University Department of Pharmaceutical Sciences Evaluative Report of the Programme Name of the Programme: University Department of Pharmaceutical Sciences Year of establishment : Is the Department part of a School/Faculty of the university? Faculty of Science and Technology Names of programmes offered (UG, PG, M.Phil., Ph.D., Integrated Masters; Integrated Ph.D., D.Sc., D.Litt., etc.) : a. PG - M. Pharm. in six different specializations viz.,
Britishlegion.org.ukGulf report 4/5/07 09:33 Page 1 a legacy of suspicion Gulf report 4/5/07 09:33 Page 2 Gulf War: a legacy of suspicion "In essence, GWS [Gulf War Syndrome] merely is a convenient descriptive term thatdescribes a phenomenon: GWV [Gulf War veterans] reporting suffering from medicallyunexplained health related symptoms. In the sense, it shares much with the other medicallyunexplained syndromes encountered in practice. The real debate surrounding medicallyunexplained conditions is not whether or not they exist, but defining their cause. In thisregard, investigators fall into two camps. One camp insists that the conditions are causedby a yet-to-be-discovered medical problem, rejecting out of hand the possibility of apsychologic origin. The other camp insists the conditions are fundamentally psychogenic,rejecting the possibility of an undiscovered medical condition. The evidence shows,however, that the conditions exist, the suffering is real, and the causes are unknown."(Gronseth, 2005) Gulf report 4/5/07 09:33 Page 3 The Extent of Gulf War Illnesses Investigations into the Prime Suspects Additional UK Research Further UK Research United States (US) Research Research Funding & Monitoring Current Compensation Arrangements Labels Applied to WarDisablement Pensions The Application of the Label‘Gulf War Syndrome' Calls for a Public Inquiry Gulf report 4/5/07 09:33 Page 4 1. Executive Summary Of the 53,500 troops deployed to the Gulf War 1990-91 there are now close to 7,000 whohave received a payment or are in receipt of a War Pension for illness or injury relating totheir preparation to deploy or active service in the Gulf (SPVA, 2007).
The Gulf War has been labelled the most toxic war in history. Troops were exposed to a rangeof vaccinations, pyridostigymine bromide, organophosphates (and other pesticides), nerveagents, depleted uranium, environmental hazards, stress and smoke from burning oil wells.
Gulf War veterans are more than twice as likely to report symptoms of ill health, and to besuffering more severely from them, than their military contemporaries of equivalent age,gender, rank and branch of service (Gray et al., 1998). However, the range of symptoms isnot unique to Gulf veterans and there is no distinct medical condition (MRC, 2003).
Symptoms affecting Gulf War veterans largely fall into four categories – musculoskeletalsymptoms, neurological symptoms, respiratory symptoms and psychological symptoms(although there are illnesses and symptoms that fall outside these categories) (Simmons etal., 2004).
Epidemiological studies used to investigate causal links with illness have been hampered bythe lack of accurate data, including service records and medical and/or vaccination records(MRC, 2003). Further barriers to effective investigation into the causes of Gulf War illnessesare in place because health surveillance was not carried out during deployment, or with thebenefit of hindsight, immediately post deployment (KCL, 2006).
The main suspects in the search for the causes of Gulf War illnesses are: medicalcountermeasures [including vaccinations and Nerve Agent Pre-treatment Sets (NAPS)];depleted uranium; organophosphates; exposure to chemical weapons (sarin and cyclosarin);and stress and psychological factors. Completed research in the UK has now discountedmost of these as the single cause of Gulf War illnesses (MRC, 2003); however, work iscurrently underway in the US, and elsewhere, investigating the possible "cocktail effect" ofthese multiple exposures.
There were multiple administrative problems with the programme of medicalcountermeasures in the lead-up to and during deployment of British troops to Kuwait andIraq. These included omitting vaccinations from medical records (Bach, 2003), breaches ofthe policy of voluntary informed consent (MoD, 1997), the use of unlicensed and unprovenvaccinations and ignoring medical advice from the DoH (Bach, 2003).
There has been some inconclusive evidence on possible links between self-reported use oforganophosphate pesticides and ill health (Cherry et al., 2001). There is a need for furtherwork regarding the hazard of occupational exposure to organophosphates (OPs) and anyadditional effects on people with reduced activity of the enzyme paraoxonase 1 (PON1).
The government gave a misleading assurance to Parliament in 1994 that only a smallnumber of Iraqi prisoners i.e. no UK personnel, were exposed to organophosphates andother pesticides. A subsequent investigation, in 1996, found that a considerable number ofUK troops, and their equipment, had been treated with OPs and that some products hadbeen purchased locally - there is conflicting evidence regarding whether or not they were Gulf report 4/5/07 09:33 Page 5 used correctly. However, it is undeniable that the false statement to MPs caused asignificant delay and hindered meaningful research.
1.10. There has been disagreement among different agencies regarding the plume modelling carried out on the destruction of chemical weapons at Khamisiyah (GAO, 2004). However,there is agreement that no further modelling of the plume should take place withoutsignificant improvements to the source data (MoD, 2005). The government has concludedthat around 9,000 UK troops were located in the area of possible exposure, but that anypossible exposure would be at an extremely low level (MoD, 2005). This lack of reliableexposure data has again hindered research which attempts to link exposure with healthoutcomes. Again, delays in identifying the scale of the incident have reduced chances ofestablishing reliable results.
1.11. Mortality data does not demonstrate an increased number of deaths among Gulf War veterans (the comparison group consisting of Armed Forces personnel of similar profile interms of gender, service, regular/reservist status and rank, who were in Service on 1 January 1991 but were not deployed to the Gulf). However, there are small increases inthe number of deaths caused by suicide and road traffic accidents. 1.12. There is a recognised need for research into rehabilitation, health and social care models that can improve the quality of life for Gulf War veterans and their families (MRC, 2003); anda range of models should be investigated.
1.13. The US continues to make significant investment into research on Gulf War illnesses (VA, 2005). The programme is segregated into five different areas, these are: brain and nervoussystem function; environmental toxicology; immune function and infectious diseases;reproductive health; and symptoms and general health. While the UK has a process formonitoring the results of this research, the results need to be regularly reported to veteransin an easily understood format. 1.14. Gulf War veterans are currently compensated through the War Pensions Scheme for illnesses or injuries relating to Service. This is the same scheme that operates for all otherveterans who became ill or sustained an injury before April 2005. 1.15. The government have argued that the label "Gulf War Syndrome" should not replace the label Signs and Symptoms of Ill-Defined Conditions (SSIDC) on War Disablement Pensionsbecause it would exclude the use of "Gulf War Syndrome" for those with recognisedmedical conditions. The government has also rightly discounted the use of a positive list ofsymptoms or disorders. However, it should be possible to use the label "Gulf WarSyndrome" as a replacement for SSIDC, and, as an umbrella label for a range of recognisedmedical conditions.
1.16. The government has continually stated that the time is not right for a public inquiry into the causes of Gulf War illnesses and the handling of the surrounding issues. The reasonsgiven for this have been the ongoing scientific and medical investigations (Crawley, 2004).
However, some scientific and medical experts have now concluded that further clinical orcausal investigations will probably not produce any further useful outcomes (MRC, 2003).
The government now needs to make a definitive statement regarding a public inquiry.
Gulf report 4/5/07 09:33 Page 6 1. Executive Summary 1.17. In 2004, Rt. Hon. Lord Lloyd of Berwick made a recommendation for an ex gratia payment for Gulf War veterans. An ex gratia payment should now be offered – based on thegovernment's failure to protect veterans, the treatment they have received and the resultinganxiety. This payment should be set at £10,000 (in line with other UK ex gratia paymentschemes), and should not be confused with compensation for illnesses or injuries. The payment should be awarded to all Gulf War veterans who have received a Gratuity orWar Disablement Pension, Gulf War widow(er)s in receipt of a Widows Pension and childrenof Gulf War veterans who are in receipt of a War Orphans Pension.
Gulf report 4/5/07 09:33 Page 7 2. Policy Priorities The government should commission research into the health effects of organophosphateexposure and reduced activity of the enzyme paraoxonase 1 (PON1), under the guidance ofthe Medical Research Council (MRC).
2.2. The MRC should be formally asked by the government to consider the preliminary work being carried out in the US into multiple exposures to neurotoxins and stress and theirsynergistic effects, and to make recommendations for UK studies in this area.
2.3. Studies evaluating a range of differing rehabilitation, health and social care models, which aim to deliver improvements to quality of life and general health, should be commissionedby the government as soon as possible.
2.4. The two research proposals recommended by the Gulf War Group should be funded by central government, subject to satisfactory peer review by the MRC.
2.5. Updates on the US research programme should be provided to all Gulf War veterans in receipt of a War Disablement Pension; this should be provided as a service by the ServicePersonnel & Veterans Agency (SPVA); it should be regular and in an easily understoodformat.
2.6. The government should agree how the term "Gulf War Syndrome" should be applied to War Disablement Pensions. Once agreed, all Gulf veterans in receipt of a War DisablementPension should be formally informed of the policy and how they can have the term applied –this process need not involve any reassessment of awarded War Disablement Pensions.
The government should announce whether or not there is any possibility of a public inquirynow or in the future. This would also be an ideal opportunity for the government to make aformal apology to Gulf War veterans for their treatment since their return from activeservice.
2.8. Ex gratia payments of £10,000 should be paid to Gulf veterans, widow(er)s and children in receipt of a War Pension (Disablement, Widow(er)s or Orphans respectively), which is in anyway linked to Service in the Gulf 1990-91.
Gulf report 4/5/07 09:33 Page 8 This document examines the issues surrounding Gulf War illnesses and the current supportprovisions for veterans of the 1990-91 Gulf War. It is intended to inform policy makers, and thosewith an ongoing interest in the issue, on the progress that has been made to date, the issuesthat remain outstanding and how they might be resolved.
Recently, Gulf War veterans and those campaigning on their behalf have been calling for "closure".
However, "closure" is a very personal consideration for veterans and what constitutes "closure"will be wide ranging and unique to the individuals involved. Therefore, while this paper looks atwhat might constitute a fair solution to some of the issues, veterans' groups will work towardsimproved treatment and support for many years to come. Gulf report 4/5/07 09:33 Page 9 The Gulf War occurred between September 1990 and February 1991. The war was a response tothe Iraqi invasion of Kuwait in August 1990. Over the period approximately 53,500 British troopswere deployed. By far the biggest contingent was from the US, who deployed close to 700,000Service personnel to the area. Troops from France, Canada and Australia were also present. Due to the possible use of both chemical and biological weapons, medical countermeasures weretaken to protect British troops. These included the provision of Nerve Agent Pre-treatment Sets(NAPS). NAPS contain pyridostigymine bromide (PB), and are used to block nerve gas agents longenough for them to be broken down by the body. NAPS were accepted for use in the ArmedForces in 1981. In addition to the normal vaccination regime prior to deployment, British troopswere also vaccinated for anthrax and plague. The Ministry of Defence (MoD) maintain that anthraxand plague vaccinations were given with informed consent. However, this has been disputed bymany veterans.
The Gulf War has been coined the most toxic war in history – labelled as such because troopswere exposed to an unprecedented range of toxic substances while in theatre. In addition tomedical countermeasures, toxins included organophosphates, used to control environmentalhazards, dust, nerve agents including sarin and cyclosarin, depleted uranium used in armourpiecing munitions and smoke from burning oil wells.
Since 1993 veterans have been reporting a range of illnesses. In September 2005 there were2,920 (Lord Drayson, 2006) veterans in receipt of a War Disablement Pension (ongoingcompensation payments under the War Pension Scheme for an illness or injury linked to Service)and by March 2004 there had been 2,235 (Lord Lloyd, 2004) Gratuities awarded under the WarPension Scheme. These figures have since risen - in April 2007, the Service Personnel & Veterans Agency (SPVA)stated that there were 6,718 Gulf veterans who had received an award under the War PensionScheme (War Disablement Pension or Gratuity), and that 1,598 of them had claimed that theircondition/s were related to Gulf War illnesses. There were 42 widows in receipt of a War WidowsPension and 2 children in receipt of a War Orphans Pension.
The MoD has not reported the number of veterans claiming a War Disablement Pension for GulfWar illnesses or "Gulf War Syndrome", as the figure can only be quantified through theexamination of each individual case. However, in November 2006, Lord Drayson made thefollowing statement: "I gave an answer earlier relating to the number of Gulf War veterans for whom the Gulf Warillness issue is of most concern. Our understanding in the Ministry of Defence, through liaisonwith the representatives of those Gulf War veterans, is that it is approximately 1,300 people." Among Gulf veterans suffering from illness, the most commonly reported post-conflict symptomsare chronic fatigue, sexual dysfunction, headaches, muscle pain, joint pain, mood swings, loss ofconcentration, memory loss, tingling and depression; however, this is not a definitive list.
Gulf report 4/5/07 09:33 Page 10 3. The extent of Gulf War illnesses Epidemiological studies are those that research the incidence, distribution and control of diseasein a population. In 2003, the MRC had the following to say about UK epidemiological studiescarried out into Gulf War illnesses (MRC, 2003): "Epidemiology looks at the patterns and distribution of disease in different groups of people, tofind out what its causes are and identify factors that make some people more susceptible thanothers.
"The MRC/MoD Gulf Veterans' illnesses research programme funded several epidemiologicalstudies. These set out first to look for common factors specific to Gulf Service that mightexplain GVs' illnesses, so that any promising leads could then be further investigated to pindown the causes.
"Independent records or measurements showing precisely what people were exposed to,produce the strongest epidemiological evidence. A dearth of such details about the 1991 Gulfconflict has consistently impeded later epidemiological studies. For this reason, most researchhas had to rely on GV's recollections, often more than five years after their Service." UK epidemiological studies, the results of which have now been widely accepted, show that GulfWar veterans are more than twice as likely to report symptoms of ill health, and to be sufferingmore severely from them, than non-Gulf War veterans (24% vs. 10%) (Gray et al., 1998). Studiestypically compare the Gulf veterans with a control group of non-Gulf War veterans, being militarycontemporaries with equivalent age, gender, rank and branch of Service. The MRC have also concluded that more than 10 years after deployment Gulf War veteranscontinue to suffer ill health, but that the range of symptoms is not unique. In short, Gulf Warveterans report similar symptoms and symptom groupings as non-Gulf veterans, albeit in greaternumbers and with greater severity. The largest epidemiological study into morbidity among Gulf War veterans was carried out in 2004(Simmons et al., 2004). This study asked both Gulf War veterans and a comparable cohort of non-Gulf War veterans to detail, in free-text, any change in health status since 1990. The questionnairealso asked the question "Do you consider that you have ‘Gulf War Syndrome'?" The paperreported on 42,818 male responders to the questionnaire. The results of the study included: "61% of GWV [Gulf War veterans] reported at least one new medical symptom since 1990compared with 37% of NGWV [non-Gulf War veterans]." "For over 85% of categories of ill health, symptom/disease prevalence was higher amongGWV. Strongest associations with Gulf War Service included mood swings, memory loss/lackof concentration, night sweats and sexual dysfunction." "In terms of the nature of self-reported ill health, we found similar results to the range ofsymptoms that have been reported elsewhere. Gray et al. study of GWV found that over 50percent of diagnoses could be classified into four large categories: diseases of themusculoskeletal system and connective tissue (19.0%), mental disorders (14.7%), diseases ofthe respiratory system (10.5%) and diseases of the skin and subcutaneous tissue (9.4%). Inour study the same four categories accounted for 50.3 per cent of all reported symptoms/ Gulf report 4/5/07 09:33 Page 11 diseases and this figure rises to over 70 per cent when the categories of fatigue and nervoussystem disorders are included." What these two different studies [one being a population based questionnaire study, the otherbased on medical examinations of US Gulf veterans participating in the US equivalent of the GulfVeteran Medical Assessment Programme (GVMAP)] show is that symptomatic Gulf veterans tendto experience symptoms associated with the: musculoskeletal system; respiratory system; and Simmons et al. also reported that in answer to the question regarding ‘Gulf War Syndrome', 5.6%of responders believed that they had Gulf War Syndrome, while 40.9% stated that they wereunsure. The high number of responders stating that they were "unsure" could possibly beattributed to the confusion over the term and its use; particularly its meaning and status as arecognised medical condition.
It has been reported that Gulf War illnesses are not connected to the branch of the Armed Forcesveterans served in, the proximity to combat or the job that was being performed. There areequally no links between illness and gender or being a regular or reserve member of the ArmedForces. When considering these factors, it seems that anyone who served in the Gulf War wasequally at risk of illness (KCL, 2006). One small study in the US (cohort of 1,548 veterans), haslinked excess health problems, in Gulf veterans from Kansas, with the type of Service performed(Steele, 2000): "The prevalence of Gulf War illness was lowest among PGW [Persian Gulf War] veterans whoserved on board ship (21%) and highest among those who were in Iraq and/or Kuwait (42%).
Among PGW veterans who served away from battlefield areas, Gulf War illness was leastprevalent among those who departed in June or July of 1991 (41%). Observed patternssuggest that excess morbidity among Gulf War veterans is associated with characteristics oftheir wartime service…" The limitations of epidemiological research in investigating Gulf War illnesses need to behighlighted further; touched on by the MRC in 2003. The majority of epidemiological studiescarried out on the health outcomes of Gulf War veterans have compared them to the healthoutcomes of other military comparison groups. The link with Service in the Gulf has usually beenverified through the use of nominal rolls, although these have been found to be inaccurate (Glasset al., 2006). The levels and types of exposure to harmful agents has also been extremely difficultto quantify due to the unavailability of reliable data; including the lack of written consent forvaccinations, lost medical records, absence of health surveillance and uncertainty surroundingchemical weapon plume modelling.
This has led to the development of other methods of linking ill health with exposures related toService in the Gulf. Self-reported questionnaires have been the most used method of exposureassessment, used because of the lack of exposure evidence collected during the conflict and theinaccuracy of nominal and medical records. These, and other problems, have led to continuing Gulf report 4/5/07 09:33 Page 12 3. The extent of Gulf War illnesses questions relating to reported exposures to harmful agents and links to the symptoms reportedby Gulf War veterans. The need for improved methods for future studies into post-combatdisorders has been identified (Glass et al., 2006): "The application of any of these exposure methods will be most effective if planned beforedeployment and the investigations take place during the deployment or soon after veteransreturn from theatre." The question that has not been asked, is that if the government knew that troops would beexposed to serious health risks, including known toxins such as nerve agents, pesticides,insecticides, rodenticides, depleted uranium (previously unused), smoke and exhaust fumes, whywere these risks not better controlled – and more importantly – why was health surveillance notcarried out at the time? This is particularly pertinent considering that "post combat syndromes have arisen after all majorwars over the last century, and we can predict that they will continue to appear after futureconflicts" (Jones, 2006). Gulf report 4/5/07 09:33 Page 13 4. Investigations into the prime suspects As stated, personnel deployed to the Gulf in the early 1990s were exposed to a number ofharmful agents. These have since become the prime suspects in the search for an explanation tothe increased number of veterans experiencing more severe illnesses post Gulf War; they are: medical countermeasures (including vaccinations and NAPS); depleted uranium (DU); organophosphates (OPs); exposure to chemical weapons (sarin and cyclosarin); and stress and psychological factors.
4.1. Medical Countermeasures (vaccinations and NAPS)
Due to the high risk of chemical and biological weapons being used during the Gulf War,extensive medical countermeasures were undertaken both prior to deployment and in theatre. Atthe time, British Service personnel were routinely given vaccinations, including yellow fever,tetanus, typhoid, poliomyelitis, cholera and hepatitis B; some personnel also received meningitisand hepatitis A. To offer troops some protection against biological weapons, they were also inoculated withplague and anthrax. The anthrax vaccine was given in combination with the whooping cough(pertussis) vaccine to boost the immune response. The MoD later explained that the boost wasrequired due to the short time available between administering the vaccine and the expectedstart of hostilities (Bach, 2003).
The MoD, in their document entitled "Background to the Use of Medical Countermeasures toProtect British Forces during the Gulf War (Operation GRANBY)" (October 1997) noted: "The overall policy was that these vaccines should be administered on the basis of voluntaryinformed consent. The MoD is aware that many veterans regard this policy as having beenbreached in practice." Many veterans recall being ordered to take medical countermeasures and it is important to seethis in a Military context i.e. failure to comply resulting in disciplinary action. Problems relating to the administration of medical countermeasures have been compounded bythe lack of evidence in this area. In October 2003 Lord Bach explained: "As you know, personal medical records (F Med 4) were generally not taken to the Gulf duringthe 1990-91 conflict, and were therefore unavailable for the recording of vaccination details.
However, the names of those who received vaccinations should have been recorded ontemporary nominal rolls compiled in theatre. Whenever possible, details should also have beenrecorded on form B Med 27, but many personnel who deployed to the Gulf did not carry thesedocuments. The details recorded on nominal rolls and B Med 27s should have been transcribedonto F Med 4s on return from the Gulf. In many cases this did not happen, and the vaccinationrecords of many Gulf veterans are incomplete as a result. Estimates of the precise extent towhich vaccination schedules were complied with in practice, therefore, are not readilyavailable. Similarly, the extent to which Defence Medical Services staff discussed with patientsissues such as what other medication individuals were receiving is not readily available." Gulf report 4/5/07 09:33 Page 14 4. Investigations into the prime suspects For these reasons, it is now impossible for the MoD to replicate the exact exposures to medicalcountermeasures experienced by Gulf War veterans. During the Gulf War there was little controlover what vaccinations or NAPS were administered or when; how consent should be sought andrecorded; or what medical information should be given to Service personnel to enable them togive informed consent. Having said this, the government continues to claim that researchconducted into the health effects of medical countermeasures replicate the experiences of GulfWar veterans. The Parliamentary Under Secretary of State and Minister for Veterans, Mr Derek Twigg, recently(October 2006) announced the final results of the Vaccines Interaction Research Programme. Inhis statement he concluded: "The overwhelming evidence from the programme is that the combination of vaccines andtablets that were offered to UK Forces at the time of the 1990-91 Gulf Conflict would not havehad adverse health effects." The key word in this statement is "offered", as the study could not replicate the combination ofvaccines and tablets actually taken, because they are simply not known. A point confirmed duringoral evidence to the Lord Lloyd Inquiry (2004) by the Chairman of the group overseeing theresearch, Professor Donald Davies stated: "I should emphasise, this was not an attempt to set up or reproduce conditions experiencedby personnel in the Gulf. It was simply to look at the interactions of vaccines and theinteractions of the vaccine with that chemical. That was the specific question for this research." The Vaccines Interaction Research Programme included three studies into the interactions ofvaccines and NAPS. The main study involved monitoring marmosets for up to 18 months(equivalent to long-term health monitoring in humans) after being administered with vaccinesand/or pyridostigmine bromide (the active ingredient in NAPS). However, an important element not included in the study was the compound or additive effect ofstress. Again, during oral evidence to the Lord Lloyd Inquiry (2004), Professor Banatvala, whocarried out the final phase of the Vaccines Interactions Research Programme, said: "There is one other point, sir, which I think is relevant because the problem of stress has beenbrought out among the Gulf War veterans time and again, and in publications and so forth, andSimon Wessley, I believe, is going to talk to you. One thing that we could not do and wouldnot wish to do was to stress our animals. That is the one major difference." The Vaccines Interactions Research Programme, including the 18-month study involvingmarmosets, rules out medical countermeasures, when given in accordance with conventionalmedical procedures, as the cause of Gulf War illnesses. However, for the reasons outlined herethey cannot be ruled out as a contributory factor for ill health in Gulf War veterans.
King's College London (KCL, 2006) also recently reported on epidemiological and immunologicalstudies which did link reported symptoms of ill health in Gulf War veterans and multiplevaccinations and stress. They concluded: Gulf report 4/5/07 09:34 Page 15 "Yes, there is a link between multiple vaccination and ill health, but we have not confirmedthat this operates via the immune system. Perhaps it is mediated by stress, or there remainsan outside possibility that despite every effort, it is still a question of bias in memory records.
We probably cannot take this story any further in studies on Gulf War veterans, but new animalstudies, and US studies in new recruits, may still shed further light." Whether or not medical countermeasures are the cause or contributed to Gulf War illnesses, theinvestigation into how vaccinations and NAPS were administered has brought into focus otherissues for concern. The first of these was the use of unlicensed products on UK troops. The MoD(1997) took this decision: "A number of the medical countermeasures used during Op GRANBY were unlicensed in theUK at the time. In each case the decision to use an unlicensed product reflected the need toprotect British troops against a specific threat in the absence of an appropriate UK licensedalternative." It is reasonable to expect that faced with a specific threat, the government would choose to takeextreme action to protect our Armed Forces personnel. However, there is further evidence whichdemonstrates that during the licensing process concerns were raised with regard to using thewhooping cough vaccine in combination with the anthrax vaccine. Specifically, at the time,whooping cough vaccine was not recommended for use in adults, and not recommended for useas an adjuvant (a substance to accelerate the immune response). For this reason the National Institute for Biological Standards and Controls (NIBSC) carried outsome preliminary work to investigate the health effects. The NIBSC gave one standard humandose (SHD) to a mouse, which is approximately 160 times the human equivalent on the basis ofbody weight. The NIBSC found that there was severe loss of condition and weight in the mice.
However, despite the massive dose, the NIBSC still raised concerns with the Department ofHealth (DoH).
The DoH brought these concerns to the attention of the MoD. However, there is no evidence thatthe research findings were taken into account (Lord Bach, 2003). Then in 1998, credibility wasgiven to the work carried out by the NIBSC back in 1990. This occurred when the manufacturersof the anthrax vaccine, the Centre for Applied Microbiology and Research (CAMR), applied toextend the shelf life of the product. The request was made through the NIBSC to the MedicinesControl Agency (MCA).
On 3 February 1998, the NIBSC wrote to the MCA to give advice on extending the shelf-life ofthe anthrax vaccine. The NIBSC recommended to the MCA that the shelf life be extended, butnot beyond November 1998. This advice was given based on the results of their earlier study onmice in 1990 and the age of the vaccine (Lord Bach, 2003). The MCA later issued an approvalletter, in this letter they stated: "The vaccine is to be used alone. There is no evidence for safe use in combination with othervaccines or medicinal products." Then in 1998 the MoD's Advisory Group on Medical Countermeasures (AGMC) finallyrecommended that UK Forces, due to deploy, should be offered immunisation against anthrax, Gulf report 4/5/07 09:34 Page 16 4. Investigations into the prime suspects but without an adjuvant (without the whooping cough vaccine). In March 1998, in readiness forOperation BOLTON, the MoD announced that vaccination against anthrax would again begin andit made clear that "no other vaccine will be co-administered with the anthrax vaccine." Further, the then Secretary of State for Defence, in a letter to all personnel stated: "…administering it on its own avoids any possibility of side-effects caused by interactions withanother vaccine used as an adjuvant." Finally, in 2003 the MoD removed their advice on the co-administration of the anthrax vaccine;they stated that the original recommendations were made because the precautionary principlewas being adopted, and due to the age of the batches in question; the advice now read (LordBach, 2003): "Anthrax vaccine must not be mixed with any other vaccine or other medicinal product in thesame syringe. If necessary, anthrax vaccine may be given at the same time as other vaccines.
Other injectable vaccines should be administered by separate injections into differentanatomical sites and, ideally, into different limbs." Anthrax and the whooping cough vaccine could again be used in combination – 13 years afterthey were first given to those deploying to the Gulf. Depleted uranium (DU)
DU is a by-product of the separation process used on natural uranium to produce Enricheduranium. DU is 1.7 times more dense than lead. This dense material is used in armour piercingweapons – such as the tank penetrating rounds used by the UK Challenger 2.
DU is radioactive, but only slightly; it is 40% less radioactive than naturally occurring Uranium, andwith a chemical toxicity roughly equivalent to other heavy metals such as lead. When DUweapons strike a target, the DU undergoes spontaneous combustion and substantial amounts ofDU are converted into a cloud of particles which can be inhaled and ingested. This is generallyhow DU enters the body; however, it can also enter the body if a person receives a DU shrapnelwound, where the metal remains embedded.
Exposure to DU through "friendly fire" incidents was particularly felt by US troops. During a veryshort period in 1991, 115 US troops were mistakenly fired upon by US forces by weapons usingDU metals. There were 11 fatalities and 50 casualties from these particular incidents. For the wounded tank crew members, and those that rescued them, there were particularly highrisks of DU contamination from inhalation and ingestion, wound contamination and embedded DUshrapnel. These veterans, referred to as "DU-exposed" have been the subject of ongoing clinicalassessments in the US. The method used to measure levels of exposure is the excretion of DUthrough urine. The most recent article on this cohort reported (Squibb et al., 2006): "The Baltimore VA [Department of Veterans Affairs] DU Follow-up Program continues toconduct health surveillance in a cohort of Gulf War soldiers exposed to DU when they were inor on vehicles hit by friendly fire involving munitions with DU penetrators. Urine U [uranium] Gulf report 4/5/07 09:34 Page 17 concentrations remain elevated in veterans with embedded DU fragments, demonstrating achronic systemic exposure to U in this group of soldiers. Not all soldiers in the ‘DU-exposed'Gulf War friendly fire cohort have embedded DU fragments; thus potential health effects fromDU exposure by inhalation, ingestion and wound contamination alone are also being monitoredthrough this programme. With the exception of the elevated urine U excretion, no clinicallysignificant, expected U-related health effects have yet been identified in veterans with orwithout embedded fragments, though subtle changes in renal function and genotoxicitymarkers in soldiers with urine U concentrations greater than 0.1µg-1 creatinine have beenobserved." In the UK, work has also taken place. The Depleted Uranium Oversight Board (DUOB) has veryrecently reported on its work over the past five years. The programme has been assessingveterans for significant exposures to DU. After establishing analytical and verification methods for the study, veterans were invited toprovide urine samples for testing; this began in September 2004 and continued until January2006.
The Minister of State, Ministry of Defence, Lord Drayson announced the results in March 2007: "The Depleted Uranium Oversight Board (DUOB) was established in 2001 to oversee ascreening programme for veterans of the 1991 Gulf conflict and subsequent Balkansoperations concerned about possible exposure to depleted uranium. Testing based on theanalysis of urine samples for trace quantities of uranium isotopes was offered between 2004and 2006. A total of 496 applicants completed the test.
The board was unable to achieve complete consensus on the interpretation and significance ofthe test results; however, no evidence of the excretion of depleted uranium was found in theurine of any of the test participants. According to mainstream scientific and medical opinion,this means that none had suffered an exposure to DU of sufficient magnitude likely to cause arisk to their health." The DUOB were also asked to consider the potential for epidemiological studies of exposure toDU and associations with health outcomes and the scope for commissioning of such research.
However, the DUOB concluded that "once it became clear that any detectable exposure would beextremely rare, this idea was abandoned." (DUOB, 2007).
The use of organophosphate during the Gulf War, and the illnesses that have since been reported,are closely linked to the use of other neurotoxins used during the conflict. This is because they allbelong to a single class of compounds that adversely affect the nervous system. This group ofnerve agents include OPs, sarin and NAPS.
Organophosphates (OPs) are a group of synthetic chemical compounds that affect thetransmission of nerve signals in the body. Nerve signals are transmitted by a molecule called N-acetylcholine. When ingested or inhaled, organophosphates inhibit the enzymeacetylcholinesterase (ACE) which breaks down acetylcholine in the body. This inability of the body Gulf report 4/5/07 09:34 Page 18 4. Investigations into the prime suspects to break down acetylcholine causes a build up of N-acetylcholine at nerve junctions and disruptsthe physiological processes. Reported symptoms of organophosphate poisoning include fatigue, memory loss, blurred vision,cold sweats, weakness, hypotension, joint and muscle pain and depression. These are generallyrelated to low-level exposures over an extended period. The MRC, in 2003, reported that "theimmediate effects of OP poisoning are headaches, diarrhoea and paralysis". With reference to thepotential exposures to OPs during the Gulf War the MRC stated: "[T]here is little information on the quantity of OP pesticides handled, or how these were used[during the Gulf War]. No cases of acute OP poisoning were reported at the time, making itunlikely that exposure levels were ever high enough to account for the kinds of symptomsexperienced later." However, one of the UK epidemiological studies did make a weak link with self-reported ill healthamong Gulf veterans and the handling of organophosphates. The study reported (Cherry et al., 2001): "The relations between exposures and ill health were generally weak. Consistent, specific andcredible relations, warranting further investigation, were found between health indices and twoexposures, the reported number of inoculations and days handling pesticides." The lack of presentation of illness at the time, particularly symptoms of headache and diarrhoea,could be attributed to a number of factors. Namely, the fact that these illnesses were probablycommon during the conflict, not presented for medical treatment, or not presented in connectionwith the use of pesticides. Additionally, as already stated, the government has admitted to theabsence of complete medical records, and therefore, the statement that "no cases of acute OPpoisoning were reported" cannot be made with absolute certainty. There are also substantial reasons for mistrust regarding the use of organophosphates during theGulf War. On 11 July 1994, the government stated in written answers that: "No organophosphateinsecticide or pesticide sprays were used by British Forces." By October 1996, the governmentwere willing to accept that there had been use of organophosphate chemicals in the Gulf andannounced that they would conduct an investigation into both the use of OPs during the Gulf Warand how previous parliamentary questions had been answered. On 10 December 1996, theMinister for State for the Armed Forces, Mr Nicholas Soames made a statement: "…[T]he investigation team discovered that OP pesticides were indeed used by our troops inthe Gulf to deal with the serious threat posed by fly-borne disease on a much wider scale thanpreviously reported. Secondly, the investigation team discovered that, with the exception ofthe possible small-scale use of pesticides obtained incorrectly, there is no evidence that theywere incorrectly used." Then on 26 February 1997, Mr Soames announced the conclusions of the further investigation –these were: "a) The answers to six PQs [parliamentary questions] in 1994 concerning pesticide usage duringOperation GRANBY were incorrect because Ministers were given flawed advice by Service and CivilService staff, who had obtained and used inaccurate information when preparing the draft answers.
Gulf report 4/5/07 09:34 Page 19 "b) The submission of flawed advice concerning pesticides to Minsters in July 1994 and againin November 1994, together with repeated submissions of the same inaccurate information atlater dates, constituted a fundamental failure of the working practices adopted by Service andCivil Service staff within the area of MoD concerned.
"c) As a result of internal confusion about the subject, the MoD gave incomplete informationto the HCDC in a memorandum dated 9 December 1994 concerning the non-OP pesticideswhich had been used during Operation GRANBY.
"d) In the course of 1995, MoD Service and Civil Service staff received a number of indicationsthat during the Gulf War British troops might have obtained locally and also used some OPpesticides, but this information was neither assessed nor followed up properly. "e) No later than early June 1996, some MoD Service and Civil Service staff knew that OPpesticides had been used more extensively during Operation GRANBY than had previouslybeen reported and that this new information would embarrass the Department. However,appropriate action was not taken.
"f) Although new information concerning OP pesticide usage during Operation GRANBY hademerged much earlier, MoD Service and Civil Service staff failed to provide Ministers withappropriate written advice on the subject until 25 September 1996. Thereafter Parliament wasinformed at the earliest opportunity that incorrect statements had been made." The lack of information about the quantities used, the names of the commercial products or evencountry of origin of the pesticides and insecticides used during the Gulf War, makes further soundepidemiological research extremely difficult; also the conclusion of the MRC (2003). However, given the lack of information about the most basic of facts, it is also difficult to reconcilethe government's position that "there is no evidence that they were used incorrectly". The counterargument being that there is also no evidence to suggest that OPs were used in accordance withSafety Data Sheets or even that the correct personal protective equipment was used. TheGovernment's position was also challenged by Paul Tyler MP in 2003: "Claims that OPs were used only by trained operatives, with proper precautions and protectiveclothing, have been specifically challenged by Sergeant Tony Worthington, who has clearphotographic evidence. He has shown that operatives were exposed to massive doses of OPsand other pesticides in vapour form. We still do not know whether those OPs, apparentlybought locally in Saudi Arabia, were of a type that was banned for use in the UK. We can besure, however, that any warnings and instructions for use were in a language that wasunintelligible for those unsuspecting Service personnel." There was an attempt made to shed some light on the amount of OPs used during the Gulf War, in1997 the Laboratory of the Government Chemist reported on tests of tent materials aimed atdetecting residues in tent materials. Lord Lloyd included this evidence in his Inquiry report in 2004: "Of twelve samples analysed one was found to contain residues of the pesticide fenitrothionin low concentrations. The authors point out, however, that greater contamination could havebeen present six years before." Gulf report 4/5/07 09:34 Page 20 4. Investigations into the prime suspects The Pesticide Safety Directorate considered the report and concluded that "…any likely humanexposure would be well within acceptable limits for this compound" (Lord Lloyd, 2004).
More recently, findings from both UK and US research have suggested that some people mightbe more susceptible to the adverse effects relating to OPs and other nerve agents. It has beenreported that people with a reduced activity of the enzyme paraoxonase 1 (PON1) might be morelikely to suffer ill health if exposed. The MRC (2003) reported: "The significance of these findings is not yet clear. PON1 breaks down different OPs atdifferent rates and has a number of other functions that relate to common health problems,e.g. cardiovascular disease." In 2005 the Health and Safety Executive (HSE) commissioned from the University of Manchesterentitled "Genetic variation in susceptibility to chronic effects of organophosphate exposure"(Cherry et al., 2005). The principal objective of the study was: "…to determine whether sheep farmers with self-reported disabling chronic symptomscontain a greater proportion of individuals with dysfunctional polymorphisms at positions 192and 55 of human serum paraoxonase than sheep farmers without these symptoms." The study was carried out by comparing people who used sheep dips containingorganophosphate and self-reported chronic ill-health (which they attributed to sheep dip) – "thecase" – and compared them with a nominated person of similar age (not a blood relative) whohad a similar dipping history and who they believed to be of good health – "the referent". Thestudy reported: "Results from this study indicating that there were differences in the case and referentpopulation in not only the PON1 genotype but also diazoxonase activity are thus consistent withthe study hypothesis that OPs contribute to the reported ill health of people who dip sheep." In relation to the specific symptoms of depression, a further study carried out at the University ofBristol concluded (Lawlor et al., 2007): "These findings suggest that the association of PON1 Q192R with symptoms of depression inoccupationally exposed groups may be driven by exposure to toxins that everyone in thegeneral population is exposed to rather than exposure to toxins specifically used by sheepdippers or Gulf War veterans, or that other mechanisms underlie the association. This isbecause the study population in which we have found an association consisted of Britishwomen aged 60-79, few of whom where sheep dippers or Gulf War veterans. When usinggenotype-outcome associations to infer causality with respect to an environmental exposuremodified by the genotype, it is important to examine these applications in general populationsand in those specifically exposed to the putative agent. The possible role of PON1 Q192R inpsychiatric morbidity requires further examination." The only thing that remains clear is that further investigation is needed. The MoD has already carried out two studies in this area. The first study carried out byManchester Royal Infirmary (MRI) was published in 2000 and "found that a self-selected group of Gulf report 4/5/07 09:34 Page 21 152 ill Gulf veterans had paraoxonase activity levels 50% less than those of healthy civilians". Thesecond study, again at MRI, reported in 2003. This study also found that PON1 activity in Gulfveterans was lower than in the control groups used. However, the MRC (2003) have recommended more work in this area: "The possibility of paraoxonase enzyme genotype studies should be explored. Comparing non-exposed and exposed individuals, with or without symptoms, might show whether symptomseverity correlates with particular enzyme subtypes." In January 2006, the MoD stated that they were reviewing a proposal for a clinical study of the levelsof paraoxonase in Gulf veterans with the MRC. It is hoped that this study can progress quickly.
Studies have been carried out, which aimed to detect evidence of OP toxicity by looking at thenervous system. King's College London (KCL) carried out neurological testing in ill veterans whoreported poor health or symptoms that might indicate neurological testing. A technique and verysensitive test called single fibre electromyography (SFEMG) was used (KCL, 2006): "The results were largely normal. Although the ill veterans reported symptoms that mightindicate damage to the peripheral nervous system, this could not be confirmed on thesophisticated tests (Sharief et al., 2002). Overall there was no evidence of any damage to theperipheral nerves, neuromuscular junction or muscles. Two years later a much larger study ofUS Gulf veterans and their families have confirmed these results (Davis et al., 2004)." Exposure to chemical weapons (sarin and cyclosarin)
The most notable exposure to chemical weapons during the Gulf War resulted from the USdemolition of weapons at Khamisiyah on 4 March 1991. What were initially thought to beconventional weapons were later identified as chemical weapons containing sarin. The plume that was created in the destruction of these weapons has since become the topic ofsome debate. The need to know size and the areas which the plume covered is importantbecause it is directly related to the number of potential exposures to sarin, and the outcomes ofepidemiological studies in this area. The MoD did not collect any meteorological data or other source data during the Gulf War thatwould enable any plume modelling of the incident at Khamisiyah. The UK government has insteadrelied on the composite model developed by the Department of Defence (DoD) and the CentralIntelligence Agency (CIA).
In 2004, the US Government Accountability Office (GAO) evaluated the validity of the DoD,Department of Veterans Affairs (VA), and the MoD conclusions about troops' exposure. Theyreported: "DoD's and MoD's conclusions about troops' exposure to CW [chemical warfare] agents,based on DoD and CIA plume modeling cannot be adequately supported. The models were notfully developed for analyzing long-range dispersion of CW agents as an environmental hazard.
The modeling assumptions as to source term data – quantity and purity of the agent – wereinaccurate because they were uncertain, incomplete, and nonvalidated." Gulf report 4/5/07 09:34 Page 22 4. Investigations into the prime suspects The GAO went on to outline the MoD position: "The MoD concluded from the 1997 DoD and CIA composite model of the Khamisiyahdemolitions that the maximum concentration of agent that British troops might have beenexposed to was below the level that the most sensitive British warning device could have beenexpected to detect. Moreover, according to the MoD, the highest theoretical dosage troopsreceived would have been 3.6 times lower than the level at which the first noticeable symptomsoccur. Finally, the MoD said, this level of exposure would have no detectable effect on health. "The MoD also determined that a number of British troops were within the boundary of theplume in the DoD and CIA composite model, and it estimated that the total number of Britishtroops potentially exposed was about 9,000.]…[However, since the MoD relied exclusively onDoD's modelling and since we found that DoD could not know who was and who was notexposed, the MoD cannot know the extent of British troops' exposure." The MoD position is easily understood, as it was based on the best possible information availableat the time. However, the GAO investigation also concluded that any exposure estimates basedon the DoD and CIA model could not be supported. Significantly, in April 2002 the DoD published their final Khamisiyah report with a revised model,which took into account improvements in modelling and analysis techniques. However, the DoDdid continue to highlight the lack of source data as a problem. The revised 2002 DoD report, andmodel contained within it, was not considered by the GAO because it was deemed to be beyondthe scope of their study.
Since then, MoD scientists have evaluated the 2002 DoD model, and "welcome the modellingimprovements implemented by the DoD" (MoD, 2005). While supporting the improvements, theMoD considered that the DoD source data assumptions were too broad and "result in a modelwhich overstates the size of the plume footprint". However, there is one thing that all agenciesseem to agree on (MoD, 2005): "Without major improvements in the quality of the source data, which are unlikely to emerge,the size and nature of the hazard potentially experienced by troops in the Gulf will remain amatter of debate. Despite disagreement over the size and nature of the plume, both the DoDand GAO agree that no further modelling of the events at Khamisiyah should be undertaken." While maintaining that the modelling used is based on limited source data and that the plumefootprint presented by the DoD is too broad, the MoD have used the model to make anassessment of exposure of UK Armed Forces personnel to chemical agents (MoD, 2005): "MoD's assessment concludes that approximately 9,000 Service personnel were locatedwithin the possible area of exposure and considers that it is possible (though not probable) thatan extremely low level exposure could have occurred within this area." Stress and psychological factors
Three-quarters of ill Gulf War veterans "have no recognised psychiatric disorder" (MRC, 2003). Aswith other symptoms, Gulf War veterans report "more psychiatric symptoms, and symptoms of Gulf report 4/5/07 09:34 Page 23 greater severity" than non-Gulf veterans (MRC, 2003). When considering Post Traumatic StressDisorder (PTSD) it has been found that only around 3% of Gulf War veterans suffer from thisdisorder; not nearly enough to provide an explanation for the ill health of this group of veterans(Lord Lloyd, 2004).
However, recognised psychiatric disorders are not the only consideration. The affect of stress onphysical wellbeing, as well as synergistic effects also need consideration. These effects areconsidered in the paper "Reflections on Gulf War illnesses" (Wessley & Freedman, 2006): "During the Desert Storm, there were several thousand documented chemical alarm alerts.
Subsequently, the consensus of opinion is that none was a true positive, and that Iraq did notuse its CBW arsenal. But at the time each alert had to be assumed to be genuine. Thus, evenif traditional military stressors were not a prominent feature of the active campaign, a well-found and realistic anxiety about the threat of dread weapons could still be important. It doesnot take much imagination to accept the potent psychological effects of operating in anenvironment where one could be subject to chemical attack, or the damaging effects ofbelieving, even erroneously, that one has been the victim of such an attack (Fullerton & Ursano1990; Riddle et al., 2003). Believing oneself to be exposed to such weapons has been foundfrequently to be associated with the development of symptoms (Unwin et al., 1999; Nisenbaum et al., 2000), sometimes very strongly (Haley et al. 1997; Proctor et al., 1998;Stuart et al., 2003)." The cocktail effect
Whilst a great deal of work has been completed on each of the suspected causes of Gulf War illnesses,little has been done on the health effects of multiple stressors and chemical exposures. During 2005two studies in the US examined how pesticides, vaccines and stress interact with a variety of enzymesystems. The first of these studies carried out on mice (Wang et al., 2005) concluded: "Our current studies suggest that stress, vaccination, and PY [pyridostigmine] maysynergistically act on multiple stress-activated kinases in the brain to cause neurologicalimpairments in GW1 [Gulf War 1990-91 veterans]." The US Department of Veterans Affairs (VA) reported in 2006 that: "These experiments are the first steps in better defining the risks (and underlyingmechanisms) represented by multiple exposures." However difficult it may now be – given the extensive official delays – it is essential that thepotential inter-relationship and interaction of various individual causes of these illnesses. For someveterans it may well have been the combination, rather than any one specific cause, that hascaused a chronic condition.
Gulf report 4/5/07 09:34 Page 24 5. Additional UK Research Gulf Veterans Medical Assessment Programme (GVMAP)
The Gulf Veterans Medical Assessment Programme (GVMAP) was established in 1993 toinvestigate the medical complaints, to diagnose and recommend appropriate treatment ormanagement. The GVMAP also collated statistical information; articles have been published in1996, 1999, 2001 and 2002. The most recent analysis was published in 2005: "An observationalstudy on diagnoses of 3,233 Gulf veterans (Op GRANBY, 1990-91) who attended the Ministry ofDefence's Medical Assessment Programme 1993-2004" (Bale and Lee, 2005). They reported: "This is the result of an observational study on 3,233 Gulf veterans who have attended ourmedical assessment programme. We wanted to determine as a result of in-depth interviews,full medical examination and appropriate investigations, whether there was any unique Gulfwar related medical condition.
"Over a period of 10 years, 3,233 veterans have been assessed. All diagnoses have been madeaccording to ICD-10 classifications. All psychiatric diagnoses have been confirmed byconsultant psychiatrists.
"75% of veterans were well. Of the 25% unwell, 83% of ill health was accounted for by apsychiatric disorder. 3% of veterans had organic conditions which could be linked to Gulfdeployment. The most common of these were respiratory disorders, followed by digestivedisorders, injuries and skin disorders. Only 11 of these cases could be linked to the use ofmedical countermeasures. A further, 51 cases (41 respiratory disorders, 6 infections, 2 skindisorders and 2 eye conditions) could be linked to environmental conditions.
"All veterans seen with health problems could be identified as per ICD-10 classification ofdisease. We did not find any medically unexplained conditions. We found no evidence of aunique ‘Gulf War Syndrome'." With reference to diagnoses of skin disorders, one health outcome that has been noted is anexcess of seborrheic dermatitis. This is of interest simply because "of its associations withimmune dysfunction" (KCL, 2006).
The first study into mortality data was published in 2000. The study found similar results ofdeaths and causes of death between deployed Gulf veterans and the comparison Group (thecomparison group consisting of Armed Forces personnel of similar profile in terms of gender,Service, regular/reservist status and rank, who were in Service on 1 January 1991 but were notdeployed to the Gulf) (Macfarlane et al., 2000). However, there was a "small excess of deathsamongst Gulf veterans attributable to accident, particularly road traffic accidents" (MoD, 2005).
There have also been reports of increased rates of suicide and more broad accidental deaths(KCL, 2006).
Since the publication of this study in 2000, the Defence Analytical Services Agency (DASA) hasreported mortality statistics every six months – it has recently been agreed to change thereporting period to 12 months (February 2007).
Gulf report 4/5/07 09:34 Page 25 Several studies have been carried out in the UK on reproductive health. The first published in 2003reported a higher number of pregnancies from both male and female Gulf War veterans whencompared with the control group – although no conclusions were drawn from this (Maconochie etal., 2003).
There were also two papers published in 2004 on male fertility. The first reported that there wasno evidence for increased risk of stillbirth, chromosomal malformations, or congenital syndromesamongst male veterans, although some links with fathers' Gulf Service and an increased risk ofmiscarriage and other less well-defined malformations (Doyle et al., 2004). The second reportedon increased risk of infertility, the researchers concluded (Maconochie et al., 2004): "We found some evidence of an association between Gulf War Service and reported infertility.
Pregnancies fathered by Gulf veterans with no fertility problems also reportedly took longer toconceive." With regard to health in general, in 2006 King's College London (KCL) reported an increase inhypotension in ill Gulf veterans compared with healthy Gulf veterans. They also found that theseveterans were more likely to be "overweight, and had higher levels of a particular enzyme(gamma GT) which is associated with alcohol intake, but is also a marker for obesity" (KCL, 2006).
More broadly they reported: "It is possible that all of these reflect the influence of problems such as fatigue and lack ofexercise, which may be part of a vicious circle of ill health, fatigue, lack of exercise, and henceincreased weight, leading to more fatigue and even less exercise." Central Nervous System
Lastly, worth mentioning is the UK study looking into damage to the Central Nervous System(CNS), which used standardised tests of neuropsychological functions. The researchers comparedill Gulf veterans to a group of healthy veterans. The results were broadly similar for both groupsdemonstrating a difference in "subjective complaints and objective tests" (KCL, 2006). However,there was one test where ill Gulf veterans fared worse (KCL, 2006): "Only on one particular test, called the Purdue Pegboard, a test of motor skills, were sick Gulfveterans impaired, suggesting an impairment of motor dexterity, which might indicate somesubtle neurotoxic damage." Gulf report 4/5/07 09:34 Page 26 6. Further UK Research "There is as yet no single, definitive, explanation for what has been observed. It is my opinionthat this is unlikely to change with the passage of time, and that the delay in commencingserious scientific study of the problems has meant that any chances that once existed ofproviding better answers on aetiology have probably vanished." (Wessley, 2006) The conclusions and recommendations of the MRC Review of Research into UK Gulf Veterans'Illnesses in 2003 stated: "Further studies to characterise symptoms and illnesses of UK GVs based on self-reportedexposures are not necessary and epidemiological studies of existing data are unlikely to lead togreater understanding.
"Most of the potential hazards have already been investigated in sufficient detail." However, the MRC did recommend in their report that "research aimed at improving the long-term health of GVs with persistent symptoms should take priority" over any other recommendedwork. The government has repeatedly stated that in order to maintain and to demonstrate thescientific credibility and independence of their research programme they have been guided by theadvice and support of the MRC.
The MRC also stated that preliminary US neuroimaging studies should be replicated in the UK.
This work is almost due to report and it is hoped that if the studies report useful outcomes, thatthis can be replicated in the UK very quickly. The MRC also recommended that "studies ofmeasurable symptoms should be piloted to see whether nervous system changes are alsopresent".
Professor Simon Wessley, Co-Director of Kings College Centre for Military Health Research, saidin a press release dated 24 March 2006: "An enormous amount of money and effort have been expended on understanding Gulf WarIllnesses worldwide. These reviews make it clear that there is no single cause, rather there area range of factors likely to be responsible. I believe there is little value in conducting furtherresearch into the causes. We should now focus our resources on rehabilitating those peoplewho are ill as a result of Service in the Gulf War." While opinions differ on the need for further investigations into the causes of Gulf War illnesses, itis agreed that work to improve health and quality of life are needed. Some work has beeninstigated in the US, particularly using cognitive behavioural therapies (CBT), but did not reportdue to the number of veterans that pulled out of the study. However, there may still be merit inthis type of work, if combined with pre-selection testing to gauge susceptibility. The MoD are alsocurrently looking to commission work in this area.
In the UK some work has been carried out on a wider group of people, but did also include GulfWar veterans. This work comes under the Expert Patient Programme (EPP), which delivers helpwith self management through the Chronic Disease Self-Management Course (CDSMC). By 2006the EPP had delivered 2,700 community courses to over 35,000 people living with long-term Gulf report 4/5/07 09:34 Page 27 health conditions. Results from the EPP pilot internal evaluation indicate the following trends (EPP, 2006): 45% said they felt more confident that they would not let common symptoms (pain,tiredness, depression and breathlessness) interfere with their lives; 38% felt that such symptoms were less severe 4-6 months after completing the course; 33% felt better prepared for meetings with health professionals. In terms of access to health services, the EPP has reported a: 7% reduction in GP visits; 10% reduction in outpatient visits; 16% reductions in admissions to Accident and Emergency Departments; and 9% reduction in physiotherapy use.
The ex-Service voluntary sector is currently looking at how this model could be used or adaptedfor interested Gulf War veterans.
Proposals from the Gulf War Group
The Gulf War Group is constituted by representatives of Gulf War veterans, parliamentarians andrelevant experts on Gulf War illnesses and related issues. The Gulf War Group monitors theprogress of both UK and US research, and has forwarded two outline proposals for further UKresearch to the MRC for their advice. They are: A comparison of endocrine abnormalities in patients with Gulf War Syndrome (GWS) versusthose with Chronic Fatigue Syndrome (CFS). The study will look at the dynamic pituitaryresponse of patients with symptomatic CFS to determine if the hormonal response isspecifically abnormal in GWS, particularly for ACTH and growth hormone. Gulf War Syndrome (GWS): investigation of pathogenesis by determining the specific geneexpression signature and identification of protein biomarker using mass spectrometry. Thestudy aims to elucidate the pathogenesis of GWS in terms of the gene expressionsignatures of messenger RNA and to identify protein biomarker that could be developedtoward a diagnostic test for GWS.
Gulf report 4/5/07 09:34 Page 28 7. United States (US) Research Research Advisory Committee on Gulf War Veterans' Illnesses (RACGWI)
The Research Advisory Committee on Gulf War Veterans' Illnesses (RACGWI) was established in2002 by the US Secretary of Veterans Affairs to advise on research relating to the healthconsequences of service in the Gulf War. Their report issued in 2004 "Scientific Progress inUnderstanding Gulf War Veterans' Illnesses: Report and Recommendations" outlines their keyfindings – those of interest to UK Gulf veterans are outlined below: A substantial proportion of Gulf War veterans are ill with multi-symptom conditions notexplained by wartime stress or psychiatric illness; Treatments that improve the health of veterans with Gulf War illnesses are urgently needed; A growing body of research indicates that an important component of Gulf War veterans'illnesses is neurological in character; Evidence supports a probable link between exposure to neurotoxins and development ofGulf War veterans' illnesses; Other wartime exposures may also have contributed to Gulf War veterans' illnesses; The health of Gulf veterans must be carefully monitored to determine if Gulf War Service isassociated with excess rates of specific diseases, disease specific deaths, or overallmortality; Important questions concerning the health of children and other family members of GulfWar veterans remain unanswered.
US Federally sponsored Research on Gulf War Illnesses for 2005
In June 2006 the Department of Veterans Affairs (VA) made their Annual Report to Congress onthe Federally Sponsored Research on Gulf War Illnesses for 2005. The following provides a briefupdate on the progress made during 2005.
The United States (US) research programme is divided into five focus areas, these are: Brain and nervous system function; Immune function and infectious diseases; Reproductive health; Symptoms and general health.
Brain and nervous system function
The majority of reports in this area were concerning physical and psychological effects of combatexposure. Gulf report 4/5/07 09:34 Page 29 One epidemiological study on amyotrophic lateral sclerosis (ALS) [motor neurone disease (MND) inthe UK] was corrected in 2005 "after correcting for under-ascertainment the risks of ALS remainedelevated among deployed veterans" (Coffman et al., 2005). However, a study on ALS mortality datafound a higher risk for men born between 1915 and 1935 who served in the military in general,compared with those who had not served (Weisskopf et al., 2005). Additionally, a literature reviewfound no consistent link between exposures to pesticides/insecticides or chemical solvents, orincreased rates of death from ALS in Gulf War veterans (Wicklund, 2005).
With regard to the study demonstrating elevated incidences of ALS, or MND as it is known in theUK, KCL considered these results and reported (2006): "…one study from the USA reports that US Gulf veterans are more likely to be suffering froma rare neurological condition known as amyotrophic lateral sclerosis (ALS).]…[However, thisfinding is controversial since as (sic) MND is a terrible disease that is usually and fairly rapidlyfatal, one would expect this to be reflected in higher death rates, which have not beenfound.]…Whether or not the American data is correct, MND is still a very rare condition in Gulfveterans, and cannot account for the large health effects that have been found." There were several studies on Post Traumatic Stress Disorder; they noted that early interventionand documentation of experiences was beneficial to treatment (VA, 2006). The 2005 research reports in the grouping environmental toxicology focused on DU and sarin. The clinical studies on veterans have already been outlined; the studies conclude that "noclinically significant uranium-related health effects were observed in these veterans" (VA, 2006).
Several studies in the US on animals exposed to DU for 6-9 months discovered changes tobehaviour and some health effects. However, the length of exposure should be noted in relatingto how Gulf veterans would have been exposed to DU.
Studies have also been carried out on animals exposed to low doses of sarin, some includingexposure to pyridostigmine bromide (NAPS). The VA reported the following (2006): "Exposure to animals to low (non-lethal) doses of sarin, with or without pyridostigminebromide, produced transient, but not permanent, alterations in blood flow and metabolicactivity in the brain (Scremin et al., 2005), as well as dose-related changes in body weight andblood acetylcholinesterase activity (Langston et al., 2005)]…[Sarin was also found to alter geneexpression profiles for proteins in the brain involved in neurotransmission (Block-Shilderman etal., 2005; Damodaran et al., 2006)]." There was a further study, which found some limitations in using mice for neurotoxicology studies(Li et al., 2005) (VA, 2006): "They demonstrated that mice, unlike humans, have substantial amounts of solubleacetylcholinesterase as well as butyrylcholinesterase (BChE) in their blood plasma. Thus themetabolism of systemically administered drugs and toxicants may differ." Gulf report 4/5/07 09:34 Page 30 7. United States (US) Research Immune function and infectious diseases
The VA reported on a UK study, which looked at the anthrax and pertussis vaccine combinations inmice. While the researchers found that the vaccine combinations cause splenomegaly andsignificant weight loss, they also stated that (Rijpkema et al., 2005): "The relatively high vaccine dose used, together with the low sensitivity of mice to anthraxtoxin, emphasises that caution should be exercised in applying these results to humanrecipients of these vaccines." The VA reported that four studies were published on reproductive health during 2005. Two studiesinvolved animals with implanted DU; one looked at the effects of the anthrax vaccine onreproductive health and the other the incidence of infants born with Goldenhar syndrome. "Noneof the studies detected an adverse impact of Gulf War related Service on reproduction" (VA,2006). Symptoms and general health
The US carried out a study which medically examined 1,061 Gulf veterans and 1,128 non-deployed veterans for 12 different medical conditions – these were fibromyalgia, Chronic FatigueSyndrome, dermatologic conditions, dyspepsia, physical health-related quality of life, hypotension,obstructive lung disease, arthralgias, and peripheral neuropathy. Of these, four were moreprevalent among Gulf veterans – fibromyalgia, Chronic Fatigue Syndrome, dermatologicalconditions and dyspepsia (Eisen et al., 2005).
There was also a study into motor vehicle accidents (MVA) which illustrated that those involved inMVAs were more likely to be younger, less educated, not married, enlisted, and deployed to theGulf War when compared to controls (Hooper et al., 2005). These findings corroborate the workdone in the UK.
Gulf report 4/5/07 09:34 Page 31 8. Research Funding and Monitoring From 1996 to 2005 the US DoD spent USD $182 million on research into Gulf War illnesses. Inthe same period the Department of Veterans Affairs (VA) spent USD $68 million and theDepartment for Health and Human Services (HHS) spent US$10 million (VA, 2006). Federalfunding totalled USD $260.6 million by 2005 (around GBP £156.4 million) - these figures excluderesearch undertaken between 1992 and 1995. Over the period 1992 to 2005 the DoD, VA and HHS sponsored a total of 300 distinct researchprojects on Gulf War veterans' illnesses. At the end of the 2005 financial year there were still 90projects either new or ongoing.
In comparison, the UK has spent a total of £8.5 million pounds on research on the causes of GulfWar illnesses; a very large proportion of this was spent on the Vaccines Interactions ResearchProgramme. The higher spend in the US is understandable due to the much larger number of troops deployedto the Gulf. Comparing research spend based on numbers of troops deployed, the US has spentGBP £223 per person, while the UK has spent £158 per person. The UK also continues to fund aGulf Health Liaison Officer, based in Washington, to monitor the US research programme.
However, the government do not produce regular updates on the progress of US research in aneasily digestible format for veterans. When asked directly how veterans are being kept informedof progress, Lord Drayson replied (November 2006): "…they [veterans] will be kept informed through a number of mechanisms. First, there is thepublication of the results in peer review journal, which we bring to the attention of veteransthrough their representative organisations, through Members of this House who representveterans, and through the Ministry of Defence website. We also need to go further, as I havesaid. We need to write to those veterans for whom this is most relevant. We need to do sowhen we are clear about the issues that will achieve final closure. I feel that there is notsufficient clarity about what that closure would be based on. We need to do more, and we areprepared to do that." Gulf report 4/5/07 09:34 Page 32 9. Current Compensation Arrangements The compensation arrangements for Gulf War veterans do not differ from those for any injury orillness caused by Service. Compensation payments are awarded through the War PensionScheme (WPS) in the case of illness, injury or death, which occurred before April 2005. Thescheme is legislated by the Naval, Military and Air Forces Etc. (Disablement and Death) ServicePensions Order 2006 (SPO06). Ongoing payments awarded (for a whole body disablement of20% or more) are referred to as a War Disablement Pension. As stated the number of Gulf veterans in receipt of a War Disablement Pension (level of wholebody disablement 20%-100%) is around 2,920 (Lord Drayson, 2006). Those who claim throughthe WPS, but are assessed as having a whole body disablement of less than 20% are awarded aGratuity, or one-off payment. As at March 2004 the number of Gulf War veterans who hadreceived a Gratuity was 2,235 (Lord Lloyd, 2004). The WPS also allows for other allowances to bepaid, for things such as lower earnings potential, age, unemployability and carers. The latest figures from the Service Personnel & Veterans Agency (23 April 2007) report that thereare 6,718 veterans who have received any type of disablement award made for recognisedconditions, and 1,598 of these are for conditions related to Gulf War illnesses.
Gulf report 4/5/07 09:34 Page 33 10. Labels applied to War Disablement Pensions For the majority of injuries or illnesses, the label that is applied to a War Disablement Pension isquite straight forward. In the case of illness, the name of the medical condition is applied e.g.
Chronic Fatigue Syndrome together with the level of disablement. However, where a claimant hassymptoms of illness that cannot be attributed to a medical condition the situation becomes morecomplicated. The burden is on the claimant to prove the existence of a particular medicalcondition based on reasonable doubt. For disabling conditions/symptoms that are not covered by recognised conditions or diagnosticlabels, it has become regular practice for the SPVA to apply the term "Signs and Symptoms of Ill-Defined Conditions" (SSIDC). SSIDC is a diagnostic category within the ninth edition of the WorldHealth Organisation Classification of Diseases (WHO ICD). This term has been replaced in thetenth edition of the WHO ICD by Symptoms, Signs and Abnormal Clinical and Laboratory FindingsNot Otherwise Classified (SSACLFNOC). However, while it has been replaced the SPVA continuesto use the SSIDC label as the diagnostic label for symptoms and illness where there is noidentifiable underlying disease. It is important to note that even if the SPVA was to adopt the newlabel, SSACLFNOC, the change would not apply retrospectively, and it would not affect any levelof award given.
It has been argued that Gulf War veterans who suffer from a range of symptoms of illness shouldapply the term "Gulf War Syndrome" instead of using the SSIDC label. It is thought that eventhough "Gulf War Syndrome" is not a recognised medical condition the SPVA could use it as adescriptive "umbrella" label in the same way that SSIDC is used. Or put another way, the label"Gulf War Syndrome" could be applied to signs and symptoms of illness that are not a discretemedical condition, but that can be linked to Service in the Gulf.
Gulf report 4/5/07 09:34 Page 34 11. The Application of the Label "Gulf War Syndrome" It has been stated on many occasions, and is agreed by all parties, that "Gulf War Syndrome" isnot in itself a discrete medical condition. However, it is worth noting that there have been claimsfor Gulf War Syndrome allowed by the Pensions Appeal Tribunals (PAT).
Where War Disablement Pensions have been awarded to veterans for accepted conditions, thephrase "Gulf War Syndrome" has been used as a descriptive label, with a list of accepted medicalconditions or symptoms of illness listed beneath. The MoD have recently highlighted somedifficulties in applying the label "Gulf War Syndrome" to particular signs and symptoms ofillnesses; in particular, they are not clear in how it can be used in any other way – because: Using it as a replacement for Signs and Symptoms of Ill-Defined Conditions (SSIDC) wouldmean that those with defined medical conditions would not be able to use it; the MoDrightly feel that applying the label to all Gulf War veterans who wanted it to be appliedwould be an important step toward closure.
Using it as a term for a basket of disorders, signs or symptoms of illness would require adefinitive list to be drafted. This could lead to some people being excluded if their symptomwas not on the positive list. Additionally, as yet, we do not have an agreed set of conditionsidentified.
However, it could be argued that the two are not mutually exclusive - this is not an either/or issue.
It is possible for the term "Gulf War Syndrome" to be used in more than one way. It could beused as a replacement for SSIDC, or, in the way it is being used now, as a label covering anumber of conditions associated with the Gulf War. When giving evidence to the Lord LloydInquiry into Gulf War Illnesses (2004) Dr Harcourt Concannon (PAT President) made the followingpoints: "Whichever you call it, whether Gulf War Syndrome or ‘Symptoms and Signs of Ill DefinedConditions' the label is, he said, [Dr Harcourt Concannon] no more than a wrapper foraccepting a set of symptoms." "Secondly, the label Gulf War Syndrome as favoured by the veterans, or ‘Symptoms and Signsof Ill Defined Conditions' (SSDIC), as favoured by the Government, are both ‘umbrella labels'.
They encompass a whole array of separate symptoms. The symptoms have to be definedbefore you can go onto the second stage of the process, as already explained, in assessing, ina particular case, which symptoms have been included in the accepted condition ofdisablement." Gulf report 4/5/07 09:34 Page 35 12. Calls for a Public Inquiry The Royal British Legion and others have been calling for a full Public Inquiry into the causes ofGulf War illness since the mid-1990s. In answer to a question by the Rt. Hon. Lord Morris ofManchester on 26 February 2004 regarding calls for a Public Inquiry into Gulf War illnesses,Baroness Crawley stated: "My Lords, The Royal British Legion and others continue to campaign for such an inquiry.
However, the Government are still not convinced that a public inquiry would help. Thepossibility that we may look again at this matter has not been ruled out. However, in thepresent circumstances, it is only through the programme of research initiated by theGovernment that we are ever likely to establish the causes of Gulf veterans' illnesses." In the continued absence of such an inquiry, on 14 June 2004, it was announced that Lord Morrishad asked Lord Lloyd to chair an independent Public Inquiry. In the process of carrying out thisinquiry, Lord Lloyd wrote to the then Secretary of State for Defence for their cooperation. Hisresponse came from Mr Ivor Caplin MP, Parliamentary Under Secretary of State for Veterans, itstated: "The Government has carefully considered the merits of an official inquiry and while we havenot ruled out such an inquiry for the present, we remain of the view that the only way we arelikely to establish the causes of ill health in some Gulf veterans is through scientific andmedical research." In his report, Lord Lloyd commented on this response: "In other words the Government's view is that although it is now over thirteen years since theGulf War, the time for a Public Inquiry is not yet ripe. This is a view which they have expressedon many occasions." It is now 16 years since the end of the Gulf War, and the government has still not announced anyintention to conduct a Public Inquiry. Significantly, the progress of scientific and medical investigation into the possible causes of GulfWar illnesses has also now deteriorated – this is particularly the case with the publication of thefinal reports of the Vaccines Interaction Research Programme and the Depleted UraniumOversight Board. Further, on 30 January 2006 the MoD wrote regarding further research into the causes of GulfWar illnesses, they stated: "They [the MRC] did not recommend further work on clinical aspects or causes of Gulf illness.
The majority of their recommendations have now been addressed." It seems that it is now the view of the MRC, and the government, that the limitations of scientificand medical research might have been reached, and that the only work of substance that remainsoutstanding relates to improving the health of veterans with persistent symptoms. If this is the case, the question must once again be asked – is now the right time for a PublicInquiry? Gulf report 4/5/07 09:34 Page 36 13. Future Compensation Arrangements The Lord Lloyd Inquiry (2004) report recommended that veterans suffering from Gulf Warillnesses should be awarded an ex gratia payment. It should be made clear from the outset that the call for an ex gratia payment is not a request foradditional compensation for illness or injury, as this type of payment is made under the WarPension Scheme. The grounds for ex gratia payments are the sustained failures of the UK government to fulfil theirduty of care to this group of veterans, including delays in investigating exposures to harmfulagents and medical research. The UK government had, and continues to have, an obligation toensure the wellbeing of Armed Forces personnel, so far as it is reasonably practicable. In the caseof Gulf War veterans, they have been negligent in this duty, and as a direct result, veterans havebecome the victims of ill treatment and suffered real hardship.
The following points illustrate the failure of government to protect and properly treat this group ofveterans: The government denied for six years that veterans' illnesses were caused by the Gulf War;while since accepting that illnesses are linked to Service in the Gulf.
This delay in accepting a new post-combat disorder also delayed the commissioning ofserious scientific research; this has significantly reduced likelihood of ever finding the causeor causes of Gulf War illnesses. King's College London recently commented that "back in1995 the UK government was not convinced of the need for the study we proposed "(KCL,2006). In 2005 it was reported (Hotopf & Wessley, 2005): "Unlike many health problems, the window of opportunity to properly investigate post-deployment health problems is brief". The MoD disposed of or lost medical records and temporary nominal rolls compiled intheatre (B Med 27s); as a result some veterans may never know how many vaccines orother medical countermeasures they were given, and/or in what doses.
The MoD failed to ask or get written consent during the administering of medicalcountermeasures, or inform Armed Forces personnel of the possible health risks. The factthat anthrax was not licensed for use with pertussis as an adjuvant was not communicated. The MoD failed to act on advice supplied by the National Institute for Biological Standardsand Control (NIBSC) that preliminary tests into the use of the anthrax vaccine with pertussisas an adjuvant were a cause for concern.
The government initially denied that OPs were used during operations in the Gulf. Thesubsequent investigation, six years later, found that there had been extensive use of OPs,including locally purchased products. This forced a U-turn by the government on the use ofOPs.
Gulf War veterans were exposed to a number of harmful neurotoxins and other toxinsincluding organophosphates, sarin, cyclosarin, smoke plumes from burning oil wells. They Gulf report 4/5/07 09:34 Page 37 were also exposed to stress. The dose rates and combinations that veterans were exposedto may never be known. Health risks associated with exposure to these agents were wellknown, as was the likelihood of post-combat disorders, however, no control measures orongoing health surveillance were undertaken as protection from this combination or"cocktail" of toxins. Health surveillance was also not carried out when personnel returned,even after the benefit of hindsight to the range of toxic exposures (KCL, 2006): "One of the reasons that we don't know, and will never know, exactly when problemsstarted is because there was no systematic monitoring of the health of the Armed Forceson either side of the Atlantic after 1991." The government has not offered an apology to veterans for this treatment.
This ex gratia payment should be set at £10,000 in line with other ex gratia payment schemes,and be payable to all veterans in receipt of a War Disablement Pension or Gratuity for conditionsrelating to their service during the Gulf War; widows and widowers whose spouses have died ofan illness or injury relating to Service in the Gulf War; and children in receipt of a War OrphansPension.
Gulf report 4/5/07 09:34 Page 38 There is no denying that Gulf War veterans are suffering from ill health and that they do so ingreater magnitude and with greater severity than other groups of veterans. The failure to properlycontrol risks from exposure and carry out appropriate health surveillance both during and postconflict has meant that meaningful research into the causes of these symptoms has not alwaysbeen possible. Research must now focus on improving the health and quality of life for Gulfveterans, and should include further clinical investigations, using objective tests, on individualsthat are suffering from illnesses. Progress on this issue has been continually hampered by multiple failures by the government toproperly address this issue. Successive governments also seem to have the inability to takeresponsibility, rectify past problems and gain the trust of veterans. More significantly, this hasexacerbated the frustrations felt by veterans and those that campaign on their behalf. All of thishas resulted in a legacy of suspicion, to which significant steps must now be taken to rectify.
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Gulf report 4/5/07 09:34 Page 40 "A debt of honour is long overdue to Gulf War veterans. Indeed, agovernment who send soldiers to war have a duty of care towards them.
It was not exercised in the first Gulf War conflict. That was compoundedby the fact that the UK government have refused since then to take realmeasures to help those veterans." (Ewing, 2003) Produced for the Gulf War Group by The Royal British LegionMay 2007Charity No. 219279
Scales, quantity & degree Lecture 1: Quantifiers Rick Nouwen (Utrecht) Scales, quantity and degree S = hX, >i or S = hX, =i 2 Modified numerals What is a quantifier? Natural language determiners Determiner phrases Several parts that move Predicate logical syncategorema Generalised quantifiers What is a quantifier? articles: a, the, . .determiners: every, most, . .number words: one, two, three, . .comparatives: fewer than five hundred, more than just a few, . .superlatives: at most five, at least twelve, . .PPs: between sixty and seventy, up to two hundred, . .adjectives: (very) many, (too) few, . .modifications: almost every, exactly five, . .coordinations: most but not all, two or three, . .