Prions terrify me as well because it seems like there's no stopping them..
> In 2015, researchers at The University of Texas Health Science Center at Houston found that plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with chronic wasting disease (CWD) was buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment
I had read this before. It's horrifying. How do you stop the chain reaction of proteins folding into lower energy states? It's not like a bacteria or virus; it's more like ice-nine, except instead of water it's your brain.
Are there many noteworthy modern science fiction authors that hold up to the Asimov / Clarke / Lem generation? I would think someone reasonably versed in science fiction would have at least heard of it -- I'm a "zoomer" and I have.
The actual writing from a lot of the golden age and New Wave sci-fi authors is... OK at best, with a few exceptions (Bradbury's distinctively poetic and dreamlike prose, for example). Tons of modern sci-fi authors write stories with more literary merit, better clarity, better-conveyed action, more believable characters and dialog, and so on. The improvements there are really obvious when reading, say, an early 70s The Hugo Winners or collections of 1950s stories, and then a 90s The New Hugo Winners.
Whether their ideas and worlds stand up to Asimov and company, or happen to be appealing to a particular reader, is another matter, but the command of writing itself is overall better, I'd say. I don't think a modern author would have much luck getting novels or stories in major magazines published with Asimov-tier dialog & characterization, for example.
Plus those eras were full of tons of garbage, in addition to what we remember. New Wave (60s and 70s) in particular tended to some very special interests that I don't think have held up too well, with some exceptions. A lot of that era's stories are very in love with sex & drugs and not in a way that really translates into a good tale. Most of those aren't exactly well-beloved these days.
On the flip side, there are definitely some modern sci-fi authors that are among the most famous but have some serious problems putting together an entirely good novel. I'll refrain from naming names but among them is maybe the only author whose book has ever made me mad at them for wasting such a good idea, setting, and opening, by just having no damn follow-through and getting super lazy in the last 1/3 or so. They're probably a top-5 sci fi name, among active authors today. But I stand by the overall quality level being notably higher on at least some dimensions, and it's even true for that guy.
> Whether their ideas and worlds stand up to Asimov and company, or happen to be appealing to a particular reader, is another matter, but the command of writing itself is overall better, I'd say.
But that's just the thing -- science fiction is about the ideas, and about the sociological and psychological impact of those ideas.
Whether a work has literary merit is neither here nor there for most people, and "science fiction" as a genre has been looked down upon by literary folks since it's inception. I don't know why anyone would be interested in praise from a community that is so invested in snobbery.
Regardless, science fiction authors of the time did have literary merit, if that's what you care about. LeGuin and Butler, are both regarded well in modern literary circles as far as I know. Vonnegut himself is regarded well also. At the time however, their books were condemned as being inadequate by the prevailing literary reviewers for various reasons unrelated to their actual writing.
Work from that time is perfectly functional and servicable for the most part, especially if you look at the places where the stories were submitted and published -- a small majority of Clarke's works ended up being published in Playboy, I don't think anyone can blame him for not creating a literary masterpiece when the majority of places that would actually pay him for his work were essentially pulp magazines.
We have a number of very good modern science fiction authors that easily rival them. While none of them may be as iconic, I think that has more to do with competition in the genre and breadth of the market.
Name some? My experience with authors like Cixin Liu and some contemporaries is that they are unreadable, this could just be bad translations in Liu's case but I'm not at all convinced modern writers rival the classical greats in SciFi.
Asimov's SF is, sadly, hard to read these days. Clarke has held up better but still a bit dated. Lem reads as fresh as ever, but he's not so well known.
(What happened to Bradbury and Heinlein?)
Gene Wolfe is only one generation younger than these guys, and he just died, but I consider him a better writer than all the others I mentioned except Lem.
I read a lot including Sci-Fi and did not find any who are close. Does not mean they do not exist. Most likely not as famous and not exposed to wide public.
> Bleach works as surface decontamination agent. They know it works for CWD, and I expect it works for others too.
I remember reading that nothing but incineration would work in the context of Food-and-Mouth disease, but it seems modern techniques in brain surgery do use bleach. Interesting.
Essentially, the only thing that works is disintegrating the prions. You can't wash them off, since you're simply washing them into the water cycle. You can't deal with them in a way that preserves other biological matter, since they are proteins, disintegrating them means disintegrating any other proteins in that area.
IIRC at the time the BSE outbreak in the UK[1] was referred to as "foot and mouth disease" and I've heard people refer to it as that since then. I wasn't even aware they were separate things.
Do you understand how irresponsible it is? It might be but it's obvious. How common are prions? How many prions get into the water cycle already? Prions probably don't go through the water cycle's gas phase. Are we worried about seafood? Surely lots of prions end up in oceans and lakes already.
It sounds a bit scary but it's not clear that it would change the risk profile.
Foot-and-Mouth disease has a vaccine. I believe burning was for economic reasons: vaccination is expensive; the reproductive cycle (and by extension the population) is essentially human-controlled and the livestock population can recover quickly; and "we don't need to vaccinate" increases livestock sales.
There is also a study from 2014 that suggests that prions were not detected in stems even though the roots of wheat plants were exposed to them. I don't know if there is conclusive evidence yet on getting sick by eating a plant based diet.
"This suggests wheat was unable to transport sufficient PrP(TSE) from the roots to the stem to be detectable by the methods employed."
Maybe this is a naive question, but your immune system works by identifying foreign proteins and killing those cells. Is there no way for your immune system to target cells contaminated with prions?
The fundamental issue with prions is that they are *not* foreign. Prions are legitimate proteins made by your own body but folded wrong. A misfolded protein acts like a catalyst to cause more misfolding. Prions are *not* alive, they have no ability to reproduce other than through misfolding existing proteins. It's basically a form of crystallization.
Antibodies are shape-sensitive though, so there could be antibodies targeting the mis-folded protein. In fact, maybe many people exposed to them where able to develop an immune response and we just don't know about it because these people never had any symptoms (think about the survivor bias, but in reverse, or from the point of view of the prion).
Whenever a topic about something that could potentially destroy humanity comes up (say, climate issues), there is always some comment that makes a reasonable argument of why things are not as bad as they seem.
The simplest counterpoint to prion cataclysm fear is that it hasn't happened yet. That implies a low chance that it'll happen anytime in the near future.
There's no evidence that any significant human population has ever been wiped out by prions at any point in the history of the species. Heck, we haven't even observed widespread (>10% infected) prion disease in any species.
At least with something like climate change, there's the fact that post-industrial activity is doing something different than pre-industrial history. But this reasoning doesn't hold for prion cataclysm. It's more like asteroid apocalypse. Yes it could happen, but statistically it's not something we have to worry about on a civilizational timeframe.
I don't see any justification for why humanity in 2021 is courting prion disaster to a greater degree than it was in 2000 BC. Animal husbandry has existed for fifteen thousand years. Maybe globalization would spread a prion outbreak faster. But the point is we've never even observed localized prion collapse. If prions were that dangerous, there should already be regional areas that have transformed into total no-go zones.
Conversely industrialized meat production is relatively recent, and so the volume of prion's being introduced into the environment is potentially much higher then the rate at which they are degrading naturally, not to mention the degree of regional cross-mixing of sources.
Prion contamination can now be shipped around the world in about 24 hours, where it can enter new populations much more easily.
Proteins do eventually break down in the environment. If you hugely multiply the number of humans and population density, you are creating a situation where prion diseases can become endemic where they couldn't have been before.
This is probably exactly what happened with CWD - deer overpopulation plus the random protein misfold created the conditions for a contagious disease where it didn't exist before.
Or could it be that we have it and don't know it. Alzheimer cases are growing as we remove other causes of death. Dementia is just accepted as a consequence of growing old. It not like we section every brain of an old person who dies.
We only noticed it on our farm animals because we brought the cycle time down as we fed downer cows to other cows as a source of protein
> I don't see any justification for why humanity in 2021 is courting prion disaster to a greater degree than it was in 2000 BC.
While the kinds of people who would fly planes into buildings, release nerve toxins in subway stations or club entire villages of outsiders to death have always existed the ability to research and manufacture prions did not exist in 2000BC.
That combination of desire to destroy the world and the legitimate ability to do it with rapidly more accessible biotechnology is a disconcerting reality that we need to account for when discussing theses things.
Imagine a religious extremists organization mass producing prions and placing them in key parts of food supply chain. We probably wouldn't have a clue until it was too late.
Biotech as a whole and its misuse by fanatics (or public servants in states with dubious moral …) is a massive concern for the 21th century, but I don't really think prions deserve a special place in this list. There's way too much scary things in here (gene drive, artificial viruses, intentional smallpox spreading, etc.)
That may be the case but it's a different issue than "Why are prions more of a threat to humanity than they were 4k years ago?"
With that said I sort of disagree with you. Prions are particularly attractive to a hypothetical bioterrorist due to the difficulty in detecting them, their durability and also the delay on effects. As I said above, once you know you have a problem it will be too late.
Keep in mind these are just the prions that nature has produced. It is quite possible that humans are able to modify existing threatening prions or develop whole new classes of threatening prions that haven't developed in nature.
Overall I think the most effective strike from a bioterrorist won't come from a single attack vector but a well timed combination of vectors. We've seen how something as minor as COVID has taken all of our attention and resources, now imagine if a terrorist timed something like COVID with a follow up strike like prions.
> hypothetical bioterrorist due to the difficulty in detecting them, their durability and also the delay on effects.
Terrorism is about fear, and that comes with spectacular actions even if it kills relatively few people, not with stealthy poisoning of big population.
You're not gonna have anything remotely as impactful as 9/11 with prions, even if you killed a million people in the long run.
Is it a good weapon for a nation state going at war, or committing a genocide. Definitely yes! But it sucks for terrorism.
> The simplest counterpoint to prion cataclysm fear is that it hasn't happened yet.
Well a prion disease (called Kuru) did affect the Fore people of New Guinea seriously in the 1950s and 1960s as I recall. Here is what Wikipedia says about the Fore people:
> Furthermore, Kuru predominantly affected women, as women more commonly partook in cannibalistic religious rituals. Because of this, there was a significant sex imbalance in Fore society.[14] By some accounts, this gender imbalance reached a 3:1 male to female ratio at its worst. This affected the family structure of the Fore, as it became commonplace for children to be raised and cared for only by their fathers.[1]
I do have the book, it's quite interesting, but I read about Kuru while it was still thought to be caused by an infectious virus. My recollection is a bit vague, but I believe it was in Time or Newsweek during the 1960s.
It was a scary sounding disease so I remembered it when years later it was discovered to be caused by prions and reported in The New York Times.
This is the right way to think about it. That said, a 1% infection rate that isn't at all a threat to the species given normal biological processes* will cause us to completely flip our shit. While we wouldn't be wiped out, everybody would be real upset for a long while. Look at COVID.
*Technology has given us things like nukes, so...could be harder to predict these days.
I'm not afraid of being hit by some asteroid hanging there, but if one day we spotted an asteroid whose trajectory was straight to earth, then being terrified would be quite legitimate.
Actually, there is some good news. Many types of prions diseases do not spread from animals to humans (so far). There have been some studies around this with CWD, but also Scapie has been around for hundreds or even thousands of years and never made the jump. Even in areas with CWD, we see that herd numbers do typically rebound. It's believed that there is some genetic factor that prevents the onset of the symptoms, like the body's proteins are less likely to fold in that way, so you only accumulate what you eat, or that the body can clean up the misfolded proteins. So it's not like it would wipe out everyone. I think I remember reading that some people are also researching prion treatments with some limited sucess. I would imagine they would come up with something even more quickly if there was a epidemic type of situation, similar to how medical researchers around the world focused on covid.
Not to be a doomer but there are scenarios where neither genetic variation nor research would solve the problem. The correct mix of virality, incubation and lethality would do it. Pneumonic plague is terrifyingly close. I wish there was a bigger interest and investment in biology, I think it’s the only viable path forward for humanity.
I was just discussing prions. Other pathogens do seem to present a bigger risk. I don't think anything would have 100% kill rate. Even weaponized microbes have like 99.8% or something. That still leaves about 16 million people. Plus there's all those preppers with their bunkers, some uncontacted tribes, people who live in isolated areas. Then it becomes more of a matter of how to organize, do they have the knowledge to survive in those types of conditions, etc. The species will survive, but it will be a very different world.
Actually there is a positive anecdote often cited. The Fore people of New Guinea engaged in ritual cannibalism which lead to the propagation of prions across generations. When they stopped, the generations of disease also stopped.
The Fora people even developed a prion that confers resistance to kuru:
> researchers [...] discovered a naturally occurring variant of a prion protein in a population from Papua New Guinea that confers strong resistance to kuru
> This community [...] has developed their own biologically unique response [...] this genetic evolution has happened in a matter of decades
You jinxed it, so I'll be the "some comment": prions won't spread everywhere all at once, so humanity will probably self-isolate in at least a few prion-free clusters.
Prion caused disease is indeed terrifying on individual level but, from its impact over the species' survival, it isn't that menacing. The decay takes decades, which is enough for breeding the next generation. Human life expectancy may get shorter, which sucks, of course, but humans lived shorter lives for most of their history. So no, it's not that bad. Even assuming that the entire human population will get infected from young age with no way to avoid it, it won't be that bad. It would come with a bit of adjustment, like having to raise kids sooner because the luxury to postpone (for life enjoyment or other pursuits) won't be there, but things will go on.
Well, prion diseases are very rare in humans (or at least their transmission is rare), and there is no evolutive pressure to create a super-prion that can infect more people, like happens with other pathogens. Thus, the most likely situation is that it will continue to be very rare until we are able to change it into virtually non-existent by technology.
They are a really scary thing, but it's a meteor strike style of scary, nobody really expects it to happen before we can deal with it.
I lived through it. I mean, it was scary, but the risks were low.
I remember my landlord and his girlfriend at the time saying they were going to give up beef due to the risks. They said this whilst smoking cigarettes.
People are so good at ignoring large daily risks and freaking out about tiny unknown risks.
Just look how many people are scared of the covid19 vaccines, but take bigger risks in their morning commute. Actually if you just stick to the AstraZenica vaccine with the risk of blood clots - you take a bigger risk just getting out of bed in the morning, even if you never leave the house.
Yes and no. The vaccines are by definition new and untested. That the blood clots appeared suggests that the unknown surface area of the vaccine is higher than we expected; whereas the almost all of the risk on your commute are known and preventable.
For example let's say the vaccine causes a side effect that appears only two years from now; then you wouldn't necessarily be correct in asserting that the morning commute is more dangerous. By contrast, the morning commute causing an unknown side effect in two years is highly unlikely.
The risks on your morning commute are not preventable by effort on your part. You can drive with care, but there is still substantial risk no matter what.
Unknown but remote risks with any vaccine are really quite substantially less dangerous than the known and quantifiable risk of your commute. We're talking like three orders of magnitude or more which leaves a lot of room for unknown risks.
I lost someone very close to me to sporadic CJD. This was some time back, but the episode is one of the most troubling moments in my life because of the suffering it inflicts on the patient - the hallucinations with no way to communicate or to stop it.
Many countries would not allow people who lived in the UK during the 80s and 90s to give blood. I ate so many burgers back then too. Our kids after they were born weren't allowed beef for years.
Yep I'm one of them. Lived in the UK in the early 80's as a child. Gave blood for the first time when I was in college in the 90's to the Red Cross here in the US, and they mailed me back saying to never give blood again but didn't specify a reason. It wasn't until a few years later that I found out why. And the fact I might have a prion disease lurking in my blood sometimes terrifies me.
I don't think it's a concern any more. The trajectory of cases that should have occurred if CJD was widespread in the community, never happened. One consequence of this is the blood donation ban has been lifted in most countries, I think.
They can’t evolve independently but biological systems that produce proteins can evolve new proteins and new ways of manipulating proteins. A nightmare scenario would be a bacterial or viral mutation that produced a deadly prion.
I don't think you need to worry too much about that, honestly. as far as bioweapons go mRNA is pretty involved.. if you need to inject your victim, that's already way too complicated. bioweapons are much more oriented towards tainting water supplies or air.
I know a huge amount about the level of technical skill required to do something with mRNA. It’s involved today.
But in many ways it’s less technically involved than (re)creating the horse pox vaccine from scratch.
And in 20 years it could be as simple as something aerosolised (there are already research projects for nasal mRNA vaccines) we don’t know quite yet where this will all lead to - PRNP is small enough at 200-odd amino acids long that it can be easily encoded on mRNA and as a fucked up disease vector that’s surely worse than anything viral - a timebomb sitting in everyone’s bloodstreams waiting 5-50 years to go off
This probably isn't possible as the folding of PrP is not encoded in the mRNA of PRNP. The fold of PrP is a post-translational phenomenon, much like its glycosylation. This is true for many mammalian proteins, especially cell-surface proteins.
I’m aware of that.
However the specific choice of amino acids can heavily influence the propensity to fold in a particular way. For example homozygotes for M129 have a much faster rate of vCJD development. Since Prion Diseases occur sporadically, the rate of mis folding can be increased and it probably wouldn’t be that difficult (even computationally) to determine how you can get it to misfold at a much higher rate.
I’m not sure what you mean by the fold being post translational, all folding is post translational, it’s literally the protein curling up into the lowest energy conformation as soon as it encounters the cellular environment, with assistance from HSPs if necessary. Unless you meant something else?
I'm not sure why this is the case. They replicate. There might be an error in replication, no? Or is that just really hard? Is it that their existence is in a sweet spot, and nothing even marginally different would work the same way?
If you took affected neural tissue and burned it to ash on a wood fire, there remains (although low) infective potential but probably only if you were trying in a lab. It takes 1000 C incineration to defeat infectivity and even then they’re still detectable.
Composting so the proteins are broken down biologically is also an alternative.
No amount of cooking prions that leave anything you want to eat makes infected material safe.
I’m not so sure about the composting - the breakdown of organic material (well, protein in this case) in soils is largely brought about by proteases and proteases are largely ineffective
`Prion aggregates are stable, and this structural stability means that prions are resistant to denaturation by chemical and physical agents: they cannot be destroyed by ordinary disinfection or cooking.`
Iirc hospitals that treat patients with prion diseases incinerate all materials that contact the patients. I don't know how they sanitize the rooms but it can't be cheap or eco friendly.
Chemical agents which cause protein-crosslinking would be the preferred method - you can broadly make every side-group reactive and cause them all to stitch together with anything else organic, which tends to inactivate them (makes them a big blob which can't do much).
But it's nasty stuff to work with, since it also happily does tons of damage to the proteins making up the humans applying it.
Apparently not: I was thinking glutaraldehyde which is used for cleaning in hospitals but reading up the advice for prions is explicitly opposed to cross-linking agents.
Sterrad sterilization machines, which use a hydrogen peroxide gas plasma, have been shown to be very effective against CJD (mad cow) and other prion diseases. However they are very expensive, and almost 20 years after their launch there are only 20k systems installed world wide.
That's not entirely true. They know that bleach can be used against CWD for surface decontamination. I would call a 50/50 bleach water solution quite common for disinfectant.
Yes they do. From wikipedia : Prion aggregates are stable, and this structural stability means that prions are resistant to denaturation by chemical and physical agents: they cannot be destroyed by ordinary disinfection or cooking. This makes disposal and containment of these particles difficult.
Yes they do, unfortunately. And there are recently discovered cases of chronic wasting disease (CWD) in elk, deer and moose worldwide. I hope it doesn't pass to humans. For the time being I'll refrain from eating game.
I would be more worried about beef. There has been no evidence of CWD jumping to humans, but there has been for BSE.
Also, do you have a link for the distribution? My understanding is that it is spread over a large geographic area, but that it's found in smaller clumps.
There are several maps and studies, depending on which country you're interested in. The best one that I've found was for Norway. Needless to say, it's spreading over an increasingly larger area every year.
Yes, BSE is also worrying, but beef that you buy at supermarkets is also checked more thoroughly compared to game meat. I'd worry more about restaurants and their suppliers.
Apparently the only options for diagnostic testing are brain biopsy and pulling CSF samples, both of which are probably a non-starter for screening purposes across a population.
Clinical Laboratory Tests Used To Aid in Diagnosis of Human Prion Disease
Allyson Connor, Han Wang, Brian S. Appleby, Daniel D. Rhoads
Journal of Clinical Microbiology Sep 2019, 57 (10) e00769-19; DOI: 10.1128/JCM.00769-19
I wonder if there have been studies on the scale of potential latent vCJD/Prion disease in the population?