Science for SciFi: Poisons

This might seem like a bit of a repeat. After all, we just learned about a few natural weapons, right? Sort of. I talked a bit about how snake venom works, but I think it’s worth our time to learn a bit about toxicology. How do poisons work? How are they administered? Can toxicity be quantified? We’ll get to those answers in a minute. But before we start, let’s get two disclaimers out of the way. First, I am not a doctor and nothing you read here should be considered medical advice. Second, some fields distinguish between toxins and poisons. For the sake of simplicity, I will be using them interchangeably.

How do poisons work? Like we saw with snake venom, poisons work by interfering with the natural processes that happen constantly in your body to keep you alive. If you think about it we are really just a leather sack filled with water and chemical reactions. If anything interferes with those systems then we’re in for a bad time.

Measuring Toxicity

Death is in the dosage. Molecules that we need to sustain life can be toxic if we have too much, and molecules known to cause death might not hurt us at all if we have too little. Determining the amount and duration of exposure that results in toxicity can be tricky, but it’s an important consideration.

Two important considerations are acute versus chronic toxicity. Does the poison kill you immediately (acute), or over time with repeated exposure (chronic)? One measure of toxicity is LD50, often denoted in terms of milligrams per kilogram, which is defined as the median dose that kills 50% of the test population. Chronic exposure is something that workers in many industries need to worry about, but the assassins in your crime novel will be more concerned with acute exposure.

But measuring toxicity can be difficult. After all, it’s hard to find willing human subjects. The easiest way to test potential toxins is to see what they do to cells in a petri dish (in vitro). These experiments can reveal a lot, like the mechanism of toxicity (eg. does it block cell receptors or bind to DNA?) but cells in isolation are a poor model for living systems. Sure, maybe a chemical is toxic to liver cells, but if it never leaves the lungs after being inhaled then its effect may be limited. Large multicellular organisms are more than just individual cells, they are complex systems comprised of many cells with many functions. Toxins may then target a specific organ or grouping or organs depending on how the body processes them.

The best way to test toxicity is to use live animal models, but for obvious reasons, not everyone has the time, resources, or inclination to perform those tests.

How Bad Are Heavy Metals?

Mercury and lead are often thought of as extremely toxic, and for good reason, there are a great deal of environmental and health risks that arise from heavy metal pollution. However, just because something contains a heavy metal does not automatically make it dangerous.

The properties of metallic compounds vary greatly depending on their structure, makeup, and reactivity. For example, heavy metal chlorides may be toxic, but heavy metal oxides may be considerably less so.

Water solubility is a big factor here. If a compound cannot dissolve in water it’s going to have a hard time reaching target systems in the human body where it can do the most damage. But factors such as pH and any reactions the metals might undergo once inside the body can also play a role.

Predicting Toxicity

By now it should be clear that toxicity is hard to predict. It’s not just a matter of what a molecule contains, but what reactions that molecule undergoes inside the body which determines how dangerous it is and what kinds of damage it inflicts.

This is a problem for researchers because not all of the chemicals found within a lab will have been fully studied in terms of toxicity. Because of this, it’s easier to assume everything is dangerous and behave accordingly. That said, there are a few things that can be done to predict a molecule’s hazardous effects.

After a few years in the field, most chemists can intuit the reactivity of molecules based on their structure.

  1. Reactions that occur once released into the environment.
  2. Reactions that occur within biological systems.

For these reasons, predicting toxicity is not as straightforward as one might think, although knowledge of structure and reactivity can give us some clues. There have even been attempts to take known reactivity data, feed it into computers, and generate toxicity predictions. These efforts are unfortunately hampered by a general lack of data in many cases and the number of environmental and chemical variables that need to be considered. Even so, progress in this area is being made.

Famous Toxins

Arsenic – a poison that was favored by Agatha Christie, rat catchers, and stylists alike. Arsenic and arsenic-containing compounds have found many uses over the years as rat poisons, pigments, medicines, and more. Because of these many uses arsenic was once easy to come by and could be bought at many pharmacies. The really dangerous form of arsenic is arsenic oxides. Once inside the body, it disrupts the production of ATP, the molecule that our bodies use for fuel. Arsenic (III) oxides are similar in structure to the phosphates that our bodies use to make ATP and so our bodies try to use them instead. Without a regular supply of energy, cell death soon follows.

Capsaicin – do you really need to know why peppers feel hot on our tongues? Do you care? Maybe peppers won’t drop you dead, but the mechanism is fascinating and very useful to science fiction authors. Capsaicin targets neurons, specifically the vanilloid receptor. In practice, they cause the same sensation as heat. So they hurt, but they could hurt more if controlled by a mad scientist. This is actually my favorite toxin here, because in real life it is relatively harmless, but could be used by a writer in a lot of interesting ways. An alien plant for example, could have a much nastier variety of capsaicin for explorers to stumble upon.

Cyanide-cyanide is a classic. No spy would be caught dead without their cyanide capsule. Like arsenic, cyanide disrupts the production of ATP. In this case, however, it functions as an inhibitor that prevents the enzyme cytochrome c oxidase from doing its part in the ATP cycle. It should be noted, that in this case when we say cyanide we actually mean hydrogen cyanide (HCN). Cyano groups (CN) are common in many areas of chemistry, and hydrogen cyanide has many industrial uses.

Sarin – famous as a chemical warfare agent and a neurotoxin. Sarin acts quickly and can strike you dead in under ten minutes. Sarin is not too different from some of the snake venom we looked at a while back. Like our example there, Sarin works by inhibiting signals sent by nerve cells, but the mechanism is different. The key to sarin’s effectiveness is the neurotransmitter acetylcholine. Sarin permanently binds to receptors and prevents muscle cells from correctly interpreting the acetylcholine signal. The victim’s muscles are then unable to process acetylcholine, hindering their movement, and the victim dies from asphyxiation soon after. Sarin is an organophosphorus chemical that evaporates quickly and is incredibly deadly.

Narrative Uses

Agatha Christie was famous for using accurate portrayals of real poisons in her mystery novels, so much so that an entire book was written about it. By doing this she was able to give her readers the chance to deduce the murderer and the means of murder before she revealed it. The clues were all there for anyone who wanted to puzzle it out.

Whatsmore, knowing what a poison is and what its other uses help to build more plausibility into your story. A worker at a chemical plant might have ample access to hydrogen cyanide, just like a pharmacist in Victorian England would have no trouble sourcing arsenic on the down-low. And of course, for you writers of science fiction, knowing about the mechanisms and effects of real-world poisons allow you to ground your fictional toxins in real science.

Sources

A Is For Arsenic: The Poisons of Agatha Christie. Kathryn Harkup.

Measurement and Estimation of Electrophilic Reactivity for Predictive Toxicology. Johannes A. H. Schwobel et al. Chemical Reviews. American Chemical Society. 2011.

Toxicity of Metal Compounds: Knowledge and Myths. Ksenia S. Egorova and Valentine P. Ananikov. Organometallics. American Chemical Society. 2017.