Vaccine A
by Mark Greener
[ bookreviews ]
During the Second World War, Japanese and Nazi doctors committed atrocities during 'medical' research. So after the trial of Nazi doctors at Nuremberg, researchers and governments agreed the Principles of Ethics Concerning Experimentation with Human Beings, which still form the ethical foundation of clinical trials. These guidelines have been updated regularly since. So surely such ethical abuses are now history?
Not according to some survivors of the first Gulf War. In the UK alone, some 6,000 veterans claim to suffer from Gulf War syndrome. The armed forces received numerous drugs and vaccines that, the sufferers claim, triggered a diverse range of unpleasant and sometimes debilitating symptoms, such as aching joints, sore muscles, weight hair, hair loss, short-term memory loss and headaches. In a new book, investigative journalist Gary Matsumoto places the blame for many Gulf War syndrome symptoms on unlicensed vaccines. If he's right - and he presents some compelling circumstantial evidence - the first Gulf War could emerge as this generation's Tuskegee.
"The Tuskegee syphilis study has come to symbolise the most egregious abuse of authority on the part of medical researchers," Amy Fairchild and Ronald Bayer wrote in Science. The Tuskegee study enrolled 399 economically deprived African American men from Rural Alabama who suffered from tertiary (advanced) syphilis. Researchers followed the men from 1932 to 1972. The study, run under the auspices of the United States Public Health Service (USPHS), did not inform the men that they suffered from syphilis or offer advice about treatment and prevention. Rather the USPHS offered treatment for "bad blood". According to Fairchild and Bayer, the USPHS withheld penicillin, introduced during the 1940s, because they "never again would ... find such a group of untreated individuals".
The African American men aged between 25 and 50 years "had their life expectancy reduced on an average of about 20%", comments Robert White, writing in Archives of Internal Medicine. By 1952, 28% of the Tuskegee group had received penicillin, a similar proportion to a control group of men without syphilis. Few of these penicillin prescriptions were for syphilis, however. White also comments that journals published by the American Medical Association (AMA) published three of the 14 papers arising from the Tuskegee study. Two of these appeared after the AMA adopted the Principles of Ethics Concerning Experimentation with Human Beings.
As White points out, Tuskegee wasn't the only example where treatment for syphilis was "purposefully and intentionally withheld". A study from Stanford University in the 1940s included "a sizable white population". For this and other reasons, some commentators question the extent to which Tuskegee represents overt racism, White notes. Nevertheless, the study casts a long shadow. Even today, many African Americans are reluctant to participate in clinical studies. Indeed, their mistrust of the medical system may contribute to the relatively poor health outcomes among this group.
Some 50 years after Tuskegee, the armed forces in the Gulf received a pharmacological smorgasbord of vaccines and drugs. Untangling the pharmacokinetic (how the body handles drugs) and immunological interactions is enough to give pharmacologists nightmares. To take one example: the blood brain barrier help keep noxious chemicals out of your brain. But extreme stress can make the blood brain barrier more permeable. Some Gulf War Veterans were exposed to a group of drugs called cholinesterase inhibitors developed as chemical weapons and to prevent insect infestations. Some pharmacologists believe that the stress of war might allow these chemicals access to the brain, thereby contributing to Gulf War Syndrome.
In Vaccine A, Matsumoto suggests that an anthrax vaccine could be responsible for many, if not most, of the symptoms of Gulf War Syndrome. The vaccine, Matsumoto claims, contained squalene, which acted an adjuvant. The anthrax vaccination schedule wasn't appropriate for the armed forces: it took too many jabs over too long a period to ensure immunity. Adjuvants give the immune system a boost, so the solider could be immunised more rapidly.
Critically, Matsumoto suggests that the armed forces were not told that the vaccine was experimental. They were not informed of the potential side effects. In other words, the soldiers didn't give their informed consent, a cornerstone of ethical clinical studies.
Ironically - and I'm no advocate for the military - the senior armed forces staff could have believed that what they were doing was right. They could have had their forces' best interests at heart. Army scientists, Matsumoto notes, believed the vaccine was safe. And, he points out, what if Saddam had launched a major biological attack? Nevertheless, Matsumoto claims that "rather than defend their actions as a hard judgement call ... military doctors deny having used an experimental anthrax vaccine and deny that the anthrax vaccine given any [sic] veteran had squalene in it."
Much of the evidence suggesting that the Gulf War veterans received an experimental vaccine presented by Matsumoto is circumstantial. He bases his argument on interviews with Gulf War veterans and their doctors as well as on extrapolations from animal studies and publicly available sources. As Matsumoto admits: "I have no whistleblower saying the experiments on military personnel ... took place. I have no copy of a memo ordering them to commence. There is hidden in plain sight, however, clinical and forensic scientific evidence that they were done."
Matsumoto's book is unashamedly popular and easily accessible to the 'general public'. He is not writing for scientists. I'm a biologist and to convince me beyond doubt, I'd need a more dispassionate, scientific, technical evaluation of the clinical, experimental and epidemiological evidence.
For example, Matsumoto claims that some Gulf War syndrome survivors developed systemic lupus erythematosus (SLE). This unpleasant condition arises when the immune system mounts an immunological civil war against proteins in the joints, skin, kidneys and almost every other body (so-called autoimmunity). The body produces antibodies against these proteins - in the same way that you produce antibodies against invading bacteria. He claims that the squalene adjuvant 'over-stimulated' the immune system triggering autoimmunity.
At first sight some of the cases are compelling. Some young male armed force members developed severe SLE. Young men rarely develop SLE, but it's not unknown. In armed forces the size of America's, you would expect the occasional case. The increase could, in theory, be coincidence. So to prove causality, you need to show that squalene triggered the SLE. Just because some people received the vaccine and developed SLE - or any other Gulf war symptom - doesn't necessarily mean that squalene caused autoimmunity.
Some supporting evidence is beginning to emerge. A series of studies from University of Florida, for example, found that squalene and several other adjuvants stimulated the formation of lupus antibodies in mice and increased production of the chemicals that the immune system produces to drive inflammation. The weight of evidence seems to support Matsumoto's case.
It's a long jump from mice to humans. But combine the animal studies, the case histories from the Gulf War Veterans and the circumstantial evidence Matsumoto uncovers, and there certainly seems to be a case to answer. Matsumoto's achievement is to highlight the need for an independent, in depth, authoritative toxicological evaluation to determine if the vaccine contributed to at least some cases of Gulf War syndrome, whether there was a cover up and whether the use of an experimental vaccine, if it happened, violated human rights. Without this investigation we won't know for sure, but Matsumoto certainly presents sufficient of a case that the authorities need to answer.
Conspiracy theorists will find much to ponder in Vaccine A, as will those who believe military intelligence is an oxymoron. If Matsumoto is right, the vaccine A story underscores that governments all too easily sacrifice ethics on altar of political pragmatism - a critique human rights activists have made for years, but rarely against the USA's or the UK's own population. That's one reason Tuskegee remains a bioethical benchmark. For 40 years, Fairchild and Bayer comment, the Tuskegee experiment violated the men's "most basic rights". Vaccine A suggests that the first causality of war isn't necessarily truth; it could be those same basic rights.
References
Fairchild AL and Bayer R Uses and abuses of Tuskegee Science 1999;284:919-921
White RM Unravelling the Tuskegee study of untreated syphilis Arch Intern Med 2000;160:585-98
Kuroda Y, Akaogi J, Nacionales DC, et al Distinctive Patterns of Autoimmune Response Induced by Different Types of Mineral Oil Toxicol Sci 2004;78:222-228
Satoh M, Kuroda Y, Yoshida H, et al Induction of lupus autoantibodies by adjuvants J Autoimmun 2003;21:1-9
Kuroda Y, Nacionales DC, Akaogi J, et al Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine Biomed Pharmacother 2004;58:325-37
