Scrapie is particularly known, deadly, and long-lived. The toxin proteins can survive for a decade in soil, and infect a new host years after it emerged.
They're all the same in my understanding, just named differently because they have been observed separately before any understanding about PrP existed. And yes, that means they're also all long-lived. These proteins do not decay like more useful molecules or more complex organic matter.
What gets me is why these prions seem to be primarily brain related. Just coincidence or is it something in the nature of mammalian brain biology that leads to prions?
There are already a bunch of prions generated in the body and hanging around neurons; the body can’t sort the invasive prions from the native ones that cause proteins to fold wrong.
Prions are attracted to or at least congregate in and around nerve cells. That's why as they spread around, they always eventually end up in the brain.
The most scary thing about prions is that they're inert. They're not even evil or agressive. They just are.
The mere shape of them causes cascading exponential system failures. And that shape happens to be very stable and requires a lot of energy to be broken up.
Like some kind of rock that falls from the sky or materializes out of thin air, and slowly the whole village turns into identical inanimate rocks.
The really scary part is that there's no real testing in our food supply. Wild animals can also spread it over crops and it can stay present in soil for years. If it makes the jump to humans, were screwed. That or dental tools (they may not get sterilized to the point of destroying prions) will be what gets us.
I believe "sterilization" is a bit of a misnomer when it comes to prions, as they can't be reliably destroyed without also destroying the object. Neurosurgical instruments are routinely discarded and incinerated rather than reused due to this risk.
Not just technically. Proteins, and the molecular machinery producing them, are just that. Look at the flagellar motor. It's a marvel of (natural) engineering.
I suppose one could go on a wild tangent here and argue that - given they're significantly more stable - prions are the correct-er form of proteins.
They just do not get any work done within how known biological life works, but that could perhaps also be read as said whole tree of life relying on a misconfiguration of that building block?
This is wildly unqualified rambling on my part, but I wonder if life could develop that is based on that prion form of proteins.
From my understanding, no. But maybe "life developing" is the wrong metric for correctness?
FWIW, The universe itself seems to be dead-set on entering the most stable configuration of everything.
That's a little like saying broken pottery is the more correct form of plates. What you're describing is the lower energy/higher entropy state, and yes everything heads in that direction because of thermodynamics. In general, life is a temporary state of higher energy achieved in exchange for waste in the surrounding environment; prions are useless because they are disordered not in spite of that.
I love the hypothesis. It would be interesting if there was research in longevity where proteins that often degrade into unfortunate forms could be slightly modified for self repairing, and bigger resilience to damage. Of course that sounds a lot like a cancer..
I like this take. With its reduction to “survival of the fittest” slogan, it is easy to forget that Evolution can be “subjective”, imprecise in the problems it is solving.
Prion diseases are one of the scarier things I've ever heard about. It is transmissible via fluids, but it can also just happen spontaneously in your body, and once that happens, it's basically a death sentence. There is so far still no cure.
It sadly sounds like it targets RNA for the production of all prion proteins (a somewhat important protein for normal brain function, but not essential) and doesn't do anything to clean up existing misfolded proteins. Even if successful, it will probably have side effects.
Looking at the list of observed changes in mice this can be anything from destroying the sleep cycle to general memory problems.
> Even if successful, it will probably have side effects.
> Looking at the list of observed changes in mice this can be anything from destroying the sleep cycle to general memory problems.
Prion diseases guarantee certain death right now though, so the side effects would need to be pretty bad for them to be worse than the disease. Even just delaying death by a few years would be pretty good, since most people die in under a year [0].
(This is somewhat similar to chemotherapy drugs, which also tend to have pretty bad side effects but are still generally accepted as better than the alternative.)
What Sonia Vallabh and Eric Minikel have been working toward since her diagnosis in 2011 is truly inspiring. The drug candidate was developed by Anastasia Khvorova and her lab at UMass Chan Medical School, in collaboration with Vallabh, Minikel, and their research teams.
What makes this effort even more remarkable is their commitment to sharing the drug development process openly, including an IND filing that would typically remain confidential.
Whatever the eventual outcome( I’m optimistic) about the possibilities, the journey, the data, and the knowledge shared along the way will be valuable.
This is not just about developing a drug; it’s about making science more transparent, collaborative, and accessible for everyone working toward the same goal.
In case anyone hasn't seen it, the story behind this couple is interesting:
https://www.cureffi.org/about/
cure foreign function interface before it gets too ubiquitous!
Prion diseases include:
-in sheep, scrapie
-in humans, Kuru and Creutzfeldt-Jacob
-in cows, BSE ("mad cow")
-in deer, Chronic Wasting Disease (CWD)
-in cats, feline spongiform encephalopathy
Scrapie is particularly known, deadly, and long-lived. The toxin proteins can survive for a decade in soil, and infect a new host years after it emerged.
https://en.wikipedia.org/wiki/Transmissible_spongiform_encep...
They're all the same in my understanding, just named differently because they have been observed separately before any understanding about PrP existed. And yes, that means they're also all long-lived. These proteins do not decay like more useful molecules or more complex organic matter.
Some of them are the same, but some aren't. CWD is a prion separate from BSE for instance, but BSE is caused by the same prion as Creutzfeldt-Jacob.
What gets me is why these prions seem to be primarily brain related. Just coincidence or is it something in the nature of mammalian brain biology that leads to prions?
There are already a bunch of prions generated in the body and hanging around neurons; the body can’t sort the invasive prions from the native ones that cause proteins to fold wrong.
Prions are attracted to or at least congregate in and around nerve cells. That's why as they spread around, they always eventually end up in the brain.
The most scary thing about prions is that they're inert. They're not even evil or agressive. They just are.
The mere shape of them causes cascading exponential system failures. And that shape happens to be very stable and requires a lot of energy to be broken up.
Like some kind of rock that falls from the sky or materializes out of thin air, and slowly the whole village turns into identical inanimate rocks.
Viruses are also not evil, they're just random DNA/RNA strands that natural selection forced to have adverse effects.
A self-replicating asbestos fiber
The scariest part for me is: it can just form randomly in one's body, and there's no way to tell until it's too late.
The really scary part is that there's no real testing in our food supply. Wild animals can also spread it over crops and it can stay present in soil for years. If it makes the jump to humans, were screwed. That or dental tools (they may not get sterilized to the point of destroying prions) will be what gets us.
I believe "sterilization" is a bit of a misnomer when it comes to prions, as they can't be reliably destroyed without also destroying the object. Neurosurgical instruments are routinely discarded and incinerated rather than reused due to this risk.
The solution will be Nanomachines, son.
Technically speaking proteins are nanomachines.
Not just technically. Proteins, and the molecular machinery producing them, are just that. Look at the flagellar motor. It's a marvel of (natural) engineering.
Yeah it sounds like God hired a malicious freelance programmer who put in a self-propagating backdoor huh.
I suppose one could go on a wild tangent here and argue that - given they're significantly more stable - prions are the correct-er form of proteins.
They just do not get any work done within how known biological life works, but that could perhaps also be read as said whole tree of life relying on a misconfiguration of that building block?
This is wildly unqualified rambling on my part, but I wonder if life could develop that is based on that prion form of proteins.
From my understanding, no. But maybe "life developing" is the wrong metric for correctness?
FWIW, The universe itself seems to be dead-set on entering the most stable configuration of everything.
That's a little like saying broken pottery is the more correct form of plates. What you're describing is the lower energy/higher entropy state, and yes everything heads in that direction because of thermodynamics. In general, life is a temporary state of higher energy achieved in exchange for waste in the surrounding environment; prions are useless because they are disordered not in spite of that.
I love the hypothesis. It would be interesting if there was research in longevity where proteins that often degrade into unfortunate forms could be slightly modified for self repairing, and bigger resilience to damage. Of course that sounds a lot like a cancer..
I like this take. With its reduction to “survival of the fittest” slogan, it is easy to forget that Evolution can be “subjective”, imprecise in the problems it is solving.
Prion diseases are one of the scarier things I've ever heard about. It is transmissible via fluids, but it can also just happen spontaneously in your body, and once that happens, it's basically a death sentence. There is so far still no cure.
If this works, this will be a game changer.
It sadly sounds like it targets RNA for the production of all prion proteins (a somewhat important protein for normal brain function, but not essential) and doesn't do anything to clean up existing misfolded proteins. Even if successful, it will probably have side effects.
Looking at the list of observed changes in mice this can be anything from destroying the sleep cycle to general memory problems.
> Even if successful, it will probably have side effects.
> Looking at the list of observed changes in mice this can be anything from destroying the sleep cycle to general memory problems.
Prion diseases guarantee certain death right now though, so the side effects would need to be pretty bad for them to be worse than the disease. Even just delaying death by a few years would be pretty good, since most people die in under a year [0].
(This is somewhat similar to chemotherapy drugs, which also tend to have pretty bad side effects but are still generally accepted as better than the alternative.)
[0]: https://en.wikipedia.org/wiki/Creutzfeldt%E2%80%93Jakob_dise...
It would be interesting if they pair it with something similar to CAR-T but targeting a specific marker in the misfolded protein.
What Sonia Vallabh and Eric Minikel have been working toward since her diagnosis in 2011 is truly inspiring. The drug candidate was developed by Anastasia Khvorova and her lab at UMass Chan Medical School, in collaboration with Vallabh, Minikel, and their research teams.
What makes this effort even more remarkable is their commitment to sharing the drug development process openly, including an IND filing that would typically remain confidential.
Whatever the eventual outcome( I’m optimistic) about the possibilities, the journey, the data, and the knowledge shared along the way will be valuable.
This is not just about developing a drug; it’s about making science more transparent, collaborative, and accessible for everyone working toward the same goal.