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November 25, 2004

Anthrax Vaccine

This is a MUST READ if you are involved in bio-trerrorism or vaccinations. If you are a veteran who has had the Anthrax Vaccine you will want to "read and weep."

Thomas Barnes
Managing Director

Vaccine-A uncovers a story of betrayal—the betrayal of the men and women who serve in the armed forces, the betrayal of medical ethics, and the betrayal of the American people by military and civilian leaders sworn to defend and protect. Veteran journalist Gary Matsumoto shows that the worst friendly-fire incident in military history came from something no soldier had any reason to think would harm him: a vaccine administered by the military's own medics. When troops went to the Middle East to fight the Gulf War in 1991 and the Iraq War in 2003, many—perhaps thousands—received an experimental anthrax vaccine instead of the FDA-approved vaccine.

Without their knowledge or consent, the U. S. government used them as human guinea pigs in a massive medical experiment that went disastrously wrong.
About the Author

Gary Matsumoto, a journalist based in New York City, has reported from thirty-two different countries on five continents, covered two wars and five popular uprisings, and won ten journalism awards. He has been the London Bureau Manager and Chief Foreign Correspondent for NBC Radio News; a National Correspondent for NBC's Weekend Today Show and Senior Correspondent for the Fox News Channel. As a broadcaster, he has covered events ranging from the toppling of the Communist Party in Eastern Europe to Desert Storm, the Tiananmen Square massacre to the death of Princess Diana. He has written about the anthrax letter attacks for the Washington Post and Science magazine. His 1998 article in Vanity Fair was the first to draw the connection between the anthrax vaccine and Gulf War Syndrome.
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 MILLION 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.

If this was completely at odds with everything Army scientists had found over the previous three decades, it was because the Fort Detrick team had added something new to the formula. It was a kind of trick, though not in the sense of something fraudulent or deceptive. The Army's scientists made no effort to conceal what they did. Quite the contrary, they reported this trick in great detail. It was an old trick. In the 80s, scientists at NIH had been promoting the use of oils in vaccines again. By now, there was a new crop of oily vaccine boosters hot off the lab bench. It was the oil emulsions that helped transform the Army's hapless protective antigen formula into a potent single-shot vaccine.

Dr. Bruce Ivins informed the workshop gathering in old cathedral city of Winchester that he had added three different adjuvants to his one-shot wonders. One was called "Tri-Mix," another "DeTox," and a third was "SAF-1," which stood for Syntex Adjuvant Formula I. They were all made with bacterial scraps from truly noxious microbes like Salmonella typhimurium and Mycobacteria tuberculosis. The British scientists from Porton Down tried a different tack—adding a preparation to the British anthrax vaccine made from the whooping cough germ, Bordetella pertussis. At Winchester, the Porton contingent called their approach "microbial supplementation." All of these adjuvants relied on bacteria, or portions of them, to stimulate the immune system.

The three additives used by Fort Detrick, however, differed from Porton Down's in one very significant way. The Fort Detrick additives were all emulsified in oil. The oils were only supposed to be "vehicles" that conveyed the bits of bacteria through the bloodstream. SAF-I, which provided less protection than the other two, contained the oil squalane. The two adjuvants that helped provide complete protection from Ames in guinea pigs, Tri-Mix and DeTox, were emulsified in squalene. At the time, no one at Fort Detrick or the NIH seems to have been aware that these oils were themselves immunostimulants.

Having invested decades into refining protective antigen to a singular purity, Ivins et al. were essentially polluting this new ultra-pure vaccine with extraneous antigens to make it work. That is what an adjuvant was—extra antigenic material for a vaccine that had been purified to such an extent that it could no longer do the job it was designed to do. Perhaps it was the importance of their apparent breakthrough that blinded these scientists to what they had done. Whatever it was, it prevented them from seeing the absurdity of their new creation, or its risks. A fully intact microbe presents dozens of different chemical binding sites an antibody can latch onto. Each of these sites is a separate target for a multi-front attack by the immune system. In pursuit of purity, Army scientists had removed all of the targets of anthrax germ but one. Now they had a dubious product that they were determined to improve, and they did it by adding targets from germs other than B. anthracis. Instead of adding more antigenic material from the anthrax microbe - as Lincoln had suggested in the 60s and as Turnbull and Melling had done in the 80s—the Fort Detrick team incorporated pieces of completely different germs.

This was Rube Goldberg immunology. The Army's vaccine whiz kids had devised the most convoluted, expensive and time-consuming way conceivable to make a virtually identical product—protective antigen—and then added material that essentially diverted the immune system's attention away to antigens unrelated to anthrax. Fort Detrick's new, souped-up single protein vaccine, like the old one, did nothing to induce an immune response to the organism itself, which could still feed, secrete toxins and multiply inside a vaccinated host. There was also one more flaw in this design: oils are potentially toxic, and the Fort Detrick team knew it. In Bruce Ivins' frequently cited paper on the Army's pursuit of an improved human anthrax vaccine, he noted that oil adjuvants "can provoke toxic, allergic, ulcerative, or lethal reactions." This should have prevented him from committing Fort Detrick to an oil-boosted anthrax vaccine in the first place, but for reasons that Ivins has never publicly disclosed, it did not deter him. Neither he nor anyone else who worked on this vaccine at Fort Detrick has published an explanation for why they did this.

Round Two

Anyone even remotely familiar with oil additives for vaccines could have told you that they were a big problem. For reasons science has yet to fully explain, oils and other fatty substances found in the body, like cholesterol and phosopholipids, are potent stimulants to the immune system. Try as they might, scientists trying to harness this property have yet to come up with an oil adjuvant safe enough to use in humans. Since the 1930's, the gold standard has been the aforementioned Freund's Complete Adjuvant—an elixir banned from human use because of its toxicity. When Freund's Incomplete Adjuvant, a vaccine additive made chiefly from mineral oil, proved too risky as well, scientists tried changing the oil.

In the early 1970s, scientists at UCLA Medical Center, including one of the most respected rheumatologists in the country at the time, Carl M. Pearson, started looking for a less toxic alternative to Freund's. They ran a series of experiments with a variety of edible oils on the assumption that because they were "metabolizable" the body could process them safely. In other words, if you could ingest them, you could inject them. Intuitively, this premise seems somewhat dubious: your body could metabolize a cheeseburger, for instance, but you couldn't liquefy it in a blender and inject the resulting slurry, and then expect to feel well in the morning. Pearson's associates, Michael Whitehouse and Frances W. Beck, injected more than dozen of these metabolizable oils into rats, including castor oil, coconut oil, olive oil, sesame seed oil, cottonseed oil, corn oil, wheat germ oil, safflower oil, cod liver oil, oleomargarine, and the commercial lubricating oil, silicone. When these were mixed with heat-killed Mycobacteria tuberculosis, the UCLA group got results it didn't expect. All of the oils were toxic; they all induced arthritis in rats with varying degrees of severity. The data changed Whitehouse's views on the safety of metabolizable oils. "To summarize very simply, I think most oils are dangerous," he now says. Based on their ability to cause arthritis, the researchers assigned the oils "arthritis scores," ranging from (+), which was moderately toxic, to (++++), which was guaranteed to cripple. Of all the metabolizable oils tested by Pearson's group, two were better than all the others at causing arthritis: squalene and squalane, the same emulsifying oils that Bruce Ivins used in his single shot anthrax vaccines.

Squalene and squalane scored (+++) and (++++) respectively. Between these two oils, squalene is the one you could definitely eat. Olive oil contains squalene; in theory, you could drizzle it onto a salad along with a little vinegar and have no worries. Your body would metabolize it along with the arugula and endive without as much as a hiccup. Injecting squalene, though, was another story. To make sure it was the oils that did the damage, Beck, Whitehouse and Pearson tried injecting rats with squalene and squalane without mycobacteria in the formula. Rats injected with either squalene or squalane all developed experimental allergic encephalomyelitis—the same MS-like disease caused by Freund's. The injected animals were left hobbled, dragging their paralyzed hindquarters through the wood chips in their cages. , The UCLA team had found what it was looking for: oils that induced autoimmune disease, but with less inflammation. Between the two of them, squalene was less desirable for UCLA's purposes. "Squalene was more arthritogenic," Beck recalls, "but it also produced a greater inflammation."

Risk v. Benefit

Given these oils proven ability to induce autoimmune disease, the Army's decision to put either of them in its second generation anthrax vaccine only makes sense when you put it in the context of the times, and in this case, a specific location. When he cancelled America's offensive biological warfare program, President Nixon also freed up some building for a more popular research effort. Arriving by helicopter at Fort Detrick's Blue and Grey Field in October 1971, President Nixon personally announced the creation of the Frederick Cancer Research Facility of the National Cancer Institute (NCI). Nixon had Fort Detrick allocate about 68 acres and 70 of its buildings as a new research campus for NCI. It was a fateful decision that would have consequences that even a president as forward-thinking as Nixon could not have foreseen. It would set in motion a series of decisions that would lead, almost inevitably, to the use of a substance that would endanger the health of hundreds of thousands of U.S. troops.

It is unclear how squalene first came to the attention of Army scientists at Fort Detrick, but one possibility is through the National Cancer Institute, now on its doorstep. Eliyahu Yarkoni and Herbert Rapp of NCI published a paper in 1979 that stirred national and international interest in the alleged therapeutic benefits of squalene and squalane. When combined with fragments of a particular bacterium, squalene and squalane had an astonishing effect. Yarkoni and Rapp reported complete tumor regression in mice injected with squalane, and nearly complete regression (92%) in mice injected with squalene. When they injected these oils directly into mouse tumors, the tumors either shrank or disappeared completely. The more oil in the mixture, the better it worked. Based on these early experiments, oils looked like they might hold the keys to the kingdom—a cure for cancer. There was, however, a hitch.

Yarkoni and Rapp knew about the UCLA data; citing the Beck and Whitehouse paper, Yarkoni and Rapp reported that squalene and squalane both caused autoimmune disease in rats—a fact that you will not find mentioned in any Army paper concerning Fort Detrick's work with squalene emulsions in the new anthrax vaccine. Even Yarkoni and Rapp barely mentioned the problem with squalene and squalane; it was limited to a single sentence at the end of their short paper. Although causing debilitating and ultimately fatal neurological damage in animals was a big downside, their concern, after all, was cancer.

Several more factors emerged in the 1980s that would affect the direction of the Army's anthrax vaccine research. The first was HIV. After the discovery of the human immunodeficiency virus in 1984, the cause of Acquired Immune Deficiency Syndrome (AIDS), the National Institutes of Health would devote billions to develop a vaccine. That year, the Centers for Disease Control reported 7,699 AIDS cases with 3,665 dead. By 1988, the number of diagnosed U.S. cases was 82,764 with 46,344 dead. That was a jump of more than 1000% in just 4 years. Mortality was 100%; for someone with AIDS, drugs could prolong life but not save it. Public health officials doing the math were horrified. No one dared make a whole virus vaccine, living or dead, from a germ like HIV. Vaccine researchers embraced gene-splicing as their only alternative—inserting HIV genes into non-lethal organisms like vaccinia. But the results were disappointing: these microbial hybrids barely elicited an immune response. That's why a new adjuvant was essential to NIH. Because of Yarkoni and Rapp's work, squalene and squalane emulsions had by then established themselves as NIH's adjuvants of choice.

HIV was threatening to become the great plague of the 20th century, worse even than the flu pandemic of 1918 that claimed more than 20 million lives. It was the public health cause célèbre of the 1980s. Rock Hudson had it; so did Liberace. When an Indiana school banned 14 year-old Ryan White from classes because he had HIV, Elton John and Michael Jackson became his friends and offered their support. Vice-President George Bush called for mandatory HIV testing. No other disease made as many headlines or pushed as many political buttons. For NIH, that translated into wide open government coffers. For researchers, it offered a shot at immortality. Any scientist who found a way to stop this new global scourge could reserve a seat in Stockholm for a Nobel Prize ceremony. A successful recombinant HIV vaccine would be just a start. The goal was to roll back all infectious diseases through immunization . if that were possible. But it wasn't going to happen without a more powerful vaccine booster. The FDA, stung by criticism from dying AIDS patients who wanted access to new drugs that could keep them alive even a few months longer, started to "fast-track" drugs through its licensing labyrinth, including experimental vaccines containing squalene. This was not without risks. The problem with the fast track was knowing when someone was playing it fast and loose.

Even NATO got on this bandwagon by sponsoring a conference in Cape Sounion, Greece, on vaccine adjuvants in the summer of 1988. The search for a new adjuvant was now a matter of national security. The U.S. Army sent a contingent from its Walter Reed Army Institute of Research led by Dr. Carl R. Alving, a proponent of vaccine boosters emulsified in squalene, in addition to his own favorite: liposomes. Liposomes are microscopic vesicles containing vaccine antigens. Think bath oil beads. Encapsulating bath oil in soluble beads makes it possible to transport measured doses of oil from the drug store where you bought them to where you ultimately want to put them—in your bathtub. Alving's liposomes were made from cholesterol, another oily substance closely related to squalene.

The Soviets Again

If anyone in the military had been inclined to ask questions about squalene's toxicity in the late 1980's, something else happened around that then that might have diverted them. In October 1989, a high-ranking Soviet biological weapons scientist defected to the West—the first one to do so. This was an extraordinary intelligence coup. At the invitation of a French pharmaceutical equipment maker, Dr. Vladimir Pasechnik of the Leningrad Institute of Ultra-Pure Biopreparations went to Paris for a conference and never went home. He left his family behind in Russia and wound up in Britain. One of the scientists who debriefed Pasechnik for the British was Jack Melling. "Pasechnik chose Britain," says Melling, "because he thought the U.S. still had an active biological warfare program and he didn't want anything more to do with making weapons. He didn't think the same of Britain." According to Melling, what Pasechnik told Britain's MI-6 raised even more alarm about the U.S. and British chemical anthrax vaccines. Pasechnik said that Moscow had created antibiotic-resistant super-strains of anthrax, plague and tularemia. Although Pasechnik's British handlers couldn't verify this, it sounded plausible enough to them; in part because making germs antibiotic-resistant was relatively easy to do, and in part because the Soviets had published several papers in the 1980's disclosing that they had developed a veterinary vaccine that immunized against all three of these microbes. Intelligence analysts had been asking themselves why Soviet livestock would need to be vaccinated against plague, tularemia and anthrax—the three agents regarded by bioweapons specialists as the most likely ones to be used in a biological warfare attack. They could not come up with a good answer.

Back in Maryland, Fort Detrick now had at least four viable prototypes of a single shot vaccine that they thought was safe. All were made from the protective antigen protein or pieces of it. Three others were recombinant vaccines; Fort Detrick had cloned the protective antigen gene into Bacillus subtilis, baculovirus and vaccinia. All of these prototypes were formulated with squalene or squalane. The ones showing the most promise were the protective antigen vaccines combined with these oils. According to Ivins and his Fort Detrick colleagues, just one dose of these new vaccines gave protection equivalent to three doses of the licensed U.S. vaccine . and the new vaccines were ready for clinical trials. All Fort Detrick needed now was the right time and place to test them.

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