This Podcast Will Kill You - Ep 17 Oh No Tetrodo: Crossover w/ TBOSP

Episode Date: January 8, 2019

Are you hungry for braaaaiiiinnnnssss? Or for fugu at the very least? We hope so, because this week we’re talking zombies and tetrodotoxin. In this crossover episode with Dr. Shane Campbell-Staton f...rom The Biology of Superheroes Podcast, we trace the origin of the modern pop culture zombie back to its Haitian roots. We explore the outrageous evolutionary arms races in which tetrodotoxin, the principal component of so-called ‘zombie powder’, has played a major part. And finally, we answer the age-old question: can a pufferfish make you into a zombie? Be sure to check out Part 1 of this crossover episode, Episode 7 of The Biology of Superheroes Podcast, where we discuss the biological basis of death, whether we’re prepared for a zombie outbreak, and behavior-manipulating parasites. You can follow Shane @superbiopodcast on Twitter. See omnystudio.com/listener for privacy information.

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Starting point is 00:01:54 And I'm Aaron Almond Updike. And this is This Podcast Will Kill You, Crossover Edition. with The Biology of Superheroes podcast. This is actually part two of a crossover in which we're going to talk about zombies. In the first episode, which was released on Halloween, we joined Shane Campbell-Staten and Aryan Darby of the Biology of Superheroes podcast to talk all things zombies. You guys should definitely go check out that episode. You can find it at the Biology of Superheroes podcast on whatever platform you listen to your podcast. podcasts. And this week, we're so excited to be joined by Shane to take a deeper dive into the
Starting point is 00:02:35 physiology, history, and evolutionary biology of zombies. Do you want to introduce yourself, Shane? Yeah, it's good to be here. I'm Shane Campbell-Staten, and I am an evolutionary biologist. Heck yes. Dr. Campbell-Staten. Please, please remember it. Also, the host of your own amazing podcast. Tell us about it. Yeah, we do our thing. So host of the biology of superheroes podcast. Yeah. So we use a lot of, you know, science fiction and use science fiction basically as a way to, you know, to talk about biology, evolution, physiology, so on and so forth. So merge in the nerd multiverse over here. I love it. Yes. And definitely everyone check it out. It's an amazing podcast. Yeah, it's fantastic.
Starting point is 00:03:44 It's really fun. We've been waiting to do this crossover since before we even started our podcast. Oh, yeah. It's been like on the books. It has been a long time coming, hasn't it? Yeah. Okay. So before we jump into that, we've got some important business to take care of.
Starting point is 00:04:06 Yeah, we do. Our quarantining. What are we drinking this week? This week we're drinking rum for your life. And it's called that because guess what it has in it. Rum. And more rum. It has so much rum.
Starting point is 00:04:26 And more rum. So we will post the entire recipe on all of our social media as well as our placebo Rita for this episode. Absolutely. You can find us at TPWKY on Twitter and this podcast will kill you on Instagram and Facebook. Let's get. We'll move on. Okay. All right. So today we are talking about zombies and basically sort of the biological basis for whether zombieification can happen via tetrototoxin. And then Shane is going to hit us with some expertise on the evolutionary history of detrototoxin. And I don't know anything about it yet. So I'm really excited because I think it's super cool.
Starting point is 00:05:32 Same. I know it's going to be super cool, I should say. We'll see how cool it is when I'm done. The coolest. Everyone's going to want to become a marine biologist after this episode. Yeah. I'm going to take you through the cultural history of the zombie, tracing the origins of the modern zombie back to its religious and spiritual roots. And we're going to have a blast because, as we talked about,
Starting point is 00:05:57 this is one of our favorite topics, all of us. Yeah. And first, I want to ask you something. have you, either of you, secretly ever wanted to be in a zombie apocalypse? To maybe see how you'd react or whether you'd be the first to die. I feel like this is a conversation that I used to have back in college. It's like one of those like 2 a.m. conversations. Man, what do you think you would be able to survive the zombie apocalypse?
Starting point is 00:06:30 Yeah, man. Yeah, I totally get a machete and this and that. and then I go up into the mountains and so on. And so, you know, meanwhile, you know, at that time, I had, like, barely, like, slept outside, you know, but it's, like, super confident that I'd be able to survive the zombie apocalypse. Yeah. Yeah.
Starting point is 00:06:48 I feel like it's, it's human nature to sort of think about these end of days scenarios. Yeah. Yeah. I think it's safe to say that we've all watched or read our fair share of zombie movies, shows, books, comics, et cetera, because we're nerds. Nerds. But I don't think zombies are necessarily nerdy, are they? Shane, you're the expert.
Starting point is 00:07:08 Yeah, I'm going to put them up as nerdy. They're pretty nerdy. Cool. Well, I like being a nerd anyway. Yeah, there's nothing wrong with that. I mean, you got to own the nerd. Yeah, exactly. So now that we are self-proclaimed zombie experts,
Starting point is 00:07:23 I want to ask you guys what you see as the unifying characteristics of zombies or zombies as they are presented today. Great question. Let's do a little list. I feel like they have to be after humans. So they've got to be like aggressive in some way. Oh, after. Okay.
Starting point is 00:07:44 Not like post-human. No, no, no. Coming after you for some reason. Okay. So driven by human flesh. Yes. Okay. Right.
Starting point is 00:07:55 Yeah, I think there's a typical sort of mangled appearance one way or the other, right? Either, you know, if you're talking about the actual walking dead or if you're talking about the actual walking dead or if you're talking about the infected. Yeah. You know, there are, you know, there's typically a, you know, very like run down, like, dirty clothes, bloody thing happening. They look unwel. Once you turn into a zombie, yeah, you start to, you know, you don't worry about taking a shower
Starting point is 00:08:19 and washing your clothes anymore. You're preoccupied by brains in general biting related activities. Yeah. Mm-hmm. And I do think the whole transmitted by bites thing, it's like, it's become pretty classic. Right. I'm not opposed to it. I'll say that much.
Starting point is 00:08:36 I'm not opposed to that idea. I mean, I haven't, I can't think of a modern zombie movie that doesn't have where a bite from a zombie turns you into a zombie. Yeah, I can't think of one either. Yeah, agreed. Yeah. So, okay. So we have that they're mangled, dead, undead, they eat human flesh.
Starting point is 00:08:56 That's the sole thing that they're driven by. Yeah. And they're infectious. Yeah. Or being a zombie is infectious. For sure. So this, the zombie that we just described is this modern zombie, which was born in 1968 when Night of the Living Dead was released, which is kind of funny actually, considering that the
Starting point is 00:09:16 word zombie is never used in the movie. Yeah. But that's so typical. And I feel like all zombie movies now do that because they did that. And it really bothers me. Like, in Walking Dead, why can't they just call them zombies? What do they call them? The walkers, the blah, blah, blah.
Starting point is 00:09:35 Walker or Biders, I think is a good one. I think it depends on the group. Like every sort of group that runs around has their own name for them. Which is so unrealistic, bro. Everyone knows it's a freaking zombie. Well, so I think in later movies, in between that time, they were called zombies and a lot of them. It's just a noise name. Well, it was actually, so George Romero only used the terms like ghouls or flesh eaters when he made this movie.
Starting point is 00:10:02 he didn't really encounter the term zombie until critics started using it when describing the film. So it was really only then when he was like, oh, these are, like, and he had taken clearly from zombie fictions. But I think it sort of he put two and two together after the fact. So he didn't know he was making the zombie movie until after it was already made? Well, no, I don't think that's necessarily true. I just don't know if he would have called them zombies or a brand new creature. because he did definitely take from zombie Fassinating.
Starting point is 00:10:34 Fills. Okay. So if you haven't seen the movie, which Aaron and I just watched it. Yesterday for research. The plot revolves around a group of people hiding out in a house somewhere in Pennsylvania as reanimated
Starting point is 00:10:49 corpses due to radiation accident swarm around the house. This movie effectively began or created an entire new subgenre of horror movie. Romero and his co-writer John Russo drew from a bunch of sources, as I mentioned, for inspiration, including a zombie called White Zombie, which I'll talk more about later, and I Am Legend, the book by Richard Matheson about a plague of vampires. But Night of the Living Dead was something really brand new in many ways. This was the first movie to depict zombies as flesh-eating, as outnumbering people, as not controlled by an outside force, as... as being contagious and a government struggling to maintain control.
Starting point is 00:11:34 This was a far cry from the early depictions of zombies in Hollywood movies. This movie, in many zombie movies that followed, used zombies as a metaphor for whatever was really threatening society or humanity, such as unchecked consumerism, the violence of Vietnam War, or the resistance against America, the threat of nuclear war, racial inequality, and so on. In modern zombie movies, zombies are used to expose the true nature of humanity. How are people going to react in a crisis?
Starting point is 00:12:04 And it's not just using zombies as this apocalyptic backdrop. The zombies themselves are scary because they occupy this uncanny valley where the familiar appearance of your neighbors or friends or spouse or child suddenly becomes horrifying when they're trying to eat your brains all of a sudden. Yeah. Then you have to shoot them in the head. Yeah. I feel it's a pretty common trope, right? There's always that moment where, you know, there's a zombie horde and they're trying to get away.
Starting point is 00:12:32 And then you see the face in the horde that's, you know, your best friend or, you know, the person who you used to love. And you're like, oh, but, but Susie, how could it be? And then Susie, like, chomps down on your jugular and then you're done. Yeah. So, and all of these characteristics of modern zombie movies have the end result of making you scared of zombies, not of becoming a zombie. So you're more scared of the zombies attacking you rather than of actually becoming one, I feel. Hmm. Interesting. So before Night of the Living Dead, though, the perception of zombies in Western culture was totally different.
Starting point is 00:13:10 The modern zombie actually has its roots in Haiti. And to understand how the Haitian zombie was warped and misappropriated into what we know as a zombie today, we have to go back a bit to the history of Haiti itself. Also, I just want to say that I'm totally out of my depth here. and I'm probably going to miss some stuff, but I'm going to do the best I can. So if there are any corrections, please send them our way as always. Yeah. Okay. At the beginning.
Starting point is 00:13:40 Christopher Columbus, great guy. Yay. Landed on the island of Hispaniola, which Haiti is the western third of Hispaniola, with the eastern two-third being the Dominican Republic. during his first trans-oceanic voyage in 1492. As you can imagine, he instantly claimed it for Spain. Set up camps there and introduced diseases that led to nearly the entire indigenous population of Taino and Arawak being wiped out. Check our smallpox episode three if you are interested in more.
Starting point is 00:14:13 Uh-huh. And with many of the rest of the indigenous population being enslaved. Over the next couple of centuries, French, English, and Dutch pirates set up base on the remote western and northern coast of Hispaniola, which grew as a trading hub throughout the 1600s, while Spanish control lessened. In the early 1700s, the French had taken control of the western part, which would later become Haiti. They ramped up export and production, and by the mid-1700, the small piece of land was responsible for producing 60% of the world's coffee. Whoa.
Starting point is 00:14:49 Yeah. And more sugar than all the British Caribbean peasant. possessions, quote unquote, combined. Whoa, dude. Yeah. I didn't know any of that. Can you guess how it got to be so productive? Slave labor. Mm-hmm.
Starting point is 00:15:04 Unbelievable amounts of slave labor. Yeah. Slaves on these plantations were treated so terribly and forced to live under such horrific conditions that at least 17,000 slaves died each year. Whoa. And the death rate outpassed the birth rate 8% to 1%. Oh, wow. Oh my God.
Starting point is 00:15:23 It's, yeah. Every year, the number of people enslaved and taken from Africa to work in the French colony increased, with around 40,000 slaves brought over every year in the years leading up to the Haitian Revolution. On the eve of the revolution, 32,000 white colonists ruled over nearly 500,000 slaves, the majority of which were born in Africa, like three quarters. Whoa, dude. So they killed off everyone. who lived there and then they just kept shipping over more human beings that they just murdered.
Starting point is 00:15:59 Well, 1791 comes around and this marks the start of a 12-year revolution that would lead to the formation of an independent Haiti, which was huge. This was the second oldest independent nation in the Western Hemisphere. Whoa. Yeah. Tell me the year again. 1791 marks the beginning of that revolution. Awesome. Thank you. So I talked a little bit. actually about the Haitian Revolution in our episode on Yellow Fever and the possible but debated role that the that yellow fever played in destroying French troops when trying to quash the rebellion. But so the takeaway from all of this is that the free country of Haiti was largely composed of people who were born in Africa and had fought very hard for their
Starting point is 00:16:43 freedom. In the decades leading up to the revolution, a religion had taken shape to unify everyone, which drew heavily from some religions in West Africa, including the Fon people living in the area we call Benin, the Yoruba people in Nigeria, and the Congo peoples in Angola and Basayr. And also, this religion incorporated elements of Catholicism and indigenous Taino beliefs and practices. Wow.
Starting point is 00:17:09 Yeah. So it was really kind of this very interesting mix. And after the revolution, the U.S. and Europe effectively cut contact with Haiti. They were like, nope, you're on your own, and they prevented trade from happening. And they also didn't allow any Catholic priests to go to the country, which the French had set up as a Catholic colony. So as a result, Haitian culture is really strongly influenced by traditions and practices directly from different African cultures without this sustained colonial presence quashing these influences the way some other Caribbean nations were.
Starting point is 00:17:46 Wow. Yeah. So this religion, or more accurately spiritual experience, continued to develop and is known as Vodoo to those outside of it. So if you are someone who practices Vodu, you don't call it Vodu. It's just your spiritual experience. It's serving the spirits. I'm not going to go into any real details of Vodu because there are many great resources for that, me not being one of them. But I will say that Vodu is this spiritual spiritual soul.
Starting point is 00:18:17 system focused on healing and spirituality. Zombies or zompification are not a part of voodoo as it is practiced. Rather, zombie making is considered a folk religious practice that derives from voodoo but isn't a part of it. Okay. So I just wanted to make that clear. So what is a zombie then in Haitian culture? Great question.
Starting point is 00:18:43 I love that asked and answered. Last and complimented. Great at self-compliments. Well, the word zombie probably came from the West African and Congo words, Nzabi, which is God or Spirit of a Dead person, and Zumbi, which means fetish. A zombie is created by a boko, which is basically a priest who practices sorcery. There are two types of zombies. One is a zombie astro, which is the soul of a deceased person, that the boko can,
Starting point is 00:19:16 used to enhance his powers. And the other is the one that we are more familiar with, the zombie of flesh. This corporeal zombie is one who has either been raised from the dead or is made to appear dead and then awakened or reanimated by a Boko. So this zombie of flesh has no will and is under complete control by the Bokor who uses the zombie to do his bidding, which often involves laboring in some way. And so the threat of Haitian zambification is different than this. modern zombification as in the movies.
Starting point is 00:19:51 The loss of autonomy, being forced to work against your will, loss of contact with family and loved ones. These are the consequences of becoming a Haitian zombie, which makes sense for a country with such a horrific history of slavery. Yeah. In contrast with the modern zombie, becoming a Haitian zombie is scarier than the zombie itself. So you're more scared of becoming a zombie than you are of the zombie.
Starting point is 00:20:13 Right. That does make sense. Yeah. I now understand how, why you. made that distinction earlier because I was like, I don't want to become a zombie because then you die. But now it makes more sense. Okay, good. So how did the modern zombie evolve from this?
Starting point is 00:20:32 Well, in characteristic manifest destiny form, the U.S. invaded an occupied Haiti from 1915 to 1934. Classic. Uh-huh. During the occupation, a bunch of ethnographers and writers, including Zorniator, Neil Hurston, who wrote one of the first books on Vodoo and Haitian culture, came to Haiti and exported stories of zombies. Many were very sensationalized, which kind of gave rise to this, like, fear and otherness of Vodoo in U.S. culture and Western culture in general. One of these stories was by a man
Starting point is 00:21:09 named William Seabrook, who wrote a sensationalist book called The Magic Island. In one chapter, Seabrook described seeing a zombie master control. rolling a group of zombies to labor for free. This was turned into a movie called White Zombie, which has all kinds of racist and sexist, I guess not really undertones, like overtones. Overtones. Yeah, sorry.
Starting point is 00:21:34 So yeah, in white zombie, the zombies are catatonic and completely under control of the Bokor, and this was the prevailing image of zombies in Western culture until Romero changed the game with Night of the Living Dead. Interesting. We're still missing, though, a piece of the puzzle, which is the how of a zombie. So what is the medical basis for zom bification? Yeah, bro.
Starting point is 00:21:59 And I think it's also just in passing we're thinking about why researchers, and I'm including us in this, feel the need to demystify some cultural or spiritual practices to reduce them to compounds or chemicals or, oh, well, this happens. this is how it can happen in reality. You know, and that's just something to kind of, I wanted to just say to think about. Because it was kind of, after reading Wade Davis's books, I was like, why are you, why? Why? Yeah, no, it's a good question.
Starting point is 00:22:29 Okay, so that aside, in general, back to zombies, there are two basic ideas as to how zombies are created. Okay, give them to me. Okay. One basically says, this is Haitian zombies. One basically says that zombies are created, through spiritual belief, and that often so-called zombies are cases of mental illness and deprivation. The other focuses more on the medical basis of zomification.
Starting point is 00:22:58 Belonging to the second category is Wade Davis. As a grad student, Wade Davis went down to Haiti in the 1980s, seeking to uncover the truth about zombieification, in particular whether it exists at all, and whether there was a plant or animal-based compound that can actually cause a zombie-like state in people. In his journeys, he came across the story of a man whose name I will definitely mess up the pronunciation of Clairvius Narcissus. I don't know.
Starting point is 00:23:28 You tried. Who had emerged after years, 16 years, actually, of allegedly being kept in a zombie-like state and forced to work. And he had been confirmed to have died and been buried. So this was like 1962, I think, is when he was buried. Okay.
Starting point is 00:23:49 And then only to emerge 16 years later. Wait, he died and was buried in 16 years later he came up? No, 16 years later, he sort of reemerged into society. Got it. Okay. He wasn't buried for 16 years. No, no, no, no. Because I would call BS on that.
Starting point is 00:24:07 Well. Anyway, so Davis sought to find out how this could have happened and he was able to gain access to various, quote, zombie powders and to observe their preparation. The contents of these powders varied region by region, but he found that a few ingredients were always present. Among them, human remains, cane toad, the hyla tree frog, and various species of pufferfish. Pufferfish, you say. In examining each of these, he found one likely candidate for making someone appear dead, the pufferfish, which contains a compound known as tootox. Do do, do.
Starting point is 00:24:45 Davis alleged that this toxin, when given to the intended zombie, could imitate death so that the person could be buried and then dug up and held under control by the use of other compounds, including the deterra plant. Aaron, please tell us how to trototoxin works and whether it is the true zombie powder. I love to. I'm excited for this part because I avoided it and I was like. Oh, great. Yeah. Then let me tell you about it. Tetrototoxin. Okay, the thing is, as I started researching this, I was like, we already did this.
Starting point is 00:25:39 We've already done this episode. It's called crossover with Matt Caneus. Yes, so you didn't. You already knew the answer. Yes. If you haven't yet listened to our crossover episode with Matt Candace of In Defensive Plants where we discuss Monkshood, aka Wolfsbane, then go listen to the that you'll probably like it because we're talking about something that has a very similar mechanism of action interesting yes and by very similar i mean the same i did listen to that episode and it was absolutely amazing thank you oh i'm brushing okay i cannot wait for the evolutionary history and i'm excited for the medical part that's okay i'm going to speed through this because i can't wait for the evolutionary history. That's what I want to hear. Listen, okay, so let me give you the briefest of rundowns. Tetrototoxin acts on something. Dinner shows up every night, whether you're
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Starting point is 00:29:55 That was cool of us. We didn't plan that. It's less cool now that you've said it, though. Again, if you want a primer on sodium channels, I really feel like I did a great job explaining them because I got real stoked on them in the last episode. And you explained it really well. Thank you. basically for those of you who are like stop talking about it I'm not going to go listen to that
Starting point is 00:30:21 episode or like I listened to it and I don't remember a thing because you did a crappy job of explaining it sodium channels are these channels that are on your nerve cells and your muscle cells and you need to have them open and close at certain times to have nervous system impulses actually transmit to your muscle cells to cause things like muscle contraction so if you want to lift your arm or move your finger or talk with your mouth, you need these sodium channels to be working. That's the briefest of rundowns I can give. So, tetrototoxin is a compound which binds directly to these sodium channels and blocks them. That sounds pretty bad. It's not great. Let me tell you. It's not great. It blocks them and what that means is that sodium can no longer get in.
Starting point is 00:31:15 sodium can't get in, your nerve impulses are not traveling, your muscles are not contracting, you're paralyzed. Yeah. That's exactly what it is. And the thing that makes this different than aconite, which is the compound in Wolfsbane that we talked about in the crossover with Matt, is that it's way, way more gnarly, way more potent. What does that mean?
Starting point is 00:31:43 Let me tell you. I wrote some numbers down because I have fun with this. If you could think of a compound that's really, really poisonous that could kill you really easily, don't guess because you might guess wrong. I'm going to tell you it's cyanide. Would you have guessed that? Absolutely. Cool.
Starting point is 00:32:06 So cyanide. You know all the answers all the time. It's like you read my mind. Get out of my head. So cyanide is a compound. that everyone knows, like, if you hear the word cyanide, even if you have no idea how it works or what it does, you know, like, don't, like, drink that. It's going to kill you really quickly. Apple seeds. Exactly. So, if I wanted to kill myself, no. If you wanted to kill me with cyanide,
Starting point is 00:32:31 you would need at least 546 milligrams of cyanide. What does that look like? Well, great question. A teaspoon of salt is five-ish grams. So that's like 5,000 milligrams. So it's a tiny amount. Okay. So it's like a little dash. Yes, it's a dash of cyanide. That's all you would need to kill me.
Starting point is 00:32:56 Not even a sprinkle, less than a sprinkle. Less than a sprank. Okay. Okay. If you wanted to kill me with tetrota toxin, 22 milligrams. How would you even measure that out? I don't.
Starting point is 00:33:08 I really tried hard to think of a way to quantify this for people. To kill you. To kill me with titrototoxin, 22 grams. Wait, wait, grams or milligrams? Sorry, milligrams. Whoa, bro. I was like, great. That's a lot of teaspoons.
Starting point is 00:33:24 No, it's very few teaspoons. Yeah, right? So, and the reason is because unlike aconite or other, there's actually a ridiculous amount of toxins. And Shane, I don't know if you're going to touch on this at all. I have a feeling you are. How many different organisms produce compounds which bind to sodium channels? It's a lot.
Starting point is 00:33:49 Yeah, it is a lot. Yeah. And it's a very diverse set of creatures. Yeah. Which is so interesting. It's fascinating. Because the thing is, we all have sodium channels. Like, like I said in the Monkshead episode, insects have sodium channels.
Starting point is 00:34:05 Right. Right. So it's this very universal thing that if you can attack that sodium channel, you can attack absolutely anything. But tetrototoxin is so good at binding to these sodium channels that we actually classify sodium channels. There's a lot of different types, like sort of subsets of sodium channels that work better. Like these ones are on your muscles and these ones are on your nerves.
Starting point is 00:34:29 But there's kind of two broad categories. One to trototoxin sensitive. One to trototoxin resistant. That's how we classify sodium channels. Wow. Because that's how strongly tetrototoxin binds. So we basically, like all of these different types of sodium channels, we divide them into, can tetrototoxin bind or can it not? Hmm.
Starting point is 00:34:53 Right? Isn't that cool? That's amazing. Yeah. It's super cool. Dido? So I know you really want to know what happens to you if you take a bite of a puffer fish just like out of the ocean. Just like the liver.
Starting point is 00:35:08 Give me the liver. Here we go. If you ingest this, generally within a half an hour, often less, the first symptom that you'll have is paristhesia, which is a fancy, silly medical word for your lips start tingling and they get a little numb and maybe they feel burny and like, just like something's not right in your lips. And then that might start to spread and then you might start salivating a lot and then you might start sweating. and then you'll get a headache because you're like, what's going on to me? And then you'll feel really weak. Oh my God, it's like a subway.
Starting point is 00:35:45 And then you'll get serious. Subway sandwiches? Yes. Not endorsed, guys. That's because I've gotten food poisoning a number of times from subway sandwiches. And so far, that's what it sounds like. Okay, well, and then you'll start to get a tremor. And then paralysis.
Starting point is 00:36:05 That's no good. No good. And the thing. that gets really dangerous and why this ends up often causing death is if you have paralysis of the muscles that you use for breathing, so your diaphragm and your intercostal muscles of your ribs, if those muscles become paralyzed, you cannot breathe. See our polio episode for more on that question. So it starts in your lips? That's just the first symptom or sign that you have. Yeah, it's often the first symptom. And that's if we're talking about someone who's eaten
Starting point is 00:36:39 Fugu or a puffer fish. And that is often the first symptom. And it's because that's sort of the first place where you're going to encounter to trototoxin. Improperly prepared fugu. Yes, improperly prepared Fugu. Right. So like you caught a puffer fish and you took a bite out of it like an apple. Right. Then the first place that you'll start to notice symptoms is in your mouth. But then quickly, you'll also get gastrointestinal symptoms, nausea, vomiting, diarrhea. But again, what ends up killing people is respiratory distress. Right. So you're not able to breathe because all of the muscles of your respiratory tract have failed and they're paralyzed. Oh my God. That sounds like a really horrible way to go. It's not a great, I wouldn't recommend it. And it happens insanely quickly. And part of that's because
Starting point is 00:37:28 it's this toxin, right? It's already, it's there. It's preformed. You just eat it or whatever. But you don't have to just eat it, right? What's the preparation that's most commonly associated with zombies? Powder. I was about to ask you that. Beach it to it. So, most people come into contact with tetrototoxin by eating it, right? That's like the most common.
Starting point is 00:37:56 But because we're not talking about a bacteria or a virus like we normally are. We're talking about a compound that it's actually produced by. bacteria. It's a toxin. Because it's already something that's formed, you can take a pufferfish, take its liver, dry it out, grind it up into powder, blow it into someone's face, and absolutely expose them to the toxin in that way. So it's not necessary that it's ingested. So is it just contact with like mucus membranes, like your eyes and nose and mouth? Yes. And I'm so glad you brought that up, Shane. Because this is a toxin that is way more deadly, for example, if it's injected. So most of the studies on this are done in mice. So they'll inject mice with the tetrototoxin. It's far more
Starting point is 00:38:49 dangerous if you inject a mouse versus if you let a mouse just nibble on a puffer fish. Okay. Same thing. I would assume I couldn't find evidence of this, but I think that's because they don't often just like blow tetrototoxin to mouse faces. But you could, one could assume that most of the ways that people, quote unquote, detoxify things, which the way that you do that is with your liver. So if you eat something, then your gastrointestinal tract absorbs it and it has to go through your liver, which takes care of a lot of the problem. Okay. If you inject it straight into your bloodstream or you breathe it straight into your nose, which basically goes straight into your blood. through your mucous membranes, you don't have that liver detoxification happening.
Starting point is 00:39:41 So it's actually a lot more potent. So it's a lot more dangerous. To inhale is a lot more. Yeah. Well, okay. I couldn't find like specific evidence of that because, again, I couldn't find studies where they blew to trototoxin on mice. But based on what I know about how things work, for example, if you take drugs sublingually
Starting point is 00:40:00 or by an inhaler, what's sublingually? Sublingually is under the tongue rather than swallowing it. it's more rapidly gets into your bloodstream than if you eat something and it has to go through your GI tract. Yeah. Can I just say like blowing tetrototoxin into the face of a mouse is like the most depressing lab job I have ever heard of in my highlight. Also, can you imagine if you sneeze and inhale? Like. Oh my goodness.
Starting point is 00:40:30 If there's a hell, that's pretty much the quickest way to get there is that except a job. like blowing tetrototoxin in the face of lab mice. Yeah. Yeah. But so really with the question that we have to answer then is what does that have to do with zombies, right? Nothing that I said was like, and then you go, you bite people or, or even like you become controlled by these powers, right?
Starting point is 00:40:54 You get paralyzed and then you die because you can't breathe. Like that's what happens. Right. So why, how could this have become a thing that people associate with zombieism? And I'm really glad that you mentioned how zombies in this non-George Romero idea, it's not like wanting your flesh and blood. It's being under someone else's power. It's also being dead and coming back to life. Now that toototoxin can do kind of.
Starting point is 00:41:28 Hmm. So I got thrilled when I learned about this. So one of the weird things about tetrototoxin from what I've read is that when all of this is happening to you, you remain conscious. Oh. Doesn't that sound awful? God. Which explains a lot, but keep going. Yes.
Starting point is 00:41:50 So you are aware of what's happening to you. But it can have such a drastic effect because, again, these sodium channels are everywhere. It can have such a drastic effect on your respiratory rate and your heart rate that you. seem like you're dead. So you can appear, for all intensive purposes, essentially dead if you've been dosed with the right amount of tetrototoxin, where it's not completely paralyzing you, right? Like your brainstem is still working. There's enough function in your diaphragm that your unconscious breathing is still breathing
Starting point is 00:42:26 and your heart is beating just enough to keep you alive, but maybe not enough to show a pulse, which can happen. Wow. Yeah. And so people can then pronounce you dead and your family can think you're dead because you, you know, you started vomiting and diarrheaing and then you kind of went limp and paralytic. And now you're not moving. It doesn't seem like you're breathing. You must be dead.
Starting point is 00:42:54 How long? Great question. This can last. So symptoms tend to set in very quickly, like within 10 to 30 minutes. It can take hours. hours also. So if you haven't ingested a lot and, you know, whatever, it can take a longer time if you ingest it versus inject it, et cetera. But when people do recover over a period of many hours, maybe 24 hours or more, they recover completely if you live. If you survive,
Starting point is 00:43:27 you recover completely. There's no neurological deficit. So once this tetrototoxin sort of just makes its way out of your system, there's no residual effects of it. So it's like the O-Town song, All or Nothing at All. Oh, my God. Yeah, sure. Yeah. Just saying that. So that's why.
Starting point is 00:43:54 So even that's, it's interesting that there, like, because I would think that there would be at least some effects of like hypoxia. having like such a, you know, having your tissues or brain being deprived of oxygen if you're not breathing very, very deeply or very often. And if your heart's not pumping very often, I'd imagine there'd be at least some effects from, from just like hypoxia and not getting enough oxygen. Yeah, but it seems like you either die or you recover completely. That's bizarre. It's super bizarre. I will say that if your respiratory muscles are affected, it's not a good sign. You're probably pretty much going to die. Almost everyone who, if the paralysis
Starting point is 00:44:39 spreads all the way to your diaphragm, you're probably going to die. So here's the thing. It's a gray area. It's not, I wouldn't say I buy it 100% that like you could pronounce somebody dead because they dosed them with tetrototoxin. But it's been used a ton in like popular culture as I'm going to fake someone's death. You know, like that happens all the time. They do it with Tertototoxin often in movies. I do feel like that's a very common trope. And I could also see, you know, back in, you know, the early, like late 1800s, early 1900s, or even earlier than that.
Starting point is 00:45:18 I could certainly imagine a doctor like, oh, well, he. He seems dead. Threw up and pooed himself and he's not moving. And I don't want to touch him because he threw up and pooed himself, right? So just call him dead and leave it at that. We didn't have EKGs. We didn't have brain scanners. You can very easily survive if you're breathing. Like there's a lot of different breath types that are really not good, but will get your body enough oxygen and release enough carbon dioxide, but might seem like you're not breathing because you're breathing so infrequently. But if your heart is still pounding, however weak it might be, then the blood is still flowing, then things are still getting oxygen. That I agree. If you are in the 1700s and you're like, you touch them and you're like, oh, they're kind of cold. They must be dead, you know.
Starting point is 00:46:08 And the stethoscope isn't invented. Oh, I don't know. Don't ask me that. But I guess also the trade-off is that, is that, you know, if you're not, if you're, like, completely still and comatose, you actually, you don't need as much oxygen as you would if you were, like, up and moving around. So you have this lower metabolic rate as well. So you're using less oxygen, so you don't need as much. Boom. So, zombies.
Starting point is 00:46:32 So, zombies, boom. But is it boom or is it just like a? Yeah, it is. That's a thing. Because it's like, okay, that's, it's an almost maybe I could kind of buy it explanation for how someone could be appearing dead and then come back to life. Beyond that, nothing. Like there's no like, and then you will succumb to my will.
Starting point is 00:46:57 Or on the other end, then you will eat fled. of humans. You know, there's none of that. So, but the other thing is, is it viable? Can you reliably make a zombie powder? No, I don't even fully buy that you could make a powder period that you could be sure would just kind of paralyze someone to the point that you could convince someone else that they're dead, but then make sure that they recover afterwards. Nah, dude. I don't buy it in the slight.
Starting point is 00:47:28 it. Like, you could, if you worked really hard, probably convince people that you faked your death by using this, maybe. I don't know. So I was going to ask, so when a person does recover, like, what has, like, how does the tetrototoxin unbind from the sodium challenge? That's like a good question. I don't, I don't know. I mean, I guess it just eventually something will come by and be able to degrade it. But I don't have a. a full answer to that. Because from what I can understand, it's not like a reversible binding, right? Like it binds and then it's bound. So it's either just like your body has to make some new sodium
Starting point is 00:48:11 channels maybe and maybe your body can make enough to compensate or eventually like nothing in your body is going to last forever. Right. So eventually like that sodium channel will be recycled or something, some macrophage will come by and like snag up that. to chototoxin or whatever. I don't actually know the mechanism of it. I'm just making things up right now. Generating hypotheses. There we go.
Starting point is 00:48:36 I like that. But that is, it brings up a good point in that we don't have any treatment for it. So the only thing you can really do is if you, if you know that someone ate a puffer fish and they shouldn't have, you can like give them activated charcoal or do a gastric lavage, like make them barf it all up. and that can help somewhat. That is a very fancy word for barf-inducing. Gastric lavage.
Starting point is 00:49:03 But there aren't any treatments. So people have tried different things. I don't want to take too much time, so I don't want to get into the various specific things that people have tried. They don't work all that well. But here's my question. Clearly, this mechanism of action, mechanism of action of involving sodium channels. It's not something new, right? Pufferfish didn't
Starting point is 00:49:30 invent this by any means. We've already talked about it with Wolfsbane. We'll probably talk about it in the future with something else that binds to the same channels. But the thing about Tetrototoxin that makes it so forking, terrifying, is that it's so potent. It's so potent that we named the channels after it. And the tiniest amount, 22 microtechamins. micrograms can kill me a full-grown human, right? 22 milligrams, sorry, get all those units mixed up. So my question, and probably everyone's question at this point, and Shane, why we brought you here, is why on earth would something as adorable as a puffer fish need to make such a potent toxin?
Starting point is 00:50:18 Do they just want to kill us? Do puffer fish hate us? Why? Tell me why. Please. That is a phenomenal question. So pufferfish, they didn't, you know, they weren't the first to invent tetrototoxin, but toototoxin is actually named after them. Well, kind of.
Starting point is 00:50:58 Tototoxin is actually named after an order of bony fish called tetraodontiformis, which includes the pufferfish, but also porcupine fish and, you know, the big floppy ocean sunfish. They're like huge and kind of flat and really goofy looking and also trigger fish. So altogether it's about almost 350 species in the order, but not all of these species have to trototoxin. You know, so it was named in 1910, actually as the principal toxin in puffer fish. And obviously the principal component of Fugu, as we were, as you were saying before, you know, since then it's been subsequently described in a really wide array of organisms across the tree of life. sort of both marine and terrestrial organisms. So several, obviously several genera, which is the plural of genus, several genera of pufferfish have it, specifically in like liver and gonads.
Starting point is 00:51:57 The marine gobi, which is another bony fish, has tetrototoxin in its skin and muscles. And then even there are several invertebrates, marine invertebrates that also have it. So there are several species of marine flatworms. There is trumpet shellfish, which is a different invertebrate that has it in a digestive gland. Horseshoe crabs apparently have them in their eggs, some starfish species. I should say one of the, I think, most interesting is actually the blue-ringed octopus that actually has it in its salivary glands, and it uses it as I, you know, as it's co-opted as a venom in that species. So that's really interesting. What the coolest love blue-ring octopus?
Starting point is 00:52:38 They're like, take this. They're so small. And they're like, you want to fight with me? And then they bite you and then you die. Oh, my God. I love them. That's the first time I've ever heard. It bites you and it dies.
Starting point is 00:52:52 Oh, my God, I love them. You don't hear that very often except on this podcast. I have a quick question, Shane. So you mentioned that the organ of a lot of where this tetrototoxin is stored for a lot of these animals, why the liver, the gonads, the intestinal whatever system? Why, why there? So that is a great question. And quite frankly, I don't think we know. So in doing research for this, I realize that there's a ton that we don't know about tetrototoxin, yeah, in terms of how it contributes to biodiversity and how the vast array of organisms that use it, how they actually go
Starting point is 00:53:36 about using it. Yeah. Yeah, that's so cool. Yeah, it's weird. It is very weird because, I mean, essentially, like, you're talking about chemical warfare, essentially, right? I mean, you're taking this super, super toxic substance and integrating it into your body in some form or fashion and then using that as a defense. Yeah. So not only does it occur in marine organisms, but they're also terrestrial species, you know, species that live on land that use it. And this is the amphibians.
Starting point is 00:54:06 So, you know, there are tree frog species in the genus Adelopis that use tetrototoxin. And then it's been most commonly studied in nutes. So nutes, what are called rough-skinned nutes. They're in the genus Tariqa. So they have really large volumes of tetrototoxin in their skin. And actually also five different genera of salamander that have Tertotoxin. What? Anyone who works long hours knows the routine.
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Starting point is 00:57:24 We need to know what's the deal here, bro. Okay. Well, so if I can, before I get to the why, the question is how? Yeah. Okay. Good question. Good first step. Is that okay?
Starting point is 00:57:37 Can we go to the how before we go to the walk? For sure. We accept. Okay. So just to give you sort of the scale of this, we're talking about hundreds of millions of years of diversity of life. Right. So if we're talking about across the tree of life between, you know, worms and other invertebrates and terrestrial organisms, terrestrial vertebrates and fish, we're talking about hundreds of millions of years of diversity. And you get these species popping up across the tree of life. that all are using this chemical warfare, like co-opting tetrototoxin, to use as, typically as defense, right?
Starting point is 00:58:13 So there are actually two major hypotheses about where tetrototoxin comes from. So one is an endogenous origin, right? So something that is genetically coded in an animal to produce tetrototoxin. And there is some support for this. And that typically comes from the tree frogs. I mentioned in that genus Atalopis. where if you take those tree frog species and you bring them into like a controlled environment where you control what you what you feed them what they're in contact with even years after that
Starting point is 00:58:45 they can maintain really high levels of toxicity and even frogs that are hatched in the lab still have amounts like measurable amounts of turtototoxin in their skin which suggests that they're actually producing it somehow whoa but yeah exactly and I and again I don't really think we know how this works yet, which is really surprising, actually. But then the second hypothesis is actually an exogenous origin, so that animals are uptaking to trototoxin, either through the food chain or through symbiosis. And a lot of evidence for this actually comes from the puffer fish. So people captively breed puffer fish for food and also for the pet trade. And puffer fish that are born in captivity are actually not toxic. They don't have any measurable amounts of tetrototoxin.
Starting point is 00:59:36 What? But if you feed them to trototoxin, they very quickly become toxic. Oh, wait. So is it possible that there are distinct groups of animals that some can produce, some, it's endogenous and for some it's exogenous? Yes. Exactly. Erin's face is so excited right now. She's just like, like, like, her. Her eyes can't contain it. Oh, my God. That's amazing. It's amazing.
Starting point is 01:00:07 Yeah, and it's this really sort of wild example of this classic question in evolutionary biology of, so the repeatability, right? If, like, you know, if you get the same results, i.e. I have tetrototoxin, don't eat me or I'll mess you up. Do you get there by the same, by the same path? Right. And it seems like, at least in this case, the answer is there are several paths to potentially get there, either through producing it or through uptaking it in the environment or, you know, which I think is an even cooler potential explanation is through symbiosis. You know, a major hypothesis is that a lot of these species that have tetrototoxin have them because they formed a symbiotic relationship with bacteria that produced the tetrototoxin. So, like, vibrio bacteria is most often suggested as the, you know, the symbiont in this case, but also pseudomonas and actenomycetes.
Starting point is 01:01:06 Yeah, but in either case, right, there remains this sort of really important question about the repeatability of evolution, right? So either you have independent origins of tetrototoxin production, right, via these endogenous means, or even if you're uptaking it from the environment, you still have to biologically incorporate. it into your own body without being affected by it. Right. So you still have to have some level of resistance. What is? This is insane. It's not like puffer fish don't have their own sodium channels.
Starting point is 01:01:36 Right. They do. Right. Like what? How? What? You can feed them to Trototox and they're like, no worry about my live will take care of this. Like my live.
Starting point is 01:01:44 Exactly. I just skipped the other half of the word that wasn't intentional. I mean, it's pretty usual. My live totes got this, bro. Exactly. Yeah. So, and this obviously like brings us to your initial question, which is, which is why. Yeah. And, you know, as I described, most of these species are incorporating it in, in their organs. and it seems that this is mostly associated with defense against predation, right?
Starting point is 01:02:14 So there are a lot of species that incorporated in different organs, but a lot also have it in their skin and in their muscle, right? So if you bit them or tried to hold on to them, you know, obviously if you're biting them, you're biting them with your mouth, which leads to, you know, a lot of the issues that you were just talking, that we were just talking about when it comes to human infection with tetroto toxin. So it seems to be associated by and large with defense against. predation, which also sort of brings us to this weird dynamic that comes out of these prey species
Starting point is 01:02:45 having to trototoxin, which are what we call evolutionary arms races. So if you're a puffer fish or if you're a rough skin newt swimming around or walking around doing your thing, you don't want to be eaten. That's generally an unpleasant experience that we all try to avoid. But if you're a predator, typically you like to eat things. This like, sort of very simple dynamic to competing factors, you know, lead to evolutionary arms races where things that don't want to get eaten, figure out ways to not get eaten, either by running really fast or growing large or growing hard parts that can't be chewed on. But then predators, you know, they find ways to get around that. And there's a really interesting case when it
Starting point is 01:03:29 comes to trototoxins, particularly in these rough skin nukes that I mentioned before. So this species ranges across the west coast of the United States all the way from like southern Canada down through Southern California and across the range they vary in their toxicity right so some populations are very highly toxic and some are only mildly toxic and across the their range there are also garter snakes like very common I'm sure we've all like seen garter snakes outside yeah sort of racing from place to place and garter snakes they occur across the same region and they're the only predator of the newt that is known to be resistant to tetrototoxin.
Starting point is 01:04:14 What? What? So they, I know, right? So these, the snakes, they eat nukes regularly, right? And this has led to a matched resistance to tetrototoxin. And so where the nukes are more toxic, the snakes are more resistant to tetrototoxin. Oh my God. I love biology.
Starting point is 01:04:32 It's so beautiful. I know. And so just to give you a. an idea. This ranges by three orders of magnitude. Oh, what? What? What? So we're talking about some snakes are 1,000 times more resistant to tetrototoxin than others. That is so cool. I know, which brings us back to this idea of the repeatability because this resistance, it seems to have evolved independently at least twice within garter snakes. So separate lineages have come up with this solution to being able to eat these rough-skinned nudes.
Starting point is 01:05:10 Are you serious? It's like different garter snakes. It's like garter snakes you think those are the same snake, but there's different populations that have evolved this different times? And clearly these nudes are a really important food source. Yeah, I mean, and it must be extremely important, right? Because, you know, this fundamental question ideal is like, well, how do you get this resistance? Well, you know, you've said, you know, how tetrototoxin affects your, your sodium channels.
Starting point is 01:05:39 But these snakes actually have mutations in their sodium channels that make tetrototoxin less efficient at binding to them. So cool. What? I said there was different kinds of sodium channels, man. They're just like, we're going to skip to all the resisting kind and just forget about these ones over here. That is so cool. Why don't we all have resistant sodium channels? Because we're not all eating pepper fish.
Starting point is 01:06:06 Because our species haven't been. Yeah. Yeah. Yeah. Yeah. But it does come out a tradeoff, right? I mean, as, you know, obviously, you know, these sodium channels, they provide a really basic biological function, right? And they help us to, you know, to contract our muscles and move around.
Starting point is 01:06:25 And snakes that have very high tetrototoxin resistance cannot move as quickly as those that don't. Interesting. Weird. Huh. So there's like a substantial trade-off. Yes, absolutely. But it would be really cool if that was the whole story, right? Mm-hmm.
Starting point is 01:06:42 But recently, actually just earlier this year in 2018, there was a study, again, in two species of rough-skinned nudes that suggest that they showed that individuals that were more toxic also had fewer parasites than less toxic individuals. We just both got so excited. I thought you would like that one. One more time, just for emphasis, please. Yes, say it again, please. So, rough skin nudes that are more toxic have fewer parasites than they're less toxic counterparts. Oh, my God. Yeah, so it seems like there's the possibility that not only does it help them in defense against predators,
Starting point is 01:07:31 but it may also help them defend against infections. That's amazing. What kind of, so parasites meaning like ectoparasites or are we also talking like bacteria viruses, et cetera? So if I remember correctly, they looked mostly at sort of larger parasites. So things like parasitic worms and even they looked at fungi as well, like parasitic fungi for that effect nudes. Things like chytrid fungus, for instance. Oh, oh. Oh, that's going to probably have to be its whole own episode.
Starting point is 01:08:03 Oh, yeah, for sure. Yeah, won't dive too deep into that one. That's amazing. Yeah, and so this brings me back to this original question, Aaron Welsh, that you pose, of like, why do we care? Like, you know, why do we want to get into, like, the mechanisms of all this stuff? I mean, obviously, hearing these stories, it's actually, it's really cool, you know, just on its own. But there is, I think, some utility and really trying to understand the mechanisms, either, you know, when it comes to zombie powder or when it comes to, you know, these crazy creatures across the tree of life that are using toototoxin, there is some inherent utility there, you know, when it comes to our understanding of basic biology and medicine. So back in, I think it was like 1929, there was this guy, August Crow.
Starting point is 01:08:53 You know, he has this, what became a pretty famous quote. And he said that for some large number of human-related problems, there will be some animal of choice for which that problem can be most conveniently studied. And this became his principle. And that's based on this sort of fundamental observation that evolution by natural selection has produced a vast array of diversity and form and function. And because of this, some species are really well suited for understanding human-related problems, right? because they've evolved extreme characteristics that mimic human disease states, or they allow us to conduct experiments that would be otherwise impossible. And this gives us fundamental insights into the diseases that plague us
Starting point is 01:09:35 and help us to design effective treatments for those diseases. So in the case of tetrototoxin resistance, right, in these species, understanding how their ion channels allow them to live with tetrototoxin may provide really valuable insights into many diseases that are thought to result from ion channel dysfunction, right? And this includes, you know, things from like colorblindness and night blindness to cystic fibrosis to Alzheimer's to Parkinson's to schizophrenia. You know, so they potentially provide some really fundamental insights into understanding how, you know, these really basic aspects of biology can be modified and improved upon.
Starting point is 01:10:16 That was so gorgeous. That was so perfectly put and fascinating. And we were both at the same time, we were forming hearts with our hands and we were putting them towards our computers. We were like, oh, my God. You got to stop that. No, but that is, oh, that was just really well set and really well put. And I think that you made a really good point that it's not just driven by this curiosity, but there is a function and a reason and an application for doing this type of research and for being even just interested in it and learning about it from a comparative angle.
Starting point is 01:10:52 or from a historical angle or from a medical angle, like there's a reason. From all the angles. Yeah. Oh, cool. I know. Science. Oh, dude. That was great.
Starting point is 01:11:06 That was a great, like I said. So should we do sources? Probably. Okay. So I read a few books or sections of books. I would recommend Invisible Powers, which is edited by Claudine, Michelle, and Patrick Belgard-Smith. and also passage of darkness by Wade Davis. American zombie gothic by Kyle William Bishop,
Starting point is 01:11:31 which kind of details the transformation of the evolution of the zombie genre in movies. Okay. Kosamba or the Congress of Santa Barbara, which is like a place to learn about and to have scholarship on voodoo. Sweet. I don't have. We'll post all of these too. Yeah, that's the thing is mine are always way too long.
Starting point is 01:11:56 I have a bunch of articles that were cool, but you can find them on our website. This Podcast Will Kill You.com. We have every single one of our episodes. We have all of our sources listed there. Shane, do you have any things you'd like to shout out besides your brain? Oh, I guess what I will shout out is the last paper I mentioned about poisons and parasites in newts. It was published earlier this year in the Journal of Animal Ecology. The lead author's last name is Johnson.
Starting point is 01:12:24 Johnson at all 2018. Sweet. That's very cool. Also, Shane, tell us where everyone can find you and stalk you and listen to your podcast. Yeah, so you can find me at S. Campbell Staten on Twitter. You can also hit up at Superbiop Podcast to check out new episodes. Shane, thank you so much for joining us. This is awesome.
Starting point is 01:12:49 It was super fun. I had a great time. Thank you guys so much. And thank you everybody for listening. We love you. You're the number one greatest. Thanks to Bloodmobile for providing all of our music. We love you so much. And yeah. Join us next time. For something else creepy. Now guess what? Wash your zomified hands. Yep. You're filthy. The animals. Don't be nasty.
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