Is there a disease that kills by preventing sleep?

with insomnia. That's oh, I thought it was because of the weather outside. Just a little play acting I got you to get us going. You know, it's weird. I got a little tired just studying this. Yeah, it's crazy. How suggestive How Stuff Works articles are. Well, yeah, not in that way, No, no, on that way. I mean, like, you know, suggestive in that way. Jerry did not get any sleep last night. We were talking about it before

we recorded. She got like a couple of hours, like one of those deals where you wake up and then you just stay awake for hours and hours. And I told her, I said, you may have been sleeping during some of that time, because you know, sometimes you'll be distressed about not sleeping, and you'd be like, man, I'm just awake, and then you wake up and you're like, was I just dreaming about being stressed about being awake? Yeah? Well, what's the answer, Jerry, she's tired. I'm going to answer

for I think you should. But um, yeah, I don't typically get insomnia, but sometimes I can psych myself out a little bit mentally with about of it. And that's when I'm laying there going like, oh man, not this. Oh yeah, once you start thinking about it, it is over. So that's that is what one might call typical standard insomnia. Yeah, that's not what this is about. No, no, Well we're talking about is a very very rare genetic disorder. Well

it's not even genetic disorder. It's a neurodegenerative disorder, I guess is what you call it. It's called fatal familial insomnia. Fatal. That should tell you all you need to know. This is insomnia that will kill you exactly like without know if sands are but you will die. And like I said, it's very very rare, Chuck. They think that possibly a hundred people since they started analyzing this or you noticed it. I think in the eighteenth century probably have died from

fatil familial insomnia. So it's a very rare disease. And but it's also you'll notice, familial. It's very frequently passed down along family lines, almost always, so they think tops forty families are touched by it. Yeah, and I already misspoke, which will correct later. But I said it's insomnia that will kill you, and that's not really a case. The insomnia is just a symptom of a larger problem in your that will kill you. Yes, but the insomnia does

not help. Sure, it makes everything worse. So Um, the history of this is a little murky, but they have traced it back to one of two people. One is a guy who they just referred to as patient zero, who possibly died in seventeen sixty five in Venice, Venice, Italy, that is uh. And the other one is a guy who died in eighteen thirty six, probably of fatal familial insomnia. Um,

also in Venice, Italy. What's going on over there, Well, there's probably maybe so tainted pasta sauce, who knows what what happened, But the whole thing, there are different ways that it could get started Um, but the these whoever the patient zero was, it's been passed down along their family. Those two families especially have did not farewell over the RS. It's very sad. It well, the diseases extremely sad. Yeah, And like I said, it's not you're not dying just

because you can't sleep night after night. Um, that is just a symptom. But what we're talking about in a larger sense is something called a preon disease. These are super rare and uh characteristic of a few things that they call it a sponge AFM disease, which means you're gonna get tiny little holes in your brain. You get a sponge sponge brain and uh there is uh neural loss. And one of the weird things is a failure to induce inflammatory response, Yeah, which I guess is that's the

body first saying, hey, something's wrong here. I'm gonna puff up. Whether it's an ankle sprain or you know, like a disease that will that will make something in flame. That's a sign of your body trying to fight something else. There's actually a lot of controversy about prion diseases because it doesn't make an any sense. It's an infectious agent, right,

But it's really just a misfolded protein. And it's really bizarre because with any other kind of infection, you have a viral infection, a bacterial infection, and a preon infection. Viral infections and bacterial infections have DNA or RNA. A protein again, is just a preon. It's just a misfolded protein, so it shouldn't be able to infect anything, but it does. So it's this crazy medical mystery that they're still trying

to get to the bottom of. But as they do, diseases like fatal familial insomnia or um uh crips Field Jacob's disease, which is like human mag cow disease. It's a spongefformed disease, spongebrain. It happens with animals and humans. I don't I think that's pretty important. So in in in many ways, it makes a lot of sense that you would be able to pass down this problematic um

it's an autosomal dominant neurodegenerative disease, fatal familial insomnia. It makes sense that it would pass down along family lines because there's a gene that UM in under normal circumstances, expresses a protein the pr PC protein, which is a normal protein. We don't know what it does, but we do know that it probably ei there has to do

with copper ion transport into the cell. It prevents cellular death until the time is right, or it helps create the sheets around your nerve endings so you're not in constant pain. They think it's one of those, right, But because it's the brain, there's still some mystery. And I don't even think it was like the midneties when they finally name this, right, Yeah, so it's pretty new on the scene as far as because it's so rare, right,

but not even just fatal familial insomnia. It wasn't until two thousand five that they the these res riachers at the University of Texas in Austin. Basically, ir irrefutally proved that preons misfolded proteins are an infectious agent. Even though we have no idea how this is happening, It's it's true. There's three ways of getting an infection in A misfolded protein is one of them. Yeah, like you said, they can occur in three ways. One is um acquired and

that means you have an infection. Well, in the case of kuru, which I guess we should talk about k you are you? That is when you get an infection because you ate someone's brain. Yeah, I think we talked

about that in the cannibalism episode, doesn't you. It seemed familiar in Papua New Guinea in the fifties, Like I guess a local I think British governor or agent started noting that there is this thing that the four A people who practiced funereal cannibalism that included the eatings of the deceased brain, um, would come down with the disease that they called kuru, which meant like trembling in fear right,

And they started investigating it a little more. And that's when we started to get the idea that there was such a thing as prion disease, that you could catch a preon uh well disease from eating brain. Yeah, and it would render them you know, they couldn't eventually walk or talk or eat. They would just lose all their motor function basically and waste away and die because they

can't swallow or chew or anything exactly. So um, that's when we first started really noticing in humans this whole idea of uh, spongebrain problems, and that's the acquired version. There's also one called sporadic which basically you just all of a sudden develop it was fatal familial insomnia, and they don't know where it comes from or how it's caused.

But doesn't it doesn't the fact that like one of those two, that there are those two different ways, and I know there's a third one, but don't they make you very suspicious of what the heck was going on in Venice in the late eighteenth century? Totally because they were both of those original patient zeros were unrelated, right yeah, because one was seventeen sixty five was six. But even still they if they were in the same family, they'd be like, well, these guys are in the same family,

so probably the one from earlier. From what I've read, they're not in the same family. They just happened to live in the same town. I think that is correct. So I wonder if people were eating some weird stuff there and one of them sporadically developed fatal familial insomnia. That's nutty. So there's a third way to right, yeah, inherited, which is for as far as fatal familial insnia it's

almost always inherited UH from from your family's genetics. Almost always, but not all prion diseases are, which is by the way, it's derived from the words protein and infection. Yeah, there's a guy in two who um coined the term UH and I ended up winning the Nobel Prize, and I think because of his early studies. Name was Stanley Pruss Prisoner. He won the Nobel in nine um And even after he won the Nobel, people are like, this is what you're talking about is impossible. There's no way a protein

can infect other proteins. But that's exactly what happens. So, like I said, there's a there's a normal protein, the pr PC protein, right, and then there's the sponge aformed version of it, the prp sc and that's after it's

been folded. Yes, that's the folded basically mutated version. So the whole thing comes down to what's called a polymorphism on a code on which is a sequence of nucleotides amino acids on your DNA right on a gene, and the specific code on these say three nucleotides say you got eyes, mean that we're going to code this protein

and under normal circumstances. On this gene, the pr PC protein is coded, but if you have a different nucleotide combination, you start coding the pr p SC protein and that's the misfolded one. Normal enough, right, Okay, Yes, we can code abnormally folding proteins. It's what cancers and all that stuff. The thing is, once the patient starts folding these proteins abnormally, those proteins go in and somehow infect the already properly

folded proteins that were expressed in the brain elsewhere before. Yeah, they bind to them, and they don't know how or why. Isn't that bizarre? Yeah, it's totally bizarre. And once that happens, you're in big trouble. You are in big trouble. And uh, we'll get into some of the symptoms and stages right after this message break. All right, So we are back with some symptoms and stages. And this is in general for all prion diseases. They're gonna share some symptoms, like

a handful of them. Um fatigue, it is one cognitive decline, like you're gonna lose some memory. You might develop dementia. Uh, rigidity with like movement and walking hallucinations. Um, but they don't all have the same symptoms. You might get some of these and not get others. Right. The hallmark of fatal familial insomnia is appropriately enough insomnia. Yeah, and that's

like when you start. One of the really sad things is once you start to notice that you're already although they can't cure it anyway, but um, sometimes it's nice to know these things early on, but once you start noticing insomnia, it's pretty far along. Yeah. And most people don't know that they have it early on because the mean age of onset is fifty years old, and it's kind of all over place, Like they have seen cases as early as nineteen. They've seen him come on as

late as seventy two. You're doing pretty good. But for the most part, it strikes you around late late forties, early fifties, and once it happens, you've got between one to maybe three years of basically a living hell before you die of this. Yeah it Um. There's generally four stages of f f i U, the first of which is gonna start with the insomnia, and over about four

months is gonna get worse and worse. But like I said, some people only notice it later on, UM, after other UH symptoms become known, you might start to have like panic attacks, phobia's paranoia. When you do manage to sleep, you supposedly have like super vivid dreams, which is interesting, but for the most part, you're having bouts of insomnia big time. Stage two it gets even worse. This stage lasts about five months on average or typically, which is to say it has in less than a hundred people

in the history of Earth. UM. But the the you enter this stage called sympathetic hyperactivity, which is where you're just keyed up all the time. UM. Do you remember we've talked about insomnia and sleep deprivation and a couple of podcasts before and how just totally unhealthy it is. One of the reasons it is so unhealthy is because your body enters a state of constant stress reaction. And

that's what UM sympathetic hyperactivity is. It's like, UM, your breathing is elevated, your heartbeat is elevated, your core body temperature is elevated. UM, you're just tuned up all the time and you're not getting the sleep to knock yourself

out of that state and to regroup and regenerate and rest. Yeah, and you're gonna at this stage you're gonna have um some memory loss, short term memory loss, mood changes, a lot of anxiety and depression, and you're gonna start to have some motor issues as well, like the way you move and the way you walk. So things are starting to get pretty bad at this point, and you're probably pretty freaked out, especially if this doesn't run in your family and you either acquired it or it's a sporadic case.

Well yeah, and you're not going to a doctor and they're going, hey, this sounds like ff I to me because I've never heard of it in my life exactly. Um, well that's not true. Doctors have heard of this, but you know what I mean, like two of them. Half. Yeah, it's not the first go to I think when you say I've been having trouble sleeping and I'm agitated, they're probably gonna ask, like, what kind of drugs you've been doing? Yeah, you know, like just lay off the pot. Well that

should make you sleep, though, right, I don't know. I guess it probably depends on what type of pot. I would think it's more I like lay off the speed. Oh yeah, you know, I probably should be gone there all right. Uh so the third stage is pretty short, it's about three months long, and that's when you're uh really delving into the hardcore. And so what's what's that in stage one? In stage two, appropriately enough, you're sleeping,

but you're only entering stage one. In stage two of sleep, which is stage one is considered um where you're just very relaxed. Stage two is where you're starting to sleep, but you can be woken up very easily, and you're not Yeah, and you're not going beyond that. You're not going into stage three or stage five, which is R A M. Sleep. They combine stage three and stage four apparently. But you're not getting to sleep. So by the third stage of fatal familiar insomnia, you're not even going to

one or two. You're just not sleeping at all. And it's been like this for um nine ten months already, so you're just basically losing it at this point. Yeah, and that will deliver you to the end stage stage four, and it's called end stage. You know where you're headed there, um serious decline in dementia, UM in brain activity. Maybe you've got about six months at that point, but you're going to lose the ability to speak and move. It's called a kinetic mutism and basically fall into a comma

and death. So with with a kinetic mutism, you actually have the ability to move and speak, but you lack the basic will to do so. Apparently, like patients who have come out of this have reported that will not necessarily f FI because it's always fatal in a hundred

percent of cases. Um, But people who have had a kinetic mutism for other reasons have said, like, like I knew I could, but in any time I got the will up to move, right, there was something else just counteracting that that was stronger, and I just couldn't move and couldn't talk. Yeah, and then like you said, you go from that into a coma right, and then death. Yes, and all prion diseases are fatal at this point and uncurable, correct I guess? So yeah, yeah, as far as they know. So, Chuck,

what's what's going on in the brain here? Uh? Well, basically your central nervous system is starting to break down. Um. The anterior ventral and medio dorsal thalamic neurons. So those are neurons in your thalamus that basically manage your motor functions, they start to die out, and instead of being replaced like your body likes to do when cells die out with healthy ones, they don't your glial cells, which when don't we talk about glial cells. We've talked about them

a few times. Yeah, we've in some brain wine before. They're basically the cleaning service for your central nervous system. Uh, and they help out with communication there they start to die and form scar tissue and the thalamus and once that happens, it's called gliosis. You've just got scar tissue instead of healthy cells exactly, pretty rapid decline from there.

It kills the communication between cells. Right. Yeah. So, um, with fatal familial insomnia like what just described as the result of any spongeform prion disease, right, which again, we're just tiny little holes in your brain. Right. So it seems like the distinction between the different spongeyform diseases is what part of the brain specifically they attack. Fatal familial insomnia they attack the thalamus, specifically the hypothalamus and specifically

the parts of the hypothalamus that help regulate sleep. Um, And there's this part of your hypothalamus that is an it has it creates what's what you could call an anti waking system, to where not only are the neurons shut off in one respect, in another, a bunch of neurons that are off while you're asleep are on and just keeping you asleep. So when you're waking normally, those

neurons are off, and when you're sleeping they're on. The problem is, if you have fatal familiar insomnia, Uh, the prions have eaten away at this system, and now all of a sudden that that anti waking system that keeps you asleep when you're asleep allows you to go to sleep, to transition from one stage of sleep to deeper stage of sleep is no longer active any longer. And so the only thing that is active is your wakefulness and

it is on all the time. So you know you're dying and there's this it's got to be some sort of madness from not being able to sleep. It just exacerbates everything, like that's just one of the symptoms. It is, and it is a symptom, but it's also uh, it's it's also directly related to the mechanism of this disease. Yeah, and it's got to speed up the process because your body is not getting the rest it needs exactly top

of everything else. And and that's the that's the devious part of the whole thing is not only is your body not getting the rest it needs, it's on all the time. So it's it's kind of like a doubly hardcore as far as diseases go. So, like we said, diagnosing it is tough a because it's so rare. Uh be the symptoms are, you know, they're always patient reported. So like I said, a doctor is not gonna like

look at this first thing. Uh, You're gonna go in with your family history and maybe get some blood test on UM, an I exam, a spinal tap. You might get an m R I or a pet scam or pet scam pet scan you've never believed in, or an e G which measures measures electrical activity in your brain. But um, it's really tough to diagnose. Well, yeah, and none of that is gonna work until you've already entered

that stage. Yeah, like you've already entered the first stage at least, because those those tests show, oh, yeah, you have insomnia. And then once they established yeah, you have insomnia, then they have to further establish that it's fatal familial insomnia. Yeah. And by this time, also, Chuck, it's say about fifty year about fifty years old, you've probably already had kids. And so now once you find out you have fatal familiar in samnia, you're also terrified that you've passed it

onto your children, you get about. Yeah, and since it's an autosomal dominant trait or disease condition, um, all you need is one parent with it to pass it on to you. Yeah. It's so sad. It's like, basically, what am I dying of? Because you can't fix me? And are my kids going to die this as well? And

then their kids? Very horrible disease. All Right, we're gonna get into I guess, finish up with a few a little information on a few more of these pre owned diseases, right for this break all right, before we get onto the other preonn diseases, we do need to talk about treatment. Like we've said over and over, sadly, there is no curative treatment, but there is palliative care, which basically means we're gonna try and help you out as much as

we can to be comfortable as you die. Uh. And weirdly one of the things that they are looking into and trying is giving patients g h by the club drug that you hear about to help people sleep, and they're actually prescribing that in some certain cases. Yeah, and they it apparently gives them quick, small, short bouts of sleep.

But that's I'm sure incredibly wonderful sleep. Nonetheless, yeah, it might decrease your heart rate and body temperature a little bit too, but um, at that point, you know, when you're taking g HB to get twenty minutes of sleep, you've got a pretty sad end coming very soon. It's very sad. The other great hope is gene therapy, where basically the delete the gene that's responsible for um making this protein misfold and insert the correct version of it.

That's got to be the future of these cures, don't you think. Yeah, that's gonna be the future of a lot of cures when we can just rewrite the code of our genes to you know, make it express properly. Yeah, But until then, there's gonna be some problems for people with spongeformed diseases because there's nothing you can do, including with fatal familial insomni you can give somebody g HP. That's about it. Should we go over a few more

of these? Yeah, they're all equally devastating. Um, I think you did mention c J D quitz felt jacob or yakup disease yaup. Maybe sure. Anytime I see j A k O B, I think of the like you know, German pronunciation. Yeah, it's probably right. This one's the most prevalent um and it is a spontaneous occurrence, which is really creepy. Well, you can get it too from eating it. Oh is that? I think ten perc and as spontaneous and the rest you get from eating it's acquired. Oh no,

it's just ten percent are inherited. Okay. So that's the one, if I'm not mistaken, that was directly related to the outbreak of mad cow. That's like human mad cow disease. Remember back in the nineties with the mad cow outbreak. Well, that all came from feeding a bunch of cattle a lot of ground up beef that included cattle brains that had pre on diseases in it, and so the cattle got mad cow disease, and from eating that cattle we

got kuuz felled yakub Okay, so that's the human version. Yes, and that's that kind of points out a huge problem with preon since they're not biological, not not living in the sense that we consider an effective agent typically like a bacteria or a virus. There's no genetic information to destroy, like using heat or bleach or whatever. It can't be killed as I saw it put somewhere else. It's the perfect pathogen. Yes, that's a mouthful. It is, but it's

also horribly scary. It is another spongeform diseases. Scrapy that just sounds good. Yeah, that is just in goats and cheap though, So humans don't need to worry about it. Um. And it is also genetic and they have no evidence right now that that humans can get it. No, we've got enough to worry about. We talked about mad cow that is officially called bob and spongebform uh encephalopathy. Nice, Is that right? I think so? Yeah, UM, deer and elk might get chronic wasting disease in the Western US.

If you see a deer that is um really skinny and drooling and can't swallow, um, they may have chronic wasting disease. I've seen that that humans can have that as well, But um, I don't know if it's the same version. No, it doesn't seem like it, because I think it's in patients that have like uh, that have died from AIDS. They'll often like waste away, like no amount of nutrients will like keep them from just losing weight until they basically just die from wasting away. But

I don't think it's related to a brain disease. And then chuck also going back to um c j D, which is what we call it now officially forever c j D. Ok Um. There was an outbreak of it in the eighties and no the nineties. These French doctors were using it in a growth hormone that they were giving as injections to kids who had stunted growth, and they were getting them from pituitary glands harvested from humans

and sold along the black market. So basically a bunch of dead people in Bulgaria had their pituitary glands removed and sold the doctors in France who were using them. Yeah, and these growth things or these growth hormone shots that they were giving kids, and like a sixty or eighty kids died the nineties. Yeah, yeah, it sounds like seventeen nineties.

So it's it's very weird because we go from not even recognizing diseases like fatal familial insomnia as a disease until the eighties, having an outbreak of mad cow disease, having an outbreak of c j D, all within a couple of decades, and all the while people are saying like, no, preons can't exist. What you're saying is is it can't be possible. And a lot of people tried to disprove preons by saying, Okay, there are different types of scrapey,

and say one hasn't a different incubation period. In this other one, you'll get this symptom, but you won't like the The sheep will talk, will speak Russian, but in this other form of scrapy they speak Swedish. And they're saying like, this proves that these preons have some sort of virus associated with them that we're just missing. Right, Another group or another argument against preons was well, Alzheimer's

disease is technically a sponge ofform disease. It's a misfolded proteins creating plaque build up scar tissue in the brain that leads to all these same symptoms as say C J. D. Right, it's not infectious. What's going on here? So they said that there is one way to prove this, and that is to create a pre on in a test tube completely from from the whole cloth and put it in

someone's brain and put in a healthy brain. And that's exactly what they did in two thousand and five at the University of Texas, and it infected the other proteins. That's right. So it's like, prions are this weird thing that we didn't know that is now infectious, was even possible, and we're finally wrapping our heads around it. Are spongy, whole filled heads. I think this has gotta be not this particular, but uh, this has gotta be what's gonna wipe out the human race one day. I don't know.

Bowl is making a pretty good case for itself lately. No, that's what I'm saying, Just some disease, Like, Uh, I don't think we're gonna blow ourselves up with or like run out of food or blow ourselves up with nuclear bombs. I think it's just gonna be another like weird plague or something that we don't understand due to our close association with live Stock, and it's not medtime soon. I don't know. Yeah, you're worried. I'm not worried. I'm just more,

you know, realistic. You give your safe room, you're building in the side of a mountain. No, that would indicate that I was worried. Okay, I'm building mine. You got anything, well? Can I come over? Good? Are you got anything else? No? Okay, Well, that's fatal familial insomnia and prions. If you want to learn more about those things, you can type those words into the search bar at how stuff works dot com.

And since I said that, it's time for a listener mail, and they call this Canadian email from a Canadian kid from Canadia. From Canadia, Hey guys, my name is Ben matt as him a seventeen year old Canadian A. He said that I didn't add that. Then that makes me think he's probably not Canadian. I've been well, he was in jest. I think I've been working my way through the backlog of episodes, and I recently listened to the

episode on serial Killers. And then he spoke of a man who killed by feeding his victims to pigs picked in huh, rob is that his name? Do you remember that because it sounds like pig pen. No, he's a pretty famous serial killer from Vancouver. This reminded me of a true story from my dad's childhood on a farm in Holland, Michigan. While he was growing up, he was often given the job of feeding pigs, a job he despised. Much of the stem back to a horrible accident that

happened to a nearby farmer. When this particular farmer was out in his barn feeding pigs, he had a heart attack and collapsed among them. When his family found him a few hours later, all that remained of his body were the palms of his hands and the soles of his feet. Hate those parts. This experience understandably and stilled fearing to my dad for many years to come. And to be honest, I don't blame him anyway. Thanks for you, guys, Thanks for all you do. A shout out would make

my day, maybe even my year. So been masked, shout out, shout out. Thanks for the email. Nice Thanks a lot. Ben. You haven't heard much about Robert Pickton. I don't think so. He was operating in like the nineties. I think and he was just like having prostitutes over and then he'd murder him and do horrible stuff like stuff like that. And he was supplying the public because you know, he had a pig farm. He's applying the public with pork.

And they think that he ground up people in it to the pork ate that and then people ate the pork. No no, no, like he ground up people and mixed it together with ground pork and then sold that at his ground pork. Oh wow, it was even worse. This is the nineteen nineties. He was a bad man. Where was he Vancouver? Jeez? I know, I thought those people are nice. Not Robert picked him. Man horrific. So if you like Ben masked shout out, I want to get in touch with Chucker me. You can tweet to us

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