Events following the anthrax attacks are revealing huge inadequacies in coping with biowarfare. Dr. Mae-Wan Ho reports.
'Bio-defence' has become number one priority in the United States since the anthrax attacks. Researchers at the Army Medical Research Institute of Infectious Disease in Fort Detrick, Maryland, accelerated their efforts to get new anthrax vaccine into clinical trials. In November, the Department of Health and Human Services announced a $428 million order for 155 million doses of smallpox vaccine from Acambis, a company in Cambridge, UK, in addition to the 54 million doses already on order. President Bush has already requested $1.5 billion to purchase vaccines and antibiotics [1].
Vaccines are still considered the cornerstone of biodefence, and research on vaccines the staple of biodefence laboratories.
Yet, two months before the September 11 terrorist attacks, the US Department of Defense (DoD) sent Congress a report by an independent panel of experts that concludes the military's system for developing vaccines to protect troops from anthrax, smallpox, and other exotic bioweapons "is insufficient and will fail"[2].
One fundamental problem is, how can vaccines be developed against unknown diseases? And how can the vaccines be tested for efficacy and safety in the absence of a substantial population of the afflicted?
In the mid-1990s, the US DoD created the Joint Vaccine Acquisition Program (JVAP) that takes promising leads from military researchers, hands them to an outside contractor, which farms them out to other contractors. Currently JVAP has 8 candidate vaccines. The programme has been described as "terrible" and "disastrous", and the independent panel called for it to be scrapped and replaced by a $3.2 billion military program that would produce it own vaccines in a government-owned production plant.
But are vaccines the answer? A disturbing picture is emerging from attempts to cope with just two of the potential biowarfare agents that top the list: smallpox and anthrax.
Smallpox has been eradicated, and declared so by WHO in 1980. The only known remaining samples of the virus are in US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and at the State Research Centre of Virology and Biotechnology in Novosibirsk, Siberia, USSR. Because smallpox vaccination itself carries some risk, vaccine production also ended, until after the Soviet Union collapsed, and fears mounted that terrorists might get hold of the Novosibirsk stock. At the same time, it was revealed that the USSR had been carrying out massive bioweapons research towards the end of the cold war.
Smallpox is considered the most serious bioterrorist threat. It has a high fatality rate of more than 30%, and spreads from person to person. Because routine vaccination ceased throughout the world nearly 20 years ago, there is now a highly susceptible population that travels more widely and frequently than ever before, thus facilitating rapid dissemination of disease.
In the United States, vaccinations stopped in 1972, so tens of millions of Americans younger than 30 years were never vaccinated, and those vaccinated decades ago may also have lost immunity.
The US government is training doctors to recognise the disease and vaccinating a small teams of experts who would rush to any part of the country to contain and treat a suspected outbreak [3].
Disease centers officials are not planning mass smallpox vaccinations. WHO estimated that about 60 million doses of smallpox vaccine are left worldwide, with about 15.4 million doses in the US. But this old vaccine and the antidote for adverse reactions arising from the vaccine are both deteriorating [4]. Another problem with mass vaccination is that there are many strains of smallpox virus in existence, most of them uncharacterised, and vaccines against one strain may not protect against other strains, particularly if genetic engineered strains are designed to escape immune detection, as they can be [5]. Yet another reason against mass vaccination is that the risks could outweigh any benefits, particularly if no smallpox case ever appears.
Among the 5.5 million Americans who received their first smallpox vaccination in 1968, eight died as a result. About two people per million who were vaccinated had an often fatal reaction known as vaccinia necrosum, that destroyed flesh and muscle, and about four per million developed encephalitis, or inflammation of the brain. Other rare side-effects include agressive eczema, and in people suffering from immune damage such as those infected with HIV, a dangerous pox infection. Today, there are hundreds of thousands of Americans with weakened immune systems from HIV and other viruses, as well as drugs used to treat cancer and prevent rejection of organ transplants. Such people could become ill from the vaccine, and infect others, precipitating an epidemic.
So, the 'standard epidemiologic response' to smallpox, we are told, is to identify the disease, isolate the cases, vaccinate everyone known to have had direct contact with infected people since the first week of symptoms and then monitor their state of health. A mathematical model published in the current issue of Emerging Infectious Diseases suggests that a stockpile of 40 million doses is needed just for the US under those circumstances [6]. In other words, a new vaccine has to be made. But how can the efficacy, let alone the safety of the new vaccine be ascertained, when the disease has been globally eradicated? And it would not be ethical to deliberately challenge human subjects with Variola in order to study the vaccine [7].
The FDA is attempting to overcome this deadlock. It published and requested comments on a proposed rule for approving new drug and biological products developed to prevent serious or life-threatening conditions based only on evidence of effectiveness derived from appropriate studies in animals, without adequate and well-controlled efficacy studies in humans. In other words, in a state of emergency, human beings will have to be guinea-pigs. Large pharmaceutical companies are being asked to manufacture some 300 million doses of smallpox vaccine within a few months as an unlicensed "investigational new drug".
There is no effective cure or treatment for smallpox. Antiviral drug cidofovir proved effective against 31 strains of variola, the smallpox virus, but only in the test tube. It also protected monkeys exposed to monkeypox. But will it protect human beings against smallpox?
Anthrax vaccine already exists, but the company, p.8 were used by the Clinton Administration for mass vaccination of troops, the remaining 24 000 doses are dedicated to the military. Bioport's vaccine is a complex broth of proteins filtered from a non-threatening strain of anthrax. Six shots are required for full protection, plus an annual booster. But this vaccine is at the centre of a new controversy [8].
Amid pressure to vaccinate civilians at risk for anthrax, evidence has emerged that unauthorized changes in the vaccine manufacturing process were made before the Gulf War that may have boosted the potency of the vaccine to dangerous levels.
The CDC has recently recommended that 800 lab technicians who are processing suspected anthrax samples receive the vaccine. It is also considering a recommendation that postal employees who work near high-speed sorting machines receive the vaccine.
But veteran groups and armed services personnel have complained that the anthrax vaccine is unsafe. Researchers at the Army's biological warfare defence lab found as much as a 100-fold increase in the concentration of the anthrax vaccine's active ingredient in batches produced after a switch to new filters in 1990.
The previously unpublished report was uncovered by investigators of the General Accounting Office, which has been studying the complaints from veterans and military personnel, and released its findings towards the end of October.
The risks are not understood. 'Protective antigen' from dead anthrax bacteria, is one of the key proteins involved in the toxicity of anthrax, and is used to stimulate the immune system to produce antibodies. But there can be too much of it.
"Overstimulation of the immune system in certain respects can lead to immunological disorders," said Dr. Jack Melling, formerly head of Britain's anthrax vaccine program and a consultant to the GAO.
The report has bolstered suspicions by veterans that the anthrax vaccine they were given in 1990 is somehow related to Gulf War Syndrome, the symptoms of which include chronic pain, skin rashes, nausea, memory loss and concentration problems.
Not surprisingly, current efforts by the Pentagon to vaccinate 2.4 million military personnel have run into stubborn opposition by soldiers, sailors and airmen who maintain that a disproportionate number of those taking the shots have suffered dangerous side effects.
Army Spc. Sandra Larson of Spokane died of aplastic anemia after taking the sixth shot in the series. Last week, her family filed suit against vaccine maker Bioport Corp., of Lansing, Mich., alleging that the vaccine is at fault.
The company maintains that the vaccine is no more dangerous than childhood vaccines used against diphtheria and whooping cough (which also has its own critics as it turns out [9]). Bioport acquired rights to anthrax vaccine manufacturing in 1998 from Michigan Department of Public Health, which had been making it since 1970. Until the Gulf War, the vaccine was used primarily by laboratory workers and veterinarians who might be exposed to the rare disease.
The army report, delivered to the House national security subcommittee, also describes how the Michigan Department of Public Health, under contract with the Pentagon, changed both the reactor vessels in which the vaccine is made and the filters with which it is refined, without FDA approval.
Russell Dingle, an American Airlines pilot, resigned from the Connecticut Air National Guard rather than take the required anthrax shots. He said the report underscores how a succession of anthrax vaccine makers flouted rules designed to assure safe medicines.
The difficulties in dealing with potential smallpox and anthrax attacks on civilians apply in different degrees to all biowarfare agents. Vaccines can be worse than useless for biodefence. The now officially recognised 'side-effects' of vaccinations may be far more extensive, as independent research by physicians and virologists are revealing [9]. Genetically engineered vaccines against HIV, for example, are inadvertently being used as slow bioweapons in large-scale clinical trials carried out in many developing countries [10].
An article in Nature Genetics warns that, compared with chemical and nuclear weapons, "biological weapons pose by far the greatest threat, because they can be as lethal as nuclear weapons and are easier to obtain" [11]. GM and bio-weapons must be regarded as the ultimate deterrent, at least on par with nuclear weapons, and should be controlled as such.
Article first published 12/12/02
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