Anthrax--where are we, almost 5 years later?

There's been quite a bit of discussion in the news lately about how safe we are (or aren't) in the light of the recent terror arrests in the UK. As we approach the 5-year anniversary of the 9/11 attacks, many changes have been made in the name of protecting us from terrorism. Some of them, including adding additional first responders and public health workers (and preparing them for a variety of emergency situations) are good in theory, but have been sorely underfunded. Other measures, unfortunately, are little more than theater as Revere suggests, including the current focus on your shampoo as a potential weapon of mass destruction.

No matter what your political leanings, it benefits us all to pay attention to what actually works to keep us safer, and not forget about issues that have been largely dropped over the past 5 years. One of these is the identification of the source of the post-9/11 anthrax attacks.

A summary of the 2001 anthrax attacks can be found here. In a nutshell, envelopes containing anthrax were sent to a number of news organizations and senators, resulting in 22 cases of anthrax and 5 deaths.

From reports, it appears that the anthrax in all the letters was not of the same grade. The anthrax bacterium (Bacillus anthracis) forms hardy spores when deprived of nutrients. These can last in the environment for an extremely long amount of time, until an unsuspecting host happens upon them, whereby they germinate and begin to multiply. This can lead to different forms of the disease, depending on how the bacterium enters the host. Gastrointestinal anthrax occurs from ingestion of the bacterial spores; cutaneous anthrax occurs due to contact of the spores with the skin, and inhalational, which is the deadliest form and occurs when the spores are inhaled and germinate in the lungs. All of those who died had the inhalational form of the disease.

The investigation into who carried out the attacks has, from all outward appearances, been stalled now for several years. I wrote a post a year ago discussing how the genetic fingerprint of the anthrax can--and is--being used in the investigation of its origins, but that can only take us so far. It was also reported that in at least some of the envelopes, the bacterial spores were very finely processed, and potentially coated with an agent that made them more likely to aerosolize upon exposure. This makes them more deadly, as the spores treated in this fashion are more likely to be breathed deep into the lungs and cause the inhalational form of the disease. The small, finely milled spores can also disseminate farther through the air and potentially spread to more victims.

Additionally, anthrax could potentially be manipulated by anyone with some basic expertise in molecular biology. For example, research has shown that the number of copies of a bacterial plasmid can affect bacterial virulence, particularly in certain lineages of the bacterium, possibly by increasing production of the bacterial capsule (the slimy outer coating that aids in resistance to phagocytosis, or "eating" of the bacteria by cells of our immune system. Theoretically, a terrorist could increase the number of plasmids in a strain, making it more virulent. Additionally, they could engineer antibiotic resistance into the strain, making traditional treatments ineffective. None of this appears to have been used in the bacteria released in 2001, but we really don't know the limits of what could be done; as recent events have shown, potential terrorists can be very creative, and a step ahead of our band-aid measures.

So, what we have is this. Someone who had access to anthrax, and the know-how to grow it up and refine it so that it would be highly deadly, remains at large. The letters were mailed from Trenton, New Jersey, so either that person lives in the country or at least had the ability to enter our borders. And, as far as we can tell, s/he (or, potentially, they) are still out there somewhere. In the meantime, a number of shortsighted approaches to security have been applied, such as this week's limitation on fluids in carry-on. As pointed out by Bruce Schneier,

Banning box cutters since 9/11, or taking off our shoes since Richard Reid, has not made us any safer. And a long-term prohibition against liquid carry-ons won't make us safer, either. It's not just that there are ways around the rules, it's that focusing on tactics is a losing proposition.

We need a severe overhaul, and we need to keep the unsolved anthrax attacks in the public eye. Someone out there has the technology to kill us--potentially, lots of us. We don't know when, where, or if he'll strike again, but the answer to the problem certainly isn't to react in a knee-jerk fashion. Instead of throwing a lot of money at problems without any rational underpinning for how it should be spent, we need to improve infrastructure--especially law enforcement and other emergency responders and public health--so that we can respond in a concerted and logical manner to threats like this.

Image from http://img.search.com/0/0a/300px-Daschle_letter.jpg

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Dr. Smith:

I agree with the thrust of your post and feel that our current scattershot protective approach is far from ideal. I wonder about your final paragraph, though. It seems to be the standard paragraph that sits at the bottom of most of our, "public health needs X," posts; and indeed at the bottom of most published articles on the subject.

My question is simply, how? Is there anyone that will advocate for this? Who are they? Who are we advocating to? What does success look like? I mean, we all obviously agree that we're up s***'s creek, so where do we buy a paddle, so to speak. Are you going to do it? Is Dr. Benjamin going to do it? I don't have an answer, and I don't expect you to either, but it's certainly worth a thought.

Thanks.

Good post. A small quibble, though, if you don't mind (part of this concerns my field - large plasmids of Bacillus a/c/t). You mention the possibility of increasing the number of plasmids (I suppose you mean copy number of pXO2, which codes for the capsule?). However controlling this would be no small feat, for various reasons - copy number of large plasmids is a very delicate question, and many years away from elucidation, I would venture. Way more effort than "basic expertise in molecular biology" would be necessary.

It would be much easier to go with antibiotic resistance. Wouldn't even have to look very far... sensitivity to ampicillin is one of the major phenotypic markers that distinguish B. anthracis it from its (very) close cousins B. cereus and B. thuringiensis. Which by the way raises another issue: accurate detection and the problem of recently isolated 'intermediate' forms of anthracis-like B.c. and B.t. that sit on the classification fence. Anyway, a solid course of antibiotics is AFAIK the only way to cure anthrax (and even then you have to catch it in the early stages in case of inhalation anthrax - you've got what, a two day window? for something that starts out looking like pneumonia... wouldn't want those odds for myself). So antibiotics = mucho important; take that away (not so hard to do), we're in trouble (I'm including us Europeans as potential targets).

If you're interested in recent developments of "anthrax science" (research has been in log growth phase since the 2001 attacks) you may want to check out the proceedings of the 2005 meeting on B. anthracis/cereus/thuringiensis published in J.Bacteriology, May 2006 (Keim et al.). On a positive note, regarding countermeasures/threat assessment, there seems to be quite a bit going on behind the scenes; one presentation at the meeting focused on assessing the threat of anthrax spores being released into a water distribution system and how it could be eliminated. Detection/differentiation is also being heavily looked into.

By the way, not to sound like a conspiracy theorist, but... I'm not so sure the 2001 case remained 'unresolved'. Maybe the truth didn't fit with your government's agenda, if you see what I mean. (Yep, got my tinfoil hat securely in place ;-))

Jimmy,

I don't have an answer. There is a lot of advocacy by various groups, but obviously, it hasn't had a lot of effect. Public health just isn't sexy, and when it's at its best, it's invisible--tough to work up excitement for it as far as funding. And while celebrity and other high-profile activists have been successful in raising awareness and funding for many specific diseases, we don't have anyone to rally around basic public health.

iGollum,

Please, quibble away--I don't do research on anthrax, so it's nice to have folks more familiar with the lit drop by and add their two cents. And yep, I'm referring to the pXO2. That's a good point that it's much more difficult to mess with the number of those than to just clone in a gene, and I certainly wouldn't have the expertise, but I think it's hard to know what's out there and what's already been done behind closed doors with regard to anthrax.

With regard to detection, is that specific for anthrax? That's a good step forward, but again, we run into the problem with--what if it's something other than anthrax? Going pathogen-by-pathogen like that is just like reacting to scares on the airlines; while we're busy checking shoes, someone else is using liquids.

Finally, as far as resolution of the case, note that I did say "from all outward appearances." I think it's unlikely that they'd be covering something up, but I guess it's one thing the administration has opened the door to by being so secretive about everything else. Additionally, of course they could have an entire task force who are just days away from cracking the case as far as I know, but they've certainly been awful quiet about it publically.

Dr. Smith:

Thanks for the answer. Not to divert from this post's topic, but the subject (advocating for basic public health systems) is one that interests me greatly, and one that I'm having significant trouble finding support for as an MPH student. If I'm interested in obesity research, or HIV research, or injury prevention, there is a list of professors I can work with. If I'm interested in public health systems research or public health advocacy, well - AJPH has a new section devoted to Government, Politics and Law, I should go read that, and that's about it.

While I might not be able to comment on some of the more clinical posts that you have, I do enjoy learning from them. Keep up the good work.

I'm quite confident there is a lot of work being done on detection of all the major pathogens, not just anthrax, although I only know specifics about anthrax because it intersects my research. My group has some contacts with another one working on microorganism detection issues with ties to military applications; apparently there was a big NATO exercise this year in which a bunch of labs tested their pet detection methods on an array of nasty bugs. I'm aware of a few civilian-led initiatives too but with commercial ties and potential patents so I can't say much beyond that they exist.

That said, I agree that these are reactive measures that cannot possibly guarantee complete protection of the public if the 'bad guys' pull a fast one with something totally different or new. Now there's a lot of talk that something 'better' should be done, but very little actual solutions being put on the table; in that I think Jimmy made a fair point.

Unfortunately, I don't see any really proactive way to protect an open society against terrorism (the good thing is, I'm not the expert in charge; the bad thing is there doesn't seem to be any).

It's a sort of arms race, and by definition, their team has the advantage of choosing the battlefield and the weapons. How do you compete with that? How do you turn the tables on them and grasp the initiative? The US government (and other world leaders, to be fair) seems to think that extending the authority of the state will bring about more security. To me it seems like a great way to foster more of the same.

And the new airport security measures? Please. There's passive-reactive, there's incompetent and then there's totally braindead. Not only are they useless, the effect on the population is extremely negative. Do our governments WANT us to feel hassled, irritated, anxious and generally miserable? (who stands to benefit from this? and where's my tinfoil hat again?)

On the plus side I hear the Eurostar's stock is on the climb. (Until that gets hit too.)

Dr. Smith: I agree that DNA analysis is not going to solve this crime. That was essentially the conclusion reached by the authors of Microbial Forensics (Academic Press 2005) In short, all Ames anthrax spores are clones.
The authors of Microbial Forensics, however, did state that the best scientific forensic evidence avaialble was non-DNA. I take it they are referring here to the silica coatings.
Forensic scientists who are part of this effort need to firstly understand exactly what the purpose of the silica coating is. Bioweaponeers working for state-sponsored labs don't usually publish their work in the open literature. However, in recent years the developers of Dry Powder Inhalational (DPI) drugs have been using techniques of silica coatings to make cutting edge aerosol drugs. Some of this work is described here http://www.angelfire.com/blog/sophie_d2/Germansilica.pdf

Note the optimum coated particle is thus described:
"Optimal results are obtained if the surface density of the coating particles is uniform and neither too small nor too large"

Also, this work tells us that the reason the silica is there is to prevent native spore surfaces from approaching within a few nm of each other. If the native spores touch they will almost irreversibly stick due to van der Waals forces (attractive forces that fall off to the sixth power of distance).

Interestingly, the above optimum description of a coated particle sounds very familiar. It's how the Leahy sample was described in Newsweek:
http://www.ph.ucla.edu/epi/bioter/sophisticatedstrainanthrax.html
"The combination of the intense milling of the bacteria and the unusual coating produced an anthrax powder so fine and fluffy that individually coated anthrax spores were found in the Leahy envelope, something that U.S. bioweapons experts had never seen."

The coated spores shown by Velsko of anthrax surrogates (see Figure 1 at this link http://www.llnl.gov/tid/lof/documents/pdf/316652.pdf ) - look rather crude. The coating is not even or uniform - and likely there is much more silkica present than is optimum.

So, the question arises - have the US authorities been able to reproduce the Leahy anthrax? And if they haven't after five years, what does that mean?

Also, what information did the FBI withold from senators on the forensic character of the anthrax, recently revealed in the deposition of Dr Dwight Adams in the Hatfill versus FBI lawsuit? And why did he withold the information?
http://en.wikipedia.org/wiki/2001_anthrax_attack
Connolly: Earlier you testified that regarding the scientific aspect of the investigation there was information that was simply in your view too sensitive to share to the public about the particular characteristics of the organism sent in the mail. Is that correct?

Adams: In so many words, yes, sir.

Connolly: I don't want to mischaracterize it. If you think I've mischaracterized it in any way then, please, put your own words on it.

Adams: No, that's fine.

Connolly: Did you feel like you had the same restrictions in informing the senate, congress, or their staff in terms of what it is you would reveal to them about the particular characteristics of the organism that was sent?

Adams: As I've already stated there was specific information that I did not feel appropriate to share with either the media or to the Hill because it was too sensitive of the information to do so

Dear Sir: I had written my opinion in other sections concerniung aides as a social -communication disease starting in the way people think-human behavior.
My thoughts get clearer on this topic daily. If we start from anthrax a skin ailiment (border boundary ailiment I think started from something under the skin)-the old moslems who added things ...
e.g 100 men 5 feet each =500 feet instead of five feet. If you add the behaviors and attitudes of ancient times through till day -past Einstein-we are a society that is based on the false belief of a third party perspective-the constant speed assigned to light at any perspective.

It is easy for men keep adding past themselves and the earth thinking of this neutral view point-anthropomorphised-pictured as manlike- as always present -an indicaton of their lives.
I am firmly convinced that the spread of AIDS SARS etc- is carried on from this old (biological expression of trouble to nature)- disease Anthrax.
Though I had worked very briefly ina research lab involving this -Army desires for a vaccination-andonly know a little of its' biology of three factors involving the skin-fever etc-I'have to review it again--the physicals to AIDS could be very criptic-at a plane to be almost undiscernable without some advanced insights and information from history and science(thanks to the efforts and data we have already collected. And we will always wind up with more of a shape(a topolocical comparison that maybe we can even get genetic with(a biological propensity in description)rather than a number like the speed of light(a physics propensity). A preoccupation with numbers -as in physics-and a failure to realize that all things are more biological (ultimately totally are form-size and shape)than physic(ycal)(a number or equation).
pertaining to the question what can we do about it?-if we have a good perspective we can stop breeding it -especially with the bad habits and learned behaviors we adopt from The past. Trim our budgets, know our redundant efforts-not collect knowledge for knwoledge sake-and be especially morally cpnscious with respect to our fellow man and animals. Understand what thinking 'a neutral existing party' has to do with our lives-what aspects of it?. I think to start -science is missing a womans touch altogether and there is a great deal of discrimination involved for those interested. If a person at first step thinks I am atheistic -that third party refers to religion and god-it is actually our science with a false belief that you are confusing this with.
Take a sabboth-look around with scrutiny to try to find where in your lives this false belief is festering.
As a start -at about world war time, the speed of light was declared a universal standard to determine length-the meter. The more I reflect on this, the more ridiculous this appears to common sense whether the velocity of light is theorized to be constant or not. We start with the unit of length-the meter first to measure speed---Habitually building constructs like the stacked heights of men to climb a wall.

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By marvin e. kirsh (not verified) on 18 Aug 2006 #permalink

I find it hard to accept that anyone would willingly -consciously dissiminate or spread a disease. All a person has is his health. Scientific deduction is only that, built on theory-ideas-intended to work one way-if they work then they work-if thwey dont, then they dont, and we will have to try something else.Nothing lost. It(science fact) is not intended to be so omnipotent that a person could release a disease as if a neurosurgeon with near zero tolerance and split second accuracy. I do think the US would have dropped its' charges against Saddam Hussein if it had the slightest supicion he was that crazy. I think there as well as here the evidence is circumstantial if not circumstantial to the point of nearly fitting our accumulated knowledge (always there are unanswered questions) aand maybe possible extrapolated criminal MOA's. I do think this finger pointing can go on to the extent thst eventually people start dropping bombs on one another. This is definately not good as I think basically anonomous cruelities are at the initial seed of our suffering. Once we start imposing our own cruelities, this is no longer the case and we ourselves become guilty..The worst case of guilt would be the induction of illness for hostility purposes.
The discovery of invisble agents was only postulated to be acting in nature in the backgrounds of our perceptions for centuries from antiquity , beyond control, and with no evidence of their existence until Mendel discovered a pattern to the inheritance of characterisitics in peas. A discovery that put us barely on the verge of knowing anyhthing at all. It is beyond comprehension how a little bit of knowledge in a vast ocean, still remaining in the dark, could have become so dangereous. If it is the case thst these incidents were accidents, perhaps we ought to put down our bombs also -A world we barely have the meagerest comprehension of can be cruel enough without them. There is also a much deeper implication to mankinds imposition of his own suffering; That he would have imposed a consciuos tangeable change to nature itself-as he is not only a part of its' whole-his conscious will is from its' will and is then a major factor in its' course. The humble and receiving of what good is placed them, should never suffer the hands of the unwise and greedy. As the world has no direct line in its' processes, any disturbances in any of its courses can not only originate anywhere but would require such great inhumanities as to be visible and not hidden unless they are again instigated by an inequality of nature and compounded by mankind. And perhaps there are thousands of us-if not millions doing our share in this respect, but let down somewhere with the self-serving and trust demanding actions of others. With respect to Iraq president Bush had stated a non-human intelligence source-and perhaps this is a bottom line -regimentation and communication failures of an over technicalization. A supposed know-it-al-ness from a meager knowledge of the world.
Recently(starting a decade ago) I read that either the Amish,Pensylavnia Dutch, or the Mormans were suffering a rebellion of the young to leave their farms and town for the big cities in conflict with their elders. This had made me curious as to what their motivations were. Sexual freedom with a mariad of new diseases?...better educational opportunities? Adolescent rebellion? I am very curious as to what they expect to find. Grow to like the social neurosises of high density living, the euphorias of technology over nature, Social definitions appearing to offer greater freedom, when there is actually less within the borders and boundaries of the grand mental poplace projections-mutual social constructs of convenience and technology, away from the strong and independant wills of the type "each man on his own" (to the perils of life-nature).. Akin to livng in close quarters for simple body heat from the cold. It does not remedy the cold or preserve body heat over time. I think the energy required to maintain a constant temperature in the wake of an adding volume is not additive itself in a constant volume-and are we not literally squeezing the world for energy to maintain our industializations-probably as not only a source,but the source of the irregular growths of our human tresspasses. Maybe as we step with our feet and blow hot air from our mouths around the world, the indirect (suffering inccuring compensations of nature) lead (retalatory or compensating)others back upon our doors with the exact 'solution' measured-judged-added by mental association somehow as the indirect tresspass is perceived (actually caused)'..anthrax. Would certainly require a very angrily motivated party(ies)
Whatever.... this is a reverse living out in psychological terms..very unhealthy. releasing living death-living out death,not life.
If we can discover what might lure a person(e.g. Amish youths to leave their homes after centuries)to such a situation maybe we will find out what has (mis)guided us all. If it is said we are all born with a thorn in our sides,there is no solution for htis. If we find two thorns in our sides, we must come to learn so and one from the other.

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By Marvin E. Kirsh (not verified) on 20 Aug 2006 #permalink