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

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