the retina occur. The report of the review
noted that it had been suggested (probably by the IAM) that good fortune rather than wise
decisions had been responsible for the safety record.
The report suggested that Porton should accept the IAM suggestion to raise the standard of
screening for people participating in miosis work. This was disputed by COSHE: "over 3,000
volunteers had been exposed to nerve agent since 1950 among them many with myopia yet
there had been not one recorded case of retinal detachment" [116]. An assessment of the
risk was deemed to be required, and a Consultant Ophthalmic surgeon at Moorfields Eye
Hospital was asked to give an opinion.
The response [117] explained that the relationship between miosis and retinal detachment
was "at best speculative and is certainly not proven". Not much information was available on
the degree of risk faced by myopes in whom miosis was induced. The consultant suggested
a moderate position: it would be wise to reject people from miosis experiments who had a
degeneration in the peripheral retina (which may occur in people other than myopes) and who
had previously suffered retinal breaks. That would exclude about 10% of the healthy
population.
Porton and the IAM agreed in July 1982 that there was no good evidence to associate
myopia with detachment of the retina. But present ophthalmic screening procedures for GB
miosis experiments were agreed to be "inadequate and inappropriate" [118]. A new eye
testing regime was instituted. The MC approved this approach [119]
9.6.4. (Single Fibre Electromyograph) SFEMG
SFEMG measures the activity of individual muscle fibres that have a common nerve motor
unit. In simple terms, the muscle fibres are driven by the same motor. They would therefore
be expected to react to the motor in a similar way. Typically, SFEMG was used to measure
the activity of two muscle fibres and compare the relationship between them. Any difference
was called "jitter". Jitter was measured in units of time, thereby giving an indication of how
different the reactions of muscle fibres were.
Some jitter was normal - nerve fibres not being expected to react in a perfectly identical way.
When SFEMG was used, 20 pairs of muscle fibres were normally studied. Jitter was thought
normal [120] if the average jitter observed from the 20 pairs was 25 microseconds (µs) or
less. Clinically, a jitter of more than 55 µs was regarded as abnormal. From the 20 pairs of
nerve fibres examined in a SFEMG experiment, one value of 55 µs or more was accepted as
normal. However, if a proportion of more than 1/20 had this value, it was accepted as an
indication of disturbed neuromuscular transmission.
As mentioned earlier, human studies with GB in which SFEMG was used to measure nerve
activity began in late 1983. By September 1984 [120] apparently abnormal readings had
been observed from SFEMG measurements.
In 1983/84 eight men were exposed to GB vapour at 15 mg.min/m 3 while having jitter
measured in 17 muscle fibre pairs. All of the men had normal levels of jitter before they were
exposed. An analysis of the jitter readings after exposure is given in a Porton report
published in 1985 [120]. The report noted that after exposure to GB:
• 5 men had abnormal jitter 3 days after the exposure;
• four of these 5 men had an equivocal (borderline normal) or abnormal jitter 3
hours after exposure;
91

• one man had 5 of 17 pairs with jitter readings over 55 µs three days after and 8 of
17 pairs in that range four months later.
The report went on to note that a previous study, in which volunteers were exposed to GB at
5 mg.min/m 3 while testing nerve agent treatment, had resulted in abnormal SFEMG readings
three days after exposure [121].
Two points might be made here:
• First, the report of the SFEMG readings published in 1985 was a preliminary
interpretation which contained some flaws. The analysis and conclusions of the
completed study were published in the open press in 1996 [122].
• Second, SFEMG seems to have been an instance where measurement
technique outstripped medical knowledge. SFEMG was extremely sensitive, so it
was difficult to understand what the measurements meant [120]. No
neuromuscular abnormality was detected in the clinical examination conducted
on the volunteers after the experiments and before they left Porton.
Notwithstanding the second point, the volunteers involved in the study were asked to return
for further examinations and specialist opinion was sought. In the interim, all exposures of
volunteers to 15 mg.min/m 3 were prohibited in September 1984 [123]. Specialist opinion was
sought from the Royal Free Hospital and National Hospitals. London Hospital agreed [124]
the SFEMG findings at Porton seemed abnormal but, because of the sensitivity of the
technique, the practical significance of the findings was open to question.
This advice was received in 1985. All human studies with GB were suspended until the
significance of the SFEMG changes was clarified [126]. The volunteers returned, when it was
convenient to them and their units, for further SFEMG studies during 1985 and 1986.
SFEMG studies were conducted at London Hospital and the volunteers also had eye
movements checked at Queen's Square and retinal function examined at Moorfields Eye
Hospital [127].
By November 1986 SFEMG examinations had been completed and the changes observed
after the exposure at Porton in 1984 were not apparent. It was concluded that any effect GB
might have on neuromuscular transmission was reversible [121, 128]. The MC concluded in
February 1987 [129] that this result posed no bar to continuing low dose GB exposures at
5 mg.min/m 3 .
The Medical Committee decided in March 1987 that SFEMG would be used as a screening
procedure for future experiments with GB [130] and, from then on, a careful watch seems to
have been maintained on SFEMG readings. Apparently abnormal SFEMG readings were
observed after exposures in 1988 and reviewed by the committee in November [131], but,
because the readings "were essentially no different to those seen previously", it was decided
that experiments could continue.
9.6.5. Electroencephalography (EEG)
A report in 1987 reviewed the toxicology of GB and GD [132]. The review was conducted by
surveying Porton documents and external reports. The points made were as follows:
92
• from the survey, it was evident that GB and GD can produce both short-term and
long-term effects at sub-lethal doses;
• most of the information on symptoms following exposure to anti-ChE compounds
comes from literature on poisoning due to OP insecticides. In the early work at
Porton into the effect of nerve agents on man, the "emphasis was on generalised
symptoms immediately following exposure, with no follow-up investigation of
persistent clinical signs (including psychological effects)";

• "the main problems, as far as volunteer studies are concerned, appear to be the
possible generation of both irreversible damage at peripheral nerve endings
(especially the neuromuscular junction) and long term changes in CNS activity
expressed as atypical EEGs or manifest as psychological disturbances; no
evidence of direct cardio-toxicity has been found in this survey. It is difficult on
the basis of information currently available to assess the potential for permanent
as opposed to reversible damage."
In January 1979 COSHE decided that EEG measurements should be taken and correlated
with ChE depression (if possible) during some GB human studies [55]. Progress in taking
EEG measurements was slow, because of the shortage of volunteers, but a start had been
made in early 1980 [56].
Human studies testing a nerve agent therapy which involved exposure to GB used EEG
measurements. In 1982 EEG was used to explore the effect of treatment and GB separately
and together [133]. A study was designed in 1984 [120] to look for EEG changes in
volunteers exposed to GB at 15 mg.min/m 3 .
EEG continued to be used until the end of the period covered by the survey, particularly in
studies of nerve agent treatments. In September 1989 [134] COSHE discussed the difficulty
in defining "abnormal readings" for EEG and the clinical significance of abnormal EEG
readings. Just as with SFEMG, medical techniques seemed to have outrun medical
understanding.
Three studies were conducted at Porton to assess the effect of GB on EEG readings of
rhesus monkeys. The first reported in 1988 [135]. As background, the report noted that a
number of clinical studies suggested that minor psychological and sleep disturbances are
induced by a single OP exposure, or a limited level of exposure, and that these effects might
persist for more than 6 months even though the blood ChE was normal. The study examined
the effect of a single 2.5 µg/kg dose, administered by IV, to rhesus monkeys. EEG readings
were taken from the monkeys at 1 month intervals for 12 months. The readings were
compared with those taken from monkeys that had received an IV dose of saline (the
controls) and from monkeys that had been given nerve agent poisoning pre-treatment before
the GB dose. The points made in the study include the following [135]:
• between the controls and the monkeys receiving GB, no major or long-term
changes were detected in electrical activity of the brain as measured at three
frequencies;
• in the monkeys given pre-treatment and then GB, increases in activity at two
frequencies occurred during the first 4 months; afterwards the activity followed
the pattern observed in the monkeys treated with GB.
The second study was reported in 1989 [136]. It considered the effect on EEG readings of
repeated doses of GB: 1 µg/kg doses were given by IM injection at 1 week intervals for 10
weeks. Under these circumstances long term changes in EEG readings were detected and
reached significance about 26 weeks after the first dose of GB. The changes persisted until
the end of the experiment at 62 weeks. However, the nature of the changes was different
from those previously reported after the administration of an acute dose of GB. The report
concluded that [136]:
"Exposure of man to repeated doses of GB could be hazardous to long term health.
It is considered, however, that not enough evidence has yet been obtained to indicate
that exposure to a single low dose of GB (e.g. producing < 50% inhibition of RBC
ChE) could be hazardous".
The third study, published in 1991 [137], explored in more detail the different effects on EEG
readings due to single and repeated GB doses uncovered by the previous two studies. The
study confirmed the differences previously observed and noted that:
93

• 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.
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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

approved this proposal in 1959 [14]. Both the proposals on GB IV and radioactive VX were
accepted in 1959 by the Minister of Supply [15], who asked the Service ministries for their
approval of the use of Service volunteers in the new experiments.
The General Election and the subsequent dissolution of the Ministry of Supply resulted in
further delay. In February 1960 the Services declared they were not prepared to allow
Service volunteers to participate in the new studies until more information had been provided
by Porton [16]. By June 1960 the Services had approved the VX proposal [17]. The SAC
noted in its annual report for 1959 (published in March 1960) [18] that "decisions about V
agent human tests could be left to the discretion of the Biology Committee". The SAC
decision suggests that the approval of the Services in June 1960 cleared the way for human
studies with VX and that any new proposals to extend VX studies could be dealt with by the
BC.
At this point the approval for VX human studies becomes confused. Although the SAC had
been happy to defer decisions to the BC, the BC meeting in July 1961 [19] noted that the
Minister had papers on both the GB IV and VX proposals. At the next meeting, in November
1961, ministerial approval for the proposals had not been received. As the Services had
approved the VX proposal but not the GB IV proposal, the BC considered whether the
proposals should be dealt with by the Minister separately [20]. The review of national CW
policy in 1962 brought an end to discussions of the GB IV proposals as they were no longer
deemed necessary [21]. No documents have been found that suggest the VX proposal was
considered separately by Ministers after 1962, although, in 1963, CDAB noted that it was "not
permitted to use Service volunteers for tests with VX" [22].
After 1963 decisions about conducting human studies with VX may have devolved, as SAC
suggested in 1960, to the BC. The duties of the BC on human studies were transferred to the
ABC when it was formed in 1965. At the ABC meeting in April 1967 it was evidently decided
that the GB tests permitted by Adrian should be extended to include human studies with VX
[23]. This was noted by the subsequent CDAB meeting in June 1967 [24].
Although precise details have not been found, it might be inferred that permission for Porton
to employ Service volunteers in VX studies was given in April 1967. But, permission to
involve Service volunteers in studies of the skin penetration of VX might have been inferred
from the decisions of the SAC and the Services by June 1960. It seems that work at Porton
aligned with these two dates, as shown in Figure 10.1.
Before June 1960 human studies with VX involved only volunteers from the Porton medical
staff. In the winter of 1960 Service volunteers took part in radioactive VX tests but, after that,
they were not involved in VX studies until 1968. This suggests Porton inferred that the June
1960 decisions gave approval for VX experiments but, when it became apparent that
Ministers were considering the VX proposal in 1961, work with Service volunteers was halted
(no document has been found which records an explicit decision to stop the work) and
recommenced only after the ABC decision in April 1967.
96

Porton
Medical
Officers
Service
Volunteers
Liquid VX
on skin
Liquid VX
on clothing
Inhaled VX
vapour
SAC & Services
decisions (Jun 60)
VX vapour
through skin
ABC decision
(Apr 67)
VX on skin Effect of VX
vapour on eyes
1958 1960 1962 1964 1967 1970
10.2. Human studies with liquid VX
10.2.1. Initial dose estimates
Figure 10.1. VX Human Studies
The 1955 estimate of LD50 for liquid V on skin of 6 - 10 mg had been revised to 4 mg by
1956 [5]. The selection of one of the V agents, VX, in 1958 allowed more precise LD50
estimates to be made. Work to find out how quickly VX penetrated skin was conducted in
1958 using animals, resected animal skin and resected human skin [25].
The resected human skin used in the 1958 work was 5 - 24 hours old, as measured from time
of death [25]. The source for the resected skin used in 1958 is not explained in the report of
the work. However, Porton reports of later work in 1962 with resected human skin outline the
source of the skin used:
"Human skin was obtained either post-mortem or at operation; it was always taken
from the mid abdomen region" [26];
"Human skin was obtained at post mortem or at operation from local hospitals" [27].
The 1958 work showed that very little of the VX placed on skin was lost through evaporation.
If left on the skin for long enough a large proportion of the VX would be absorbed into the
system. However, VX penetrated skin very slowly. The study, therefore, considered the rate
at which VX was absorbed.
• After being placed on the skin there was a short delay (typically 15 minutes)
before liquid VX penetrated. Thereafter, liquid VX penetrated steadily and at a
fairly constant rate [25].
97

• The rate of penetration during this steady period was measured. The units used
were "µg penetrating per min per mg of the dose of VX applied to the skin
(µg/min/mg)". In effect, the units measured the percentage of the dose applied
which penetrated during each minute the VX was left on the skin.
• The rate of penetration through resected human skin was found to be 0.3
µg/min/mg. Penetration rates through resected back skin from a rabbit and
through the back skin of an "intact" rabbit were found to be similar. From this it
was concluded that VX would penetrate through the skin of man at a rate of 0.3
µg/min/mg.
This rate of penetration was applied to derive LD50 estimates for man. Clearly, a specific
amount of VX had to be absorbed before a man would be killed. If that amount was known it
would be possible to find out, using the penetration rate, how long a dose of liquid VX had to
be left on the skin for that amount to penetrate.
The report of this work assumed that the absorbed amount to cause death was 15 µg/kg for
man. For a man of an average weight of 70 kg, this is 1.05 mg. This figure appears to have
come from US studies which administered VX by IV injection, from which the IV LD50 for man
was estimated as 0.5 - 1 mg per man [28]. Using this amount, the study estimated LD50 for
VX on skin:
• a dose of 4 mg of liquid VX on skin would kill if left for about 15 hours
(equivalently, LD50 for 15 hour death in man is 4 mg);
• death would result earlier if a larger dose were used 10 - a dose of 40 mg of liquid
VX applied to skin would kill if left for about 2 hours.
Clearly then, LD50 varies according to the dose and the amount of time that dose is left on
the skin. One consequence of this variation is that any estimate of LD50 for liquid VX on skin
should cite how long it is assumed the dose is left on the skin. Very rarely in documents
which mention VX was this time given: one exception appears in the next section. In 1959,
the LD50 of VX was assumed to be 15 mg/man, although it "may be as high as 25 mg per
man" [29]. The variation may be due, in part, to different assumptions about how long the
liquid VX dose would remain on the skin.
10.2.2. Studies with volunteer medical officers
Two studies were conducted with liquid VX in which volunteers from the Porton medical staff
took part: one with VX applied to the bare skin and the other with VX applied onto clothing
laid over the bare skin.
In 1958 two volunteer medical officers each had a drop of 50 µg of radioactively tagged VX
applied to their left forearm so that the rate of penetration of VX could be studied [30]. The
drop was left on the skin for 30 minutes, during which time a Geiger counter was used to
measure the rate of penetration. After 30 minutes the skin was swabbed, and then resected
"down to the muscle". ChE was measured before exposure and at various times after the
skin had been resected. The main results were that [30, 31]:
• the penetration rate observed was about the same as predicted from the study
with animals and resected human skin;
• no depression of RBC, plasma or whole blood ChE was observed, although the
BC in reviewing the work suggested that measurements should have been taken
more frequently and the amount of VX secreted in urine should also be
measured.
10 Recall that the penetration rate is expressed as a percentage of the dose applied which is absorbed
every minute. So increasing the dose applied increases the amount absorbed every minute.
98

The second study with volunteer medical officers, to assess the penetration of VX through
clothing, was carried out in 1960 [32] and had two parts:
• three trials were conducted in which clothing contaminated with liquid VX was
worn for periods of 4, 6 and 8 hours;
• after "careful consideration of these experiments", two more trials were
conducted with contaminated clothing left in place for 24 hours.
Each of the five trials used 200 mg, which was then agreed as the LD50 dose for clothed man
if the dose was left in place for 24 hours. [The second part of the experiment, therefore,
exposed volunteer medical officers to the accepted LD50 dose: 200 mg on clothing left in
place for 24 hours.] The clothing used was an outer layer of battledress serge over an inner
layer of flannel shirting. VX drops of 1 - 2 mg were applied on this assembly over an area of
about 160 cm 2 . The main results from this work were as follows [32, 33].
• In the first three trials no depression of ChE was observed, even after the trial in
which the clothing was left in place for 8 hours.
• In the 24 hour trials, ChE did not begin to fall until 14 hours into the experiment,
and minimum levels of ChE occurred 24 hours after the contaminated clothing
was removed. In one subject the maximum ChE depression was 74%, in the
other 36%.
• Plasma ChE was affected less than RBC ChE, recovering more quickly and to
within 90% of normal by one week after the experiment;
• The accepted 24 hour LD50 estimate of 200 mg was agreed [33] to be far too
low, although that dose seemed to inhibit ChE by about 50% [32]. Animal
experiments had suggested that the lethal dose was four times the dose which
inhibited ChE by 50%. The 24 hour LD50 estimate was suggested to be 800 mg.
10.2.3. Studies with Service volunteers
Studies of the penetration of liquid VX through skin were conducted with Service volunteers in
November 1960 [34]. The report of this work was published in 1963 [35]. Drops of
radioactively-tagged VX were placed on the skin in one of three locations: the back, the
forearm, or the palm of the hand. The chosen area, excepting the palm, was shaved with an
electric razor and a ring was attached to the skin. The rings used on the forearm and the
palm were made of polythene with an internal diameter of 2.5 cm; those on the back were
made of brass measuring 7 cm in diameter.
VX was placed on the skin inside the ring in drops of 2 - 4 µg. Nylon film was stuck over the
top of the ring. The assembly and VX were left in place for 6-10 hours, during which time a
Geiger counter was used to take measurements. The assembly was then removed and the
skin decontaminated, first by stripping with adhesive tape and then by washing with
isopropanol and soapy water. The details of the exposures are given in Table 10.1.
According to the volunteer records [34], 16 men took part in this study. No details are given
of how the exposures shown in Table 10.1 were divided between these men.
99

Site of skin Number of
men
Average total dose (µg)
Average time dose
was left on skin
(minutes)
Palm 8 26 360
Back 8 25 510
Forearm 14 15.7 577
Table 10.1. Liquid VX studies with Service volunteers
ChE depressions observed were small, varying from 1.9% to 3.9%. After a brief delay the
penetration of VX through the forearm and the back was "regular and rapid": on average, 8%
of the VX dose penetrated through back skin and 15% through forearm skin in 8 hours.
10.3. Human studies with VX vapour
10.3.1. Inhalation of vapour
Eight volunteers from the Porton medical staff took part in a study involving the inhalation of
VX vapour in 1961 and 1962. It had been demonstrated in previous work that ChE recovers
to normal levels rapidly after an exposure to VX [37]. Therefore, this study involved the
volunteers being exposed to VX vapour several times. In total the study featured 54
exposures. No man was exposed either for the first time or subsequently unless his ChE was
within normal limits.
Only the head and neck were exposed. Vapour was delivered down a tunnel at the end of
which the subjects placed their head and neck. At the end of the exposure, no washing of the
face or any form of decontamination was allowed for 8 hours.
19 exposures involved men with no respiratory protection. Fifteen of the exposures lasted
either 3 minutes or 1.5 minutes, at 0.6 - 3.6 mg.min/m 3 . The remaining 4 exposures lasted for
6 minutes or 7 minutes, at 4.8 - 6.4 mg.min/m 3 . The following effects were noted [36]:
• the maximum ChE depression observed was 70% in RBC ChE but plasma ChE
was very much less depressed than RBC ChE;
• miosis developed 1-3 hours after exposure and usually passed off 36 hours later.
The remaining 35 exposures involved the same men being exposed but with respiratory
protection: a mouthpiece and a clip over the nose. Twenty five of the exposures lasted
between 1.5 minutes and 4 minutes (exposure levels of 0.7 - 20 mg.min/m 3 ). The remainder
were longer (9 - 24 minutes, 7.7 - 25.6 mg.min/m 3 ). In practical terms, men undergoing these
exposures did not breathe in VX vapour, but the following results were recorded [36]:
• no symptoms were observed during the exposure, although nearly all subjects
developed miosis 30 minutes after exposure;
• ChE was depressed, in two of the exposures by more than 50%.
The second result was quite startling: it suggested that VX vapour was absorbed quite rapidly
through the skin of the face and neck, so that even with protection a man would be vulnerable
to VX vapour. In reviewing this result, the BC noted that VX vapour absorbed through the
skin could be as great a danger to a masked man as GB was to an unmasked man [38].
The study generated estimates of the L(Ct)50 dose in man for VX vapour, based on the
doses necessary to depress ChE by certain percentages [36]. These estimates are
summarised in Table 10.2. The estimates are given as a range as there was disagreement
between the US and the UK on the ratio of L(Ct)50 to doses which induced either 50% or
90% ChE depression. The estimates were not accompanied by an indication of the length of
the exposure.
100

Condition Respiratory protection? L(Ct)50 (mg.min/m 3 Neck and head exposed to
)
vapour
Yes
203 - 305
Whole body exposed to
vapour
No
Yes
No
Table 10.2. Estimates of lethal doses of VX vapour
48 - 82
65 - 102
39 - 70
The significance of these estimates was that all-over protection was required against a threat
of VX vapour [38]. The study also showed that miosis resulted from very small doses of VX
vapour, but more work was required to establish the threshold dose [36].
10.3.2. Absorption of VX vapour through skin
Another study examined the absorption of VX vapour through skin in 1962. Most of the work
conducted in this study was with animals, but one volunteer from the Porton medical staff had
a forearm exposed to VX vapour.
The concentration of VX vapour used was intentionally chosen so as not to induce any
depression of ChE. The forearm was shaved and exposed to VX vapour at the end of the
tunnel for 3 minutes. The exposure was 0.16 mg.min/m 3 . After exposure the man was
moved to another chamber and the absorption of the residual vapour on the forearm was
measured. The nature of the absorption was examined by stripping the skin 20 times with
adhesive tape and analysing the VX content of each tape. The main conclusion of the study
was that the main barrier to skin absorption of VX vapour was not the skin itself but the air in
immediate proximity to the skin [39].
10.4. Human studies of eye effects of VX vapour
Service volunteers took part in three studies of the eye effects of VX vapour in 1968 and 1969
[40]. The studies were prefaced by animal work to establish the VX vapour doses which
would induce certain levels of miosis [41]:
• to induce miosis of 50% (that is to halve the pupil area) in rabbits, a dose of 0.04
mg.min/m 3 was necessary;
• to induce miosis of 90% in rabbits a dose of 0.23 mg.min/m 3 was necessary;
• the degree of miosis induced was influenced not just by the dose of VX vapour
but by the speed with which the vapour travelled across the eye, generally a
lower speed meant a lesser degree of miosis.
The first study in which Service volunteers participated investigated the effect of speed [42].
Twenty five volunteers took part. Their eyes were exposed to different concentrations of VX
vapour, 0.025 - 0.92 mg/m 3 , passed over the eyes at different speeds, 0.01 - 2.2 m/s. As
vapour at higher wind speeds was expected to cause more miosis, lower doses were used.
In all, 25 volunteers underwent 101 exposures, counting each eye as one exposure. The
main conclusions of the study were [42]:
• at low wind speeds (0.01 m/s), 90% miosis resulted from VX vapour at 7
mg.min/m 3 ;
101

• at higher wind speeds (2.2 m/s), 90% miosis resulted from VX vapour at only
0.09 mg.min/m 3 ;
• VX vapour exposure levels to induce 90% miosis were smaller than those of GB.
The second study [43] explored the effect of miosis on the ability to see in dim light. Similar
experiments were conducted for GB, as described in the previous chapter, and the procedure
used in those to measure acuity was repeated for the VX work. Here, 7 volunteers had one
eye exposed to VX vapour, while the other was not exposed. The degree of miosis induced
was always greater than 50%. The study showed (as for GB miosis) that mild miosis (70% or
less) had practically no effect on visual acuity in dim light but miosis of 90% or more
constituted a handicap.
The third and final human study with VX [44] considered the effect of miosis on the eye's
ability to recover to seeing in dim light after exposure to a bright light. Again, this study also
considered miosis induced by GB (as described in the previous chapter) and the procedure to
measure recovery after miosis induced by VX was identical. In this study 5 volunteers had
their eyes exposed to VX vapour. Two were rendered miotic in both eyes, three in one eye
only. Some were exposed to VX vapour through goggles. In all cases, the degree of miosis
induced was less than 50%. The results mirror those described in the previous chapter.
10.5. Field trials
No VX human studies were conducted after the visual acuity trials in 1969. No field trials
were conducted with VX. But some field trials relevant to VX are worth reporting. VX
evaporates very slowly and would be expected to persist on the ground and on surfaces for a
long time. Therefore, there was concern that men moving over terrain contaminated by VX
would pick up a lethal dose. A series of field trials was conducted to explore the problem,
specifically to determine which parts of the body (feet, knees, head etc.) were likely to pick up
VX from contaminated grass, shrubs and trees.
These trials were often referred to as "pick-up" trials. They did not use VX, but a harmless
simulant for VX called diethyl phthlate (DEP). DEP was found to have similar physical
properties to VX in 1956 [45]: it evaporated and was broken down by water at the same rate
as VX. DEP was used in pick-up trials, usually dyed green or red.
Because the pick-up trials did not expose volunteers to CW agents, they are not described in
detail; but typically some part of the Porton range was contaminated with dyed DEP to the
same extent as might be anticipated with a VX attack. Men then carried out duties while
dressed in white overalls, white boots and white headgear so that any dyed DEP picked up
could be clearly seen. In some trials men crawled over a grass contaminated with dyed DEP
[46, 47] or walked through scrub (actually juniper bushes on the Porton range) [48]. One trial
saw men setting up a camp and defensive shallow trenches on grass contaminated by dyed
DEP [49].
Two field trials were carried out in which men were sprayed from the air with DEP. The first
was conducted against men taking part in an exercise in which deployments anticipated in
the face of nuclear attacks were practised. Here some men in the exercise were sprayed
with undyed DEP from a Sea Venom aircraft [50]. The second trial sought to find out the
degree of contamination that might be expected if VX were sprayed onto men who were
partially dug in. In this trial men constructing weapon and shelter trenches were sprayed with
dyed DEP from a Dragonfly helicopter [51].
102

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Chapter 8
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103

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Chapter 9
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104

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105

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106. WO195/12063. CDAB 21 st meeting 6 Nov 52.
107. WO195/12139. BC 10 th meeting 7 Jan 53.
108. WO195/13279. BC 15 th meeting 5 May 55.
109. WO195/14984. CDAB 44 th meeting 9 Jun 60.
110. Porton Note 240. Neurotoxicity of organophosphorus compounds. 31 Jan 62.
111. Technical Paper 282. The delayed neurotoxicity of nerve agents and other organophosphorus
compounds. Jun 80. [R]
112. Technical Note 120. A "follow up" of volunteers to GB (Sarin). Feb 72. [R]
113. Technical Note 175. A long-term "follow-up" of volunteers exposed to GB (Sarin). Jul 73. [R]
114. Technical Note 1010. Possible long term sequelae of exposure to nerve agents: a retrospective study.
Aug 89.
115. COSHE Proceedings. Statement on exposure of myopic subjects to nerve agents Med IT4010/82 25 Jan
82. [C]
116. COSHE 148 th 3 Mar 82. [C]
117. COSHE Proceedings. Safety Requirements for exposure to GB. Letter from Moorfields Eye Hospital
Consultant Ophthalmic Surgeon 8 Apr 82.
118. COSHE 151 st 19 Jul 82. [C]
119. MC meeting 19 Nov 82. [C]
120. COSHE Proceedings. Protocol S02/2 Memo dated 4 Sep 84. [C]
121. Technical Note 684. Single Fibre Electromyography following low dose GB exposure in man. Nov 85.
[UK C]
122. SFEMG changes in man after OP exposure. Human & Experimental Toxicology (1996) 15, 369-375.
123. COSHE Proceedings. Loose Minute RLM/JD dated 3 Sep 84. [C]
124. COSHE 165 th 6 Feb 85. [C]
125. Annual Establishment Report: 1986 review. [S UKEA]
126. Annual Establishment Report: 1986 review. [S UKEA]
127. COSHE 168 th 24 Feb 86. [C]
128. COSHE 171 st 24 Nov 86. [C]
129. MC Meeting 6 Nov 86. [C]
130. MC Meeting 26 Mar 87.[C]
131. MC meeting 10 th Nov 88. [C]
132. Technical Note 820. Toxicology of Sarin and Soman - a review Mar 87. [UK C]
133. COSHE 149 th 19 Apr 82. [C]
134. COSHE 183 rd meeting. 4 Sep 89. [C]
135. Technical Note 916. A long term study of the effect of a low dose of GB on the primate
electroencephalogram (EEG). Feb 88. [R]
136. Technical Paper 544. Effect of chronic administration of low doses of GB on the electroencephalogram (EEG).
Nov 89 (R - but a sanitised copy has been placed in the House of Commons Library through GVIU 25/6/99).
137. Technical Paper 627. Effect of acute and chronic administration of GB on the electroencephalogram.
Dec 91. [UK C]
138. The effects of acutely administered low dose sarin on cognitive behaviour and the electroencephalogram in the
common marmoset. Journal of Psychopharmacology 13(2) (1999) 128-135.
Chapter 10
1. WO195/12549. CDAB 24 th meeting 5 Nov 53.
2. WO195/13544. BC 16 th meeting 15 Dec 55.
3. WO195/13556. SAC Report for 1955. 6 Jan 56.
4. WO195/13279. BC 15 th meeting 5 May 55.
5. WO189/864 Porton Technical Paper 539. A preliminary investigation into the use of V gases in chemical shell.
2 Apr 56.
6. WO195/13512. CDAB 30 th meeting 3 Nov 55.
7. WO195/13227. A preliminary report on the toxicity of aerosols of C11 series. Ptn/TA2310/1730/55 12 Apr 55.
8. WO195/14473. CDAB 39 th meeting 9 Oct 58.
9. WO195/14086. Nerve gas trials at CDEE with human observers - paper produced by Porton on 24 Jun 57 for
consideration at special meeting of SAC and CDAB on 3 Jul 57.
10. WO195/14048. BC 18 th meeting 25 Apr 57.
11. WO195/14704. BC 22 nd meeting. 5 Jun 59.
12. WO195/14321. BC 20 th meeting 20 Mar 58.
13. WO195/14221. BC 19 th meeting 29 Nov 57.
14. WO195/14797. CDAB 42 nd meeting 8 Oct 59.
15. WO195/14983. BC 24 th meeting 17 May 60.
16. WO195/14900. CDAB 43 rd meeting 4 Feb 60.
17. WO195/14984. CDAB 44 th meeting 9 Jun 60.
18. WO195/14876. SAC Report for 1959. March 60.
19. WO195/15217. BC 27 th meeting 18 Jul 61.
20. WO195/15289. BC 28 th meeting. 23 Nov 61.
106

21. TG1009 Policy regarding tests on human subjects. Experiments with Physiological Observers at CDEE.
HQ/TA/32/07/5848 2 Feb 62. [R]
22. WO195/15563. CDAB 52 nd meeting. 28 Feb 63.
23. WO195/16462. ABC 4 th meeting 26 Apr 67.
24. WO195/16496. CDAB 65 th meeting 16 Jun 67.
25. Porton Note 24. Penetration of skin by V agents. 25 Apr 58. [R]
26. WO189/497 Porton Technical Paper 999. Some effects of heat, pH and chemicals on the impedance and
permeability of excised human skin. 27 Feb 69.
27. WO189/496 Porton Technical Paper 998. The rates of penetration of some V agents through human skin. 27
Feb 69.
28. WO195/14824. BC 23 rd meeting 5 Nov 59.
29. WO195/14781. Conclusions and recommendations of 14 th Tripartite Conference - Medical Aspects. Ptn/IT
4205/4138/58 Oct 1958.
30. Porton Note 44. Rate of absorption of V agents through human skin. 12 Sep 58. [S]
31. WO195/14514. BC 21 st meeting 20 Nov 58.
32. WO189/1067 Porton Technical Paper 753. Penetration of VX through clothing. 20 Jan 61.
33. WO195/15154. BC 26 th meeting 24 Feb 61.
34. Experimental Summary Book MPG 47 1959 to 1989.
35. WO189/361 Porton Technical Paper 839. Passage of VX through human skin. Jan 63.
36. WO189/352 Porton Technical Paper 830. Human exposure to VX vapour. Jan 63.
37. WO189/359 Porton Technical Paper 837. Recovery of blood ChE in man after exposure to VX. 14 Feb 63.
38. WO195/15609. CDAB 53 rd meeting 6 Jun 63.
39. WO189/414 Porton Technical Paper 899. Cutaneous absorption and desorption of VX vapour. 13 Mar 64.
40. Experimental Log MPG 67. 1968 and 1969.
41. Technical Paper 64. Estimation of the concentration of nerve agent vapour required to produce
measured degrees of miosis in rabbit and human eyes. Jul 71. [C]
42. Technical Paper 103. The effect of wind-speed on the miotogenic potency of GB and VX vapour. Jun
72.[C]
43. Technical Paper 111. The effect of miosis on visual acuity in dim light. Sep 72. [C]
44. Technical Paper 121. The effect of miosis on the delay time to recovery of visual acuity in dim light after
exposure to bright light. Oct 72. [C]
45. WO189/891 Porton Technical Paper 568. The estimation of diethyl phthalate, tricresyl phosphate and dyed
diethyl phthalate as simulants for V agents. 16 Nov 56.
46. Porton Note 70. Contact hazards: the pick up of contaminant on crawling over a contaminated grass
area. 27 Jan 59. [R]
47. Porton Note 107. Contact hazard: pick-up of contamination by crawling on lightly contaminated
grassland. 25 Jun 59. [C]
48. Porton Note 135. The pick-up of contamination during passage through scrub. 26 Jan 60. [C]
49. Porton Note 102. The pick-up of contamination by troops in bivouac on contaminated grassland. 17 Jun
59. [C]
50. WO189/997 Porton Technical Paper 680. A preliminary investigation into the hazards of CW spray attack on
deployed troops. 14 Apr 59.
51. Porton Note 211. Vulnerability of infantry to direct spray contamination and to subsequent pick-up of
contaminant: troops digging field fortifications and not reacting to spray attack (intermediate report). 15 Feb
64. [C]
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108