Hacker News new | ask | show | jobs
by dnautics 1886 days ago
This comment is spot on (I'm a former prion researcher).
5 comments

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.

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.

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

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.
"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?

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

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.

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/

No lengua tacos? What will I get now?
Cabeza. Which is usually the cheek meat. Avoid sesos, of course.
But lenguas?!?
CWD hasn't jumped to humans ever, correct?
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...

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

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.
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.

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

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

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

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.
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?

> 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.

As a former prion researcher, do you eat meat or do you have reservations around that?
I don't have reservations about it. I'm also not generally afraid to die.
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.