Virus does not "want" to exist either - they just happen. There is no success criteria or will, just a structure that happens to cause self-replication, with variants that cause more aggressive replication being more present and common.

Prions are in that sense no different - they are just less successful.

I definitely see where you're coming from, but viruses do have modes of transmission that evolve over time to counter immune defenses. Unless I'm mistaken, with prions, you either have to ingest infected tissue or apparently prick yourself with a needle with infective material on it.

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.

It is all a matter of definition. They are both merely a physical structure, they both have to interact with very specific tissues in very specific ways to do anything, they both make our own matter replicate into additional copies of itself, they both have "preferred" areas of attack which are simply areas that they are more successful in, they both tend to "accidentally" cause behaviors that make us assist in spread (e.g. biting), and they both cause various bad things to happen as a side effect of their means of operation.

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.)

There's a lot we don't know about prions and a heck of a lot I don't know, but I would be surprised if prions turned out to be something substantially different from a misfolded protein.

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 major difference is that prions do not evolve from selective pressure.

That we know of - which seems to be more due to the ‘being less successful at wide spread replication’ part. Which we can all be thankful for.

But there is a difference between e.g. crystals and viruses. Both "want" to exist under some conditions. Crystals will even "evolve" to a small extent that more stable/lower-solubility polymorphs will dominate, and there have been cases of polymorph "infection" (ritonivir) between production facilities. Prions are like crystals in this aspect.

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.

https://www.pnas.org/content/100/5/2180.

Comparing a crystal to a prion or virus is a fun exercise, especially as they all appear in the body and causes health issues. Kidney stones, sugar crystalization around nerves, etc.

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.

I think it’s debatable as to the meaning of “want” of non-thinking/non-living things. Viruses continued existence depends on reproduction however, which they’ve been doing for billions of years. That’s a “want” in my book as far as something seemingly inanimate can want.

Viruses that don’t “want” reproduction fail to do so and disappear.

I'm not sure it's entirely correct to refer to this instance by the term of "anthropic reasoning" too, but:

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).

Still not sure I get the distinction with prions that you're making.

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.

> 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.

A protein can misfold in countless ways, and there are countless of proteins to misfold.

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.

> A protein can misfold in countless ways, and there are countless of proteins to misfold.

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 largest protein we produce is about 27k amino acids, more complicated than most virophages. That is merely the biggest we produce. I know of no upper limit on protein complexity, and that is before even taking folding options into consideration.

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 largest protein we produce is about 27k amino acids, more complicated than most virophages

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?

They may be suggesting that prions don't have a large space to evolve within through random mutation

By that metric, everything just happens though. Humans just happened, we didn’t will ourselves into existence. Human free will cannot be proved and may very well just be an illusion in our perceiving of a cosmic causal chain. Are our “desires” for reproduction any different? Or are they artifacts of our internal calculations of the future? When we are optimistic, we reproduce. When we are pessimistic, we don’t. That seems more like opportunism than free will to me. And that seems very much like what a pathogen would encounter: favorable or unfavorable conditions.

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.

I think another way to state this without getting into philosophy or semantics is that viruses are capable of evolving methods of being more successful at infection. Prions are not, because their method of operation involves remaining single molecules.

I like to tell people that early humans lived in close contact with animals for hundreds of thousands of years, and until a few generations ago, when most people were still farming for a living. If prions had the potential to end the human race, they would already have.

I think prions are a bigger problem in crowded single-species environment than in comparatively sparse mixed-species pre-industrial world.

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).

Feeding the output back into the input definitely makes it a bigger problem, however Chronic Wasting Disease in Elk and Dear in North America is becoming a huge problem and is a prion disease, and they’re living wild.

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.

The advent of agriculture and animal husbandry is generally thought to be much more recent than your comment makes it sound. More like ten thousand years ago.

The slight problem there is, prions probably did end a bunch of tribes which were sufficiently local - and then left the area alone long enough that the prion contamination in the environment broke down.

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.

I always wonder how much more truth there is to haunted houses and forbidden lands than we think. Just superstition? Maybe, but maybe not.

It is hypothesised that Kuru (and vCJD) in some individuals (due to genetics) might take 40-50 years to develop if introduced through intestine. Well after the individual had a chance to reproduce.

We're actually having a worse situation re/ animals than our ancestors. We nowadays cram farm animals in stables so tightly that without antibiotics and medical treatment the animals would almost immediately perish. Our farms and our animal "care" practices have been the breeding ground for all recent global pandemics (swine flu, bird flu, SARS/MERS/SARS2). Not to mention the conditions that farm and slaughterhouse workers have to work and live in (as evidenced by massive COVID outbreaks).

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...