Novichok, Raman, and Why the Sea is Blue

If you want to know what goes on inside a nerve gas detection lab, read on.

(Guardian) Salisbury nerve agent attack: expert criticises lack of information. Quoting,

De Bretton-Gordon said he had reassured people who contacted him asking if he thought they were at risk. “…The CBRN regiment was disbanded in 2011 as part of a cost-cutting defence review. “I expect we need a new one as soon as possible,” he said.

He added that the UK was “blindsided” by the Salisbury attack. “…We thought we had considered everything but not this scenario. There are not many people around with current and deep experience of things like this…. Now we’re paying the price. If [Russian president Vladimir] Putin is responsible, he probably doesn’t think anything’s going to happen because we haven’t done anything about chemical weapon use in Syria and Iran.

I would quote the whole thing, but for “fair usage.” Read it. As for the lack of information, let’s take a virtual trip inside one of the labs who so assiduously worked to identify the poison as one of the Novichok agents. What follows is inevitably incorrect in detail, offered only because the actual capabilities are of necessity secret, and because nobody else has written it. It is a schematic view.

The most poisonous substances known are all organophosphates that contain fluorine. The organophosphates include many insecticides. The nerve poisons bind with acetylcholinesterase, putting it out of action, so that it cannot  break down the neurotransmitter acetylcholine. Without the “ase”, the “message” never stops sending. This has two effects:

  • It causes all the muscles in the body, both voluntary and involuntary, to spasm and then stop working completely.
  • The switched-on state of the neurons in the brain causes them to overload and die.

The remarkably small amounts of a nerve poison required to kill are because these molecules are designed for specificity. Upon entering the body, these poisons prefer to bind with acetylcholinesterase. To the agent molecule that does not hit this target, two other things happens to a nerve agent inside the body:

  • The molecule can be metabolized. Metabolism is the normal process by which nutrients, as well as bodily reserves, are recomposed to serve needs of the organism. Some substances that are not useful to the body, such as alcohol, are disposed of in this way. Since poison is not a food, metabolism doesn’t go all the way. With  Sarin, the metabolites are detectable in the blood. But Novichok is so potent, the metabolites are correspondingly less. On the other hand, it is less volatile.
  • The poison molecule can form an adduct.  The entire molecule of poison joins another molecule, probably something a little fatty — hence, a new compound.

Once inside the body, one of the above things happens. This means that the search for a pure sample relies on luck. With luck, some of the agent lands on a nonreactive surface, like a porcelain tile.  In the case of the brother of Kim Jong-un, a huge amount of VX landed on his face, ample for direct detection.

So we are really looking for footprints, not the assassin himself. Most of the Novichok doesn’t reach the synapses. Most of it clings desperately to the first approachable fatty thing. Among the infinity of choices, squalene comes to mind. It’s simple and ubiquitous.

If we have any sample of Novichok, it’s very small. We can’t taste or smell it. There isn’t enough for fractional distillation. But things have advanced a long way since the days of the beaker and alembic.  It has to do with why the sea is blue, Raman scattering, which also gives us a look at tiny bits of matter, much smaller than a grain of sand, perhaps microscopic.

This is why the Raman microscope exists. It illuminates the sample with a laser. All molecules vibrate like these Russian belly dancers, doing a Salsa Rumba (You didn’t know Russians can rumba? You should see their molecules!) If you’re in the audience, and tag a dancer with your laser pointer, she vibrates even more wildly. But she flings some of your light back at you (sequins?) The Raman effect shifts the color (wavelength) of the light just slightly, spreading the even green of your pointer into peaky green shades, the Stokes shift. A spectroscope attached to the microscope records all of this.

The dozens of peaky shades that come off the sample comprise the fingerprint of the molecule. Only Chiquita can do her rumba. If a move isn’t hers, it isn’t her. But we’re not looking for the Novichok, because it’s gone or hidden. We’re looking for adducts.

The number of possible adducts is staggering. If our microscope points at more than one at a time, the fingerprint is smeared. So we have to separate them. Two mainstream, commonplace methods are used, chromatography, and electrophoresis. Both amount to hop races for molecules, over an obstacle course that could be a viscous liquid, or a strip of paper. The speed of a molecule varies according to what it is. Talent is not required. So they separate out into bands, each one a pure adduct — or nearly so.

The workflow looks like this:

  • Field workers collect samples from the environment.
  • Processors  use many techniques, including   those described above, to purify the samples. Many steps are required.
  • Fingerprint makers deliberately combine known pure Novichok samples with various fatty substances, all pure, to make adducts. Each adduct has a Raman fingerprint, which goes into a database. Without this, there would be nothing to compare to.
  • The Raman specialists  examine the samples  with Raman microscopes, obtaining the fingerprints of the field specimens.
  • The data analysts compare the fingerprints of the field specimens with the fingerprints in the database.
  • Everybody works as fast as they can.

Even though we are comparing adducts, not the Novichok itself, the fingerprint is so specific, it takes very few comparisons to eliminate doubt.

Unlike older nerve agents, no simple chemical tests exist.  But even if a test strip existed that satisfies the NATO requirement, to detect wide area dispersal of tons of agent, it might fail when the agent is precisely delivered, as with an e-cigarette. And Novichok is not one agent. Developed in the age of designer drugs, it comprises over a hundred compounds. To effectively counter the Novichok family requires active machinery, a “lab-in-a-box”, not a test strip. It’s not impossible, but  expensive.

This  oversimplified article neglects the myriad techniques available to the modern laboratory.  I’ve tried to take at least a little of the mystery out of it. But we were terribly unprepared for this, even though the Novichok formulas were made public years ago.

It’s time to catch up.