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Besides having some sound medical advice in them, the powder laden with anthrax spores in those letters was far less pure than the ones mailed to Senators Daschle and Leahy in Washington DC, which resulted in the deaths of five people.

I have had a really hard time writing about the anthrax letters. Every now and again I take a walk through the Senate office buildings and try to imagine what the people who worked there at the time went through. People there don't speak about it, in much the way I don't speak easily about my experiences on September 11th. I suspect this is common amongst witnesses to tragedy.

To understand the reality of bioterrorism, we have to face the reality of what happened with the anthrax letters in unpleasant detail. Without such understanding, we are left with the now dulled panic caused by the attacks and the subsequent backwards rhetoric that fueled widespread misunderstanding of bioterrorism in the US.

Anthrax is a bacterium that spends most of its life in the soil as a benign spore. Occasionally, it infects cattle and even more rarely it will infect humans. Before the letters, the last human death from anthrax in the US was in 1976. The theory is that the man, who had not been near a farm, had breathed in spores that were on a wool sweater he had gotten from Afghanistan. This is a pretty far-fetched explanation, but plausible. Many bacteria can go into a dormancy stage where they transform into spores when conditions are not conducive to growth. Anthrax can stay in this state for tens of years. We actually don't know exactly how long they can stay dormant, but when it enters a growth phase it is for very brief periods of aggressive growth.

There are three main ways you can become infected with anthrax: coetaneous, gastrointestinal and inhalation. Coet-aneous infection is by far the most common form and is caused by spores that gain access through a break or cut in the skin. This does not have to be a big cut, just a minuscule break in the skin. Theoretically you only need a single spore to cause an infection although spores usually come in clumps, so it is more likely that you'd get a bunch in.

Let's put it in Bush speak. 'Ya see, the spores are real small. Tiny. Can't see 'em. You put on yer glasses, still can't see 'em. It's really a faith thing. Ya have to believe they're there. Once they find a good ol' place to nestle in, they grow. It's hard work, but they do it. They change and grow and make a liaison.'

Too far? Once the spores enter a growth phase a skin lesion forms at the site of infection. The great majority of infections from the letters were coetaneous and were easily cured with antibiotics. Coetaneous anthrax infection is very rarely fatal, and most of the time will not progress further than the initial infection point.

Next is gastrointestinal infection, caused by eating food that is tainted with anthrax spores. This type of infection is very rare and is also cured pretty easily with antibiotics if caught in time.

Finally, there are inhalation anthrax infections - by far the deadliest, mostly because by the time doctors figure out what is going on, it is already too late. The five people who died in 2001 all had inhalation anthrax. Once inhaled into the lungs, the immune system sends specialized cells called macrophages to swallow the spores, which develop into bacteria, which are then transported to the lymph nodes. At this point, the infected individual will start to show symptoms similar to the flu. In the lymph nodes they divide and make their way into the bloodstream, where they start to expel a toxin. Death comes quickly from toxic shock and organ failure. Inhalation anthrax can be treated with antibiotics, but once it is in the bloodstream it is often too late.

A lot has been said about the anthrax letters, some of it correct, some of it speculation. Let's play detective and see what we can figure out. First, the anthrax strain used was first isolated in Texas, but was named the Ames strain after Ames, Iowa, the location of the facility that identified it as pathogenic and unique. It has been used by the US biodefense program since it was identified as being very virulent.

A good way to understand what a bacterial or viral strain is is to think of horses. Horses are all the same species, and mostly look alike, but some are better suited for running and others are better suited for jumping. This has to do with their genetics. Bacteria are similar. Genetic changes that make one strain grow faster than another can mean the difference between a strain that is pathogenic and one that is relatively benign. You can think of them like twins. They look alike and they are genetically almost identical, but in the process of growing separately, small changes can happen that make them genetically distinguishable. When geneticists looked at the DNA from the anthrax found in the letters, they were able to identify it as the Ames strain. Some have estimated that there are as many as 50 or so labs that have this particular strain of anthrax, almost all of which are in the US. The truth is that it is really hard to tell who has the strain because it was distributed to so many places by the US government and the records were quite poor.

'Wait, wait, wait. Didn't the US sign the Biological and Toxin Weapons Convention of 1972 that bans our development of bioweapons like anthrax?' Excellent question. Yes we did, which is why, officially, the US does not have any biological weapons development programs and why we do not officially stockpile any biological or chemical weapons. But notice that we do not organize our military under the moniker 'War Department' any more either. We call it the Department of Defense. Under the convention, we can use the same logic to undertake any number of research projects to develop countermeasures to bioterror agents, and this means making bioterror agents that are at least as dangerous as our enemy has. The US therefore did develop biological weapons in the process of preparing for what our enemy might do, despite the fact that it meant that we had to develop bioweapons further than we had in 1972. These activities, while not necessarily in direct conflict with the convention, do go against the spirit of the deal. Also, the US

has refused to sign on to an agreement to allow inspections of its biodefense facilities, which some have also said implies that we have not followed the convention to the letter.

This was most certainly the appropriate approach during the Cold War, since we know that the Soviet Union had a very sophisticated bioweapons program that concentrated on anthrax, smallpox and other agents. Their anthrax program has been well-documented by ex-Soviet scientists now working in the US and through a disastrous event in 1979 when anthrax was accidentally released from a Soviet military facility, resulting in at least 94 deaths. We also know of or suspect at least 18 other countries of having biological weapons or biodefense programs. Research into countermeasures to the agents being developed in these countries is a prudent strategy. The question is: do we need to make weaponized versions of an agent to make a vaccine or antibiotic to fight them? Most people in the drug-making business would say no. But to test vaccines and other countermeasures, you have to know how they will act, and thus many believe that weaponizing them was necessary.

Detailed information on our bioweapons program is of course classified, but we know that research on the Ames strain has been going on at Fort Detrick, Maryland, and at the US Army facility at the Dugway Proving Ground in Utah;some claim that the CIA has an advanced program. The Dugway Proving Ground is larger than the state of Rhode Island and has thefacilities to make very high-grade weaponized anthrax. The Proving Ground has some of the most sophisticated weaponizing facilities in the world. It used to weaponize anthrax spores, ship them to Fort Detrick to be gamma irradiated so they were no longer dangerous, have the spores shipped back and use them in outdoor dispersal tests.

The FBI initially thought that it was likely that a single US-trained scientist or person with some medical training was likely behind the anthrax attacks. While this is certainly a pos sibility, based on what we know it could have been more than one person involved in making the powder, or one very skilled biological weapons maker. Since the letters were such a significant series of events in the history of bioterror, I think it's important to understand the basics of making weaponized anthrax. Also, understanding what is involved in weaponizing anthrax could give us significant clues about who was responsible for the letters.

To weaponize anthrax, you have to take the following steps. First, you have to acquire the strain. It would not have been trivial to get hold of the specific Ames strain, but the letter sender might have had access without doing anything out of their normal routine. We are talking about one of the most dangerous bacterial strains in the world, but nonetheless, many labs had it. Next you have to grow a bunch of it, first on a culture plate and then in a flask with special nutrient rich liquid that is optimized for anthrax growth. If you do it wrong, other bacteria will grow in the liquid. So, the person who made it at least knew how to grow the bacteria. Then you have to starve the anthrax so it turns into a spore. In nature, anthrax turns into spores when conditions are too harsh for it to grow. At this point you will have a mixture of dead anthrax cells and spores that could cause coetaneous anthrax but would not aerosolize well. The process is easy enough to do with a little more training and there are thousands of people who could easily learn to do this. Not just any schlub off the street can turn bacteria into a spore;in fact, most PhD level biologists wouldn't have a clue as to the specifics of doing this for anthrax.

According to congressional testimony by scientists who examined electron micrographs of the spores from some of the letters and several other sources, the first letters, mailed to newsrooms in New York, did not have a high concentration of spores in the powder. They did have bits of dead bacterial cells and the sizes of the clumps of spores were larger and more varied than the letters mailed to Senators Daschle and Leahy. That indicates that the person(s) had access to anthrax at different stages of preparation or prepared multiple batches. The letters sent to the Senate had an extraordinarily high concentration of spores and with smaller clumps of spores, which are more easily aerosolized. This is an important fact. It is thought that the spores in the second batch were concentrated enough and small enough so they could make their way through the pores in the paper in the letter and envelope, or were just forced out and easily aerosolized as the letters shot through a mail sorter. Once they squeezed through, they became aerosolized.

To purify anthrax spores, you have to mix them in liquid and centrifuge them to get rid of all the larger dead bacteria parts. This might have to be repeated to get the spores really pure. This takes some skill in the lab as well and significant know-how about spore purification. Next you dry the anthrax and weaponize it. Two basic ways to do it have been described: milling and spray drying. The purpose of both of these techniques is to make smaller particles containing fewer spores or (better) single spores. Milling spores involves drying out the purified spores and grinding them up to make smaller particles. Spray drying involves mixing the spores in liquid which is sprayed into an enclosed tube and blasted with hot air. The hot air evaporates the liquid, leaving spores.

There were some controversial reports that the spores in the Senate letters were coated with silica. It is still not clear if the spores were treated with this additive or not, but if they were, it is quite telling. The reason that additives like silica are used is simple. The silica acts like little ball bearings that reduce the tendency of spores to stick to each other;in other words, it reduces clumping. The silica can also take on a static charge, which can repel the spores from each other, further reducing clumping. Finally, coating agents like silica can absorb some water and keep the spores dry. This class of additives has but one purpose in microbial research: weaponizing agents. They are not used to produce aerosol ized medications that are designed to be inhaled because the body cannot easily clear the silica from the lungs. Silica on its own can cause silicosis and other significant health problems. We don't know how many people in the US know how to concentrate, anthrax, use silica additives to aerosolize spores, and spray dry or mill them, as well as having access to the facilities to do so, but it is fair to say that it is not many. Cross-reference that with the number of labs that would have the Ames strain and persons who received an anthrax vaccine, which would certainly have been required, and you have a very narrow field.

The anthrax research community is quite small relative to other forms of research. Someone out there worked with or trained the person who sent the letters or works in a facility that allowed someone access to a dangerous weapon.

One reason the FBI believes that the attacks were likely done by a single American scientist is that the person probably did not intend a lot of people to die. Sounds crazy -right? Think about it. The person warned about the contents of the envelope in the letter. If this person had the expertise to handle anthrax, then they also knew that once a victim is warned that they have just been exposed, they can take prophylactic antibiotics and won't die. Also, putting it in a letter is a pretty ineffective way of spreading inhalation anthrax, as seen by the relatively low number of people that were infected. The letters were folded in a way consistent with someone who tried to contain the powder, a so-called pharmacist's fold. If the attacker had just sprinkled the powder into the mailboxes, hundreds or thousands more people would have been infected with inhalation anthrax because it would not have relied on the spores leaking from the letters. The mail carrier would not have given the odd powder that was coating the letters much thought, and a much larger spread of spores and death across the country would certainly have occurred. This person wanted to wield power and wanted to scare people. It just doesn't make sense that they planned for spores to be filtered through the paper of the letter and envelope and be aerosolized. Whoever did it was a sociopath, but not stupid. They just didn't consider the leakage issue.

The wording in the letters implied that the person who sent them was from the Middle East and was Muslim. But that doesn't make any sense either. The Washington letters were addressed to quite liberal Democrat Senators. If the person was mad at the US government, why would they send them to two men who don't have a history of making reckless statements about Arab countries (as the President and several Republican congressmen have) and did not advocate force in dealing with international diplomatic situations. One might think that the letter writer, if he is indeed American, has a thing against Democrats.

It's a grim suggestion, but one that is not getting the kind of play in the press that it should. Most acts of terrorism are home-grown. Even groups like Al Qaeda have recognized that locally organized terrorism is harder to detect. The train bombings in Madrid and London were organized and executed by local terrorists, not people who immigrated to the country they were trying to attack. The attacks on the Pentagon and the two attacks on the World Trade Center, 1993 and 2001, were unusual in the terrorism world. Here, domestic terrorist acts are traditionally born right out of the hate and dismay we have right here in the great ol' US of A, the most notorious being Ted Kaczynski, Timothy McVeigh and Eric Rudolph. The same holds true for attacks in other countries. The combined evidence - access, weaponizing expertise, targets, a desire to scare but not kill people, language meant to redirect hatred towards Arabs - puts the focus on a military-trained scientist, and that is where the FBI started their investigation. This most certainly does not mean that the person wore a uniform. Most of these facilities employ many civilian staff, so this misconception ought to be rejected out of hand.

That the letters were mailed from New Jersey implies that the mailer could have been working at the Fort Detrick facility, a short drive down the turnpike. But it is also possible that the mailer deliberately mailed the letters in close proximity to Fort Detrick and that he was not the person who made the anthrax. There have been many reports that the US military biological weapons labs have had lax security, sloppy bookkeeping and some serious job satisfaction issues. The investigation by the military and FBI got very quiet very quickly when the press started to piece together the puzzle.

At one point, the finger was pointed in the press and through officials associated with the investigation at one particular man who worked at Fort Detrick. The FBI called him a 'person of interest.' As it turns out, this man was probably wrongly accused. His career and life were dragged through the mud like the security guard initially accused of the Olympic bombing in Atlanta. The FBI apparently hounded this man relentlessly and he has filed suit against former Attorney General John Ashcroft and the Justice Department. Behind the scenes in the biosecurity community, a select few pointed the finger at him in the press, mostly without actually naming him. The whole situation makes me sick. It's as if we have learned nothing.

The FBI and the DoD have not been open with the American public about the investigation. Not the details, just the progress. The Washington Post revealed in September 2005 that the FBI had reduced the number of agents on the case from 31 to 21. They have issued over 5,000 subpoenas, interviewed over 8,000 people, and chased leads on four continents. Yet with all those efforts, they remain interested in Fort Detrick, the Proving Grounds and Louisiana State University. They even drained a pond looking for evidence. If we put aside the conspiracy theories, then we are forced to accept that we are living with someone in our midst who has the potential to kill thousands upon thousands of people. If so, then maybe it's time to talk more candidly about the bioweapons work that went on in the US. In the end, I think we can count on the public being more interested in Janet Jackson's breast and the American Idol finals than the ugliness of our bioweapons programs.

Since the initial anthrax attacks in 2001 there have been hundreds of fake anthrax letters mailed in attempts to scare the hell out of people. These letters have been filled with white powders ranging from powdered sugar to rat poison, but we have had no news on the suspect or suspects who killed five people, disrupted the lives of thousands and attacked the United States Congress.

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