Molecular Assassins

by Sophie Parekh

So this is an article about common poisons and their biochemistry. Because that’s what everyone loves reading. No satire, just science. Well, maybe a little bit…

So, there is a distinction between poisons and toxins, according to the internet at any rate. Poison is an all-encompassing term that denotes any substance that could potentially be harmful to humans on a chemical level. For example bleach is poisonous, but a coin is not. It’s a choking hazard, but it’s not poisonous (*ahem* NHS website, you’re wrong *ahem*). But a toxin is specifically a naturally occurring substance that is harmful, like snake venom or belladonna.

I tried to find the most common poisons used to kill people, but unfortunately there is no such list… I wonder why… but the good old NHS has a lovely section of common poisons from which I shall pick out my favourites. And maybe some off-list ones because I’m feeling rebellious.

Click here for the NHS Webpage on poisons:

If you’re really interested in this sort of thing, then I strongly advise you to seek professional help. Just kidding: read Molecules of Murder by John Emsley; it’s got some really interesting case studies and all the biochemistry of the poisons involved. But now, on with the killing things!

1. Paracetamol (C₈H₉NO₂)

Initially, not looking so deadly, but it causes around 500 deaths per year in the USA. The recommended dose is 10-15mg per kg ever 6-8 hours, so that’s 750 - 1125mg for a 75kg adult every 6-8 hours, so you could have about 3-4g of the stuff a day, which sounds like a lot. However, once you start getting 10g or more into your body, then you start having major problems.

Fairly soon after you take it, paracetamol begins to be metabolised by your liver. This involves it binding to sulfates and glucuronic acid and excreted pretty sharpish. This what happens to about 90% of the paracetamol. 5% is excreted unchanged, but the other 5% has some hydrogens knocked off and becomes this nasty stuff called NAPQI. Initially, it binds with glutathione, which makes is harmless and your body can excrete it with no problems. However, when you start taking more and more paracetamol, NAPQI starts building up as well and soon your liver has used up all the glutathione and supply can’t keep up with demand, which is when the problems start occurring. 

NAPQI likes to bind with useful things like proteins and nucleic acids, which stops them from working and liver can’t cope so it is destroyed, basically. The symptoms include, but are not limited to, jaundice, loss of coordination and trembling (due to low blood sugar). You tend to die a few days later, but it could be up to a week. Thankfully, you can treat NAPQI poisoning with acetylcysteine within about 48 hours of the overdose. What an uplifting start. 

2. Carbon Monoxide (CO)

This one’s probably the most dangerous and is the only inorganic one I think. It is often called the silent killer, (a) because gases can’t speak, and (b) because you become unconscious before you die and so have no clue what’s going on. Carbon monoxide is a colourless, odourless gas, which binds to the haemoglobin in your red blood cells much more strongly than oxygen does to form carboxyhaemoglobin, so at high concentrations of CO, there isn’t much haemoglobin left unbound to transport oxygen. And if your blood can’t transport oxygen, then all your vital organs become starved of oxygen and shut down because they can’t function without oxygen which causes dizziness, shortness of breath, unconsciousness and eventually death. Usually within 30 minutes. Lovely.

Carbon monoxide is formed from the incomplete combustion of fuels, so it’s produced by things like cars and power stations albeit in very low concentrations. However, the main cause of carbon monoxide poisoning is from faulty gas appliances in people’s houses. The faulty appliance for example a boiler, could burn the gas incompletely and produce carbon monoxide in high enough concentrations to kill you. But, this is very rare and you can get carbon monoxide detectors and alarms just in case.

3. Diamorphine (Heroin) –

Heroin? Really? But it isn’t a poison! Now that’s where you’re wrong. It was the weapon of choice for the infamous serial killer Dr Harold Shipman, who killed 120 people, or thereabouts. It’s a derivative of morphine, just with acetyl groups, which means it can cross the blood-brain barrier more easily and is more soluble in the lipid tissue. Enzymes in the brain remove the acetyl groups, which means heroin can do its job, blocking the µ - opioid receptors which means the brain can’t register any form of pain. However, a side effect of this happening is that by blocking the µ -receptors, it slows respiration. Heroin also interferes with the brains ability to detect how much CO₂ is dissolved in the blood and so if your breathing slows down and your brain can’t detect the increased CO₂ then you have a problem, because the CO₂ builds up and not enough oxygen counteracts this effect, then you die, effectively of oxygen starvation.

4. Hyoscine (Scopolamine – medical name)

Hyoscine is a naturally occurring substance found in plants such as the deadly nightshade or mandrake. In small doses, it leads to feelings of elation and in larger doses, it leads to mental confusion, hallucinations and eventually produces a long, dreamless sleep after which the person will awake with no memory of what had happened. Hence Shakespeare’s use of mandrake in Othello when Iago says to Othello, “Not poppy, nor mandragora, nor all the drowsy syrups of the world shall ever medicine thee to that sweet sleep, which thou ow’dst yesterday”, referring to the hallucinogenic, sleepy effects of Hyoscine in the mandrake (mandragora). Sorry, just a weeny bit of English in there. 

Anyhoo, hyoscine is a competitive inhibitor of acetylcholine, the main messenger molecule in the nervous system. Hyoscine blocks its path causing the nerve impulses to be interrupted. This means chemical signalling isn’t as effective as it should be, and so results in the destruction of short term memory, which is useful to the criminals of Colombia. They could harvest hyoscine from the Borrachero tree that grows all over the place, but instead they buy it from neighbouring Ecuador, where it’s grown legally to use as the active ingredient in motion sickness tablets, to sedatives. The criminals use it to effectively ‘date-rap’ their victims; a small dose can cause someone to turn into a zombie effectively, they’re conscious, but docile and extremely compliant. This makes it very easy for criminals to access bank details, or gain entry to properties. This is a huge problem in Colombia a something they’ve been tackling for many years. Yeesh, that got serious really quickly.

5. Ricin

What’s the most creative way to kill someone? Why, with an umbrella-gun of course. In 1978, this is how the KGB decided to murder former agent George Markov, for defecting to the West and embarrassing their wonderful dictatorship. An air rifle was disguised as an umbrella, and was used to deliver a tiny pellet containing a lethal dose of the toxin ricin. Ricin is extracted from the seeds of the castor bean and as little as 0.1 µg of ricin per kilogram of body weight is a lethal dose. This is because a single ricin molecule is enough to kill a cell. Ricin is a globular protein composed of two chains: chain A and chain B. Chain B acts as the delivery molecule, attaching to carbohydrates on the outside of the cell and letting chain A into the cell. The disulphide linkage between the chains is then broken and chain A can get to work. It inactivates the ribosomes (the organelles that make proteins in the cell) by removing a single adenine base from the sarcin/ricin loop, permanently inactivating the ribosome. The scary thing is however, is that one single chain A molecule, can inactivate 1500 ribosomes per minute, ultimately killing the cell. So if protein synthesis stops in the body´s cells, then it can´t function on a cellular level and all your organs die and so do you. The symptoms usually include diarrhoea, vomiting, nausea, fast heart rate, low blood pressure and some more lovely things like that. But what I found most terrifying, is that there is no actual antidote for ricin, only a vaccine, so if you get poisoned and didn´t get the vaccine … well, I can’t say I’d want to be in your shoes.  

Ok, so that went really off-list. I don´t think heroin´s listed by the NHS, but hyoscine and ricin definitely aren´t. But yes, that concludes my top 5 poisons, hopefully you´ll have learnt something about how poisons actually do what they do… maybe…

DISCLOSURE:

I´m not encouraging anyone to go around poisoning people, in any way. Even if you did want to, all of these are either illegal, detectable in the doses you need to kill someone, or really hard to find good enough quality to outright kill anyone. So really, it's not worth the trouble.