Tools for the Toolbox: The Pellet With The Poison

Here are all of the fictional poisonings I can name off the top of my head in a minute. (Okay, two minutes. Okay, three.)

The Court Jester (my childhood movie…you Disney kids got nuthin!)
Doctor Who (folds in Agatha Christie)
Hercules (aka: why you never see Hercules wearing a shirt anymore)
Gosford Park (If you haven’t seen it, you must! Excellent ensemble piece.)
James Bond (I’m thinking of the one in the poker game; I’m sure there are others too.)
Romeo and Juliet (with extra tragedy action!)
Rosencrantz and Guildenstern Are Dead (I’m cheating…didn’t want to do two Shakespeare plays in a row, so this is my way around it.)
Chuck (spies always like poison)
Wizard of Oz (I’m counting the poppies.)
Harry Potter (Basilisk!)
Lamentation (by Ken Scholes)
Batman (Batman!)
Socrates (okay, that’s historical, I know. But admit it, it’s fun having Batman and Socrates next to each other on a list.)

Okay, my *mumble* minutes are up. That’s a pretty wide-ranging list, isn’t it?

So poisons are everywhere in the stories we like to tell.

But what exactly is a poison?

It’s a thing you put into someone’s drink that makes them suddenly keel over at the dramatic turning point of your novel!

Well, yes…but why does it make people keel over?

Hint: it has to do with biochemistry.

NOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Hey, you survived the last biochemistry post!

?

Yes, exactly.

I’ll let David Tennant tell you how poisons work. (Note: I’m using the long version of this scene not because it’s medically plausible, but because Tennant and Catherine Tate have such a fun comedic dynamic.)

“Something’s inhibiting my enzymes,” says The Doctor.

Enzymes are proteins that are basically little molecular machines that make things happen faster in a molecular reaction. Biochemical processes are just strings of molecular reactions. So, enzymes are proteins that facilitate biochemical processes.

Uh…try that again, please?

Okay. Pretend you have Red Molecule and Blue Molecule, that fit into each other like puzzle pieces to make Purple Molecule. If they were left alone, they’d just bounce off each other in a very molecule-y way, and only rarely manage to bounce into the proper orientation where they click together to become Purple Molecule.

Enter Enzyme McAwesome.

Enzyme McAwesome is a protein that’s wrapped into a configuration that’s designed specifically to grab Red Molecule. When it grabs Red Molecule, the presence of Red Molecule makes the structure of Enzyme McAwesome change so that it now has a part that loves to grab Blue Molecule. When it grabs Blue Molecule, the presence of Blue Molecule changes the structure again so that Enzyme McAwesome slams Red Molecule and Blue Molecule together, in exactly the right orientation to make Purple Molecule. Then Enzyme McAwesome lets go of Purple Molecule, and is ready to grab another Red Molecule and start the process all over again.

If something inhibits Enzyme McAwesome, Red Molecule and Blue Molecule don’t get together quite as fast as they would with the help of Enzyme McAwesome.

Now say that Enzyme McAwesome catalyzes the vital step in a biochemical pathway that creates ATP, the molecule that stores energy for use in molecular actions. If Enzyme McAwesome is inhibited, ATP gets created much, MUCH slower than it would with Enzyme McAwesome’s help. The cell doesn’t make as much ATP as it’s used to making, and so molecular actions are far less likely to be “funded” in an energy-supplying way. If molecular actions don’t get the energy they need to actually action, the cell shuts down. And there’s the end of the cell.

Organs are made up of cells. If enough cells shut down in an organ, the organ will fail. And if enough organs fail in the human body (or the wrong single organ fails), the person will die.

See what poisons are now? Poisons are simply substances that interfere with important biochemical pathways. They basically throw a block in the marble run, causing backups and overflows, and getting in the way of anything getting where it’s supposed to get. Sometimes they will block a branch of a biochemical pathway and direct the substrates down a secondary path where they create toxic molecules which then go on to make trouble of their own.

Poisons can be pretty much anything.

Lead causes problems by binding to enzymatic, receptor, and structural proteins. It is also structurally similar enough to calcium to interfere with metabolic pathways that use calcium. This makes problems in particular in the mitochondria, the “powerhouse” of the cell where most of the ATP is generated.

Carbon Monoxide “poisons” hemoglobin, interfering with the proper binding of oxygen to heme.

Cyanide “poisons” the electron transport chain, which is a vital component of the biochemical process that makes ATP using glycolysis and the Kreb Cycle. It basically passes off the extra electrons from the process to an oxygen molecule, which then combines with hydrogen to make water. If the electron transport chain is inhibited, the electrons don’t get passed along, and the marble run starts to back up. And then ATP just doesn’t get made aerobically (that is, with the help of oxygen) (that is, the most efficient way to make ATP); the substrates get shunted to the anaerobic pathway (the one that doesn’t require oxygen). That pathway makes less ATP, and also generates lactic acid, which is what you can feel burning in your muscles when you’re exercising beyond your oxygen supply.

This picture is a graphic representation of the Electron Transport Chain, an important series of membrane proteins in mitochondria that help facilitate ATP production. See the blue words with the 'T' shapes pointing out from them? Those are poisons, and the crossbar of the 'T' points to where they interfere with the Electron Transport Chain. Cyanide is the one labeled 'KCN', which is 'potassium cyanide'.

Warfarin is a fun example because it’s a poison…that’s used as a medicine! It was historically used as rat poison. Now it’s used as a blood thinner. Basically, warfarin interferes with the Vitamin-K-dependent formation of gamma-carboxyglutamate, which is essential for the proper function of a number of clotting factors. The upshot is, warfarin “poisons” the pathway that makes clotting factors, which basically “poisons” the clotting cascade. This can be helpful for people who are at risk for conditions relating to over-clot-ification, such as pulmonary embolism and stroke. This can also be very harmful if it’s not carefully monitored.

There's that 'T' shape again, telling you where warfarin interferes with the process. The negative signs also indicate interference or antagonism, and the positive sign indicates facilitation or agonism.

Water can even act as a poison, if there’s too much of it in your system!

So I’m a little unsure about how to advise you to approach poisons in your fiction. I’m sure you can see that poisons are very, very biochemistry-oriented, so it may be difficult as a layperson to navigate the whole poisoning thing in a completely medically accurate way. So you might want to go the way of the not-precisely-medically-accurate-but-at-least-medically-plausible.

Here are a couple of tips to help you out:

-Pick an organ system (like the gastrointestinal system or the neuromuscular system), and keep the symptoms of the poisoning to that organ system. It helps you organize the symptoms instead of flying all over the map in a medically-implausible way.

-Poisons can hit many organ systems at once, but try to keep symptoms to a minimum; if your character turns blue, their hair falls out, their tongue cramps into a ball, their eyeballs pop out, their heart skips every third beat, and they start pooping blood….well, people are going to start rolling their eyes. But if your character gets poisoned and slowly develops vague stomach problems that get worse and worse and worse until she dies in writhing agony…..that’s a little more plausible.

-This is another situation in which lack-of-specificity is your friend. Non-specific symptoms such as gastrointestinal distress (nausea, vomiting, diarrhea), headache, and/or muscle weakness are good ways of avoiding pitfalls of non-believability. You can add them to specific symptoms, but again, think about keeping your specific symptoms to maybe one or two, and fill any “this-doesn’t-look-serious-enough” gaps with non-specific symptoms.

-If you find yourself at a loss, try modeling the symptoms for your made-up poison after a real-life poison. (You don’t have to name the real-life poison in your work; just steal the symptoms. Although, many medical people will be able to recognize which poison you’re borrowing from. Just keep that in mind.) This will help you organize the symptoms to a biochemical distribution without actually having to understand the biochemistry.

For the more biochemically adventurous:

-Try and figure out which cellular process it’s going to interfere with. Remember that cells need food (glucose), oxygen, and water and electrolytes in physiological balance. Some types of cells need to replicate in order to perform their function; all cells need their replication controlled by regulator proteins or else they become cancerous. Many cells are triggered to certain actions by chemical signaling in the body, and many cells are inhibited from performing certain actions by chemical signals. And on and on and on. You can pick any one of these functions to “poison”.

-Try to decide which organs might be most affected by the process you’ve chosen. If you’re interfering with glucose uptake, the brain will be very strongly affected since it’s dependent on glucose and can’t survive on nutritional substitutes (such as ketone bodies) like most other cells can.

-The liver and the kidneys are usually responsible for cleaning poisons out of the blood, so many poisons will hit the liver and/or kidneys hard.

-Try to match the symptoms of the poisoning to the organ system involved. A person with carbon monoxide poisoning won’t necessarily gasp for air, but they’ll be suffocating on a cellular level. A person with an overdose of warfarin will have trouble with bleeding issues; they’ll bruise easily and get nosebleeds and hemorrhagic strokes and all those other things that go along with not being able to clot your blood.

Okay, I think that’s enough from me for now. Where have you seen fictional poisonings? What makes them seem more or less plausible to you?

References:

StatRef! http://online.statref.com

Pictures:

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Published in: on May 30, 2010 at 4:02 am  Comments (18)  
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18 CommentsLeave a comment

  1. What a great list to be a part of! Thanks Doctor Grasshopper! 😉

    • Thanks for visiting, Ken Scholes! Loved Lamentation!

      Dr. G

  2. Another great article, Dr. G. Thanks!

  3. There was an interesting Agatha Christie plot that I read where a character was poisoned with digitalis while the rest of the dinner party was fed foxglove leaves (which apparently look like sage) to make it look like she just got a particularly large dose. (Yet more proof that vegetables are bad for us!)

    So here’s a related question: how do medical examiners go about figuring out how a person was poisoned?

  4. This is more of a question–make that two questions–than a comment.

    Some years ago I read a mystery in which the victim was poisoned at a barbecue. It seems that one set of the lovely hand-carved skewers was made of oleander wood.

    Can anyone identify the mystery?

    Is this a plausible method? I know oleander’s poisonous in root, branch and pretty pink blossoms, but would there be enough on a couple of kabobs to do someone in?

  5. Hi there, John Murphy and Jane! I hate to do this, but I’m going to have to beg off your questions for the moment….I’m about to embark on a harrowing cross-country move, and I have absolutely no time for research right now. Oh, and all of my books are packed.

    I’m so sorry. They’re such delicious questions, too! 😦

  6. This is a really helpful explanation about what actually happens when someone gets poisoned!

    I’m guessing that when you have a substance that poisons one species but not another (e.g. mistletoe is poisonous to humans but not to birds), it might be because Species A uses Enzyme X for the process, but Species B uses Enzyme Y, so the poison that interferes with Enzyme X doesn’t do anything to Enzyme Y. Or possibly Species B has some other chemical in their system that binds the poison molecule before it can damage anything, and Species A lacks that chemical?

    • Yeah, Castiron, I think that’s the case. Glad you liked the post; thanks for reading!

      Dr. G

  7. lovely! there was this House episode involving possibly a mistake between Warfarin and Aspirin…

  8. ummm, am I mistaken in thinking that all meds are poisonous if not used properly/in the right dose?

    • Water is poisonous if not used properly/in the right dose. 😀

  9. I’m not sure if you’re still answering questions on these things( and I’m not sure there are answers to be had—or maybe I need to find a more history focused blog to ask), but I have had an oddity come up in my family history research…basically, a great-great-aunt who died as a toddler from accidental poisoning—except that all info I can find on the substance mentioned on the death certificate says that would probably not actually kill you at all( though long-term exposure would be bad)—specifically, used motor oil( from what had to be one of the very first cars in the state at the time, I think this was even before the Model T), rather oddly specified as “containing brass filings”—which my reading indicates is a diagnostic for a particular engine problem, at least in modern vehicles. So I’m wondering if you happen to have any insights as to what actually happened? I guess the likeliest scenario is that the doctor screwed up and made things worse somehow, but I am just one of those people who likes to have as much info as possible and goes nuts from curiosity.

    • Hi there! Um….I’m not really sure how to help you with this one, sorry about that. Best of luck, though!

      😀

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