- Email: [email protected]
Long-term effects of sarin
Comment
7
8
Sereti I, Imamichi H, Natarajan V, et al. In vivo expansion of CD4CD45RO CD25T cells expressing foxP3 in IL-2-treated HIV-infected patients. J Clin Invest 2005; 115: 1839–47. Sereti I, Anthony KB, Martinez-Wilson H, et al. IL-2-induced CD4 T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation. Blood 2004; 104: 775–80.
9
10
Hengge UR, Goos M, Esser S, et al. Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients. AIDS 1998; 12: F225–34. Douek DC. Disrupting T-cell homeostasis: how HIV-1 infection causes disease. AIDS Rev 2003; 5: 172–77.
Long-term effects of sarin Like the riot-control agent CS, sarin is named after the chemists, German this time, who developed it in the late 1930s as a candidate pesticide. This cholinesterase inhibitor (isopropylmethylphosphonofluoridate or GB) was not used in the 1939–45 war because Germany feared retaliation. In fact the Allies were as ill-prepared for nerve gas in the 1940s as they had been for the chlorine released over their lines at Ypres, Belgium, in 1915. After both wars there was catching-up to do, and one focus of attention in the 1950s was the nerve “gas” sarin (a highly volatile liquid). During the Cold War, fears of nerve gas attacks were very real, and NATO for a time had sarin as an approved weapon. Treaties now ratified make the use of sarin in war illegal. In the UK, the research side of that catching-up was conducted at a chemical defence establishment that has had eight different names since it opened in 1916.1,2 “Porton Down”, as it is widely known, is seldom out of the news for long. On Oct 19, 2005, the European Court of Human Rights held that, for one of six related claims, the UK Government had violated the human rights of a former soldier who had sought information about his time as a Porton volunteer in mustard and nerve gas experiments in the 1960s.3 Mr T M Roche’s belief that his long-term ill-health should be attributed to the experiments he took part in is currently under re-review by the Pensions Appeal Tribunal. A final judgment on the death in 1953 of Ronald Maddison, a British airman who died in an experiment with sarin, is also awaited. This death, the only one recorded among more than 20 000 volunteers who have attended Porton Down over the years, was labelled as a misadventure. However, in November, 2004, that inquest verdict was overturned and replaced by a verdict of unlawful killing.4 The Ministry of Defence has apologised to the man’s family. The test on May 6, 1953, had been undertaken “notwithstanding the fact that an identical test on 4 May 1953 resulted in an adverse blood test result in one serviceman”. Any claim for compensation www.thelancet.com Vol 367 January 14, 2006
“would be considered favourably on the basis of the negligence referred to above”.5 Nonetheless the Ministry wished to challenge the verdict of unlawful killing, and has been given the court’s permission to do so. The exposure to sarin estimated to kill 50% of a human population is 50–70 mg per m3 of air per minute of inhalation.6,7 In 1953 the fatal dose if sarin was dropped onto bare or battledress-covered human skin was not known for sure. One way to find out indirectly, it was thought, would be to measure red-blood-cell acetylcholinesterase activity before and after exposure to different doses and then extrapolate. It is these experiments in particular that are under scrutiny. What is known of longer-term effects of exposure to nerve gases, experimentally or in other settings? This question is relevant because Mr Roche is not alone among Porton volunteers in claiming that participation in chemical defence experiments has caused illness later in life and because more recently there have been nonexperimental exposures to sarin. The former claim is compounded by the view of some former volunteers that their consent was not properly sought. Porton’s research was secret and to a large extent it still is. However, thanks to the painstaking investigations of Rob Evans,2 we know a lot more than we did, and basic facts about sarin are generally available today in a way they would certainly not have been half a century ago.8,9 Fully informed consent on a secret project is probably impossible. Furthermore, recollections vary as to what was revealed to volunteers2 and it is legitimate to ask how far medical research generally had taken on board the importance of informed consent in the 1950s. The notion of fully informed consent by research volunteers may be older than the codified versions of it, but in 1967 The Lancet, commenting on Pappworth’s controversial Human Guinea Pigs,10 had to agree “that many researches would have been better left undone, that some were disastrous errors, and that the question of true consent by the patients was often glossed over or ignored”.11 Progress has 95
Comment
Getty Images
Rights were not granted to include this image in electronic media. Please refer to the printed journal
Guards at Porton Down's gates, June, 1963
been made since those days, and Porton has moved on too. That the volunteers might have been deceived is a more serious allegation and is not easy to explore. The UK Medical Research Council (MRC) Common Cold Research Unit opened its doors to volunteers in 1946. It was not a neighbour of Porton, being the other side of the city of Salisbury. However, both Porton and the MRC unit struggled at times to get sufficient volunteers, and both advertised. The Ministry of Defence denies deception and also notes, with questionable relevance, that no cold research was ever done at Porton.12 The early MRC volunteers were students, and service personnel are not prominent in accounts of the volunteers at this unit, such as Thompson’s.13 However, influenza vaccine trials were done at some military establishments so there was room for misunderstanding, especially if notices about research into respiratory afflictions were put up on barrack room walls side by side with Porton’s appeals. Frustratingly, a Ministry of Defence inquiry into the Porton Down Volunteer Programme 1939–89, announced more than 4 years ago,14 has been completed but not yet published. More light may come from that report, or from a recently announced Wellcome Trust grant.15 How likely is it that volunteers’ experiences at Porton account for illnesses afflicting them today? No researchdriven prospective programme on volunteers’ health was set up at Porton but we do have an uncontrolled study of 111 self-selected volunteers from the Porton Down Volunteers Assessment Programme.16 Disease patterns were much as one would expect in a group of men now of median age 62 years. The MRC’s retrospective study of the medical records is not expected to finish before 96
September, 2006.17 Evidence from the USA does not yet permit a clear-cut conclusion.18,19 From studies on firemen and policemen involved in the Tokyo subway sarin incidents, we know that rates of sister chromatid exchange can be raised,20 and the possibility of organophosphorus-ester-related neurotoxicity remains on the table.21 Published clinical follow-up of the victims of the Tokyo subway sarin poisoning22 includes posttraumatic stress disorder.23,24 Sarin (or a related agent) was used by Iraq in the Iraq-Iran war, and sarin was used by Iraq on its own Kurdish people, but rigorous epidemiological study of those incidents is difficult. US and UK troops were exposed to sarin when a stock of it was blown up in Iraq in 1991; modelling exercises are reassuring, but the 9000 UK troops were never closer than 130 km.25 Follow-up of the US personnel reveals no evidence of long-term harm.26 Gulf War syndrome, also ascribed by some to chemical and other exposures, shows how difficult it is to sort out claims of this sort, but on present evidence, medically significant late sequelae of sarin exposure seem hard to prove. David Sharp c/o The Lancet, London NW1 7BY, UK I am a Contributing Editor for The Lancet. 1
2 3
4
5 6
7
8 9
10 11 12
13
Ministry of Defence. Porton Down volunteers: a brief history of Porton Down. Dec 17, 2001: http://www.mod.uk/issues/portondownvolunteers/history. htm (accessed Dec 1, 2004). Evans R. Gassed: British chemical warfare experiments on humans at Porton Down. London: House of Stratus, 2000. European Court of Human Rights. Grand chamber judgment Roche v. the United Kingdom. Oct 19, 2005: http://www.echr.coe.int/Eng/Press/ 2005/Oct/GrandChamberjudgmentRochevUnitedKingdom191005.htm (accessed Oct 24, 2005). Evans R, Laville S. Porton Down unlawfully killed airman in sarin tests. Guardian Nov 16, 2004. http://www.guardian.co.uk/uk_news/story/ 0,,1351938,00.html (accessed Nov 18, 2004). United Kingdom Parliament. Porton Down: the death of Ronald Maddison. Lords Hansard Dec 21, 2004: column WS117. Ministry of Defence. Gulf Veterans’ illnesses, annex A: British chemical warfare defence during the Gulf conflict. http://www.mod/issues/gulfwar/ info/medical/ukchemical/annexa.htm (accessed Dec 2, 2004). Bide RW, Armour SJ, Yee E. GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB). J Appl Toxicol 2005; 25: 393-409. WHO. Public health response to biological and chemical weapons. Geneva: World Health Organization, 2004. Centers for Disease Control and Prevention. Emergency preparedness and response: facts about sarin. May 17, 2004: http://www.bt.cdc.gov/agent/ sarin/basics/facts.asp (accessed Oct 25, 2005). Pappworth MH. Human guinea pigs. London: Routledge Kegan Paul, 1967. Anonymous. Responsibilities of research. Lancet 1967; 2: 1144. Ministry of Defence. Porton Down volunteers: the Common Cold Unit. http://www.mod/uk/issues/portondownvolunteers/ccu.htm (accessed Dec 1, 2004). Thompson KR. Harvard Hospital and its volunteers: the story of the Common Cold Research Unit. Warminster, Wiltshire: Danny Howell Books, 1990.
www.thelancet.com Vol 367 January 14, 2006
Comment
14
15
16 17 18 19 20
Ministry of Defence. Historical survey of the Porton Down Service Volunteers Programme. Feb 21, 2002: http://www.mod.uk/issues/portondown volunteers/survey.htm (accessed July 9, 2005). Wellcome Trust. Death of a serviceman: will a study of a 50-year old death help us safeguard medical ethics in these troubled times? http://www. wellcome.ac.uk/doc_WTX023670.html (accessed June 25, 2005). Lee HA, Gabriel R, Bale AJ, Welch D. Clinical findings in 111 ex-Porton volunteers. J R Army Med Corps 2004; 150: 14–19. Medical Research Council. Porton Down update February 2004. London: MRC, 2004. Page WF. Long-term health effects of exposures to sarin and other anticholinesterase chemical warfare agents. Mil Med 2003; 168: 239–45. Institute of Medicine. Gulf war and health: updated literature review of sarin. Washington, DC: Institute of Medicine, 2004. Li Q, Hirata Y, Kawada T, Minami M. Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo disaster 3 years after the event. Toxicology 2004; 201: 209–10.
21 22 23
24
25
26
Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Envir Health 2003; 58: 484–97. Ohbu S, Yamashina A, Takasu N, et al. Sarin poisoning on Tokyo subway. South Med J 1997; 90: 687–93. Ohtani T, Iwanami A, Kasai K, et al. Post-traumatic stress disorder symptoms in victims of Tokyo subway attack: a 5-year follow-up study. Psychiatry Clin Neurosci 2004; 58: 624–29. Tochigi M, Otani T, Yamasue H, et al. Support for the relationship between serum cholinesterase and post-traumatic stress disorder; 5-year follow-ups of victims of the Tokyo subway sarin poisoning. Neurosci Res 2005; 52: 129–31. Ministry of Defence. Review of modelling of the demolitions at Khamisiyah in March 1991 and implications for UK personnel. Jan 27, 2005: http://www. mod.uk/issues/gulfwar/info/khamisiyah2005/conclusions.htm (accessed June 25, 2005). Smith TC, Gray GC, Weir JC, Heller JM, Ryan MA. Gulf War veterans and Iraqi nerve agents at Khamisiyah: postwar hospitalization data revisited. Am J Epidemiol 2003; 158: 457–67.
Big pharma and the UK Government In March, 2005, the UK House of Commons Health Select Committee reported on the influence of the pharmaceutical industry.1 The committee began its inquiry in June, 2004, took evidence from 50 witnesses during nine public sessions, made four site visits (including trips to Brussels and Australia), and received nearly 160 written submissions. Its overall findings were clear: the influence of the pharmaceutical industry is enormous and out of control. The committee learned that while the industry’s influence was traditionally targeted at health professionals, today, big pharma’s tentacles penetrate much more widely, reaching patients, health departments, regulators, managers, researchers, and medical charities, and then on to academics, the media, carers, school children, and politicians. Other parallel issues also arose. Could patients be disadvantaged by the fact that the large multinationals design, sponsor, orchestrate, and control the publication of all the key drug trials; produce, market, and promote the medicines we take; and virtually determine how medicines are prescribed? Big pharma works hard and spends vast amounts to gain influence, and a key question facing the committee was whether such a pervasive influence could be in the interest of public health? Moreover, if the influence of big pharma is so ubiquitous, and assuming that its aims are achieved by legal means, can anything be done to curb its effects? Most of the committee’s 48 recommendations were directed at the UK Department of Health. Other recommendations reflected wider concerns and addressed, for instance, the Department of Trade and Industry, universities, patients’ and professional groups, and, of course, big pharma itself. www.thelancet.com Vol 367 January 14, 2006
The Government published their response in September.2 In many areas, the Government intends to make changes and these are to be welcomed. But the response reveals how aspects of Government remain aloof and out of touch. The committee’s most telling recommendation was the call for a public inquiry into the workings of the Medicines and Healthcare Products Regulatory Agency—
97
7
8
Sereti I, Imamichi H, Natarajan V, et al. In vivo expansion of CD4CD45RO CD25T cells expressing foxP3 in IL-2-treated HIV-infected patients. J Clin Invest 2005; 115: 1839–47. Sereti I, Anthony KB, Martinez-Wilson H, et al. IL-2-induced CD4 T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation. Blood 2004; 104: 775–80.
9
10
Hengge UR, Goos M, Esser S, et al. Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients. AIDS 1998; 12: F225–34. Douek DC. Disrupting T-cell homeostasis: how HIV-1 infection causes disease. AIDS Rev 2003; 5: 172–77.
Long-term effects of sarin Like the riot-control agent CS, sarin is named after the chemists, German this time, who developed it in the late 1930s as a candidate pesticide. This cholinesterase inhibitor (isopropylmethylphosphonofluoridate or GB) was not used in the 1939–45 war because Germany feared retaliation. In fact the Allies were as ill-prepared for nerve gas in the 1940s as they had been for the chlorine released over their lines at Ypres, Belgium, in 1915. After both wars there was catching-up to do, and one focus of attention in the 1950s was the nerve “gas” sarin (a highly volatile liquid). During the Cold War, fears of nerve gas attacks were very real, and NATO for a time had sarin as an approved weapon. Treaties now ratified make the use of sarin in war illegal. In the UK, the research side of that catching-up was conducted at a chemical defence establishment that has had eight different names since it opened in 1916.1,2 “Porton Down”, as it is widely known, is seldom out of the news for long. On Oct 19, 2005, the European Court of Human Rights held that, for one of six related claims, the UK Government had violated the human rights of a former soldier who had sought information about his time as a Porton volunteer in mustard and nerve gas experiments in the 1960s.3 Mr T M Roche’s belief that his long-term ill-health should be attributed to the experiments he took part in is currently under re-review by the Pensions Appeal Tribunal. A final judgment on the death in 1953 of Ronald Maddison, a British airman who died in an experiment with sarin, is also awaited. This death, the only one recorded among more than 20 000 volunteers who have attended Porton Down over the years, was labelled as a misadventure. However, in November, 2004, that inquest verdict was overturned and replaced by a verdict of unlawful killing.4 The Ministry of Defence has apologised to the man’s family. The test on May 6, 1953, had been undertaken “notwithstanding the fact that an identical test on 4 May 1953 resulted in an adverse blood test result in one serviceman”. Any claim for compensation www.thelancet.com Vol 367 January 14, 2006
“would be considered favourably on the basis of the negligence referred to above”.5 Nonetheless the Ministry wished to challenge the verdict of unlawful killing, and has been given the court’s permission to do so. The exposure to sarin estimated to kill 50% of a human population is 50–70 mg per m3 of air per minute of inhalation.6,7 In 1953 the fatal dose if sarin was dropped onto bare or battledress-covered human skin was not known for sure. One way to find out indirectly, it was thought, would be to measure red-blood-cell acetylcholinesterase activity before and after exposure to different doses and then extrapolate. It is these experiments in particular that are under scrutiny. What is known of longer-term effects of exposure to nerve gases, experimentally or in other settings? This question is relevant because Mr Roche is not alone among Porton volunteers in claiming that participation in chemical defence experiments has caused illness later in life and because more recently there have been nonexperimental exposures to sarin. The former claim is compounded by the view of some former volunteers that their consent was not properly sought. Porton’s research was secret and to a large extent it still is. However, thanks to the painstaking investigations of Rob Evans,2 we know a lot more than we did, and basic facts about sarin are generally available today in a way they would certainly not have been half a century ago.8,9 Fully informed consent on a secret project is probably impossible. Furthermore, recollections vary as to what was revealed to volunteers2 and it is legitimate to ask how far medical research generally had taken on board the importance of informed consent in the 1950s. The notion of fully informed consent by research volunteers may be older than the codified versions of it, but in 1967 The Lancet, commenting on Pappworth’s controversial Human Guinea Pigs,10 had to agree “that many researches would have been better left undone, that some were disastrous errors, and that the question of true consent by the patients was often glossed over or ignored”.11 Progress has 95
Comment
Getty Images
Rights were not granted to include this image in electronic media. Please refer to the printed journal
Guards at Porton Down's gates, June, 1963
been made since those days, and Porton has moved on too. That the volunteers might have been deceived is a more serious allegation and is not easy to explore. The UK Medical Research Council (MRC) Common Cold Research Unit opened its doors to volunteers in 1946. It was not a neighbour of Porton, being the other side of the city of Salisbury. However, both Porton and the MRC unit struggled at times to get sufficient volunteers, and both advertised. The Ministry of Defence denies deception and also notes, with questionable relevance, that no cold research was ever done at Porton.12 The early MRC volunteers were students, and service personnel are not prominent in accounts of the volunteers at this unit, such as Thompson’s.13 However, influenza vaccine trials were done at some military establishments so there was room for misunderstanding, especially if notices about research into respiratory afflictions were put up on barrack room walls side by side with Porton’s appeals. Frustratingly, a Ministry of Defence inquiry into the Porton Down Volunteer Programme 1939–89, announced more than 4 years ago,14 has been completed but not yet published. More light may come from that report, or from a recently announced Wellcome Trust grant.15 How likely is it that volunteers’ experiences at Porton account for illnesses afflicting them today? No researchdriven prospective programme on volunteers’ health was set up at Porton but we do have an uncontrolled study of 111 self-selected volunteers from the Porton Down Volunteers Assessment Programme.16 Disease patterns were much as one would expect in a group of men now of median age 62 years. The MRC’s retrospective study of the medical records is not expected to finish before 96
September, 2006.17 Evidence from the USA does not yet permit a clear-cut conclusion.18,19 From studies on firemen and policemen involved in the Tokyo subway sarin incidents, we know that rates of sister chromatid exchange can be raised,20 and the possibility of organophosphorus-ester-related neurotoxicity remains on the table.21 Published clinical follow-up of the victims of the Tokyo subway sarin poisoning22 includes posttraumatic stress disorder.23,24 Sarin (or a related agent) was used by Iraq in the Iraq-Iran war, and sarin was used by Iraq on its own Kurdish people, but rigorous epidemiological study of those incidents is difficult. US and UK troops were exposed to sarin when a stock of it was blown up in Iraq in 1991; modelling exercises are reassuring, but the 9000 UK troops were never closer than 130 km.25 Follow-up of the US personnel reveals no evidence of long-term harm.26 Gulf War syndrome, also ascribed by some to chemical and other exposures, shows how difficult it is to sort out claims of this sort, but on present evidence, medically significant late sequelae of sarin exposure seem hard to prove. David Sharp c/o The Lancet, London NW1 7BY, UK I am a Contributing Editor for The Lancet. 1
2 3
4
5 6
7
8 9
10 11 12
13
Ministry of Defence. Porton Down volunteers: a brief history of Porton Down. Dec 17, 2001: http://www.mod.uk/issues/portondownvolunteers/history. htm (accessed Dec 1, 2004). Evans R. Gassed: British chemical warfare experiments on humans at Porton Down. London: House of Stratus, 2000. European Court of Human Rights. Grand chamber judgment Roche v. the United Kingdom. Oct 19, 2005: http://www.echr.coe.int/Eng/Press/ 2005/Oct/GrandChamberjudgmentRochevUnitedKingdom191005.htm (accessed Oct 24, 2005). Evans R, Laville S. Porton Down unlawfully killed airman in sarin tests. Guardian Nov 16, 2004. http://www.guardian.co.uk/uk_news/story/ 0,,1351938,00.html (accessed Nov 18, 2004). United Kingdom Parliament. Porton Down: the death of Ronald Maddison. Lords Hansard Dec 21, 2004: column WS117. Ministry of Defence. Gulf Veterans’ illnesses, annex A: British chemical warfare defence during the Gulf conflict. http://www.mod/issues/gulfwar/ info/medical/ukchemical/annexa.htm (accessed Dec 2, 2004). Bide RW, Armour SJ, Yee E. GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: new method for estimating acute human toxicity (GB). J Appl Toxicol 2005; 25: 393-409. WHO. Public health response to biological and chemical weapons. Geneva: World Health Organization, 2004. Centers for Disease Control and Prevention. Emergency preparedness and response: facts about sarin. May 17, 2004: http://www.bt.cdc.gov/agent/ sarin/basics/facts.asp (accessed Oct 25, 2005). Pappworth MH. Human guinea pigs. London: Routledge Kegan Paul, 1967. Anonymous. Responsibilities of research. Lancet 1967; 2: 1144. Ministry of Defence. Porton Down volunteers: the Common Cold Unit. http://www.mod/uk/issues/portondownvolunteers/ccu.htm (accessed Dec 1, 2004). Thompson KR. Harvard Hospital and its volunteers: the story of the Common Cold Research Unit. Warminster, Wiltshire: Danny Howell Books, 1990.
www.thelancet.com Vol 367 January 14, 2006
Comment
14
15
16 17 18 19 20
Ministry of Defence. Historical survey of the Porton Down Service Volunteers Programme. Feb 21, 2002: http://www.mod.uk/issues/portondown volunteers/survey.htm (accessed July 9, 2005). Wellcome Trust. Death of a serviceman: will a study of a 50-year old death help us safeguard medical ethics in these troubled times? http://www. wellcome.ac.uk/doc_WTX023670.html (accessed June 25, 2005). Lee HA, Gabriel R, Bale AJ, Welch D. Clinical findings in 111 ex-Porton volunteers. J R Army Med Corps 2004; 150: 14–19. Medical Research Council. Porton Down update February 2004. London: MRC, 2004. Page WF. Long-term health effects of exposures to sarin and other anticholinesterase chemical warfare agents. Mil Med 2003; 168: 239–45. Institute of Medicine. Gulf war and health: updated literature review of sarin. Washington, DC: Institute of Medicine, 2004. Li Q, Hirata Y, Kawada T, Minami M. Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo disaster 3 years after the event. Toxicology 2004; 201: 209–10.
21 22 23
24
25
26
Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Envir Health 2003; 58: 484–97. Ohbu S, Yamashina A, Takasu N, et al. Sarin poisoning on Tokyo subway. South Med J 1997; 90: 687–93. Ohtani T, Iwanami A, Kasai K, et al. Post-traumatic stress disorder symptoms in victims of Tokyo subway attack: a 5-year follow-up study. Psychiatry Clin Neurosci 2004; 58: 624–29. Tochigi M, Otani T, Yamasue H, et al. Support for the relationship between serum cholinesterase and post-traumatic stress disorder; 5-year follow-ups of victims of the Tokyo subway sarin poisoning. Neurosci Res 2005; 52: 129–31. Ministry of Defence. Review of modelling of the demolitions at Khamisiyah in March 1991 and implications for UK personnel. Jan 27, 2005: http://www. mod.uk/issues/gulfwar/info/khamisiyah2005/conclusions.htm (accessed June 25, 2005). Smith TC, Gray GC, Weir JC, Heller JM, Ryan MA. Gulf War veterans and Iraqi nerve agents at Khamisiyah: postwar hospitalization data revisited. Am J Epidemiol 2003; 158: 457–67.
Big pharma and the UK Government In March, 2005, the UK House of Commons Health Select Committee reported on the influence of the pharmaceutical industry.1 The committee began its inquiry in June, 2004, took evidence from 50 witnesses during nine public sessions, made four site visits (including trips to Brussels and Australia), and received nearly 160 written submissions. Its overall findings were clear: the influence of the pharmaceutical industry is enormous and out of control. The committee learned that while the industry’s influence was traditionally targeted at health professionals, today, big pharma’s tentacles penetrate much more widely, reaching patients, health departments, regulators, managers, researchers, and medical charities, and then on to academics, the media, carers, school children, and politicians. Other parallel issues also arose. Could patients be disadvantaged by the fact that the large multinationals design, sponsor, orchestrate, and control the publication of all the key drug trials; produce, market, and promote the medicines we take; and virtually determine how medicines are prescribed? Big pharma works hard and spends vast amounts to gain influence, and a key question facing the committee was whether such a pervasive influence could be in the interest of public health? Moreover, if the influence of big pharma is so ubiquitous, and assuming that its aims are achieved by legal means, can anything be done to curb its effects? Most of the committee’s 48 recommendations were directed at the UK Department of Health. Other recommendations reflected wider concerns and addressed, for instance, the Department of Trade and Industry, universities, patients’ and professional groups, and, of course, big pharma itself. www.thelancet.com Vol 367 January 14, 2006
The Government published their response in September.2 In many areas, the Government intends to make changes and these are to be welcomed. But the response reveals how aspects of Government remain aloof and out of touch. The committee’s most telling recommendation was the call for a public inquiry into the workings of the Medicines and Healthcare Products Regulatory Agency—
97