This Podcast Will Kill You - Ep 16 Scratch and Sniff Diphtheria Membrane

Episode Date: December 24, 2018

This episode is so good that we’re putting it out a full day early. Pour yourself a quarantini and cozy up with us as we tell you a story of a bacterium that slowly strangles children to death, a scientific quest that helped shape the understanding of infectious diseases, and a great dog sled race across wild and frozen lands to stop death in its tracks. The main character of this story is, you guessed it, Diphtheria. This dreaded disease still lingers, infecting children throughout the world today with its stinking pseudomembrane. But don't worry, it's not all bad news... we have a vaccine. See omnystudio.com/listener for privacy information.

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This is a job for Indeed sponsored jobs. The disease began in various ways, but commonly with chills and heats. pressure and pain in the head, soreness of throat and hoarseness, some cough, sickness of the stomach, frequent vomiting and purging. These symptoms occurred more frequently in children and were then very severe. In adults, they were less emphatically expressed. Commonly on the uvula, tonsils, vellum, palatinum, and back part of the pharynx, several whitish or ash-colored spots appeared scattered up and down, which oftentimes increased very fast, soon covering one or both of the tonsils. These eventually proved to be the sloughs of superficial ulcers. The tongue at this time,

though only white and moist at the top, was very foul at the root and covered with a thick, yellowish, or brown coat. The breath also now began to be very nauseous. The offensive smell increased hourly, Some instances became quite intolerable, even to the patients themselves. By the second or third day, the sloughs were much enlarged and of a darker color, and the surrounding parts tended much more to a livid hue. The breathing became more difficult, with a kind of rattling sturture as if the patient was actually strangling, the voice being exceedingly hoarse and hollow. Yeah, it's pretty intense.

So what does that sound like to you? Sounds like diphtheria? That's right. The topic of today's episode. All right. Hi, I'm Erin Welsh. And I'm Aaron Umbuds. And you are listening to This Podcast Will Kill You.

Diphtheria edition. Yep. So. I'm really excited. I am really thrilled. You've been talking about this one for a while now. I know. And there's also, there's been something in my part that I have been dying to tell you about.

And I've been keeping it secret and keeping it safe. Keeping it secret. Keeping it safe. I can't wait to hear it. Good. I guess, though, that we should start first with our quarantinis. So what do we have to drink tonight? Tonight we're drinking The Strangling Angel.

Oh, that sounds menacing. It's a little bit. But it's also quite delicious. It's actually quite good. It's kind of a very. on a penicillin, which who knew that was a real cocktail? Maybe we should have. We do now.

We do. We do. It's got, what, whiskey, lemon juice, either bourbon or rye. And lemon juice. Ginger liqueur. And a little maple syrup. And in addition to our quarantini's this episode, we'll also be making, what are we

calling them, placebo ritos? Yeah. Plessy burritos. Guys come up with a better name for that. And we'll be put. posting the full recipe for the quarantinis and the placebo. Ritos. We'll be posting those non-alcoholic versions online as well on all of our social media channels so you guys can find those and drink along with us.

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So diphtheria is caused by a bacterium known as carini bacterium diphtheriae. And I did, in fact, look up how to pronounce that. Oh, good. That's like the first time for me ever. Well, it's a strange spelling. Yeah, I looked at it and I was like, I'm going to look this one up.

Karine bacterium diphtheriae. It's a gram positive rod, so it's shaped like a little tube, not a ball or anything. Like a little good and plenty? Yeah, good and plenty. That's a great one, actually. And one thing that's interesting about this disease is that the disease that we associate with diphtheria is not caused by the bacterium itself. It's caused by a toxin. And this toxin is produced by a virus, a bacteria phage that actually infects the bacterium. What? Yeah. So a lot of the toxins, we talked about toxins in the Mersa episode, a lot of the toxins that bacteria,

that quote unquote bacteria produce are actually produced by viruses. So it's this little mutualism? I mean, I guess. Or commensalism? Yeah, commensalism. I haven't really seen, I mean, presumably, at least in the case of humans, which are the pretty much only reservoir for diphtheria, you might be getting more sick. So I guess if that's beneficial, then you could call it a mutualism. But I don't know if that actually, like,

I don't know that the bacteria survives any better with this bacteriophage or not. Okay. So maybe someone else who knows can tell us. That's really interesting. Yeah. So it's not the bacterium itself. So there are strains out there that are what are called non-toxicenic strains. Those can still infect you. They can still cause some disease, but they generally don't cause as severe of disease and not the type of disease that we might associate with diphtheria. Okay. So, ready? So diphtheria, and from now on, whenever I talk about it, we'll just assume that it's a toxicogenic strain of the bacterium. So it's making toxin. It's trying to kill you. Gotcha. It's transmitted via aerosols, so coughing, spitting, sneezing, et cetera. Lovely. The incubation period is two to five days.

So if I cough on you two to five days later, you're going to be getting sick, most likely. And historically, not to step on your toes or anything. No worries. My toes are safe. But historically, diphtheria has been a disease of childhood, very specifically of childhood, meaning babies didn't usually get it and adults didn't usually get it. Do you have a guess as to why? Hmm. I'm guessing that in babies it would have to do with maternal antibodies.

from breast milk. Boom, nailed it. And adults, I would assume that most of the adults would have had been asymptomatic and been exposed to it and then developed immunity. Or just had it and survived it. Yeah, exactly. So they definitely were exposed and either got the infection and survived it or they were asymptomatic carriers, which is very common in diphtheria, meaning just because someone looks healthy,

doesn't mean they are. Dun-d-da-da-da. All right, so let's get into what actually happens when you get infected. Okay. So the first place that diphtheria tends to colonize is your nasopharynx. So that means your nose and your throat. Okay. It is possible to only infect your nasal passages,

in which case the disease that it causes is more like the common cold. It's not as severe. You get a lot of bloody mucus and pus coming out of your nose. Oh, God. Yeah, that's pretty gross. But it's less common. So more commonly, it's actually going to kind of go straight to the back of your throat. And that's its sort of favorite spot to infect.

So the progression of the disease I saw described as insidious, which is not a good. No. You don't want something in your body to be. There's a negative connotation to that word, I think. Pretty negative. So here's how it begins. You start with a fever. But not like a crazy high fever.

So maybe not one that makes you go, I need to get to the doctor, right? You're running like 100, maybe 101 max. So you're feeling crappy. You're feeling tired, maybe weak. You've got just generally like malaise. You're like, God, I'm coming down with something. Maybe it's the flu. I don't know.

And then your throat, like it really hurts. It hurts pretty bad. So then because you're feeling crappy and your throat hurts, you've got anorex. right you don't want to eat anything you don't want to swallow and you just feel bad so anorexia is just just means not wanting to eat anything yeah exactly it means not eating and so you're like wow maybe it's strep throat maybe that is that what i've got i don't know but then within two to three days you're not getting better and at the back of your throat you'll see this thing and it starts out white just sort of attached to like the roof of your mouth and like back near your tonsils and then it gets bigger i don't like this it just

keeps getting bigger and it starts out white but as it grows to cover your entire soft palate it can turn green oh my or gray or black god black yeah and it's not really pus because pus you can kind of spit that out right like mucus you could sort of of put your finger back there and scrape it off. Oh, ugh. You can't do that with this because it's stuck on. And if you try, like if you really, really try in there, you're just going to cause yourself to bleed a lot because it's stuck on there.

And at this point, it might be getting kind of hard for you to breathe. So if you finally were to go to the doctor and they put a stethoscope up to you, they'd hear a sound something like this. Was that good? Oh, my. God. I am feeling like the need to breathe very deeply. This is, I'm feeling very stressed right now. Yeah, Aaron's, I really, I've made her very anxious. I am highly anxious. So that sound that I mimicked, I'm pretty proud myself for that I practiced. It was excellent. Thank you. It's called strider.

It's not a good sign. It's a very, very bad sign. So at this point, if you've progressed this far, you have two fates. Either you recover somehow. or you die. It's pretty much a 50-50 chance. The end. Just kidding. I'm just letting this sink in because I have read, obviously, like it's come across my research about sort of the membrane and the dying. But it's, it's, when you hear the whole.

When you hear the whole thing and you just imagine this. Well, first of all, I'm going to be terrified for every time I get a cold from here on out. I'm going to be constantly checking the back of my throat. You don't need to do that. You've been vaccinated, Aaron. Some of us are just nervous by nature. Yeah. Not naughty by nature.

So, yeah. So this thing that's on the back of your throat is called a pseudomembrain. I don't know why they call it that, but that's what they call it. It seems like a pretty real membrane and not a pseudo one, but that's what they're calling it. And basically what happens, and one of the very common ways that you end up dying from diphtheria is that this thing grows so large. And then your surrounding lymph nodes will also swell up that basically your airway is blocked off and you suffocate. Oh, my gosh. Now, that's not the only way that you can die from diphtheria.

But before we talk about the other ways that you can die, we'll take a step back. And let's talk about what's actually going on inside your body. Okay, good. Why are these specific symptoms happening? So like I said, the primary thing that's actually causing this disease is a toxin, diphtheria toxin, not the bacterium itself. So what happens is this toxin is released from the bacterium, made by the bacteriophage inside, inside, released from the bacterium into your body. It enters your cells.

So it can actually attach to certain receptors on your cell and get inside of your cell. And once it's in your cells of like the epithelium of your body, throat, right? It basically inhibits protein synthesis. One of the main things that cells do is make protein. If your cells cannot make protein, they will die. Yeah, so inhibiting that seems pretty bad. It's not good. So it basically causes cell death. So this toxin gets into your cells, stops them from doing their job, and then results in their death. The pseudomebrane that you're actually seeing on the back of somebody's throat is a direct result of this. toxin. It's made up of a whole bunch of dead cells that have been infected by this toxin

and then killed. And then what happens is because the bacteria are also there, right? So there are colonies of bacteria. You've got macrophages and neutrophils, which are white blood cells that are coming in to try and eat the bacteria and also clean up after all these dead cells that are now in the back of your throat. And when there's dead cells, what they do is they lay down this stuff called fibrin, which is like scar tissue. And so that's why it's adherent to the back of your throat. It's not like when you get sick with another like strep throat, for example, and you might have a bunch of mucus. That mucus is also just white blood cells and bacteria. The difference here is that because you have a bunch of cell death, you have fibrin being laid down and that's, everything is

attached still to your healthy living tissue. That makes sense and is also that much more horrifying you know? Yeah, definitely. Yeah. Because there's no just like, oh, let me just hack cough really hard and hack this thing up. Right. You can't. You can't hack it up. And it suffocates you. Sufficcates you. I feel claustrophobic. I can tell. It's a small room. But like I said, asphyxiation is not the only way that you can die. Cool. So the toxin is released into your bloodstream and your nasopharynx, especially the back of your throat, is just rife with blood supply, which means that this toxin can make it into your blood supply and then it can go to the rest of your body. Cool, cool, cool, cool, cool, cool, cool, cool, cool. It can travel to your

heart where it will do the same thing that it does in the back of your throat. So it's going to infect your heart cells, cause cell death, and then fibrosis or scarring. And what happens when you have scarring on the muscles of your heart is the conductance, the electrical activity that controls your heart is impaired. So you've got a bunch of scars from everywhere where you've got dead cells because this toxin killed yourselves. And now your heart can't send impulses so it can't pump correctly. So you end up with arrhythmias. Your heart's not beating in sync with itself. So you can die because your heart stops beating correctly. You can also die. There's more. You can just, you can just, your heart will just stop beating.

You go into like a like a tachycardia or an arrhythmia where your heart is not beating correctly. Like maybe you're going to have atrial fibrillation, which means the top part of your heart is like, like, say what my hands are doing because I can't. What do you call this? Fibriation. I don't know. I mean, that looked like jellyfish tendrils. Okay, so it's kind of like that. Like instead of being like dung-dunk, dung, dung.

your heart's like, it's fluttering. Yeah, exactly. So that can happen and that'll kill you, right? Because if your heart's not dunk-dunking, it's not pushing blood out. That's what dunk-dunk is, right? You also could just become paralyzed. Cool, great. Because it can infect your nervous tissue.

And if it infects your nerve cells, then your nerve cells die, then you can't transmit electricity. Yeah, so it's pretty gnarly. You also can get cutaneous diphtheria, which, is basically a giant ulcer on your skin. It's pretty, it's pretty gnarly looking. We should post a picture, but I don't know if we should post a picture. Maybe we can do like a click to see graphic content. Yeah, because it's pretty gross. Now, is that again with the, the fibrin? No, it's actually usually a non-toxicogenic strain that infects your arms. Interesting. Well, not just arms, but your skin.

I'm not exactly sure why, but I have some good news because it looks like you could use it. Yeah, I'm very tense right now. My arms are folded. She's very well-ed off. I feel like my heart is a-rhythmic right now. Untreated, I guess I have a little more bad, and then we'll get to the good. Untreated, the mortality rate is up to 50%. So about half of people who get infected and do not have any treatment will die from diphtheria.

So high. It's pretty high. Treated. so we do have a treatment treated the mortality is between 5 and 10%, which is still kind of high. It's very high. And in young children, it's actually as high as 20%.

And the thing that's really sad is this case fatality rate has not improved over the last 50 years. So we're not any better at treating it now than we were in the 1940s and 50s. That's scary. Yeah. But do you want to know how we treat it? It's kind of cool. Yeah, yeah. So there's two things that you have to do. The first is give an antitoxin. You do that to actually treat the symptoms. The thing about this treatment, the antitoxin, is that it only works on toxin that is not already bound to yourselves. So you have to be treated very, very early in the course of disease because any cells that are already infected with the toxin are screwed. Okay. And then on top of that,

that you also treat with an antibiotic. And that's both to kill the bacterium itself, so it stops making more, and to protect those around you. So to make sure that you don't spread this disease to anybody else. Gotcha. And the best news is that there is a vaccine, but we'll talk more about that later. Mm-hmm. So tell me, how did we get here?

Excellent question. Dip theory. Where to begin? Before I started researching this, the word diphtheria didn't really mean much to me on its own, right? It was more just like part of a vaccine lumped in with other diseases that you don't really hear much about anymore, except more recently with the whole anti-vaccine movement, which I'm sure we'll get into a bit later. Yeah. Anyway, but as I read more about the history of this disease, I found that the mention of diphtheria in a village or a city could cause a huge panic. Wow. And it was, yeah, it was one of the most feared diseases in pre-vaccine times for a few reasons.

One, it attacked children primarily. So it causes horrible, slow suffocating death that you just talked about. Yeah. It just sounds so awful. Yeah, you just like watch your kid suffocate. 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. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture. It's non-greasy, unscented, and absorbs quickly. A little goes a long way. Moistrization

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or pursuing a lifelong passion, our programs are designed for people who never stop. You bring the fire, APU will fuel the journey. Learn more at APU. breaking news everybody not everything is terrible i repeat not everything is terrible the ripple effect with jennic kim jones is proof that the internet it hasn't ruined humanity entirely let me start by saying it's a great day to be a gray shirt team rubicon you know it truly is a team those folks myself included all had one desire which is helping folks in disaster trying to be

a little bit of hope in a really really bad situation it's like magic you guys so Put down your doom scroller and pick up your faith in humanity and join me, Jenna, for the ripple effect. It's a reminder that you can start a ripple that changes everything. You really can. We give just that nugget of hope, helping other people. For some of our gray shirts, it's during a time when they need help. And by helping others, it helps them. Listen to the ripple effect with Jenna Kim Jones on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. Yeah. Like, I cannot imagine.

Yeah. It's pretty bad. And also, too, it would show up suddenly and tear through an entire town or village and nothing seemed to stop it. So let's just check off the etymology of this disease before going into any more of its gory historical details. Diphtheria didn't get its name until 1826. Whoa, that seems super late.

Yeah. And so in this year, a French pathologist named, Pierre Bretonoe came up with diphthyite or something like that, which is from the Greek root diphthera meaning leather, which is of course what that tough membrane in the throat resembled. Leather. Leather. It's like a football. Yeah, and apparently it smelled really bad according to the first hand account.

Okay, I really think that was just poor hygiene. I saw every, like there were so many first-hand accounts that I read that were like it smelled disgusting. It does make sense because it's just like a bunch of dead stuff in the back of your throat. But like some of that description in the first hand account was like its tongue was brown. I'm like, bro, that's you, man. Okay. Well, fair enough. But it was one of the, when in reading some of this, it seemed like there was a characteristic diphtheria smell. Yeah. But the naming itself was really important in the history of diphtheria because before this outbreaks of sore throat were called by a bunch of different names, which made tracking and monitoring outbreaks difficult, not to mention

developing any kind of treatment that was reliable or consistent. Right. Okay. So the name didn't come about until the 19th century, but this wasn't a new name given to a new disease. This disease has really characteristic signs like extreme sore throat, leathery membrane. So you would think that tracing the history of diphtheria would be somewhat easy, at least compared to diseases like staff, which is much more...

Right. It's like everywhere and everything and causes so many different types of disease. Exactly. Yeah. But it actually doesn't have that much of a history before the 1700s. What? Yeah, at least that I found. And I could be wrong and I could be looking in the wrong places.

But there were some mentions. In the 5th century BCE, Hippocrates writes about a disease that sounds an awful lot like diphtheria. And there's another mention a few hundred years later. by Eritus, the Cappadocian, in which he describes ulcers in the throat and warns that, quote, if it spreads to the thorax by the windpipe, it occasions death by suffocation within the space of a day. Yep. And that, quote, children until puberty especially suffer. Yep.

So. That does sound a lot like diphtheria. Probably. And that's really more or less the last mention of the disease until the late 1500s and early 1600s. Weird. And so that's when there was a series of epidemics of sore throats resulting in suffocation that swept through Spain and parts of the new world. This epidemic was referred to as El Anno de los Garitos, essentially meaning the year of strangulations. Oh!

That was one translation I found for it. I got chills. So bad. But, yeah, it sounds terrifying. A year of strangulation. Yeah. But it remains a bit of a mystery as to why there's no mention of this disease for over a thousand years. And so I was starting to wonder, well, are we just missing historical accounts?

Or did it not really act as an epidemic disease for all that time? Or were the ancient descriptions of the disease actually something else that just happened to resemble diphtheria? Yeah. I couldn't really find a whole lot of information on that, on this missing puzzle piece. but I did see somewhere that the bacterium is thought to have come from domestic herbivores, which means it probably has ancient origins. Right. Maybe the incorporation of the bacteria phage was more recent, and then the toxin was more recent, but I don't know.

I don't know. And the thing is that humans, from what I read, are the only reservoir. So these aren't, it's not like currently a zoonotic disease. Right. So that would further point to an ancient origin. Yeah, exactly. I don't know. Weird.

In any case, diphtheria emerged with a vengeance in 1735 when outbreaks of the illness occurred in New England, Great Britain, France, and the West Indies. People called it throat distemper. Yeah. And sufferers either died from suffocation by the thick, grayish membrane covering their throat. She's going to say that like a hundred more time. It just is the most horrible thing to me. I don't know why. or if they survive that, they could just drop dead a week or two later.

Yep. As we've heard. Cool, cool, cool, cool. Love it. This outbreak disproportionately affected children and some families lost all of their kids. Like entire families, just kids all gone. I know it is quite infectious. And so it does make sense that if you've got a bunch of kids, it's going to go like chicken pox from one to the next to the next and then boom, boom.

Awful. In Kingston, New Hampshire, a third of all children in this town died from the disease. Whoa. A third of all the children. And the state itself lost 5% of its entire population. So that's really crazy because that means it's not just like always there. It's like coming into these communities wiping them out and then moving on. Exactly.

Because otherwise you would just have like low levels of death all. the time. Right. Weird. I never knew that. It's an epidemic disease. It's not an endemic. So then it's even weirder that there's not more accounts of it. Yes. What? I know. Sounds like, yeah. Yeah. It's bizarre. That is super bizarre. Obviously, with such a huge loss of life comes people seeking answers or at least where they can point fingers. And many Puritan ministers said that the people had brought it on themselves by straying too far from the religious path, which I'm sure is exactly what they needed to hear as they have lost their entire children. Oh, God. It's your own fault, mothers. Right. The wanton mother. The wanton mother.

Ridiculous. Anyway. So after this first big diphtheria epidemic in 1735, Outbreaks showed up every 25 years or so. Whoa. Yeah. And it slowly shifted from this epidemic rural disease to a more endemic cosmopolitan disease by the mid-1800s, and it seemed to increase in virulence the entire time. Yeah.

It was during these outbreaks in the 1800s that diphtheria got its name, The Strangling Angel, which is the name of our quarantine, if you remember. in an outbreak in New York City in 1857, the case fatality rate was 42%, which is, I mean, as we know, that's just what you said, but that's still so high. Yeah, I mean, that's almost boobonic plague level. And it's children, right? Children. So you've got a school house with 100 kids in it. They're all going to get infected, right?

Like, realistically. 42 of them are. going to die. Yeah. You now have 58 kids in your class. Is that right? That's right. Thank you. That's what? And no amount of therapy or supportive treatment could save the lives of those suffering. And so they died this slow, terrible death. God. So physicians deeply feared diphtheria because they felt pretty much helpless against it. Yeah. And even more, helpless than the parents because the parents would take their children to them, expecting this person to try to make things better? And no. So it was a parent's absolute nightmare to watch their child suffering so horribly. And for this reason, diphtheria played a prominent role in the development of germ theory in the 1800s. Our fave. Oh, yes. All right. So it's the mid-1800s. Let's take a minute to consider some of the prevailing thoughts on what caused disease. bad sexual habits.

Okay, wait, that's actually true. My bad. I'm sorry, let me try that again. Not praying enough. Actually, I don't really have that in here. I think by that time it was not so. It wasn't so much about the morality. Oh, okay.

Bad air. Bad air. Yes, absolutely. So my asthma, that kind of thinking, which if you remember from John Snow and the Cholera, Broad Street cholera outbreak. Episode four, if you haven't listened to it. Yes. That was all thought to be my asthma. So, and then there's also humorism or humoralism, which we've talked about during tuberculosis.

Episode nine. Mm-hmm. And then there's germ theory. Yes. So the idea that many diseases are caused by microorganisms. So this idea was around, but not necessarily widely accepted quite yet. because humorism was still kind of the prevailing thought. But it pretty quickly fell out of favor as formal medical research focused on specific tissues or cells as indicators of disease.

Importantly, they started asking whether if a specific tissue or organ was inflamed, there could be multiple causes for the same symptom. For instance, diphtheria, scarlet fever, and strep throat all result in inflammation of your throat. wrote, does that mean that they are one disease or many? So this is a big shift in the way that people thought about disease. Yeah. So the answer might be obvious to us now. Yeah. Of course, these are different diseases.

They have different symptomology, blah, blah, blah. But back then, before germ theory had taken hold, this wasn't straightforward. And the concept of multiple causes for the same disease symptoms was really huge. And it partially paved the way for germ theory, especially the one germ, one disease concept. With diphtheria, one thing seemed certain. It was contagious. If it showed up at a school, in one kid, it was only a matter of time before the entire class, as we illustrated, it was sick at home or in the hospital or dead. Now that we knew it was contagious, it was like, okay, well, we need to know which microbe caused the disease, which was difficult to do because the mouth and throat

normally contains this really diverse array of microbes. So being able to say that one specific microbe was the cause of a disease wasn't simple. But there was at least a jumping off point, the membrane. By the late 1800s, this dude named Clebs found two types of microbes in the membrane. Clebs like Klebsiella? It might be. Oh, how exciting. But he didn't know which bacterium was responsible. So that question was solved a few years later in 1884 by a dude named Friedrich Loughler. Oh. He also discovered that the bacillus was only found in the membrane and didn't invade deeper into the body. But diphtheria also causes effects in a more distant parts of your body, so he figured that the distant effects of disease could be caused by a toxin.

Wow, what a smart guy. Right? We had the causative agent. But there was still the mystery of why an outbreak of diphtheria would suddenly show up without any warning and sweep through a village or school. Where did it come from? Yeah. Well, a couple of years after the causative agent of diphtheria was identified, there was an epidemiological survey of children in Berlin that showed that 5% of healthy children

carry the bacterium in their throats. So this was the first evidence that carriers of the disease existed. And this was a big deal because it helped to explain the mystery of these sudden outbreaks, and it also led to forced quarantine for people who were suspected to be carriers. Uh-oh. Yeah. People were held for months in isolated hospital units. There were quarantine stickers or plaques to put on people's houses if there was an outbreak of diphtheria in a certain house.

Soon after the discovery of diphtheria carriers, Pierre Paul email Rue, who was Loughler's assistant, found the diphtheria toxin by showing that if you passed bits of diphtheria secretions, like from the membrane, through a superfine filter that would keep the bacteria out in other cells and then injected the filtrate into an animal, you could cause diphtheria-like symptoms in the animal. Wow, that's cool. I mean, not cool for the animal, but... But it's kind of like boom, toxin. Yeah.

Got it proof in hand. When a couple other microbiologists named Emil von Bering and Shubasa Burro Kitasato heard about the discovery of the diphtheria toxin They were like, we know what to do with this information. Because if we can fight the toxin, we can fight the disease. So they began working towards developing the diphtheria antitoxin, which was first used in the 1890s. Wow.

Yeah. And for this research, Von Bering was awarded the first Nobel Prize for Medicine in 1901. What? Yeah. For diphtheria antitoxin? Oh, cool. Diphtheria was a big deal. Yeah.

I definitely had. I definitely had no idea that it was such a big deal. Yeah. Like it was, it's just the D in T-DAP. Exactly. It's all it was to me. Yeah, it was a lot more and it really left a mark. And it's kind of funny because it seems like so much of diphtheria's history is squeezed into just a few decades.

It was only in the 1850s that the disease became endemic in cities and within 50 years, the bacterium had been identified, its toxin isolated, and a moderately effective treatment. produced. Wow. Boom, boom, boom. But diphtheria was in no way defeated or forgotten. It was still one of the illnesses that most terrified parents and racked up a hefty death toll. Even with the advent of antitoxin, it remained the number one killer of children in some countries, killing thousands of children every year.

For instance, in the U.S., 13,000 to 15,000 children died every year from diphtheria. This is in the early 1900s. Oh, my God. And in January, 1925, it would take the front page of so many newspapers in a dramatic race against time. Race against time? Okay. Let's take a quick trip to Nome, Alaska. Yes.

Do you know where this is going? No. Okay, great. In 1924, Nome is still a baby city. It had been founded only 27 years early. by a few gold prospectors, which then led the way for hundreds more to rush to this extremely remote part of Alaska, which was still just a U.S. territory and not a state. Gnome is just a couple of degrees south of the Arctic Circle and extremely far west on the

Seward Peninsula, and we'll post a map. In 1924, it was one of the most remote cities on Earth. Noam was closer to Siberia than it was to any other. major town in Alaska. Whoa. Its population had shrunk from around 20,000 during the peak of the gold rush to around 1,500 brave or crazy people that made it their home in 1924. Wow.

For most of every year, from around October or November to July, Nome was more or less shut off from the rest of the world. The port was inaccessible due to freezing water. No train reached that far. west and planes hadn't yet been designed to withstand the extremely harsh winters. Oh my God. Yeah. Until July?

Yeah. No, thank you. I think that's like when the ice melt was... Uh-uh. I'm complaining about 50s over here. So that left sled dogs as the only reliable way to get around. So before those ships left for the winter, you really had to make sure that you really had to make sure that you had everything you needed or wanted for that long winter and spring and half of summer ahead of you.

In the summer of 1924, Nome's only doctor, Curtis Welch, sent a request for more diphtheria antitoxin after he noticed that the units that he had were expired. But when the last ship of the year came and went without any new antitoxin, he crossed his fingers. and hoped for the best. Uh-oh. Being so isolated might protect them from any outbreaks coming their way, and they had been lucky avoiding diphtheria in previous years. But the 1918 flu still lingered on everyone's minds. I don't know if I mentioned this in our flu episode since it was like 100 years ago.

It was about a year ago. But this part of the world suffered some of the highest death. rates during the flu. In Nome, 50% of the population of Alaska natives died. You know, you did mention that. Okay, I thought so, because it's such an intense, it was such a high mortality rate. Yeah. And so, on Christmas Eve, 1924, when Dr. Welch heard of a seven-year-old girl who had a very sore throat, he worried. If this was diphtheria, Nome was on its own, with enough expired antitoxin to help just a handful of people. And in particular, he worried about the thousands of Alaska natives living in the area who had lower resistance to diphtheria.

Oh, no. A few days later, on December 28th, the girl died, and several more cases of sore throat began popping up. Welch didn't officially diagnose anyone with diphtheria until mid-January, and by this time, at least five children were dead of the illness. And this isn't a really small, super isolated town. Yeah. So now is the time to panic. He sent out a telegram to the U.S. Public Health Service pleading for antitoxin. Some way, get it to gnome, please.

Getting together that much antitoxin wasn't a problem, but the issue was getting it too gnome. By sea was impossible because of ice. By plane was considered too dangerous, but by a sled dog was another story. Oh, my God. This still doesn't sound familiar to you? No. Okay. Wait, wait, wait. Is this a book or something? Well, it is a book, but it's also a movie.

It's it, Balto? Yeah. Stop it. Yes. This is Balto. Yes. Bolto is about diphtheria. Yep. I had no idea.

That's why I was so thrilled. Your face is so happy right now. It's like so satisfied. Oh, I love it. Well, Balto was, so Bloodmobile, who provides all the music for this episode and all of our episodes is my brother Dan and we've blown his cover he i think we already said that he was obsessed with balto like we had to watch it over and over and over again that's adorable yes i've always loved it okay so she's still so happy anyway so officials decided that they would use a relay of dog sleds to transport the serum, the 674 miles, or 1,085 kilometers.

Nice. From Nenana to Nome. Wow. Nenana's close to Fairbanks. Okay. The heroic efforts of the sled dogs and their handlers were on the front page of every U.S. newspaper. Oh, my God. And much of the population waited anxiously to see whether the antitoxin would successfully make it to gnome.

these handlers, most of whom were Alaska natives, and their dogs had to endure extreme winter conditions. Dogs lost their lives, people lost their fingers, or suffered permanent damage from frostbite. But in just five and a half days, so an area of 674 miles. Of frozen. Frozen. This is in January. Over a thousand kilometers in January, mid-January. Oh, my God.

Yeah. The antitoxin arrived in Nome, carried by Gunner Kossin and his lead dog, Balto. Baltho. About whom the movie was made. But I want to do my part to clear up a historical misrepresentation about Balto and the serum race. Even though Balto and Kassin were the ones to deliver the serum to Nome, they were only the last ones in a long. relay, which involved many more dogs and handlers. Among these is the dog considered the true hero of this story, Togo. Togo. And his handler, Leonard Sepola. Togo ran more than 261 miles. Oh my goodness. 420 kilometers during this relay, and his leg of the relay was 91 miles, 146 kilometers,

which is more than twice any other team. He safely led his team through some of the worst conditions and across the treacherous Norton Sound, which is this frozen inlet of the Bering Sea. So over frozen seawater. Oh my God. Yeah. But Togo didn't get any of the recognition,

or at least not nearly as much, especially right after the serum got there, that Balto received, which, like, there's a statue of Balto in New York City's Central Park. And Sepulah, who was the handler, was super salty about this. Well, yeah, it would be too, because he was with him. Yeah, I know. The outbreak in Nome was small.

Only six or seven children died, and maybe 500 to 100 people were infected with diphtheria. But the numbers could have climbed a lot higher had the serum race not been successful. And maybe Togo will finally get the recognition he deserves because apparently there's a live-action Disney movie. in the works called Togo Stop it. In which

Willem Defoe, everyone's favorite hero, what? Will play Leonard Sepula. No. Mm-mm. Mm-mm. No, veto.

Oh, well. We'll see. Sorry, Will. I'm definitely going to keep an eye out for that, though. So I tell this story about Nome and Togo and Baltho to underline just how scary this disease was.

Right. People were willing to go to pretty extreme lengths to protect this tiny little town. And they were captivated. Like this was on the cover of every newspaper. A few years after the gnome serum race, a diphtheria vaccine was created using the toxoid,

which was the inactivated form of the toxin. And it went into wide use in the 1930s, and the disease really dropped off to where most doctors today have no idea what a diphtheria membrane looks like. Only in pictures. Or smells like. I think that's why we don't, like,

It's not in a picture. Yeah, exactly. Scratch and sniff. Yeah, we talk a lot about smells of some bacteria specifically that like the bacteria make a smell. Right. But with this, my guess is that it's just like a bunch of deadness that is making the smell. I just want to repeat again what I said about a scratch and sniff book. Scratch and sniff pseudomebrane.

Scratch and sniff medical textbook. Oh. Grody, dude. No, I would not. I would not buy. No, but somebody would buy it for you. Yeah, that's true. That's basically all I've got. Is it?

Yeah. You're done? I'm done. You're like, and then they made a vaccine story over? Well, that's because I think that's where you pick it up. And you tell me about how the anti-vaccine movement might be changing things. Okay. Let's do it.

So just because we invented a vaccine doesn't mean we've pulled a smallpox. This has not been eliminated from the world. It has not been eliminated from the United States. Still exists. But in the United States, it is actually a pretty huge success story. So, for example, in 1921 in the United States, so before there was any kind of vaccine, there were 206,000 cases of diphtheria reported.

That's a lot. Yeah, there were also over 15,000 deaths. Oh, my. I know. Most children. Yeah. But since 1980, there have not been any double-digit year cases. So no double-digit cases.

This is a weird way to say it. Fewer than 10. Fewer than 10. There you go. And in many years, zero cases in the United States have been reported. That's great. It's very great. It's not so across the globe.

So the World Health Organization, and I'll actually post this because I think, I don't think I'm the only one who'll find it interesting, has little fact sheets about the number of cases of all of the vaccine preventable diseases of which diphtheria is one and how many or what percentage of people are actually vaccinated across the world. So this is aggregated all of the countries of the world, how many actual case reports there have been of all of these diseases. So keep in mind as always that, you know, it's just the reported cases. There's a lot of underreporting and many places who might not reported at all, et cetera, et cetera. But the numbers have been generally getting better for the most part.

In 1980, worldwide, there were over 97,000 cases of diphtheria reported. Well, hold on. 1980. 1980. 97,000. 97,000. Okay. 1990, that number had dropped to 23,000.

Holy crap. Way to go, world. Right? That's because of the vaccine. I mean, the vaccine has been in use since the, you know, 20s. Well, sure. but I mean like vaccination rates.

Yeah, they went up from 31% in 1980 worldwide to 88% in 1990. Whoa. Yeah. That's for one dose of the vaccine. So one thing I will say is that the vaccine for diphtheria, it's usually given in combination with tetanus and pertussis. So you might hear people say DTP or Tdap or DTAP or DTAP.

There's a lot of different versions of it. Yes. So these are all different combinations of diphtheria toxoid, which is just an inactivated toxin, tetanus toxoid, inactivated tetanus toxin, and pertussis, either the whole bacterium or parts of the bacterium. And because in all of those cases, you're giving a killed toxin and not a live bacterium, your immune system only mounts a partial response to it. So one dose is not enough to actually give you full immunity. So in the U.S., children actually get five doses of DTAP,

up until they're about six years old. And then after that, it's recommended that you get a booster every 10 years. Worldwide, one of the biggest challenges is making sure that people get all of the recommended doses of vaccines like the DTP vaccine. Because giving just one is good, but giving three or four or five is a lot better. Right. So globally, the rates of like giving the rates of children who have received at least one DTP vaccine is pretty high. But the rates that have received at least three, which is what's recommended by WHO is a bit lower.

Okay, so where were we? We were in 1990, right, with 23,000 cases worldwide. Yeah. Cut to 2000. Still doing great. Only 11,000 cases. All right. All right.

2013, 4,000. What? It's great. 2014. 7,000? Must have been a fluke. 2015, back down to 4,000. What's up?

2016, 7,000? Okay. 2017, 8,800. Okay, not a fluke. Not a fluke. It's not great. It's hard to say, sure what the cause of this is because globally vaccination rates, at least reported vaccination

rates have not changed. Globally, that is not true in the United States. But what it basically means is that at least over the last five years, we haven't really gotten better, right? We haven't made huge strides in the last few years in terms of actually reducing the burden of diphtheria. And it definitely still exists. And something that I thought was really interesting that I definitely didn't realize is that if you were to, like, randomly screen a whole bunch of people's noses or nasopharynxes in the United States, even in areas where you have relatively high or I suppose what someone would think would sound relatively high vaccination rates, like, say, 80%, which sounds high. But for vaccination rates is actually not good. Yeah. You can find a lot of people colonized with diphtheria in the United States.

So this bacteria still exists here. So even though we haven't had a case of diphtheria in the United States since in 2012 we had one. And before that it was 2003. Okay. We had one. So even though the case rates of diphtheria in the United States are very low, that doesn't mean that it's, not here, right? Right.

The R not of diphtheria is 6 to 7, which is really high. It's really high. It's second to like measles, which we haven't... How have we not talked about measles yet? Because there are tons of diseases. Okay, but we need to put that high on the list. Yeah. But yeah, so it's really high.

So what that basically means is that, yeah, for every one infected kid, you could potentially infect six or seven more kids. That's crazy. It's crazy. It's scary. It's really scary, especially also because, so the T-DAP, D-TAP, whatever you call it, vaccine, and they're different vaccines, but whichever vaccine it is, is recommended for pregnant women. And that's because since you have this waning immunity, you want to make sure that a pregnant woman is immune

so that she passes on those immunoglobulins to her baby because babies don't actually get vaccinated until two months old. So for those first two months, they're super, super susceptible. Gotcha. If you don't give a, if a woman maybe doesn't have access to prenatal care or doesn't have health insurance or things like that and doesn't get that, then you can potentially have babies that are completely susceptible. And so that's why this whole vaccination thing becomes really important is that it's not just about like your individual risk. It's about the fact that there are a lot of people in the community that either are too young to be vaccinated are very old so they just don't have a good immune system left. Right. Are already immunocompromised, whether it's from something like HIV or leukemia

or other immune disorders so they can't be vaccinated. Right. And so those are the people who are most at risk when you have low levels of vaccination in a population. It just blows my mind after reading about this disease and hearing about this disease from you and the progression of disease that there are people who choose to go, no, I'm just going to take my chance. I think the thing is, though, that we don't hear about this. It's not on the front page of our newspapers because one kid has gotten it since 2012. In the U.S. But it's also, it's not in everyone's face and it's not every day and it's not everywhere. So it's very easy individually to say that problem is elsewhere and it's not going to affect me. I mean, I think that's why it's just

about making sure that people are aware that these diseases still do exist and that's why these vaccines are important. It's scary. The disease itself is scary. What's the scariest thing is that there are people who can be protected against it and can by doing that protect other people against it and they are choosing to not do that. Yeah. That's the scariest part to me. Yeah. Yeah, it is. It's scary. It is scary. Well, I would. wish I had some happy note. I mean, worldwide vaccine coverage is about 85 to 90%, which is great. Yeah, that's good old diphtheria. Who knew, quite honestly. I didn't know most of this stuff. Yeah. Yeah, there's, I feel like there's, there's a lot more to diphtheria than I knew was going to be out there.

And I'm really glad that we covered this. Yeah. And, um, thanks balto. I mean, Togo. Thanks, Togo. Sources? Yeah, I have a few. Okay. So the story of Balto and the whole sled dog race and the race for the anti-toxin, it's called The Cruelest Miles, and it's by Gay and Laney Salisbury. And I also use the Cambridge World History of Human Disease, the epidemic streets by Anne Hardy,

and a couple of papers. But I also wanted to plug. I read this book in middle school, and when it came up in the searches, I was like, I definitely recognize that cover. And it's called Running Out of Time by Margaret Peterson Haddicks. It is quite dark. So no wonder, I loved it. Anyway, you should definitely read it running out of time.

I want to read it. Yeah, you should. Also, we'll definitely add that book to our Goodreads list, which, as a reminder, you can find all of our sources, including all of the articles and books that we read for each episode as well as links to our good reads list on our website. This podcast will kill you.com. Thank you as always to Bloodmobile. Also,

Balta's number one fan. Yep. And to all of you for listening. Also, don't forget if you aren't already to subscribe to all of our social media situations, rate, review, subscribe on iTunes. Well, until next time, wash your hands.

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