This Podcast Will Kill You - Ep 3 Gnarlypox

Episode Date: November 14, 2017

This week we pay tribute to one of the gnarliest diseases of all time, and the only human disease that's ever been eradicated (thus far). That's right, people- we're talking smallpox! It's gonna get grody. Smallpox has a depressing history, a fascinating biology, a moderately uplifting present, and a precarious future. We'll cover it all. See omnystudio.com/listener for privacy information.

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This is a job for Indeed sponsored jobs. The red areas spread into blotches across the face and arms, and within hours the blotches broke out into seas of tiny pimples. They were sharp feeling, not itchy, and by nightfall they covered the face, arms, hands, and feet. Pimples were rising out of the soles of the feet and on the palms of the hands, too. During the night, the pimples developed tiny, blistered heads, and the heads continued to grow larger, rising all over the body at the same speed, like a field of barley sprouting after the rain. They hurt dreadfully, and they were enlarging into boils. They had a waxy, hard look, and they had a waxy, hard look, and they were,

seemed unripe. Fever soared abruptly and began to rage. The rubbing of pajamas on the skin felt like a roasting fire. By dawn, the body had become a mass of knob-like blisters. They were everywhere, all over, but clustered most thickly on the face and extremities. The inside of the mouth and ear canals and sinuses had postulated. It felt as if the skin was pulling off of the body, that it would split and rupture. The blisters were hard and dry. The blisters were hard and dry and they didn't leak. They were like ball bearings embedded in the skin with a soft velvety feel on the surface. Each puschule had a dimple in the center. They were pressurized with an opalescent pus. The pustules began to touch one another and finally they merged into confluent sheets that covered the body like a cobblestone street.

The skin was torn away across the body and the pustules on the face combined into a bubbled mass filled with fluid until the skin of the face essentially detached from its underlayers and became a bag surrounding the tissues of the head. Tongue, gums, and hard palate were studded with postules. The mouth dry. The virus had stripped the skin off the body, both inside and out. And the pain seemed almost beyond the capacity of human nature to endure. Oh, my God. Hi.

Hi. Welcome to episode three of this podcast will kill you. This week we're talking about smallpox. Clearly. That was smallpox. Yeah. It's horrifying. Oh, my God.

And that quote was from The Demon in the freezer by Richard Preston. Wow. So how about a little something to take the edge off? Yeah, let's take that edge off. What are we drinking this week? Today we're drinking smallpox on the rocks. That's gross. Yep.

I don't know if I want to drink that anymore. You know, it takes the edge off. Yeah, sure, sure. What's in smallpox on the rocks? Basically, it's a whiskey sour. Sign me up. That's pretty straightforward. I'm already signed up.

It's, if you'd like to drink along at home, you can make your own smallpox on the rocks by mixing two ounces of your favorite whiskey. Woodford Reserve. That's the Kentuckians. That's my plug. She would know, you know. Like, she does know. Rye is good too, but you know, let's go with bourbon. And the juice of half a lemon, which is literally every recipe, and I looked it up, it's about

three tablespoons of lemon juice. That's the juice of half a lemon. No, that's a juice of a whole lemon. Oh, you're right. So it's one and a half tablespoons of lemon juice. I mean, maybe more is better. We did it one and a half tablespoons per two ounces of bourbon. And about a half a teaspoon of sugar, shake it up.

over ice, drink it on the rocks. Cheers. Cheers. I wonder what that sounded like. I don't know. I hope it was good. You do. We need better clinky glasses.

Yeah. Let's define a few words for this week. What are the words that we're going to be defining this week? Let's start with endemic. So in terms of disease, endemic is a disease that is regularly found among a particular people or in a certain area. So, for example, there are certain areas of the world where malaria is considered endemic. And if you see malaria in those areas, that's sort of normal.

Whereas if you were to see malaria outside of those areas, that would be considered an epidemic or an outbreak. Gotcha. All right. Next one is bioterrorism. Bioterrorism is pretty straightforward. It's essentially just terrorism that includes the release of a biological toxic agent. That's it. Clear, clear to me.

Clear as day. Clear as day. Let's talk about what a reservoir is. So a reservoir for disease is a long-term host of a pathogen that often do not show symptoms or have sort of subclinical infections. So in lepros we talked about armadillos. Armadillos are reservoirs for the leprosy bacteria. Eradication. Eradication is a fun one.

Yeah. A happy one. It's a happy one. So eradication of a disease, according to the CDC, is the permanent reduction to zero of worldwide incidence of infection caused by a specific agent that is the result of deliberate efforts in order to eradicate that disease to the point where intervention measures are no longer needed to control that disease. There are two diseases in the world that have been eradicated. Aaron, what are those diseases? Oh, smallpox. Oh, that's fun. The topic of today. And actually, the other one, which you may not have heard of, it's called Rinderpest, and it is a disease of cattle.

Yep. Both domestic and wild. So ungulates. Undgulates. And they're both gone, so that's awesome. Go humans. And hopefully soon, polio, guinea worm, some of the other diseases will be also on that list thanks to the Carter Foundation. Right?

It's the Carter Foundation? Is it? I don't know. It's Jimmy Carter. Cool. Jimmy Carter's doing a lot of work for eradication. That's awesome. That's awesome. Now that we've defined those terms, let's jump into the biology. Erin, tell me all about smallpox. I'd love to, Aaron.

Okay, so smallpox. This one is a doozy, no lie. This is... I know. I mean, we were already hit pretty hard at the beginning of this episode. Just starting us off with a bang. So here are the basics. Smallpox is a virus. It's a DNA virus. So if you remember influenza was an RNA virus.

This is a little bit different. It is in a family of viruses known as the pox viruses. And I feel the need to tell you that chicken pox is not a pox virus. That's an important clarification. It really is. Chickenpox is caused by a herpes virus. So it's a totally different family of viruses. But there are a ton of other pox viruses besides smallpox.

There are pox viruses that infect basically every vertebrate that you can think of. There is monkey pox, turkey pox, gerbilpox, camel pox, dolphin pox, penguin pox, snake. There's crocodile pox. I think we get the point. Yeah, literally. That wasn't even the whole list. What about fish? Well, there's dolphin pox.

Dolphins aren't fish. Oh my gosh. Are you serious? There actually is dolphin pox. That's not a lie. And yeah, I mean, reptiles can get various poxes, snake pox. So I think there could be fish pox as well. This is probably a really old family of viruses. Yes. There are also insect pox viruses. And those are gnarly because insects don't have skin. So they basically turn into a giant ball of pox jelly. It's gnarly.

That's not a lie. I want to Google that. You should. Let's post a picture of an insect infected by some sort of pox fettos to Instagram. It's just going to be goo. Just goo. So smallpox itself has two major forms, varriola major and variole minor, that are basically named because major is a major problem. Minor was a minor problem.

We're not really going to get into the distinction for this episode. Most of what you hear about in terms of the statistics about this disease have to do with variaola major. Okay. Even though there are pox viruses that can infect tons of other vertebrates, smallpox itself is an exclusively human-specific virus. It likely jumped into humans from some type of rodent. We don't know exactly what kind.

Really? Yeah. It's most closely related to a rodent pox virus. And this likely happened around the time of the agricultural revolution about 10,000 years ago. But estimates really vary on that. It's not exactly clear when this first happened. But the reason that we think it likely was around the agricultural revolution is because math models have shown that this virus needs a really large human population size in order to sustain itself. So, but not just human population size, but human population density. Exactly. Exactly. Yes. That's right.

Okay. So let's get into the disease itself. Yes. We've already heard a little bit. It's just going to get worse, better? I don't know. Probably worse. Yeah, and also better. I mean, it'll get worse and then it'll get better. We're not sure where we're going to end up. Well, we'll find out. So smallpox has an incubation period, which if you remember from the last episode is the time from when you're exposed to when you show symptoms, is about 12 days, 10 to 14 days, but 12 days on average. That's a long time. It's a pretty long time. The one good thing, and I really think this is the only good thing about the smallpox virus, like no joke, is that it does not tend to be infectious until you start showing symptoms. And you are the most infectious, that is, you're shedding the most virus when you

have some of the more severe symptoms, which are? Well, let's get into it. The progression of the disease. So it starts off with fever and body aches and sometimes vomiting. And this is not just a typical fever and body aches. This is you are too sick to continue on with your daily activities. And this generally lasts for about two to four days. After that, you'll get a rash and redness that generally starts on the face, especially in your mouth and on your tongue. Oh, no. Yeah. So inside your mouth, you'll get sores that may break open, and these sores are literally filled with viral particles. Oh, my. my. Yeah. So then when somebody is nursing you and being like, oh, let me make you feel better. Right. And you turn to them and cough a little bit. Yeah. So it's important. This is a respiratory virus. So this is shed by breathing, coughing, etc. So yeah, if you're infected all up in your mouth and then you're coughing on the people trying to help you, baboom is gnarly. Oh my gosh. So then the rash will spread to your body, to your

arms to your legs. Unlike leprosy, this starts sort of in the middle of your body and then spreads outwards, right? Okay. This stage generally lasts around four days and it is the most contagious part of this infection. Then you start to get these lesions, these sores that are filled with fluid. They can become really firm and like you described earlier, they get this characteristic dimple in the center. Then you'll move on to the puscular rash and scab. No. Stop, please. I can't stop.

I just can't. This is described as peas under the skin, right? Oh, my God. It's so disgusting. They're sharply raised. They're firm to the touch. This lasts for about 10 days. This is a long, this is a long infection.

10 days of pee pimples. Yes. And after about five days, they'll start to crust over. And I also want to point out that these sores are long. literally covering your entire body. Your entire body. Confluent. Yeah.

All over. Confluent. Whatever. All over your body. These scabs. And then eventually they'll begin to scab. And then they'll fall off. And you continue to be infectious until the last scab has fallen off your body.

That's if you survive that long. And not only are you infectious, but your scabs are too. Exactly. So if you imagine like, I mean, today, we have when when was the vacuum invented the vacuum yeah oh gosh like the early 1900s there you go so imagine that you're cleaning up after your you know family member who is sick and they're dropping scabs all over the place and then you go to vacuum them up and now you're spewing scab dust into the air and then you breathe it in that's for real or for instance i just made that up blankets yeah you'll

talk a lot about that yeah i'll get into that so yeah that's if the person that's if the person survives all this, they're contagious for that entire time. And how many people did survive this? In general, the mortality rate is about 20 to 40%, usually considered about 30%. So on average, about one in three people infected with smallpox will die. Oh, my God. Now, it gets a little bit worse. No, how?

What I just described was the progression of what is called ordinary smallpox. Ordinary. That's the ordinary version. So that's, if you're lucky, this is the most, this is the baseline. This is the baseline, exactly. So some people who were vaccinated, this is the good version, would end up with what's called modified smallpox, which is basically a less severe form. But a large number of people, I don't know a large number. About 5 to 10% of cases would be what's called malignant.

These have a longer pro-drome period, which is the period at the beginning when you just have like a fee. lever and a mild rash. So they'd have a longer period of that. So it's not like they would be infectious longer. Not necessarily. No. But then when they started to get a rash, the pustules that they would get were slower growing and they would stay flat rather than being raised. And their skin would stay, this is a quote from the CDC, soft and velvety. Ew. Isn't that yucky? What do you, what does velvet skin feel like? I don't know. But, what is a velvet skin feel like? I don't know. it doesn't sound good. I don't think it sounds right. We're feeling our faces. I don't think they're velvety. I need to put lotion on. Yeah. That's the lesson we've learned. But this form of the disease is

almost always fatal. And what's really sad is about 72% of the malignant cases were in children. Oh. Yeah. There's a worse one too. The even worse one. How? Yeah. It's called hemorrhagic smallpox. Oh, okay. That's how. Yeah. So hemorrhagic, meaning bleeding. out, essentially. So instead of just forming these postules under the skin, you would literally just bleed underneath your skin. You'd bleed into your eyes. And your skin would sluff off. Your skin would just be like puddles of blood. Like your whole skin, you bleed into your eyes to the point where the whites of your eyes would turn black because they're just full of dried blood. You could even get, this is, this might be getting too.

But you could even get, you're bleeding so much that in your capillaries, blood is clotting as it's leaking out. So you have just blood clots and blood everywhere in your body. And it's described as very thick and very dark. You would bleed out of all of your mucous membranes out of every orifice. People would turn purple. Yes, exactly. Because there would be so much blood under their skin. Exactly.

this is about 2% of cases overall but somewhere between 3 and 25% of all fatal cases so this as you can imagine was almost always fatal was do you know anything about why a case would become hemorrhagic versus you know I tried to find information about that and I really couldn't find good explanations it makes sense that there weren't yeah I don't know if it's just immune related right that's what I would guess but I don't really know. Another thing to make all of this that much worse is that people infected with smallpox, you can imagine that if you're infected with a disease that makes you this sick, you're probably not aware of what's going on because your body is just in overload. But with smallpox, you stay

weirdly very conscious and aware of everything that's happening to you. That would be horrible. I think, isn't that your actual worst nightmare? It's one of them. Personally. I have a lot of worse nightmare. It's gnarly. Narly is the word of my... Narlie is going to be said a lot.

Yeah, the most in my notes. Yeah. So that's smallpox in a nutshell. Okay. So now that we have a, let's call it, baseline understanding of just how awful this disease can be. I really, I have to be honest. I did not. know just how horrible this disease was until I really started reading about it. It is beyond

anything that I could have imagined. It's really scary. It's terrifying. Let's hear more. Let's hear about how terrifying it was for people throughout history. Let's learn. I want to learn it all. So like you said, the smallpox virus probably made the leap from domesticated animals or rodents, as it turns out, about 10,000 years ago estimates. Rodents were like when we domesticated animals, it's like we practically domesticated rodents by accident because they were living in all of like the grains and things that we started storing. So we had huge booms in rodent populations at the same time.

Scientists aren't exactly sure which animal it came from. But it probably originated in the same place geographically that agriculture and livestock domestication took off, which is the river valleys of Africa and India. And we actually see our first physical evidence of smallpox from around 1500 to 1000 BC. What? In Egyptian mummies, whose preserved skin shows telltale pockmarks from the disease. Oh my God. Yeah. You can see the pockmarks on mummies, actual, like on actual mummies. Yeah. We're going to post a picture. Oh my God. That's so cool. It's really cool. That's insane. Smallpox is what we refer to as a crowd disease.

In order for the virus to successfully establish in a population, there needs to be enough people in close contact with one another so that it can be transmitted and maintained. Otherwise, it'll just blow through a population or village and die out. Right, because it just kills people like... Yeah. Ooh, I hope that snap got... It sounded good.

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Around 100 AD, smallpox caused a devastating epidemic. epidemic in the Roman Empire, and this epidemic was called the Plague of Antonius. Oh. Yeah. Like with the 1918 flu pandemic, soldiers returning home were probably responsible for facilitating the spread of the smallpox virus. Always them soldiers. And at the height of this particular epidemic, 2,000 people died daily in Rome.

Oh, my. Wow. Yeah. This is real bad. I feel like there wasn't that many people in Rome to die. Some historians actually suggest that smallpox, along with malaria, contributed to the fall of the Roman Empire. I love information like that. I know because no one really talks about the role of infectious disease in history. Yeah.

They do, but it's not, I feel like it's not as. It's not as big of a deal as like, and then the 300 people came and they knocked people down or whatever. Yeah. It's all about. We're going to talk about it. It all comes back to infectious disease people. the point of what we're trying to teach you here. Yeah, it is. After wreaking

havoc in Rome, smallpox made its way to the rest of Europe, probably through the Huns or returning Crusaders around like the 12th and 13th century were the Crusaders. Okay, I was going to say like, I don't know. Yeah, I know, I know, I had to look it up. I was like, Crusaders, yeah, that's sure.

That was a time that happened? Well, in either case. As global population continued to grow, smallpox epidemics grew more frequent and more, intense and in many areas it became endemic. There's a word, callback, more of a childhood illness. Okay. Let's talk about, yeah. Your face got real serious.

Because here comes one of the most, for me, classic smallpox periods of history. One of the things that history teachers, in high school at least, tend to gloss over here in the U.S. is the devastating impact that small packs and other old world diseases had on the native north and South American populations. Oh, this is where it gets really depressing. Yeah, it's going to be that way for a while. Yeah. Yeah, buckle up.

I'm buckled. Your history teacher. Oh, wait, let me have another sip of mine. Just drink. Drink up. Here's the time. Bottoms up. It's not yet.

It's just going to get worse. Your history teacher may have forgotten to tell you how. smallpox blankets were given to Native Americans intentionally by invading Europeans in an often successful attempt to deliberately infect them with this devastating disease. Like smallpox blankets as in some white dude was like, hey yo, I got a blanket. I'm going to rub it all around a person with smallpox and then I'm going to give it. That means that they knew enough to know that this disease was transmitted. You sound like you want a direct quote.

I do, thank you. I'm happy to provide. In the war of 1763 between England and France for control of North America, the British troops were asked, could it not be contrived to send the smallpox among those disaffected tribes of Indians? We must, on this occasion, used every stratagem in our power to reduce them. That's a direct quote. And wait a second, it's not done yet.

because there's a return letter from the ranking British officer who said, quote, I will try to inoculate the Indians with some blankets that may fall into their hands and take care not to get the disease myself. What? That really happened. Even in the instances when it's not entirely clear how deliberately smallpox is spread, like whether it was deliberate or not. Sounds pretty deliberate. I mean, yeah.

For instance, that case is. certainly deliberate. But still, Europeans definitely use smallpox to their advantage. Yeah. Take, for instance, Spanish conquistador Hernando Cortez. He, along with around 600 men or so, landed in the Yucatan Peninsula around 1521. Okay. And headed to the Aztec capital city of Tenochtitlan, which is now Mexico City,

to try to take over the Aztec Empire. He and his fellow conquistadors were soundly defeated in their first fight with the Aztecs and they expected to lose again when the inevitable second blow would come but it never came more than a little confused and apprehensive yeah that's what I wrote and tired of waiting the Spanish stormed the city once inside they found that smallpox had devastated the city oh my god Cortez and his men had probably all been exposed to smallpox's children and so the disease didn't affect them. Seeing this furthered the belief among the Aztecs that the invading Spanish were gods.

A belief that the Spanish did nothing to discourage. Wow, that's so sad. It is, it is. And that is how Cortez and his band of around 500, 600 conquistadors toppled the 25 million people strong Aztec Empire. That was it. That was the end of the Aztec Empire for all intends. intents and purposes. Oh my God.

This is mirrored. I just... In the fall of the Inca Empire. This is a really depressing episode. Yep. The Inca Empire, which was mainly in Peru and Ecuador in South America, this time when Pizarro, so this is another Spanish conquistador, and his 128 specifically men, when they arrived, they found an already decimated empire, as smallpox had...

had preceded their arrival, and they found these huge structures, these huge towns, these huge buildings, and they looked around and thought there's no way that these few people could have actually done this. Right. What has happened? Right. Because the, yeah, people were starving because they were dying of smallpox, and then they had no one to take care of them.

It was, I mean, no one to take care of the fields, no one to farm. So even if you survive smallpox, you had no food. Right. It was absolutely terrible, terrible. I think I'm going to cry. Well, we're not done. You're going to get more depressing? Yeah.

I mean, because we have to talk about North America. Oh, yeah. Historian Elizabeth Fen tracks a massive smallpox epidemic in North America in the late 1700s, coinciding with the time of the American Revolution. In her book, Pox Americana, she describes British soldiers who were more protected from smallpox infection because inoculation was more popular in England than it was in the U.S. at the time. Okay. Anyway, so she describes British soldiers and officers deliberately trying to infect American soldiers

where inoculation wasn't as widely accepted. So is this where they started to decide that all is fair in love and war? They're like, we're just going to... I mean, it's always been all fair in love and war. But also, you're like, I'm not going to try and actually fight. you, I'm just going to, like, get you sick. Like, come on, man, that's not, that's not cool.

Bioterrorism. It's not bioterrorism. That's what it is. You're right. Bio-warfare, at the very least. Yep, yep, yep, yep. She describes, and so this smallpox epidemic that she describes around the late 1700s was not isolated to the colonial states at the time. So the areas of New England and the eastern seaboard, it spread across the country. And this is you said American Revolution, right?

So 1770, the years she describes are 1777 to 1785. Okay. The reason or one of the reasons is that smallpox was so devastating for Native North and South American populations is because these were completely naive. Right. They had never been exposed to smallpox before. And so, for instance, the Spanish conquistadors had been probably exposed as children or the English. they across the board had lower mortality rates ranging around 30, whereas some, to read about it, some Native American groups had mortality rates upwards of 90%, 100%. I mean, it was unbelievable.

But like one of the ways that they figured out how to end up with the vaccines is that if people were exposed to other forms of pox viruses by living with other animals, then they could, even if they never got smallpox, if they were exposed to another form of pox virus might have had some sort of immunity, which is why you saw lower mortality rates in the European population. This is a nice little segue into talking about inoculation and vaccination. And the relevance to the fight against smallpox. Inoculation as a practice had been around for hundreds of years in certain cultures and regions, such as among groups in Western Africa and in Turkey. Okay. But Western medicine had ignored the practice, chalking it up to old wives' tales and uneducated

nonsense. So can you explain, like, what inoculation is? Sure. Inoculation is the practice of taking material, so usually like pus or skin, from a person who had active smallpox infection. Ew. Yeah. Taking that and then injecting it or inserting it in some way into an individual who,

who had never been exposed to smallpox. Basically, like, exposing them directly to the infectious gunk. But through a non, but through a root which was not as common. Right, because it's a respiratory virus. Right. And so what was the usual outcome of inoculation was a mild smallpox infection? Okay. The majority, the vast majority of patients who were inoculated survived.

Okay. So the mortality rate for inoculation was 2.5%. Wow. That's a lot lower than 20 to 40%. Right. So you were way better off becoming inoculated. Yeah. It's 10 times lower.

Yeah. And so you had a mild infection and you generally recovered without any scars or pock marks. However, during the time that you did show symptoms of your mild smallpox infection, you were infectious to others. And so it was still really a dangerous practice in some ways. Okay. That makes sense. Inoculation was not very popular then.

in Western cultures, so in Europe, or in parts of Europe and in North America. Okay. But then, around the same time in the early 18th century, which is the early 1700s. I was going to ask because I'm the worst at those. Okay. It's okay. Numbers. Two people on two different continents.

One, a high-born woman in England, whose name was Lady Mary Montague. Ooh. And the other, a reverend in colonial Boston named Cotton Mather. Yeah. Cotton. Cotton. Good old Cotton Mather. Where did you say he was?

Boston. Oh, that wasn't a good Boston accent. I just, I wonder how that name fell out of style. Anyway, these two took note of these practices and tried to bring them to the places they lived. The story goes that Lady Mary was a beautiful, popular woman. Aren't they all? And then she got smallpox at 26. Oh, baby.

Which left her pockmarked eyelashless. That's if you are a woman, especially at that time, does it? I mean, forget about it. Thank God she was already married. Oh, thank God. And horribly fearful of the disease, which had killed her favorite brother in the same epidemic. Wait, her favorite brother? Yeah, that's from the book.

She had like an outward, you can't have an outward favorite. That's not, I mean. Okay, whichever brother is listening to this, you're my favorite. That's rude. She moved with her husband to Turkey, where she saw that smallpox wasn't viewed with the same terror as it was in England. There, she first encountered inoculation, the practice, like we said, of grafting a bit of smallpox into an unexposed person. Okay. So she got smallpox before she learned what inoculation was.

Yes. Okay, got it. Lady Mary immediately saw the enormous potential. potential of inoculation and ordered her children to be inoculated. Yeah, me too. Oh, yeah. Upon her return to England, she tried to popularize it, but most doctors and the general public were horrified.

Yeah. One, they figured that actively giving yourself a disease was basically suicide. I mean. And crazy. It sounds pretty crazy. Sounds pretty crazy. And two, that this was going against the will of God. Oh, got to bring God into it at some point.

Because if God wanted you or your kids to die of smallpox, then so be it. Wow. Yep. To combat some of this incredibly stupid nonsense, Lady Mary and a few pro-inoculation doctors designed an experiment in which they would inoculate a bunch of people who had never had smallpox to show to the public and also themselves, because they weren't entirely sure, that inoculation was a safe practice. I hope that they got like permission.

Guess who they chose. Oh, let me guess. Prisoners and children maybe. What kind of children? Foster children. Orphans. Orphans. Yes.

Prisoners and orphans. Prisoners and orphans. Always at the end of the short stick. Medical ethics. Was not a practice at this time. No, no. Well, regardless, the experiment worked. Whoa, that's good.

Which is good at least. Yeah. A somewhat similar sequence. of events occurred in Boston, except that there was no formalized experiment on repressed populations, just people going up to this doctor named, you ready for this, Dr. Zabdiel? Oh, geez. Boylston. Boylston?

Yeah. That's a terrible, but also very appropriate for the occasion. I mean, it was the early 1700s. Boylston studying smallpox. Yeah. And asking him to inoculate them. Okay. So at least in this case, it was willing volunteers.

For the most part. That's got to be the first time that the U.S. has done it right. Just kidding. I don't know. I mean, who knows? He did catch a lot of flack, though, for inoculating people because it was also hugely unpopular and actually survived several assassination attempts. Oh, wow. Interesting.

Eventually, the numbers couldn't be ignored. Inoculation carried a mortality rate of 2.5, while, like you said, natural infection was upwards of 30. Yep. Inoculation became patchly popular throughout the 18th century, but was dethroned by vaccination in 1793. Oh. You're probably somewhat familiar with this story, or at least the name of its star, Edward Jenner. Eddie was just going about his life as a country doctor. Eddie.

When he noticed that milkmaids, who had once been infected with cowpox, never got smallpox. So cowpox is a much milder infection in humans with basically no chance of mortality. Because I'm guessing that it is a virus that generally infects cows. You're right about that. Oh, I'm so good at the guessing. He decided to try to take some of the pus of an active infection of cowpox and then put it into the skin of a completely unexposed person to cow or smallpox. Interesting. So it's kind of like an inoculation but with a different virus. A more mild virus.

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or in Lego retail stores. And Jenner tried this out on eight-year-old farm hand James Phipps. Hello, Medical Ethics Board. Where are you? Still? No, no word. James was like, ooh. He was like, I guess I got no choice. Poke you.

But was Jenner supposed to just sit around and wait for smallpox to come to James Phipps? Nope. Smallpox would. come to James via Jenner, who directly exposed him. Luckily for James and the rest of the world, his previous exposure to cowpox fully protected him.

Awesome. Yeah, it's really, I mean, it's actually a huge step. Hold on. Wait. He, so he gave James Phipps, poor little kid, cow hand, stuck him with cowpox, and then he exposed him to smallpox? Yeah. Wow.

That's the sequence. That's awful. I'm so glad it worked. Yeah, I also, so is James. Jenner decided to call this practice vaccination. Vaca, meaning cow, in Latin. Yeah, so that's where vaccination comes from. It's pretty cool.

That is awesome. So literally the word vaccination that we use now for all vaccines. All vaccines. Is because of smallpox. Yep, VACA. That is so cool. Yeah. Like inoculation, vaccination took a little bit to catch on,

but once it did, it spread faster than the smallpox. pox virus around the world. That was a really good one. Thanks. And enabled doctors to eradicate this disease which had plagued humanity for millennia. Which brings us to eradication. Yeah. The gold star on this story.

The bright shining moment to lift you up. I think for most of us, smallpox feels ancient like a thing of, I don't know, history. Like the 1600s. I mean, when Columbus came over, like, it feels so far removed from where I am in terms of thinking about people who are actually infected by it. But did you know that in the 20th century, smallpox killed over 300 million people? Oh my God. That's more than all 20th century wars combined, World War I, World War II, Vietnam War,

so many wars, and also more than the 1918 flu. It's also the population of the United States of America. Yeah. Like, there's what, 350 something? 300 million people. That was in the 20th century alone? Uh-huh. Oh my God.

Now, thankfully, though, it is a thing of the past. Yeah. Smallpox death toll in the 21st century? Zero. So far, but I'm getting ahead of myself. In 1966, the World Health Organization, the WHO, proposed a plan to eradicate smallpox and put D.A. Henderson in charge of carrying it out. Over the next 12 years, thousands of people travel to some of the world's most remote corners,

living in extremely challenging conditions and working in conflict-ridden countries to administer smallpox vaccine in an attempt to eliminate it completely. And it worked. The last natural case of smallpox infection occurred in Somalia on October 31st, 1977, over 40 years ago this month. This, wow. Well, next month. Not anymore. Yeah. And it happened in a 23-year-old cook named Ali Mao Malin, who had actually once worked as a smallpox

vaccinator, despite never having been vaccinated himself. Wait, so he worked administering the smallpox vaccine to people, never got vaccinated, and then was the last natural case of that's... Isn't that funny? That is really funny. I did not know that. Yeah. Once news of his infection reached the WHO, a team was sent to vaccinate the around 90 people who had come into contact with him.

Isn't that crazy? 90 people that he came in contact with before they were able to be like, oh man, we need to isolate this person. Luckily, he survived the infection and no more cases emerged. The world was declared smallpox free. on May 8th, 1980. And this guy, actually, Ali, went on to work very hard for the Carter Foundation to eliminate polio. Oh, wow. But he died last year of malaria.

Oh, that's sad. Sorry. He was 63. He was, oh, that's so young. Yeah. Oh, God. I wish the story of smallpox could end here. But I have a stad story to share.

Oh, why? Remember how I said Malin was the last natural case of smallpox? Yeah. I used that qualifier because. there was another case after his. What? In England, August 11th, 1978. A medical photographer, Janet Parker,

became ill and started showing signs of smallpox. It turns out... In England? In England. What? That's ridiculous. Oh, yeah. Just listen on. It turns out she had used a phone booth in a building which shared an air duct with a smallpox research lab, and some of the virus must have escaped through the dust.

into the booth where she inhaled it. She and her mother both came down with smallpox and possibly her father, but he died of a heart attack before symptoms appeared. Oh my God. Her mother made it. Janet did not. The scientist whose lab it was, Dr. Henry Bedson committed suicide after his whole ordeal. Oh my.

The person who was the one in the building studying smallpox when he heard. He felt responsible. Oh. I'm sorry to end on a side note. Yeah. What the heck? We could have stopped it with eradicated. But smallpox is gone, mostly.

Yeah. At least it remains the only human infectious disease to have been eliminated. Wow. Though I'm hopeful that those words will be wrong within a few years when polio and guinea worm are gone. Wouldn't that be great? Yeah. So, Aaron, smallpox is eradicated. Does that mean we don't have to worry about it?

Oh, hell no. Oh, no. No, I'm also really worried about it. No, yeah. No, no lie. Me too. Basically, we're all forked. I read something in one of the books about how a Russian scientist defected to the U.S. After he had been working in a lab whose goal it was to make a more virulent vaccine-resistant strain of smallpox. Yeah.

This was in the 80s. Yeah. And it turns out that this lab had not been listed on any register as to the remaining. places that smallpox was supposed to be held. Yep. So in case you don't know, smallpox is officially... On paper, at least... exists in two labs.

One in the U.S. Right. Two specific buildings. One, the building is called Corpus 6. It's at Vector, which is a research institution in Russia. The other place that it exists on paper is in the maximum containment laboratory at the Center for Disease Control in at least. Atlanta in the United States. Those are the only two places in the world on paper that smallpox virus exists.

But you're a fool if you believe that those are the only places it is because North Korea definitely has smallpox. I have a whole list of a bunch of countries. Not that we're that worried about France, but you know. I'm worried about France. I don't know why. I'm just saying. I'm just worried about a whole lot of people. I'm just worried about every, let's see, India. Pakistan, China, Israel, Iraq, North Korea, Iran, possibly China, possibly Taiwan, possibly France. Yeah, dude, that's a whole lot of countries. I mean, who's going to go, oh, yeah, here's all the smallpox, wink, like everyone.

The World Health Organization, back when they were sort of trailblazing on this eradication effort, they were getting really close to eradicating the disease, they started sort of strongly suggesting that everyone who was doing research on smallpox either destroy their stores of the vaccine or send them to the U.S. and Russia. There was a date around 1995 when everyone was supposed to have just either... Actually, okay, sorry.

So prior to 1995, all these countries were supposed to have sent their samples to Russia or the U.S. Exactly. And then in 1995, they were Russia and the U.S. were supposed to destroy the samples. And so basically what has happened is every few years since then, there is a convention and people decide should we destroy everything or should we wait a few years for research purposes. And that has literally been what has happened every few years until this day. Those stores still exist. People maybe are still doing research.

It's really hard to find any information about what type of research might be happening. Well, they certainly were following 9-11. Yeah. Well, before. Yeah. Before and during. And so, and but since 9-11, since the anthrax scare, smallpox has been considered to be one of the more viable threats for in terms of bioterrorism. Yeah.

Because it is so fatal. It is so infectious. Right. Or at least infectious enough. And it can be dispersed very easily. Right. It's airborne. It's airborne.

It's airborne. And so it's a really interesting ethical issue. It is. Because there's no more smallpox in the world. Right. Do we continue, how do we justify the continued research funds, research animals? Yeah. And at this point, really, the only reason that it is quote unquote justified to keep these stores of smallpox virus is because of the threat.

of bioterrorism. And so we need to be able to develop vaccines. We need to be able to do research. But then that is only because we think that there are other people out there doing research to potentially make this a weapon. But there are. That has been verified. Well, yeah, but that's the thing is, I mean, it's not like it's just one person or one entity that's doing that. And then everyone else is just trying to defend against it. Right. It's likely everyone who is doing research on how to weaponize it. I mean, this is just us talking, but I mean, this is also logic. I think it's a very real fear that this could be weaponized because there was research done on mousepox to have, and so a group of researchers in Australia manipulated the mousepox virus to

defeat the vaccine so that vaccinated mice died or were susceptible to mousepox virus. And that is very easy that could be very easily done with smallpox as well and the other thing is that the smallpox vaccine is extraordinarily imperfect. Imperfect is is sort of a nice word to use for it. Currently today about 20% of people would not be eligible to be vaccinated for the smallpox vaccine. Right. So before you go jumping to your doctor and trying to get a hold of smallpox vaccine first of all it's not going to happen. They're never going to give it to you. Second of all you may not be eligible. So anyone with eczema or who lives in a household or who has family members with eczema is not eligible to get the vaccine.

If you live in a house with babies, you cannot get it. What else if you're auto-compromised? Yeah. If you have any sort of autoimmune disease or are on chemotherapy or have HIV or honestly if you probably live in a household with an immunocompromised person because the thing is that the current vaccination for smallpox is another virus. it is not a modified, killed form of the smallpox virus. It is a live active different virus that they inject you with under your skin that actually causes a viral infection. It's just very localized

to one pock essentially. Right. So you've probably seen the scars. Yes. And I used to actually think that that scar was because the way that they injected the vaccine was like a big. I did too. That's what I So there are things that are vaccine guns, which they use. So did you see this? Well, but that's what I used to think that the scar is from. But it's not at all. It's because it's because that's the way the pock formed. Yeah, there was an actual pock there. And actually, this reminds me, one of the things that makes smallpox such a good candidate for eradication, there are multiple reasons. One, you can easily tell who has been vaccinated or not, judging from the smallpox scar that they have or the vaccination scar. The second is, you know, the is that the vaccine itself, when freeze-dried, has really long, or has really high longevity. Okay. And it's really stable. Right. And so you can transport it to these tropic countries where there tend to be a lot of more cases of

smallpox. And the third is that there is no known animal host. Reservoir. Thank you. Reservoir. And so even if, for instance, if you eliminated it entirely from humans, if it still could infect animals or was or animals were a reservoir for it. Right. It means that you could still potentially, humans could still potentially be exposed.

Right. That's why there are so many diseases that as much as we would like to eliminate them, it's nearly impossible because there are animal reservoirs for so many diseases. The other thing about the smallpox vaccine, besides the fact that about 20% of the population could not be vaccinated in case of an outbreak, is that though there are probably swaths of the population that were vaccinated either as children or I double-checked with my brother-in-law. Some active duty military people also get vaccinated depending on where they, I don't know if it's what branch of the military they're in or if it's where they're going to be sent to. But they are

also given the vaccine, but immunity tends to only last about four to five years. So if you were vaccinated a few years ago or when you were a child, you're no longer immune, essentially. So if there were any sort of outbreak that happened today... Sorry. Yeah. It does you know good. I mean, it could be the case that you have a lesser infection, like a lesser degree of infection. You might end up with the sort of mixed form or whatever.

Is that what it's called? Modified. Modified. You might end up with the modified form, but still pretty gnarly. I think our point is how scared should you be of smallpox? Pretty scared. Really? really forkin scared. Seriously. Seriously. I didn't even, I mean. I mean, I think it's smallpox,

despite having been completely eradicated, is so important and so relevant for today for a number of reasons, one of which is bioterrorism. The other which is the vaccine scare, which I don't want to get into the whole nitty-gritty on, oh, vaccines are bad for you. We're going to get too angry at this time of night, I think, if we get into that. But if, if, think it is really fascinating to see these parallels between vaccination when it was first introduced and nowadays and the pushback against that and the reasons why. And I think that the absence of diseases, such a visible disease is, such a smallpox, really lead people to forget how important vaccination actually is. That's the thing is it's really easy when you're so far removed.

The thing that I think is so crazy is that not a single physician, in the world who has been trained since the late 1970s has ever seen a case of smallpox, ever, ever will. Hopefully. But. Oh, I think it's incredible. It is absolutely incredible because the thing is, like, I mean, I'm in medical school right now. We have never talked about smallpox besides to say that this is a disease that has been eradicated.

We've never talked about the symptoms in depth. Don't worry. It's eradicated. The WHO is gotcha. Right. And so to think that if there were to be, even if you don't think about it from a sort of large-scale bioterrorism aspect, if you just think of what if a few particles somehow got out. In a lab accident, such as happened to Janet Parker.

Exactly. And so, I mean, if something like that were to happen, could we even diagnose it? in order to contain it. Oh. Isn't that scary? I thought of that while doing all this research. Is there a movie that is smallpox? Not that I know of.

There should be. Screenwriters, get on this. Yeah. Are you hearing this, guys? This is a great... This is scarier than the movie Contagion. Oh, way scarier. Yeah, so if we were...

At one point, we talked about doing a sort of threat level on all of these episodes, like terror threat level, orange or whatever. This is threat level wear a diaper because you're about to pee your pants. Oh, yeah. We have no scale. No scale. Yeah, we don't have a scale. But in reality, yeah, be really scared.

Smallpox is awful. It's really terrifying. But wait, we've been using the wrong verb tense. Smallpox was awful. It was. Thank goodness. Thank you, world health organization. It's actually amazing.

what they accomplished. It really is. We should let people know if they'd like to read more because some of these books are really amazing. You've got a list. I've got a list. Hit me with them. If you want to know more about inoculation and the development of inoculation as a practice in England and the U.S., you should read The Speckled Monster by Jennifer Lee Carroll. If you are interested in the nitty-gritty of the epidemic that happened to, in North America from 1777 to 1785, you should check out Pox Americana by Elizabeth Fenn. Smallpox, the death of a disease by D.A. Henderson is a book penned by the leader of the eradication effort himself. And it is an is amazing book. It is really great. Also, don't you have a signed copy

of that book in your personal collection? I got it on like A-Books or Amazon and it's signed. I'm so thrilled. By literally the person who was the reason that we were able to eradicate this disease, D.A. Henderson. Props. The other book that I think you should read is called The Demon in the Freezer. And it's by Richard Preston. It reads like a movie script. It is really exciting.

It's more about the eradication effort of smallpox and then anthrax in terms of bioterrorism. Yeah. It's a little dated, but it's really still really. good. The Power of Plagues by Irwin Sherman. It's a compilation book with chapters on different diseases or on different topics in terms

of plagues and epidemics throughout history. And all of those are great. We recommend them. So if you're interested, read more. Yeah, check it out. Check it out. Fact check us. That'd be fun. If we're wrong, let us know, man. Yeah, we would love to hear. Yeah. Because we're just doing this for fun. Yeah,

it's very fun. It is. And so what's happening next week? Speaking of more fun. I don't know. What is happening next week? Colora. Callera. Yeah.

Oh, man. That's going to be fun. Collar is going to be good. Get ready for some good John Snow puns. The King in the North. That was my first attempt. The King of the Colora. We'll work on it.

Yeah. We've got a long way to go. Please, please, please, please, please, rate and review us on iTunes or wherever you get your podcast. And subscribe. And that is how other people, are able to find this podcast. So if you like us, then you think other people will like us, then you should definitely rate and review us so that other people can find us in the first place. We are also on all these other podcast hosting websites. We're on Podbean. You can find us on

Stitcher, on Google Play, anywhere else you get your podcast. And we also have a Facebook page, an Instagram page, and a Twitter page. So please follow us on each of those if you want to see some really cool pictures of disease or see some cool facts or get our recipe for whatever quarantine we're drinking. Yep, we post that every week. This podcast will kill you. Our Twitter is our acronym. I can't spell it.

T-P-W-K-Y. That's it. All right. I think that's it. Yeah. All right, everyone. Wash your hands. Yeah, filthy animals.

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