Botulinum poison targets proteins your body uses to make cholinergic neurons release acetylcholine. It binds to them and prevents them from doing their job, which is critical to normal operation of billions upon billions upon billions of very important neurons in your body. However, if you were to estimate the total mass of all of these very important and specific proteins in your body, you would probably get an answer in the… drum roll please… nanogram range. There is simply not a lot of the target compared to the sheer volume of Other Stuff hanging around.
Another important thing to consider is that the bacteria that produce botulinum toxin have had billions upon billions of years to evolve small changes to the genetic code for the toxin, and there is some logical evolutionary pressure on forms of the toxin that are better at binding to the target (and poorer at binding to the Other Stuff). It only takes nanograms to kill in part because the botulinum toxin is so precisely refined towards performing its functions and ONLY its functions, which are binding to and inactivating stuff it would like to inactivate. This is also the reason why levels of common steroid hormones like testosterone and estrogens are universally in the nanogram range — that’s all you need when billions of years of evolution have ensured that this square peg can only, ONLY, fall into the square hole.
(Also, the steroid hormones are poorly soluble in water, so you can really only get nanogram concentrations into the blood/cytosol anyways, but that’s outside the scope of this discussion and not totally relevant.)
Your body and all its inner processes are based on the exchange of certain chemicals. The fact that you have to pee is a chemical released based on a signal in the brain. Your blatter will pick this chemical up and start the “flow”. A feedback mechanism based on chemicals and recepting cells (certain keys or chemicals fit on certain locks or recepting cells). This poison is nothing more than a chemical that tells the recepting cells of the organ(s) (in this specific case nerve system) to STOP. The key happened to fit the lock by accident. This is the same reason why dogs can’t eat chocolate, the key fits the lock.
One way of destroying a car would be to bomb it. But if the goal is to prevent it from running you only need to disable the engine. This could still include blowing up the engine. Or fouling the fuel. Or something as tiny as clipping a wire that controls how much air and fuel get in, which cuts off one or both.
If the tiny amount of poison messes up chemical reactions that are very important, like keeping the lungs or heart going, then smaller amounts are needed to be lethal. Botox basically disconnects the nerves from the muscles, including those needed to breathe. Depriving the brain of oxygen gets very bad very fast.
What you have to get out of your head is weight or mass of biochemical toxins. It’s not weight but numbers. Cyanide kills you when a certain amount of the cyanide ion is present throughout the body to arrest cellular respiration. That amount is based roughly on multiplying the number of mitochondria in the body by atoms of CN-. There are a lot of mitochondria but mitochondria are huge compared to a carbon-nitrogen atom. A nanogram of cyanide might still be a trillion times a million molecules of CN. Botulinum toxin is no different although it’s much larger than cyanide. Each muscle in your body is controlled by a few molecular switches. And there aren’t that many muscle cells , maybe a few billion? But a billion molecules is nothing when you try to weigh them. A billion molecules of say insulin would weigh so little no scale on earth could detect it – in fact that’s about a nanogram. So a nanogram of botulinum toxin could be visualized as keys. Trillions of keys. And each key can lock down a muscle cell. Lock enough cells into the off position and you stop breathing or your heart stops pumping
First of all, your instinct is very good. It’s not average of any poison to be so toxic that a few nanograms kill someone. Let me walk through how poisoning works in terms of biochemistry.
Let’s first imagine a crowd, like a concert full of people. Imagine a man and wife arriving separate and not finding each other (not even knowing the both are there). What’s the chance of them finding each other? Assuming that they both walk around randomly at their usual speed, it only depends on how big the entire crowd is. In a small crowd they have better chances to bump into each other than in the huge stadium .
Now imagine that we clone them, so we have several copies of both the man and the wife. The more copies there are, the bigger the chance is that one copy of the man bumps into one copy of the wife. But it also depends on the crowd size, in a bigger crowd you need more copies for the same odds of meeting. The ratio of the crowd and the number of the person of interest is called *concentration* in chemistry.
Very similarly, in biochemistry, molecules and their reaction partners (such as toxins and their partners) wander around in our body, cluelessly. And they find each other based on the concentrations.
But there’s one more thing to add to the equation. Let’s get back to the man and wife at the concert. Let’s assume if they meet, they give each other a quick hug and then they go on. Yet another meeting between another copy of them, hug, repeat. But what if the man has his lover around the concert too, and when they meet, they keep hugging? Those husband clones that are in the hug with the lover, are out of the equation from the perspective of the wife.
Molecules in biochemistry are basically the same. Some partners like to stick together longer than others. And it has a very important consequence. You see, for each partner there are two ways of spending the time: alone (wandering around) or together (hug). If the hug time is long, then for the same amount wandering time you get much more hug time.
In other words, if you want to have a given amount of hug time happening, then you can either mix short-huggers in large numbers (large concentration), then they will *often* meet, hug a bit and go on. Or, you can mix long-huggers in a low concentration, they will rarely meet, but once eventually they do, they will hug forever. In chemistry, the length of hug is called affinity. High affinity means two molecules love each other a lot.
Now in life, there’s a lot of reaction that must happen at the exact amount it needed. Low affinity is not a bad thing, if that reaction needs to go at low rates. We have all of the different things in our body some work at low concentration and low affinity (because we need just a very little of that reaction) some with high concentration and low affinity etc.
So for something to be extremely poisonous you need two criteria.
One is that the poison must have high affinity to the target. It means that if you have a very few molecules of poison wandering around in your body, once it bumps into the target, they stay together forever, blocking the whatever thing the target would normally do. If the affinity is lower, you need more poison for the same effect, to compensate the shorter hug times with more meeting events.
And the other criteria is that the target molecule must be rare. With a 100 molecules of poison, you can occupy 100 molecules of target. If you have 1000 or 5000 target molecules in the body, then no matter how high the affinity is, you need much more of the poison.
In case of botox, both criteria are met. The botox acts on things called neuromuscular junctions, the points where the brain controls the muscles. Even though there are things that are more rare in our body, but these are also sort of few. Also we can’t afford losing too many of them because they make our muscles move. The more we lose the more muscle go paralyzed. Imagine losing 10% of heart muscle control due to losing 10% of overall neuromuscular junctions.
As well, botox has a very high affinity to the target which means you need very few molecules to completely occupy a lot of the target.
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