That article (and all the Wikipedia articles on TSEs) repeat the claim that certain alleles are protective against TSEs, bur the post above claims that's been debunked. I am confused.
Wikipedia claims that some genotypes are less susceptible than others. The debunked claim is that a specific genotype in humans is completely immune. The debunking is cited to an article saying that there are significant differences in disease progression between the different genotypes.
Generally a good review, but IMO it would have benefited from giving more background information. Or at least answering, pretty early in the review, the question,
”What exactly is a prion, and why is it deadly?”
Like, you can eventually pick up from context that it is made of proteins, and that it affects the brain somehow, but I ended up having to pause mid review to google more information on prions. Even something as simple as:
“Normal prion protein is found on the surface of many cells. Prion diseases occur when this protein becomes abnormal and clumps in the brain. It then causes brain damage. This abnormal buildup of protein in the brain can lead to memory problems, personality changes, and trouble with movement.”*
Would have been helpful.
From context, it looks like the reviewer has a a medical background, so the source of the problem could be that they overestimate what average people know about prions (I had never heard of them before today,) and so does not give as much background as would be helpful.
Still a very interesting review, even before I knew what it was walking about.
Also, for those curious, Wikipedia has a pretty good description of why prions are deadly:
Prions are a type of intrinsically disordered protein, which continuously change their conformation unless they are bound to a specific partner such as another protein. With a prion, two protein chains are stabilized if one binds to another in the same conformation. The probability of this happening is low, but once it does, the combination of the two is very stable. Then more units can get added, making a sort of "fibril".[11] Prions form abnormal aggregates of proteins called amyloids, which accumulate in infected tissue and are associated with tissue damage and cell death.[12] Amyloids are also associated with several other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[13][14]
Whenever I read about the Gajduseks of the world traveling to places where they can still get away with behavior considered abhorrent in the rest of the world, it always reminds me of this passage from Gravity's Rainbow:
>How provoking, to watch one's subject population dwindling like this, year after year. What’s a colony without its dusky natives? Where’s the fun if they’re all going to die off? Just a big hunk of desert, no more maids, no field-hands, no laborers for the construction or the mining—wait, wait, a minute there, yes it’s Karl Marx, that sly old racist skipping away with his teeth together and his eyebrows up trying to make believe it’s nothing but Cheap Labor and Overseas Markets. . . .Oh, no. Colonies are much, much more. Colonies are the outhouses of the European soul, where a fellow can let his pants down and relax, enjoy the smell of his own shit. Where can he fall on his slender prey roaring as loud as he feels like, and guzzle her blood with open joy. Eh? Where he can just wallow and rut and let himself go in the softness, a receptive darkness of limbs, of hair as wolly as the hair on his own forbidden genitals. Where the poppy, and cannabis, and coca grow full and green, and not to the colors and style of death, as to ergot and agaric, the blight and fungus native to Europe. Christian Europe was always death, Karl, death and repression. Out and down in the colonies, life can be indulged, life and sensuality in all its forms, with no harm done to the metropolis, nothing to soil those cathedrals, white marble statues, noble thoughts. . . .no word ever gets back. The silences down here are vast enough to absorb all behavior, no matter how dirty, how animal it gets.
Don't confuse modern fiction for historical reality. While sex tourism was occasionally a thing especially for pederasts like Gajdusek colonial white communities were very small, moralistic and tightly knit. Paris and London had far bigger and wilder sex scenes than some dusty colonial outpost.
I know nothing of the geneology of the people involved - for all I know they could have moved there from Denmark or somewhere and adopted local names - but:
This *is* the island settled by Bounty mutineers who basically pulled another "Rape of the Sabine Women" to establish a breeding population? That stuff has to have a cultural impact, in so many ways.
>This is the island settled by Bounty mutineers who basically pulled another "Rape of the Sabine Women" to establish a breeding population? That stuff has to have a cultural impact, in so many ways.
Yup, Many Thanks! ( While I probably watched "Mutiny on the Bounty" decades ago, I don't remember anything from it, so don't have a side on _that_ part of the history. ) I presume that they would have been considered outlaws under British law due to the mutiny, so it is unsurprising for them to wind up with an outlier, corner case culture... If nothing else, I'd expect them to be less enthusiastic about the rule of law than typical Englishmen if said law would have hanged them...
"Fatal familial insomnia is an autosomal dominant disorder. This implies that if the doctor had FFI, his sibling must have also had it". Uh, what? This is wrong on several levels. If the doctor had it, one of his parents must have had it (unless it was a de novo mutation!), which means that the sibling would be 50% likely to have it (assuming it's so rare that having two copies amongst the parents' 4 chromosomes is vanishingly rare).
Agreed, good point! Perhaps the sentence should have read "This implies that if the doctor's nephew had FFI, then the doctor's sibling almost certainly also had it."
Fun side note: the UK minister who tried to feed his daughter the beef burger was John Selwyn Gummer, who was later ennobled (apparently trying to cover up a dangerous disease isn't that bad, honest) as Lord Deben. Under this name he is very active in promoting policies relating to mitigating climate change; it appears he is not aware of how his presence causes people to question the validity of his case.
I'd like to say I'm pretty sure poor sleep itself is a major causative factor.
I say this due to some personal experience, and encounters, as well as a few relayed anecdotes, and some more obvious Alzheimer's research.
Some critical energy intensive metabolic step gets jammed, the body demands energy, and if this state is induced chronically, prions and the like fail to get quarantined, or something.
I liked it. Still, I wouldn't recommend it as reading material. It would be much better to have some actual descriptions for the diseases as diseases and not cases. How many people have FFI today? How many other pathologies are in this cluster? If there are (many and different) animal models for cancers, are such models possible for the prion diseases? There is no sense of scope to it.
"The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie?"
Wikipedia suggests the most likely transmission route for CWD is fecal-oral i.e. deer shit in the woods, other deer eat plants contaminated by that.
Deer have 3 specific behaviors that probably are highly involved in transmission in the wild (in addition to stuff like poop food):
1. Scrapes. Deer communicate, in part, via rubbing their pre-orbital scent glands on communal sticks along key travel corridors. Almost every deer that walks down a trail will hit up these sticks (often peeing underneath it as well). Of course CWD prevalence in this fluid is damn low, but OTOH it's a set of sticks that all does living in an area and many bucks that visit the area (during rut or otherwise) will rub their fluids all over/feed near it/lick it/lick the ground under it.
2. Autophagy: Deer eat fallen antlers off deer as rich sources of key nutrients.
3. Communal Eating. Does and the associated fawn groups are communal animals (fully matriarchal society, the boys are kicked out (depending on area) somewhere around 1.5 years old). These doe family groups often eat nose-to-nose, even when feeding in natural settings or ag lands. If you watch deer eat acorns or other hard mast crops you'll see how it's likely they're exchanging a good bit of salvia during the process.
The studies often focus on penned deer (lamp problem, we study what we can study) and it's a lot harder to track/study stuff like this in wild deer.
It's very, very hard to figure out exactly how it's spread in the wild and many people disagree strongly on this. There's a lot of motivated reasoning as well b/c you have people very tied into specific theories. Also, the various state wildlife management agencies are (err) not particularly well trusted by many members of the public.
You could also (for Northern regions) add deer yards as 4th. Certain areas will vacuum in deer b/c of favorable winter foods/safety/shelter and from about the 45th parallel and up they pack themselves into these "yards" in the winter living much more closely than in the summer.
This has been low-key kicking around since at least the mid-00s, but it is a viable transmission pathway AND given deer-in-the-wild behavior (tons of transmission, tons of shared salvia) is probably at least a significant driver of wild CWD transmission.
We've stomped out (most) baiting, cracked down on salt licks, and deer farms are better (while still being horrible). Yet, CWD continues to spread in the wild in areas following standard of practice (even without incredibly high deer density).
Hmmm, OK, I'm not a vet so I will defer to those who have studied the matter with deer - but there are no credible cases in humans certainly of prion diseases being spread via saliva.
This "book review" clearly isn't limited to the book, which is fine, but makes me feel like it's incomplete without including (at least) a mention of (at least) DTM's 2013 article about Minikel+Vallabh: https://www.newyorker.com/books/page-turner/a-prion-love-story
I liked this but had a weird feeling like it was from an alternate universe where prion diseases remained something most people thought about a lot. Like this review is written as if there was a covid-level prion disease, but I am not aware of anything more prominent than Mad Cow. Is there something I am missing about the world? Are there prominent conditions I'm not appreciating as prion diseases?
My understanding is that the author is saying that we could have rampant prion diseases right now and not be aware of it: prion diseases are hard to identify, take years or decades from infection to symptoms, and we’re not really looking for them anymore because nobody really worries about them anymore. That people could be dying of them all the time and we misdiagnose it as something else.
I mean, I think about it every time I see a deer that appears to be emaciated. Although more evidence than that is needed to determine if the deer has wasting disease--I'm just going by looks. But, going by looks, there sure are a lot of very thin deer around.
Overpopulation is also a big factor in deer being thin - all plants are not equal in nutritional value to deer, and if they get too overpopulated they'll just destroy all the local plant species they like. There's a wilderness preserve in Pennsylvania where deer hunting is forbidden and now it's so overpopulated literally nothing can grow except for invasive Japanese stiltgrass, which deer hate above all else. (They can't just un-forbid hunting, because the land was bequeathed by a rich person who hated hunting and wrote the ban into the contract.)
Rereading, it looks like their main worry is the "1 in 5000 deaths are due to prion disease" statistic, which is surprisingly high for a disease that "nobody gets."
However, that number is the *lifetime risk.* The article that statistic comes from is careful to point out that "everyone dies of something" - a very low incidence in the general population can lead to a high death rate if you roll the dice for a long enough time, and deaths from prion disease are concentrated among old people while the population is generally young.
So I think the correct interpretation of this figure would be something like "If you live long enough, and heart disease or cancer or pneumonia doesn't get you first, then eventually a misfolded protein will find its way into your brain and that will kill you." Important for researchers - it suggests that prion disease is responsible for a surprising number of "deaths from old age", and perhaps that our bodies have some way to fight prions which degrades with age - but you shouldn't be terrified that there's an invisible plague sweeping through the US.
I think they're worried because of the "1 in 5,000 people die of prion diseases" stat, which suggests that prion diseases are endemic in our population and more common than the "one in a million" quote we hear.
However, if you follow the link they provide to where that stat came from, they explain it and it's a little less scary. 1 in 5,000 is the *lifetime risk*, and prion diseases are concentrated in older people. Everyone dies of something, and if you keep rolling the dice all your life then you'll eventually land the one-in-a-million chance of a prion disease. (Or maybe these prions are everywhere and at some point your brain just stops being able to clean them up? Or maybe it takes decades for the prions to build up to cause a problem?)
On one level this is worrying - if you're worried about Alzheimer's, there are potentially a lot of "Alzheimer's-likes" floating around out there, mostly ignored and filed under "dying of old age." But you don't need to worry that there's an unseen mad cow pandemic sweeping the country, it's more like "if heart disease and cancer and pneumonia don't get you in your old age, eventually a misfolded protein will work it's way into your brain and that will *definitely* kill you."
I would like to engage with this question, but I'm honestly not sure where to even start. In case anyone else is also starting work on a detailed reply, maybe we could use this here comment as stub to start a subthread?
1. First, a meta point. I think there are some parts of the text that read, to me, as being misleading or confusing. I am tempted to think that the author themself may be confused about some things. However, I am very hesitant to impugn the author here in a forum where they cannot reply to defend themself while remaining anonymous. So I will attempt to focus only on the text and not on what the author may or may not have believed or intended while writing it. (But this will be hard and I will probably screw up, so I apologize in advance!)
2. The text mentions Minikel's estimate of "1 in 5000 people dying of prion diseases", and then mentions several different contexts in which, the text seems to me to imply, this number seems surprisingly/alarmingly high. But that implication does not seem justified upon careful examination. Minikel's linked post explains some of the subtle differences of statistics involved. I highly recommend a careful read of that post to anyone confused by the text here.
The first context mentioned is "A genetic disorder that affects one in five thousand people is pretty common!". But the "1 in 5000" number is for all prion disease (genetic + infectious + sporadic), and, as Minikel's post explains, the _genetic_ prevalence is perhaps (very roughly) 10 times less.
The second context mentioned is "random people I’ve met in my life in a non-medical context". As Minikel's post explains, for this context it would be more appropriate to consider the _prevalence_, "the number of people sick with a given disease at any given moment in time, per population", not the _lifetime risk_, which is what the "1 in 5000" number is. For example, if the author is from the U.S. and the random people they've met in their life are also mostly in the U.S., then they would have to meet about a million people in order to expect to find one who was, at that moment, sick with prion disease. (And because prion sufferers often have such rapid decline, many of them basically can't be met in a non-medical context because they are hospital-ridden for much of the disease's course. Also, if someone is suffering from prion disease but mildly enough that you can meet them in a non-medical context, how would you even know you'd met a prion sufferer?). The author does not specify how social they are nor how old, but it seems likely to me that they've met less than a million people (and, if the author is young, probably the people they've met are disproportionately young, while prion sufferers are disproportionately old), so this observation does not seem surprising or alarming or incompatible with Minikel's numbers.
The third context mentioned is "I don’t think anyone in my extended family knows someone who died of a prion disease." This is indeed an appropriate context for the "lifetime risk" number of "1 in 5,000". But has the author's extended family known 5000 people who have died? The author does not say how big that extended family is, nor how old, but attending 5000 funerals (or rather, knowing the deceased well enough to know their cause of death) seems unlikely to me. So again this does not seem surprising or alarming or incompatible.
3. The text claims that "up to 1 in 2000 people in the UK have latent vCJD" and links to Gill 2013. This is neither the link nor the summary that I would have used. Gill 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244468/ , incorporating later research, put the prevalence of Immunohistochemically-detectable abnormal PrP in preserved U.K. appendectomy samples at around 1:4200.
Is it fair to say that someone with abnormal PrP in the appendix has "latent vCJD" without citing evidence that such people are at increased risk of developing vCJD symptoms? (I'm not aware of any such evidence, but perhaps it is found somewhere in the citations of Gill 2020.)
(The later study also compared the prevalence of samples taken before, during, and after the known dietary exposure to BSE and found no statistical difference (despite being well-powered), concluding: "Either there is a low background prevalence of abnormal PrP in human lymphoid tissues that may not progress to vCJD. Alternatively, all positive specimens are attributable to BSE exposure, a finding that would necessitate human exposure having begun in the late 1970s and continuing through the late 1990s.")
My favorite so far. I don't have personal experience with any of the subject matter, except the deer. In New York state, it is illegal to feed deer. I don't mean just in the baiting them into a shooting range kind of way; a restaurant whose main attraction was watching deer out the windows was just levied a massive fine for deer feeding. The NYS DEC is concerned about chronic wasting disease, one of the prion relatives of mad cow and scrapie. I know there are clubs and organizations that are still feeding deer, hoping they won't get caught due to their remote locations. I'm not sure how much CWD actually impacts the deer population. In the Saint Lawrence River valley, where there are no predators and the winters are milder than in the Adirondacks, the deer population is massive. You can see hundreds of them driving through a few miles of farm country on the right day.
This was my favorite so far. It made me laugh, it made me cringe, it made me fear for my life. Also sold the book really well, which is criteria number one for ratng book reviews
I was kinda hoping to get an answer to "what the hell is a prion anyway?" though. A minor pet peeve is that named sections/better structuring would help it a lot
A prion is the level of disease below "virus". As is briefly passed over in the text, it is similar to a virus, but without the genetic material. Nothing but a protein.
But it's a protein that makes more copies of itself, presumably by bumping into other proteins and altering them.
"DTM refers to this as Quality Deer Management, but I think he’s wrong? QDM seems to be a particular attitude towards hunting that avoids shooting young bucks to optimize antler development, while shooting more doe than a pure “kill all the cool-looking ones” strategy will to avoid overpopulation. You can do QDM with or without supplemental feeding. I might be wrong – I know very little about deer hunting"
The problem here is QDM is essentially an umbrella term that covers a bunch of stuff, including supplemental feeding, appropriate trigger control (which might mean shooting lots of does and young bucks or not depending on the area and situation), food plots, baiting (where legal), out-of-season feeding (where legal), habitat restoration/reconstruction. Someone saying QDM tells you NOTHING about what they want to do, other than they'd probably like to see larger bucks (but might be doing stuff orthogonal or opposed to this goal (in other people's opinion).
There is an organization that used to go by the name of QDMA (Quality Deer Management Association) and now is called the Deer Management Association (the place with the link you provided). The problem is that everything in that article requires you to know the history of QDM practices and what they're arguing against to really understand anything they're talking about.
What that linked article is about is basically the deer hunting version of BigAg (Trophy Hunting) vs Permaculture (QDM), with the sides just about as fired up.
Why does the article talk about British teenagers dying from mad cow disease? Does the disease more affect teenagers than other ages, or were those just the cases the media focused on?
The average age was 28, so teenagers were common enough. I hadn’t realized Kuru also affected children until reading that in the review. Maybe there’s a similar mechanism.
I think it's just that teenagers don't usually die of *any* disease (if they die at all, it's usually from things like car accidents), so the sight of teenagers dying of a disease is shocking.
How would prions have made Pasteur's flask look like a failure? They wouldn't grow into anything visible and if consumed wouldn't make anyone ill until many years later....
I was thinking the same thing, though I wonder: if it was the right kind of prion, could it have formed amalgamations with the proteins in the broth? And if so, could that have created something visual to the eye, like threads or cloudiness? I don’t know enough to say.
Even calling a disease "non-prionic" is bizarre on the level of describing an animal as a "non-girrafe". Prions basically only exist as a very very particular glitch in a single protein found in some mammals, as far as we know.
"When we look at people – or deer, or sheep, etc – who are genetically resistant to prions (more on that later), we find that serious resistance can be conferred by single nucleic acid changes in the PrP gene. Tweak one single letter of DNA in the right place, and their PrP just doesn’t bend into the prion shape easily. If the infection takes, it proceeds slower – slow enough a person might die of old age before the prion would kill them."
So I wonder if the V/V thing might be real. In retrospect, it might make sense for single gene mutations to have an effect on a condition caused by very small changes in a single protein. The review suggested that people have since found cases without the gene, but maybe it changes likelihood without being a sure thing?
Eukaryote also says:
"At first glance, and to a first approximation, I think everyone living in the UK for a while between 1985 and 1996 or so (who ate beef sometimes) must have eaten beef from an infected animal. That’s approximately who the recently-overturned blood donation ban in the US affected. I had thought that was sort of an average over who was at risk of exposure – but no, that basically encompassed everyone who was exposed. Exposure rarely leads to infection. "
...which makes me better understand why the author of the review was so scared. We came within a few nucleic acids of approximately the whole population of Britain (minus the vegetarians?) dying horribly.
Possibly wasn’t known at the time, but prion diseases are very hard to spread.
Consensus at the moment is that you can’t get them from eating an animal or person infected with it unless you eat their brain - and even then there is probably a low penetrance. (After all, it has to get from your gut to your brain, and proteins are all digested in the gut.)
I did a lumbar puncture once on someone suspected of having prion disease and was surprised to learn there were no additional precautions for discarding the gown and gloves I used during the procedure.
The main concern is actual brain tissue. And it’s difficult to wash prions off because they are proteins that don’t respond to antiseptics. Neurosurgeons throw away their tools between every procedure.
So is the 1 in 2000 latent vCJD figure an aberration, did lots of people in the UK eat offal pre-1996, or do you regard this prevalence as evidence for "very hard to spread"? To me it seems quite high and evidence for "hard to spread" but not "very hard".
OK, makes sense. You are saying the risk per exposure is very low. This is so even if one accepts the 1 in 2000 lifetime incidence number, which should perhaps really be 1 in 4000+ according to other comments, and also seems only somewhat predictive of developing symptoms of disease.
Hm. One of my old zoology professors at university, now retired, once told me that at the height of the Mad Cow he considered writing an althist book in which prions had a much longer latency, much higher infectivity, and 100% lethality, so that a few years later the world was populated only by Hindus and vegetarians.
The vision in my head is like neutrons smashing into each other, possibly setting off a chain reaction, but only under the right circumstances and slowing as the marginal energy required to continue is too great. I don’t think this is a perfect description because of the chance of those nucleic acid but it calibrates my terror at the whole thing. It really is hard to spread or else it would show up everywhere (and I reserve some confidence that fighting aging will have to contend with prion diseases at some point).
For one, the spread of prion diseases is another mysterious gut-brain interaction that keeps popping up e.g. GLP-1s where nobody seems to really know what’s going on but insists it’s good. (GLP-1s definitely seem like a good bet compared to the known all-bad side effects of obesity, but it’s still a bet.)
Two, releasing experimental deer with prion disease into the wild seems like an environmental disaster. Here I was thinking that I couldn’t think less of the public health community and they found a way.
Three, I don’t get a sense that Eukaryote took that analysis very rigorously. Shades of Chernobyl’s “3.6 roentgen, not great, not terrible”. That is unfair considering the poster’s effort to summarize the issue, but it still felt like a strong conclusion from weak understanding of the evidence. I’d like to see a sensitivity analysis based on transmission rates because it seems like everyone is getting wildly different numbers, the Brits are not really testing, and it could be far more prevalent than we know.
Finally, given how resilient the disease is in deer and their massive position as a food source for wild animals, prions have a huge number of chances to crossover to other species. I wonder how close the PrP shape is on those other predators.
While this is much smaller than "chance of contracting a horrible and fatal disease just by eating your dinner", it also had a knock-on effect on cattle and beef exports from Ireland; confirmed cases of BSE turned up in the late 80s and this caused great consternation. The long incubation period meant that infected cattle might have gotten into the human food chain:
"BSE has a long incubation period. This means that it usually takes four to six years for cattle infected with BSE to show signs of the disease, such as disorientation, clumsiness and, occasionally, aggressive behaviour towards other animals and humans.
...The first case in Ireland was confirmed in 1989, when there were 15 cases confirmed. Most experts agree that BSE was most likely spread by cattle eating feed that contained contaminated Meat and Bone Meal (MBM). MBM is produced in a process called rendering. This is where otherwise unused animal products are taken from the carcass and are cooked for a long time to produce MBM. MBM was incorporated into cattle feed until it was banned in the 1990s."
I remember Gummer trying to shove a beefburger down his daughter's face at the time:
PrP-null mice have been bred. Debate exists on how their cognition differs from other mice, but it's a knockout that leaves a viable rodent. And the organism cannot propagate the prion disease if it does not make the protein that becomes the prion.
Very well done indeed! The witty and knowledgeable reviewer has the updated info to enhance the already fascinating - and often horrifying - accounts in the book, yet doesn't upstage them.
True story: I first learned about kuru and prions by hearing Carleton Gadjusek give a talk in 1989. Great speaker, compelling narrative.
I was a 10-year-old boy at the time, a precocious kid taking AP biology for fun and intellectual profit: I attended the talk as a class field trip. I remember asking a couple of questions, and knowing the intensity of curiosity I had then I am sure I would have wanted to stick around to ask more. Very glad, in retrospect, that I didn't!
Once there was an office worker whose monitor stopped working. To help diagnose, they had their colleague try hooking up their known-good monitor to the computer - still no luck, must be the machine. Then the colleague brought their monitor back to their desk, only to find it no longer worked! Oh no! They got another known-good monitor to see what was going on with their own machine, and now yet a third person had monitor problems. This went for another couple of iterations.
The DVI connector on the original monitor had gotten a pin bent in a particular way, that caused the receptor to also get bent, in a way *that would make it bend the pin on healthy cables in the same way*. You've heard of computer viruses, now get ready for computer prions!
While I enjoyed this review, I feel obligated to push back on the Maybe Prions Are About To Kill Your Grandmother hysteria.
Prions are fascinating because they challenge our notion of "life" and "infectious diseases." They are not a bacteria, not a virus, not a living thing in any way - just a protein that is misfolded that can cause other proteins to misfold in a similar way.
But they are extraordinarily rare. It is not a coincidence, at all, that Pasteur discovered germ theory some 150 years before Prusiner discovered prions. They account for a few hundred deaths per year. In comparison, sepsis (a life threatening bacterial infection) kills 11 million per year, and influenza kills tens of thousands.
This is partly because they are extremely difficult to spread. No one knows exactly how they are spread, because diseases caused by them are so rare, but the mad cow epidemic in the UK was probably caused by cows being ground up and fed to other cows, possibly including contaminated brain and neural material. Kuru, as the author notes, was also spread by cannibalism, in particular the habit of the inhabitants of Papua New Guinea to eat the brains of the deceased - once they stopped doing this, the disease stopped spreading.
Basically, avoid eating other people's brains, and you'll be OK. Use any other energy you got from reading this to start an exercise routine and eat more vegetables.
The author wonders if prions are more common than we give them credit for, which is possible, but it really beggars belief to think that they may be 20x more common - 1/5000 as opposed to 1 in a million? Highly implausible, I think myself and the reviewer agree on this, given the distinctive nature of the symptoms - neurologists would have noticed something by now. This figure cannot be credible.
The Alzheimer's connection is also extremely thin. Pituitary growth hormone treatment can spread them both - OK, pituitary growth hormone treatment also leads to a large nose, does that mean large noses are caused by prions?
More seriously, it is true that Alzheimer's (along with almost every other neurodegenerative disease - Parkinson's, Lewy body dementia, Huntington's, even the weird and wonderful ones like Friedrich's ataxia) are caused by an abnormal accumulation of proteins within neurons. It is also true that mice that have genetic defects in clearing damaged proteins from the cell cytoplasm all develop neurodegenerative disease at an abnormally young age. But the key difference is endogenous vs exogenous - we know what the misfolded protein is in all of these diseases (from the top: tau, alpha-synuclein, huntingtin, frataxin) and they are proteins that are normally expressed as part of neural physiology. These are not prions, these are us.
Why is the brain so vulnerable to protein accumulation and what can be done about it? That's the multi-billion dollar question - Alzheimer's has famously resisted almost all attempts at disease modifying drugs; we've invested decades of research and billions of dollars into finding a cure and have strikingly little to show for it. More power to Prusiner if he finds something down the prion line of research, but I'm not holding my breath, and plan to continue eating my vegetables.
I agree with most of what you said, but Minikel's linked post explains that the "1 in 5000" number refers to lifetime risk, while the "1 in a million" number is a reasonable estimate for either incidence or prevalence. They measure different things, and can both be true at the same time. (Also: 1:5000 is 200x 1:1million, not 20x, though that's not important because these numbers should not be compared to each other in the first place.)
I wonder if the disgust reaction to prions has variation on the left/right political axis? Haidt's moral foundation theory posits that left and libertarian people don't use the "purity" foundation directly, but a common criticism is that the purity taboos creep into politics and other realms of life.
I try to keep my views about politics (where I am just a guy with an opinion) separate from my medicine posts (where I do have some domain specific expertise.)
But since you mention it, there is research that purity rituals/cleanliness/disgust reflex is associated with right wing political views. For example if you expose people to priming stimuli that makes them think of germs (eg hand sanitizer) they’re more likely to express sympathy for right wing views on subsequent questionnaires.
Researchers have hypothesised that conservative political views evolve together with susceptibility to infectious diseases, which is why right wingers are more conspicuously concerned about illegal immigration and more likely to be puritanical about sex.
Who knows? Maybe the general drift leftward of Western society over the past 100 years is all downstream of the discovery of penicillin.
But this is particularly interesting when it comes to Covid, where the roles seem to be reversed and leftists are now more conspicuously concerned about masks and disease spread.
The right wing line on this is all a backlash to elite distrust. And granted, opposing mandates and lockdowns certainly fits in with traditional right wing emphasis on freedom.
But this is where I diverge from a lot of right wingers. If the elites tell you it’s raining, even if we accept they have lied in the past, that doesn’t make it sunny.
So with vaccines. It used to be, vaccine refusers were overwhelmingly from the left. The whole MMR vaccine-autism “link” took decades to die down and thousands of hipster children tragically died from measles in that time. It’s a shame (in my opinion) that right wingers are now buying into this. Vaccines work guys, it’s the lockdowns that suck and violate freedom and are authoritarian. We should all have been lining up to get vaccinated at the earliest possible opportunity, and then lockdowns should have ended immediately.
Of course I doubt if I can convince anyone in this tiny corner of the Internet - even Trump couldn’t convince his followers to get vaccinated…
I'm pretty much in the same place as you regarding covid and the vaccines.
My criticism of the purity stuff is that I think the research was focused too narrowly - I suspect they had the ideas about immigration and sex, and picked questions that focus on them, and stopped there. (After reading the book, it turned out that the categories weren't distilled from factor analysis, but were picked through intuition, so they're less scientific than I'd hoped.) A lot of modern left-wing politics seems to me to be heavily purity-based. Cancelling, boycotting, elaborate verbal rituals, ever-increasing lists of forbidden words, and that's just the stuff that makes headlines. There's also a disgust reaction when it comes to anything that might smack of the other side, which I've seen in people's faces, but I obviously can't quantify that. But if you ask someone about dating a Trump supporter, it looks identical to the reaction to bad cheese. And then there's the non-political stuff, like covid paranoia (I have perfectly healthy friends who still mask everywhere) and the obsession with food purity and being "all-natural" and avoiding "chemicals" (just listen to commercials, you'd think they were Hitler talking about the Aryan race), and then there's this whole undercurrent in environmentalism that treats "nature" as some perfect unchanging thing that must be kept free of filthy human contamination.
Yeah I was going to say this as well. It’s really interesting how left and right come to be associated with different things over time. When I was a kid, the party that was ambivalent about free speech was the right - particularly the conservative Christian fundamentalists who would say things like “don’t argue with the Devil, he’s better at it that you.”
Now the judging opposing views rather than engaging is, well, both sides to some extent, but IMO much more on the left.
And disgust - I think disgust towards fellow humans is a really dangerous emotion. It’s historically been the precursor to the worst atrocities in history. After all fascism is an ideology primarily motivated by disgust - as in Hitler’s comparison of Jews to rats and cockroaches.
I read this book a few years back because I work in an associated field and prions have always creeped me out beyond belief. Was an incredibly nice read!
Well, that explains why Hanya Yanagihara's "The people in the trees" didn't work for me as magical realism/sci-fi - turns out that the thin veneer of fiction she put over the true story wasn't enough to make the pure weirdness of real life feel believable. It's a bit like green I guess. The greens found in nature, if painted exactly as they are, appear garish and unreal. To make a painting appear realistic you have to dull all the greens a shade or two because our brains are used to tuning them out
Excuse my ignorance, and please someone more knowledgeable correct me if I'm just misunderstanding genetics.
Isn't it incorrect to compare
1) variations within the prion gene with
2) the various dead-end candidate genes.
It's not like researchers found a dubious statistical connection between a random gene and prion disease. PRNP determines what version of the prion protein you have in your body (correct?) so it seems likely that some versions might be more or less likely to fold into the infectious version. (Perhaps they misfold at such a slow rate the disease never had much effect).
When at least 3 adults testify that their treatment as children by the alleged abuser was distressing then it seems weird to describe it as "copacetic".
I don't mean to apply that designation to anything that's described herein, it's more that I'm just irritated by the framing, which I perceive to be a house of cards of moral perscriptivism. True enough that it's not happy stories that make the headlines, generally.
In the North American vernacular, you're a pedophile if a person of age 17 years 11 months 364 days or less has ever given you positive corporeal feelings. But the important thing is not pedophile / hebephile / "normal", it's just to respect people's actual agency / consent and the particulars of particular situations, which means admitting for the possibility of good yeses in addition to thanks but nos.
I'm a bit confused about the number of prion diseases there apparently are. The fact that PrP^Sc (the infectious form) can trigger the formation of more PrP^Sc is basically just an unfortunate coincidence, right? It seems implausible that there would be multiple different mis-folded forms, each of which would be able to specifically create more of itself, but then doesn't that imply that all the prion diseases based on this same protein (which is nearly all known mammal prion diseases) are basically the same disease, with the only distinction being how it was acquired (so that at least kuru and vCJD, which are both transmitted by eating infected material, would be exactly the same)? In any case, there will be at most very few possible variants, so it's reassuring to know that these diseases have little to no ability to mutate to become more infectious or treatment-resistant (if treatments are invented) at least, unlike normal infectious diseases.
When reading more about prions on Wikipedia, I found the sentence "Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another." which also seems confusing. I don't see why human PrP^Sc would have a higher affinity for human PrP^Sc than for sheep or deer PrP^Sc, given that this affinity is not an evolutionary adaptation in the first place.
I had the same impression, that all prion diseases were basically the same, until I read this extract from Wikipedia posted in one of the comments here:
Prions are a type of intrinsically disordered protein, which continuously change their conformation unless they are bound to a specific partner such as another protein. With a prion, two protein chains are stabilized if one binds to another in the same conformation. The probability of this happening is low, but once it does, the combination of the two is very stable. Then more units can get added, making a sort of "fibril"
I think the pop-sci version of prions, something like the Ice-nine cascade from Cat's Cradle for protein conformations (which I what I had in mind), is misleading: intrinsically-disordered proteins are more complicated things.
I assume you mean the difference is that the monomer of PrP^Sc isn't actually stable in that form unless bound to more of itself? I get that, but it doesn't get around the objection that it'd be weird if there were multiple such forms. Each conformation being able to selectively bind more of itself just isn't chemically plausible without the molecule being specifically designed/selected for that. Even DNA doesn't have that high a replication fidelity without a lot of complicated proofreading machinery.
My intuition for prion-proteins and their conformation-space is admittedly weak, but the current model I have in mind (note that it's not based on much beyond that paragraph from Wikipedia I quoted ) addresses that objection.
I illustrate the different conformations with different ascii characters. Imagine there's a single chain that goes through a range of different monomeric forms, none of which last very long. So, say, it first looks like "&" and then like "6" and then like "R" etc., with none of these admitting stable dimeric forms. But if by happenstance (this is the single rare trigger) when looks like "}", it meets another monomer the same conformation, it forms "}}" which then can't untangle (on reasonable time-scales) because the conformation change of the two units needs to be concerted. So this "}}" sticks around forever, and so will eventually meet another protein in "}" state, forming "}}}" and so on.
In this view, "}}}}}}}}}}" isn't a particularly special form: things like "))))))))))" and "]]]]]]]]]]" work just as well. With this intuition, it isn't weird at all that for there to be many forms that can do this: one side looking like the negative of the other isn't unusual.
That doesn't feel intuitively plausible to me, although I'm having some degree of trouble explaining why. Part of it is that proteins are lumpy strings, and lumpy strings don't really lie flat against each other like that. Even laying sheets of thin fabric on top of one another will gradually lose detail the more layers you add, so it needs to be able to snap into distinct conformations, but the fact that it's intrinsically disordered kind of suggests it doesn't do that. Furthermore, the affinity of one conformation for another with a local change (say "]" and "⌋") would be nearly as great as the affinity of that conformation for itself. The shape would therefore not be preserved across many replications unless the shapes are highly distinct, which just gets back to it being a weird coincidence it has all those conformations. (If you're familiar with the Ising model from statistical mechanics, this relates to the fact that the one-dimensional Ising model has no phase transition.)
I managed to find a paper on the topic (https://www.nature.com/articles/s41467-022-30458-6), and it looks like the protein monomers in the prion form actually are flat, and there are multiple conformations, so I guess take my comments as expressions of confusion rather than actually claiming you're wrong.
I've thought about it a bit more, and I think the flat shape (which is not how I had been imagining it) does mostly explain the things I was confused about. If I'm now understanding it correctly, PrP is just an intrinsically disordered protein (so it doesn't have some other fixed conformation that would get in the way of it forming prions) that happens to contain several sections that are capable of binding to copies of themselves (mostly as beta-sheets). Pretty much any stable flat-ish configuration in which the relevant segments are all in the correct orientations is therefore relatively likely to work as a prion, and the possible configurations differ from each other in several places, giving a high specificity. Also, this explains why different species' prions are less likely to infect, since the slightly different proteins won't line up as well.
It claims there are only two known prions that affect humans: 1) kuru, which is very adapted for spreading in humans) and 2) mad cow disease/BSE/CJD, which is very adapted for spreading in cows but not great at spreading quickly in humans.
Other prions, such as scrapie and chronic wasting disease in deer and other mammals, do not have any known human disease cases.
That post also clarifies that all known animal prions are misfolds of just one protein group called PrP. PrP varieties are similar but not the same between mammalian species. (Claude adds that non-mammalian animals get prion diseases too, but we're not sure about plants.)
That partially answers one of my first thoughts, which was: there are tons of proteins that exist. Are there non-brain protein prions? Eating brains is rare, but muscles have lots of proteins and are commonly eaten. What if there's a muscle prion? The fact that the only known animal prions are related to PrP suggests probably not. I would guess this has more to do with muscle protein shapes being inconvenient than any sort of evolved immune strategy against prions.
Humans and cannibalism aside, lots of animals eat the brains of closely related species. Doesn't this seem risky? Are they just getting lucky? Or maybe those unknown prion diseases are so slow compared to other causes of animal death that nobody notices? Sounds like something Brian Tomasik would consider ineffective but ok.
This also makes me think about the efforts in recent years to solve protein folding questions with computer assistance. I'm sure there are beneficial uses for that, but could a bad actor now design new prions? Probably there are quicker and easier routes to go if you want to bioengineer a pandemic, but it might appeal to cartoon villains.
Given what I said above, you should probably not take me as a reliable source on this topic, but:
Prion folding seems like a kind of different question to protein folding, to the point where any aspiring supervillains would at least need to do a decent amount of independent research. In addition to the usual criteria of, I guess, thermodynamic stability and kinetic reachability of the conformation that determine how it folds upon emerging from the ribosome or chaperone, there's the specific sort of flat stacked structure that seems to be required for prions. This actually seems like it might be an easier problem than general protein folding, because the flatness condition makes the search space so much smaller.
Presumably there are many proteins which, even if there is some prionic form they could take theoretically, can't actually switch from their normal form to that because their normal form is sufficiently strongly bound that the barrier to the reaction would be too big.
This is a generalisation from a single example, but perhaps brains are more prone to prion issues because of the low cell turnover compared to most tissues? I would expect that if mammalian muscles had any proteins vulnerable to prion disease, those diseases would already exist. Sporadic Creutzfeldt–Jakob disease is rare, but not that rare.
I notice that the last two posts have heavily featured cannibalism. Is that now a thing? Will we be discussing the betting markets regarding 'allegations of cannibalism for presidential candidates' on Monday?
Also, I would argue that even without prion diseases, cannibalism in human societies is generally maladaptive from a physiological point of view in all but the most extreme circumstances. If you eat a different species, there is a good chance that whatever infectious agents it had at the time of death won't flourish in your body. If you eat a member of your own species, you will be susceptible to most of the diseases it has.
Compared to the amount of nutrients a human consumed in their life-time, the amount of digestible nutrients in that human at the point of their death is basically nil, so eating routinely eating your dead is not worth it, especially if they were also cannibals. Killing and eating people from other polities might be seem more sustainable, but in terms of risk per protein gained few other animals make as poor a prey as humans. Much more efficient to kill or enslave them and take their food sources.
(There are also indirect, cultural reasons. If the surrounding cultures have decided that cannibalism is way out of their overton window (as they have in contemporary Europe, for example), this will impose some serious drawbacks. While most cultures will tolerate the consumption of unclean animals or different attitudes towards cousin marriage or slavery in their neighbors, cannibalism is much less tolerated.)
While cannibalism will thus be selected against by the forces shaping cultural evolution, there is plenty of leeway for weird customs which are probably mildly harmful to survival. We still are born with an appendix, after all. So if a warrior eats the heart of another great warrior he defeated once or twice in his lifetime, the selection pressure might be very small.
Of course, this is not what the Fore did ([1], citing Lindenbaum 1979):
> When a body was considered for human consumption,
none of it was discarded except the bitter gall bladder. In the deceased’s old sugarcane
garden, maternal kin dismembered the corpse with a bamboo knife and stone axe. They first removed hands and feet, then cut open the arms and legs to strip the muscles. Opening the chest and belly, they avoided rupturing the gall bladder, whose bitter content would ruin the meat. After severing the head, they fractured the skull to remove the brain. Meat, viscera, and brain were all eaten. Marrow was sucked from cracked bones, and sometimes the pulverized bones themselves were cooked and eaten with green vegetables. In North Fore but not in them South, the corpse was buried for several days, then exhumed and eaten when the flesh had “ripened” and the maggots could be cooked as a separate delicacy.
How to put this delicately? The Fore were not dealt a slightly disadvantageous hand by cultural evolution, like an unfortunate jawline might be dealt by biological evolution. Instead, their culture is about as handicapped as a human with an odd number of chromosomes. Kuru was bad luck, but any number of infectious diseases would probably kill cultures which behaved like this. Bubonic plague, 1917 influenza, whatever.
But it is interesting to notice that a disgust reaction to rotting human corpses is not a human universal.
Also, there is a culture war aspect to cannibalism as well, as Lindenbaum writes in [2]:
> The notion that cannibalism as a social custom did not exist, however, was finding a receptive anthropological audience (Arens 1993). Although discredited today, the denial of cannibalism was kept alive during the 1980s and 1990s by a generational shift in the human sciences, glossed as postmodernism, which studied metaphor and representation, providing new life for the idea that cannibalism was nothing more than a colonizing trope and stratagem, a calumny used by colonizers to justify their predatory behavior.
> While most cultures will tolerate the consumption of unclean animals or different attitudes towards cousin marriage or slavery in their neighbors, cannibalism is much less tolerated.
Is that true? It was my understanding that Christians were commonly understood to be cannibals, because of their common religious practice of claiming to eat human flesh.
Now I was working so hard on not taking a cheap shot on Christianity, and here you come. For the record, I think that eating the divine parts of a god/human hybrid would probably not qualify as cannibalism.
So Wikipedia does not have an article called 'christian views on cannibalism' for some reason.
I tried to search for 'Mosaic law on cannibalism', and got [1], which confirms that there is no explicit statement against it, though the vibes where it is mentioned imply it is a terrible evil.
This was kind of surprising me. I would have thought that somewhere between 'don't worship idols', 'don't eat pigs' and 'stone to death men who have fucked with other men', there would be something about 'eating humans is bad'.
Still, I think the reason it is not mentioned is that cannibalism was already a non-issue when the laws were codified. (Of course, this is akin to reasoning 'the fact that we have not caught any Japanese spies means just proves how insidious they are'.)
In general, cultures with high population densities and a lot of pathogen exchange with a huge reservoir of people (such as the Fertile Crescent and the Mediterraneans) will likely develop norms against unrestricted cannibalism, because the ones who think it is a great idea to dismember and eat uncle Bob after he just died of the bubonic plague will not stick around.
I was more interested in the degree to which non-Christian states interacting with Christians (1) believed that the Christians were cannibals, and (2) tolerated them anyway. My impression was that enough of this went on to undermine the contention that cannibalism is so anathema that it's not even OK for your neighbors to do it.
But, I'm not well informed on this.
> Still, I think the reason it is not mentioned is that cannibalism was already a non-issue when the laws were codified. (Of course, this is akin to reasoning 'the fact that we have not caught any Japanese spies means just proves how insidious they are'.)
People can be fairly vehement about prohibiting things that nobody wanted to do anyway. If you eliminated all the laws against incest, you wouldn't see more incest.
I don't have a problem with the theory that "the reason [cannibalism] is not mentioned is that [it] was already a non-issue", but I don't think any grand theory can make such a statement; it would have to just be the way things happened to work out.
> I tried to search for 'Mosaic law on cannibalism', and got [1], which confirms that there is no explicit statement against it, though the vibes where it is mentioned imply it is a terrible evil.
That writeup bothers me, because every citation goes to a reference about parents eating their own children, or in one case children eating their own parents. I didn't investigate context at all and it's possible that this is just a dramatic way of referring to general cannibalism within a society. But if it literally refers to parents eating children or children eating parents, I don't think it's necessary to posit that cannibalism in general was viewed as evil in order to explain why that particular kind of cannibalism was.
To my understanding it serves an important role as a reservoir of healthy gut flora for recovery after severe diarrhea. That's less critical than it was historically, but arguably still a net benefit.
> The Fore were not dealt a slightly disadvantageous hand by cultural evolution, like an unfortunate jawline might be dealt by biological evolution.
Instead, they looked at the would around them, applied their rational minds, and picked up $100 bill that was lying on the floor because other cultures were so hidebound by tradition! It's perfect. All their correct reasoning couldn't have saved them from this one random piece of data that they had no way of learning.
Well, part of my point is that they were not picking up $100 bills, more like a few cents.
It is generally hard to know which parts of a culture represents Chesterton's fences which were learned the hard way, and which parts of a culture are just arbitrary noise.
While the British have strong norms against cannibalism in humans, they lacked such norms in their livestock. Or norms against eating sick animals.
$100 isn't a huge amount for me at the moment, but there were times when it was. I wonder how much an average human male could go for, if our meat were priced like pork?
That bit about the British response to mad cow was worse than I'd remembered. :-(
I used to work in a Wisconsin lab studying CWD. Interesting fact: we had a grad student who went out and scraped up roadkill to test it for CWD. As I recall, we found it spread to at least possums, skunks, and squirrels.
This piece would have benefited from defining "sporadic", which ordinarily means "periodic, but with an irregular period". As used here, it appears to mean "spontaneous".
Wikpedia's article on prions also describes them as potentially occurring "sporadically", where the word "sporadically" links to wiktionary. Wiktionary provides no gloss other than the one I give above (in wiktionary's words: "at an occasional, infrequent, or irregular frequency"), but if you take the initiative to look up "sporadic" rather than "sporadically", an obsolete sense of the word is noted: "(of diseases) occurring in isolated instances; not epidemic".
That still doesn't explain the usage here; in that sense, a disease that occurs "sporadically" would be so characterized because of the pattern of infection ("not very many people get infected"), not because of the manner of infection ("spontaneous generation within the patient").
Maybe I'm misinformed about this, but I thought the M/V polymorphism at PRNP position 129 *did* confer prion resistance, but it did not confer immunity. Is that not correct?
This paper even hypothesizes this is a balanced equilibrium:
"In 1862, Louis Pasteur boiled broth to kill the microscopic life in it, put some of the liquid in a goose-necked flask, and showed that if nothing living ever reached the liquid, no life would ever grow there. The experiment had enormous practical impact; it gave doctors the knowledge they still use to save lives by showing that because infections were living, reproducing things, if you could keep an environment sterile, you could keep a patient healthy. Had infectious prions been in Pasteur’s flask, curative medicine would never have gotten started. Doctors would still be competing with shamans and medicasters."
I do not understand how that makes sense, and think it does not.
A broth containing prions would be infectious, but still, no life would grow from it, because for life to grow, you would still need living things, like bacteria or fungi. The prions might change the shape of other proteins in the broth, but noone would notice.
If someone drank it, they might develop the disease, possibly years or decades later, but Pasteur would not have linked these events, and anyway, he didn't feed his pasteurized broth to people which then never got a disease.
Excellent review. Alternately chatty and punchy where appropriate, and designed to let the subject shine with its own light. Did not feel too long or too short, but instead seemed just right for the subject. It didn't try to wrap everything up with a bow, but pointed out lots of dangling ends that someone who's interest is piqued could follow on their own. Included some speculation at the end, but of a relatively restrained and grounded sort. I feel as though I know enough at the moment, but I also am left with the impression that if I did want to learn more, this book would be a great place to start.
The subject seems good too. Fascinating and creepy topic, with a complicated history and much less current scientific consensus than I'd assumed. I do get the impression that the book is less of a work of art on its own, and it's instead mostly a historical survey of the topic, much like how the review is a survey of the book, but that's OK if the topic is compelling enough? I'm less persuaded that I should read *this particular* book on the topic, as that I should read *a* book on the topic and this book would be a good one to start with.
Also, good follow-up. Especially for non-fiction, I want historical context and a sense of how the field has changed since the writing.
Great review for what's probably a great book! Very informative, very troubling conclusions, and my candidate for secret Scott review :)
> The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie? They didn’t eat the sheep, presumably.
My first guess is "eating excrement" (does scrapie get to excrement?).
I'm no anthropologist, and am generally sympathetic toward the benefits of "uncivilized" life, but my impression based on this review is that Papua New Guinea had a pretty hellish set of incentives and constraints under which to develop a culture.
"Kill all outsiders" seems like it was a common recipe for success, especially near the shore.
Perhaps the Fore had the different response of welcoming foreign influence not only because they hoped it would rid them of kuru, but also as part of a broader strategy of openness?
They apparently went from no cannibalism to inventing cannibalistic rites in a fairly short time. And the rites involved eating not only brains but also bodies that had been buried for days, and the maggots thereon. That seems like the sort of thing that would be selected against in most cultures.
It's harder to convince someone that doing disgusting, frequently tabooed stuff is a good idea or ritually necessary, if, when that person checks with their grandmother, she says "nah, in my day we didn't bother with any of that."
So I'm imagining the Fore as having a high bar for disgust and a cultural tendency toward trying wacky new things.
Maybe that came in handy having 850 neighboring groups around, because the Fore could adopt superior tools, tactics, etc. from anyone.
Maybe this “take chances, make mistakes, get messy” recipe fails 90% of the cultures that try it, but lets the remaining 10% be flexible enough to give them an edge, as early adopters of new technology or as the ones best positioned to quickly fill any new niche that opens in a crowded landscape.
That's my imagined version, anyway. If it's not literally true for the real Fore, it's still an interesting thought experiment.
My favorite so far. Well written, interesting exploration into a biology subject I'm not that familiar with. Great (and terrible) characters too!
Also my favorite so far.
This is definitely a "Mom, come pick me up, I'm scared" type of review. Great job!
This article: https://eukaryotewritesblog.com/2023/06/24/chronic-wasting-disease/ suggests it's not really as bad as you might (and I DID) think.
That article (and all the Wikipedia articles on TSEs) repeat the claim that certain alleles are protective against TSEs, bur the post above claims that's been debunked. I am confused.
Wikipedia claims that some genotypes are less susceptible than others. The debunked claim is that a specific genotype in humans is completely immune. The debunking is cited to an article saying that there are significant differences in disease progression between the different genotypes.
Makes sense, thanks!
this is pretty long and casual for a book review
I think the winning reviews are usually more accurately described as summaries.
I kind of assume the book reviews will imitate Scott's style and this is no exception.
Generally a good review, but IMO it would have benefited from giving more background information. Or at least answering, pretty early in the review, the question,
”What exactly is a prion, and why is it deadly?”
Like, you can eventually pick up from context that it is made of proteins, and that it affects the brain somehow, but I ended up having to pause mid review to google more information on prions. Even something as simple as:
“Normal prion protein is found on the surface of many cells. Prion diseases occur when this protein becomes abnormal and clumps in the brain. It then causes brain damage. This abnormal buildup of protein in the brain can lead to memory problems, personality changes, and trouble with movement.”*
Would have been helpful.
From context, it looks like the reviewer has a a medical background, so the source of the problem could be that they overestimate what average people know about prions (I had never heard of them before today,) and so does not give as much background as would be helpful.
Still a very interesting review, even before I knew what it was walking about.
*https://www.hopkinsmedicine.org/health/conditions-and-diseases/prion-diseases#:~:text=A%20prion%20is%20a%20type,humans%20by%20infected%20meat%20products.
Also, for those curious, Wikipedia has a pretty good description of why prions are deadly:
Prions are a type of intrinsically disordered protein, which continuously change their conformation unless they are bound to a specific partner such as another protein. With a prion, two protein chains are stabilized if one binds to another in the same conformation. The probability of this happening is low, but once it does, the combination of the two is very stable. Then more units can get added, making a sort of "fibril".[11] Prions form abnormal aggregates of proteins called amyloids, which accumulate in infected tissue and are associated with tissue damage and cell death.[12] Amyloids are also associated with several other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[13][14]
>the source of the problem could be that they overestimate what average people know about prions
Obligatory xkcd: https://xkcd.com/2501/
Yes, I had that XKCD in mind as well
:-)
I knew what prions were but had no clue how they related to FFI and also felt like that connection was just never explained.
Whenever I read about the Gajduseks of the world traveling to places where they can still get away with behavior considered abhorrent in the rest of the world, it always reminds me of this passage from Gravity's Rainbow:
>How provoking, to watch one's subject population dwindling like this, year after year. What’s a colony without its dusky natives? Where’s the fun if they’re all going to die off? Just a big hunk of desert, no more maids, no field-hands, no laborers for the construction or the mining—wait, wait, a minute there, yes it’s Karl Marx, that sly old racist skipping away with his teeth together and his eyebrows up trying to make believe it’s nothing but Cheap Labor and Overseas Markets. . . .Oh, no. Colonies are much, much more. Colonies are the outhouses of the European soul, where a fellow can let his pants down and relax, enjoy the smell of his own shit. Where can he fall on his slender prey roaring as loud as he feels like, and guzzle her blood with open joy. Eh? Where he can just wallow and rut and let himself go in the softness, a receptive darkness of limbs, of hair as wolly as the hair on his own forbidden genitals. Where the poppy, and cannabis, and coca grow full and green, and not to the colors and style of death, as to ergot and agaric, the blight and fungus native to Europe. Christian Europe was always death, Karl, death and repression. Out and down in the colonies, life can be indulged, life and sensuality in all its forms, with no harm done to the metropolis, nothing to soil those cathedrals, white marble statues, noble thoughts. . . .no word ever gets back. The silences down here are vast enough to absorb all behavior, no matter how dirty, how animal it gets.
Don't confuse modern fiction for historical reality. While sex tourism was occasionally a thing especially for pederasts like Gajdusek colonial white communities were very small, moralistic and tightly knit. Paris and London had far bigger and wilder sex scenes than some dusty colonial outpost.
>colonial white communities were very small, moralistic and tightly knit.
There is one odd corner case:
https://en.wikipedia.org/wiki/2004_Pitcairn_Islands_sexual_assault_trial
I know nothing of the geneology of the people involved - for all I know they could have moved there from Denmark or somewhere and adopted local names - but:
This *is* the island settled by Bounty mutineers who basically pulled another "Rape of the Sabine Women" to establish a breeding population? That stuff has to have a cultural impact, in so many ways.
>This is the island settled by Bounty mutineers who basically pulled another "Rape of the Sabine Women" to establish a breeding population? That stuff has to have a cultural impact, in so many ways.
Yup, Many Thanks! ( While I probably watched "Mutiny on the Bounty" decades ago, I don't remember anything from it, so don't have a side on _that_ part of the history. ) I presume that they would have been considered outlaws under British law due to the mutiny, so it is unsurprising for them to wind up with an outlier, corner case culture... If nothing else, I'd expect them to be less enthusiastic about the rule of law than typical Englishmen if said law would have hanged them...
I enjoyed this very much, prion diseases were definitely one of the topics that got me interested in Neuroscience back in the day.
Same for me! So creepy.
"Fatal familial insomnia is an autosomal dominant disorder. This implies that if the doctor had FFI, his sibling must have also had it". Uh, what? This is wrong on several levels. If the doctor had it, one of his parents must have had it (unless it was a de novo mutation!), which means that the sibling would be 50% likely to have it (assuming it's so rare that having two copies amongst the parents' 4 chromosomes is vanishingly rare).
But his sibling's child had it, which means his sibling must have too.
Agreed, good point! Perhaps the sentence should have read "This implies that if the doctor's nephew had FFI, then the doctor's sibling almost certainly also had it."
Great, now * I * can't sleep either.
Fun side note: the UK minister who tried to feed his daughter the beef burger was John Selwyn Gummer, who was later ennobled (apparently trying to cover up a dangerous disease isn't that bad, honest) as Lord Deben. Under this name he is very active in promoting policies relating to mitigating climate change; it appears he is not aware of how his presence causes people to question the validity of his case.
Great review.
I'd like to say I'm pretty sure poor sleep itself is a major causative factor.
I say this due to some personal experience, and encounters, as well as a few relayed anecdotes, and some more obvious Alzheimer's research.
Some critical energy intensive metabolic step gets jammed, the body demands energy, and if this state is induced chronically, prions and the like fail to get quarantined, or something.
That's the hypothesis at least.
Well, shit.
I liked it. Still, I wouldn't recommend it as reading material. It would be much better to have some actual descriptions for the diseases as diseases and not cases. How many people have FFI today? How many other pathologies are in this cluster? If there are (many and different) animal models for cancers, are such models possible for the prion diseases? There is no sense of scope to it.
"The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie?"
Wikipedia suggests the most likely transmission route for CWD is fecal-oral i.e. deer shit in the woods, other deer eat plants contaminated by that.
Deer have 3 specific behaviors that probably are highly involved in transmission in the wild (in addition to stuff like poop food):
1. Scrapes. Deer communicate, in part, via rubbing their pre-orbital scent glands on communal sticks along key travel corridors. Almost every deer that walks down a trail will hit up these sticks (often peeing underneath it as well). Of course CWD prevalence in this fluid is damn low, but OTOH it's a set of sticks that all does living in an area and many bucks that visit the area (during rut or otherwise) will rub their fluids all over/feed near it/lick it/lick the ground under it.
2. Autophagy: Deer eat fallen antlers off deer as rich sources of key nutrients.
3. Communal Eating. Does and the associated fawn groups are communal animals (fully matriarchal society, the boys are kicked out (depending on area) somewhere around 1.5 years old). These doe family groups often eat nose-to-nose, even when feeding in natural settings or ag lands. If you watch deer eat acorns or other hard mast crops you'll see how it's likely they're exchanging a good bit of salvia during the process.
The studies often focus on penned deer (lamp problem, we study what we can study) and it's a lot harder to track/study stuff like this in wild deer.
Is saliva a known transmission route for prions?
Yes, but with the caveat that it's a lot less effective than (say) eating ground up spines with spleens sprinkled over them. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446902/
It's very, very hard to figure out exactly how it's spread in the wild and many people disagree strongly on this. There's a lot of motivated reasoning as well b/c you have people very tied into specific theories. Also, the various state wildlife management agencies are (err) not particularly well trusted by many members of the public.
You could also (for Northern regions) add deer yards as 4th. Certain areas will vacuum in deer b/c of favorable winter foods/safety/shelter and from about the 45th parallel and up they pack themselves into these "yards" in the winter living much more closely than in the summer.
ETA:
Deer yard = Deer Wintering Complex https://www.michigan.gov/dnr/managing-resources/wildlife/deer/deer-wintering-complexes
No. You’re more likely to catch HIV by hugging someone. (Which is to say not at all.)
This has been low-key kicking around since at least the mid-00s, but it is a viable transmission pathway AND given deer-in-the-wild behavior (tons of transmission, tons of shared salvia) is probably at least a significant driver of wild CWD transmission.
https://russell-cwd.webhosting.cals.wisc.edu/foi/transmission-mechanisms/
https://www.cidrap.umn.edu/bse/chronic-wasting-disease-may-spread-saliva
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126547/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446902/
We've stomped out (most) baiting, cracked down on salt licks, and deer farms are better (while still being horrible). Yet, CWD continues to spread in the wild in areas following standard of practice (even without incredibly high deer density).
Hmmm, OK, I'm not a vet so I will defer to those who have studied the matter with deer - but there are no credible cases in humans certainly of prion diseases being spread via saliva.
This "book review" clearly isn't limited to the book, which is fine, but makes me feel like it's incomplete without including (at least) a mention of (at least) DTM's 2013 article about Minikel+Vallabh: https://www.newyorker.com/books/page-turner/a-prion-love-story
Thnx for sharing, what a beautiful story.
I liked this but had a weird feeling like it was from an alternate universe where prion diseases remained something most people thought about a lot. Like this review is written as if there was a covid-level prion disease, but I am not aware of anything more prominent than Mad Cow. Is there something I am missing about the world? Are there prominent conditions I'm not appreciating as prion diseases?
That was unclear. The reviewer may have meant Alzheimer’s, or an undetected scourge of prion diseases.
My understanding is that the author is saying that we could have rampant prion diseases right now and not be aware of it: prion diseases are hard to identify, take years or decades from infection to symptoms, and we’re not really looking for them anymore because nobody really worries about them anymore. That people could be dying of them all the time and we misdiagnose it as something else.
I mean, I think about it every time I see a deer that appears to be emaciated. Although more evidence than that is needed to determine if the deer has wasting disease--I'm just going by looks. But, going by looks, there sure are a lot of very thin deer around.
Overpopulation is also a big factor in deer being thin - all plants are not equal in nutritional value to deer, and if they get too overpopulated they'll just destroy all the local plant species they like. There's a wilderness preserve in Pennsylvania where deer hunting is forbidden and now it's so overpopulated literally nothing can grow except for invasive Japanese stiltgrass, which deer hate above all else. (They can't just un-forbid hunting, because the land was bequeathed by a rich person who hated hunting and wrote the ban into the contract.)
<sarcasm>Has anyone suggested reintroducing wolves?</sarcasm>
It does have a slight conflict with the "free-range kids" movement...
Rereading, it looks like their main worry is the "1 in 5000 deaths are due to prion disease" statistic, which is surprisingly high for a disease that "nobody gets."
However, that number is the *lifetime risk.* The article that statistic comes from is careful to point out that "everyone dies of something" - a very low incidence in the general population can lead to a high death rate if you roll the dice for a long enough time, and deaths from prion disease are concentrated among old people while the population is generally young.
So I think the correct interpretation of this figure would be something like "If you live long enough, and heart disease or cancer or pneumonia doesn't get you first, then eventually a misfolded protein will find its way into your brain and that will kill you." Important for researchers - it suggests that prion disease is responsible for a surprising number of "deaths from old age", and perhaps that our bodies have some way to fight prions which degrades with age - but you shouldn't be terrified that there's an invisible plague sweeping through the US.
I think they're worried because of the "1 in 5,000 people die of prion diseases" stat, which suggests that prion diseases are endemic in our population and more common than the "one in a million" quote we hear.
However, if you follow the link they provide to where that stat came from, they explain it and it's a little less scary. 1 in 5,000 is the *lifetime risk*, and prion diseases are concentrated in older people. Everyone dies of something, and if you keep rolling the dice all your life then you'll eventually land the one-in-a-million chance of a prion disease. (Or maybe these prions are everywhere and at some point your brain just stops being able to clean them up? Or maybe it takes decades for the prions to build up to cause a problem?)
On one level this is worrying - if you're worried about Alzheimer's, there are potentially a lot of "Alzheimer's-likes" floating around out there, mostly ignored and filed under "dying of old age." But you don't need to worry that there's an unseen mad cow pandemic sweeping the country, it's more like "if heart disease and cancer and pneumonia don't get you in your old age, eventually a misfolded protein will work it's way into your brain and that will *definitely* kill you."
> What am I missing?
I would like to engage with this question, but I'm honestly not sure where to even start. In case anyone else is also starting work on a detailed reply, maybe we could use this here comment as stub to start a subthread?
1. First, a meta point. I think there are some parts of the text that read, to me, as being misleading or confusing. I am tempted to think that the author themself may be confused about some things. However, I am very hesitant to impugn the author here in a forum where they cannot reply to defend themself while remaining anonymous. So I will attempt to focus only on the text and not on what the author may or may not have believed or intended while writing it. (But this will be hard and I will probably screw up, so I apologize in advance!)
The author could make a temporary anonymous account and reply this way. Several authors did this in previous years.
2. The text mentions Minikel's estimate of "1 in 5000 people dying of prion diseases", and then mentions several different contexts in which, the text seems to me to imply, this number seems surprisingly/alarmingly high. But that implication does not seem justified upon careful examination. Minikel's linked post explains some of the subtle differences of statistics involved. I highly recommend a careful read of that post to anyone confused by the text here.
The first context mentioned is "A genetic disorder that affects one in five thousand people is pretty common!". But the "1 in 5000" number is for all prion disease (genetic + infectious + sporadic), and, as Minikel's post explains, the _genetic_ prevalence is perhaps (very roughly) 10 times less.
The second context mentioned is "random people I’ve met in my life in a non-medical context". As Minikel's post explains, for this context it would be more appropriate to consider the _prevalence_, "the number of people sick with a given disease at any given moment in time, per population", not the _lifetime risk_, which is what the "1 in 5000" number is. For example, if the author is from the U.S. and the random people they've met in their life are also mostly in the U.S., then they would have to meet about a million people in order to expect to find one who was, at that moment, sick with prion disease. (And because prion sufferers often have such rapid decline, many of them basically can't be met in a non-medical context because they are hospital-ridden for much of the disease's course. Also, if someone is suffering from prion disease but mildly enough that you can meet them in a non-medical context, how would you even know you'd met a prion sufferer?). The author does not specify how social they are nor how old, but it seems likely to me that they've met less than a million people (and, if the author is young, probably the people they've met are disproportionately young, while prion sufferers are disproportionately old), so this observation does not seem surprising or alarming or incompatible with Minikel's numbers.
The third context mentioned is "I don’t think anyone in my extended family knows someone who died of a prion disease." This is indeed an appropriate context for the "lifetime risk" number of "1 in 5,000". But has the author's extended family known 5000 people who have died? The author does not say how big that extended family is, nor how old, but attending 5000 funerals (or rather, knowing the deceased well enough to know their cause of death) seems unlikely to me. So again this does not seem surprising or alarming or incompatible.
3. The text claims that "up to 1 in 2000 people in the UK have latent vCJD" and links to Gill 2013. This is neither the link nor the summary that I would have used. Gill 2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244468/ , incorporating later research, put the prevalence of Immunohistochemically-detectable abnormal PrP in preserved U.K. appendectomy samples at around 1:4200.
Is it fair to say that someone with abnormal PrP in the appendix has "latent vCJD" without citing evidence that such people are at increased risk of developing vCJD symptoms? (I'm not aware of any such evidence, but perhaps it is found somewhere in the citations of Gill 2020.)
(The later study also compared the prevalence of samples taken before, during, and after the known dietary exposure to BSE and found no statistical difference (despite being well-powered), concluding: "Either there is a low background prevalence of abnormal PrP in human lymphoid tissues that may not progress to vCJD. Alternatively, all positive specimens are attributable to BSE exposure, a finding that would necessitate human exposure having begun in the late 1970s and continuing through the late 1990s.")
My favorite so far. I don't have personal experience with any of the subject matter, except the deer. In New York state, it is illegal to feed deer. I don't mean just in the baiting them into a shooting range kind of way; a restaurant whose main attraction was watching deer out the windows was just levied a massive fine for deer feeding. The NYS DEC is concerned about chronic wasting disease, one of the prion relatives of mad cow and scrapie. I know there are clubs and organizations that are still feeding deer, hoping they won't get caught due to their remote locations. I'm not sure how much CWD actually impacts the deer population. In the Saint Lawrence River valley, where there are no predators and the winters are milder than in the Adirondacks, the deer population is massive. You can see hundreds of them driving through a few miles of farm country on the right day.
This was my favorite so far. It made me laugh, it made me cringe, it made me fear for my life. Also sold the book really well, which is criteria number one for ratng book reviews
I was kinda hoping to get an answer to "what the hell is a prion anyway?" though. A minor pet peeve is that named sections/better structuring would help it a lot
A prion is the level of disease below "virus". As is briefly passed over in the text, it is similar to a virus, but without the genetic material. Nothing but a protein.
But it's a protein that makes more copies of itself, presumably by bumping into other proteins and altering them.
I listened to a good series on BBC Sounds recently called The Cows Are Mad. This seems like a good follow-up book.
"DTM refers to this as Quality Deer Management, but I think he’s wrong? QDM seems to be a particular attitude towards hunting that avoids shooting young bucks to optimize antler development, while shooting more doe than a pure “kill all the cool-looking ones” strategy will to avoid overpopulation. You can do QDM with or without supplemental feeding. I might be wrong – I know very little about deer hunting"
The problem here is QDM is essentially an umbrella term that covers a bunch of stuff, including supplemental feeding, appropriate trigger control (which might mean shooting lots of does and young bucks or not depending on the area and situation), food plots, baiting (where legal), out-of-season feeding (where legal), habitat restoration/reconstruction. Someone saying QDM tells you NOTHING about what they want to do, other than they'd probably like to see larger bucks (but might be doing stuff orthogonal or opposed to this goal (in other people's opinion).
There is an organization that used to go by the name of QDMA (Quality Deer Management Association) and now is called the Deer Management Association (the place with the link you provided). The problem is that everything in that article requires you to know the history of QDM practices and what they're arguing against to really understand anything they're talking about.
What that linked article is about is basically the deer hunting version of BigAg (Trophy Hunting) vs Permaculture (QDM), with the sides just about as fired up.
Why does the article talk about British teenagers dying from mad cow disease? Does the disease more affect teenagers than other ages, or were those just the cases the media focused on?
The average age was 28, so teenagers were common enough. I hadn’t realized Kuru also affected children until reading that in the review. Maybe there’s a similar mechanism.
I think it's just that teenagers don't usually die of *any* disease (if they die at all, it's usually from things like car accidents), so the sight of teenagers dying of a disease is shocking.
It might be worth noting that the children Gajdusek was into specifically were boys, which might be related to why he was entrusted with children.
How would prions have made Pasteur's flask look like a failure? They wouldn't grow into anything visible and if consumed wouldn't make anyone ill until many years later....
I was thinking the same thing, though I wonder: if it was the right kind of prion, could it have formed amalgamations with the proteins in the broth? And if so, could that have created something visual to the eye, like threads or cloudiness? I don’t know enough to say.
Even calling a disease "non-prionic" is bizarre on the level of describing an animal as a "non-girrafe". Prions basically only exist as a very very particular glitch in a single protein found in some mammals, as far as we know.
Someone linked Eukaryote Writes' essay on CWD, which I also recommend: https://eukaryotewritesblog.com/2023/06/24/chronic-wasting-disease/ . It mentions:
"When we look at people – or deer, or sheep, etc – who are genetically resistant to prions (more on that later), we find that serious resistance can be conferred by single nucleic acid changes in the PrP gene. Tweak one single letter of DNA in the right place, and their PrP just doesn’t bend into the prion shape easily. If the infection takes, it proceeds slower – slow enough a person might die of old age before the prion would kill them."
So I wonder if the V/V thing might be real. In retrospect, it might make sense for single gene mutations to have an effect on a condition caused by very small changes in a single protein. The review suggested that people have since found cases without the gene, but maybe it changes likelihood without being a sure thing?
Eukaryote also says:
"At first glance, and to a first approximation, I think everyone living in the UK for a while between 1985 and 1996 or so (who ate beef sometimes) must have eaten beef from an infected animal. That’s approximately who the recently-overturned blood donation ban in the US affected. I had thought that was sort of an average over who was at risk of exposure – but no, that basically encompassed everyone who was exposed. Exposure rarely leads to infection. "
...which makes me better understand why the author of the review was so scared. We came within a few nucleic acids of approximately the whole population of Britain (minus the vegetarians?) dying horribly.
Possibly wasn’t known at the time, but prion diseases are very hard to spread.
Consensus at the moment is that you can’t get them from eating an animal or person infected with it unless you eat their brain - and even then there is probably a low penetrance. (After all, it has to get from your gut to your brain, and proteins are all digested in the gut.)
I did a lumbar puncture once on someone suspected of having prion disease and was surprised to learn there were no additional precautions for discarding the gown and gloves I used during the procedure.
The main concern is actual brain tissue. And it’s difficult to wash prions off because they are proteins that don’t respond to antiseptics. Neurosurgeons throw away their tools between every procedure.
So is the 1 in 2000 latent vCJD figure an aberration, did lots of people in the UK eat offal pre-1996, or do you regard this prevalence as evidence for "very hard to spread"? To me it seems quite high and evidence for "hard to spread" but not "very hard".
I don’t think it’s at all plausible that 1 in 2000 people in the UK will eventually develop vCJD. Where did this number come from??
And yes I would consider that “very hard” considering probably >90% of the UK population ate meat from an infected cow at some point
OK, makes sense. You are saying the risk per exposure is very low. This is so even if one accepts the 1 in 2000 lifetime incidence number, which should perhaps really be 1 in 4000+ according to other comments, and also seems only somewhat predictive of developing symptoms of disease.
Gets into the lymphatic tissue as well, which tends to be the problem with consumption.
...I want to read the alternate history where 21st-century Britain is majority Hindu. It sounds like a good companion piece to *The Peshawar Lancers*.
Hm. One of my old zoology professors at university, now retired, once told me that at the height of the Mad Cow he considered writing an althist book in which prions had a much longer latency, much higher infectivity, and 100% lethality, so that a few years later the world was populated only by Hindus and vegetarians.
Does milk still transmit mad cow?
The vision in my head is like neutrons smashing into each other, possibly setting off a chain reaction, but only under the right circumstances and slowing as the marginal energy required to continue is too great. I don’t think this is a perfect description because of the chance of those nucleic acid but it calibrates my terror at the whole thing. It really is hard to spread or else it would show up everywhere (and I reserve some confidence that fighting aging will have to contend with prion diseases at some point).
For one, the spread of prion diseases is another mysterious gut-brain interaction that keeps popping up e.g. GLP-1s where nobody seems to really know what’s going on but insists it’s good. (GLP-1s definitely seem like a good bet compared to the known all-bad side effects of obesity, but it’s still a bet.)
Two, releasing experimental deer with prion disease into the wild seems like an environmental disaster. Here I was thinking that I couldn’t think less of the public health community and they found a way.
Three, I don’t get a sense that Eukaryote took that analysis very rigorously. Shades of Chernobyl’s “3.6 roentgen, not great, not terrible”. That is unfair considering the poster’s effort to summarize the issue, but it still felt like a strong conclusion from weak understanding of the evidence. I’d like to see a sensitivity analysis based on transmission rates because it seems like everyone is getting wildly different numbers, the Brits are not really testing, and it could be far more prevalent than we know.
Finally, given how resilient the disease is in deer and their massive position as a food source for wild animals, prions have a huge number of chances to crossover to other species. I wonder how close the PrP shape is on those other predators.
While this is much smaller than "chance of contracting a horrible and fatal disease just by eating your dinner", it also had a knock-on effect on cattle and beef exports from Ireland; confirmed cases of BSE turned up in the late 80s and this caused great consternation. The long incubation period meant that infected cattle might have gotten into the human food chain:
https://www.fsai.ie/business-advice/running-a-food-business/food-safety-and-hygiene/microbiological-hazards/bse
"BSE has a long incubation period. This means that it usually takes four to six years for cattle infected with BSE to show signs of the disease, such as disorientation, clumsiness and, occasionally, aggressive behaviour towards other animals and humans.
...The first case in Ireland was confirmed in 1989, when there were 15 cases confirmed. Most experts agree that BSE was most likely spread by cattle eating feed that contained contaminated Meat and Bone Meal (MBM). MBM is produced in a process called rendering. This is where otherwise unused animal products are taken from the carcass and are cooked for a long time to produce MBM. MBM was incorporated into cattle feed until it was banned in the 1990s."
I remember Gummer trying to shove a beefburger down his daughter's face at the time:
http://news.bbc.co.uk/2/hi/uk_news/369625.stm
Great review! As an American, I think my favorite single line was:
>These deer were released into the wild.
Now _that_ sounds like a high-impact decision. OMG.
One other bizarre wrinkle. How's this for a brand name choice:
https://www.kurufootwear.com/
PrP-null mice have been bred. Debate exists on how their cognition differs from other mice, but it's a knockout that leaves a viable rodent. And the organism cannot propagate the prion disease if it does not make the protein that becomes the prion.
Have PrP-null sheep been tried?
In goats, not technically a knockout but functionally the same: https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-019-0731-2
And a naturally occurring premature stop found in goats: https://veterinaryresearch.biomedcentral.com/articles/10.1186/1297-9716-43-87
I'm not seeing any in sheep though.
Very well done indeed! The witty and knowledgeable reviewer has the updated info to enhance the already fascinating - and often horrifying - accounts in the book, yet doesn't upstage them.
This is the best one so far.
Putting "primitive society willingly gets colonized to cure a horrible disease" in the notes for my next science fiction story.
True story: I first learned about kuru and prions by hearing Carleton Gadjusek give a talk in 1989. Great speaker, compelling narrative.
I was a 10-year-old boy at the time, a precocious kid taking AP biology for fun and intellectual profit: I attended the talk as a class field trip. I remember asking a couple of questions, and knowing the intensity of curiosity I had then I am sure I would have wanted to stick around to ask more. Very glad, in retrospect, that I didn't!
Once there was an office worker whose monitor stopped working. To help diagnose, they had their colleague try hooking up their known-good monitor to the computer - still no luck, must be the machine. Then the colleague brought their monitor back to their desk, only to find it no longer worked! Oh no! They got another known-good monitor to see what was going on with their own machine, and now yet a third person had monitor problems. This went for another couple of iterations.
The DVI connector on the original monitor had gotten a pin bent in a particular way, that caused the receptor to also get bent, in a way *that would make it bend the pin on healthy cables in the same way*. You've heard of computer viruses, now get ready for computer prions!
Great story! I've passed that on to two of my friends. Which, of course, makes it a computer-prion-induced-meme...
While I enjoyed this review, I feel obligated to push back on the Maybe Prions Are About To Kill Your Grandmother hysteria.
Prions are fascinating because they challenge our notion of "life" and "infectious diseases." They are not a bacteria, not a virus, not a living thing in any way - just a protein that is misfolded that can cause other proteins to misfold in a similar way.
But they are extraordinarily rare. It is not a coincidence, at all, that Pasteur discovered germ theory some 150 years before Prusiner discovered prions. They account for a few hundred deaths per year. In comparison, sepsis (a life threatening bacterial infection) kills 11 million per year, and influenza kills tens of thousands.
This is partly because they are extremely difficult to spread. No one knows exactly how they are spread, because diseases caused by them are so rare, but the mad cow epidemic in the UK was probably caused by cows being ground up and fed to other cows, possibly including contaminated brain and neural material. Kuru, as the author notes, was also spread by cannibalism, in particular the habit of the inhabitants of Papua New Guinea to eat the brains of the deceased - once they stopped doing this, the disease stopped spreading.
Basically, avoid eating other people's brains, and you'll be OK. Use any other energy you got from reading this to start an exercise routine and eat more vegetables.
The author wonders if prions are more common than we give them credit for, which is possible, but it really beggars belief to think that they may be 20x more common - 1/5000 as opposed to 1 in a million? Highly implausible, I think myself and the reviewer agree on this, given the distinctive nature of the symptoms - neurologists would have noticed something by now. This figure cannot be credible.
The Alzheimer's connection is also extremely thin. Pituitary growth hormone treatment can spread them both - OK, pituitary growth hormone treatment also leads to a large nose, does that mean large noses are caused by prions?
More seriously, it is true that Alzheimer's (along with almost every other neurodegenerative disease - Parkinson's, Lewy body dementia, Huntington's, even the weird and wonderful ones like Friedrich's ataxia) are caused by an abnormal accumulation of proteins within neurons. It is also true that mice that have genetic defects in clearing damaged proteins from the cell cytoplasm all develop neurodegenerative disease at an abnormally young age. But the key difference is endogenous vs exogenous - we know what the misfolded protein is in all of these diseases (from the top: tau, alpha-synuclein, huntingtin, frataxin) and they are proteins that are normally expressed as part of neural physiology. These are not prions, these are us.
Why is the brain so vulnerable to protein accumulation and what can be done about it? That's the multi-billion dollar question - Alzheimer's has famously resisted almost all attempts at disease modifying drugs; we've invested decades of research and billions of dollars into finding a cure and have strikingly little to show for it. More power to Prusiner if he finds something down the prion line of research, but I'm not holding my breath, and plan to continue eating my vegetables.
I agree with most of what you said, but Minikel's linked post explains that the "1 in 5000" number refers to lifetime risk, while the "1 in a million" number is a reasonable estimate for either incidence or prevalence. They measure different things, and can both be true at the same time. (Also: 1:5000 is 200x 1:1million, not 20x, though that's not important because these numbers should not be compared to each other in the first place.)
I wonder if the disgust reaction to prions has variation on the left/right political axis? Haidt's moral foundation theory posits that left and libertarian people don't use the "purity" foundation directly, but a common criticism is that the purity taboos creep into politics and other realms of life.
I try to keep my views about politics (where I am just a guy with an opinion) separate from my medicine posts (where I do have some domain specific expertise.)
But since you mention it, there is research that purity rituals/cleanliness/disgust reflex is associated with right wing political views. For example if you expose people to priming stimuli that makes them think of germs (eg hand sanitizer) they’re more likely to express sympathy for right wing views on subsequent questionnaires.
Researchers have hypothesised that conservative political views evolve together with susceptibility to infectious diseases, which is why right wingers are more conspicuously concerned about illegal immigration and more likely to be puritanical about sex.
Who knows? Maybe the general drift leftward of Western society over the past 100 years is all downstream of the discovery of penicillin.
But this is particularly interesting when it comes to Covid, where the roles seem to be reversed and leftists are now more conspicuously concerned about masks and disease spread.
The right wing line on this is all a backlash to elite distrust. And granted, opposing mandates and lockdowns certainly fits in with traditional right wing emphasis on freedom.
But this is where I diverge from a lot of right wingers. If the elites tell you it’s raining, even if we accept they have lied in the past, that doesn’t make it sunny.
So with vaccines. It used to be, vaccine refusers were overwhelmingly from the left. The whole MMR vaccine-autism “link” took decades to die down and thousands of hipster children tragically died from measles in that time. It’s a shame (in my opinion) that right wingers are now buying into this. Vaccines work guys, it’s the lockdowns that suck and violate freedom and are authoritarian. We should all have been lining up to get vaccinated at the earliest possible opportunity, and then lockdowns should have ended immediately.
Of course I doubt if I can convince anyone in this tiny corner of the Internet - even Trump couldn’t convince his followers to get vaccinated…
I'm pretty much in the same place as you regarding covid and the vaccines.
My criticism of the purity stuff is that I think the research was focused too narrowly - I suspect they had the ideas about immigration and sex, and picked questions that focus on them, and stopped there. (After reading the book, it turned out that the categories weren't distilled from factor analysis, but were picked through intuition, so they're less scientific than I'd hoped.) A lot of modern left-wing politics seems to me to be heavily purity-based. Cancelling, boycotting, elaborate verbal rituals, ever-increasing lists of forbidden words, and that's just the stuff that makes headlines. There's also a disgust reaction when it comes to anything that might smack of the other side, which I've seen in people's faces, but I obviously can't quantify that. But if you ask someone about dating a Trump supporter, it looks identical to the reaction to bad cheese. And then there's the non-political stuff, like covid paranoia (I have perfectly healthy friends who still mask everywhere) and the obsession with food purity and being "all-natural" and avoiding "chemicals" (just listen to commercials, you'd think they were Hitler talking about the Aryan race), and then there's this whole undercurrent in environmentalism that treats "nature" as some perfect unchanging thing that must be kept free of filthy human contamination.
Yeah I was going to say this as well. It’s really interesting how left and right come to be associated with different things over time. When I was a kid, the party that was ambivalent about free speech was the right - particularly the conservative Christian fundamentalists who would say things like “don’t argue with the Devil, he’s better at it that you.”
Now the judging opposing views rather than engaging is, well, both sides to some extent, but IMO much more on the left.
And disgust - I think disgust towards fellow humans is a really dangerous emotion. It’s historically been the precursor to the worst atrocities in history. After all fascism is an ideology primarily motivated by disgust - as in Hitler’s comparison of Jews to rats and cockroaches.
I read this book a few years back because I work in an associated field and prions have always creeped me out beyond belief. Was an incredibly nice read!
“to straighten out Pauling’s ideas about proteins”.
Love it!
Well, that explains why Hanya Yanagihara's "The people in the trees" didn't work for me as magical realism/sci-fi - turns out that the thin veneer of fiction she put over the true story wasn't enough to make the pure weirdness of real life feel believable. It's a bit like green I guess. The greens found in nature, if painted exactly as they are, appear garish and unreal. To make a painting appear realistic you have to dull all the greens a shade or two because our brains are used to tuning them out
My takeaway is that I am never going to Britain
Sorry, didn't even finish reading this. Badly structured, unclear writing.
https://en.wikipedia.org/w/index.php?search=incategory%3A%22American_Nobel_laureates%22+incategory%3A%22American_people_convicted_of_child_sexual_abuse%22
Now I can't stop wondering how many other pairs of wikipedia categories have exactly 1 page in their intersection.
>Carleton Gajdusek is one of the characters who dominates The Family That Couldn’t Sleep. He couldn’t not.<
I'm absolutely reading this as "he couldn't not sleep." "You could put him in a car commercial and he'd be asleep before you left the driveway."
To battle this hereditary terminal insomnia, we've mobilized the world's most narcoleptic man.
Excuse my ignorance, and please someone more knowledgeable correct me if I'm just misunderstanding genetics.
Isn't it incorrect to compare
1) variations within the prion gene with
2) the various dead-end candidate genes.
It's not like researchers found a dubious statistical connection between a random gene and prion disease. PRNP determines what version of the prion protein you have in your body (correct?) so it seems likely that some versions might be more or less likely to fold into the infectious version. (Perhaps they misfold at such a slow rate the disease never had much effect).
Copacetic sexual activity, even if illegal, is only disingenuously rape.
When at least 3 adults testify that their treatment as children by the alleged abuser was distressing then it seems weird to describe it as "copacetic".
I don't mean to apply that designation to anything that's described herein, it's more that I'm just irritated by the framing, which I perceive to be a house of cards of moral perscriptivism. True enough that it's not happy stories that make the headlines, generally.
Yeah, and even the "pedophile" accusations strike me as dubious: I see no evidence that his sexual partners were prepubescent.
In the North American vernacular, you're a pedophile if a person of age 17 years 11 months 364 days or less has ever given you positive corporeal feelings. But the important thing is not pedophile / hebephile / "normal", it's just to respect people's actual agency / consent and the particulars of particular situations, which means admitting for the possibility of good yeses in addition to thanks but nos.
Indeed, the description would have been merely deliberately misleading if he'd not also explicitly called it a "paraphilia". It's pretty much the classic Onion "Naked Lady Fetish" (https://www.theonion.com/area-man-has-naked-lady-fetish-1819564926).
EDIT: Upon consideration, he was definitely a homosexual, so maybe it's a defensible description after all. I maintain that it's still misleading.
I'm a bit confused about the number of prion diseases there apparently are. The fact that PrP^Sc (the infectious form) can trigger the formation of more PrP^Sc is basically just an unfortunate coincidence, right? It seems implausible that there would be multiple different mis-folded forms, each of which would be able to specifically create more of itself, but then doesn't that imply that all the prion diseases based on this same protein (which is nearly all known mammal prion diseases) are basically the same disease, with the only distinction being how it was acquired (so that at least kuru and vCJD, which are both transmitted by eating infected material, would be exactly the same)? In any case, there will be at most very few possible variants, so it's reassuring to know that these diseases have little to no ability to mutate to become more infectious or treatment-resistant (if treatments are invented) at least, unlike normal infectious diseases.
When reading more about prions on Wikipedia, I found the sentence "Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another." which also seems confusing. I don't see why human PrP^Sc would have a higher affinity for human PrP^Sc than for sheep or deer PrP^Sc, given that this affinity is not an evolutionary adaptation in the first place.
I had the same impression, that all prion diseases were basically the same, until I read this extract from Wikipedia posted in one of the comments here:
Prions are a type of intrinsically disordered protein, which continuously change their conformation unless they are bound to a specific partner such as another protein. With a prion, two protein chains are stabilized if one binds to another in the same conformation. The probability of this happening is low, but once it does, the combination of the two is very stable. Then more units can get added, making a sort of "fibril"
I think the pop-sci version of prions, something like the Ice-nine cascade from Cat's Cradle for protein conformations (which I what I had in mind), is misleading: intrinsically-disordered proteins are more complicated things.
I assume you mean the difference is that the monomer of PrP^Sc isn't actually stable in that form unless bound to more of itself? I get that, but it doesn't get around the objection that it'd be weird if there were multiple such forms. Each conformation being able to selectively bind more of itself just isn't chemically plausible without the molecule being specifically designed/selected for that. Even DNA doesn't have that high a replication fidelity without a lot of complicated proofreading machinery.
My intuition for prion-proteins and their conformation-space is admittedly weak, but the current model I have in mind (note that it's not based on much beyond that paragraph from Wikipedia I quoted ) addresses that objection.
I illustrate the different conformations with different ascii characters. Imagine there's a single chain that goes through a range of different monomeric forms, none of which last very long. So, say, it first looks like "&" and then like "6" and then like "R" etc., with none of these admitting stable dimeric forms. But if by happenstance (this is the single rare trigger) when looks like "}", it meets another monomer the same conformation, it forms "}}" which then can't untangle (on reasonable time-scales) because the conformation change of the two units needs to be concerted. So this "}}" sticks around forever, and so will eventually meet another protein in "}" state, forming "}}}" and so on.
In this view, "}}}}}}}}}}" isn't a particularly special form: things like "))))))))))" and "]]]]]]]]]]" work just as well. With this intuition, it isn't weird at all that for there to be many forms that can do this: one side looking like the negative of the other isn't unusual.
That doesn't feel intuitively plausible to me, although I'm having some degree of trouble explaining why. Part of it is that proteins are lumpy strings, and lumpy strings don't really lie flat against each other like that. Even laying sheets of thin fabric on top of one another will gradually lose detail the more layers you add, so it needs to be able to snap into distinct conformations, but the fact that it's intrinsically disordered kind of suggests it doesn't do that. Furthermore, the affinity of one conformation for another with a local change (say "]" and "⌋") would be nearly as great as the affinity of that conformation for itself. The shape would therefore not be preserved across many replications unless the shapes are highly distinct, which just gets back to it being a weird coincidence it has all those conformations. (If you're familiar with the Ising model from statistical mechanics, this relates to the fact that the one-dimensional Ising model has no phase transition.)
I managed to find a paper on the topic (https://www.nature.com/articles/s41467-022-30458-6), and it looks like the protein monomers in the prion form actually are flat, and there are multiple conformations, so I guess take my comments as expressions of confusion rather than actually claiming you're wrong.
I've thought about it a bit more, and I think the flat shape (which is not how I had been imagining it) does mostly explain the things I was confused about. If I'm now understanding it correctly, PrP is just an intrinsically disordered protein (so it doesn't have some other fixed conformation that would get in the way of it forming prions) that happens to contain several sections that are capable of binding to copies of themselves (mostly as beta-sheets). Pretty much any stable flat-ish configuration in which the relevant segments are all in the correct orientations is therefore relatively likely to work as a prion, and the possible configurations differ from each other in several places, giving a high specificity. Also, this explains why different species' prions are less likely to infect, since the slightly different proteins won't line up as well.
I found it helpful to read this post, linked to from a different comment:
https://eukaryotewritesblog.com/2023/06/24/chronic-wasting-disease/
It claims there are only two known prions that affect humans: 1) kuru, which is very adapted for spreading in humans) and 2) mad cow disease/BSE/CJD, which is very adapted for spreading in cows but not great at spreading quickly in humans.
Other prions, such as scrapie and chronic wasting disease in deer and other mammals, do not have any known human disease cases.
That post also clarifies that all known animal prions are misfolds of just one protein group called PrP. PrP varieties are similar but not the same between mammalian species. (Claude adds that non-mammalian animals get prion diseases too, but we're not sure about plants.)
That partially answers one of my first thoughts, which was: there are tons of proteins that exist. Are there non-brain protein prions? Eating brains is rare, but muscles have lots of proteins and are commonly eaten. What if there's a muscle prion? The fact that the only known animal prions are related to PrP suggests probably not. I would guess this has more to do with muscle protein shapes being inconvenient than any sort of evolved immune strategy against prions.
Humans and cannibalism aside, lots of animals eat the brains of closely related species. Doesn't this seem risky? Are they just getting lucky? Or maybe those unknown prion diseases are so slow compared to other causes of animal death that nobody notices? Sounds like something Brian Tomasik would consider ineffective but ok.
This also makes me think about the efforts in recent years to solve protein folding questions with computer assistance. I'm sure there are beneficial uses for that, but could a bad actor now design new prions? Probably there are quicker and easier routes to go if you want to bioengineer a pandemic, but it might appeal to cartoon villains.
I guess that source's list of two known human prion diseases doesn't include FFI, though, oops.
Given what I said above, you should probably not take me as a reliable source on this topic, but:
Prion folding seems like a kind of different question to protein folding, to the point where any aspiring supervillains would at least need to do a decent amount of independent research. In addition to the usual criteria of, I guess, thermodynamic stability and kinetic reachability of the conformation that determine how it folds upon emerging from the ribosome or chaperone, there's the specific sort of flat stacked structure that seems to be required for prions. This actually seems like it might be an easier problem than general protein folding, because the flatness condition makes the search space so much smaller.
Presumably there are many proteins which, even if there is some prionic form they could take theoretically, can't actually switch from their normal form to that because their normal form is sufficiently strongly bound that the barrier to the reaction would be too big.
This is a generalisation from a single example, but perhaps brains are more prone to prion issues because of the low cell turnover compared to most tissues? I would expect that if mammalian muscles had any proteins vulnerable to prion disease, those diseases would already exist. Sporadic Creutzfeldt–Jakob disease is rare, but not that rare.
I notice that the last two posts have heavily featured cannibalism. Is that now a thing? Will we be discussing the betting markets regarding 'allegations of cannibalism for presidential candidates' on Monday?
Also, I would argue that even without prion diseases, cannibalism in human societies is generally maladaptive from a physiological point of view in all but the most extreme circumstances. If you eat a different species, there is a good chance that whatever infectious agents it had at the time of death won't flourish in your body. If you eat a member of your own species, you will be susceptible to most of the diseases it has.
Compared to the amount of nutrients a human consumed in their life-time, the amount of digestible nutrients in that human at the point of their death is basically nil, so eating routinely eating your dead is not worth it, especially if they were also cannibals. Killing and eating people from other polities might be seem more sustainable, but in terms of risk per protein gained few other animals make as poor a prey as humans. Much more efficient to kill or enslave them and take their food sources.
(There are also indirect, cultural reasons. If the surrounding cultures have decided that cannibalism is way out of their overton window (as they have in contemporary Europe, for example), this will impose some serious drawbacks. While most cultures will tolerate the consumption of unclean animals or different attitudes towards cousin marriage or slavery in their neighbors, cannibalism is much less tolerated.)
While cannibalism will thus be selected against by the forces shaping cultural evolution, there is plenty of leeway for weird customs which are probably mildly harmful to survival. We still are born with an appendix, after all. So if a warrior eats the heart of another great warrior he defeated once or twice in his lifetime, the selection pressure might be very small.
Of course, this is not what the Fore did ([1], citing Lindenbaum 1979):
> When a body was considered for human consumption,
none of it was discarded except the bitter gall bladder. In the deceased’s old sugarcane
garden, maternal kin dismembered the corpse with a bamboo knife and stone axe. They first removed hands and feet, then cut open the arms and legs to strip the muscles. Opening the chest and belly, they avoided rupturing the gall bladder, whose bitter content would ruin the meat. After severing the head, they fractured the skull to remove the brain. Meat, viscera, and brain were all eaten. Marrow was sucked from cracked bones, and sometimes the pulverized bones themselves were cooked and eaten with green vegetables. In North Fore but not in them South, the corpse was buried for several days, then exhumed and eaten when the flesh had “ripened” and the maggots could be cooked as a separate delicacy.
How to put this delicately? The Fore were not dealt a slightly disadvantageous hand by cultural evolution, like an unfortunate jawline might be dealt by biological evolution. Instead, their culture is about as handicapped as a human with an odd number of chromosomes. Kuru was bad luck, but any number of infectious diseases would probably kill cultures which behaved like this. Bubonic plague, 1917 influenza, whatever.
But it is interesting to notice that a disgust reaction to rotting human corpses is not a human universal.
Also, there is a culture war aspect to cannibalism as well, as Lindenbaum writes in [2]:
> The notion that cannibalism as a social custom did not exist, however, was finding a receptive anthropological audience (Arens 1993). Although discredited today, the denial of cannibalism was kept alive during the 1980s and 1990s by a generational shift in the human sciences, glossed as postmodernism, which studied metaphor and representation, providing new life for the idea that cannibalism was nothing more than a colonizing trope and stratagem, a calumny used by colonizers to justify their predatory behavior.
[1] https://hal.archives-ouvertes.fr/hal-00499057/file/PEER_stage2_10.1016%252Fj.exger.2008.05.010.pdf
[2] https://web.archive.org/web/20180915122011/http://www.medanthrotheory.org/read/5049/annotated-kuru
>especially if they were also cannibals.<
If you eat a person, you're eating every person that person's ever eaten.
Witness the analeptic alzabo in Gene Wolfe's Book of the New Sun.
> While most cultures will tolerate the consumption of unclean animals or different attitudes towards cousin marriage or slavery in their neighbors, cannibalism is much less tolerated.
Is that true? It was my understanding that Christians were commonly understood to be cannibals, because of their common religious practice of claiming to eat human flesh.
Now I was working so hard on not taking a cheap shot on Christianity, and here you come. For the record, I think that eating the divine parts of a god/human hybrid would probably not qualify as cannibalism.
So Wikipedia does not have an article called 'christian views on cannibalism' for some reason.
I tried to search for 'Mosaic law on cannibalism', and got [1], which confirms that there is no explicit statement against it, though the vibes where it is mentioned imply it is a terrible evil.
This was kind of surprising me. I would have thought that somewhere between 'don't worship idols', 'don't eat pigs' and 'stone to death men who have fucked with other men', there would be something about 'eating humans is bad'.
Still, I think the reason it is not mentioned is that cannibalism was already a non-issue when the laws were codified. (Of course, this is akin to reasoning 'the fact that we have not caught any Japanese spies means just proves how insidious they are'.)
In general, cultures with high population densities and a lot of pathogen exchange with a huge reservoir of people (such as the Fertile Crescent and the Mediterraneans) will likely develop norms against unrestricted cannibalism, because the ones who think it is a great idea to dismember and eat uncle Bob after he just died of the bubonic plague will not stick around.
[1]: https://www.gotquestions.org/cannibalism-Bible.html
I was more interested in the degree to which non-Christian states interacting with Christians (1) believed that the Christians were cannibals, and (2) tolerated them anyway. My impression was that enough of this went on to undermine the contention that cannibalism is so anathema that it's not even OK for your neighbors to do it.
But, I'm not well informed on this.
> Still, I think the reason it is not mentioned is that cannibalism was already a non-issue when the laws were codified. (Of course, this is akin to reasoning 'the fact that we have not caught any Japanese spies means just proves how insidious they are'.)
People can be fairly vehement about prohibiting things that nobody wanted to do anyway. If you eliminated all the laws against incest, you wouldn't see more incest.
I don't have a problem with the theory that "the reason [cannibalism] is not mentioned is that [it] was already a non-issue", but I don't think any grand theory can make such a statement; it would have to just be the way things happened to work out.
> I tried to search for 'Mosaic law on cannibalism', and got [1], which confirms that there is no explicit statement against it, though the vibes where it is mentioned imply it is a terrible evil.
That writeup bothers me, because every citation goes to a reference about parents eating their own children, or in one case children eating their own parents. I didn't investigate context at all and it's possible that this is just a dramatic way of referring to general cannibalism within a society. But if it literally refers to parents eating children or children eating parents, I don't think it's necessary to posit that cannibalism in general was viewed as evil in order to explain why that particular kind of cannibalism was.
> We still are born with an appendix, after all.
To my understanding it serves an important role as a reservoir of healthy gut flora for recovery after severe diarrhea. That's less critical than it was historically, but arguably still a net benefit.
Wikipedia writes:
> The appendix was once considered a vestigial organ, but this view has changed since the early 2000s.
It seems you are correct.
> The Fore were not dealt a slightly disadvantageous hand by cultural evolution, like an unfortunate jawline might be dealt by biological evolution.
Instead, they looked at the would around them, applied their rational minds, and picked up $100 bill that was lying on the floor because other cultures were so hidebound by tradition! It's perfect. All their correct reasoning couldn't have saved them from this one random piece of data that they had no way of learning.
Well, part of my point is that they were not picking up $100 bills, more like a few cents.
It is generally hard to know which parts of a culture represents Chesterton's fences which were learned the hard way, and which parts of a culture are just arbitrary noise.
While the British have strong norms against cannibalism in humans, they lacked such norms in their livestock. Or norms against eating sick animals.
$100 isn't a huge amount for me at the moment, but there were times when it was. I wonder how much an average human male could go for, if our meat were priced like pork?
That bit about the British response to mad cow was worse than I'd remembered. :-(
I used to work in a Wisconsin lab studying CWD. Interesting fact: we had a grad student who went out and scraped up roadkill to test it for CWD. As I recall, we found it spread to at least possums, skunks, and squirrels.
Will definitely add to my tbr.
This piece would have benefited from defining "sporadic", which ordinarily means "periodic, but with an irregular period". As used here, it appears to mean "spontaneous".
Wikpedia's article on prions also describes them as potentially occurring "sporadically", where the word "sporadically" links to wiktionary. Wiktionary provides no gloss other than the one I give above (in wiktionary's words: "at an occasional, infrequent, or irregular frequency"), but if you take the initiative to look up "sporadic" rather than "sporadically", an obsolete sense of the word is noted: "(of diseases) occurring in isolated instances; not epidemic".
That still doesn't explain the usage here; in that sense, a disease that occurs "sporadically" would be so characterized because of the pattern of infection ("not very many people get infected"), not because of the manner of infection ("spontaneous generation within the patient").
I am much more worried about prion diseases than AGI wiping out humanity right now
Maybe I'm misinformed about this, but I thought the M/V polymorphism at PRNP position 129 *did* confer prion resistance, but it did not confer immunity. Is that not correct?
This paper even hypothesizes this is a balanced equilibrium:
https://pubmed.ncbi.nlm.nih.gov/12690204/
"In 1862, Louis Pasteur boiled broth to kill the microscopic life in it, put some of the liquid in a goose-necked flask, and showed that if nothing living ever reached the liquid, no life would ever grow there. The experiment had enormous practical impact; it gave doctors the knowledge they still use to save lives by showing that because infections were living, reproducing things, if you could keep an environment sterile, you could keep a patient healthy. Had infectious prions been in Pasteur’s flask, curative medicine would never have gotten started. Doctors would still be competing with shamans and medicasters."
I do not understand how that makes sense, and think it does not.
A broth containing prions would be infectious, but still, no life would grow from it, because for life to grow, you would still need living things, like bacteria or fungi. The prions might change the shape of other proteins in the broth, but noone would notice.
If someone drank it, they might develop the disease, possibly years or decades later, but Pasteur would not have linked these events, and anyway, he didn't feed his pasteurized broth to people which then never got a disease.
So I do not think that is sound.
Excellent review. Alternately chatty and punchy where appropriate, and designed to let the subject shine with its own light. Did not feel too long or too short, but instead seemed just right for the subject. It didn't try to wrap everything up with a bow, but pointed out lots of dangling ends that someone who's interest is piqued could follow on their own. Included some speculation at the end, but of a relatively restrained and grounded sort. I feel as though I know enough at the moment, but I also am left with the impression that if I did want to learn more, this book would be a great place to start.
The subject seems good too. Fascinating and creepy topic, with a complicated history and much less current scientific consensus than I'd assumed. I do get the impression that the book is less of a work of art on its own, and it's instead mostly a historical survey of the topic, much like how the review is a survey of the book, but that's OK if the topic is compelling enough? I'm less persuaded that I should read *this particular* book on the topic, as that I should read *a* book on the topic and this book would be a good one to start with.
Also, good follow-up. Especially for non-fiction, I want historical context and a sense of how the field has changed since the writing.
Great review for what's probably a great book! Very informative, very troubling conclusions, and my candidate for secret Scott review :)
> The pen in which the deer were kept also housed sheep, which, it turned out, were scrapie carriers. The deer somehow acquired scrapie – there’s a huge unanswered question here, which DTM doesn’t address. How did they get scrapie? They didn’t eat the sheep, presumably.
My first guess is "eating excrement" (does scrapie get to excrement?).
I ingested bovine adrenal tissue for about a year, a decade ago, as part of an adrenal supplement. I wonder how much that multiplies my risk?
If I come down with CJD one of these years, I'll email Scott and offer to do an AMA or something.
I'm no anthropologist, and am generally sympathetic toward the benefits of "uncivilized" life, but my impression based on this review is that Papua New Guinea had a pretty hellish set of incentives and constraints under which to develop a culture.
"Kill all outsiders" seems like it was a common recipe for success, especially near the shore.
Perhaps the Fore had the different response of welcoming foreign influence not only because they hoped it would rid them of kuru, but also as part of a broader strategy of openness?
They apparently went from no cannibalism to inventing cannibalistic rites in a fairly short time. And the rites involved eating not only brains but also bodies that had been buried for days, and the maggots thereon. That seems like the sort of thing that would be selected against in most cultures.
It's harder to convince someone that doing disgusting, frequently tabooed stuff is a good idea or ritually necessary, if, when that person checks with their grandmother, she says "nah, in my day we didn't bother with any of that."
So I'm imagining the Fore as having a high bar for disgust and a cultural tendency toward trying wacky new things.
Maybe that came in handy having 850 neighboring groups around, because the Fore could adopt superior tools, tactics, etc. from anyone.
Maybe this “take chances, make mistakes, get messy” recipe fails 90% of the cultures that try it, but lets the remaining 10% be flexible enough to give them an edge, as early adopters of new technology or as the ones best positioned to quickly fill any new niche that opens in a crowded landscape.
That's my imagined version, anyway. If it's not literally true for the real Fore, it's still an interesting thought experiment.
In April of this year two hunters who ate deer meet infected with Chronic Wasting Disease also developed sporadic CJD. Spooky.
https://www.neurology.org/doi/10.1212/WNL.0000000000204407