» Introduction
The Greatest Story Never Told
For the past 17 years, the Army has been working on a new anthrax vaccine that contains no anthrax, and is made with an ingredient that it does not want to name. That ingredient is called squalene. Squalene is an oil. Without it, the new vaccine will not work any better than the old one. In fact, for all intents and purposes, without squalene the new vaccine is the old one. What makes squalene so important is its proven ability to stimulate a strong response from the immune system. That is something the main ingredient of the new vaccine, the now ultra-purified protein secreted by the anthrax microbe—recombinant protective antigen—cannot do by itself. It is too weak.
Immunologists have a special name for substances used to boost feeble vaccines. They are called adjuvants. Adjuvants are arguably the most extensively researched pharmaceutical product in the last quarter century that you never heard of. I have used the word adjuvant three times in this paragraph so far and that is probably three times more than you have ever seen it in print before. This is partly because the most effective adjuvants, those formulated with oils, are too dangerous for human use. That is squalene's other proven ability, causing incurable disease, which is why it is such a touchy subject with the Department of Defense.
The word adjuvant comes from a Latin word that means "to help." But with oil adjuvants like squalene that term is misleading. Today, only one adjuvant—an aluminum salt called alum—is licensed for human use. All the oil adjuvants are so noxious that their use is restricted to experiments with animals, and even then, governments have written strict regulations to govern how they are used. The classic oil adjuvant, called Freund's Complete Adjuvant, is considered too inhumane to even inject into animals. It does a terrific job of stimulating the immune system, though. Unfortunately, Freund's Complete Adjuvant can cause permanent organ damage and incurable disease. As early as the 1930s, these oil additives were notorious for inducing illness. By the 1950s, scientists knew these illnesses were specifically autoimmune. Today that is their chief use in research—inducing disease instead of preventing it. Scientists studying autoimmune disease cannot wait around for its spontaneous appearance in a lab animal; they inject it with Freund's Complete Adjuvant to reproduce autoimmunity on demand. Oil adjuvants made with squalene equally effective at this job, and regrettably according to Dutch scientists, equally inhumane. , ,
Autoimmune diseases are chronic and progressively debilitating ailments; some, like multiple sclerosis and lupus, can be fatal. They occur when the immune system loses its ability to distinguish what is "self" from what is foreign. Under normal circumstances, your immune system ignores the constituents of your own body; immunologists call this "tolerance." But if tolerance is broken, the immune system turns relentlessly self-destructive, attacking the body it is supposed to defend.
Adjuvants can break tolerance. In 1956, Dr. Jules Freund, the Hungarian born scientist who gave his name to the adjuvant he created, warned that animals injected with Freund's developed terrible conditions: allergic aspermatogenesis (stoppage of sperm production), experimental allergic encephalomyelitis (the animal version of multiple sclerosis) and allergic neuritis (inflammation of nerves that can lead to paralysis), allergic uveitis (an inflammation in the eye that can cause blindness). There was no reversing any of these conditions.
Scientists are still unsure why oil adjuvants do this. One theory is that oils have the ability to hyperactivate the immune system. "The cause is probably that when injecting these molecules, you create a chaos in the immune system," says Dr. Johnny C. Lorentzen, and immunologist with the Karolinska Institute, which awards the annual Nobel Prize for Medicine. He says these oils induce "an extremely powerful response," so powerful, in fact, that the immune system goes haywire and starts attacking things it would otherwise leave alone. Another possibility, which has not been explored very much, is that this harmful phenomenon actually has something to do with one of the greatest distinguishing characteristics of the immune system—its specificity. Over eons in time, this extraordinarily elegant and powerful system has evolved to respond very precisely to what it deems potentially harmful to the body. Our bodies contain all sorts of oily molecules. It could be that when an oil is injected, the immune system actually responds to it with a high degree of precision - just as it responds to everything else - but because the adjuvant resembles too closely those oils found in the body, the immune system begins attacking those too. In immunology this is called a "cross reaction." Neither proposition - chaos or specificity - has been proven so far. But however oils do their damage, it is well known that they do.
Army scientists have been as aware as anyone else of the harm that injecting oils can do. The problem for military personnel is that these scientists learned this lesson by injecting oils into troops in experiments that in some cases they did not agree to participate in. The central question in this book is whether such an experiment has been done again with the new anthrax vaccine and squalene.
Round One
Despite their dangers, oil adjuvants have come to exert an irresistible, almost magical allure on researchers. If they could truly stimulate the immune system safely, oil additives could help defend mankind from diseases like malaria and HIV. For germs such as these, no one dared make a classic vaccine - the kind made from the germ itself - for fear of accidentally infecting someone with an incurable, if not fatal infection. By splicing off just little bit of such a germ - not enough to make anyone sick - and combining that shard with an adjuvant, scientists hoped to protect people from lethal microbes. If they could do it for HIV, they reasoned, they could do it for any germ in creation. This siren song was so powerful that it did more than induce researchers to indulge in cynical risk/benefit calculations; in some cases, it made them forget the risks altogether.
The first time Army scientists succumbed to this allure was in 1951 at Fort Dix, New Jersey in an experiment that involved 44,459 troops. More than 18,000 of them got injected without their informed consent with a newly formulated oil additive for vaccines. The Army thought it had something new and safe. The world's best additive that no one dared inject into humans, Freund's Complete Adjuvant, was more than just mineral oil. It also contained Mycobacterium tuberculosis, the germ that caused TB. The mycobacteria were dead, but scientists thought they still might be in some way responsible for the problems associated with this concoction. So they removed the mycobacteria in hopes that the oil alone could do the trick; they called this new adjuvant "Freund's Incomplete Adjuvant." The incomplete adjuvant was just mineral oil in water, and a detergent to keep the oil evenly dispersed. Using it was a risky thing to do, but the Army considered the risks of not running this experiment even higher. This "incomplete" additive had been incorporated into an experimental flu vaccine. It was the flu that really worried the Army.
By all accounts, the great Spanish Flu pandemic of 1918 wasn't really Spanish at all. It was American. In fact, it was an Army flu. The first victim, the "index patient," was an Army private named Albert Gitchell who worked as a cook at the Army's Camp Funston on the vast Fort Riley military reservation in Kansas. It is believed that U.S. troops heading to Europe brought this flu with them. Before it was over, more than 20 people had died of influenza around the world—the deadliest natural disaster in world history. Army scientists wanted to prevent another global killer from emerging from an Army post where new recruits might become an unintended hatchery for some vicious new flu strain that once again could wipe out millions of people. Trying out a new oil additive on troops seemed like a relatively modest risk in comparison to the benefits of a better flu vaccine.
The Fort Dix experiment took place with the blessing of Fort Detrick. It was funded by the U.S. Army Medical Research and Development Command (USAMRDC), which would later oversee the development of the new anthrax vaccine and newer oil additives too. The Armed Forces Epidemiological Board (AFEB), which would be sponsor a large number of the experiments conducted on military personnel, would later recommend the injecting an experimental flu vaccine containing oil into every man and woman in the U.S. military without their informed consent. The risk of an outbreak of killer flu seemed too great to do otherwise. To run this experiment, the Army would contract none other than Jonas Salk. Salk had already tested Freund's Incomplete Adjuvant on medical students at the University of Pittsburgh under the sponsorship of the Armed Forces Epidemiological Board, and with funding from the Army Surgeon General. Based on this study, Salk thought it was safe.
Over the next two decades, the entire U.S. public health establishment - civilian and military - kept watch on what happened to the troops from Fort Dix. Everyone wanted in on the act. USAMRDC funded this study and its follow-ups. The National Academy of Sciences, the Walter Reed Army Institute of Research (WRAIR) and the Walter Reed Army Medical Center (WRAMC) did the initial round of surveys. Then the list started to grow. The National Academy of Sciences and the National Research Council organized more studies at the request of the Veteran's Administration, the Army and the U.S. Public Health Service "in collaboration with the Armed Forces Epidemiological Board." At the 17-year mark, academia got involved too. An AFEB scientist on the faculty of the University of Michigan School of Public Health organized yet another follow-up. No one, it seemed, wanted to be left out of such an important experiment.
And the experiment that seemingly had no end. Twenty-one years after Salk first injected unsuspecting soldiers with a theoretically new and improved flu vaccine, the Fort Dix troops were under the microscope yet again. The list of sponsors included many of America's most respected public health institutions: the National Academy of Sciences-National Research Council, the American Cancer Society, the Veterans Administration, the Department of Defense, the U.S. Public Health Service and the Commission on Influenza of the Armed forces Epidemiological Board. USAMRDC bankrolled this study, just as it did the first one. What was remarkable about this 21-year project - involving the military, civilian public health authorities and a major university - is that at no time during its execution did any of the scientists involved publicly discuss whether it was ethical to run a medical experiment on people without telling them. If these doctors had any concerns, they did not publish them.
Long before the last study was completed, AFEB proposed the adoption of an experimental flu vaccine with oil for everyone in the military. In 1963 and 1964, AFEB recommended injecting every man and woman in the armed forces with the new vaccine. The board also recommended that Department of Defense also commence studies with oil added to tetanus and diphtheria toxoids, and polio vaccines. , Army doctors seemed determined to add oil to every vaccine they could.
Here is what they were not telling anybody. By 1964, the year when everyone in the military was supposed to get immunized with an oil-boosted influenza vaccine, the Army already knew the risks this vaccine presented for a very specific type of illness. AFEB's Colonel Abram S. Benenson had drawn up a list of diseases that investigators should watch out for in veterans injected with the oily flu vaccine at Fort Dix. Benenson's list read like the contents of a chapter on autoimmune disease in an immunology textbook. It included multiple sclerosis, myelitis, Guillain-Barré syndrome, uveitis, neurodermatitis circumscripta and disseminata, amyloidosis, lupus erythematosus, dematomyositis, scleroderma, chronic pericarditis, Raynaud's disease, rheumatoid arthritis, rheumatoid myositis and acute glomerulonephritis—all of them autoimmune diseases.
The final study on the Fort Dix troopers had data that none of the previous ones had: autopsy results. The soldiers had grown older and many of them had died. Epidemiologists, mainly working for the National Research Council and the American Cancer Society, reported a "significant excess of deaths" in soldiers given the oil-boosted vaccine, which the investigators related to "ill-defined vascular lesions of the central nervous system." They attributed this fact to the greater number of autopsies available for the soldiers given the oil-boosted vaccine. But there were hints of a problem with autoimmunity. Ten percent of the soldiers studied, who were injected with the oil-boosted vaccine, developed a "collagen disease," which is a term doctors used to use interchangeably with autoimmune disease. Still, the number of patients in this study was too low to extrapolate any reliable conclusions from the data. That did not prevent government and military doctors from doing just that. They concluded that the oily flu vaccine was safe. Nevertheless, what the government then did not do was telling. The FDA never licensed the vaccine, or the oil adjuvant, for human use.
The Fort Dix experiment was the first time Army doctors and scientists injected an oil-boosted vaccine into U.S. troops without informed consent; there is now clinical evidence that it was far from the last. For more than a half century, factions in military medicine and in the U.S. public health establishment have actively campaigned to get an oily vaccine additive licensed, seemingly at any cost.
The Emperor's New Clothes
When scientists at Fort Detrick, following Joe Jemski's 1992 talk, reviewed the existing literature on the Wright vaccine, it didn't look good. Even with 6 shots, the vaccine did not protect very well. Guinea pigs vaccinated with the licensed human vaccine died when exposed to certain strains of anthrax. In 1986 the bad news got worse. In discovering that the licensed vaccine protected against the Army's old weapons strain, Vollum - from which the vaccine had been derived - Stephen Little and Gregory Knudson also discovered 8 more anthrax strains for which the PA vaccine did not work. Among them was the now notorious Ames strain that was mailed in 2001 anthrax letter attacks. Like the Army's previous research, the data confirmed that a live spore vaccine provided better protection against more strains. "The fact that the spore vaccine provided protection against all isolates tested suggests that other antigens may play a role in active immunity," they concluded. Which would argue for a live anthrax vaccine, but Fort Detrick's scientists expressed an age old concern about problem with living vaccines that could be traced all the way back to Pasteur: "Since this vaccine is a live immunogen," they warned, "safety factors must be considered before its use." Little and Knudson did not rule out the possibility of resorting to a live spore vaccine, but that is not what they then chose to pursue.
When they, along with Fort Detrick scientists Bruce Ivins and Sue Welkos, began working on a new anthrax vaccine, they chose a design that was all the rage at the NIH—subunit plus adjuvant. "Subunit" refers to small fragments of a germ. For safety, NIH scientists were using subunits of lethal viruses like HIV to be the chief component of their new generation of genetically engineered vaccines. These ultra-pure vaccines, which reduced an immunization to mere molecules from a microbe, were safe, but at a price. They were weak. In some cases, they afforded no detectable level of protection at all. This is why the NIH wanted an adjuvant more robust than alum for its new vaccines.
The subunit that Little, Knudson, Ivins and Welkos chose for the Army's new anthrax vaccine was a little surprising. It was protective antigen—the same main ingredient in the vaccine they were trying to replace. Although all the data from both U.S. and British military experiments from the 60's forward indicated that more components of the anthrax microbe needed to be in any effective anthrax vaccine—a fact that even Little and Knudson acknowledge in their 1986 paper—Fort Detrick's newest generation of anthrax investigators did just the opposite. In fact, they did one better. With recombinant DNA technology, their new vaccine would eliminate every extra molecule of anthrax unrelated to protective antigen. It would be purest PA formulation ever made, and would hence be the weakest anthrax vaccine ever made. Remember, in immunology, purity equals weakness.
Yet when Fort Detrick's scientists traveled to England in 1989 to report on their new vaccine to the International Workshop on Anthrax, they had some startling results to announce: Fort Detrick had found what everyone had been looking for: a single-shot anthrax vaccine. In guinea pigs, the new anthrax vaccine produced complete protection against the Ames strain with just one dose.