Posts tagged: biology

Bad chemistry I – Poisoning

A writer’s guide to poison, poisoning, and poisonous things

This article is going to provide a brief overview of toxicology, highlighting the concepts and considerations that I believe will be most useful to writers.

This will be a series of articles, the next will discuss individual poisons in more detail, with others talking about types of chemical hazards as well as radiation.

I’m therefore not going to spend much time listing exotic poisons or talking about individual substances in this article, although I will be giving examples where relevant.

 

Confusing words-

These are the words with the important definitions.

Poison – This refers to any substance that interacts with the functioning of a biological organism in a negative way.  It’s the umbrella term. As this definition could actually encompass just about every known substance, the term tends to be used only to describe substances in the specific context that harm is likely to occur, or substances that are particularly prone to negative interactions with biology.

Toxin –  Toxins are poisons that are produced by a biological organism. Toxins are poisons, but not all poisons are toxins. This is not helped by the way that most words that derive from the same Greek root, such as toxicology, toxic, or intoxication, are all general terms.

Venom – The next step down, a venom refers specifically to a toxin that is injected directly into another organism, whether by sting, fang or claw.

So, arsenic introduced into food is a poison, but not a toxin or a venom. Ricin, which is derived from the caster oil plant, is a toxin, but not a venom. If you are bitten by a snake, then the venom that it injects, is also a toxin and a poison. All three substances are toxic.

There are grey areas here, but in practical terms you just need to consider the origin of the substance at hand. If it came from an animal or plant, you can call it a toxin, if it was injected by that creature, it’s also a venom. If neither of those apply, you should just call it a poison.

So, what makes a substance poisonous?

 

Mechanism –

There a lot of different ways that a poison can interfere with biology, this can involve a relatively crude chemical reaction, such as the corrosive destruction of tissue, an overloading of normal biological processes, or very specific and complicated interactions with biochemistry.

In general, the biologically derived toxins tend to be large complicated molecules, often proteins, which have complex interaction with biological processes. Venoms, especially, are often composed of multiple discrete substances, often with separate modes of action.

The more complex the molecule and interaction, the more likely it is that the poison will be specific to a given organism, tissue, or situation. As I’ve discussed at length in an earlier article, complex interaction between unrelated biochemical systems is unlikely, something which may become a problem when writing “hard” science fiction.

 

Dosage-

Probably the most important concept in toxicology, famously stated by Paracelsus, who is considered the father of modern Toxicology –

“All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.”

In large enough amounts even water can be toxic, and I’m not talking about drowning here.

In the abstract, any living organism can be considered as a very complicated series of chemical reactions, and so, if you throw enough of any other chemical at them, eventually bad things will tend to happen.

Conversely, many substances which are widely recognized as poisons are present in small amounts all around us. Chances are that you have accidentally consumed an apple pip at some point in your life, without immediately expiring as a result of the tiny quantities of cyanide that it contained.

It is dosage then that is most often used when comparing the toxicity of substances. You may have seen this expressed as LD50 values, a rather grim notation in which the figure indicates a quantity of a given substance required to kill half the organisms exposed to it.

LD50 values must be approached cautiously for a number of reasons. Firstly, for reasons that should be obvious, human toxicology data is seldom acquired by careful and systematic experimentation, rather from anecdote and reconstruction of tragic events, contributed by people who were often too busy at the time to take careful measurements. Human data is often missing altogether for many substances, and estimates can only be made by extrapolating data from other organisms.

Beyond that there is still room for confusion. LD50 values should specify weight and administration, but this information is often omitted in favor of lowest possible LD50 value. Consider that a 6’3” male can readily weigh 50% more than a 5’2” women and more than three times as much as a 5 year old child. For some substances the dosage will not scale well with mass anyway. Children or the elderly or those in poor health, or with specific conditions, may be more susceptible, and, as will be discussed, genetics and behavior often play important roles as well.

 

Administration route-

It’s not uncommon to hear journalists describe any large, allegedly newsworthy, accumulation of toxic substances according to the number of people that could potentially be poisoned, as in “enough botulinum toxin, to kill 1000 elephants”. This is a lot like describing the contents of a knife shop by trying to estimate the number of people that could be stabbed. Poisons do not magically distribute themselves amongst and within the population that they may be intended to poison.

Some substances are readily absorbed through the lungs, or directly through the skin, but others must be ingested or even injected directly, something that is less likely to happen by accident.

Even after the poison enters the body, it still has to reach the susceptible target tissue. It’s quite possible for an injected poison to become trapped in muscle tissue rather than reaching the bloodstream. The brain is protected from many toxic substances by a system of filtration, termed the blood-brain barrier. Certain diseases can reduce the effectiveness of this barrier, which will render the sufferer susceptible to those toxins.

If a poison is in the form of a gas, or absorbed through skin contact, it is likely that many times the lethal dose will be needed to ensure that enough is taken up by the target.

 

Metabolism-

What happens to the poison after it enters the body is also important. The body is effective at removing molecules that shouldn’t be present, or which no longer serve a purpose. This is a progressive, but surprisingly predictable process, where the offending molecules are cut up into progressively smaller metabolites by metabolic enzymes and then excreted.

For toxic substances this often means neutralization, but other substances that weren’t initially harmful may actually be transformed into a toxic form.

An important concept here, that you might come across when researching this subject, is that of first pass metabolism, which describes the way that drugs absorbed in the stomach, will pass immediately through the liver, where a lot of metabolic processes take place. This means that even some substances that are absorbed well by the stomach will be dramatically influenced by injecting them directly. It also means that the precise site at which an injection of toxic substances occurs, both relative to the target tissue and relative to the liver can be important.

These metabolic pathways are often shared, and can potentially be overloaded. The reason that alcohol is contraindicated when taking many types of medication is that it shares a common metabolic pathway with them. Other substances can directly inhibit metabolic enzymes; this is true of chemicals contained within Grapefruit of all things, the fruit of nightmares, if you are a pharmacologist.

This can all have interesting implications. In the case of ethylene-glycol (anti-freeze) poisoning, the toxicity results from metabolism by the alcohol metabolizing pathway. Because the pathway has a much higher affinity for the alcohol, the poisoning can be treated by giving the victim large quantities of ethanol until all the antifreeze has been excreted, essentially, treatment involves getting as drunk as possible.

Metabolic pathways can be up-regulated or down-regulated by the body over time, in response to prolonged exposure to the offending metabolite. This is the mechanism by which people build up resistance to poisons, medication, or drugs of abuse, which will, in turn, influence their susceptibility to other drugs or poisons metabolized in the same way. Metabolism can also vary as a result of genetic factors, especially across different ethnicities. The enzyme complicit in paracetamol’s (acetaminophen) toxicity, for example, has been observed to vary by a factor of as much as 50 between individuals, and will increase with chronic alcohol exposure, increasing the risk of poisoning.

 

Elimination-

Some substances are metabolized or are excreted from the body almost immediately, but others persist for a very long time. This means that repeated exposure to relatively small amounts of that substance over a long period of time can result in poisoning. This is particularly common with heavy metal toxicity.

Aside from normal metabolic processes, the toxicity of substance is also influenced by what happens to individual molecules whilst exerting their harmful effect. A poison that is consumed in that reaction is usually going to be less problematic than one which can as a catalyst for other reactions, as this means that the molecule itself will persist and continue to produce harm. Some enzyme molecules are individually capable of catalyzing more than a million reactions per second without being used up.

Also important is the fate of whatever substances that the toxin is reacting with. Some toxins are eliminated quickly, but irreversibly destroy the target molecules or tissue, and the body’s ability to quickly replace these substances or repair the damage is limited. Nerve agents, for example, work by binding to an enzyme anticholinesterase involved in nerve transmission, often producing permanent bonds with the molecule, which would otherwise be taken back up and recycled by the body, resulting in prolonged poisoning. One of the drugs used to treat poisoning of this type, Pralidoxime Chloride acts to reactivate the enzyme and restore normal function.

Speaking of which…

 

Antidotes and other treatments-

Almost as important to fiction as the poison, is the concept of the antidote, the magical wonder drug that will infallibly reverse poisoning in seconds, if administered at any point before death (the time of which can be estimated to the second).

Needless to say, it’s not quite that simple in reality.

It’s important to realize that, whilst many types of poisoning can be treated with a specific drug, these treatments are not often fast, infallible, or even safe. Some substances oppose the effect of poison by producing an opposing effect, in essence poisoning the patient in the opposite direction, others do nothing to repair harm, but facilitate the breakdown or excretion of the poison, prevent it from binding to its target, or even just compete to produce the same mischief in a more reversible way.

Because animal toxins toxin molecules are often composed of large and complex molecules, antibodies produced by the immune system are sometimes effective against them, allowing an immune response to the toxin to develop. This is exploited in order to manufacture antiserum, extracted from animals deliberately exposed to the toxin. However, these treatments can produce a severe immune response from the patient themselves, especially on repeated exposure, and are sufficiently risky that, in reality, not introducing the antiserum to the patient is often judged the lesser risk.

More apparently cinematic antidotes do exist, but even then there can be unexpected problems, Opioid poisoning can be spectacularly reversed in seconds, by injection of the drug naloxone (which also produces the instant onset of withdrawal symptoms if the poisoning was caused by abuse), but the effects of the antidote are of shorter duration than the underlying poisoning, meaning that unless the patient is given subsequent doses, they will relapse when it wears off. Preventing a spectacularly withdrawn drug addict from leaving the emergency room in search of another fix, after being apparently cured of their overdose can be a real problem for a doctor.

When writing dialogue it’s probably sensible to avoid having a doctor or biologist use the term antidote at all, they may use it in individual cases, especially when talking to patients, but in general they are more likely to think and talk about these substances in terms of “medication” or “treatment”.

Just as important to the real world treatment of poisoning is the physical reduction of poison absorption. If the poison has been taken in by mouth this means inducing vomiting (when safe to do so), pumping out the stomach, or introducing activated charcoal into the stomach, which will neutralize a lot of substances before they can be absorbed.

If the substance is absorbed through the skin, the victim can be washed (often with a mild bleach solution). If the poison has been injected it is sometime appropriate to attempt to recover the poison by suction or use a tourniquet to prevent its spread into general circulation.

A writer’s guide to genetics

As with many of my other articles this will not be an exhaustive guide, but rather more of a conceptual roadmap of the subject. I’m going to be going through what I think are the most important concepts for the largest numbers of my readers to understand (ideally, both of you).

I’m not just going to be talking about genetics though, because I tend to the view that it can only be properly understood when viewed in a slightly wider framework

 

You’re going to feel cheated if I don’t tell you what the letters stand for, right?

DNA – Deoxyribonucleic acid. Composed of two separate polymeric chains of nucleotides, each containing one of four bases. It is the sequence of these bases, Adenine, Cytosine, Guanine, and Thymine, that encode the information.

DNA, when collected in large quantities, smells strongly of vinegar, is apparently edible, and I am informed that it tastes just as disgusting as you might expect.

Your genome is the sum total of genetic information within an organism, this term can refer to a specific individual, but is often used in reference to entire species, such as with the human genome. Much of your genome actually consists of junk DNA, this isn’t unimportant, but it doesn’t contain useful information.

 

Blueprint of what?

The word blueprint is thrown around a lot when people talk about genetics, but this is somewhat misleading. DNA actually contains information about the individual parts, not the whole.

For DNA to do anything, it must be expressed. This process involves translating the DNA first into RNA, which can be considered to be a temporary, working version, of the original master copy. This RNA is then translated into a polypeptide.

Polypeptides are chains of amino-acids, of which there are twenty different types, each of which corresponds to a three base sequence (or codon) from the original DNA (the gene).

 

Turns out our biology is largely based on origami

These polypeptides fold into proteins, which may incorporate multiple polypeptide chains, as well as non-peptide molecules.

The resulting proteins form most of the complex molecules within your body, and it is the interactions between them that actually determine most of what happens within it.

Imagine that every single item in your house was produced by squirting out chains of lego bricks that folded themselves into everything you could possibly need. I’m not just talking about your chairs and mugs here, I’m talking about your television, your fridge, your new conservatory. No assembly or planning would be required, the mechanisms that control all of this folded from the little chains too.

There is no possible way for words to do justice to the complexity of the entire system. I talked a little while ago about translation of DNA into Polypeptides. The animation linked here covers the proccesses that make this happen in more depth, and it is mind blowing.

 

The point of all this

This is the thing that you absolutely need to understand. There is nothing in your  DNA that says “arm go here” Your arm happened because some proteins fold into cells and those cells respond in specific ways to their chemical signals, neighbouring cells, pressure gradients, and a thousand other things, and that happens because of a system of interaction between proteins that has continued uninterrupted pretty much since proteins first happened.

The specific system of protein interactions within an organism is termed the Proteome, the study of it is called Proteomics, and its practitioners should probably be termed Masochists. We tend to fixate on genetics, mainly because it is much easier for us to understand and influence, but it is only part of the picture.

This is a wildly complicated, emergent system that has arisen over millions of years, with no limitations to the factors that could influence it, no logic or requirement for consistency evident in its processes, and with no part of how it actually works documented anywhere, including your DNA. You probably can’t comprehend the true horror of this, unless you have worked in IT.

Essentially your DNA is just the HR filing system for the corporate entity that is your body. Every so often a Mummy corporation, and a Daddy corporation, will love each other very much, and little spin off company will be sent into the world, but they won’t succeed or fail solely on the quality of the paperwork that they inherit.

We all started out as a single cell, and that cell had DNA in it, but it also had a payload of additional biochemistry which was  important too.

I suspect that there is also joke in here about editors, but I’m worried that, if I find it, the metaphor police might actually start issuing warrants.

Anyway, this stuff has implications, even for writers.

 

Sample implications, provided for your convenience

1)      It’s very difficult to reconstruct an organism solely from genetic information – You can’t reconstruct the organism without recreating the proteomic environment that can use that information. Whilst the genome will contain the information for the pieces of that of proteome, it doesn’t tell you how it fits together, and without context you probably can’t decode the genome anyway, much less how they correspond to proteins. This is a chicken and egg situation that involves actual eggs.

Say we find some dinosaur DNA, it’s very unlikely that we can plug that DNA into the egg (in the sense of the actual ovum cell) of any modern creature to produce a dinosaur, but it’s possible that we could use our understanding of genetics and proteomics to reconstruct a viable egg, that will in turn produce a dinosaur, and then, as Hollywood teaches us, some kind of theme park and a whole bunch of lawsuits.

But if we found some Alien DNA analogue, then even if it worked in a very similar way to ours, even if we could identify patterns and codes at the genetic level, it would still be almost impossible for us to work out anything about the proteome of the organism, because the DNA doesn’t actually contain information about how proteins work.

 

2)      Complexity in biotechnology tends to scale exponentially – Say you want to turn an organisms skin green. You find a green protein somewhere, plug it into the target organisms DNA, and then try to get it expressed in a way that doesn’t interfere with anything vital. Organism is now green.

If instead you want to make an organism grow scales. You need to physically change the shape of cells, but you can’t do this without understanding the processes that govern the shape of the cell membrane, and understanding exactly how to change the peptides to achieve that. You need to be sure that changing the shape of the membrane doesn’t change the function of all of the important receptors and channels that go through that membrane, or interfere with its ability to take in nutrients, or the resources required for the cell to live.  Now, you need to consider how changing one cell affects its interactions with other cells, how to get the tissue formed by those cells to grow into new shapes, and then stop growing into new shapes. Can the organism still perspire? If it can’t how are you going to deal with that? What about circulatory changes, proprioception…? I could go on all night.

 

3)      Genetics will probably always involve experimentation, probably on living beings – Protein interactions are incredibly hard to predict. In the example given above, expressing a green protein to turn the organism green has a fair chance of working, and is relatively simple. Predicting in advance, however,  that a tiny corner of that molecule won’t interfere cataclysmically with some random cellular process, is the exact opposite of relatively simple. You could try growing the cells in a petri dish first; your first test subject could still die of liver failure because your green protein can’t be metabolized. And this is just the simplest case, the more complicated the changes, the harder it gets to predict the outcome.

 

4)      It’s not plagiarism if you are a biologist – The easiest way of dealing with the complexity issue is to find biology that has already happened and steal it. Any kind of DNA tampering is much more plausible if you can find something similar in a closely related creature or, better still, lingering in the organisms own genome. That junk DNA that I was talking about earlier contains an awful lot of old information from evolutionary history.

 

5)      Biological systems are simultaneously fragile and resilient – Related to the last point, when I described the complexity of protein interactions earlier, it’s possible that I left you with the impression that biology is entirely at the mercy of its own chaotic processes. This is not really accurate.

Biological systems tend to be highly resilient to familiar challenges but vulnerable to the totally unexpected.

Crude interactions with biology can be startlingly effective, because there are other systems that can cope with the problems that you have caused; but there  needs to be a reason for those systems to have evolved in place.

 

Using this stuff

As always, don’t let the facts get in the way of the stories, find ways to use the facts. Genetics is always going to be a subject that sees the facts get in the way of some of the fun, but temporarily getting in the way of the fun is not actually incompatible with storytelling.

Acknowledge the problems, then let your characters figure out how to overcome them, conquering the world with an army of lizard men will be so much sweeter for them if you make them really work for it.

Don’t worry too much about systematic research, but trawling wikipedia for random genetics facts can’t fail to land you plot hooks.

I do think that proteomics represents a massively under explored areas of science fiction. Anything that can be done to an organism with genetics can also be done, at least temporarily by interacting with the proteins directly.

The mainstream fixation on DNA could be a weakness to be exploited; perhaps your antagonist could develop an alternative mechanism for inheritability, his super soldiers enhancements don’t show up in the genetic screening because they aren’t in the DNA.

Conversely, if you someone, or something, could overcome the complexity issues, genetics and proteomics in tandem genuinely offer limitless potential to screw around with living organisms, genes can be switched on and off at will, and pretty much anything could lurk in the forgotten depths of our genomes.

I’d also suggest that that there is a lot of inspiration here for those of you who might be interested in writing about nanotechnology. Go back and watch that video again if you don’t believe me.

 

Coming attractions and matinee performances

If you like this article you might also want to check some of my earlier articles on interactions with alien biology, or plausible medical responses to weird unexpected stuff.

I’m intending to use this article as a springboard for a couple more articles, one on mutation, which is going to be taking a slightly more Saturday morning cartoon approach to this subject, as well as talking a bit more seriously about inheritance, and the other is going to talk about viruses.

Hope to see you back for them.

WordPress Themes