4 ms·

It's definitely not a duh (I got three years into a computational biology PhD before coming out to silicon valley). Prions are fundamentally different from oth

by jforman 16y ago

It's definitely not a duh (I got three years into a computational biology PhD before coming out to silicon valley). Prions are fundamentally different from other diseases in that they're very dumb. Both viruses and bacteria have enormously complicated systems for infection that are specifically tuned to human physiology. A virus is many orders of magnitude too large to diffuse into a cell, so it has surface proteins that attach to human cell surface proteins in order to gain entry. A protein doesn't have this (one can easily assume), but it's also too large to diffuse into a cell. So, yeah...I wonder what the molecular mechanism of this is? I have no idea.

Groxx 16y ago
If it attacks your nerve cells, and you can get it by consuming it, why wouldn't you expect to be able to get it by sniffing it?
- jforman 16y ago
  That's...a very good question. So much for my vaunted Ph.D. I'm going to Google Scholar to figure out how the hell a consumed protein can get into a nerve cell...
  - jforman 16y ago
    A 15-minute search yields: we don't know how prions infect a cell. "the underlying mechanism of infection remains unresolved" http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.0060100 http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjo... "the exact physiological function of PrPC and the mechanism of neurotoxicity are still unknown" http://www.ingentaconnect.com/content/ben/cp/2010/00000007/00000001/art00004 http://www.ingentaconnect.com/content/ben/cp/2010/00000007/0... ...I did run across this interesting paper suggesting that prions could be a widely-used regulatory mechanism rather than an aberration, however: http://www.nature.com/nrm/journal/v11/n12/abs/nrm3007.html http://www.nature.com/nrm/journal/v11/n12/abs/nrm3007.html
- Nelson69 16y ago
  Is that known and understood? Prions aren't terribly well understood, there aren't a lot of them. If I'm not mistaken there are doubters that don't believe the some of the diseases attributed to prions are actually caused by them. I know it's still just theory how it is that they work. At Colorado State University there are stables where deer were stabled while chronic wasting diseases was being studied and they are off limits forever now. On the upside, it seems like they tend to be slower acting diseases but it's still a bit scary to think they can aerosolize.
  - Groxx 16y ago
    >Is that known and understood? Since mad cow disease, the neural and consumable parts were, yes. The cause was not, hard evidence that prions were the cause took a while, and a lot of people didn't / still don't believe it. But a lot of people still think the sun goes around the earth, so that's not a very good measure of something's accuracy. So lets take this from another stance: You have a chronic, deadly, incurable, unknown-cause disease that turns brains to mush. Lets study it without respirators prior to animal testing of aerosoled forms! That's sure to end well! edit: why do people go on down-vote sprees? This whole line, and a few bystanders, just got nailed within a minute of each other. Is it a mis-placed sense of justice? Do I have enemies? Do they honestly think it works?
    - ghshephard 16y ago
      I didn't downvote, but with one exception, most posts to this thread appear to be from people going off of their imagination plus a scientific American article or two. HN tends to have a bias towards experts, and the layperson sometimes gets caught in the crossfire - particulary if the appear to posting with some authority on a topic they don't appear to have.
      - Groxx 16y ago
        Certainly. But downvotes tend to be followed with reasons where the reason isn't plain - ie, spam. Which nothing here has been. People can take issue with my tone in the top level comment - I have no problem with that, especially because I am serious about what I said; I honestly wonder if this kind of "safety" might have been hand-waving by a higher-up to save money rather than prevent deaths. But the others?
rdtsc 16y ago
> Prions are fundamentally different from other diseases in that they're very dumb Anthropomorphizing such things is a silly because it confuses people. There is no intelligence in one or another. It is hard to discuss which one is more "advanced "because it is a function of how you define what " advanced" is. One can postulate that advanced means : "how well it can spread". Clearly prions can spread well enough and are very hard to eradicate. Perhaps then are more advanced than a virus. A virus has a lot more machinery involved while prions are just information based. Their folding state _is_ the infection mechanism. There is nothing else extra required to infect, just a different configuration of an existing protein. That is truly fascinating. Even more fascinating is that the configuration state can be spread to other proteins without the need of DNA or RNA mechanisms. This is as efficient as it gets, it beautiful, deadly, and terrifying, all at the same time.
- jforman 16y ago
  > Anthropomorphizing such things is a silly because it confuses people The rest of my post gave a very high-level explanation of how a virus infects a human cell. To explain it in full would take many hours verbally (it took me months in my program to even get up to speed on molecular biology, having come from a CS background). I'll give some more detail, though: when I say "specifically tuned to human physiology" I mean "tuned" to an extreme level. A human cell is a bag of water, protein, and nucleic acids enveloped by a lipid bilayer. This lipid bilayer physically prevents anything larger than...I think a subset of very small molecules from entering the cell? I am very weak in biochem, so I don't know the exact parameters around this, but I do know for certain that a virus is many orders of magnitude too large to just "get in" to a cell. In order to gain entry to the cell, the virus has to have a protein that is extremely specifically targeted to a human protein that sits on the surface of a human cell. Like, antibody-to-antigen level specific - this is the product of many many generations of evolution. After attaching to that protein, the virus performs a very biochemically specific action to inject its payload into the cell. > Their folding state _is_ the infection mechanism Er, not really. It's the infection mechanism once the prion is in the cell (since the proteins to which the infection spreads are in a cell). How does the protein get in the cell in the first place? ...that's what nobody knows. It can't just float in, again because of the lipid bilayer. It needs to be actively pulled into the cell. Why would that happen?

by jforman 16y ago

Groxx 16y ago

If it attacks your nerve cells, and you can get it by consuming it, why wouldn't you expect to be able to get it by sniffing it?

jforman 16y ago
That's...a very good question. So much for my vaunted Ph.D. I'm going to Google Scholar to figure out how the hell a consumed protein can get into a nerve cell...
- jforman 16y ago
  A 15-minute search yields: we don't know how prions infect a cell. "the underlying mechanism of infection remains unresolved" http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.0060100 http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjo... "the exact physiological function of PrPC and the mechanism of neurotoxicity are still unknown" http://www.ingentaconnect.com/content/ben/cp/2010/00000007/00000001/art00004 http://www.ingentaconnect.com/content/ben/cp/2010/00000007/0... ...I did run across this interesting paper suggesting that prions could be a widely-used regulatory mechanism rather than an aberration, however: http://www.nature.com/nrm/journal/v11/n12/abs/nrm3007.html http://www.nature.com/nrm/journal/v11/n12/abs/nrm3007.html
Nelson69 16y ago
Is that known and understood? Prions aren't terribly well understood, there aren't a lot of them. If I'm not mistaken there are doubters that don't believe the some of the diseases attributed to prions are actually caused by them. I know it's still just theory how it is that they work. At Colorado State University there are stables where deer were stabled while chronic wasting diseases was being studied and they are off limits forever now. On the upside, it seems like they tend to be slower acting diseases but it's still a bit scary to think they can aerosolize.
- Groxx 16y ago
  >Is that known and understood? Since mad cow disease, the neural and consumable parts were, yes. The cause was not, hard evidence that prions were the cause took a while, and a lot of people didn't / still don't believe it. But a lot of people still think the sun goes around the earth, so that's not a very good measure of something's accuracy. So lets take this from another stance: You have a chronic, deadly, incurable, unknown-cause disease that turns brains to mush. Lets study it without respirators prior to animal testing of aerosoled forms! That's sure to end well! edit: why do people go on down-vote sprees? This whole line, and a few bystanders, just got nailed within a minute of each other. Is it a mis-placed sense of justice? Do I have enemies? Do they honestly think it works?
  - ghshephard 16y ago
    I didn't downvote, but with one exception, most posts to this thread appear to be from people going off of their imagination plus a scientific American article or two. HN tends to have a bias towards experts, and the layperson sometimes gets caught in the crossfire - particulary if the appear to posting with some authority on a topic they don't appear to have.
    - Groxx 16y ago
      Certainly. But downvotes tend to be followed with reasons where the reason isn't plain - ie, spam. Which nothing here has been. People can take issue with my tone in the top level comment - I have no problem with that, especially because I am serious about what I said; I honestly wonder if this kind of "safety" might have been hand-waving by a higher-up to save money rather than prevent deaths. But the others?

rdtsc 16y ago

> Prions are fundamentally different from other diseases in that they're very dumb Anthropomorphizing such things is a silly because it confuses people. There is no intelligence in one or another. It is hard to discuss which one is more "advanced "because it is a function of how you define what " advanced" is. One can postulate that advanced means : "how well it can spread". Clearly prions can spread well enough and are very hard to eradicate. Perhaps then are more advanced than a virus. A virus has a lot more machinery involved while prions are just information based. Their folding state _is_ the infection mechanism. There is nothing else extra required to infect, just a different configuration of an existing protein. That is truly fascinating. Even more fascinating is that the configuration state can be spread to other proteins without the need of DNA or RNA mechanisms. This is as efficient as it gets, it beautiful, deadly, and terrifying, all at the same time.

jforman 16y ago
> Anthropomorphizing such things is a silly because it confuses people The rest of my post gave a very high-level explanation of how a virus infects a human cell. To explain it in full would take many hours verbally (it took me months in my program to even get up to speed on molecular biology, having come from a CS background). I'll give some more detail, though: when I say "specifically tuned to human physiology" I mean "tuned" to an extreme level. A human cell is a bag of water, protein, and nucleic acids enveloped by a lipid bilayer. This lipid bilayer physically prevents anything larger than...I think a subset of very small molecules from entering the cell? I am very weak in biochem, so I don't know the exact parameters around this, but I do know for certain that a virus is many orders of magnitude too large to just "get in" to a cell. In order to gain entry to the cell, the virus has to have a protein that is extremely specifically targeted to a human protein that sits on the surface of a human cell. Like, antibody-to-antigen level specific - this is the product of many many generations of evolution. After attaching to that protein, the virus performs a very biochemically specific action to inject its payload into the cell. > Their folding state _is_ the infection mechanism Er, not really. It's the infection mechanism once the prion is in the cell (since the proteins to which the infection spreads are in a cell). How does the protein get in the cell in the first place? ...that's what nobody knows. It can't just float in, again because of the lipid bilayer. It needs to be actively pulled into the cell. Why would that happen?