5 ms·

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

cogman10 6y ago
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.
- CountDrewku 6y ago
  CWD hasn't jumped to humans ever, correct?
  - deleted 6y ago
    [deleted]
  - giantg2 6y ago
    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-deer-disease-what-happened-people-ate-cwd-meat/2926840002/ https://www.usatoday.com/story/news/health/2019/02/21/zombie...
    - deleted 6y ago
      [deleted]
  - danesparza 6y ago
    No. But Mad Cow Disease (also caused by prions) sure did. More info: https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopathy#Spread_to_humans https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...
- dnautics 6y ago
  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.
  - danesparza 6y ago
    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 6y ago
      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 6y ago
        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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114482/
nikartix 6y ago
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.
- chasil 6y ago
  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/ 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 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 6y ago
    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 6y ago
      Even if they can't, it's probably better for them to build up in macrophages, dendritic cells, etc. rather than in neurons.
      - dnautics 6y ago
        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.
boringg 6y ago
As a former prion researcher, do you eat meat or do you have reservations around that?
- dnautics 6y ago
  I don't have reservations about it. I'm also not generally afraid to die.
  - boringg 6y ago
    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.
eggy 6y ago
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 6y ago
  That's real. Moderately high temperatures do not effectively destroy prions/amyloid. Note that "burning to ash" is not that hot.
  - eggy 6y ago
    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 6y ago
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 6y ago
  > 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.

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.

CountDrewku 6y ago
CWD hasn't jumped to humans ever, correct?
- deleted 6y ago
  [deleted]
- giantg2 6y ago
  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-deer-disease-what-happened-people-ate-cwd-meat/2926840002/ https://www.usatoday.com/story/news/health/2019/02/21/zombie...
  - deleted 6y ago
    [deleted]
- danesparza 6y ago
  No. But Mad Cow Disease (also caused by prions) sure did. More info: https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopathy#Spread_to_humans https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...
dnautics 6y ago
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.
- danesparza 6y ago
  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 6y ago
    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 6y ago
      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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114482/

nikartix 6y ago

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.

chasil 6y ago
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/ 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 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 6y ago
  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 6y ago
    Even if they can't, it's probably better for them to build up in macrophages, dendritic cells, etc. rather than in neurons.
    - dnautics 6y ago
      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.

boringg 6y ago

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

dnautics 6y ago
I don't have reservations about it. I'm also not generally afraid to die.
- boringg 6y ago
  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.

eggy 6y ago

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 6y ago
That's real. Moderately high temperatures do not effectively destroy prions/amyloid. Note that "burning to ash" is not that hot.
- eggy 6y ago
  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 6y ago

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 6y ago
> 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.