[purpleflame1257]

Counterpoint: The Fore people of NZ had kuru from ritual cannibalism. Then they stopped. Eventually, the disease stopped too. Prions are nasty, but we've had 3.5 billion years of protein folding and none of it has ended the world yet.

[dnautics]

This comment is spot on (I'm a former prion researcher).

[cogman10]

What do you make of CWD?

That one scares me more than current known human prion disease. Mainly because it seems to spread really easily. Other prion diseases seem to practically require cannibalism to spread.

[dnautics]

Cwd is essentially the same as bse and cjd and scrapie. It's actually the one that you have to worry about the least. For unknown reasons, there is not species crossover between deer and cow/sheep/humans (I was briefly investigating the molecular mechanisms for this but finished my phd before getting results).

As for why the grazing animals can spread prion, my guess is that the prion protein is highly concentrated in the tongue, and grazing animals are likely to be able to pass the protein down to the ground via the saliva. Scrapie and bse are cross-transmissible

Incidentally, you probably shouldn't eat beef tongue.

[hajile]

The CDC disagrees with your assessment. Do you have any sources about this?

According to the CDC, CWD is spread NOT just through saliva, but also feces, blood, urine, etc.

In addition, it CAN spread to Squirrel monkeys. The long-term affects on macaques is still being established (on of the reasons kuru took so long to discover was that it took decades for the monkey to develop symptoms).

If exposure is dangerous to humans, what could we do? In the areas it has been in, it is spread everywhere the deer travel as they shed bodily fluids into the soil.

source -- https://www.cdc.gov/prions/cwd/transmission.html

[dnautics]

So I should have disclaimed that my information is as of 2009, which is the last time I touched this stuff, but that site said there was not successful transmission into monkeys in another experiment by the lab. I mean these experiments are extreme, high dose boluses of material straight into the brain. If at least one experiment failed to do that into monkeys that says something, even if they managed to get it in a later one, unless there was some revelation that they had done it wrong the first time.

[giantg2]

"there is not species crossover between deer and cow/sheep/humans"

I thought the theory was that CWD started in a domestic herd that was raised in an area that previously had scrapie infected sheep?

[dnautics]

These things can also happen autogenously (there is sporadic cjd) so who knows.

[danesparza]

Wait, wait, wait. Your advice seems contradictory: "there is not species crossover between deer and cow/sheep/humans"

and

"Incidentally, you probably shouldn't eat beef tongue."

Can you clarify?

[dnautics]

Sorry, the grouping was unclear.

There is not deer <-> sheep, deer <-> cow, deer <-> humans.

There is cow <-> sheep, maybe cow <-> human. I don't know off the top of my head about sheep <-> human

If there had been, the us food supply would be trashed. Cwd is highly endemic among wild deer and wild deer co-graze with cows all the time.

Also unknown if the relationship can be transitive. There might be a species X where deer <-> X <-> human.

[chasil]

Scrapie appears to have been the ultimate cause of a human CJD outbreak:

"...in 1996, with the recognition in young people in Britain of a “new variant” of Creutzfeldt-Jakob disease (nvCJD, or the Will-Ironside syndrome) that has since been traced with near certainty to the consumption of tissue from cattle infected with spongiform encephalopathy (BSE), they having in turn consumed meat and bone meal contaminated with rendered sheep carcasses infected with scrapie... There are currently just over 30 verified cases of nvCJD, and four to five new cases a year: whether they represent a small group of susceptible people or are the leading edge of a major epidemic is still moot."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114482/

[wil421]

No lengua tacos? What will I get now?

[dnautics]

Cabeza. Which is usually the cheek meat. Avoid sesos, of course.

[mgarfias]

But lenguas?!?

[CountDrewku]

CWD hasn't jumped to humans ever, correct?

[giantg2]

They don't really know, but the evidence suggests that it doesn't, or at least hasn't yet. There have been a few studies following up on groups of people who consumed CWD positive deer.

https://www.usatoday.com/story/news/health/2019/02/21/zombie...

[danesparza]

No. But Mad Cow Disease (also caused by prions) sure did. More info: https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...

[nikartix]

How old are these proteins? If the do spread and remain dormant in soil they would have been a threat for entire existence of life on this planet. Exponential growth would only cause every place, especially a bio-reach locations to be full of it as food chain making more and more of the protein and animals remains are not handled in any way in the wild.

[dnautics]

They're old. Yeast have genes that transmit information generationally via the same mechanism. Probably the same "exponential" mechanism is involved in diabetes, alzheimer's, melanin storage (not a disease, the actual normal process).

Proteins, eventually degrade, even prions. We probably have an enzyme that accelerates degradation of them (my bet is it's insulin-degrading enzyme).

[AnimalMuppet]

I don't think proteins will live forever in the wild. Between bacteria, fungi, and just oxidation, I'm pretty sure a protein just sitting out there on its own is going to have a finite half-life.

[chasil]

It appears that the first mention of scrapie in scientific literature is 1755, and the disease increased with inbreeding (and lessened when this practice was stopped):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114482/

The wiki also indicates that a sheep vaccine distributed in 1935 caused an epidemic, as it contained contaminated neural tissue:

https://en.wikipedia.org/wiki/Scrapie

It also seems to me that the recent mRNA vaccines could be repurposed to target a section of a prion, so the immune system could clean them from the blood. An interesting question would test mRNA vaccine effectiveness in the cerebrospinal fluid, where microglia would be required to perform this function, as macrophages (and friends) are not present there.

[eximius]

This is a very interesting idea! But, is it known that macrophages are able to break down prions? My understanding of the problem is that part of it is that they're just quite hardy.

[chasil]

Even if they can't, it's probably better for them to build up in macrophages, dendritic cells, etc. rather than in neurons.

[dnautics]

Disagree. Every single antibody alzheimer's drug that has targeted the amyloid plaques and none of them have succeeded.

You're just as likely to elicit an immune response to the prion plaques, stabilize them, and recruit inflammation to the point of deposit, making matters worse.

[eggy]

Curious, I had heard of research where the brain of a sheep that was infected with a prion disease (not sure which), was burned to ash, and that ash placed on the exposed brain of a healthy sheep (via trepanation?), and it also developed the prion-caused disease. Is this anecdotal nonsense, or is it close to a real study done on prion diseases? Thanks!

[dnautics]

That's real. Moderately high temperatures do not effectively destroy prions/amyloid.

Note that "burning to ash" is not that hot.

[eggy]

Wow, thanks for that! I don't know why I thought it would be so hot when I used to weld and cast metals. I remember when I was a kid we used to say something like, "I'll burn you to ashes" when playing. Still amazing that you can burn it and it's still potent.

[aeternum]

What are your thoughts on the risks of AlphaFold and prions?

It seems like prions don't have much chance to evolve/mutate naturally since any change makes them unable to duplicate. However with these simulation systems, are man-made prions a concern?

[dnautics]

> naturally since any change makes them unable to duplicate.

That's not true.

Don't worry about alphafold. Even if it's a really good extrapolation engine (and not a really good interpolation engine) the amyloid fold is unusual enough that I doubt that alphafold can heuristically solve structures much less assess energetic or kinetic factors (which is not what it was designed to do). Note that I am an alphafold optimist and am on record here saying that I consider alphafold to have solved the basic protein folding problem. More to the point, we don't have many reliable solved structures of amyloid folds, it's clear that they are heterogeneous anyways, and iirc no one has bootstrapped an infectious prion in vitro, which means we don't know exactly what makes something infectious... We can make prion amyloid in vitro but it isn't infectious unless it was seeded by an infectious prion amyloid.

[boringg]

As a former prion researcher, do you eat meat or do you have reservations around that?

[dnautics]

I don't have reservations about it. I'm also not generally afraid to die.

[boringg]

Was curious if your research had tainted concerns around eating meat similar to commercial fisherman not eating fish due to work environment revelations.

Glad to hear you aren't generally afraid to die though - sounds like a good stance to have.

[falcolas]

Globalization is a fairly new thing (on the 3.5B year timescale at least), allowing for the spread of any disease quickly. Whereas isolation and evolution has saved us in the past, it might not have the necessary time in the future (imagine if Covid had been even more deadly, for example).

[masklinn]

Prions don't really spread on their own though, yes they are extremely hardy and can survive in soils but that doesn't do anything, if it did and isolation was the only solution we'd have thousands of prion-infested red zones where humans couldn't set foot.

> imagine if Covid had been even more deadly, for example

It'd have been taken more seriously, and it would have had a higher chance of burning itself out. Covid's such a pain in the ass because it hits such a sweet spot, of spreading fast, being highly infectious, and being benign enough (with many of the infected spreading it asymptomatically). For the hell that it is, the one "saving grace" of Ebola is that it debilitates and kills fast enough it's very hard for it to spread, especially as it doesn't have great transmission vectors.

[im3w1l]

What I remember from middle school biology is that nutrients flow in a cycle. Organic matter in the soil will be composted and consumed by earth worms, funghi and microorganisms.

And to them, prions are just organic matter like any other.

[ravi-delia]

In addition to the points other people made, proteins are really a whole different thing from viruses in terms of numbers. You make so many proteins every moment, at this point every possible screwup has been cooked up somewhere.

[andy_ppp]

If COVID were more deadly like Ebola it tends to not have long gestation periods where it can be spread without symptoms.

[est31]

tends to is not going to cut it in this instance. If 99% of diseases are either easy to spread, or deadly, we still need to worry about the 1% that are both. It only takes one such disease to cause a wipeout like event.

[andy_ppp]

I was going to add a flow up edit to add more clarity to my answer; the point is if 50% of people are dying from an airborne disease, getting to zero is going to be treated with much more importance than COVID with a ~2% (? maybe) fatality rate. People who think masks are a political tool to control us suddenly are less paranoid about that (and vaccines, and social distancing) when the bodies are bing piled up in the streets.

I think we'd probably handle a more severe disease with much less flippancy than we did COVID and we'd have to treat lockdown and other tools with much more reverence in such a situation.

This does happen with Ebola outbreaks being managed in Africa now so if they can do it there I think we can do it here.

[stickfigure]

0.7%, not 2% (according to the US CDC). Which does make it "worse" for the reasons you point out.

[est31]

> getting to zero is going to be treated with much more importance than COVID with a ~2% (? maybe) fatality rate. People who think masks are a political tool to control us suddenly are less paranoid about that (and vaccines, and social distancing) when the bodies are bing piled up in the streets.

I agree with the first sentence, but not with the second. Yes, governments might eventually put more care onto reducing covid counts. But a) it might be too late. Just check how long it took for travel restrictions to be imposed.

And b) the panic that people will be in will be even bigger, especially those who think that masks and vaccines are a way to spread microchips and 5G. These folks aren't rational.

Last, there is a non zero chance you'll be dying in the next few years. At that point, do you really care about rules? The governments will impose even stricter lockdown measures. But this will cause even more unrest as people are confined to their homes.

Ebola is in the category of "deadly but not easy to spread". Yes, it can be spread but by the time you spread it you physically can't leave your bed. That's a great help in preventing spread. I'm talking about a disease that at the start has few symptoms, allowing for easy spread, then gets severe and deadly further down in disease progression.

[jMyles]

If COVID19 had been significantly deadly, presumably it would have burned out at the pace of SARS1.

It seems to be close to the sweet spot in terms of being able to spread but still occasionally kill.

[beiller]

If it was more deadly it would spread less quickly. That's how diseases work from my vague university memories of an epidemiology course. They are on a spectrum of deadly to contagious.

[derekp7]

What actually causes this though? For example, take something like HIV that takes a long time to show symptoms, but have an airborne version of it. Do the things that make viruses airborne also keep them from having a long gestation period and also highly lethal?

[akiselev]

> Do the things that make viruses airborne also keep them from having a long gestation period and also highly lethal?

Surviving airborne before the advent of buildings meant surviving outside in direct sunlight with little in the way of protection from droplets or anything else. Organisms have a limited amount of abstract "evolutionary capital" and the costs, so to speak, of developing adaptations to survive airborne and evade an active immune system are astronomical. It's not impossible, but the two "features" work against each other during the development phase.

[danaris]

(Not an immunologist/virologist/biologist of any stripe. The following is my rough layman's understanding of the answer to this question. Would love to be corrected by someone with more formal knowledge of the subject.)

My understanding is that the main reason is a biological application of the principle of parsimony: Evolutionarily, organisms don't generally evolve lots of different things all at once. Thus, if you have a novel variant of a virus, it is highly likely to be mostly like existing variants, but with a very small number of changes.

Basically, you can think of it as the virus having to hit a particular threshold of a mutation direction that increases transmissibility to become widely-spread, but also has to hit a particular threshold of a mutation direction that increases lethality in order to become very dangerous.

As soon as it hits that transmissibility threshold, that is the version of the virus that's going to spread, and hitting both those thresholds at the same time is going to be incredibly rare.

What's much more likely (and genuinely concerning) is the possibility that a virus that has already become highly transmissible evolves more in the "lethality" direction and goes from being a widespread nuisance to being a deadly pandemic. The longer we let something like COVID remain widespread, as I understand it, the more likely we are to see a variant emerge that retains its high transmissibility but also gains a higher lethality. However, as we can see from the fact that the bodies are not piling up in the streets, even after nearly a year and a half of a pandemic form of a particular virus, it's by no means guaranteed that something like that will happen, even at a small scale.

[ASalazarMX]

This is such an interesting question, I hope it doesn't get buried before someone knowledgeable answers it.

We all know the more aggressive a pathogen is, the more it paints itself into a corner because it's burning its bridges. Something like airborne HIV would be really scary.

My guess is that airborne diseases are not weaker, but that evolution has selected for resistance against those because they spread fast among the population.

[lazide]

This is unfortunately just not correct in real life. It’s a good representation of general behavior/trends, but for instance Smallpox was around since at least 500 BC, and still had a 35% fatality rate until it was eradicated in the 70s.

The more times you roll the dice, the more often you’ll get that magic combo of lethal and highly transmissible. For the most part it doesn’t favor it, but that just makes it an outlier when it does, not impossible.

[Sebb767]

At least a part of it is probably the human factor. The big "PR" problem we have with fighting the epidemic is that a lot of people won't have much (visible) problems. If COVID would lead to a slow and painful death 99% of the time, there were probably far fewer people trying to get it or using the herd immunity strategy.

[beiller]

I don't think we know what causes it. It is mainly just observed. What causes this is a very active area of study. Probably some output of a "evolutionary" process of how viruii mutate but my knowledge is very little :)

[vanderZwan]

Sure, but this does not in any way favor prions over other options.

[bradrn]

(Quick correction: PNG, not NZ.)

[danesparza]

Agreed. Prions almost strike me as an interesting boundary condition for stupid behavior. But if most of the world's meat supply becomes effected by prion caused diseases (think: Chronic Wasting Disease https://www.cdc.gov/prions/cwd/index.html ) then I think we truly might be in a tight spot.

[Igelau]

IIRC, BSE (Mad Cow) was spreading among cattle because the industry was using meat-and-bone feed from infected cattle. It was tainting the meat supply because captive-bolt guns spray more brain around than more traditional hammer-oriented methods of slaughtering beeves.

So yeah, cannibalism and brain spray. Stupid behaviors.

[adrianN]

Luckily humans can survive quite well without any meat at all.

[odyssey7]

I’m not sure this would save you. The deer get CWD by eating the grass other deer have been around. A zoonotic CWD would find its way into plant-based diets.

[hourislate]

The article suggests it's transmissible through plants and even air. You can't even sterilize surgical equipment under normal protocol to kill them.

It is basically a juggernaut.

[danesparza]

Agreed. What 2020 has shown us is that many humans can't cope with change well. This is what would cause us to be in a tight spot (IMHO)

[bregma]

If it was deadly enough, that problem would take care of itself quite quickly. Tragically, but quickly.

[Mordisquitos]

So can deer.

[kijin]

Unlike deer, at least some humans are capable of not pooping and drooling on other people's food.

[rjsw]

ITYM affected, not effected.