These prions sound horrible, less defensible against than viruses, and at the same time much simpler in form than viruses so much more common (easier to appear).
What is the reason that we can thank for prion diseases not being much more common?
What is the reason that we can thank for prion diseases not being much more common?
Another way to look at it is that the combined lifespans of the organisms of a food chain are shorter than the time it would take for one mis-folded protein to be likely to occur and then also cascade to a degree that would affect the health of the top organism. Prion diseases only show up when you introduce a loop in the food chain.
One reason is that we don't eat each other which would spread certain prion diseases like https://en.m.wikipedia.org/wiki/Kuru_(disease)
They don’t “want” to exist, even to the minimal extent of a virus, they just happen.
Prions are in that sense no different - they are just less successful.
I don't believe they reproduce in any but the broadest sense either. Don't they just cause other proteins of the same type to misfold as well? It's not really a transfer of genetic material, it's a change in the emergent structure of the protein.
The prion's mode of operation isn't just "bump into stuff". It reaches the brain, causes other materials (DNA aptamers) to clump together, and causes other prions to be created.
That one happens to have a part that looks like genetic material and the other looks like a misfolded protein is merely a small implementation detail to me.
(Disclaimer: I, like everyone else I'm this thread, is not a qualified source of medical information.)
I've never heard of prions targeting certain tissues. I need to do some reading, as it's been a while since my last bio course. Do you have an article that explains how that works? In order to have that ability, they would have to be more complicated than I understand them to be.
The difference is that viruses have many more tools available in order to evolve and adapt. Prions, like crystal polymorphs, merely have the configuration space of the molecule. Viruses have the configuration space of dozens of proteins, and complexity can increase, so in theory there is no upper bound.
So I guess yes, they are all replicators that differ in extent by the amount of phase space available to their lifecycle. But the complexity jump between prions and viruses is huge, and prions are inherently bounded.
One main "behavior" difference between crystals, prions and viruses is that a crystal only forms by recruiting its equals when in high concentration - growth, but no replication.
Most virus is way more complicated than prions as you say, but a blue whale is also more complicated than a single-celled myxozoa and yet they are both animals. I do not think a comparison of complexity is meaningful in this debate.
One should also consider that there are countless proteins to misfold in any number of ways, so the prion space is not necessarily that limited. Virus do have the upper hand by using our well-oiled evolutionary machinery though.
Viruses that don’t “want” reproduction fail to do so and disappear.
The viruses we see are common because they reproduce, it's not that they reproduce because they have some drive to become common.
Thus prions are less common because they aren't as successful in spreading (for some reason(s) I don't know either).
The essential idea is roughly "we end up with more of the things that replicate more". Despite the redundancy, there is a crucial idea in here. If we allow the use of the word "want" metaphorically then anything that replicates "wants" to reproduce including memes, crystals, prions and computer viruses.
Maybe you're just saying that a prion isn't as good at replicating as a virus? It seems like a difference of degree rather than kind.
They are qualitatively different.
A virus infects a cell, and critically, can quickly adapt (through random mutations) in an unthinking war between the various forces of the immune system and transmission mode efficacy; A prion does not evolve, it's a misfold of a single type of protein. If you want to compare it to a virus, it's like a virus that is incapable of replicating anything other than an exact copy - and can also only replicate itself using a particular cell (one type of protein).
Why the human body cannot effectively defend itself against particular propagating misfolded proteins is a mystery to me though... perhaps it's too low level to be identified by the immune system as something to attack, much like a poison.
That a virus can be a big and complicated structure does not mean that smaller and simpler structure is fundamentally different.
Viruses themselves also have many different modes of operation, with things like virophages, satellite virus and giant virus showing just how unclear the term "virus" is.
They are countable, but yes there are many ways, but that alone doesn't mean it's capable of meaningfully evolving. It's a search space multiple orders of magnitude smaller than a piece of DNA, so it's easy to see how a different successfully propagating misfold will be significantly less likely when starting from an existing propagating misfold.
If you are suggesting one propagating misfolded protein can, by chance, misfold into another propagating misfolded protein at a rate fast enough to become adaptive... then it's qualitatively the same as a virus, but I don't see this as likely given the significantly smaller search space.
The space of possible proteins - and thus prions - is not at all limited, neither figuratively nor literally. It is most certainly not "countable" without some Nobel-prize inducing discovery.
The only known human prion proteins seem to be a few orders of magnitude smaller than that though, and they don't appear to adapt.
Are you saying it's possible for prions to emerge from large proteins with the ability to adapt?
I guess what I am saying is that either you are right and that can be extrapolated all the way up the chain to humanity. Or that you are wrong and you can apply free will all the way down the chain.
In particular when you feed cows proteins made from dead cows it's making it more likely to create prion problems than when wild animals live in small herds in forests (and the ones that are sick are killed by predators or starvation before they can infect others more than likely).
So it doesn’t require it, it just increases the odds (and they don’t eat each other to spread it - it’s highly infectious and demonstratively infects if they share browsing/grazing land).
It doesn’t appear to spread between them and humans, but it definitely makes me nervous.
Today we have international animal shipping and trade, and global distribution. Prions are able to spread from exposure to shared pastures. A couple years of contamination used to be no big deal - today, if missed, it can spread all through the food supply.
The chance of any infectious agent "jumping the species" due to cramped conditions or because of exposure of workers to contaminated animal parts in unclean slaughterhouses is immense - the current SARS-CoV-2 pandemic in my opinion is a warning signal of something much worse to come, and no matter what kind of agent it will be, we're pretty much screwed. Half the population or more of the world doesn't believe in vaccination, a quarter or more don't have access to vaccines or any kind of modern medicine at all, we are already running out on reserve antibiotics...
Viruses rely on the machinery of nucleic acids to replicate. That machinery is complex and robust and the result of some long period of continuous evolution, which means viruses exists in a fairly smooth fitness space where mutation and recombination are effective means of improving fitness.
Prions by contrast seem more like isolated spikes in a much sparser fitness space. Presumably the equivalents of mutation and recombination for prions lead to molecules that almost never retain the capacity to replicate, so they have limited potential to become fitter over time.
Prions can't self replicate from raw resources: they depend on inducing conformational change in other proteins. The host has to produce, and use, the specific protein they can target in an accessible location.
The upshot of this for prions is that lacking genetic code, or a need for replication machinery, and being a variant of the protein they target, they are perfectly adapted for their environment and host and currently impossible to destroy without also damaging the normal correct protein form.
I’m far from knowledgeable in this area, but the model in my head is: the $foo_protein can be folded in at two important ways, $foo_v1 is what you want, $foo_v2 is a catalyst for refolding $foo_v1 into $foo_v2 but doesn’t refold much (or anything?) else.
A human analogy might be a disgruntled but charismatic worker who starts spreading a disruptive attitude until morale and productivity plummet in their department. As long as one of that team remains, the issue can still spread. Coincidentally, both the potted plants and highly compensated leadership are unaffected.
Not really on both parts. It's only transferred by eating meat so the defence is as soon as prion infection is detected all possibly infested livestock is culled and severe bans on trading are placed. Cannibalism in animal feed is also disallowed which makes transmission rare. Being vegetarian is also a complete defence.
They're also rare to appear, otherwise eating livestock would have regularly wiped out humans already. They're basically non-existent if you don't eat humans and livestock isn't fed to livestock.
Tell that to deer dying of CWD.
Your condescending sic is, ironically, misplaced.
Lady in the story could have been a Vegetarian yet still died from a Prion. As others have pointed out swimming in bodies of water is possible vector for prions.
But: consuming bush meat, brains, feeding dead animals to other animals, being careless with sharps and so on are all excellent ways to contract them.
We kinda take this for granted, but it may be the case that our deeply-rooted psychological disgust and aversion to eating human flesh is a product of prion disease killing populations of ancestors who did. Or perhaps, even our tendencies to ceremonies of death helped us: those that feared the bodies of the dead, or were more likely to create rituals of destruction and avoidance, were more likely to persist and pass on their genes :)
In addition, your body probably has evolved to use proteins that aren't particularly susceptible to misfolding AND accumulation. (Perhaps a long time ago, it WAS quite common?)