|
|
|
Did Chemical Exposures of Servicemen at Porton Down Result in Subsequent Effects on their Health? The 2005 Porton Down Veterans Support Group Case Control Study. First Report.
Chris Busby Saoirse Morgan
Occasional Paper 2006/2 Green Audit Aberystwyth
Summary
The Porton Down Veterans Support Group mailed 505 questionnaires to members in order to investigate any possible connection between exposures at Porton Down and subsequent ill health. Members were asked to obtain controls of the same age. There were 261 questionnaires which were returned by veterans together with 123 control questionnaires. This enabled us to conduct a case-control analysis of health in the veterans compared with the controls. For some conditions like cancer, birth outcomes or health in the children we were able to compare the rates in the veterans with national data. The mean age of the 261 veterans who responded was 69.0 (SD = 7.1) and of the 123 controls was 67.6 (SD = 6.1). Most of the experiments were conducted between 1950 and 1960 although some had been carried out as recently as 1989. Cases reported being exposed to Mustard Gas, Sarin and other nerve gases, CS gases and riot agents, to mind altering substances like LSD and to a range of other toxic substances and unknown compounds. Respondents recorded the effects on them at the time and in the period after. The experiments and the immediate effects were bizarre, frightening and often clearly involved major clinical symptoms. Some volunteers were blinded, others woke up in hospital, some took considerable time to recover. We examined cancer in the cases relative to the controls and national data. Levels of cancer in the controls were lower than expected on the basis of national rates. For all malignancy combined, using cancer diagnosed in the period 2001 to 2005 Standardised Incidence Ratio (SIR) based on England and Wales 2002 data was 1.02 in the veterans, equal to the expected level. Significantly high levels of prostate cancer were reported by the veterans (15 cases, SIR 2.6, CI 1.57<RR<4.26; p = 0.0001) and also malignant melanoma (3 cases, SIR = 8.0, CI 1.93<RR<26.8; p = 0.008). The melanoma excess is interesting as it is a biologically plausible cancer following skin exposure to a carcinogen like mustard gas. Comparison of cases with controls for current treatment for on-going conditions showed a significant excess of heart disorders (OR 2.37; CI 1.17-1.89, p= 0.01), arrhythmias (OR 6.7; p = 0.04), respiratory disorders (OR 10.3, 1.44-207, p = 0.01) and diabetes (OR = 4.7 (1.01-7.2; p = 0.03). Cases showed significantly higher levels of many other conditions and illnesses than controls but for some of these e.g. strokes, comparisons with the Welsh Health Survey showed that the levels were not significantly different from those that might be expected in the age group. We examined miscarriages, infertility and child health in the 549 children born to the veterans and the 272 children born to the controls. There were significantly more miscarriages (OR = 2.23, 1.07<OR<4.75, p = 0.02) in the veterans and significantly more infertility (OR infinity based on 28 vs. 0). In addition, the children were significantly more ill with 4.39 times the reported health problems (OR 4.35; 2.08<OR<9.43, p = 0.00001). There were twice the number of child deaths (OR = 1.86 on 38 deaths), mental health problems (11 vs.0), epilepsy (3 vs. 0) and brain damage (5 vs. 0). There was an astonishingly high rate of child cancer reported in the offspring of the veterans including two child leukemias. This represented and SIR of 153 for leukaemia 0-14 (based on 2 cases, p = 0.00000) and 80 for all cancers 0-14 (based on 4 cases; p = 0.00000). Amazingly, there was one child leukaemia reported in the controls, the only child cancer in the controls. Overall, the infertility, the miscarriages and the health of the children of the veterans and their cancer rate, is consistent with genetic damage in the parents. The data supplied on smoking and alcohol was unable to explain any of the observed effects. Veterans were not significantly more likely to have smoked or drunk alcohol than controls and the effects on cancer were second order to the status of the cases. Questions about emotional problems and physical illness or pain and its effect on social behaviour showed the veterans to be significantly more limited than controls. Logistical regression analysis showed such an effect at the p = 0.0001 level for classification of status as a veteran or a control on the basis of effects of both pain and health on social behaviour. Examination of a range of 27 symptoms and conditions (e.g. loss of memory, chest pain, forgetfulness, sleeping difficulties, etc) all showed significantly higher response rates in the veterans than controls with OR ranging from 2.5 to 6.5. Finally the question of whether these effects found in the veterans and their children could be a consequence of selection bias was approached on the basis of analysing the range of diseases manifested in the veterans compared with the range in the controls and in average men of the same age. It is suggested that the peculiar range of illnesses and conditions exhibited by the veterans imply that at least some of their illnesses are the consequence of exposures at Porton. It is argued that if the increases in ill health shown in the veterans were due entirely to self selection then the range and spectrum of conditions would be the same as in the controls, merely the magnitude would be different. It is therefore concluded that this preliminary analysis shows that the Porton Down Veterans have suffered some serious long term health problems as a result of their exposures. The exact extent to which selection bias has affected the results is difficult to asses at this stage. Further statistical work on the data might illuminate the situation.
Introduction
The study is an attempt to examine the question of the long term effects of exposures to various chemical agents used in experiments carried out on army volunteers at the Porton Down establishment in Wiltshire. These experiments on ‘human volunteers’ occurred in the UK mostly between 1950 and 1965 although some experiments were carried out before and after this period and some as recently as the 1990s. The experiments involved exposures to lethal chemical warfare agents including nerve gases and mustard gas and also behaviour altering agents like LSD and crowd control agents, tear gases and to antidotes to these substances. The chemicals were delivered by inhalation, by droplet, by skin contact with impregnated cloths or impregnated clothing. Results were often alarming, resulting in hospitalisation and on at least one occasion in death. Those who were experimented upon in the period of National Service before 1960 have complained in this survey that they were not told the nature of the substances they were being exposed to, and in many cases were told that they would be engaged in research into the common cold. The majority of the living survivors of these experiments are currently aged between 65 and 75. Many are suffering various illnesses and are subject to various conditions which they believe may have been the result of their exposures. This is biologically plausible since some of the agents that were used at Porton Down are known to have serious long term effects. Mustard Gas, for example, is a potent DNA alkylating agent, mutagen and carcinogen; nerve gases may have long term effects on brain function. In order to examine the hypothesis that the exposures may have had any long term effects, the Porton Down Veterans Support Group discussed with Green Audit the possibility of conducting a questionnaire study of their members. It was clear that such a questionnaire had to be short enough for the veterans to be likely to fill it in, contain sufficient questions to bracket the types of health conditions and illnesses that were likely consequences of any chemical exposure, and also be sufficiently open ended enough to pick up any conditions that might define a consequence of exposure that was uncommon in the normal population. In addition, the questionnaire allowed respondents to write about their experiences at the time and shortly after the exposures: it was thought that such a record might be valuable for historians of the events. In order to define the group that was being examined, and in the absence or normative values in the national population for the age group involved, it was necessary to obtain a control group with which to compare the cases. This posed something of a problem given the resources available, yet without a control group, many of the questions being answered would be difficulty to interpret. It was decided to ask each of the cases to obtain a control. In order to avoid the argument that the cases would be choosing particularly healthy controls the cases were asked to choose controls of the same age on the basis of a list of choices that was pre-defined i.e. brother-in-law, nearest neighbour of same age, friend and so forth. Whilst it is conceded that this is not ideal, we believe that this inexpensive approach will give a group of men of the same age that may be used to compare the cases with on some level and that a certain amount of analysis can be employed to examine the general health of this group with that of the exposed cases and obtain meaningful results. For certain illnesses and conditions, e.g. cancer, the cases can, of course, be compared with national data. There remains one major problem with a study of an organisation that has formed in response to concerns about exposure and health, and that is the selection bias that this involves. Clearly it may be argued that such a group may already be selected for ill health, as those veterans of exposures at Porton Down who feel themselves to be healthy may be less likely to join such an association. This is a fair argument. In addition, there is also scope for elective bias in the way in which the survey was conducted. Thus of the 500 questionnaires which sent out only 250 were returned, and it may be argued that those who returned these were from the members who were more ill and that therefore had some need to explain their illness. However, there may be way in which the elective bias in the sample can be analysed. For example, if there is elective bias, it is difficult to see how it could select for certain specific illnesses and conditions. It might be that the veterans represent a more sick group than the controls, for all the reasons given, elective bias, choice of controls etc, but if the spectrum of rates of various illnesses in the controls and the veterans were significantly different, then this would suggest that there is a real effect, a real difference between the controls and the study group, that is, the veterans who were exposed. So these are the problems faced by anyone studying the health of the veterans, and must inform caveats regarding any conclusions that are drawn.
2. The survey The questionnaire (Appendix B) was posted to 505 members of the Porton Down Veterans Support Group in September 2005 and responses returned over the next two months. The questionnaire was accompanied by a letter (Appendix A) which explained its purpose and also explained how each veteran was to try to obtain two controls from among their friends and relations. These controls of roughly the same age and sex were to be picked in the following order:
This process was intended to ensure that veterans were less likely to choose controls who were well, though of course, we have to take on trust the choices of those who returned the questionnaire, and indeed, many veterans were unable to find any controls. In the event, some 123 controls were obtained, less than the number needed to ensure complete balance for a case control study of 261 cases. Nevertheless the number of controls was sufficiently high to ensure that some useful conclusions could be drawn about the health of the exposed group, as the results will show. The questionnaire itself together with the relevant extract of the accompanying letter is attached in Appendix C. It can be seen that in order to make the questionnaire reasonably short, yet obtain the maximum amount of useful information, some questions are open ended and allow the respondent to explain the existence and nature of any health condition that they feel is relevant.
3. Results
3.1 Age groups and period of testing. Returned questionnaires were coded into a database. The numbers and ages of those responding are shown in Table 1 and the distribution of the ages of the cases are plotted in Fig1 and Controls in Fig 2. The groups were fairly similar in distribution of ages with the cases having mean ages slightly higher than the controls. There were 9 cases under the age of 50 years with the youngest being 43. There were only two controls under the age of 50 years; both were aged 49.
Table 1 Ages of those filling out questionnaire
Fig 1 Age distribution of Cases. Mean age 69.08; Standard Deviation 7.1
Fig 2 Age distribution of controls; mean age = 67.65, Standard Deviation = 6.1
Fig 3 Distribution of years that cases were experimented on. Mean = 1956
Cases were experimented upon between 1939 and 1989 but the main period of the experiments was the post war period when there was national service, between 1950 and 1960. This is clear from the histogram of the results given in Fig 3.
3.2 Exposure substances reported (Question 12) Many of the responses contained claims that the respondents had been told that the research was associated with a cure for the common cold. The types of exposure reported were divided by us into three categories: Mustard Gas, Sarin and Other. Not all the respondents remember what the exposures were, but Table 2 shows the number of cases by category of exposure as reported. Table 3 lists the other exposures reported.
Table 2. Numbers of volunteers reporting exposures by category.
Table 3 Some of the substances in the ‘Other Exposures’ category reported in responses.
3.3 What sort of tests were reported (Question 13) This open ended question was generally answered but the answers have not been yet coded into the database as there are many different answers. Tests involved exposure to gases, to droplets on the skin, to substances saturated in cloths and clothing. Men were exposed naked and photographed, were exposed in full protective suits, had to wear underpants saturated with unknown liquids which burned their skin, the procedures were often bizarre and frightening.
3.4 Clinical and physical responses to the tests at the time (Question 14 and 15) These responses have been entered into the database and are listed in the Appendix B Table B1. They show a wide range of clearly major and frightening clinical effects caused by the exposures immediately after the tests. Some volunteers were temporarily blinded. Some woke up in hospital after passing out. We know that at least one volunteer died. In addition there were significant effects in the first few months after the tests and these are listed in Table B2.
3.5 Cancer Cancer reported by the cases and the controls as having been diagnosed in the last five year (2001-2005) is listed in Table 4 below and in Table 5 is listed all the numbers of individuals reporting cancers diagnosed. For Table 5, if there are two cancers reported in the same individual both cancers are included. The raw data is reproduced in Appendix B Tables B3 and B4. In Table 6 are given the Relative Risks for the main cancers reported in the last 5 year period 2001-5. These are calculated as Standardised Incidence Ratios based on England and Wales National incidence rates for 2002 (Office for National Statistics Series MB 1 No 32).
Table 4 Cancers reported in the cases and controls in 5 years between 2001 and 2005; where the year of diagnosis was not give the possible total is bracketed.
Table 5. All cancers reported in the cases and controls by site irrespective of when diagnosed. If an individual reports more than one cancer, the cancer is included.
NMSC = Non melanoma skin cancer.
Table 6 Relative Risks 2001-2005. Standardised Incidence Ratios are calculated on England and Wales rates for 2002 and represent the risk of cancer relative to the national average after allowing for age. Thus for melanoma, there are eight times the number in the cases that would be expected on the basis of the national rates in 2002 after allowing for age. Significant cancer incidence sites are given a *.
There is clearly a statistically significant 2.6-fold excess of prostate cancer in the veterans, both relative to the controls and to the national population. There is also a significant eight-fold excess of malignant melanoma reported together with a small, non-significant excess of colorectal cancer. Looking at the overall reported cancer, it seems that the cancers reported are from regions of the body that are near the lower abdomen. Thus we see 6 bladder cancers, 4 colorectal cancers, 2 testicular cancers and 18 prostate cancers. Prostate, lung and colorectal cancer are the most common cancer in men of this age group. We see here a preponderance of prostate cancer with no reports of lung cancer in either the cases of the controls. This may be because of the fatality of lung cancer, but it still seems unusual and suggests that the prostate cancers are significant in the group. The melanoma incidence rate of 8-times the national average is unusually high, but this is based on three cases and it is suggested that a larger study concentrate on this, especially since many of the exposures were to carcinogenic substances applied to the skin.
3.6 Current treatment for any health conditions Question 20-21 One open ended question asked if respondents were currently being treated for any chronic or on-going health condition by a doctor. Responses were reduced to the database and are listed in Table B5. In order to compare the prevalence in the cases and controls we gathered the conditions into groups which were roughly based first on the standard classifications of causes of death and second on recognised illnesses. Comparisons of the cases and controls was then carried out and the results given in Table 7. In Table 8 are listed conditions reported by the cases that are not shown in the controls. From these results it seems that the cases more generally sick than the controls and are being treated for various condition that separate them from the controls. These conditions are listed in Table 9.
Table 7 Comparison of cases and controls for current chronic and on-going health conditions which are manifested in both groups. Conditions where the excess reported prevalence is statistically significant are shown * in the Odds Ratio column.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
