Wasn’t sure what to flair.
Prion diseases are terrifying, the prions can trigger other proteins around it to misfold, and are absurdly hard to render inert even when exposed to prolonged high temperatures and powerful disinfectant agents. I also don’t know if they decay naturally in a decent span of time.
So… Why is it that they are so rare…? Nigh indestructible, highly infectious and can happen to any animal without necessarily needing to be transmitted from anywhere… Yet for the most part ecosystems around the world do not struggle with a pandemic of prions.
To me this implies there’s something inherent about natural environments that makes transmission unlikely, I don’t know if prion diseases are actually difficult to cross the species barrier, or maybe they do decay quite fast when the infected animal dies.
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It’s truly awful, but read about Kuru sometime.
Prions are rare because by far the easiest way to spread the diseases involve cannibalism. This isn’t common in nature and was quite uncommon in civilization as well until modern factory farming techniques started “recycling” animal parts. Mad Cow Disease spreads amongst cows via cannibalism, then humans eat the cannibal cows and get it. Humans don’t spread it to other humans (edit: without eating them).
There is a fundamental flaw with your assumptions: prions are not terribly infectious. Animals with prions die off pretty quickly and to catch the disease you must consume the misshapen protein directly. It isn’t like Covid where someone coughs and spreads it.
And once the host dies, unless something consumes it pretty soon thereafter, the prions won’t be spreading.
Prions have some pretty big weaknesses as well.
On the most basic level, prions aren’t alive. They aren’t even sort of alive like viruses. A prion reproduces by misfolding properly folded prp proteins. There’s no genetic material involved and very limited options in terms of heritability…a few different ways to misfold the protein, and that’s it. A mutation in genetic code can’t produce a new trait that’s carried on in the next generation. So prions can’t evolve…they can’t get better at being prions, because there’s fundamentally only one way to be a prion. They can only misfold the one kind of protein. They can only misfold in a few separate ways. They can only be transmitted however that protein can conveniently be transmitted.
This also means that if an animal develops resistance to them, they can’t really "get around" that resistance. And that’s possible, some species seem totally immune from prions, and non mammal species don’t even use the same protein (though some have their own prion like diseases).
In part because they can’t evolve better transmission, prions tend not to efficiently transmit in a repeated way. Consider the standard mode of prion transmission…something eats something and gets prions from it. Consider, for example, a herbivore gets prions spontanously. It gets eaten and passes them on to the predator. Right there, that’s a bit of a problem, since diseases fail to thrive if they are only passed on 1:1. A person with a cold can pass it to lots of people, an animal with prions is probably just eaten by one predator…maybe shared with a few but usually not. And then the predator, even if it gets prions and dies, is very unlikely to be eaten by multiple herbivores to recycle the chain.
So generally prion transmission chains die out unless you do something silly like grind up herbivores and mix that into the food supply of many other herbivores.
There are exceptions like Chronic Wasting Disease in deer, where deer in crowded conditions get prions from each other, but that’s unusual.
To my understanding, prions aren’t actually living, so they can’t be traditionally killed. Incineration the only thing that removes them from the environment.
Nature deals all diseases the same way, through natural selection and evolutionary gains. Nature has lots of time, and doesn’t really care about the here and now. That’s a Human concept, due to our extremely short lifespan.
Mad Cow disease, Bovine spongiform encephalopathy (BSE), is a great example. In Humans, it’s called Variant Creutzfeldt–Jakob disease (vCJD).
Cows develop BSE through cannibalism via inadequate feeding regulations allowing same species food lines. The natural food chain doesn’t appreciate self consumption in most cases.
We eat from an infected cow’s meat, and it’s potentially boom! vCJD.
Reminds me of ‘Soylent Green’! If you’ve never seen that movie, it’s a definite Must Watch! Charlton Heston! Has nothing to do with Mad Cow! Just a great movie!👍
Prion diseases are rare because of the method of transmission – you have to consume the affected tissue, usually the brain. See: CJKD, BSE, kuru
Those animals who do get infected usually die pretty quickly. Those prions are misfolded proteins so they’re going to degrade eventually, and won’t spread to another organism unless consumed.
They’re not transmitted via aerosols, air droplets, or on surfaces like, for example, cold and flu viruses are.
Prions are extremely durable, but not particularly infectious, particularly across species.
Outside of situations humans create, it’s uncommon for herd animals to live as densely or to repeatedly frequent the same gazing areas as they do now.
Outside of situations humans create, herd animals are almost never consuming the bones and brains of many other individuals of their species.
Animals that regularly eat the bones and brains of other animals have never been particularly dense on the landscape, so wouldn’t be at particular risk of eating each other, and are even less dense now, and so aren’t able to clean up corpses of herd animals that have died of prion diseases or to kill them before they’re super sick.
The ecology of prion diseases has been created by humans.
By dying. You’d be surprised how much nature just lets specimens die from. That’s how it works, part of the population dies off and the rest are either resistant to or avoid the cause. This mirrors the behavior of our constituent microorganisms which die off and are replaced to continue the perpetuation of the whole. And on a larger level, whole populations or even species can die off to maintain the balance in the ecosystem. Nature is more fond of the whole than it’s parts.
Professional Neuroscientist, PhD etc, worked in neurodegenerative diseases research, Parkinson’s disease primarily for 10 years.
Prions are really interesting but are almost closer to virus than any other type of disease causing agent. They are not a living entity. Unlike viruses, they don’t really evolve but are closer to an anomaly rather than an infectious agent.
Prions kill their host quickly, are very resilient, but not necessarily highly infectious. These are actually terrible qualities for an infectious host. Ideally, an infection should be able to replicate, preserve its host, and be as transmissible as possible to survive optimally.
If we look at Covid (sars-cov-v2) as an example, Covid became less lethal but more infectious. That is the natural evolution pathway. A virus is more likely to survive by spreading itself as much as possible.
Prions should not evolve theoretically. They are an artifact. They hijack a protein ‘s folding process, cause it to misfold, and disrupt an otherwise important cellular process. This causes the otherwise important protein(s)to become useless. They also exhibit a secondary quality of being hard to remove by the cell, so they stick around and continue to be disruptive. As a result, they accumulate and cause cellular distress and death. They also exhibit a 3rd quality, in that they are propagatable from cell to cell within an infected host.
The outcome of your cells be diseased and dying may not actually be a problem until we hit irreplaceable and non dividing cells. Neurons are the poster child
For non replaceable cells. I use non replaceable because the ongoing theory is more murky.
neurons are the cells that are highly susceptible to prion disease. They cannot clear the misfolded proteins, become dysfunctional and die. This is eventually kills their host quickly host.
These qualities also exist in Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease. In each case a protein misfolds and takes on an amyloid structure. It’s highly resistant to degradation by the cell, templates misfolding of its shared disease protein. In the case of Parkinson’s disease it’s alpha-synuclein and in Alzheimer’s its beta amyloid or hyper phosphorylated tau.
Hyperphosphorylated tau is also found in TBI and hyper encephalitic events and diseases.
It’s theorized that diseases are prion-like caused by an event that induces a misfolding in their respective diseases.
This doesn’t mean you’re going to get the disease by being in contact with the these people. However, I would not recommend you eat their brains.
There was a paper published about 20 years ago which posited that most humans (or Europeans at least) had evolved to be resistant to transmissible spongiform encephalopathies – acquired prion diseases – due to widespread cannibalism among our human and proto-human ancestors. And it does appear true that most people possess genes that, at a minimum, drastically increase their incubation period.
I CANNOT EMPHASIZE THIS ENOUGH. Prions don’t misfold proteins, well they do, but only other prion proteins. PrP^c is a single normal protein that exists at the highest concentration in neural tissue but other places as well. When it becomes misfolded it becomes PrP^sc. PrP^sc can misfold other PrP^c proteins into PrP^sc to propagate. It’s a misconception that PrP^sc just misfolds any other ‘ol protein, that’s not true, just PrP^c which is a tiny fraction of a brain’s total protein makeup. That is a major reason why prions don’t just spread like a deadly nanobot plague.
Why it is so rare is not really known. There is still a lot we don’t know about prions. One of the things to keep in mind is prions quite often can take at least a few years to show any symptoms. And you would be surprised by the average life span of say a deer in the wild. Many probably get infected but simply don’t live long enough to get to the symptomatic stage. And those that do get symptoms will be quickly taken out by predators. So in the later case you are not seeing these before they are eaten.
As we are learning, and there is much research to be done, is for various prion diseases we have identified in humans genetic polymorphisms in the healthy prion protein that does not allow infection by any of the known prions that can infect humans. There are also species barriers between some prions and humans. Here again the slight differences in protein structure in a deer’s healthy prion protein is a little different than that of a human. And the pieces need to fit together like a puzzle. The healthy protein the the brain and the disease prion need to have a structure that matches and allows the disease prion to convert the healthy protein to the disease form. CWD seems to match the healthy protein in the deer and other animals but does not infect humans. And while more research is needed it may well be that the puzzle pieced do not fit together perfectly and thus the prion cannot transform human healthy prion proteins in the brain to the disease form, whereas Mad Cow is a match that can for example. But as I said we have identified people with polymoophisms resistant to all know human infecting prions so there are at least some people, not sure what the percentages are that are resistant to infection. And while we have a general sense of how prions infect we don’t have a good idea on how easily they infect. A fair number of people at Mad Cow contaminated beef in the early 2000’s. We would expect to start seeing vCJD in them maybe 10-20 years later. We did see the cases rise but it was no where near as many as you might have expected. Why that is is not clear. Not eating enough for an infectious dose? More polymorphisms out there resistant than we know about? We don’t really know at this point. But the numbers of vCJD cases in the UK were much lower than I thought they would be, surprisingly so.
So factors we need to study more to answer your questions: how many do you need to eat to have a good chance of being infected? What factors during exposure either facilitate infection or reduce it’s chances? Is eating them the main infection route or is it something else like handling the raw meat and say touching your nose or eyes? In the case of Mad Cow the prions are predominantly in the nervous tissue, less in the meat, so maybe this lower dose is not enough to cause massive infection numbers? How many people out there have polymorphisms that are resistant to infection? If they are common that may account for why prion disease are quite rare in people and we have identified at least some polymorphisms that do this in people. Is it possible that it is actually few people susceptible to these, rather than most? Lots of answers we need to fully answer the question. One thing we do know though is the stability of the prions. They can remain in the environment for a decade or perhaps more. So that is unlikely the main factor.
How does nature deal with prion disease you ask? Easy.
They dont.
The thing about prions is their neither a virus, nor a bacteria, they arent even a disease in the traditional sense. It’s a really bad recipe, from a misfolded protein that teaches normal proteins to misfold too. And the way it does this by acting as a template for each other, which means there are two possible vectors to stop this process, but ill take that up at the end.
Now, we do not really know the origin of prions, or animal prions, but we do have two solid guesses, we know they spontaneously appear, which might just be it just… Happens, but we also know there is a genetic method, and since animals can be carriers without being sick, much like humans can, i mean how do you explain kuru in the human brain? So chances are there is something there as well. Because in the case of Mad Cow Disease, we know it primarily occours due to cattle being feed ground up cows, and they consume the neural tissue which causes the primary infection, and from there is can spread via all the fluids.
Now, the three methods of srpeading is spontaneous, genetic, and infectious, genetic examples are creutzfeldt-jakobs disease, whose genetic variant, is a dominant mutation, which means that if both parents carry the gene, then the child will get it, and chronic wasting disease which is what deers get, spread via salvia, urine and feces, where touching noses is enough for spreading, and when they die in nature they can infect that area as well for quite some time.
Now, the primary reason prions stick around in nature, is their insanely long incubation time, so an infected animal can live for years as a super-spreader.
So yeah, nature doesnt ‘deal’ with it, at best it slows it down.