Military Loses Quarter-Teaspoon of VX Nerve Agent

So this is fun:

Some 1,200 to 1,400 people were locked in the 1,200 sq-mile Dugway Proving Ground for several hours after a vial containing a quarter of a teaspoon of VX nerve agent was reported missing. [BBC]

A complete lock-down was by no means an overreaction. VX nerve gas is extraordinarily lethal. The lethal dose is ~30 μg. To put that in context, according to Wolfram Alpha*, that's about 1,240,000 lethal doses if dispersed effectively. Enough to destroy the city of San Diego. For comparison, Nagasaki and Hiroshima bombings combined resulted in 199,000 casualties (dead and injured.) This sort of thing is dead serious, and it's no surprise that the base went into quarantine until it was found. Of course, I don't want to be alarmist, the chances that this was in the wrong hands or had a chance of being widely dispersed is slim. More likely than not, it was misplaced in a lab, or someone forgot to appropriately log the return or destruction of the specimen. These labs and storage vaults are likely (if reports of biological and chemical weapon labs are to be believed) keep under negative air pressure and from a civil engineering perspective built for containment. It's certainly no joking matter, but the danger in this case was minimal.

So I wanted to take this current event and use it as an opportunity to discuss the role of enzymes. Biochemistry is fascinating, but it's not my favorite kind of chemistry. Still the role of enzymes has always filled me with a certain awe. Enzymes are how nature really does its best chemistry, and so far, we can't really beat enzymes at what they do, though we've managed to harness them using biochemistry and genetics. Think of them as the teeny weeny craftspeople of the lab. They act as catalysts, allowing the human body (or other complex systems) to undertake complex molecular transformations in fractions of a second. If biological systems had to do the sort of slow plodding chemistry that we're used to doing in the lab to complete certain reactions, complex life as we know it could not exist.



First though, a word on catalysis in general. In the non-biological world, there is such a thing as chemical catalysis. However the kind of catalysis chemists do uses rare and/or expensive metals that often act as a surface on which we can mount individual ions and molecules and almost pluck at them like circuit boards. This is a vast oversimplification, catalysts aren't always solid, chemists can't "see" the molecules mounted on the surface, and it's done more than one molecule at a time. Generally though, using catalysts means less energy is needed and fewer steps. Due to the peculiarities of certain molecules, doing something that sounds simple; like attaching two molecules together to form a bigger one, is actually quite complex and can involve multiple steps. Using a catalyst can take down the number of steps required to a handful. Some common candidates for catalysts are titanium, osmium, platinum, palladium, iridium, and gold. Sometimes, they can contaminate a reaction, leading a chemist to believe that a reaction can happen at room temperature, or at impressive rates; when in fact they've just been given false hope, since repeating the experiment won't give the same results.

Whether we're talking about chemical catalysts or enzymes, they have something important in common: They aren't consumed by the reactions they speed up. The same substrate or enzyme molecule can be used over and over again. This is why the catalytic converter in your car, which uses platinum, doesn't require you to replenish the metal every so often. A good thing too, since platinum is very expensive.

Now an enzyme isn't like your basic metal catalyst. They can be huge structures made of multiple proteins called macromolecules. A well known example of a macromolecule (but not an enzyme) is hemoglobin:

Hemoglobin carries oxygen in the bloodstream. It's tremendous, but it only carries one oxygen molecule at a time. Now in the case of nerve function, there's one really important macromolecule that is actually an enzyme:

Okay, so acetylcholinesterase looks more like this. Work with me here.

A common feature in enzymes is the active site. This is where the products come to bind or break down. In keeping with the visual metaphor here, they're AChE's hands. What AChE does is break down acetylcholine, a neurotransmitter. When you want to send a signal to a neuron or muscle, acetylcholine is what tells the neuron to fire, or muscle to contract. There are other neurotransmitters, but acetylcholine is a major one, and we're going to concentrate on it for now. Now of course, you don't want the muscle to stay contracted or the neuron to be perpetually firing, so AChE's very important job is to go in and start breaking down acetylcholine as fast as it can.

Oh, like you've never had a Rhianna song stuck in your head.

Remember how I keep pointing out that enzymes make reactions happen faster at lower energies? Considering you need to be able to fire your muscles and send and receive data quick enough to do a circle-strafe in Halo or swerve to avoid a pothole, AChE needs to be fast, and fast it is. A single molecule of AChE can break down 25,000 molecules of acetylcholine in one second.

Go on. Count 'em. No really, it's a great use of your time.

This is where VX and other nerve agents come in, they do something called allosteric inhibition. You see, enzymes, while truly amazing little beasts, aren't invincible. They often only work in a certain temperature range and pH. But, the one thing that will really shut an enzyme down is allosteric inhibitors. I've made the point before that sometimes how a molecule is shaped is more important than the specific ions or elements in it. Of course, the specific elements are important in reaching the "correct" shape, but it doesn't necessarily mean they're a big part of the main reaction. Allosteric inhibitors, like VX or sarin, latch onto a certain part of the molecule, where they form covalent bonds. It forces the molecule to change shape, including the shape of it's active site. End result? It's a not-so-active site. At this point, it's like a Vulcan nerve pinch. The molecule is out of commission, unable to bind substrates.

"I didn't want to do this AChE, but now I've got that stupid song stuck in my head."

In the human body, the result is death. The nervous system is completely jammed, and since acetylcholine plays an important role in the autonomic nervous system, we're talking about a lot of bodily functions that are extremely necessary but that we do without thinking: Digestion, heartbeat regulation (the heart has its own nerve clusters so it doesn't need the brain to beat, these are affected by the poison directly), breathing. All of that goes into overdrive. This is of course in addition to being unable to control movement, but that's really the least of your worries. Twitching, tightness in the chest, and drooling are early effects of the poison. Treatments usually involve drug cocktails that block acetylcholine receptors, and restore functionality to affected AChE molecules.

Chemical weapons like VX are deadly, effective, and potent. The problem is, like other WMDs they're indiscriminate. Actually, I take that back, they're not indiscriminate- they tend to kill the kinds of people least likely to be wearing masks and suits that protect them from the effects: Non-combatants. This is why the CWC, or *inhales* the Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction *inhales again* has set a timeline for the destruction of all stockpiles of chemical weapons and munitions. By April 2012, 100% of chemical weapons should be destroyed. Currently, the United States has destroyed ~81%.