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> Most importantly, viruses and bacteria innately "want" to spread. Prions do not have any biological mechanism for their own propagation - they are just an unfortunate mistake of nature. And this seems to be key why there has never been a massive prion outbreak.

I disagree here, and but it's not fatal to your argument. Anything that reliably reproduces "wants" to. Hell, I bet prions can evolve too on large enough time scales (heterogeneous induced refolding), so we can say they are alive. But sometimes the tortoise is too patient and the race ends before the hare tires.

In order to evolve there has to be some kind of genetic information passed on to descendants. But for prions there is no such mechanism. A lower energy state is assumed and that's that.

So prions are simply a result of entropy? Am I understanding that correctly?

All evolutionary change (and life itself) is due a combination of differences of entropy (aka an energy gradient existing), combined with randomness in the current environment allowing mutation/change and hence selection pressure.

I would say life is an artifact of non-erodicity. Rare things that self-replicate are over-abundant in hindsight.

There does not have to be genetic information for evolution.

Evolution only requires "descent with modification". DNA is a mechanism for this, but it is not necessarily the only one.

And prions don't have descent with modification. It's a regular mammal brain protein that got accidentally constructed backwards. There's nothing to pass on, nothing to modify.

Err, I think I remember a couple pretty famous articles that contradicts that prions generally don't have descent with modification, which may be what the person above us is referring to:

https://pubmed.ncbi.nlm.nih.gov/20044542/

https://pubmed.ncbi.nlm.nih.gov/17142317/

That's really neat. Still there should be a limited number of possible variants right? Like the energy landscape is fixed and will only admit so many possibilities?

FWIW Wikipedia says:

> Prion replication is subject to epimutation and natural selection just as for other forms of replication, and their structure varies slightly between species.[19]

[19] is https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848070

descent without modification sounds pretty hard to achieve for all but the simplest things.

This got me wondering: what is the advantage of genetic information (DNA / RNA) over a self-replicating entity without those convenient molecules?

My impression is that DNA / RNA-based organisms have a high tolerance for changes to their DNA / RNA, such that many genetic changes won't cause them to lose their self-replicating ability. This is great for evolution.

Prions, on the other hand, seem like they would have a low reproductive tolerance for changes to their structure.

The prions are not involved in the formation of new proteins, so it's very^100 difficult that they can evolve to create more efficient versions. [I try to not use "impossible" because life finds a way ...]

Virus instead use their own material as the original to make copies, so any new good or bad variation will be copied in the offspring, and they can evolve.

> I have to imagine that vegans have an incredibly low risk profile for prions.

What do you reckon the risk profile of vegetarians would be? Are prions likely to end up in eggs and milk?

In general I think we should be trying to eat foods that are really biologically dissimilar to humans to avoid being sickened by our foods' diseases. Plants and fungi don't seem to cause pandemics. Mammals do (SARS, covid, swine flu, possibly Spanish flu). Birds can make us sick (salmonella). Fish, mollusks, insects, probably safer, parasites aside.

Does your second point suggest that we should avoid eating beef?

For people who are intensely worried about prions, it seems that eating less meat will decrease their chance of exposure.

I mean, there are a lot of reasons to not to. And I say that as a meat eater.

I think there's better arguments than a risk of prion disease for cutting beef (or meat in general) from your diet - not sure if your comment is meant as a joke that I'm not catching, so I'll hold out on going into details unless you're interested :-)

Not meant as joke. I'm aware that there are lots of good reasons for not eating beef, I was wondering if prion exposure risk is one of them, as the meat/no-meat argument is one I try to revaluate regularly as new info comes to light. I eat beef once or twice a week as I have found it hard to get sufficient iron, protein, b12 and enough calories in general without it (and other meats). That and it tastes good, but I'm always receptive to new counterpoints.

I take a liquid supplement called Floradix for b12/iron. It is made from yeast and vegetables. I'm prone to anemia and it has been immensely helpful.

Prion concentration varies greatly from one part of a cow to another, because prions gravitate toward nerve tissue for some reason. The brain is definitely dangerous to eat. So are the eyes, the spinal cord, and parts of the intestines. Muscle tissue on the other hand is said to be much less dangerous. I don't know how much less, though.

Remember that all risks are relative. Just like radiation, there's likely to be a background level of prions in the soil that you can't avoid even if you only eat vegetables. The question is how much prion exposure you can tolerate without having noticeable symptoms within your lifetime.

I don't think prion disease currently is a significant enough risk to make it an argument against eating meat. It's a rounding error compared to for instance increase in colon cancer

I eat meat occasionally as well. I tried going vegetarian for a six months, but I lost an unhealthy amount of weight (my BMI dropped from 19.2 to 17.8) and I think the health risk from malnutrition, as you also mention having struggled with, is much more severe than that of prion disease

Yeah this is exactly the situation I find myself in. I regret the ethical and environmental consequences of eating meat, but I found it very hard to replace it completely and still have a balanced diet.