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Comment by giantg2 | Hacker News Reader

Prions are concerning. We know very little about them and have no cures. There are forms for common animals that we eat, like cows. Our processing of these animals leads to 100s or 1000s of unique DNA being identified in a single package of ground beef. They do not test for BSE unless the cows are symptomatic, but it's unlikely they would be symptomatic when they have a typical market time of only 18 months. BSE is thought to be a potential cause of CFJ in humans.

In my opinion, our industrialization of the food supply will lead to mass prion distribution/infection at some point.

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Prions are indeed very concerning on a concrete per-instance basis, but —unlike viruses— not that concerning in the abstract as a generic threat. Prions as a phenomenon do not exploit an essential feature of our metabolism, and cannot 'evolve' per se, but are limited to the specific cases in which a) a given protein sequence can stably misfold rendering it ineffective, b) exposure of already functionally 'eufolded' proteins to the misfolded one can trigger subsequent misfolding, and c) misfolded versions of the protein can and do consistently come in contact with non-misfolded functional ones.

I'm not trying to downplay the threat and incredible difficulty of preventing known prion diseases, particularly with regards to destroying the infectious prions. However, to illustrate the rarity of the phenomenon on a per-protein basis, consider how the processes involved in cooking have themselves been denaturing (i.e. mifolding) an unimaginable number of all kinds of proteins in a myriad of ways all since human prehistory, and yet we have no known examples nor even hints of new prions having been created in the process.

The mass processing of food could be the additional mechanism allowing mass distribution of prions, no?

Through processed foods, an apex predator like humanity comes into contact with proteins from several orders magnitude more animals than our ancient hunter gatherers or farmers. This problem is compounded as our livestock eat processed foods themselves.

Perhaps prions were not as dangerous for most of evolutionary history as they simply lacked a distribution vector?

> The mass processing of food could be the additional mechanism allowing mass distribution of prions, no?

My grandmother was from "the old country" and would never allow us to buy ground meat in a package. She made us ask the deli to grind her selected cuts, in front of her.

Back then, I wrote this off as some kind of old world silliness. I remember being embarrassed about the whole kerfuffle.

I know she wasn't thinking of prions, just contamination in general.

Now I realize that I was the silly one, and she was very wise.

Probably more about getting known cut/fresh meat. Easier to see what you're buying before it's ground.

Also they don't can't sterilize the grinder between customers so doubt it does much for hygiene.

This is very common around here.

I was in grad school with a bunch of people from other countries (a common situation, obviously). Almost to a person, they were deeply suspicious of ground meat.

If the feed restrictions don't work, we don't have any checks in place. With stuff like CAFOs and an 18 month time to market, it's possible we create conditions that can spread prions quickly buy they get to slaughter before they become symptomatic. We won't know until it's already a massive issue.

https://www.texastribune.org/2018/01/10/time-oprah-winfrey-b...

It already has with the BSE crisis, and I'm not sure if we 100% understand how close to a much greater crises we came. I remember there was period in the UK back in the nineties where there was the grim prospect of hundreds of thousands of cases - thankfully it never came close to that. And there are European countries where I still can't donate blood, because I lived in the UK during the outbreak.

"I'm not sure if we 100% understand how close to a much greater crises we came."

That's basically my point. It doesn't seem like we changed our practices that much. I would have thought we'd test the animals, process them separately, etc.

There were lots of changes that permeated far beyond Britain. There was a time when every cow was tested in Germany if it was merely alive during the time when contaminated animal-based feed was going around, even if it wasn't fed anything like that. The EU only lifted general testing like 10 years ago - 20 years after the original outbreak. People have also completely stopped using the kind of feed ingredients that allow transmission of the disease to livestock intended for human consumption in most parts of the world. It was a shitty situation, especially in Britain, and many people there probably still carry the disease without knowing it because it can take up to 50 years to show symptoms. That's also the reason why many countries still won't allow you to donate blood if you lived in Britain at the time as the other comment mentioned. So saying that we didn't learn from it or changed nothing is just wrong. Another outbreak like the original one is basically impossible in the western world.

My understanding is that one of the changes we made is we stopped feeding cow brains to other cows, which was the root cause of the problem.

There's also the non-typical BSE - or BSE that is spontaneous. Typically this only affects older cattle.

The interesting thing is that for other prions like scapie and CWD are thought to spread through body fluids and feces and be available in the environment for years. But I don't see any of these concerns listed with BSE. Makes me wonder how much is guess work and how much is confirmed about any of them. But I suspect environmental contamination could be a possible vector. If spread through stuff like urine and feces, CAFOs could be a significant source. This could be a problem if they can be infected for years before symptoms arise, while time to market is 18 months.

My personal pet theory was that prions are an evolutionary mechanism which prevents cannibalism in mammals.

I know nothing about evolutionary biology, and I wonder if there is any chance that this is true.

I think your theory makes a lot of sense if you reverse the causality: Mammals have evolved to not engage in cannibalism to avoid prions. Other diseases as well, of course.

One of the first thing you learn in evolutionary biology is that evolution doesn’t have intent.

Yeah, I guess even I know better than that and should have chosen my words more carefully.

Also not a biologist, but as I understand it: Every living creature synthesizes proteins. Every time you synthesize a protein, there is a tiny tiny chance that it synthesizes "backward". Backward proteins are physically incompatible with "forward" proteins, and also increase the risk that more proteins synthesize backward. It leads to a cascade of errors where lots of proteins synthesize backward and the cells and internal structures can no longer function. It's like you fall apart due to half your Lego bricks being upside-down. And, this is all a statistical probability that could occur in any moment to any living organism.

The evolutionary defenses are to break apart all incoming proteins and reassemble them yourself, and have a cycle of life that starts new organisms from scratch. Large carnivores can't hope to break apart every incoming protein, though. So, basically our lifespans and reproduction method of growing up from a single cell are the evolutionary defenses against the natural phenomenon of prions. But yes, prion disease is probably what forces all higher foodchain animals to avoid cannibalism.

This is not at all how it works. Prion diseases are not at all to do with synthesising proteins 'backwards'. It's entirely because of one protein found in the brain which has a very stable misfolded form which will induce other copies of it to misfold as well (and this misfolds all stick together into something the body struggles to break down, which is what eventually causes the damage). It's not something that can happen to just any protein (lots of other proteins do misfold or are otherwise not made correctly, all the time. But they don't induce other proteins to misfold and the body can easily break them down or otherwise get rid of them)

(in fact, the misfolded form is so stable it can survive cooking, autoclaving(!), sitting in soil for years, and digestion. The main reason it's not a big threat is that it needs to somehow get from the environment into the brain, generally via the gut, which is not a particularly easy process for an inert clump of amino acids: a significant percentage of UK residents actually have detectable levels of this prion in their gut already, but only a very small fraction will develop the disease)

So that has raised an interesting question in my mind. But as far as I know the only significant case of prion disease amongst human beings, excluding CJD which seems to be generically determined, was the instance of Kuru among the Papau New Guinea tribes; however we know other societies practiced cannibalism at a certain scale such as the Aztecs in which people were eating other people all over the place, yet we don't have widespread evidence of Kuru.

Is there something distinct about Brian tissue which puts it at a higher risk for prion disease formation?

Just a bystander shooting from the hip, but does the fact that brain nerve cells aren't recycled and rebuilt but live as long as the person does mean they are more prone to accumulating bad proteins?

Other tissue like skin or muscle that regularly break down and regrow would offer a lot more opportunity for the body to filter out the prions, but once in the brain cells, there's nothing for them to do but accumulate.

It's because the prion protein is in the brain. As in, there is basically only one protein in mammals which actually has this problem (that we know of), it's not a general issue with proteins. The variants which exist are essentially because of the small variations in this protein across species, or specific inheritable mutations which make sponteneous formation of the misfolded form more likely.

(this protein, by the way, is not essential for life, but lacking it seems to slow brain development in mice)

‘Prevents’ is an odd way of putting it.

A thing eating dead instances of its same family is already a near ideal situation for passing disease, no fancy evolutionary mechanism required. Frankly, hard to imagine a better one.

If mammals needed a ‘anti cannibalism’ evolutionary mechanism there are plenty of other mechanisms - like disgust responses - that would actually prevent disease.

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