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Prions, Nearly Indestructible and Universally Lethal, Seed the Eyes of Victims (scientificamerican.com)
433 points by tshannon 3 months ago | hide | past | web | favorite | 189 comments



Prion disease is exceedingly rare. CJD is the most common, with an incidence of 1 per 1,000,000 person-years worldwide, inclusive of all transmission vectors (including medical procedures).

Iatrogenic transmission is a rarer subset still: the riskiest transplants (with respect to CJD) are in the central nervous system. The UK tracked their transmission rates from 1970 to 2003 (a long period is needed because surgical transmission usually occurs in folks with long incubation periods - up to ten years or so) for dura transplants (something that goes into the CNS) and found a total of eight.

This article is one good step above scare-mongering, but only one.


Infectious disease is one area where fear of the unknown is rational. We don't just need to defend against existing diseases, but also diseases yet to emerge. Just because CJD is rare doesn't mean that the next prion disease will be, so it would make sense to take measures to prevent transmission of prions now.


We take measures now, for tissues where prions are a possible transmission risk. The article mis-represented that. But:

(1) there are only so many resources to go around. Should we be devoting them to vanishingly rare things rather than things that might actually affect you?

(2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein. One step up from that - encoding the protein for space constraints and encapsulating it - is called a virus.


> (2) prions will never be a wildfire plague. They have little or no tranmissive ability, by nature of being absolutely naked protein.

Chronic wasting disease (CWD) (affects deer) can be transmitted by infected saliva. One of the symptoms of symptoms of CWD is excessive saliva production. It is very transmissible, and is devastating captive populations of deer, although it is relatively rare in the wild.

I think if a similar TSE affected humans, spreadable by infected saliva, it would absolutely be a wildfire plague.

https://en.wikipedia.org/wiki/Chronic_wasting_disease


Is there any mammalian prion disease not linked to the PRNP gene (which is fairly conserved across mammals)?

At first I assumed that 'prions' came in many flavors, like virus. However from my brief lit search, it seems like people are talking about (p)rion proteins as if they were't all (P)rion proteins (PRNP). If all mammalian 'prion' disease can be traced to a single conserved gene, I think the risk of another 'prion-like' disease cropping up is pretty low.

But then again, who knows? Prion disease still seems shrouded mystery, which I find odd given (1) how inherently interesting this topic seems, and (2) we've gotten really, really good at molecular biology.

I feel like we are missing a key piece of the puzzle when it comes to understanding prion disease. The literature seems to want people to conceptualize the disease etiology as such: an alternately folded (disease causing) variant of PRNP protein (PrPs) bumps into a normal version of PRNP (PrPc), causing a normal copy of PrPc to also misfold into PrPs. Rinse, repeat. So you can basically think of it like an enzyme that catalyzes a conformational change on versions of itself, in a feed-forward cascade. I feel like an alternative hypothesis however, could be one of an autoimmune response. The mammalian immune system, particularly the antibody system, is mind blowing. This system can recognize virtually any foreign protein -- it can even recognize specific sub-moieties and conformations of proteins (antigens). It must, do this while never mistaking an endogenous protein to be foreign; if it does, you get an autoimmune disease. My idea is basically that PrPs is just slightly different enough from PrPc to get tagged as foreign by the antibody system (which it absolutely can do, given that we can perform western blots to detect the PrPs variant), but also just similar enough for the antibody system to mistake some endogenous PRNP for the foreign version.


Scrapie, a prion disease of goats and sheep, is severe enough that there are national efforts to combat it.

What if this were suddenly transmissible to humans?

https://en.wikipedia.org/wiki/Scrapie

"In the United Kingdom, the government has put in place a National Scrapie Plan, which encourages breeding from sheep that are genetically more resistant to scrapie. This is intended to eventually reduce the incidence of the disease in the UK sheep population."


That is interesting, and new to me. I’ll have to read up on it more. Thank you for the link.


Nitpick but the step between virus and prion is a viroid; a naked piece of RNA. They mostly exist in plants to my knowledge and are basically the smallest possible infectious disease. The smallest viroids clock in at around 120 base pairs (240 nucleotides).


Prions are like gamma-induced bit flips, Viroids are like small code patches, and Viruses are self-deploying code patches.


What blows my mind is these aren't really analogies, they are in fact mostly truth.


To be precise, these aren’t really analogies, they are in fact similes. :)


To be precise, similes are a type of analogy



A virion is the singular noun for a viral particle. The viral genetic material plus capsid equal an individual virion.


Virion and Viriod are two different things. The former is about 10 to 100 times larger than the later.


> (2) prions will never be a wildfire plague. They have little or no tranmissive ability

Mad Cow Disease was caused by a prion[0].

[0]:https://en.wikipedia.org/wiki/Bovine_spongiform_encephalopat...


And it was spread by the livestock industry.


The example in the article has very little transmissive ability because it grows in the brain and eyes. If there were a respiratory prion disease that could be much different. By nature of being a protein they are simpler and harder to eliminate than bacteria or viruses:

> In a particularly vexing twist, prions are also nearly impervious to destruction, even when attacked using a strenuous combination of disinfectants, heat, and pressure.


> If there were a respiratory prion disease that could be much different.

Not really. The point your parent is making is that prions themselves don't reproduce like viruses and bacteria. Its basically impossible for a large scale breakout to occur and spread.


Can you explain why? I'm not saying this is wrong, but they definitely replicate (by encountering and warping other proteins), so are you (and grandparent) saying that the replication rate is too slow? If so, why? Are you saying we have no means of transmitting proteins? (that sounds wrong, though I've been wrong before)

From my (ignorant, despite being interested in prions for decades now) perspective, you have something that (1) can replicate, (2) is durable (3) is harmful, and only the relative rarity of prions in general (because 1 and 3 are physically unusual to combine) have kept them from being a general problem. As we tinker with DNA and thus look into creating new proteins and factors that would influence protein-folding, I'd think it's worth taking the matter seriously (though not fear-mongering), certainly as part of our need to understand proteins better anyway.

What are my faulty assumptions?


A prion can't arbitrary replicate from "food" or "host", its replication is more like a damaged version of protein X that can damage that same protein X if it encounters it. In many aspects it stays the same protein - the exact same DNA, the exact same sequence, just folded differently.

A virus can overtake a cell and mobilize its resources to create a bajillion copies of that virus. A prion can transform only as much copies of that protein as that cell has made in its normal processes.


A bacteria replicates at a much smaller rate than a virus.

A virus requires a cell to replicate, bacteria require a much more limited range of hospitable environments.

Both bacteria and viruses "attempt" to create exact copies, just as a prion does. Admittedly prion replication probably has more accuracy, but that prions occur at all indicates the process allows for natural selection.

These don't seem to put prions outside of the "replication" category - they replicate by encountering other proteins, so they are in a body. Their rate of replication is limited (or boosted) by the rate of encountering these proteins. They attempt to create copies of themselves with the chance of failure or different end result.


But they do reproduce, by causing other proteins to misfold. If they didn't reproduce at all, then ingesting a few prions wouldn't cause any problems.

They can't reproduce outside of the body, but neither can viruses.


Yes but they can only warp their own specific kind of protein not take over an entire reproductive ability of the native cell.

It’s orders of magnitude less reproduction.


How is this at all a "twist"? The reason you cannot deactivate prions using these methods is that they are meant to denature protein. Prions are "amyloids"/beta-sheets, which means they are already in the lowest-energy state. This lowest-energy-state is exactly why the presence of prion can serve as a nucleation point for other proteins to denature into beta-sheets.


I don't care whether or not it's a "twist". I care that there is an entire class of pathogen that we don't know how to sterilize a surface of.


It’s been said a few times in this thread that that is a misrepresentation by the article. Allow me to quote at length from an article on the topic by Brown and Lee:

One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denature, or modify proteins do have activity against prions [7]. The PrP purified from the brains of scrapie-infected animals (PrPSc) can be inactivated by prolonged autoclaving (at 121ºC and 15 psi for 4.5 hours), or immersion in 1N NaOH (for 30 minutes, repeat three times), or immersion in concentrated (>3 M) solutions of guanidine thiocyanate [10]. However, certain cautions prevail; it appears that inadequate autoclaving can establish heat-resistant subpopulations that fail to diminish with a further cycle of autoclaving [11]. Stainless steel instruments also may retain infectivity even after treatment with 10 percent formaldehyde [12,13].

Newer decontamination techniques are being investigated. There has been some success in sterilization using a combination of sodium dodecyl sulfate (SDS), proteinase K, and pronase [14]. A radio-frequency gas-plasma treatment has been shown to effectively decontaminate surgical instruments [15]. Another group has tested a decontamination formula combining copper metal ions with hydrogen peroxide [16].


OK, but how do ophthalmologists typically decontaminate their instruments?


You just use bleach and then autoclave:

>"combining autoclaving (even at 121 degrees C) with a sodium hydroxide treatment is extremely effective." https://www.ncbi.nlm.nih.gov/pubmed/10658760


Bleach is sodium hypochlorite; sodium hydroxide is lye/caustic soda.


Yea, sorry. Earlier in the abstract it mentioned sodium hypochlorite then I didnt read closely: "Strong sodium hypochiorite solutions achieve inactivation but other chlorine-releasing compounds are less effective"

Usually there is some sodium hydroxide in standard sodium hypochlorite bleach solution as well though, perhaps that explains why they reported it is the most effective of the chlorine bleaches.


If any of the proteins involved in respiration were susceptible to lower free energy confirmations (different foldings that were entropically favorable in vivo) then they likely would already be present, there would be such a prion and life that used those proteins would be highly selected against. Respiration is very common in animals.

As it is, very few proteins in humans have alternate favorable form (by luck or selection?). The exception appears to be the extremely complex and relatively new nervous system of mammals. I'd guess that our immune systems might be another place to look, but that is very highly tested.

Frankly, this seems like a susceptibility that is rare because it is chemically odd not that there is a lack of potential exploitation. Luckily, the range of creatures that share our respiration system far exceeds the range of creatures which share our recently evolved nervous system.


Is there someone advocating that we don't take measures now? Because we do take measures now. Example: there are a bunch of rules about what you can feed cows, and how to keep their nervous tissues out of meat at slaughter time.


The fear may be rational, but the response to it needs to be rational as well. That means treating the things that are known to do the most damage currently, while maintaining containment procedures that can handle your black swan epidemics.


Your “next prion disease” is entirely hypothetical. Given that, it is pure speculation how to prevent its transmission. Why would you assume specific precautions taken would apply?


The same way standard protocols are used to prevent transmission of viruses & bacteria. Apparently they don't work on prions:

> In a particularly vexing twist, prions are also nearly impervious to destruction, even when attacked using a strenuous combination of disinfectants, heat, and pressure.


I don't think that's true. Prions aren't bacteria or viruses that evolve and transmit. They're mostly just a misfolded protein that occurs spontaneously. (They can then be transmitted.)

I'm not sure there will ever be a prion that hasn't already existed, whereas I am sure there will be new viruses and bacteria.


If they can replicate imperfectly, they're subject that evolutionary processes.


They don't replicate. Prions can't themselves make more prions like viruses do.


I think the main difference is an imperfectly-replicated virus or bacteria might still be viable.

A prion only makes itself. Even if it replicated imperfectly, the odds of a slightly different misfolded protein becoming another prion are vanishingly small (otherwise we'd all be dead) because there probably just are very, very few configurations possible. The vast majority of misfolded proteins just do nothing.

There are several billion humans who are each replicating millions of copies of each of the 20,000 or so proteins during their lifetimes. It seems pretty unlikely that there are many misfolds that haven't occurred. It's just that only a handful become prions. And even if they do, prions are thankfully very hard to communicate (again, we'd all be dead if they weren't).


They can induce correctly-folded proteins to misfold, effectively replicating.


But shouldn't the number of misfolds be very limited or just one so that evolution cannot occur? It almost sounds like fearing that fire will evolve.


> fearing that fire will evolve.

Well now I have new nightmares... :)

But in seriousness, I don't know much, but I believe that protein-folding is a hugely complicated problem that still lies at the edge of our understanding, therefore I conclude that we can't really conclude that the options for a replicating, harmful prion are basically harmless.

I mean...we don't even really know how common prions are, right? We only have noticed a handful because they have dramatically bad symptoms. A large number of replicating but harmless prions could exist (right?).

Obviously there's no reason to panic, but considered caution and study seems a better reaction than overconfident dismissal.


I don't know how many conformation changes could plausibly be caused by a prion or how many of them would be stable (and I'd imagine it depends heavily on the protein), but the number of possible conformations is incredibly large for any reasonably large protein.


Viruses can't replicate themselves either. Cells replicate viruses. And prions replicate by deforming healthy proteins.

Whether that replication can be incorrect and produce a different kind of prion, I don't know. If it can, evolution will do its work.


Not exactly. Presumably almost all imperfect replications lead to dead ends (or we'd all be dead). Also, because they transmit poorly from host to host, even if one did evolve, which might be impossible, it'd probably die when it's host did.

Given that each human replicates each protein many millions of times over the course of their life, and that there have been several billion humans alive, if that were possible we'd probably have experienced it by now and again all be dead.


With the same effect I can argue that viruses and bacteria are just misarranged RNA :)


I think this underestimates the complexity of proteins.


It is also an are where our innate fears, fears that modern society tells us are unacceptable, might have a place. There is a deep-seated fear of diseased people that once kept us healthy. Modern science has given us an understanding of disease that means there is often no need to physically separate paints where we know the disease is not easily transmitted. The shunning of an aids victim, or a child with cancer, is totally unacceptable in polite society. But prions, and especially research into possible links to various forms of dementia, suggest some dark futures. Maybe it isn't a great idea for the kids to visit grandma in hospital.


As stated in the parent comments that the likelihood of prions spreading in an infectious disease like fashion is very slim. Articles like this, ironically from a science-oriented publication, really don't help the conversation. Luckily modern medicine is fact based and not fear based.


Given that I have been exposed to the BSE prion, and so can never donate blood in north america, this is not a theoretical issue. The transmission of prion diseases are the subject of policy debate.


Is your username… related?


"Prions no threat, nothing to worry about," says Prions. Hmmmmm. :P


Nitpick note:

The phrase is actually “deep seated.”


You are correct. I've heard it both ways and ascribed slightly different meanings, but deep-seated was what I meant.


It's an eggcorn!


Oxford, Cambridge and Merriam-Webster say no.


Why do you say this? And why phrase it so tersely?

Merriam-Webster at least (the only one I've checked) says that "deep-seated" is the only correct version:

  Definition of deep-seated 
  1 : situated far below the surface
  2 : firmly established
  https://www.merriam-webster.com/dictionary/deep-seated

  “deep-seeded”
  The word you've entered isn't in the dictionary.
  https://www.merriam-webster.com/dictionary/deep-seeded


I was trying to make it clear that whiddershins was wrong to say that ‘deep seated’ is the correct usage in contrast to ‘deep-seated’ when Oxford, Cambridge and Merriam-Webster say that ‘deep-seated’ is indeed a correct usage.

P.S. Inconsistency: I assumed that whiddershins was complaining about the hyphen, rather than correcting ‘seeded’, which had been changed to ‘seated’ by the time I first saw it.


I see. You were pointing out the hyphenation or lack thereof? I think you might have missed that the earlier discussion was regarding "seated" versus "seeded". Thus your brevity made it looked like you were claiming that the "seeded" form was correct. I don't think anyone else was concerned about the hyphenation.


Now we have three variants in the wild. The correctly folded "deep-seated" and its harmless but slightly anomalous "deep seated". Worryingly, there's this new configuration "deep seeded" that a significant but unknown number of HN readers may have been exposed to. Although the original infection source has been neutralised, we must remain vigilant against sporadic recurrence in future.


Yes, I was indeed concerned by my wrongly perceived concern of whiddershins over the parent’s usage of the hyphen.


On the contrary, this falls within Nassim Taleb's Minority Rule. Prions, being nearly indestructable, are an intransigent minority that will eventually hold sway over the rest of us.

Many on this board point to the inelasticity of their transmissible potential and call this fear-mongering. However, it is that same inelasticity that makes them intransigent. Once they have compromised an instrument, that instrument will remain compromised until each prion has specifically been destroyed. When you pair that intransigence with its lengthy incubation period, you actually have a force multiplier that, while not viral, would be scary enough to change behavior.

Fortunately, the article hints that retinal scans may eventually be used for initial diagnosis.


The article does a good job of mentioning small likelihoods but large stakes, and is intellectually honest in doing so.


> Prion disease is exceedingly rare.

Isn't that begging the question? I mean, the author's concern seems to be that the prevailing belief hasn't been well-tested compared to the potential impact of it being wrong.

It's already happened before: There was a period of time when most medical practitioners were adamant that their actions could possibly be transferring disease, and it was an uphill fight to get regular disinfectants and hand-washing.


Is alzheimers a prion disease, or maybe just Prions are involved?


My understanding is that there is some evidence that Alzheimer's is transmissible (e.g. higher rate of incidence in caregivers and neurosurgeons), but more study is needed.


A study showed that if they wired two mice's circulatory systems together, one with Alzheimer's and one without, the second one would eventually develop everyone's favorite brain plaques.

https://www.newscientist.com/article/2151909-alzheimers-may-...

So while wiring together two bloodstreams is a bit extreme, and likely to result in most things being transmissible, there's nonzero evidence that you can have a bad day from a blood transfusion.


There's also been observations of particularly large amounts of certain human herpes viruses in the brains of Alzheimer's patients.


I believe Alzheimers is recognized as a metabolic disease now (some have even said Type 3 diabetes). It's in no way related to Prions.


The diabetes/metabolic theory was one pitched theory, and it isn’t even a terribly mainstream one. There is no consensus that Alzheimer’s is a “metabolic disease”. Even thought ApoE is implicated, that association could be explained by numerous mechanism, even viral.


Thanks for clarifying. I'm no expert just passing on things I've read.

Regardless, it's unrelated to prions.


No expert, but the latest studies have been about the correlation with the herpes virus and how the plaque build-ups that are part of Alzheimer's may be the immune system's attempt to protect the brain.


An incidence of 1 per 1,000,000 may not seem that scary, what are the odds of knowing someone who gets CJD? Obviously, much greater.


> This article is one good step above scare-mongering, but only one.

I agree. Could a moderator please change the title at the least?

"Prions, A Rare and Lethal Infection, ..." would be slightly better.


In lue of the downvotes, would anyone like to defend the efficacy of the article's title?


There is a great hypothesis that I remember my dad telling me recently, although I can't remember where he heard it from, that the reason that prion disease is so rare in humans is because we're, historically, very cannibalistic, so resistance to prions was heavily selected for.


The very opposite of this hypothesis is actually more likely to be true. Kuru is a manifestation of this same prion disease (PRNP gene variant disease) that is essentially only found in people from New Guinea who practiced a form of cannibalism in which they ate the brains of dead people as part of a funeral ritual.


This is exactly the wrong interpretation. We know that cannibalism causes prion disease, and we have known that for as long as we have known about prion disease. the question is not whether cannibalism causes prion disease, which it definitely does, but whether past cannibalism was common enough to have selected for some innate resistance to it.

http://www.virology.ws/2015/06/12/resistance-to-prion-diseas...


Like you said, we know that cannibalism causes prion disease. We know this. Thus, we are not resistant to it. So from an evolutionary perspective you could make a strong argument that what actually happened was that those humans who didn't engage in cannibalism and die of prion disease were heavily selected for. Which is probably why you don't see many humans eating the dead. Now that last bit is speculation, but all this is speculation. But based on my own introspection, I'm imagining myself stumbling upon a recently dead human corpse, I'm almost certain my innate reaction -- (well, almost surely innate, and not socialized, since I've never been explicitly taught how to react in such a situation) -- is that I'm definitely not going to fucking eat that corpse. In fact, the only humans that do seem to still engage in cannibalism do it out of some social ritual.


the prevalence of the PNRP gene is much better explained by periods of time when humans were very cannibalistic. This makes more sense behaviorally as well, since humans are very difficult to program with instincts. I would bet dollars to donuts that the average hunter gatherer/early farmer had no such revulsion. Meat is meat.


Well here is the major point: there is only one prion (PRNP), for which all mammals seem to be susceptible to disease. It would be odd if deer and sheep had coevolved the same resistances and susceptibility to PRNP due to human cannibalism


prevalence is not existence.


Not sure what that means


to nitpick, you probably WERE taught how to react by countless books, movies, stories in which people don't even think of eating corpses


True, but u could make the same argument for (literal) shit. Life reflects art reflects life, and so it goes.


I had project in college on Prions. Some interesting things I remember:

* Kuru (laughing disease) was transmitted from cannibalism. Women and children of the tribe were more likely to contract it because they were more often given the less palatable parts of the bodies, which included brains

* Some countries do not trust American cattle because our standards for Prion screening are too low

* Kentucky has issues with Prions because Squirrel brains are a popular dish

Try not to eat animal or human brains and you can dramatically reduce your chances of getting Prions


Born and raised in Kentucky (Lexington). I've never heard of squirrel brains as a dish. That's an interesting tidbit. Would it be fair to guess that the parts of KY this is popular are on the south eastern part of the state on the border with West Virginia? All of the normal rules of everything are different when you're in Appalachia.


Here's some info from a quick google: http://www.mad-cow.org/~tom/victim23.html

Looks like the dish is called Burgoo

> The center of the burgoo universe is Owensboro, Kentucky


Just when I thought my home state couldn't embarrass me more by being backwards...

Thanks!


I wouldn't be embarrassed. Those squirrels were probably wild caught (vs factory farmed), and the fact that they didn't waste the brain shows their resourcefulness.

Those are,after all, the same things we (rightfully) laud in the consumption of other types of more normative food animals. Just because it's a squirrel shouldn't change that.

EDIT: Added editorial wording to second paragraph.


Absolutely. Though as someone who has eaten squirrel (WV native. Yes it tastes like chicken.), I am amazed that someone took the time to get the brains out and eat them. It takes several squirrels to make a decent meal. I can't imagine how many it would take to have a substantial amount of what must be very small brains.


Aw don't be embarrassed. It's a cool little bit of history. Growing up in the bible belt, I remember many charity events were accompanied by a stew. You could buy it by the quart. My local volunteer fire department made a stew twice a year and everyone in the community looked forward to it. My grandfather and father used to cook stews for my birthday. The act of cooking a stew was an all day affair and pretty fun by itself. Everyone would sit next to the stew cauldron and fire on a cold fall/winter day and take turns adding ingredients and stirring.


That group cooking is super cool.

I am going to arrange a family event where that happens.


I've heard more about my home state's alleged consumption of squirrel brain outside the state than in it. And I have a couple kitschy KY cookbooks with recipes for burgoo, entirely rodent free. Every place will have hillbillies who eat odd game meat, if you search hard enough. KY just seems to be a popular target for this topic.


There’s a recipe in the new Appalachian cookbook by Ronnie Lundy, Victuals.


Clearly you contract the disease if you get behind on the salary to the black preacher.


Cooked goat and cow heads are a delicacy in some regions of Tunisia. Obviously, this includes the brain. I now wonder if Prions have ever been an issue in Tunisia...


http://n.neurology.org/content/35/6/894

Maybe it is an issue but goes underreported? Prions related diseases were historically easy to misdiagnose because they can present in so many different ways. I'm sure medical science has caught up in 1st world countries but maybe lags elsewhere?


Goat heads in Iceland too.


Calve's brains in Quebec.


A few questions:

* Do we have a good grasp on the number of prions in the world? My recollection from when MadCow became a big thing in the late 90s was that prions weren't even looked for and were hard to find as a general rule, but that was 20+ years ago. Might there be many common-but-harmless prions that we haven't even noticed?

* WHY is brain consumption (both in humans and in animals) such a source of prions? What makes that situation more likely to create prions?


Get this... there is only one (1) prion protein! All mammalian prion diseases are directly related to the PRNP gene.

People talk about Mad Cow, Kuru, Creutzfeldt-Jacobs, Chronic Wasting Disease, Scrapie, and a dozen other diseases like they are not all manifestations of the same underlying problem with PRNP gene variants.


I am not a doctor or scientist.

From what I remember on the topic, we do not have a good grasp on prions disease. There is a good chance that some other diseases in history may have actually been misdiagnosed prions disease. It can present as a form of dementia and the incubation period can be so long that many people are middle-aged before symptoms occur.

Tissue of the brain and spine are better for Prions propagation. Prions cause other proteins to misfold themselves. The proteins they affect are related to brain matter.


Why are prion diseases typically brain diseases?

Or is that the only organ where they manifest in symptoms?


iirc they reproduce most rapidly in nervous tissue. thus brains have the highest concentration of them.


Wow, the Wikipedia page for Kuru says there’s a mutation of the Kuru prion that confers immunity to Kuru. That’s crazy to me, but makes sense from a selection perspective.


Also caused by a prion mutation is Fatal Familial Insomnia (F.F.I.).

https://news.ycombinator.com/item?id=18653241


Eating sheep's brain is pretty common in certain parts of India

Is it a big issue out there?

If I've eaten sheeps brain twice myself, how soon should I plan my funeral?


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052957/

iirc, incubation periods can be decades long. I believe the more you injest, the shorter the incubation period


The research article you linked to is for sporadic Creutzfeldt-Jakob disease, not variant Creutzfeldt-Jakob disease. Sporadic CJD has no link to brain consumption.

Honestly there’s a lot of fear mongering in this thread about brain consumption...if anything it’s healthy for you. The main issues are most likely when the animal eaten has participated in cannibalism. For example, Cows were fed bovine blood meal which is what led to the Mad Cow scare, kuru is caused by cannabilistic human tribes, squirrels are known to be cannibalistic, etc. Lamb/sheep don’t participate in cannibalism. No need for unnecessary fearmongering


Sheep suffer from Scrapie

Scrapie is a fatal, degenerative disease affecting the central nervous system of sheep and goats. It is among a number of diseases classified as transmissible spongiform encephalopathies (TSE). Infected flocks can experience significant production losses.


> Try not to eat animal or human brains

Now all I can think about is the dinner scene at the end of Hannibal.


One of the Indiana Jones movies featured a monkey brain dish... blech


I wonder if the correlation between prion diseases and brains indicates either:

1. Symptoms show up soonest in brains and so can be distinguished from other causes of impairment or death.

2. Humans already some immune mechanism that helps protect against prions, but brain tissue is particularly susceptible because of it's less-usual immune-system setup.


If you're interested in prions and some heavy science, I would highly recommend reading the research blogs of Eric and Sonia.

http://www.cureffi.org/ and http://www.prionalliance.org/blog/

> Wife-husband team Sonia Vallabh and Eric Minikel are on a very personal mission to find a cure to prion diseases. When Sonia was diagnosed as a genetic carrier of a rare disease called Fatal Familial Insomnia (FFI), she and Eric quit their regular jobs and began studying molecular biology to learn as much as they could.

Theirs is an incredible story so far. https://www.newyorker.com/books/page-turner/a-prion-love-sto...


This is pretty inspiring. Thanks for posting it.


A few months ago I was talking at a family gathering and learned that one of my distant relatives has CJD. They're a high-ranking company executive, but their cognition is rapidly wasting away and will be dead within a few years. Another family member that was a nurse in Kentucky(?) said they have a high rate of prion disease due to farmers inhaling contaminated dirt for years.

There are a few comments here about how talking about prion diseases are basically fearmongering. It shook me a bit, though. I always thought of CJD as one of those freak diseases that you hear about in the news, but is such low likely hood that it's basically non-existent. Not so much anymore.


> A few months ago I was talking at a family gathering and learned that one of my distant relatives has CJD. They're a high-ranking company executive, but their cognition is rapidly wasting away and will be dead within a few years

Are you sure it's CJD? Article says 95% of CJD patients won't live 12 months after diagnosis.

> Another family member that was a nurse in Kentucky(?) said they have a high rate of prion disease due to farmers inhaling contaminated dirt for years.

What kind of prion disease and what kind of dirt?


I was told mad cow disease and CJD interchangably, which looking it up seems to be slightly different. I don't know the difference between CJD and vCJD and Wikipedia isn't helping much. Honestly, I don't know how fast it's progressing, so it may in fact be months. They may already be dead for all I know, but it sounded like they were diagnosed several months before - they don't know how long ago she got it though, due to the long incubation. The family member mentioned mood swings, improper outbursts in conversation, and memory degeneration and how they're nearly bedbound now due to loss of balance.

The nurse family member said cow farmers, so I assume cow feces contaminated dirt, and that their brains looked "like Swiss cheese". This was also in the context of mad cow disease. I checked my notes from the day and it was North Carolina, not Kentucky.


As someone with anxiety and eye problems, I'm not feeling great.


Same here. I've had strange eye problems that my doctor hasn't been able to explain, and I feel like my cognition is declining. It's easy to buy into unknowns like this which seem to explain everything wrong with you, but it's exceedingly unlikely.

More likely is that my eye problems are from wearing contacts in for too long and staring too long at a computer in a low-humidity environment and never blinking. My cognitive issues are probably from not eating healthily, not getting enough sleep, not exercising, and from being depressed.


> I've had strange eye problems that my doctor hasn't been able to explain, and I feel like my cognition is declining

You could also explain this with low-level heavy metal exposure, e.g. mercury, as well as a large amount of other possibilities :-)

I thought hard if I should write this, as a joke and only the above line at first, but here it goes. Having read your second paragraph too, that is pretty much exactly what I said to myself a decade ago and before. Then some things escalated a little bit and I was forced to either accept all my increasing issues, or do some research myself.

Turned out I had chronic heavy metal poisoning from mercury. Fortunately diagnosis was made easy because I actually had high levels of it in hair and blood (and urine - same as blood since that's where that comes from). Anyway, the scale of the problem was only made clear during chelation therapy, when both I as well as my (university clinic researcher) doctor were amazed at all the things that improved, including "miracles" such as thyroid normalization (had been enlarged and with a nodule for decades, completely gone within half a year of DMPS chelation, left the endocrinologist speechless, literally, he checked me twice with ultrasound to make sure he had not make a mistake). This issue is next to impossible to diagnose with today's methods, unlike acute poisoning, because how much you see in blood, urine or even hair does not say anything about the size of the problem, it only shows up when it actually moves around the body which it only does after exposure.

I had had dry eyes too, and of course the ophthalmologist as well as I myself attributed it to too much screen work. Today, after years of chelation, I sit in front of a monitor much more than ever before - but now I have zero issues. Same with RSI. Sooo many little things are completely gone from my body, depression too.

The crazy thing is, up to that point ~10 years ago when I had to confront that something was not quite right, I called myself "healthy". And why not? I could run a half marathon just for fun and still come back feeling relaxed. All the many little issues I had, such as a few warts on the feet (more and more over the decades but I ignored the trend), winter depression (many people have that, it's normal!), eye problems (not really severe, so not worth thinking about it) and many many other, my brain refused to think about it. The reality my brain created of my world was highly distorted, but I did not know it. Only the huge and unexpected changes happening after I began chelation (DMPS, later DMSA) showed me the extend of the thus far ignored problem.


Can I ask how you were exposed to mercury?


Beginning the story indirectly, when I began the treatment I was not even close to being sure about it all. The only reason I had even tested for mercury was because I was desperate, there just was no other option left, after consulting many doctors finding nothing. After having been given PPIs for the problems that had forced me to start looking in the first place my issues exploded in severity: I had never felt so bad in my life. With barely any stomach acid from the PPIs - I could hardly digest anything, it would lie in my stomach for way too long - I had reflux near constantly. Each time I lay down to sleep, really every single time. With much reduced stomach acid, which seemed to have a very strong opposite effect of what it was intended to do. I also had incredible bloating and my mouth felt funny. The professor gastroenterologist treating me thought it was just nerves.

The first thing I found was, after having first dismissed it as esoterics when I found it on the net, that I had a candida problem. Proven by the significant immediate effect of taking Nystatine (anti-fungal) and a doctor confirmed it. Later I even got Fluconazole, an internal antifungal, again with huge effects. Just an aside, funnily enough, the warts on the sole of my feet that every doctor would say were caused by a virus disappeared by 95% after Fluconazole.

Anyway, I learned Candida never is a cause but itself just a symptom, and since I had none of the conditions that are listed in the text books that might cause it I had to continue looking. Heavy metal poisoning was one of the only options that would explain the Candida, but also everything else. And I had only one possible source: amalgam fillings.

When the tests confirmed high levels of mercury in my hair as well as in my urine I still was not completely sure: It was high but not high enough to explain the severity of my issues. The doctor I went to said it was high enough to justify starting chelation, but I must have something else. I had the remaining three fillings removed with special equipment and protection. I had had three or four removed decades earlier without protection, just normal drilling, at the beginning of my CS study, and now something made sense: At the time I had suddenly, out of nowhere and pretty much overnight, developed almost-asthma level pollen allergy, and for half a year I had severe problems with the right leg joint. I never went to a doctor for the joint because the symptoms clearly showed me it was not "physical", I can't explain it with a few words. I also developed severe insomnia and - as I understand now but not at the time - "dumb". I had always been good at math, for example, but suddenly it was a problem. Stuff that today, after all my chelation, again looks very easy to me. I still passed and I was still very good at everything more practical so getting through the study was no problem. At the time I completely ignored all those sudden issues and took it as "that's just live".

Everything started to improve greatly during the first year of chelation, and after the fifth or so DMPS treatment in the following weeks the tissue around my right-side thyroid became very active. That was very curious, because I had had a double-sized right thyroid with a nodule for at least two decades, re-diagnosed just a year prior. Recommendation back then was surgery to get rid of the nodule. The tissues in that area became active after two or three DMPS treatments. I went to the endocrinologist again when I felt nothing else there. He did an ultrasound, and when he was done he started casually looking through his notes and became more and more agitated. He asked me to lie down again and he repeated the ultrasound, right side only this time. At the end the result still was this: Thyroid size nearly completely normal, and the nodule had disappeared completely. That was the point when I actually believed that yes, I had found the source of the problem.

Regarding an even more clear proof for amalgam fillings as the cause:

After about a year the doctor wanted to make an injection in to my buccal mucosa. It's just mucosa, so you don't need any force, but his needle ended up deep inside jaw bone. He found several places where the needle easily penetrated into bone. All those places where where amalgam fillings had been for two or three decades. He injected DMPS and just like in the thyroid area the are began to "work". Very actively. A year later the needle could not penetrate anywhere any more. The jaw remained a very very active area though for years, and it still reacted to chelation. An aside: The are had been OPG x-rayed a few times in the years before because I had finally gotten my crooked teeth fixed and jaw extension surgery too (now I have perfect bite and teeth, wonderful!!!). No doctor ever saw anything in my jaw. One wasn't sure about seeing a tiny shadow near one root - the one where I had the most issues and that was the most active later during chelation - but didn't take it serious enough and didn't follow up (when patients don't complain why would you if it's so subtle). But bone that can be penetrated by a needle easily is very broken. This shows how much (more) broken something has to be to show up even in an OPG x-ray.

My doctor never found anything else and now he too thinks that the only problem there ever was were the amalgam fillings. A lot - a lot! - of very interesting stuff happened to me, the chelators only paved the way out and started it, 99% of the actual work was done by my body (most chelators only work in extracellular space anyway). For example, there were three months of nightly 3-4 am kidney pain, but after the nephrologist found that despite elevated protein levels in urine there was no sign of kidney disease I didn't worry about it. It fit into the pattern of stuff happening at various times all over my body and my brain, a new phase starting every few months in another area of the body. For those three kidney pain months I simply got up when it started at 3 am or so, went to bed when it stopped at 5 am and slept until 10 and still got my sleep. No problem.

Even tough I'm a CS person, I actually have a background not in medicine, but (for fun and out of interest) I've also have many courses in biology, chemistry, org.chemistry, biochemistry, anatomy, physiology, neuroscience, several courses in each. I don't care about pathologies, I only wanted to understand the basics of biology and life and of human physiology.


also really interested in hearing the background


> I've had strange eye problems that my doctor hasn't been able to explain, and I feel like my cognition is declining

Ageing? And basically what you describe. I wouldn't worry about it :)


The top comment sheds some light on the rarity of the disease and the article just being some sort of fear mongering -- https://news.ycombinator.com/item?id=18648393


If you don't eat brains, you're pretty much safe.

If you eat brains, your risks go up by multiple magnitudes.


I wonder if it's limited to brain. If a cattle has prions and if you eat its tissues other than brain, can't you still contact prions via motor neurons?


Sounds like PR from the brain lobby.


Fear not, Thomas Bayes will rescue you!


Yep. I didn’t even finish reading it.


In related prion news, does anyone have insight into the recent studies suggesting that Chronic Wasting Disease (CWD, increasingly prevalent in North American deer and elk) may be transmissible from infected animals to humans via cooked muscle meat?

In 2017, there was a Canadian study that seemed to show that feeding macaque monkeys raw muscle meat from infected deer was capable of transmitting the disease. I don't think the study has been published yet, but it's described in detail in this Norwegian report (https://vkm.no/download/18.25950e0715e84a118a6ec492/15069251...) and forms the basis of an advisory by the Canadian government (https://www.thetyee.ca/Documents/2017/06/24/Risk-Advisory-Op...) suggesting that consumption of all potentially infected meat be avoided.

Then in 2018, a separate seemingly very similar American study was published (http://sci-hub.tw/10.1128/JVI.00550-18) , saying that no evidence was found for transmission to macaques, even after direct cerebral exposure. The NIH issued a press release (https://www.nih.gov/news-events/news-releases/nih-study-find...) with the headline "NIH study finds no chronic wasting disease transmissibility in macaques".

Suffice it to say, there seem to be contradictory messages here. Is there some overview that would help to clear things up?


I don't have studies but I did email the National Prion Disease Pathology Surveillance Center asking "is there a breakdown of cases of the individual Animal Prion Diseases by location and possibly by year (i.e. cases of human prion disease acquired by eating contaminated meat)?" and here was their response:

> To date, in the US, there have been no known cases of variant CJD, or human prion disease acquired by eating contaminated beef. Here at the NPDPSC, we have diagnosed 4 cases, but they were all acquired out side the US; 1 case in 2044 acquired in UK, 2 cases in 2006 acquired in Saudi Arabia, and 1 case in 2014 acquired in the middle east.

> In several western US states, Canada, and now South Korea and Norway, there is concern that chronic wasting disease (CWD), the prion disease of elk and deer, may be transmissible to people who hunt, butcher, or eat the affected animals. Although transmission of CWD from animals to humans is unlikely, recent data indicate that the barriers between species may be weakened when CWD has been transmitted from animal to animal several times (as may happen in the wild). The NPDPSC, along with the CDC, Department of Health, and the Game and Wildlife Administration, is carefully monitoring any possible case of acquired CWD in humans.

Asked for extra clarification, "So although there is a concern with CWD crossing that barrier, there still haven't been any recorded cases?"

> That is correct.


This is such a great comment. Thank you for doing that legwork, and for sharing it.


Here is excellent documentary https://www.youtube.com/watch?v=vw_tClcS6To&list=PLdO1m6dMye... anyone wants to see documentary related to Kuru (Prion Disease)


Not all prions are bad [1]. We still need to study them and their protein precursors to understand them more.

[1] https://www.the-scientist.com/features/the-bright-side-of-pr...


About 20 or so years ago I was feeling bad about my chances of developing the type of CJD associated with mad cow disease because of all the burgers I'd eaten over the preceding years.

There were also human cases getting reported at a rate that some suggested matched the pattern for the early days of an epidemic.

Luckily that never materialised. Still though having lived in the UK during a certain time period precludes one from donating blood elsewhere, to this day.


Sorry friend. Not off the hook yet:

> patients with very long incubation periods of at least 34 years, and probably more than 40 years.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...


The uptick in cases should have started in about 2014 (if 34 years ) or 2020 (if 40 years) and start to tail off a decade later.


> There were also human cases getting reported at a rate that some suggested matched the pattern for the early days of an epidemic.

An epidemic is by definition a statistically significant deviation from historic baselines.

Every single upswing within the normal rates of variability - all of the sin curve living above 0 - looks like “early epidemic.” We have one every month.

That was scare-mongering, too. Everyone loves to report an incipient disaster, at least until people get numb and the ratings fall down.


I stopped eating beef from that time due to that mad cow outbreak. A few years before that I was worrying about the Ebola outbreak in Zaire. I was no where near these regions either. As kid and into my teens I was pretty paranoid about disease and death.


There were certain feeding practices that were banned or reduced that were thought to contribute. I.e. many places quit feeding meat and bone meal of other livestock to cattle.

https://en.wikipedia.org/wiki/Cattle_feeding#Mad_Cow_Disease


That surely helped but as always, some enterprising folks found a way to "launder" the goods by feeding the banned products to poultry and then feeding their remnants and droppings to cattle.

Compare US position: https://www.feednavigator.com/Article/2017/07/22/USDA-Feed-n...

VIC position: http://agriculture.vic.gov.au/agriculture/livestock/beef/fee...


The part about the possibility of contracting these from your doctor's equipment when you go in for an eye exam is truly scary:

"Undiagnosed CJD patients may seek testing. And the diagnostic equipment used to test them may then become contaminated, the authors write. They recommend single-use instruments or the adoption of new decontamination procedures for opthalmological equipment with better effectiveness on prions."


The fear of contracting something from equipment is one reason why I go to an eye doctor who uses contactless air-puff glaucoma diagnostic machines rather than the older style which touches the eye.

In my last several visits, nothing has touched my eye at all.


Slightly worrying given that I had a cataract operation in my mid-30s. OTOH, I suspect I should be far more worried about the health impact of filthy diesel.


Isn't cataract surgery removing something, only?

FWIW, both my parents had cataracts removed, and my father who'd worn eyeglasses since the 1940's said he'd never seen better in his life. So, chin up.


cataract surgery involves replacing the lens with a new lens, now generally an artificial lens

https://www.allaboutvision.com/conditions/cataract-surgery.h...


Yes, but the article says that the instruments used in opthalmology can be vectors for the prions. OP is fine though assuming his operation was more than a year ago and he's not currently dead.


https://www.ncbi.nlm.nih.gov/pubmed/11721058?dopt=Abstract

> we estimate that the mean duration of the incubation period is 16.7 years

https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

> A comprehensive statistical analysis had earlier reported that the mean incubation period was between 10.3 and 13.2 years, but the tail of the distribution was long. Using these estimates, we calculated that the upper 0.4% quantile was 40 years, and even larger for those infected young (>50 years), very much in line with these new observations.


No, it quoted the speculation.

> them may then become contaminated, the authors write. They recommend single-use instruments or the adoption of new decontamination procedures for opthalmological equipment with better effectiveness on prions.


Prion diseases have incubation periods that are very long (5 to 20 years). It is only after symptoms appear that the end is near (a year or less).


The year is from the onset of the first symptoms. It said nothing about incubation period.


Sadly I'm blind in that eye - the operation was to allow better monitoring. Other eye is fine, fingers crossed.


the odds of this are about zero. the donor would have to have CJD, which is already exceedingly rare.


It's the surgical instruments I was thinking of. But yes, the risk being exceedingly low was kind of my point when mentioning diesel exhaust - a single lungful of which causes my chest to tighten up!


Well that's made me a bit more worried about my cornea transplant next year.


Given that prions are proteins, why can't we use immunotherapy and vaccinate?


Well the immune system needs to be able to do something of use in response. Just putting it in even with an immune sensitizing agent would add another prion that it can't do anything useful about. But antibodies, if we had ones that worked for a strain and weren't essentially prions themselves we could vaccinate for it or use it to "chelate" assuming the prion grabbers wouldn't cause other unacceptable problems.


Passive immunization might indeed be a feasible option, but of course requires timely detection.


Couldn't we immunize before exposure as we do with, say polio, TB, influenza et al? Then no detection would be needed.

Or are the abnormal prions in CJD and the like not uniform enough for general prophylaxis?

I really have a naive understanding of immunotherapy, so sorry if my question is dumb.


Whatever it is isn't that simple given that CJD is just a standard of care. I'm more an enthusiastic dabbler who occasionally checks if I could have been capable technically than an expert admittedly.

I did some more cursory research. Interestingly I was half-wrong about the immune system - while I was right about it not being equipped to stop it can do something. Monoclonal antibody treatments delay it. However another problem is that the body's own proteins which are deformed into prions aren't recognized as foreign bodies. Given that notes mention that mice vaccines only delay the onset along with monoclonal antibody treatments. Some sources seem to indicate that it only blocks prions from deforming as opposed to eliminating combined with the fact that native proteins will keep on cascading.

I wonder how much processing power would be required just to get a candidate 'prion grabber' - never mind going through ones which won't turn out to be horrifyingly toxic in other ways.

Here are a few sources I skimmed I would be glad to know where I went wrong.

https://www.researchgate.net/publication/233941323_Immunothe...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063508/


Thanks for replying (some people have downvoted my question, which is weird).

I don't completely understand your answer, due to my ignorance of the immune system. I thought the immune system could target specific proteins (e.g. how snake venom vaccines work) rather than using the proteins to identify target cells. Is this correct? I as assuming such a mechanism would be able to do something useful with the target.

The other part of your answer I did understand, and that was helpful, thanks!


It's definetely being looked at, for example: https://www.ncbi.nlm.nih.gov/pubmed/18215090/ (paywalled).


I guess, this is the weapon of choice for any patient spy unwilling to send a message. One pinbrick, and the nuclear scientist/dissendent/oppossitional spy has half a year to write his/her memoir.

Are there statistics on Creuzfeld-Jakobs in Langley?


It would seem the solution is to treat deceased CJD victims as bio hazard like ebola


Prions are one of the things that makes me go, hey wait maybe we do live in a simulation. They're basically corrupted code (which we've yet to figure out how they get that way in the first place) that corrupts other code... what is that?!?! Reminds me a lot of the WoW 'corrupted blood incident'.

I understand how something like bacteria or a virus enters a host and replicates, but an anomalous protein corrupting other protein is just so strange. I'm sure science will adequately explain it someday but until then it's a pretty WTF anomaly to me.


At the molecular scale, everything is effectively made of springs (molecular and intermolecular bonds). Proteins are a big complicated tangle of springs, and that means they have multiple possible configurations they can spring to if you let them relax. If you bump another protein of the right shape against them, you can nudge them into a different spring configuration.

Think of "slap bracelets", those curved metal strips that spring around your wrist. If you push two straight ones together, nothing happens. But if you push a curled one against a straight one it will make the straight one curl up too. The curled slap bracelet is acting like a prion.


>Think of "slap bracelets", those curved metal strips that spring around your wrist

Wow, I've not heard someone mention those in probably 2 decades.


But prions aren't code. DNA is code. Proteins are factory robots, and the prion protein is a factory robot involved in the process of making factory robots.

Neural proteins are very complicated, so they need other proteins to help them fold properly. One of these protein-folding-proteins (PRNP) can be mis-folded in such a way that it mis-folds other proteins in the same way that it is mis-folded itself.

When most factory robots break, they simply stop working and they get recycled. But when a robot-making robot breaks in just the right way, it starts producing robot-making-robots that are broken just like itself.


>But prions aren't code.

It was an analogy and reading https://en.wikipedia.org/wiki/Proteopathy#Seeded_induction it sounds very much like they act like a piece of code corrupting another piece of code

>Some proteins can be induced to form abnormal assemblies by exposure to the same (or similar) protein that has folded into a disease-causing conformation, a process called 'seeding' or 'permissive templating'

That sounds a lot like many computer viruses

>A computer virus is a type of malicious software that, when executed, replicates itself by modifying other computer programs and inserting its own code


It's actually relatively simple. Proteins, very roughly speaking, are things that change other things into something we need. You could think of proteins required for breaking down sugar, which do more or less exactly that: they take a molecule of sugar, break a part off of it and hand it to the next protein in the chain.

What makes prions so weird is that they are a protein that has been mismade (misfolded, generally). That something is being made broken isn't that weird in biology. Mostly, the body degrades them pretty quickly. However, prions, while not being able to do what they're meant to do, can take well-made versions of itself and break them in the same manner.


>What makes prions so weird is that they are a protein that has been mismade (misfolded, generally).

And science doesn't know how they get misfolded in the first place then they basically go "hey other protein, boop you're like me now, let's burn this mother to the ground" and then you get something similar to the 'corrupted blood incident' https://en.wikipedia.org/wiki/Corrupted_Blood_incident except you lose your mind and die.

As far as saying we know how proteins misfold, I'm going purely by what I've read both on and on wikipedia as I'm not an expert in proteins and amino acids...

>It is not known what causes the normal protein to misfold

Second sentence of: https://en.wikipedia.org/wiki/Prion


Proteins fold based on minimizing energy states. Any amino acid sequence (large molecules) can be folded in many different ways. For example enzymes binding to proteins can cause desired protein folding changes. Generally if a protein gets misfolded (happens all the time) it doesnt do anything, in some cases misfolding causes bad effects.

Prions misfold in a way that induces other of the normal version to misfold in the same way and therefore spread.

On the plus side prions kills pretty quickly and so there is unlikely to be much underlying mutation in their form or function.

Protein folding is incredibly complicated but I could imagine enzymes which could snip the prion or another similar protein which induces it to fold back into the preferred state. I doubt we have the science to explicitly design such a thing, but you could expose prion molecules in bacteria and put them under evolutionary pressure and they might eventually develop something that disables/fixes the prion.

You would essentially align survival of the bacteria to disruption of the prion molecule.

This link has an image of the two versions

https://www.mayoclinic.org/diseases-conditions/creutzfeldt-j...


There are plenty of ways that a protein could be mis-folded. There is a lot of bumpiness in a cell (though this is unlikely to lead to this). A random mutation (through some sort of radiation) could change a piece of DNA or RNA, causing the protein to be made incorrectly. All of these are frighteningly unlikely. But happen so often they are almost certain to do so in a large enough time, with a large enough population.

The similarities to the 'corrupted blood incident' start and end with them both spreading to others in a local area. Prions don't really suggest that life is a simulation.


"Prions don't really suggest that life is a simulation."

If life is a simulation, prions suggest either the simulation is run at an extremely high degree of verisimilitude, indeed simulating QM at a particle level for living things, or that the simulator has an incredible desire for accuracy, and has put a lot of non-trivial work into ensuring it. Almost anything you can think of that would reduce the computational load for simulating a human being would eliminate the possibility of prions arising in the first place, since "protein folding" is one of the first things you'd want to get rid of to cut the load down.


>If life is a simulation, prions suggest either the simulation is run at an extremely high degree of verisimilitude, indeed simulating QM at a particle level for living things, or that the simulator has an incredible desire for accuracy,

These are both somewhat my logic for even believing we live in a simulation. Obviously humans seem to be the largest factor on Earth given how we are rapidly changing the planet and directly, and indirectly, affecting all life on the planet.

We already have things like folding@home, weather modelling, climate modelling, asteroids@home, cosmology simulations from universe sandbox to supercomputer level, etc etc so on and so forth.

People love to immediately dismiss a simulation hypothesis "stuff is too detailed!" "why would someone use such specificity!". Well, why would anyone watch the Kardashians or eat hair (Trichophagia) or smoke cigarettes because none of these things are rational... however having a highly detailed simulation has all sorts of potential applications from seeing how ancestors may have evolved to seeing how a designer organism might potentially play out on a sterile world you plan to seed to being someone's incredible version of the Sims.

I mean, WE have the desire to do this sort of stuff. The above mentioned distributed computing and supercomputer applications shows some level of desire for this sort of thing but then you have games like SimLife from 1992 that allowed players to simulate an ecosystem and to modify the genetics of the plants and animals in the game.

'Junk' DNA, prions, viruses, erm consciousness, burning fossil fuels to the tune of roughly 40 gigatons of carbon dioxide emissions this year, living in coastal cities at or below sea level even AFTER disasters do considerable damage, the rapid adoption of social media and reality television, all of these things seriously make me wonder if we in fact are some sort of simulation just to see how a species can deal with both environmental and self-caused disasters.

Throw in many other things like the fact we've not detected life off-world, we've yet to detect any signs of another intelligent species (mind you we're just starting to really look), the rapid advances we've made in technology just in the 33 years of my life, technology allowing for us to fake audio and video of people that enough reference data exists for and things like this Chinese virtual news anchor, etc and it becomes really easy to go "huh, maybe we DO live in a simulation".


"Throw in many other things like the fact we've not detected life off-world,"

I do consider the simulation hypothesis to be one of the answers to the Fermi paradox, because "not deeply simulating the observable universe" is definitely another one of those obvious ways of cutting the load exponentially. Again, lots of attention to detail; if the external universe is something other than a full QM-level (or true ToE-level) simulation, it's obviously running on one heck of a detailed model... but it could still be exponentially less detailed than it superficially seems to be.

Of course, even if we are an island of advanced simulation, there could be others out there, surrounded by much-lower-detail areas.


Are you saying that the more complicated things are, the more it hints at a simulation?

Here, let me ask the most important question: What evidence about how things work on earth would make you less likely to believe the world is a simulation? Because it's always possible to come up with a justification after seeing evidence.

(Other planets are a different issue entirely.)


Speaking for myself, I can not imagine what evidence would disprove the Simulation hypothesis.

At the moment, reality is indistinguishable from being "real", for appropriate values of "real". There are things that would increase the likelihood of us being in a simulation, like us finding a QM effect of some sort where we can prove that what's actually happening is a computationally tractable simplification of what the theory presents. Instead, in the real world, every torture case we put QM to, QM keeps on QM'in just fine, regardless of what our intuitions think.

So I would say that for me, the simulation hypothesis is more-or-less as improbable as it can get. However, that isn't zero, and I can't see how it would ever be zero, and I have to admit that the "not zero" in question is not merely a pro forma "not zero, but 10^-huge number", but some sort of non-trivial "not zero". No idea how to put a precise number on it, though.

(As Scott Aaronson has said, one interesting reason to pursue quantum computers is that they are the things that will allow us to run experiments to see if reality does perhaps give up after a certain amount of entanglement and turn the system classical again despite there being no QM reason to do so. It's probably not the best reason to do it, but it is a reason to do it. If quantum computers turn out to be truly impossible, and not just an extremely hard engineering challenge, the reasons why can't help but teach us something profound about the universe.)


> Speaking for myself, I can not imagine what evidence would disprove the Simulation hypothesis.

I'm not talking about absolute proof.

I'm saying that for a claim that evidence makes it "more likely", you can't just come up with a plausible reason. You have to weigh plausible reasons for and against it.

For every "more likely", there has to be a corresponding "less likely".

I can come up with plausible reasons that "less complex world" implies simulation, and I can come up with plausible reasons that "more complex world" implies simulation.

But unless I'm using conspiracy theorist logic, I have to weigh those against each other, and say that one of those pieces of evidence would overall make me less likely to believe in a simulation.


>Are you saying that the more complicated things are, the more it hints at a simulation?

No, I'm saying that the fact that we can see down to a subatomic level which adds considerable complexity to a hypothetical simulation is not evidence that it is impossible that we live in a simulation.

If you tried to describe a 2018 smartphone to Konrad Zuse in 1936 he'd have thought you were either quite mad or a science fiction author. To him it would almost certainly be unfathomable as reality, even with him knowing that he created the first programmable computer. Hell, if you actually showed an iPhone to most of us in the 70's, 80's, or early 90's we'd likely have had a rough time processing it at first, especially if you loaded a VR game or some 4k video.


> No, I'm saying that the fact that we can see down to a subatomic level which adds considerable complexity to a hypothetical simulation is not evidence that it is impossible that we live in a simulation.

Okay, but I suggest you be a bit more careful with wording in the future. "These are both somewhat my logic" made it sound like the complexity was reinforcing the idea, rather than merely not completely disproving the idea.

With that clarified the rest of what I said is useless and a waste of both our time.


>It is not known what causes the normal protein to misfold

Second sentence of: https://en.wikipedia.org/wiki/Prion

>Prions don't really suggest that life is a simulation.

To you, to me they do. I imagine with the logic you're using, nothing suggests we live in a simulation. I however recognize this as one of dozens of things that are like "hey wait a minute". No where in my replies have I stated "THIS IS IRREFUTABLE PROOF REALITY IS A LIE!" I said this is one of the things that makes me seriously consider the simulation hypothesis. One. Of many.

>The similarities to the 'corrupted blood incident' start and end with them both spreading to others in a local area.

One is an anomalous protein that causes other proteins it comes in contact with to become anomalous spreading out of control and ultimately killing the host the other was code meant to do a specific thing, in a specific area, that due to a bug (that allowed the infection to leave restricted areas) caused anything that it came in contact with to become corrupted spreading out of control.

I didn't say "ermagerd this is the thing that happened on gorkamorka" I said 'this reminds me of the corrupted blood incident', which it in fact does.


To be blunt. I think you are jumping to conclusions with saying this implies/suggests life is a simulation. You are completely right to point out that is is a bit weird. But then there are a bunch of logical steps (such as looking for a more likely solution) to take before starting to think this would suggest life is a simulation.

There are a bunch of things I think that are more indicative (though, all have other possible, plausible solutions) of the simulation hypothesis. Some of the reasoning behind reality being a hologram (which I am not 100% on understanding).

For the corrupted blood, I wouldn't call it a bug. There was no problem with the software, just a wayward pet.


We do live inside a simulation... of particles, called... the Universe.


Protein chains are used by all living cells to manufacture the molecules we're made of. They arrange soure material into new molecules. Many proteins are intended to manufacture themselves. This capability is usually tightly regulated by availability of the source materials within cells.

Prions are proteins too. And they can create themselves from source material too. But their source material are proteins which are not intended for processing. As such, prions are defined like weeds in a garden: They're not supposed to be there.

Marvel at the wonderful world that is biology: https://en.wikipedia.org/wiki/Protein




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