The Russian “New Guy:” Novichok

Understanding the most dangerous nerve agent in human history

It’s a bright spring day in Salisbury, England. As busy passerby continue on with their days, a gruesome scene is unfolding outside a local restaurant — and it will soon test the very limits of international relations, the ethics of warfare, and the human body itself.

Sergei Skripal, a former Russian spy, and his daughter Yulia Skripal have been found in “an extremely serious condition.” Yulia is foaming at the mouth, her eyes wide open, yet completely white.

Paramedics, and the world, have never seen anything like it, but this mysterious situation is an important marker of a much larger storm brewing on the horizon… And with it dawns a new (and deadly) era of chemical warfare.

Novichok: Overview, Function, Symptoms & Cures

The Novichok agent (Russian for “new guy”) is a solid nerve agent developed in Russia which consists of two distinct, non-toxic substances which become dangerous only when combined. For this reason, Novichok is known as a binary agent. It is usually found as a powder, but may exist in liquid and gaseous forms as well. Nerve agents are a member of the organophosphate family, the same family which houses pesticides.

Novichok functions by blocking the normal breakdown of a neurotransmitter known as Acetylcholine, which results in disturbed brain-to-muscle communications.

Nerve agents have a complicated and conflict-ridden history, as shown below, and Novichok is certainly no exception.

Novichok works through exploiting biological human functions. Neurotransmitters (a type of “chemical messenger”) are carried by vesicles from one neuron to another. Acetylcholine is one such neurotransmitter, responsible for muscle contractions, blood pressure, breathing reflexes, etc., and is used heavily in the autonomic nervous system.

Essentially, Acetylcholine will carry chemical messages between neurons.

However, if left unattended, Acetylcholine will relay the same message over and over again, leading to an unwanted buildup of the neurotransmitter. In order to control this build up, an enzyme known as Acetylcholinesterase periodically destroys Acetylcholine after it has done its job.

A nerve agent will interfere with Acetylcholinesterase, leading to a buildup of Acetylcholine. This can lead to symptoms of Novichok poisoning, including excessively stimulating the nerve supply, which causes fatigue / paralysis, and spasms leading to asphyxiation. Other effects include nausea, vomiting, cough, drooling, abnormal blood pressure and heart rate, and in extreme cases, breathing failure and death.

As of now, there is no cure available for Novichok poisoning, although antidotes have been created. Atropine will block one type of Acetylcholine receptor to limit potential build up, while Pralidoxime Chloride blocks Novichok from binding to Acetylcholine at all. The effectiveness of either antidote depends on the dosage received, and time between poisoning and treatment.

Going Deeper: The Biology Perspective

Acetylcholine, as previously mentioned, is a neurotransmitter whose job is to transmit nerve impulses within the central and peripheral nervous systems. It plays a role in everything from muscle contractions to controlling heart rate.

When a nerve impulse occurs, Acetylcholine is discharged from a terminal of one neuron (the presynaptic neuron), and binds to the receptors on the postsynaptic membrane of other cells.

Additionally, Acetylcholinesterase is an enzyme which rapidly destroys Acetylcholine at the neuromuscular junction — the point of contact between the nervous system and muscles — in order to prevent build up.

To do so, it engages in a decomposition reaction wherein it splits Acetylcholine into acetate and choline, and the choline is then re-transmitted back into the neuron to produce more Acetylcholine and start the whole process again.

Switching Gears: The Chemistry Side of Things

A Agents are not naturally-occuring, meaning that they need to be synthesized before use. Let’s take a look at this process first.

The synthesis of A Agents is a 2-step process. To begin, phosphorous trichloride will react with a di-alcohol (a compound with two hydroxide ions) in a reaction which resembles a double displacement reaction because the phosphorous atom will displace the hydrogen atoms, while the hydrogen atoms will bond with the chlorines from the initial phosphorous trichloride to create a second product. Ultimately, two products are formed — two molecules of hydrochloric acid, and one complex compound with phosphorous, oxygen, chlorine, and the “R1” and “R2” from the di-alcohol.

Once this is complete, a second reaction occurs. In this reaction, an unknown fluoride will react with the complex compound produced in the first reaction in yet another double displacement reaction. In this case, a single fluorine atom will displace a single chlorine atom.

In the end, depending on which di-alcohol was among the initial reactants, one of three forms of Novichok can be formed — Novichok ?, Novichok 5, or Novichok 7.

Now, we get to the fun part… Reactions within the human body.

The newly formed Novichok will now be introduced to the human body, where it will interact with Acetylcholinesterase. Ordinarily, the hydrogen found in Acetylcholinesterase’s OH molecule will split Acetylcholine into acetate and choline via a decomposition reaction. However, Novichok interferes with this process. By displacing the Acetylcholinesterase’s OH molecule with its own phosphorous atom, the naturally-programmed decomposition reaction cannot occur. As a result, Acetylcholine continues to build up.

In the end, even when an antidote is introduced, it will take a long time for the Novichok compound to be split from the Acetylcholinesterase compound. For this reason, this is called “aging,” since it can take hours or days to restore functionality to the body.

In Short…

Through a series of complex chemical reactions, starting from the synthesis of the nerve agent itself, to its harmful interference with the breakdown of Acetylcholine through double displacement reactions with the Acetylcholinesterase compound, it’s no surprise that Novichok is an entity banned by the Chemical Weapons Act

Unfortunately, this nerve agent is a grave reminder of when science falls into the hands of the “bad guys.” The case of Sergei and Yulia Skripal caused strained relations between the U.K. and Russia, showing how the impact of chemical warfare extends far beyond just the victims.

Especially since Novichok poisoning still has no cure, one can’t help but wonder — is it just a matter of time before the next attack… Perhaps even closer to home this time?

Works Cited can be found here.