This Podcast Will Kill You - Ep 48 Botulism: Why are you the way you are?

Episode Date: April 14, 2020

You don’t look surprised to see this in your podcast feed - or is that just the botox? This week we’re taking a tour of the wonderful world of Clostridium botulinum and the toxin it produces, at once both poison and prescription. First, we delve into how botulinum toxin acts to paralyze your muscles and under what circumstances you might encounter it. Then we iron out the wrinkles of the why of botulinum toxin, an answer that involves migratory birds, maggots, and marshes. The story continues with blood sausages, an unfortunate funeral party, and a massive shift from toxin to treatment as the therapeutic potential of botulinum toxin is explored. And the best part of this episode? Georgia. Hardstark. You’ve heard the always amazing, ever hilarious, and one of our personal heroes Georgia Hardstark on My Favorite Murder, but now listen to her share her firsthand experience with getting botox facial injections. This episode ranks among our top favorites we've ever recorded, and we hope you love it as much as we do! See omnystudio.com/listener for privacy information.

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Janice Torres here. And I'm Austin Hankwitz. We host the podcast, Mind the Business, Small Business Success Stories, produced by Ruby Studio, in partnership with Intuit QuickBooks. We're back for season four to talk to some incredible small business owners. The big thing about working at tech is that it's ever evolving, ever changing. everyone's a rookie. That's how fast the industry is changing. So what I'm really excited about is to be part of that change. So listen on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Hi, I'm Georgia Hardstock, and I co-host the podcast, my favorite murder. And of course, I had heard about Botox for years.

I think everyone, you know, knew about it, knew what it was. And it didn't even cross my mind until I had a friend who got it done. and she was, you know, we were both in our mid-30s, so you're thinking like, well, I don't need it yet. And then I saw her face and it looked, it's just, you know, she didn't, she looked awake, I guess, was the thing that really struck me. And then I was in this really cool, like secret Los Angeles ladies Facebook group. And they all got it done. And so I kept, like, it normalized it for me. And we were all, you know, they were in their, from their mid-20s to 30s to 40s, it was all ages. So it didn't suddenly feel like this thing that only, you know, you had to get when you're older and already, you know, having issues. The way I read about it was that it was preventative, which I found really interesting.

Because, you know, the less you're making those furrowing your brows and making those creases, the less the lines are going to stick around. And I was really nervous because it's, you know, I had to get past feeling vain about it, which I think is a normal thought. And then I, you know, I just realized there were these little things about my, you know, wrinkles that were bothering me. And I think that's the main thing is like it's not for everyone and everyone and wrinkles are beautiful and not everyone, you know, is going to want to do it. And I think that's totally fair. But I think if it's, for me, it's like a simple fix that will make me just feel a little more confident. you know, which is a big huge plus for me. So, you know, it's not going to change your face. It's not going to

change your life. But, you know, yeah. So I went, it was, and I got it the first time right before mine and Vince's wedding. So I was like 35 or 36. And I was super nervous. I was going to, I was scared I was going to completely change my face. You know, it's a little needle. So of course, it's not going to feel good. And then, you know, they poke it in. And so you want to do a lot of little spots. You don't just do it in one spot. And I get it done in my forehead and between my eyebrows and on my smile lines.

And so you get a, it's a couple different pokes, like maybe, I think mine are like 12 pokes total. And you can kind of, it's really gross. You can kind of hear when they're injecting it. it's like a squish in like your inner ear you can hear it that's the only horrible part um yeah it doesn't it hurts because it's a needle but i feel like with that and like tattoos when you're excited about what you're doing it doesn't hurt as bad and they give you a you know a stress ball to squeeze and it's over so quickly and um you know it's just part of it if you if you're totally afraid of needles obviously you're not going to want to do it but um and it takes like two weeks to

start showing up. So it's kind of good that it's slow and subtle. It's not this like right away change. And so when I finally, you know, no one knew that I had gotten it done. None of my, even my closest friends hadn't known. So when I finally told like my best friend, she was shocked. And she was like, now that you're saying it, I see it. And I was like, I look like I was, I'm 30 again. And she is, she blurted, you look better. than that. Now, I was like, okay, I like this. Well, that was one of the most exciting things to ever happen. Absolutely thrilling. Thank you so much, Georgia, for being a part of this and sharing your story and wealth of knowledge. Yes, thank you, thank you. That was thrilling. Oh, my gosh.

Definitely made my Friday. Uh-huh. And much more uplifting than other firsthand accounts of the subject of today's episode, which is botulism. Botulism. Well, like botulinum toxin. Sure. Clastridium botulinem. How about that? Yeah. How about that?

Hi, I'm Erin Welsh. And I'm Aaron Elman Updike. And this is, this podcast will kill you. Today we're talking. You know what we're talking. Bachelinum. Oh. Well, we have a couple of pieces of business.

to get into before we start this episode, which I know we say this all the time, but I am so excited for this. It's a nice. It got to the point where I was telling, because I know I didn't want to tell you the things I was learning yet, but I was like texting everyone else, like, oh my gosh. No, yeah. I do the same thing. Like yesterday, I was like, Brett, did you know?

And I just like started shouting Botox facts at him. Yeah. Well, I'm glad that we finally get to lit it all off our chests today. Me too. It's going to be, it's going to be a good one. I think so. Okay. So like I said, though, some business. Number one is that we are going to keep doing these regularly scheduled episodes or whatever. And we are going to keep them COVID free. We are COVID. This is a COVID free zone right now. Yeah. So we promise we won't even say it. too many more times. And so what we're doing is, as you may have seen in your feed, we're going to keep dropping those COVID-19 episodes every so often. Just on a, we don't really have a particular schedule for that. It's just sort of whenever they happen.

But in order, but we also recognize that people may not want to hear about what's going on or it might be too stressful or whatever. And we totally get that. And so all of these normal episodes will just be. normal episodes. Dinks. Okay. All right. Number two, we have now joined the affiliate program of this organization called bookshop.org. And so what this is, is it's a website that it's an online bookstore website that works with independent bookstores. And so as an affiliate, we have a page where you can see

are lists that we have curated for what books, you know, nonfiction books, fiction books, memoirs about disease and about health and stuff like that. And so if you are so interested, you could go on our website under the Books tab and you'll find a link to bookshop.org. And also we have links in each of our, so in each of our episodes where we list our sources, we will provide links to those books on Bookshop if they exist. There. Cool. Cool. One other piece of business, if you are not aware yet, we have now alcohol-free episodes available on our website if you'd like to use those for whatever reason. If you don't

want to hear us talk about quarantinis, you can find those on our website. Yep. Cool. Speaking of quarantinis. It's quarantini time. It is. What are we drinking this week? This week we're drinking a can of germs. And we have a big thank you to Bloodmobile for providing that name. The quarantini name for this episode and all of our episodes. Just kidding. A lot of our episodes, though. Thank you, Bloodmobile slash Daniel, my brother.

Really, that's a phenomenal drink name. Can of Germs. For botulism. Oh, my gosh, you guys. It's incredible. What is in can of germs? It is rum, canned pineapple, of course. Honey, also, of course, we'll talk about it.

And lime juice. Yeah, it's pretty good. It's pretty good, actually. Yeah. Yeah. It's not bad. Awesome. All right, then.

Anything else, or can we just get into this episode, Aaron? Let's get into the episode, please. Awesome. Right after this break. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip.

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They are so comfortable. The fit is amazing, and they come in a bunch of different washes, so I'm about to go order some more. Refresh your wardrobe with Quince. Go to quince.com slash this podcast to get free shipping on your online. order and 365-day returns, now available in Canada, too. That's Q-U-I-N-C-E.com slash this podcast to get free shipping and 365-day returns, quince.com slash this podcast. So when we talk about botulism, when we talk about botulinum, Botox, whatever, we're talking about a specific pathogen that I'm very excited, Erin, for you to tell me about where this pathogen came from,

because you specifically told me not to look that up. Oh, I was very adamant. Like, don't read about this. I didn't read it at all. All caps text. You're not going to talk about this, are you? Nope. I am not.

But we will talk a little bit about the bacterium itself. So this bacterium is called Clostridium Botulinum. You may have heard the term Clostridium, if you've ever heard of, for example, Clostridium difficile, C-Diff. Yeah, a lot of people. probably have. This is another clostridium species that causes disease in humans. It causes massive, very serious diarrhea. It's a pathogen of pretty big concern, especially in hospitals. So, Clostridium botulinum is another bacterium in the same genus. These claustridium species are gram-positive, which means they stain purple when you look at them under a microscope.

That's what we always say on this podcast. It means that they have a thick cell wall. Clostridium species are rod-shaped, so they look like little tick-tacks. And very importantly, they are what we call spore-forming anorbes. It's a lot of technical terms. Let's talk about what they mean. So anorobes means that this is a bacteria that grower. grows and lives without any oxygen.

Okay? That's really important. So it can't just grow like on your table out in the open or on your fingernail or in your nose or something like that. Okay. I don't know why I said fingernail. The fingernail is my favorite frame of reference. Man, I want to swab my fingernail now and see what's growing there.

I mean, you'd probably find some weird stuff, but not Clostridium species. Okay. our atmosphere, of course, is 21% oxygen. So how can this bacteria survive if it's, like, surrounded by oxygen all the time? Quick question. Did you know that off just like the back of your hand that it was 21%? Yes, I did. Did you?

No. Oh, well, now you know. Listeners, did you know? Huh? It's, yeah, that's, I did know, that's a, that's a trivia fact I did know, in fact. Awesome. It's important because we talk about it in medicine, because, you know, when you put someone on oxygen, you have to think about how much oxygen they're getting and what that is compared to what is, what they're normally breathing in at room air. Right. So, if they're on 21% oxygen, that's actually like room air. Oh. So. Awesome. Yeah. Oh, how fun. Look, medicine teaches you things. Who knew. Okay, so how does this bacterium survive if it's surrounded by oxygen and it needs to live and grow in an environment without oxygen?

The answer is that it's a spore former. I can't remember if we've talked on this podcast before about spore forming bacteria. So let's talk about what spores are. So bacteria that are spore formers, here we're talking about specifically what are end. endospores. So these are things, for lack of a better word, that bacteria produce that are super environmentally stable. They're basically a stripped down structure that contains the DNA of the bacteria, but can persist in the environment for a really, really long time. So these are not reproductive structures. When you hear the word spore, you might think of like a fern spore or a mushroom spore. Those are like reproductive things. So endospores, bacterial endospores are not reproductive structures. They're basically just a form that the bacteria can produce in order to resist bad

environmental conditions. Yeah. Just kind of like a wait and see, a little blueprint for the future. Exactly. Right. And so when a bacteria senses that environmental conditions might be deteriorating to the point where they're not going to be able to survive and continue to reproduce, they begin to form this endospore. And then if those environmental conditions deteriorate and the bacteria around that endospor dies and deteriorates, the endospore stays alive, essentially. It doesn't do anything. It just exists until conditions are right, and then it can reactivate. Okay? And go on to form another living, reproducing bacteria. So these endospores are really important because they're resistant to things like UV. They're, in the case of anaerobes, they're resistant to oxygen,

which could kill reproducing claustridium botulinum. They're resistant to alcohol, to soaps, to hot, to cold, to certain levels of radiation. They're really, really hearty little packets of DNA, which can make them especially dangerous in a hospital. setting if things aren't sterilized properly. And so that's part of the reason why C. diff, Clostridium difficile, is really scary in hospital settings because, like, just using alcohol-based hand sanitizer doesn't kill the spores of these bacteria. Right. And we'll do a whole episode on C-Diff in the future at some point because it's definitely worthy of its own massive episode. Absolutely. And we're also going to do another episode at some point on another Clostridium species,

Tetanus. Oh, yeah. Oh, my gosh. I forgot that tetanus was... Another spore former. Another toxin producer. I think that's why, yeah, I went back and watched the sketchy micro videos for this. And like, tetanus and botulism are kind of opposite ends of a spectrum, which is really interesting. And so I remember, like, comparing the two between them. So maybe I thought that we had done tetanus already.

I don't know. The only other spore former I can think of off the top of my head is anthrax. And I haven't done that. You haven't done that. Yeah. We'll do that eventually too. Anyways, there's more, but those are the big ones. Yeah.

Okay. But the spore isn't actually the story here. Okay? Of course not. Of course not. It's part of the story, but it's not the story that we're focusing on on this podcast will kill you. What we want to talk about, of course, is the part of this bacteria that makes you sick.

So we're here today to talk about botulism. It turns out that botulism is caused not by the bacterium itself, not by the spore itself, but by the toxin that that bacterium produces. Okay? Oh yeah. This is called botulinum toxin. So what I want to do first is we'll talk about that toxin itself, the mechanism of action of that toxin, which will pretty clearly tell you what the symptoms that you're going to see are. are of this, like, of poisoning from botulinum toxin. And then we'll talk about the ways that you can get exposed to this toxin because there's a few

different, very distinct ways that you can be exposed to this toxin. Okay? All right. So first of all, what is botulinum toxin? We've definitely talked about toxins a lot on this podcast because lots of bacteria produce different kinds of toxins. It's basically just usually proteins that a bacteria produces that have an effective. effect that do something for that bacterium. Okay. So like cholera toxin.

Exactly. Chlorotoxin. We talked about Staphoreus produces a lot of different toxins that have different effects. Right. So in the case of botulinum toxin, this is a neurotoxic protein that the bacteria produces. So it has effects specifically on our peripheral nervous system. And largely on our somatic nervous system. So if you remember in our episode on Belladonna, way back when. Let's cast my mind back to. Way, who, poop, poop, poop. We talked about there's a lot of different ways that you can divide up the nervous system, right? We have our central nervous system, which is like your

brain and your spinal cord. You have your peripheral nervous system, which is everything outside your brain and your spinal cord, like where your nerves go to your muscles and your organs. You can also divide it into your somatic and your autonomic nervous system. So your somatic, meaning like your sensory and muscles nervous system. And then your autonomic nervous system, which is like your parasympathetic and sympathetic, rest and digest versus fire or flight. Remember that? Kind of?

Okay. So in this case, the effects of botulinum toxin, they act on a couple of different places. They act both on the parasympathetic nervous system, but largely on the somatic peripheral nervous system. Uh-huh. So let's first talk about what that nervous system is and how it works so that we understand how botulinum toxin interferes with that process. Excellent. Okay. So I'm also not a neurologist or a neuroscientist, so this is real basic, okay?

So your brain, of course, is what controls all of the movements of your body. So how does your brain do that? You have nerves. Your brain is connected to your spinal cord, which is connected to nerves that innervate your muscles, okay, or your organs. So the way that this kind of happens is that electrical signals in your brain are transmitted along those nerves, along what are called axons of those nerves. And then when they get to the end of the nerve, which is called a synapse, there's a gap between that nerve and, for example, your muscle. And so in order for that electrical signal in the nerve to transmit across that gap and have an effect on the muscle, that electrical signal has to be translated into a chemical signal. and then the chemicals can travel across that gap, that synapse between the nerve and the muscle,

and they can propagate that signal into the muscle. Does that make sense? Yeah. Cool. That's the first time I've ever explained that, so that was fun. Okay. So when you're looking at the synapse, the gap between the end of your nerve and the start of your muscle, there's the pre-synaptic end.

that's basically the nerve that came like from your spinal cord and then the post-synaptic end, you can think of that as your muscle. It turns out that for your muscles especially, like your skeletal muscles, the transmitter, the chemical signal that is used to transmit that signal is called acetylcholine. Okay. Acetylcholine is released at the presynaptic. So from the nerve ending, acetylcholine is released. It travels across that gap and binds to a receptor on your muscle end.

And then that is what actually causes your muscle to go, hey, I'm going to contract and boom, contracts. Gotcha. So acetylcholine is really important in that. So how does botulism work? So it turns out that botulinum toxin blocks the release. of acetylcholine from that presynaptic nerve ending. Gotcha. Okay?

So you have an electrical signal that's transmitted from your brain. It gets to the end and botulinum toxin is there and says, nope, you can't release acetylcholine. So then your muscle goes, it's got nothing. Are there toxins or venoms or something that block from the other end, from the muscle binding site? We already talked about one, and that was Belladonna. Yeah. So Belladonna, and Belladonna tends to act only on the parasympathetic receptors because there are two different types of acetylcholine receptors. There's muscarinic and nicotinic.

And so botulinum acts on the presynaptic end. So it blocks all acetylcholine release. Oh, my gosh. Atropine binds to the receptor, but only the muscarinic receptor, so not the ones in your skeletal muscle. Oh my gosh. This is so thrilling. I know, right? I'm so glad you find it thrilling because I do too. This is so exciting. Yeah. Oh, wow.

So yes, there absolutely are things that, you know, do. And there's other toxins as well, too. There's other, there's other venoms. There's other toxins that interfere with this acetylcholine and whether they do it. And so that question is really important because in the case of botulinum, by blocking the release of acetylcholine, you leave those acetylcholine receptors on the muscle empty, which means the muscle is not getting a signal to contract, which means the muscle is relaxed. So the symptoms that we see of botulinum poisoning are a flaccid paralysis.

Rather than a contracted paralysis, which we see in other toxins that have different mechanisms of action. Like tetanus? Like tetanus. Yeah. Yeah. That's really cool. I know. Okay? It's very cool. I love it. I mean, I don't love it.

It's horrible. Okay. So now that we know the action of botulinum toxin, it's acting at the neuromuscular junction, the synapse between nerve and muscle, and it's blocking the release of acetylcholine, which means your muscles are getting no signal, which means they are relaxed and flaccid. So we pretty much know what the symptoms of botulism are, right? They're a flaccid paralysis. These symptoms are the same, no matter how you get exposed to botulinum toxin. Right. Because this is a toxin, it's traveling throughout your bloodstream.

Once it gets into you, no matter how it gets in, it's going to travel through your bloodstream and it's going to act on any nerve ending that it comes in contact with. Okay. Is the flaccid paralysis just sort of generally distributed throughout your bloodstream? body or is it concentrated depending on your root of exposure? Great question, Aaron. So what's very interesting about botulism specifically is that it causes a descending paralysis. Okay. So the paralysis starts in your face and your head. It starts with your cranial nerves. It causes a bilateral, so both sides, symmetric cranial nerve palsies that then eventually,

travels down and will cause flaccid paralysis throughout, no matter the root of entry. And we'll talk about the specific different routes of entry. This is botulism. Yeah. So you're exposed to enough toxin that it is distributed throughout your body and causing botulism. If you are exposed, for example, like in our first-hand account, to a very small amount of very, very dilute toxin in a very specific place, there's a very small amount. there's not enough of that toxin to travel throughout your body and cause systemic effects.

Right. It's a dosage thing. Exactly. Yeah. And so all of the symptoms that we see with botulism, even with botulism, are dose dependent. Right. Of course. Yeah. Why does it start in your head? It's such a good question. And I don't know. I couldn't figure out the exact answer to this. And what's interesting, though, is that it does distinguish. So if you clinically see someone, with paralysis, a flaccid paralysis, you know, you have, as a clinician in your head, a list of what you call differential diagnoses. What could be causing this? What are all the different things that could be causing the symptoms that I'm seeing, right? And there's a few

different things that you have to think about, things like Gianne Bray, for example. But Gianne Burray causes an ascending paralysis. So knowing the timeline of symptoms, like where they began and how they've changed over time is really important in trying to diagnose botulism. And I think that this is also partly why, for a long time, it was thought that this was a central nervous system toxin because your cranial nerves are closest to your brain, right? Yeah. They're coming out, like, directly from your brain stem.

Right. But it's actually a peripherally acting toxin. It's acting at the neuromuscular junction. So it's very interesting that your cranial nerves are still the first ones affected. This is fascinating. I know. Okay. So here are the symptoms, right? So the first signs and symptoms are things like blurred vision as the muscles that innervate your eyes become affected. Then you'll get tois, which is a great word, that means your eyelids are droopy, okay? Because your eyelid muscles are not working right. Then you'll get slurred speech as the muscles of your mouth and face get affected. Then the paralysis will continue moving down your body. You can get dry mouth and throat because, again, that parasympathetic nervous system is also. affected. So that's actually similar symptoms as to what we saw in Belladonna poisoning. Dry mouth, dry as a cracker or whatever.

I don't remember what that one was. Dry as a bone. Mad as a hatter. And a chicken. Mad as a hatter. Dry as a bone. Dry as a bone. Et cetera. Yeah. And then your voluntary muscles will start to become paralyzed. So first your neck, your shoulders, your upper arms, lower arms, upper legs, lower legs. Eventually, everyone would end up with constipation as the muscles that innervate your gut are paralyzed because gut in order to have poop at all, your gut has to be able to contract. Cause of death is usually respiratory arrest, and there's two different ways that this sort of ends up happening.

The muscles that control your breathing, your diaphragm and your intercostal muscles of your ribs, those become paralyzed, just like everything. and you can also get airway obstruction. As the muscles of your pharynx are paralyzed, your airway can kind of collapse inward and you can't. So it's kind of a combination of those two that ends up causing death in the case of botulism. Cool, cool, cool, cool, cool. That's horrifying.

It's horrifying. The rate that this progresses, so how long this all takes, and how far it actually progresses. So whether it makes it all the way to your respiratory muscles or whether you just have like only facial palsy depends largely like I said on the dose of toxin exposure. Right. However, and this part's really important, botulinum toxin binds irreversibly. So you cannot undo any damage that has already been done.

But your body does eventually regenerate those acetylcholine channels on the nerve terminal. It's just a slow process. So it's not like if you have facial palsy, you're not going to have a paralyzed face forever, but you can't undo that paralysis. You just have to wait for it to resolve. So how long are we talking? Generally weeks, possibly months. Okay. A couple questions.

The first is something that I read somewhere about maintaining consciousness. Erin, this is what I have next. Really? Okay. For you, this is just for you, Aaron. Okay, your sensory system is generally unaffected and your intellectual function is unaffected. So, yes, Erin, it's your greatest fear. It can leave you essentially locked in.

Cool, cool. Awesome. Because. Why do we keep doing these? Yeah, because you're paralyzed. And here's what's really scary is that because the muscles, like the voluntary muscles of your face and your throat and things are paralyzed. As you begin to have respiratory distress, you don't show any of the outward signs or symptoms of respiratory distress. There's no agitation. There's no restlessness.

You're not gasping or thrashing or flailing because you're paralyzed. Great. So the way that you know that someone is in respiratory distress is because their oxygen saturation is dropping on a monitor. So if you're at home, then you wouldn't. At that point, what can be done? So that is jumping the gun, but let's talk about treatment. The good news is there, there is treatment for this. It's absolutely can be fatal, but it is also treatable. We have an antitoxin. This antitoxin neutralizes circulating toxin and prevents it from binding to the nerve terminal. So it doesn't do anything for the toxin that's already bound, right? We can't unbind that toxin.

But it can neutralize any additional toxin that's circulating. So it's really important if these signs and symptoms start to appear that you get to a hospital for treatment because then they can continue supportive care, even if it gets to the point where you have like respiratory distress and things like that. Right. To get the antitoxin early is clutch. Yes. earlier the better is clutch is right. Okay, so that's like what botulism looks like clinically what the picture looks like. So how do you get it?

How do we avoid it, right? How do we not get it is what we want to know? There's three main ways and then a couple of ancillary ways as well. The first most famous, I think, is food poisoning, right? So if food is contaminated. with clostridium botulinum bacteria. And then those bacteria live in an environment that allows for them to grow. So no oxygen, not too low of pH, so not too acidic.

And just basically like a good environment for them to start growing and reproducing, they will then produce that toxin. You get botulism when you ingest that toxin. Not by ingesting the bacteria themselves. Gotcha. Yeah. So this is the same way that you might remember when we talked about in our Stafforius episode, our Mercer episode, you get food poisoning from Staff Oreas from the toxin, right? This is the same thing.

You get infected with the toxin. So if you have, for example, like canned tomatoes are a really good example because they're actually not that acidic. So if tomatoes are canned improperly and you have. a bunch of clostridium botulinum growing in there and then producing toxin, even if you reheat those tomatoes, you might kill the bacteria, but that toxin is still going to be there. So you can still get sick from it. Okay. But you can neutralize the toxin.

You can, absolutely. Yeah. If you, like, boil it for, I don't remember how long exactly. Yeah. You can definitely boil. Yeah. Okay. But that's why it's like so common in foods.

The bacteria can die, you know, after a certain. period of time, but that toxin can still be in those cans of food. Right. So that's one way. That's the most common way, food poisoning, botulism, okay? Yep. Now, you can get infected with the bacteria themselves, or the spores, which you're more likely to come in contact with in the environment, right?

Mm-hmm. In a couple of different ways, the least common, but less depressing, is wound botulism. Oh, yeah. Okay. So if you have a wound that gets contaminated either with clustered in botulinum bacteria or their spores, which are very common in the environment, if that wound festers, it can become anoxic in that environment. The bacteria or those spores can reactivate and begin to reproduce and produce toxin. So then you, the bacteria are making toxin in your own body. The effects are the same as if you got body. botulism from food poisoning. Mm-hmm. Okay, they're the same. Because this is a toxin that has neuromuscular effects.

So it's overall, it's the same. Right. Now, the most common and I think the most depressing form of botulism, of course, is infant botulism. Right. It's always depressing when it's babies. So, and this is different, even though this happens when an infant ingests, like, so it's technically a food poisoning, it is not the same as when an adult gets botulism. And that's because infant botulism happens when infants ingest the spores of claustridium botulinum.

So unlike adults, infants, especially of a certain age, so it's usually greater than like three weeks but less than one year old, they have a very naive and naked gut flora. So their guts are not able to inactivate or prevent those botulinum spores from becoming activated and colonizing their guts. Gotcha. So then the bacteria in the infant gut reproduce and produce toxin inside of the baby rather than the baby eating toxin directly. Yeah, that's horrible. And infant botulism is often called floppy baby syndrome. Okay.

That makes sense with the flaccid paralysis. Exactly, right. It is possible, however, it's extremely, extremely rare for an adult to become colonized with Clostridium botulinum and then have that same syndrome as infant botulism. It's called adult intestinal toxemia. It's just very rare because we have other microflora that are much better at competing and out-compete those Clostridium species. It's similar with Clostridium difficile, like that's an opportunistic infection, right?

It's not good at taking over our gut flora. Right. So usually it's like following a huge rounds of antibiotics and stuff like that. Right. Yeah. One question is where do infants get exposed to, yeah, honey. So that's like. And it's just because honey is a...

It just has a ton of spores. Like it, there are a lot of clostridium botulinum spores very commonly found in honey. and because an infant gut can't neutralize those spores, they can get infected with botulism or with clostridine and develop botulism from honey. It's not the only thing in the world, but it's sort of one of the most common roots of exposure. So that's why infants under 12 months can't have honey. Yep.

Shouldn't have honey. Yeah. It's also possible to be infected through aerosolized toxin so you could in theory inhale this. I don't know that it's ever been recorded. It would have to be intentional. Right. I'll have to like. Oh, great.

Just a little. And then, of course, you could get it through injection as well. So if you injected a large amount of this toxin into your veins or muscles, then it could spread through your body and cause botulism that way as well. Cool. But now. What's... So botulinum toxin is considered the most potent toxin that we know of. Are you going to talk more about that, Erin?

Well, I can drop the knowledge right here if you want me to. Let's, because I want to know about it. Okay. Well, all I know about in terms of that is I read somewhere in one of these papers that because the amount of botulidum toxin that it takes to kill an average human is X and whatever amount. Yeah, some very small amount. Some tiny, tiny, minuscule, unfathomably small amount.

If you multiplied that by the number of people on Earth, estimates are that it takes approximately 40 grams of botulinum toxin to wipe out humanity. That's why you wanted me to weigh out 40 grams of something? Yeah. I texted you and I was like, so can you just put like how many slices of bread is 40 grams? Because I need to visualize this. So how many slices of bread is 40 grams? Okay.

The sourdough bread that I have right now, one slice of it weighs 45 grams. Okay. For another visual, a half a cup of coffee beans is 40 grams. There you go. That's how much botulinum toxin it would take to kill all of the humans on the planet right now. That's what I, yeah, I have, and I have the paper, I'll cite the paper on our website so you can go and read it for yourself. But yeah, like 39.4 grams or something. Whoa. Isn't that wild? Yeah, man. That's, whoa. well, that's botulism.

Oh, that was it. That's it. It's all I got. We already talked about how you treat it. Oh, cool. It's a little terrifying, but we'll talk later about how innovative people have gotten with something that is so terrifying. Yeah, I'll talk about it. It's really fascinating.

This is, I think, one of my favorite episodes so far to have read about. I don't know why. Tell me about it, Aaron. How did we get here? where did this thing come from? How did it evolve? Why does it have a toxin that can kill all of humanity? Like, what's up with that? I'm so glad you asked. I will answer as well as I can after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief.

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We're offering our listeners 15% off their first order of O'Keef's. Just visit O'Keef's Company.com slash this podcast and code this podcast at checkout. I'm Austin Hinkwitz. And I'm Janice Torres. Join us for Season 4 of Mind the Business, Small Business Success Stories from Ruby Studio and Intuit QuickBooks. We're back and talking to more inspiring small business owners about everything from the changing business landscape to the rise of artificial intelligence and how QuickBooks on the Intuit platform helps you outdo what you're capable of. So outdo it with Intuit QuickBooks. Working in QuickBooks just makes it easier to run the business.

There's so much that you need to do when it comes to running a business, building products, setting up marketing campaigns. And to run a business, you have to make sure that your finances aren't order. So it removes my anxiety from one side of it so that I can focus on everything else. Listen to new episodes of Mind the Business, Small Business Success Stories, every other Thursday on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is Bethany Frankel from Just Be with Bethany Frankel. Listen, I have a bone to pick with these dog food brands calling themselves fresh, natural, healthy. Sounds great, but a lot of these quote unquote fresh dog foods in your fridge are not eating. even 100% human grade, which is why feed your babies, just food for dogs.

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capping full Broadway performance every single night. So I do care about the food I feed big and smalls. So go to just foodfor dogs.com for 50% off your first box, no code, no gimmicks, just real fresh food. Okay. Doesn't this remind you of an episode of one of our crossover episodes with Matt? 100% yes. Yeah, that's why I kept talking about atropine and stuff.

Exactly. Matt, we miss you. Yeah. We'll do another crossover soon. Yeah, we will. He doesn't know it, but he doesn't know it. We want to do another crossover soon, Matt. Okay. So just like you asked, why does this toxin exist? Why does this bacteria produce this toxin? And so that's what I want to start off by trying to answer. Basically, why are you the way you are? So in our normal episodes, this type of question is generally pretty easy to answer, right? Because it mostly has to do with the pathogen increasing its chances of transmission or something like that. That's generally the pattern that we see. Like, for example, as we mentioned earlier, the toxin that the cholera bacterium produces makes you poop out a ton of vibrocholera cells so it can spread

to other people. I'm so excited about this. I can't wait. Yeah. Why then? But with botulism, Humans seem more like unfortunate bystanders than the stars of the show, right? Right. So it's not spread from person to person, really. So what purpose does this paralytic or fatal toxin serve? How does it actually help the bacterium? Does it even help the bacterium? To answer that question, I got to talk a little bit about the ecology of Clostridium Botulinum.

Your favorite? My favorite. A lot of the research on botulism. focuses on humans, like outbreaks at potlucks, the toxins used in therapeutics, the physiological mechanism of the toxin itself, et cetera. But to these bacteria, humans play a very small role. Right. Aaron, this is jumping the gun, but around how many cases of botulism do we see a year in the U.S.? Like 182 in 2017? Yeah, like very low. Yeah. But it's a lot. But it's a lot. It's a whole other story for some other animals, especially migratory birds.

Really? Really. Botulism is one of the biggest, if not the biggest, disease of migratory birds, especially those that like water, like shorebirds and waterfowl. Swampbirds. This is literally blowing my mind. I'm so excited that it is. A typical outbreak of avian botulism, so they have.

happen pretty much every year, it seems, like they're pretty common, might claim the lives of 50,000 birds or more. But there have been outbreaks with over a million birds dying. What on earth? Yeah. And most of these outbreaks, and you didn't really talk about types, but just FYI, it's like types of toxins because it's a whole other can of germs. Oh, my gosh. Oh, cool. Good one. That was good. But these are just for. for reference type C botulinum toxin. Okay. Yeah. Okay. So the reason that we see these outbreaks occurring among these water-loving birds is that the environments where they like to hang out, it can be full of decaying organic matter, which can make for a perfect setting for the growth

of these anaerobic bacteria. And these anaerobic bacteria can then be easily ingested by like a dabbling duck or a filter-feeding shoveler. A dabbling, that's like an actual term. Oh, really? It's much as a cute little alliteration there. You know, when they kind of like, dip, dip, dip up across the surface and they duck their heads in and they like their little butt stuck out, that's like a dabble, a dabbling.

You're making me like birds, Aaron. Also, apologies to any bird people who are like, wow, you're getting all this wrong. So, I'm doing the best I can. We're going to get an email from like Fred and Nick. And Maria. And Maria. And we have a lot of birds. bird friends. I know. I'm sorry. Okay. So let's say that one of these birds, one of these dabbling

ducks, ingest some swamp stuff containing clostridium bochalinum. The bacteria may colonize that birds' intestines or liver without any apparent effects maybe. Okay. Yeah. And then let's say the bird dies for whatever reason. Maybe it's because of the toxin. Maybe it's because it hit a power line. maybe it's because it ate some whatever. Maybe it just dies, right? Okay. That decomposing bird is a great environment for clostridium botulinum. It's warm, it's anaerobic, it's everything you could ask for.

Okay. If you're a clostridium botulinum. Yeah. Soon, that carcass is teeming with C. Botulinum and it's toxin. Okay. And it's also hosting a ton of other decomposers, for instance, some invertebrate. decomposers like blowfly larvae. Yeah, yeah. And so normally, waterfowl won't directly munch on vertebrate carcasses, but do you know what they will munch on? Blowflies. Magets, yes. So the larvae that these

blowflies laid in the carcass become loaded with botulinum toxin, and invertebrates are not affected by the toxin. And so other birds eat these maggots, die from the excessive amounts of toxin, and that leads to more toxic maggots and so on. Whoa. And so that's how these avian botulatum outbreaks can be absolutely explosive. It's called like the carcass. Hold on. Let me find it.

It's like the carcass maggot cycle. What? How have I never heard of this, Aaron? I know. It blew my mind. Oh my. Because they don't affect invertebrates. Uh-huh.

Oh, my gracious. And then, of course, other vertebrates might directly feed on the contaminated carcass and then die, which would then create another amazing anaerobic environment for the bacterium to replicate. And then that would spread the bacteria of the environment and provide more anaerobic ground. It just sort of the cycle continues. Oh. I'm getting chills. I know.

This is why I was so excited for this episode. Okay, so I went into all of this to show like a natural cycle of C. Botulinum and its ecological role. And I did this to get at the question earlier, why are you the way you are? Yeah. It could be accidental. But most researchers believe that by killing a vertebrate host or even increasing the probability of a host dying, it carves out a space for itself to represent. and produce more toxin. Totally.

And so the mechanism of that, like the paralysis and blurred vision and so on, those are things that even if the toxin doesn't necessarily kill you outright, it will in the wild greatly increase your chances of becoming a carcass. Absolutely. Of becoming a carcass. Also, I think that that's our title, Aaron, is why are you the way you are? Why are you the way you are? Okay.

I love it. It's fantastic. It should just be C botulina. No, it has to be botulism, but botulism, why are you the way you are? It's so good. So good. I also liked no wrinkles in time, which was a contender for our... That's funny, but this is better. But yeah, so, and so if you think about it, we've done so much laboratory research, not we, but the world has done so much laboratory research on botulinum toxin, but those are under laboratory settings. And so the amount that it takes to kill an animal in a lab setting is much, much, much greater than what it takes to lead to death in a natural setting. Yeah, yeah, yeah. Yeah. Oh, that makes so much sense. Yeah. Oh. So that, I think, is why this toxin exists.

That is episode over. That's all I need to know. It's so cool. I know. I honestly had the time of my life. What a fun fact. I know. I know. Yeah. What a clever little bacterium, though. I know. I know. Yeah. I think the whole like, clever, but, you know. Comparative evolution. And there's, so there's so much more that goes into this, like, ecology. Like, why are there multiple toxins? Why is there variation among their toxicity or potency or whatever? Why, you know, why do we see these different seasonalities, what triggers these avian botulism outbreaks. Why quite so potent? You know what I mean? Like, why couldn't you be like, you know, the amount? It's, yeah. Yes. It's, I mean, yeah, we could spend all day talking about just this part of it. But that's not this podcast. Let's go back to the human side

of things, I guess. Okay. So see botulinum as, you know, an environmental bacteria. is probably super old, you know, like, and it doesn't really seem, though, to have a long evolutionary history with humans because of this more incidental nature of infection or impact. Yeah. But at the same time, it has not been a stranger to humans throughout history, like probably all of human history. That makes sense. Yeah. I mean, essentially, as soon as humans started to try to preserve or store food, there were cases or outbreaks of botulism.

Right. And probably honey. Honey is one of the oldest foods in the world. Yeah. So infant botulism. Boom. And so while in ancient times, people may not have recognized exactly what was causing food-related paralysis or death that they may have seen, it does seem like they took note

of the foods where it seemed more likely to happen, like blood sausages or cured ham or fermented fish. Interesting. Yeah. Let me give you a couple of examples. The powder of blood sausage, dried under anaerobic conditions, appears as an ingredient in at least one recipe for a deadly potion. Ooh. And Emperor Leo, the sixth of Byzantium, who ruled in the late 9th and early 10th centuries.

Just go with it. He outlawed blood sausages. Like the production of them and the whatever. Aaron, where you get your facts. Just love it. But some researchers think that him outlawing blood sausages is tied to blood sausages being a more common source of botulism. Okay. And some descriptions of poisoning with atropine, aka Belladonna, may have actually been botulism instead because they describe a different, they describe like the consciousness and then like the full plastic paralysis.

Right, yeah, because you don't get that with atropine because it doesn't affect your skin. skeletal muscles. Right. Yeah, cool. Oh, yeah. But Cibachalinum really began to get the widespread recognition it deserved, starting in the late 1700s. Napoleon had been waging his wars all throughout Europe and kind of devastating the land. Like these wars devastated the land. There was tons of poverty. Hygiene went way down, particularly in central Europe. And one of the victims of this was apparently safety standards in food production. I don't know exactly what safety standards were like for food production in the 17th century. They really went downhill.

Yeah. Whatever they were, it just went down from there. And so the number of fatal food poisoning cases jumped in a region in the southwest of Germany called Apologies for the pronunciation, Wurttemberg, whatever. And in one outbreak in 1793, 13 people became sick and six died. Wow. And the cases had one thing in common, blood sausages. A blood sausage can be many things, but it's generally a pig's stomach stuffed with meat, grease, blood, herbs, bread, cereals, sometimes the pigs innards.

And it's smoked and then boiled and then eaten. If you don't boil it long enough, guess what can happen? Over the next couple of decades, these reports of fatal food poisoning continue to pour in, and the terms sausage poisoning became the in vogue term to describe them. Okay. In a small town in this Vertemberg region, a 29-year-old medical officer by the name of Justinus, I'm not sure, Kerner, had become very interested in this sausage poisoning situation. He, and he would end up making enormous strides in research on C. Botulinum even before germ theory had been developed.

Cool. This is very cool. All right. So let's go through his various discoveries. Number one, he began doing his own groundwork on sausage poisoning cases. And in 1820, he published case reports of 76 patients and the first clinical description of botulism that tracks very closely with how it's described today. Wow. So I'm going to read this and I want you to just like, this is 1820.

And just say wow, Aaron. Just react for me. my job during this section anyway. Okay, quote, the tear fluid disappears, the gullet becomes a dead and motionless tube. In all mucus cavities of the human machine, the secretion of the normal mucus stands still, from the biggest, the stomach, toward the tear canal and the excretory ducts of the lingual glands. No saliva is secreted. No drop of wetness is felt in the mouth. No tear is secreted anymore. No ear wax appears in the auditory canal, also signs of drying out of the Eustachian tube become apparent. No mucus is secreted in the nose. No more sperm is secreted. The testicles decrease.

Urination can only be performed by standing and with difficulty. Extreme drying out of the palms, the souls, and the eyelids occurs. That is a great description. Yeah. 1820. I especially loved that he said, the human machine. The human machine. That is my new favorite term. Oh, yeah. No, yeah, that's, now I will say that that description could also have been belladonic, because he didn't really talk about the paralysis aspect of the skeletal muscles. He does in other, so that was like an excerpt from this.

Yeah, yeah. And as we'll see, yeah, he did, he did tons and tons of work. So he did, like, expound more upon the paralysis aspects of it. It's a good, like, you should, we should use that in school to talk about the effects of the parasympathetic. nervous system because he did a really good job of going through them all. Yeah. Nice. Yeah.

Good job, Kerner. Okay. Number two, that's only number one. Okay. Wow. Number two, he didn't stop with just describing sausage poisoning. He wanted to understand what exactly was causing these symptoms and how. So he collected the sausages that he suspected were involved in the poisonings and he compared

their ingredients. And the only two commonalities he found were salt, which he believed to be innocent. and fat. So he came to the conclusion that fat, what he called fatty acid, was the cause of this sausage poisoning. Okay. And so he attempted to isolate this fatty acid or sausage poison from these poison sausages and conduct some experiments to see if he could recreate the symptoms. And so he fed this fatty acid to birds, cats, rabbits, frogs, flies, locust, snails,

and so on. Wow. Some of these experiments worked. Yeah. And some of these experiments worked. Like they developed paralysis. And he also experimented on himself a few times and described what happened there. And then his professor was like, dude, what are you doing?

Stop doing that. You're going to die if you do that. Dude, stop doing that. Stop doing that. Oh, my God. Yeah. All right. So number three, through these experiments, he was able to closely.

examine the stages of paralysis and even developed some hypotheses as to just how the toxin causes these symptoms, basically deducing that it was through an interruption of the peripheral and autonomic nervous signal transmission. What? Isn't that amazing? Wow, that is incredible. This is what he wrote. Quote, the nerve conduction is brought by the toxin into a condition in which its

influence on the chemical process of life is interrupted. The capacity of nerve conduction is interrupted by the toxin in the same way as an electrical conductor by rust. Chilis. 100%. In 1820. Like, this is incredible. Wow. That is phenomenal.

You're about to be even more blown away. Oh my gosh. Because number four, he went on to suggest possible ways to prevent sausage poisoning through longer boiling times, through storing the sausage in dry in aerobic conditions. And he also suggested. suggested a way to treat it. He invented an elastic tube that some people view as the first gastric tube to make sure that his patients got enough nutrition and didn't choke to death or didn't aspirate. Yeah. Wow. Okay. Number five, this is the last one. He went on to propose that this toxin could be used therapeutically to calm overexcited nervous systems.

he suggested it could be used to cure St. Vitus' dance, remember from dancing plague episodes? Yeah. And also some other things, which are a little less grounded in reality mechanism, excess sweat, rabies, plague, yellow fever. Again, it was pre-germ theory days, so we can give him a break on that. But it's amazing that he would recommend therapeutic applications like 150 years before they were put into practice. Phenomenal.

Amazing. Okay. So to recap real quick. Number one, the first clinical description. Number two, isolation of the toxin. Number three, explanation of the mechanism of the toxin. I mean, and also number two, it's a little hand-wavy, but he was able to actually, whatever. He tried.

Number three, explanation of the mechanism of the toxin. Number four, prevention and treatment methods. And number five, suggestions for therapeutic use. Incredible. Human ingenu. Right there. Human ingenuity. That is the kind of human that Dr. Who is like all about.

Yeah. Yeah. No, exactly. Anyways. Wow. Yep. Wow. His work on sausage poisoning earned him a bit of notoriety as the leading expert,

and he was known as Verst Kerner, Sausage Kerner. Also, he was apparently a very accomplished poet, especially in his later years. You can read his story. Poetry online. Very cute. Okay, so I've gotten this far in the history of botulinum, toxin, C. botulinum, botulism, whatever. And I have yet to talk about etymology.

Oh, Aaron. Botulism, like the term botulism, it got its official name in 1870 and its scientific name for C. Botulinum in 1897. And I'll tell that story in a second about that. Okay. But first, clostridium botulinum. Originally, it was called bacillus botulinum. Bacillus is basically, as you said, meaning rod-shaped.

But it was later renamed Clostridium from the Greek closter, meaning spindle, because the colonies of bacteria in this genus apparently resembles spindles. Okay. And botulinum from the Latin word botulis, meaning sausage. Stop it. Uh-huh. Sausage. sausage. Not what I was expecting, but after that story, not surprised. Spindle sausage. Spindle sauce.

Isn't that incredible? That is hilarious. Sausage. Wow. So by the late 1800s, botulism and its association with sausages was well known throughout Europe, but it would take a funeral with pickled ham, nearly three dozen people falling ill, and three dead for it to be recognized. as being caused by bacteria. Ooh. In December of 1895, in a small town in Belgium, around 34 musicians in the local brass band gathered to play at the funeral of 87-year-old Antoine Crouture, a town elder.

Oh. After the funeral was over, they were given dinner at the local inn, and this dinner consisted of, among other things, smoked or pickled ham. Unfortunately, it hadn't been preserved or cured properly, and within a few days, the entire band began showing signs of botulism, the entire band. All 34 members? All 34.

Three ended up dying. Oh, dear. A microbiologist named Emil Pierre Van Ermengam, Germ. Ermeng. Irman gem? I don't know. Anyway, he was professor at the University of Ghent at the time, but he had previously worked with Robert Koch, and he had caught wind of the outbreak. He examined the ham and tissues from those who had died and went about looking for microbes, and he found them and called them bacillospotulinum.

It would take nearly another 30 years for the toxin itself to be discovered and isolated, but during that time, people grew to realize. that this was certainly not just a disease of sausages or ham or fish. It could also come from white beans in one of the first canning outbreaks, olives, or basically anything. Cases of botulism continued to rise as the technology to can or preserve food continued to develop into the 20th century, and both commercial and home canning or food preservation carried risks of botulism, and it took many, many outbreaks, both from mass-produced cans and home-can foods, for people to gain an understanding of the techniques you had to use to properly prevent botulism from happening or the toxin from developing.

Right. And because treatment for a good portion of this history was not an option. Like, we didn't have the antitoxin until relatively recently, I think, the past few decades. Would just be supportive care in that case then, yeah. Mm-hmm. Okay. So in 1820 at the University of California, a researcher named Dr. Herman Sommer Summer was finally able to isolate a botul atom toxin type A, if you're interested. It makes sense that it was A, so it was the first one.

Mm-hmm. An additional research showed it to be the most toxic substance known to humans, as we discussed earlier. So why do you think this research was being conducted? Why were people interested in botulism? Oh, I don't know, maybe like bio-warfare or something like that. There you go. Yeah. So it was probably a good thing that it was isolated, that the toxin was isolated a couple

years after World War I ended. Oh, dear. But guess what was just around the corner? World War II. Not that World War II was exactly looming on the horizon in 1920, but, you know, kind of, whatever. There was always, you know, a reason to. be able to produce a bio weapon, right? So the U.S. Army Biological Warfare Laboratories at Fort Dietrich in Maryland had a special interest in developing botulism or botulidum toxin as a weapon to use

in the war during World War II. And supposedly, supposedly, they had even developed a plan to try that out that involved having people assassinate high-ranking officers in the Japanese army by dropping a gelatin capsule containing botulinum toxin into their food or drink. Whoa. The plan was abandoned when the capsules were tried out on donkeys and had no effect. They didn't make a good enough capsule or something? Well, so one of the hypotheses is that donkeys are immune to botulinum toxin, but that seems to be really debated. And so it just seems unclear.

Interesting. Yeah. In any case, botulinum toxin was abandoned as a bioweapon for a lot of the same reasons that ricin was abandoned, if you remember in that episode. It doesn't spread person to person. The dosage is hard to control. It's easily inactivated. And it now can be treated. So, you know, in terms of a bioweapon, it's not great.

It also, like, it's not super fast acting. I don't know if that's a good thing or a bad thing in terms of bio-weapons. I've never. I don't know what the objective is, like, to terrorize people. then, you know. Then it's not that great. Yeah. And now, you know, Fort D. Trick is now all about biodefense rather than offense.

So anyway, it was abandoned. Okay. So in keeping with the theme of poisons that we usually use for these types of, for those crossover episodes that we do. Right. Yeah. I think it's time to chat about the other side of the coin or cans. Yes. The other side of the can.

The other side of the can. Okay. Tell me about it. Okay, botulinum toxin in therapeutics. So Kerner suggested it in 1820. Way ahead of the game. Way ahead of the game. But it wasn't until the 1960s or 1970s that it was developed for treatment purposes.

Cool. The first pilot study of type A botulinum toxin to treat strabismus in humans, basically cross-eyedness, right? Yeah, misalignment of your eyes. Here we go. This first study was done in 1978. and was shown to be effective. The FDA approved its use a year later. Cool.

And that really opened the door for doctors to use it to treat all kinds of involuntary muscle contractions. Yeah. And Erin, I'm sure you're going to talk more about what those treatments are. Absolutely. In the next section. But before we get to that, we have one more little piece of business to cover the Botox business, to be precise. How did this begin?

So let's head to. 1987. Bachelinam toxin had been used for these various things about 10 years at that point. Okay. And an ophthalmologist named Dr. Jean Carruthers had been shooting botulinum toxin into her patients to treat abnormal and voluntary blinking. Do you know what the technical term is for that? God, I feel like I should. So to the B ends in spasm. Oh, blarphospasm or something. Yeah, blephorospasm. It's a very awesome. awkward sounding word. It really is, yeah. So she noticed that when she did this, when she injected this botulinum toxin into her patients near their eyes, their frown lines disappeared. Some of the

wrinkles around their eyes disappeared. So she went home and mentioned it to her husband, who happened to be a dermatologist. And they were like, holy cow, we just stumbled upon what might be the most revolutionary cosmetic procedure yet. Yep. And they worked on it for about 10 years before publishing their first report in 1996. And since then, it has become perhaps, and you'll maybe talk more about this, perhaps the most widespread and profitable cosmetic treatment. By far.

So, that's kind of where my story ends, from sausage poisoning to wrinkle reducing, the glorious story of Clostridium, botulinum. Wow, that is so fun. Isn't that fun? Migratory birds, blood sausages. What an interesting story. Do you see why I was like so, it's like one of my favorites. It just feels, you know, I don't know.

I agree. It's very satisfying the whole story. It is satisfying. It is so fun. And there's a lot too. Like, you know, I didn't mention sort of the food outbreaks that have happened throughout the 20th century because there have been a lot. But I didn't go into detail on those.

But I will say, there have been many. Yeah. So let's talk about where we stand with botulism and claustrating botul item today. Let's take a quick break. So let's talk first just about kind of the depressing botulism part of it. Get that out of the way so we can end on happy notes, okay? Yeah. Okay. So in 2017, in the United States, like I mentioned already when you asked, there were 182 laboratory confirmed cases of botulism reported to the CDC.

Botulism is a reportable illness because it is very rare and serious. Most of those, the vast majority, and this has been true, like at least since the 80s, the vast majority of botulism cases are infant botulism. So like 70 to 80% of all cases of botulism in the U.S. are infant botulism. About 10% are foodborne, or at least in 2017 they were. And about 10% were wound botulism. Okay. There were, at least in 2017, three classified as other. So two of them were iatrogenic, so they somehow got infected through like hospital procedures or something like that.

And then one was suspected adult intestinal colonization, which I mentioned can happen, but is, of course, exceedingly rare. Cool? Yes. And so I don't really have a lot of details on, like, these are the foods that are most common to cause botulism because I don't, I just don't really find it that interesting. Like, in theory, almost any canned food, if it doesn't have enough acid in it, can be a medium for clostridium botulinum to grow. Right. therefore could put you at risk. It's like there's there's like a decent temperature range and a decent pH range where this bacterium can reproduce under anaerobic conditions. And so you can

Google that. And then if you're going to can food, just do it properly. That's fine. No big deal. But anyways, it's, you know, it is still possible. It absolutely still happens. But the vast majority of cases are infant botulism and most of those are from honey. So, uh, yeah. Okay. So let's talk about the more interesting and kind of fun, cool aspects of botulinum toxin. And that is all the different ways that we use it currently. Okay. Botulinum toxin is used medically to treat a lot of different dystonias, which is what you mentioned, Aaron. A dystonia is inappropriate muscle contractions. And these can be really, really painful. So one of the most common uses for botulism is to treat cervical dystonia, which is a contraction of your neck muscles that can be really, really

painful. It's also used to treat laryngeal dystonia, so contraction of your larynx that's inappropriate. It has been used to treat tremors, certain types of tremors. It's often used in the treatment of cerebral palsy, which is you have a lot of inappropriate contraction in cerebral palsy. Interestingly, it's more recently been used. used to treat headaches, both migraine headaches and chronic contraction, like muscle-type headaches. I saw that. How does that work?

It's such a good question. We don't really know because from what I understand, there have been a number of studies, although not a ton, but a number of studies, like placebo-controlled studies that show that injection of Botox, like in your, like, paravertebrals, like a near-yourverect. is more effective than placebo in treating chronic headaches. But when they have tested, like, whether your muscles, like whether you can still have pain conduction, that is intact and it's the same as placebo.

So they don't actually understand what the mechanism is that is relieving these headaches. But we also don't really understand what causes a lot of headaches. That's what I was going to say. we don't really know about headaches and migraines. That's very interesting. Yeah. It's very interesting.

And they just discovered this by accident? No, I think it was because a lot of the, a lot of treatments for migraines have to do with like vascular dilation and things like that. So like, and a lot of, you can achieve that type of dilation by relaxing the muscles around the blood vessels as well. So I don't know if that was the thought process behind it. But also not just, it's not just migraine headaches. It's other tension headaches as well, which is not maybe that has to do with, you know, muscle tension. Right, right, right. That's so interesting.

Also, going still in your head and neck area, TMJ has been treated with Botox. I know. I was like, can I get some of that anyways? You mentioned that it was suggested to be treated for excessive sweating. that is actually a use of Botox today. Yeah. So hyperhidrosis, which is excessive sweat, you can treat that with Botox. Turner got one thing, right?

He sure did. I have to tell you, this is really fun. I have injected Botox into someone. Ooh. Me, personally. I have injected Botox into the detruser muscle of the bladder during my Obiegine rotation. Oh, that's exciting. So this is a treatment for overactive bladder.

Oh, that makes sense. Uh-huh, yeah, you relax that muscle. I want to say that the physician that was doing the surgery actually stuck the needle in and was guiding the camera. I literally just pushed the plunger, so I was very well supervised in doing this. So yeah, there are a lot of different ways that Botox is one. of the, like, trade names, I guess, for botuline and toxin. It's like registered or copyrighted or trademarks or whatever. Yeah.

There's a whole bunch of different forms of it. There's, so in addition to Botox, which was the first one, there's one called Dysport. That's actually a type B toxin, where Botox is type A. There's myoblock, there's neuroblock. There's a brand in China called Hengli. There's a lot of different types, but Botox was like the first. that was commercially available botulinum toxin. Right.

Okay. So then let's talk about Botox. Because when you hear Botox, you think of... Face injections for wrinkle reducing. Yes, you think of face injections, wrinkle reducing Botox. Mm-hmm. And this is absolutely without a doubt not only the most common use of Botox, but also, or of botulinum toxin, but also the most common cosmetic procedure by far.

So according to the 2018 Plastic Surgery Statistics Report put out by the American Society of Plastic Surgeons, there were, in 2018, over 7 million Botox procedures. Wow. Isn't that? Amazing. Yeah. It's a lot. That's a lot.

That's a lot of procedures. It is by far the most common minimally invasive cosmetic procedure. And this has grown a ton. So it was licensed by the FDA for cosmetic use in 2002. And it's increased in like popularity and demand like over 750% in the years. Yeah. So it's just on the rise. Because at first when I was looking up statistics on how many.

people get Botox or how many Botox procedures. Because this is not people who get Botox. This is Botox procedures. In 2014, it was like 6 million that they estimated. So now we can see in 2018 it was over 7 million, close to 8 million actually. Gotcha. Gotcha. 7.5 million.

So, yeah, it just, it's really, really increasing, which is, it's fascinating. So I want to talk about a few things having to do with boats. Botox. Okay. So the reason that Botox works to reduce your wrinkles is because you inject a very small, very, very small, very dilute amount directly into the muscles. And that toxin is going to affect the neuromuscular junction. It's going to block the release of acetylcholine and it's going to cause those muscles that are innervated by those nerves to relax. Okay. And if you have relaxed muscles, then you're not going to have the appearance of wrinkles because those are caused by muscles contracting in different ways.

Okay? Mm-hmm. However, even though botulinum toxin binds irreversibly to those nerve terminals, eventually your body regenerates the ability to release acetylcholine. So eventually, you're going to have movement of those muscles again when your body, is able to kind of work around the fact that those have been blocked by botulinum toxin. Does that make sense? Yeah.

So the effects of Botox or botulinum toxin don't last forever, which is why you have to re-up your Botox every however many months. And it depends, you know, how much you inject and also just person-to-person variation, how often that is going to be. The other thing I want to say is that because, so this is a, obviously a very, very, very potent toxin. This is a drug that is highly regulated. I found at least one paper that I don't think was legit.

That was like someone collapsed and died in a beauty salon after Botox injection. And I just want to say that like even if someone were to die from getting too much Botox, because in theory that is, of course, possible because it's a very very very, deadly toxin. Getting too much Botoxes and too much botulinum toxin. Right. Not the treatment. Yeah, yeah, yeah, yeah, exactly. Too, like inappropriate use of botulinum toxin injection. Not just like, you know, you win a little heavy or whatever. You wouldn't die right away, right? That's not how botulinum toxin works. You wouldn't just collapse and die. Yeah. Even the effects of Botox take time to work. It's not something that happens.

automatically, this isn't a toxin that just like blocks all of your nerve signals and kills you right away or anything like that. That's not the mechanism of how you would die from botulinum toxin to begin with. So if you ever see something like that, that's not real. That's not how it works. And I found it on a cursory search, so I feel like I need to put that out there. But it's very, it's very interesting. I think it's very fascinating that we have so many uses for some things. that is so deadly. It's so cool. It's so cool. I think it's amazing. I mean, it's just more of those, like, I don't know, being very innovative with and open-minded in terms of like, what can we do and then, and also testing it out in like very regulated ways and sort of letting it build upon

what we see. Yeah, absolutely. Amazing. I feel like this is such a big, like this topic is so much bigger than I thought it was going to be starting out. Yeah. And it's so much more fun. Like, I mean, botulism poisoning is really depressing, but... Of course. But the overall story of Clostridium botulinum and of botulinum toxin is fascinating and fun. It's so interesting. It's just so interesting. Yeah. I love it. Cool. Okay. Well, sources? Sources. I have a bunch of But I want to highlight a few that I really enjoyed or relied heavily on. The first is a chapter called avian botulism in a book titled Infectious Diseases of Wild Birds. Okay.

And the other one, someone named Urb Guth, wrote many, many papers on the history of botulism. Okay. And so there are several of those. One that I'll call it in particular was from 2008. And then another paper about sort of the why of botulism is by Mansfield and Doxy from 2018. It's titled Genomic Insights into the Evolution and Ecology of Botulinum Neurotoxins. And then finally, Montecucco and Risotto from 2015 titled on Botulineum Neurotoxin Variability. Awesome.

I have a couple really in-depth papers on the toxin of Clostridium botulinum, especially if you want to know more about all the different types, because there are a lot of different types of this toxin. Those are old papers, but they're still valid. There's a nice clinical infectious diseases paper just titled botulism that I used if you want to know kind of about the disease syndrome of botulism. and then a few other papers that I'll put up about kind of botulism botulinum toxin use in clinical scenarios. So yeah. Cool. All right. Is that it? I think that's it.

So, wow, cool. Thank you to Bloodmobile for providing our quarantini title and the music for this episode and all of our episodes. And thank you to you listeners for a list. listening. And also, we want to especially thank everyone who keeps jumping on the quarantini posts and stuff and saying, TPWKY did it first. We love you. We really do. I get a warm feeling in my heart every time I see those. Me too. Also, it came to our attention that apparently we didn't really do it first, that it was on an episode of Scrubs, but I genuinely, like, I haven't watched that show. And you, like, definitely, we thought that you came up with it. So, like, in our hearts, we.

Yeah. We tried. So, you know, I mean, I think that just goes to show that there's nothing new ever invented ever. Ever. That's fine by us. Except Botox that first time. Except Verst-Contur did it first. What was his name? Verst. Verst, Kerner. Verst-Kerner. He did it first. The sausage king. The sausage kernel king.

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