8 ms·

These prions sound horrible, less defensible against than viruses, and at the same time much simpler in form than viruses so much more common (easier to appear)

These prions sound horrible, less defensible against than viruses, and at the same time much simpler in form than viruses so much more common (easier to appear). What is the reason that we can thank for prion diseases not being much more common?

nikanj 5y ago
No ready vector for spreading. It needs to come into direct contact with your proteins to affect them
- pcthrowaway 5y ago
  Doesn't that just mean physical contact? Our skin is made out of proteins, is it not?
  - littlestymaar 5y ago
    Not all proteins can exist as prions. (In fact, it's amazing that some can even exist: think about it: a protein that exist in two stable shapes where the shape that does not normally exist in the body can cause the other shape to make the switch!)
    - McBeige 5y ago
      Like a seed crystal causing super cooled water to suddenly freeze in seconds?
      - immibis 5y ago
        Yes, like that
  - kijin 5y ago
    The outer layer of your skin is mostly made of dead cells. It's cold, dry, exposed to the elements, constantly discarded, and has the wrong pH for most biochemical processes that are optimized for the inside of your body. It takes a fairly invasive pathogen to break that barrier.
  - washadjeffmad 5y ago
    Anything expressed by DNA is a protein, but not all proteins are the same. Prion infections are caused by proteins that change the same proteins in the same way, like how crystals replicate. A human analogy might be a disgruntled but charismatic worker who starts spreading a disruptive attitude until morale and productivity plummet in their department. As long as one of that team remains, the issue can still spread. Coincidentally, both the potted plants and highly compensated leadership are unaffected.
  - ben_w 5y ago
    “Protein” isn’t just one thing. I’m far from knowledgeable in this area, but the model in my head is: the $foo_protein can be folded in at two important ways, $foo_v1 is what you want, $foo_v2 is a catalyst for refolding $foo_v1 into $foo_v2 but doesn’t refold much (or anything?) else.
donatj 5y ago
I think it largely comes down to there being no benefit to the prion. It’s more of a lightly continuous sort-of-poison than an actual actor looking for its own reproduction. Viruses and bacterias existence depends on reproduction. Prions just kinda appear naturally from folding errors. They don’t “want” to exist, even to the minimal extent of a virus, they just happen.
- Victerius 5y ago
  I like to tell people that early humans lived in close contact with animals for hundreds of thousands of years, and until a few generations ago, when most people were still farming for a living. If prions had the potential to end the human race, they would already have.
  - XorNot 5y ago
    The slight problem there is, prions probably did end a bunch of tribes which were sufficiently local - and then left the area alone long enough that the prion contamination in the environment broke down. Today we have international animal shipping and trade, and global distribution. Prions are able to spread from exposure to shared pastures. A couple years of contamination used to be no big deal - today, if missed, it can spread all through the food supply.
    - darkerside 5y ago
      I always wonder how much more truth there is to haunted houses and forbidden lands than we think. Just superstition? Maybe, but maybe not.
    - Gare 5y ago
      It is hypothesised that Kuru (and vCJD) in some individuals (due to genetics) might take 40-50 years to develop if introduced through intestine. Well after the individual had a chance to reproduce.
  - phreeza 5y ago
    The advent of agriculture and animal husbandry is generally thought to be much more recent than your comment makes it sound. More like ten thousand years ago.
bopbeepboop 5y ago
XorNot 5y ago
They are super, super-specific. Prions can't self replicate from raw resources: they depend on inducing conformational change in other proteins. The host has to produce, and use, the specific protein they can target in an accessible location. The upshot of this for prions is that lacking genetic code, or a need for replication machinery, and being a variant of the protein they target, they are perfectly adapted for their environment and host and currently impossible to destroy without also damaging the normal correct protein form.
rnestler 5y ago
> What is the reason that we can thank for prion diseases not being much more common? One reason is that we don't eat each other which would spread certain prion diseases like https://en.m.wikipedia.org/wiki/Kuru_(disease) https://en.m.wikipedia.org/wiki/Kuru_(disease)
- jacquesm 5y ago
  Indeed, cannibalism is an excellent way to get something like this to the point where it sustains itself.
- solididiot 5y ago
  Yeah we only do that metaphorically in the modern world.
- asdfasgasdgasdg 5y ago
  Another aspect is that a prion disease requires a much more specific confluence of circumstances. It requires a protein, which can be misfolded, and a misfolding that, when in contact with other proteins of that same type, causes the same misfolding to occur.
dtech 5y ago
> less defensible against than viruses, and at the same time [...] so much more common (easier to appear). Not really on both parts. It's only transferred by eating meat so the defence is as soon as prion infection is detected all possibly infested livestock is culled and severe bans on trading are placed. Cannibalism in animal feed is also disallowed which makes transmission rare. Being vegetarian is also a complete defence. They're also rare to appear, otherwise eating livestock would have regularly wiped out humans already. They're basically non-existent if you don't eat humans and livestock isn't fed to livestock.
- s_dev 5y ago
  >Being vegetarian is also a complete defence. Lady in the story could have been a Vegetarian yet still died from a Prion. As others have pointed out swimming in bodies of water is possible vector for prions.
  - lazide 5y ago
    Swimming in water was pointed out as a vector for amoebas (some of which can be ‘brain eating’ in some areas), not prions.
  - dtech 5y ago
    Second part is incorrect, first part is a nitpick. She got it from working in a lab. If I say abstinence make you immune from HIV are you going to "counter" that by saying you could get it from being transfused or pricking with infected blood?...
- KMag 5y ago
  > Being vegetarian is also a complete defence[sic]. Tell that to deer dying of CWD.
  - quesera 5y ago
    "defence" is one of the correct spellings for the word. Your condescending sic is, ironically, misplaced.
nrdvana 5y ago
As I understand it, prions are just an ever-present rare tiny probability of a cascading malfunction of your physical composition. They are rare because they need to be, in order for a biological system to survive. (any biological system that had a high probability of prions would die off) They can never fully be eliminated because your body is built on probability, not mathematical certainty. Most organisms live less than 100 years, so the probability is good enough not to affect species survival. As long as young organisms don't eat old organisms, the chances remain low. Another way to look at it is that the combined lifespans of the organisms of a food chain are shorter than the time it would take for one mis-folded protein to be likely to occur and then also cascade to a degree that would affect the health of the top organism. Prion diseases only show up when you introduce a loop in the food chain.
Enginerrrd 5y ago
I suspect the issue is that, prions require a fairly large series of coincidences to be viable, so the biological niche is a pretty small one. I think they're much more specific conditions than that required of viruses. In addition, your body probably has evolved to use proteins that aren't particularly susceptible to misfolding AND accumulation. (Perhaps a long time ago, it WAS quite common?)
awhitby 5y ago
Not a biologist, so this is just a guess, but I imagine their simplicity is their weakness. Viruses rely on the machinery of nucleic acids to replicate. That machinery is complex and robust and the result of some long period of continuous evolution, which means viruses exists in a fairly smooth fitness space where mutation and recombination are effective means of improving fitness. Prions by contrast seem more like isolated spikes in a much sparser fitness space. Presumably the equivalents of mutation and recombination for prions lead to molecules that almost never retain the capacity to replicate, so they have limited potential to become fitter over time.
jacquesm 5y ago
That they don't spread through the same mechanisms that viruses and bacteria use. You'd have to have much more direct contact between the organisms to transfer prions from the one to the other, they are internal and don't self-replicate in the way that bacteria and viruses do. The lack of selection pressure on prions is what keeps them in their lane. But: consuming bush meat, brains, feeding dead animals to other animals, being careless with sharps and so on are all excellent ways to contract them.
patcon 5y ago
> What is the reason that we can thank for prion diseases not being much more common? We kinda take this for granted, but it may be the case that our deeply-rooted psychological disgust and aversion to eating human flesh is a product of prion disease killing populations of ancestors who did. Or perhaps, even our tendencies to ceremonies of death helped us: those that feared the bodies of the dead, or were more likely to create rituals of destruction and avoidance, were more likely to persist and pass on their genes :)

nikanj 5y ago

No ready vector for spreading. It needs to come into direct contact with your proteins to affect them

pcthrowaway 5y ago
Doesn't that just mean physical contact? Our skin is made out of proteins, is it not?
- littlestymaar 5y ago
  Not all proteins can exist as prions. (In fact, it's amazing that some can even exist: think about it: a protein that exist in two stable shapes where the shape that does not normally exist in the body can cause the other shape to make the switch!)
  - McBeige 5y ago
    Like a seed crystal causing super cooled water to suddenly freeze in seconds?
    - immibis 5y ago
      Yes, like that
- kijin 5y ago
  The outer layer of your skin is mostly made of dead cells. It's cold, dry, exposed to the elements, constantly discarded, and has the wrong pH for most biochemical processes that are optimized for the inside of your body. It takes a fairly invasive pathogen to break that barrier.
- washadjeffmad 5y ago
  Anything expressed by DNA is a protein, but not all proteins are the same. Prion infections are caused by proteins that change the same proteins in the same way, like how crystals replicate. A human analogy might be a disgruntled but charismatic worker who starts spreading a disruptive attitude until morale and productivity plummet in their department. As long as one of that team remains, the issue can still spread. Coincidentally, both the potted plants and highly compensated leadership are unaffected.
- ben_w 5y ago
  “Protein” isn’t just one thing. I’m far from knowledgeable in this area, but the model in my head is: the $foo_protein can be folded in at two important ways, $foo_v1 is what you want, $foo_v2 is a catalyst for refolding $foo_v1 into $foo_v2 but doesn’t refold much (or anything?) else.

donatj 5y ago

I think it largely comes down to there being no benefit to the prion. It’s more of a lightly continuous sort-of-poison than an actual actor looking for its own reproduction. Viruses and bacterias existence depends on reproduction. Prions just kinda appear naturally from folding errors. They don’t “want” to exist, even to the minimal extent of a virus, they just happen.

Victerius 5y ago
I like to tell people that early humans lived in close contact with animals for hundreds of thousands of years, and until a few generations ago, when most people were still farming for a living. If prions had the potential to end the human race, they would already have.
- XorNot 5y ago
  The slight problem there is, prions probably did end a bunch of tribes which were sufficiently local - and then left the area alone long enough that the prion contamination in the environment broke down. Today we have international animal shipping and trade, and global distribution. Prions are able to spread from exposure to shared pastures. A couple years of contamination used to be no big deal - today, if missed, it can spread all through the food supply.
  - darkerside 5y ago
    I always wonder how much more truth there is to haunted houses and forbidden lands than we think. Just superstition? Maybe, but maybe not.
  - Gare 5y ago
    It is hypothesised that Kuru (and vCJD) in some individuals (due to genetics) might take 40-50 years to develop if introduced through intestine. Well after the individual had a chance to reproduce.
- phreeza 5y ago
  The advent of agriculture and animal husbandry is generally thought to be much more recent than your comment makes it sound. More like ten thousand years ago.

bopbeepboop 5y ago

XorNot 5y ago

They are super, super-specific. Prions can't self replicate from raw resources: they depend on inducing conformational change in other proteins. The host has to produce, and use, the specific protein they can target in an accessible location. The upshot of this for prions is that lacking genetic code, or a need for replication machinery, and being a variant of the protein they target, they are perfectly adapted for their environment and host and currently impossible to destroy without also damaging the normal correct protein form.

rnestler 5y ago

> What is the reason that we can thank for prion diseases not being much more common? One reason is that we don't eat each other which would spread certain prion diseases like https://en.m.wikipedia.org/wiki/Kuru_(disease) https://en.m.wikipedia.org/wiki/Kuru_(disease)

jacquesm 5y ago
Indeed, cannibalism is an excellent way to get something like this to the point where it sustains itself.
solididiot 5y ago
Yeah we only do that metaphorically in the modern world.
asdfasgasdgasdg 5y ago
Another aspect is that a prion disease requires a much more specific confluence of circumstances. It requires a protein, which can be misfolded, and a misfolding that, when in contact with other proteins of that same type, causes the same misfolding to occur.

dtech 5y ago

> less defensible against than viruses, and at the same time [...] so much more common (easier to appear). Not really on both parts. It's only transferred by eating meat so the defence is as soon as prion infection is detected all possibly infested livestock is culled and severe bans on trading are placed. Cannibalism in animal feed is also disallowed which makes transmission rare. Being vegetarian is also a complete defence. They're also rare to appear, otherwise eating livestock would have regularly wiped out humans already. They're basically non-existent if you don't eat humans and livestock isn't fed to livestock.

s_dev 5y ago
>Being vegetarian is also a complete defence. Lady in the story could have been a Vegetarian yet still died from a Prion. As others have pointed out swimming in bodies of water is possible vector for prions.
- lazide 5y ago
  Swimming in water was pointed out as a vector for amoebas (some of which can be ‘brain eating’ in some areas), not prions.
- dtech 5y ago
  Second part is incorrect, first part is a nitpick. She got it from working in a lab. If I say abstinence make you immune from HIV are you going to "counter" that by saying you could get it from being transfused or pricking with infected blood?...
KMag 5y ago
> Being vegetarian is also a complete defence[sic]. Tell that to deer dying of CWD.
- quesera 5y ago
  "defence" is one of the correct spellings for the word. Your condescending sic is, ironically, misplaced.

nrdvana 5y ago

As I understand it, prions are just an ever-present rare tiny probability of a cascading malfunction of your physical composition. They are rare because they need to be, in order for a biological system to survive. (any biological system that had a high probability of prions would die off) They can never fully be eliminated because your body is built on probability, not mathematical certainty. Most organisms live less than 100 years, so the probability is good enough not to affect species survival. As long as young organisms don't eat old organisms, the chances remain low. Another way to look at it is that the combined lifespans of the organisms of a food chain are shorter than the time it would take for one mis-folded protein to be likely to occur and then also cascade to a degree that would affect the health of the top organism. Prion diseases only show up when you introduce a loop in the food chain.

Enginerrrd 5y ago

I suspect the issue is that, prions require a fairly large series of coincidences to be viable, so the biological niche is a pretty small one. I think they're much more specific conditions than that required of viruses. In addition, your body probably has evolved to use proteins that aren't particularly susceptible to misfolding AND accumulation. (Perhaps a long time ago, it WAS quite common?)

awhitby 5y ago

Not a biologist, so this is just a guess, but I imagine their simplicity is their weakness. Viruses rely on the machinery of nucleic acids to replicate. That machinery is complex and robust and the result of some long period of continuous evolution, which means viruses exists in a fairly smooth fitness space where mutation and recombination are effective means of improving fitness. Prions by contrast seem more like isolated spikes in a much sparser fitness space. Presumably the equivalents of mutation and recombination for prions lead to molecules that almost never retain the capacity to replicate, so they have limited potential to become fitter over time.

jacquesm 5y ago

That they don't spread through the same mechanisms that viruses and bacteria use. You'd have to have much more direct contact between the organisms to transfer prions from the one to the other, they are internal and don't self-replicate in the way that bacteria and viruses do. The lack of selection pressure on prions is what keeps them in their lane. But: consuming bush meat, brains, feeding dead animals to other animals, being careless with sharps and so on are all excellent ways to contract them.

patcon 5y ago

> What is the reason that we can thank for prion diseases not being much more common? We kinda take this for granted, but it may be the case that our deeply-rooted psychological disgust and aversion to eating human flesh is a product of prion disease killing populations of ancestors who did. Or perhaps, even our tendencies to ceremonies of death helped us: those that feared the bodies of the dead, or were more likely to create rituals of destruction and avoidance, were more likely to persist and pass on their genes :)