Hello friends.

First of all, a heads up.

We're talking about smallpox today and descriptions of the disease may be upsetting for some listeners.

It was pretty awful and we're super lucky we don't have to deal with it anymore.

Second, I'm heading to the UK in August.

The Royal Society is sending me to the Edinburgh Book Festival.

I'm going to be doing events on August twelfth and the thirteenth, and on August twelfth the Royal Society will announce the shortlist for their twenty twenty five book Prize at the end of the event i'm doing.

If you're at the book Festival, please come by and introduce yourself.

I would love to meet you.

All Right on with the show.

No disease has ever been so instantly recognized or so widely known and feared.

Smallpox was hideous and unforgettable for me.

The memory of award full of smallpox victims thirty five years ago in Dhaka, Bangladesh is still vividly etched in my mind.

Anxious, pleading, pock deformed faces, the ugly penetrating odor of decaying flesh that hung over the ward, the hands covered with pustules reaching out as people begged for help.

Neither water nor food offered comfort.

Puss filled lesions covered the insides of their mouth, making it painful for them to even chew or swallow Flies were everywhere, thickly clustered over eyes half closed by the pustules.

More than half the patients were dying, and there was no drug, no treatment that we could give to help them.

This was a paragraph from D.

A.

Henderson's twenty nineteen book Smallpox, The Death of a Disease.

Smallpox is estimated to have taken hundreds of millions of lives, and the story of how humanity eradicated smallpox is the story of one of our greatest victories.

Coordinating across cultures and continents, we harnessed science to spare future generations from this devastating scorge.

Today, we're going to talk about a project coordinated through the World Health Organization and led by D.

A.

Henderson to drive smallpox out of our bodies.

However, smallpox remains in our labs, and we'll talk about the risk that poses for humanity.

Welcome to Daniel and Kelly's Smallpox Free Universe.

Hi, I'm Daniel, I'm a particle physicist.

I've never had smallpox.

I did have chicken pox, and I've always wanted to say, a pox on both your houses.

I'm Kelly Waiter Smith.

I study parasites and space.

I have also never had smallpox, thank goodness.

I don't think anyone has had smallpox since the nineteen eighties.

And I also lived in the era of chicken pox and had that pox upon my house.

Welcome to Talk some Pox, new podcast.

I'm pretty glad I never had to see my kids with chicken pox.

Hmm, Yeah, I remember it being pretty miserable.

Yeah, it's like a few days home trying desperately not to scratch all those itchy spots.

Well, you know what was even worse.

So Zach got chicken pox, and when you're older, shingles is essentially chicken pox waking up.

Yeah, And right after our second child was born, Zach got shingles on his back, and our son wasn't vaccinated because he had just been born, and I didn't want him to get chicken pox, and so I had to stay upstairs with our newborn and didn't let Zach up, and Zach stayed downstairs with our three year old, who did not at all care that Zach was suffering mightily, and so she would like smack him on the back where he had his shingles spot, and she'd be like, take me to the oo, carry me around.

Then he was such a saint because he was miserable.

Shingles is the worst.

Yeah, And shingles is also like maybe the most terrifying name for a disease.

Yeah, you know the other ones like cow pox, smallpox, measles, whatever.

It's sort of an abstract thing, but shingles makes me feel like you're gradually turning into a house or something.

I don't know.

The visual that conjures up in my mind is terrible.

Yeah, I think because I was reading about smallpox and I saw a bunch of pictures of people with smallpox.

That is a worse image to me than a house.

Yeah.

I think I'd rather turn into a house than a smallpox victim.

Well, it's unfortunately an appropriate time to be talking about smallpox and vaccinations and the science behind disease and pathogens and infection.

So we're dedicating today's episode to that topic.

Yes we are.

Yeah, it's a scary time.

I just got a message my daughter's starting a summer school, and I got a message about measles being in the area and how we all need to be alert to make sure our kids don't bring measles to camp or I'm home with measles from camp.

Killers of the past are returning like ombies.

Yes, but let's hope smallpox doesn't come back, which we will return to at the end of the episode.

All right, so you asked our listeners a question about smallpox.

Yeah.

So, while we are living in a moderately depressing time in terms of measles making a comeback, at least in the US, there is a lot to be excited about that has happened in the past in terms of disease control.

And so I asked our listeners.

D A.

Henderson led the effort to eradicate which deadly disease.

And I will tell you that DA Henderson is one of my heroes, and I think everybody should know his name because many of us probably owe our lives to the fact that this man lived on this planet.

So let's see what our listeners had to say.

Could it have been polio?

We will be a gift.

But to extrap a light from eradication, I have to guess to these small books.

Da Henderson worked tirelessly to help eradicate disco fever.

I have no idea what disease da Henderson tried to eradicate.

I don't recognize the name.

But there's only two diseases that have been eradicated, smallpox and renderpest.

Might be one of those, or it's something that he tried to eradicate and did not succeed, in which case I have no idea.

I do believe that we've only eradicated one actual disease and the rest are just minimized but still happened.

So I'm going to guess at smallpox that I don't know.

This person in their work just goes to show that a lot of research and effort goes into saving lives and making lives better without notoriety.

I don't know what dia Henderson helped that with.

Maybe polio or tuberculosis, but I don't know.

I think you you're the disease of using initials for first and middle names.

Good mix of answers here.

What are da Henderson's first and middle names and why does he go by initials?

Well, let's look it up already, Like good start all right, Donald Ainsley Henderson.

That's not so bad.

Why did we go by Da?

I don't know someone whose last name is Wienersmith.

It sounds totally reasonable to me.

I'm not sure what he's so embarrassed about.

He should be loud and proud.

But as I suspected, there actually weren't a lot of people who immediately were like DA Henderson helped eradicate smallpox.

I know that name, yeah, you know, it's as important a name to me as Lincoln or something like that.

But this man probably saved many, many, many lives.

Smallpox was a horrible scourge on humanity for like thousands of years, and he played a huge role in eradicating it.

So how much do you know about smallpox, Daniel?

I know that it sounds terrible, okay, and that I don't have to worry about it, for which I'm grateful to people whose research is actually practical unlike mine.

And I would like to point out how amazing it is that smallpox is not at the forefront of like anyone's mind in our generation.

You know, I was born in eighty two, which is two years after the declaration that smallpox was eradicated, and so I don't think much about this, but if you were born in the eighteen hundreds, for example, there was a good chance that you would lose someone in your family to smallpox.

I think it has interestingly a different cultural impact than polio.

Polio we sort of know more about, and we've heard maybe more about the vaccination and the success there.

And I wonder if it's because polio didn't kill all of its victims, it left them paralyzed.

And so there are people around today like Mitch McConnell who suffered from polio as a kid and like can talk about it, whereas smallpox' victims are like, you know dead.

Well, polio still is around, right, Polio is coming back you Yeah, smallpox is gone.

Yeah.

No one has had smallpox for what forty plus years now or something, which is incredible wood knock on wood.

But but I mean people who did have it, it was horrible.

So there's Yeah, smallpox is caused by a virus, and there's two main versions.

There's Variola major and veryola minor.

The major one is majorly awful.

It kills something like thirty percent of the people who get infected.

Oh wow, Yeah, it was really common in asia, and then there's variola minor.

The death rate is lower, it's about one to two percent, which still, like, you know, if my kid got infected by smallpox, I wouldn't like those odds.

That's petrifying.

Nobody wants to roll that die.

Yeah, no, absolutely not.

And it was miserable.

So you mentioned that polio leaves a lot of people debilitated for the rest of their lives.

Smallpox creates you know, sort of like chicken pox, but much worse, pos all over your body.

Often they scar and they'd leave sort of pits in your skin that you'd have for the rest of your life.

And if the smallpox ended up getting into your eyes, you would also go blind.

And so smallpox was a leading cause of blindness, and so it would also leave a life of people debilitated if it didn't happen to kill them.

Right, And how does it actually work?

Like what is the virus doing?

Well?

So, typically the way you get infected by the viruses you breathe it in.

So like if somebody talks in some of their like saliva, it gets aerosolized and then you breathe it in.

A couple days later, you start showing symptoms.

The symptoms include puss filled lesions that cover your entire body, including inside of your mouth.

Oh and yes, and these lesions start, you know, like weeping puss, and that puss is contagious, and it becomes almost impossible to drink water, to breathe, and I think your you know, your immune system probably just gets overwhelmed.

To be honest, I'm not one hundred percent sure what it is that's killing someone, but you just end up covered in these horribly painful lesions.

And we didn't have a treatment, so if you got it, you just had to work your way through it.

There wasn't like a medicine for it.

So no antivirals, no treatment even for the symptoms.

Uh no, wow, No, I mean so like there's a quote for the opening from da Henderson where he was describing seeing this in a hospital in Bangladesh and they were just all of these people suffering, they couldn't drink water, and he was lamenting that there was just nothing we could do for them once they got infected.

But for a while, we actually did have some pretty good ways of preventing people from getting infected.

So smallpox is one of our early stories about figuring out ways to vaccinate people, which is kind of amazing.

Initially we did this thing called vari elation.

And so the idea here is that there's some strains of smallpox that are more lethal than others.

And so if somebody in your family comes down with a mild case of smallpox, you like managed to hit that incredible jackpot where they got smallpox, but not the really bad one.

Ye, you would take the puss from one of their lesions and you would use a needle to like inject it under your own skin.

Oh my god.

Couple things.

So, One, you're getting a less virulent strain, and if you breathe that in, it's worse for you than if you get it through your skin.

I don't think we totally understand why that is the case.

But the big picture strategy here is get infected by the lesser one, which will protect you against the worse one.

Yes, exactly, but you know, you'd still often get covered in those pocks and you'd be you know, scarred for the rest of your life, but you had a better chance of surviving.

But a problem with this method is you were still infected by smallpox, and you were more mobile, you could move around more because you had a less bad case.

Oh so you're spreading it exactly, Yes.

So you're breathing it out.

And there's some stories about people like sending vary related individuals into war ones to try to like get the other side infected by smallpox.

Oh gosh, I know, absolutely horrible, like early examples of biowarfare.

How far back in history is this, Like have people been infected by smallpox for all of human history?

Or is it a recent thing?

Yeah, so we don't know exactly when it first popped up.

We think that it was first infecting rodents, and what probably happened is there were a couple instances where it jumped from rodents to humans and then it probably fizzled out and didn't go from human to human.

But one of those times when smallpox jumped from a rodent to a human, it also had the ability to go from human to human after that.

Are we blaming this on rodents with good data or we just bigoted against rats because I'm pro rat.

We have established that you and I are both pro rat.

I've been looking into adopting a rat, but it would have to live in my office, and then it might mess up our audio, So I think I might not adopt a rat.

I think the listeners would like hearing a few stups from a rat now, and then I think they might.

They might have could play in my lap while we're having these conversations.

We'll see we can interpret it sounds as whether it's agreeing with you or disagreeing with you.

It'd be fun.

I vote yes.

I vote rat include citations, Kelly, workshop that joke a bit more, Kelly, calm down, rat it to me.

I'll get to it.

I think we're envisioning the rats like those grumpy guys on the Muppets, you know, sitting in the theater.

I love those two those But anyway, back on track, So are.

The rats really to blame here or are they just escapegoat or escape rat?

Yeah, we can't be one hundred percent sure, but there's pretty good evidence that smallpox is similar to viruses that you find in rats, So there's a good chance that it jumped.

So why didn't we call it rat pox?

Because the other one we call it cowpox or chicken pox, right, so why do we call it rat pox?

I believe that those are also not very well named poxes.

I think that we encounter cow pox when it's in cows, but I think that that also is often in rats, And so I think these viruses are often in rats, but then it jumps into other organisms that we interact with more regularly, and then we name it after that.

So rats are to blame for rat pox and cowpox and chicken pox.

I no, I'm not going on the record for all of those.

I'm sure there's some variability, but I think I remember reading that cow pox also is often in rats.

But you know, that's not relevant to us.

What's relevant is that when we're milking the cows, we see the pustules.

All right, so we think it came from rats.

But how long ago are we talking about?

What's the earliest record forward evidence of smallpox?

I don't know exactly when the earliest recorded evidence is.

I did come across in eleven fifty seven BC.

Ramsey's the fifth in ancient Egypt, appears to have died from smallpox.

You can see the like pox in his mummy.

Wow.

So it's been around for a while.

And you know, we were talking about variolation, which is when you like pass less virulent strains.

We have evidence that that started in India sometime around one thousand BC, and about two thousand years later it was introduced into China.

And so we've been as a species dealing with this thing for thousands of years.

But this very clever species that we are managed to eradicate it in the nineteen eighties.

So that's pretty amazing.

Actually, it is amazing when you live in a turning point in human history, right where you have like thousands of years where we live one way and then we've done something to change fundamentally to human experience.

That's incredible to live in those moments.

Right, Yes, Yeah, I mean like when my daughter was born, I had very high anxiety post part of anxiety, and so almost every day I would think to myself, I am so lucky that I don't have to worry about smallpox on top of everything else, Like, there's no way my daughter's getting smallpox.

How lucky am I?

But yeah, no, this is a fundamental difference in what parents and people need to worry about.

I'm like an anxious person also and a worrier as a parent, but I've never worried about smallpox.

I've worried about cars, I've worried about lightning.

I've worried about coyotes.

I've worried about all sorts of crazy stuff, but never a small fox.

That's amazing.

Where did that even come from in your mind?

When my daughter was born, I had trouble sleeping at night, and Da Henderson's story about eradicating smallpox.

Where a bunch of these facts today come from was what I read in the middle of the night when I couldn't fall asleep.

And maybe not a great idea from middle of the night reading I'm a new parent.

No, I made a lot of bad choices with my reading materials back then.

But that was the same year where we found in one of the labs in the United States old vials of smallpox that somebody had not destroyed like they were supposed to.

They had forgotten them, and they were in a closet somewhere.

And if that had gotten out, yea, we would have like And so anyway, I was thinking, oh my gosh, do we still have like vaccine stockpiles somewhere?

What would happen if smallpox came out?

But anyway, we're going to get back to that at the end.

So getting back to solutions.

So for thousands of years we've been suffering with smallpox.

We had this variolation strategy to minimize the impact of smallpox.

When did things change?

When did humanity like step up our approach to this.

Well, so the variolation technique was great.

It brought death rates from like thirty percent to one percent, but it was still a risky procedure.

You know, there was still some chance that you were going to end up killing your kid when you variolate to them.

So in seventeen ninety six, Jenner makes this amazing observation, which is that women who work with cows who like milk cows, they'll get these like pustules on their hands.

So the cows get cow pox, which is a closely related but different virus causing these poxes.

The women who are milking the cows, you know, become very close to the puss that's produced by these pustuls, and they end up getting cow pox on their hands.

But it's not a big deal.

But that virus is closely related enough to smallpox that getting those pustuls on your hands was correlated with not getting smallpox throughout the course of your life.

And so this had become sort of anecdotal, and then someone started taking it seriously and they were like, hold on, what if we just start purposefully infecting people with the puss from these you know, these poxes on cows and see if we can use that to protect people from smallpox.

Let's go from correlation to causation.

Yeah, that's right.

And so they started like purposefully infecting people with puss from these like boils on the cows.

And the people who got this method of vaccination and it was called vaccination because vodka is a word for cow.

Oh my gosh, isn't that where vaccine comes from?

From vodka?

I had no idea.

Yeah, so cool, so cool.

We should call it vakapox.

It rolls off the tongue a little bit.

Better better than cow box.

But I mean, this was like about one hundred years before the germ theory of disease, and there was just this like correlation that someone picked up on and they were like, let's try it, and many lives were saved.

But it also wasn't a perfect method, do you.

Know what they were thinking?

Like, they didn't have the germ theory, but they obviously were being kind of scientific about it, right, They're looking for evidence finding, correlations making, hypotheses, testing these things.

Did they have an idea for why it would work?

Yeah, So I can't say that I have read widely what people were thinking at that time, but I would guess that the thought process wants something like you only get smallpox once in your life, Like if somebody lives through smallpox, they're not going to get it again.

And we knew that, and they probably noticed that, like, look, this other person is getting some sort of pustial POxy related thing and then they don't get smallpox.

And I don't know why that is, but let's lean into it, like, you know, assumed it was some kind of immunity.

And that might sound sort of like ad hawk to people, But don't forget that there's lots of modern medicine that we rely on because it's effective, but still don't fully understand how it works.

Like Katrina was telling me the other day, we don't understand the molecular basis for like tile and all, wow, why exactly that works?

Well?

All right, but we have a lot of data that it does, so we feel safe.

And we talked a couple episodes ago about how we don't really understand how general anesthesia works at a like molecular level, but you know, you make these steps forward and you kind of try to figure out why they worked after the fact.

But if it works, you know, you keep moving forward.

And this is a really important point for public health, right because in fundamental science, we can like you know, twitter around for years wondering about what's the nature of space and time and try to figure it out and take a decade or whatever.

But public health, like you have to make decisions.

You got to say, like what are we doing, are we doing this, we're doing that?

Are we recommending this to kids?

And were recommending that?

And so the scientific debates can and should still canntinue, but you also have to make policy decisions even without perfect information.

So it's like super.

Challenging, Oh my gosh.

And in the next segment we're going to get into more detail about how difficult it was.

You know, when you decide that you need to vaccinate like most of the world to try to eradicate smallpox, what do you do about the people who say, I don't want to take the vaccine.

Yeah, yeah, it's complicated.

And so this vaccinating using cowpox worked great, but there were some problems.

You know, cows aren't always producing lesions at the time when you want to vaccinate people.

Sometimes cows get puss filled lesions caused by other stuff, and so instead of actually vaccinating somebody, you've just injected some bacteria into their body and so not perfect.

And then often what would happen is that you would use the lesion from the cow to infect the first person, and then that person would get a lesion on their arm, and then you would transfer it from one person to another.

So there's stories about kids with lesions on their arms getting sent across the sea to like move that vaccine from person to person to like bring the vaccine to America, because it was easier to do that than to do it with a cow.

Children are smaller than cows, that's true.

It's easier to shift than I found.

Yeah, it's a smaller box required.

Right, Some of them cooperate better than cows.

Two not all of them, but at least they're smaller, so you know, you can push them around.

But sometimes they would also transmit tuberculosis, and not necessarily for the children, but if you were doing this with adults, sometimes you'd transmit syphilis from person to person.

So also not a perfect method.

All right, so we moved past just suffering through smallpox and pasted variolation to minimize the impact into early forms of vaccination.

Let's take a break, and when we come back, we'll hear more about the modern approaches to vaccination and the role played by D.

A.

Henderson and keeping Kelly up at night.

All Right, we're back, and we're hearing about humanity's struggle and victory against smallpox, the macroscopic beings finally winning out over the microscopic It's amazing that we can eradicate smallpox, but not rats, right, Rats just seem like they're going to be here forever.

Yeah, No, they absolutely are.

I would not center your hopes high for eradicating rats.

There's a lot of kinds of rats.

It's complicated.

Yeah.

Yeah, And I like rats anyway, So I'm not saying we should.

I'm just saying it's amazing how we can actually squash out an entire form of life because we decided it's too dangerous.

Yeah.

So, I mean, we were successful at squashing smallpox, but we've tried.

I mean, the amount of money that has gone into trying to squash malaria has been intense, but we have not succeeded.

And we were trying at the same time to eradicate malaria as we were trying to eradicate smallpox.

But one of the quote unquote nice things about smallpox is that it just infects people, and so that makes it a little bit easier to eradicate.

And we were able to create a vaccine that was effective, whereas attempts to eradicate malaria using vaccines haven't been as successful.

And I'm queuing up an episode with an expert on why it's so hard to make vaccines for parasites.

But we got lucky that smallpox was easy to control with the vaccine and only impacted people, so we didn't have to also control something like mosquitoes.

All right, So then tell us about how we started to make more rapid progress against smallpox.

Yeah, So this method of using cows to help vaccinate people and then vaccinating arm to arm was difficult and laborious, and it was hard to do mass vaccination.

But then we figured out ways to dry the vaccine and then rehydrate it so that you could essentially have a farm with loads of cows.

You could collect a bunch of pus.

You could dry it out and then it would be stable for longer periods of time, and then you could rehydrate it wherever you decided that you needed it.

But we're still using essentially cowpus as a vaccine for smallpox, that's right, Yeah, And you said that started in the late seventeen hundreds.

How long did.

That go on for till we eradicated smallpox?

As much as possible, We were using cowpox to vaccinate people instead of smallpox because it was just safer.

So early part of last century, early nineteen hundreds, were still using cowpus to fight smallpox.

So when I was reading about this in the nineteen fifties, they were talking about how they learned how to freeze dry the viruses for the vaccine, and they were still using cows, and they thought it was cow pox that they were using, but then when they genotyped it later on, it looked like they were using vaccinia, which is another closely related virus, and so maybe that virus got into cows, but we were using stuff collected from cows, is the point, because it was just less likely to kill people.

But it was still a problem for immunocompromise people.

There were still some people who had very bad reactions and some who passed away from using this vaccine.

So we started out not knowing at all how it worked.

And then we developed germ theory while we were still doing this, and then we kept using it even after we had a deeper understanding of like the microbiology of what's going on here.

That's fascinating.

Yeah, I mean, we kept using it, but we got better, and you know, we ended up with better techniques, and at some point, like during the World Wars, we had created essentially this like vaccine gun where somebody would come by and it was like hydraulically operated and it would like inject the vaccine and then you could get the next person in and now you could do a thousand people in an hour, and that really sped things up.

But the method that ended up being used to eradicate smallpox was much easier.

So they created this cheap, very short needle that was bifurcated, so it's like a fork with only two times, and what you do is you would stick it into vaccine that had been freezed, dried, and then rehydrated, and surface tension would hold the water with the virus particles between the times.

Like a fork.

We're talking a fork basically.

Like a fork.

Yeah, and then they'd stab you in the arm a bunch of times and it didn't hurt that much because it didn't need to like go too far in, but they would like get it under your skin by doing that over and over and over again.

But they could do it really fast, and then when they were done, they'd put it in another container and at night they would sterilize those containers and you could use the needles over and over and over again.

And they were cheap.

They didn't require a lot of training.

You could literally train someone by giving them an orange and being like practice stabbing this orange, and then they'd be good.

So then when you're sitting down to get stabbed, and you asked your nurse have you done this before?

And she says, oh, I vaccinated lots of oranges, mangoes, soap apples, I'm super experienced.

Yeah, that's right.

Any fruit you can think of I have stabbed.

Thank you to all the oranges who suffered so the humans could survive.

Really, that's taking it for the team.

Yeah, So this is really a step forward, not in terms of like virology or microbiology, but in engineering, right, this is just like, how do we get this vaccine rapidly to a lot of people?

I mean yes and no.

So like that jet injector we were talking about, that was an amazing step forward at the time, but it still broke a lot and you needed to bring replacement equipment with you.

And when you're going to really remote places, if you ran out of replacement equipment, you'd be in a lot of trouble.

Where's these bifurcated needles?

This was a very simple solution.

It was about five dollars for a thousand of them.

They could be reused one hundred times.

You could sterilize them in boiling water.

It becomes much easier.

And so sometimes it's not about like the most complicated engineering solution, it's just finding the thing that is cheap and efficient, and in this case, it was a bifurcated needle.

But I think that is the best engineering solution, right, not like over engineered, but just like, how can we use our manufacturing process and deal with the reality situation to solve this problem efficiently, effectively and cheaply.

I think that's great engineering.

Yeah, yeah, amazing, and they even like would shorten the needle to get the cost down so that they could, you know, use less metal for each one.

Okay, so that is how we made and delivered the vaccine that eventually eradicated smallpox.

And so we're still again using the cow sourced one, right, Yeah, that's surprising me.

I thought this whole story was gonna be like and then we figured out how to actually build a vaccine again smallpox by like crippling it or one of the typical vaccination strategies.

But you're saying we used one disease against another the whole time.

Yeah, it's incredible.

That's amazing.

What that is?

Amazing?

Yeah, all right, so tell us about the campaign to eradicate smallpox.

Amazingly, it kind of starts with the Soviet Union.

So during the Cold War, the Soviet Union kind of like backed away from the international community, and after Stalin died, thank goodness, Stalin died.

Wish he had died sooner, but he didn't.

So anyway, speaking ill of the dead, is that what you're doing?

He just decided, like millions of people, Yes, I am so.

Anyway, in nineteen fifty nine, the Soviet Union is like stepping back into the World Health Assembly and trying to get involved in the international community again.

And they propose, hey, let's eradicate smallpox and we we will volunteer to donate freeze dried doses of vaccines, literally millions of them, and this is their way of kind of like getting good with the international community and the international community.

I think the idea at the time was, you know, we probably can't actually eradicate smallpox.

There have been some efforts to eradicate other diseases that had kind of fallen flat on their face.

People weren't super optimistic this was going to work, but they were sort of humoring the Soviets because they were happy that they were back.

And so while this proposal was accepted, not a lot of momentum happened.

Not a lot of people were dedicated to the project.

There wasn't a lot of money dedicated, but it was clear that the Soviets were on board.

So around the mid nineteen sixties, USAID, which I'll note we tanked, got doged.

Yes, right, so USAID got doged.

Doesn't exist anymore, which I think is devastating.

But anyway, so they teamed up with the Center for Disease Control, or the CDC in the US, and they started trying to eliminate smallpox and measles from twenty countries in West Africa.

So they were starting to get the ball rolling and momentum is starting to build, and the World Health Organization, with the US's input, passes this proposal that Okay, we're going to take eradicating smallpox seriously.

And there was a bit of contention here, so there was enough members of the community thinking that this was actually impossible that when it kind of got pushed by the US DA, Henderson got put in charge almost as punishment.

So the guy in charge of the World Health Organization thought this was going to fail, and because the Americans had pushed it, he wanted an American leading it so that when it failed, the blame would fall on the Americans.

Wow, the politics, the politicist.

So but tell us who is Dea Henderson.

Now he's appeared in our story.

But what's he been doing this whole time?

Yeah, so he's been studying public health.

He was working at the CDC on that project where they were trying to eradicate smallpox and measles.

And it turns out he's it's just really great at organizing stuff.

He's a really great administrator, and he is really good at like cutting through the bullsh and just getting stuff done.

And he sort of gets a really good reputation for being a person who makes things happen.

And it's fascinating that this is basically the obstacle, right, Like, at this point, we have the technology, We even have the engineering to manufacture these things so they're simple and cheap and robust.

He's just a question of like getting all these things to all the arms in the world.

Right, it's really just a paperwork and organization.

Yeah, it's paperwork and organization, but it's also like the cleverness to think through the right system.

So initially the thought was, you know what if we can vaccinate eighty percent of the people in the countries where you're still getting smallpox, right, we'll get what's called herd immunity.

And the idea is that there's enough people who are resistant to the disease that it will run out of people can infect and it'll fizzle out.

But it turned out eighty percent just wasn't high enough.

There were still there were enough people being born, especially in places like India, where population density is really high, that this herd immunity at eighty percent wasn't doing the.

Trick walking me through the thinking here.

So even if you have twenty percent of the population that still is susceptible to smallpox, they're like surrounded by a buffer of people who are immune, and so the disease just like fizzles out because it can't jump into another host.

How do you calculate that eighty percent number?

Doesn't it depend on like density and interactions and all sorts of stuff.

Everything you said is correct.

Oh yeah, they started off thinking eighty percent was going to be enough, and then when they actually started observing things out there, they would hit eighty percent, and the disease still had plenty of people to infect, plenty of new babies being born, and it could still it's so contagious that that twenty percent that were left, ye, were enough to keep that disease going.

Because if I had to calculate this, like eighty percent seems like, I don't know, it's a reasonable figure, But if I had to estimate it, I would have guessed like ninety nine points something.

Yeah, because as it is an infectious disease, right, and it came from one origin, right, so in principle, one person with it still out there could infect new.

People absolutely, and so that ended up being the reality on the ground was that eighty percent was not enough, and there was some discussion about, well, maybe if we kick it up to ninety percent, and so, you know, part of it I think is well, what number do we think mathematically will work, and then another part of it is well, what realistically could we accomplish.

And another problem they were experiencing was like, so you know, the Soviets were donating a lot of vaccine, but a lot of the vaccine they were donating was low quality and wasn't working, and so that was also causing them some problems.

And what they ended up deciding was that, like, look for this disease in particular, hitting some percentage is not going to work.

So what they did was they vaccinate as many people as they could, and then they would do contact tracing, so essentially they would wait to hear if someone got infected, and when they got the message that there was an infected person in some city, some village, some herding community, they would go out there.

They would lock down that person, they would figure out everybody that person had interacted with, and then who those people.

They would kill them and they would kill them.

No, and no, they.

Would send them to a farm where they can run and jump all day long.

No, no, it was much nicer than they would offer them free vaccines.

Oh okay, yes, but they've already been infected, right.

Well maybe yes, maybe no.

And so you know, just because you have encountered somebody doesn't necessarily mean you got infected.

And then also to try to make sure, like if those people did get infected, you want to make sure that they don't pass it to other people.

And so you not only vaccinate the first group of people who you think contacted the initial infected person you know of, you also vaccinate all of the contacts of those people.

And in this way you make the most use of your vaccine, and you like take the oxygen out of the fire that could have started there.

So you're pouring water on all the embers just to make sure they don't spread uncontrolled.

Yes, exactly.

And one of the things that we lucked out with is you know, like with a disease like syphilis, there's also a sort of moral judgment that gets passed on the person who gets infected smallpox didn't have that kind of moral judgment, and so people were more likely to come forward if they had a case, they would be less likely to hide it.

And in some cases and in some countries, to try to really encourage people to come forward or to encourage people to rat out other people, we would offer monetary rewards.

Listen to you using the word rat in a negative way.

Oh maybe, I mean language, This is where it comes from, Kelly.

You're propagating anti rat bigotry.

Thank you so much for pointing that out.

I will work on doing a better job.

You need to be in a rat ally.

I mean really, I think of myself as a rat ally as long as they're not in my chicken coop.

I didn't like them there anyway.

But this is a good point where we need to know where the outbreaks are and we can only know that if people report.

So it's important that people are not embarrassed.

Yeah, yeah, that's right.

It's important that people aren't embarrassed.

And the other thing that I think what's important to learn here is they learned over the course of the work that they were doing, and they adjusted the way that they were working.

You know, so when you're doing science, so often you start off with one plan and then when the rubber hits the road, you need to be like, this isn't working.

What can we do that's better?

And so they adjusted and man, this is an amazing story of people adjusting to so many different conditions.

For example.

For example, so when the World Health Organization decided that they were going to really try to eradicate this disease, it was still pretty common in about thirty one different countries and there were a lot of complicated things happening in those countries.

So, for example, they had wiped out smallpox in Bangladesh and then partition happened and the war broke out between Pakistan and Bangladesh.

And when that happened, Bangladeshis crossed the border into India en mass where they picked up smallpox again refugee camps, yes, And then India went in and kicked out the Pakistanis and the Bangladeshis went back home and they brought smallpox with them.

Oh boy.

So the World Health Organization was in there and they were trying to keep people from getting smallpox and trying to contain it as it moved back into a country, but there were a number of different cases where civil wars or wars of one sort or another would break out, and there were people who were trying to eradicate smallpox who would sort of die through this process.

But they were, you know, doing the best they could to figure out, like how do you vaccinate people when you have all of these refugees moving from one place to another, and how do you track things?

But amazingly they did it.

And then there were a couple cases where, you know, we talked about how there's not really a stigma around smallpox, there was a stigma around being a nation that still had smallpox in an era where it was being eradicated.

So there was a setback.

In nineteen seventy one, Iran got a case of smallpox, but they didn't want anybody to know because they wanted to commemorate the two thy, five hundredth anniversary of the Persian Empire.

So the Iranian government wanted to have this big celebration.

But you don't want people from all over the world descending on your country if you have smallpox.

Yeah, and so they were trying to eradicate it with a mass vaccine campaign sort of kept on the down low, but their stocks were of poor quality and it wasn't working.

So the World Health Organization eventually got involved.

They brought their better freeze dried vaccine and they managed to wipe it out.

But there were all of these cases of like things came up, and you know, I can just imagine that if I was at the World Health Organization at smallpox broke out, and it was because some countries rulers were like trying to make sure I didn't find out about it.

Man, at some point you got to be like, how are we ever going to do this?

Like this is never going to happen.

I quit, amazing, But Dea Henderson never quit.

He just kept going and it's amazing.

And what was he like as a bureaucrat?

Was he like a rule follower?

Was he like a tyrant?

He was not a rule follower.

If you read the book that he wrote about eradicating smallpox, it is mostly a story about how he was told to do one thing and he did another.

And that's how you get stuff done, folks.

Well that's how he got this done.

And you know, each different nations would have different bureaucracies that you had to understand or route around.

So, for example, there were instances where he had to send mail through an intermediary and he wouldn't get a response back on a timescale that was useful for trying to attack an outbreak.

And so even though he was supposed to send the mail through an intermediary, he started sending the mail to the intermediary at the same time as he sent it directly to the other person.

And he knew he wasn't supposed to do that, but there were all sorts of cases where he was like, look, if I don't break this rule, we are not eradicating small box.

So I'm doing it.

And so yeah, he was he was a bit of a character.

Well, sometimes you got to break a few constitutional eggs to make me Onlet right, and so let's take a break, and when we come back, we'll hear about the last gasps of smallpox, eradicating it finally and string humans from that suffering.

All right, we're back, and we're hearing about the story of smallpox, humanity's victory over the microbe.

So we're near the end of this.

Tell us what were the last battles in eradicating smallpox?

So towards the end India still had about sixty percent of the remaining cases.

There's a lot of people in India.

That density and the fact that this country is huge made it really hard to eradicate.

And as we mentioned, there was that conflict happening with Pakistan and Bangladesh.

There were people crossing borders.

It was getting really hard to get this stuff under control.

Additionally, there was an issue because there was a small community who had a religious leader that was refusing the vaccine and was refusing the vaccine for the rest of the community as well.

So we talked earlier about like, you know, what, what do you do in this case?

Like so, at this point, almost all the countries in the world had smallpox eliminated.

They were closing in on being able to eradicate this disease which has killed millions of people millions of people in our history for thousands of years yea for thousands of years.

And so the question is do you respect this religious leader's desire to not get the vaccine when it has been documented that smallpox cases are popping up in this community and are then spreading to surrounding regions.

And so this is not something that will burn out on its own this has been causing problems that are spreading.

And what they end up deciding they need to do is they essentially pin the religious leader down and vaccinate him wow, against his will.

And once he's vaccinated, he says something to the effect of, all right, well I guess that was God's will.

Everybody else should ge vaccinated to that's a good handle, yeah, I guess, and so but yeah, so there were some very difficult ethical questions.

I think in general, what they would try to do is they would in every country where they started a program for eradication, they would try to find local medical people and get them on board and have talked to them about how the vaccine worked and help them talk to the community so that people could have their questions answered.

And this could be done in the most like ethical, not like pushy way possible.

But at the end there, I don't think there were a lot of cases where people were pinned down and vaccinated, but at the end there they were like, look, we are closing all the loops.

Yeah.

Well, it's a fascinating question and a real puzzle for policymakers, right how to deal with these things and their arguments for it on both sides.

Right, it's clearly a balance between like public good and individual freedom.

Yeah right, It's not clear where to draw that line, and it's different in every case.

And I'm a philosopher or an ethicist.

You know, imagine somebody is like walking around shooting guns out them directions in public areas.

You'd be like, yeah, that's not allowed.

That's clearly over the line.

You could make the argument that, you know, walking around spreading a disease is similar to that, And so I'm not making that argument.

I don't want to be authoritarian about lockdowns whatever.

I know this is a really touchy subject.

Yeah, I just want to highlight that there's never an easy answer here for public health officials.

You know, so many times during COVID I would hear people complaining about how things were being managed, and my response every time was, I am so glad I'm not in charge right now.

Like me too, I would hate to make these decisions because you know, lives are on the line.

Every decision that you make has a downside no matter what you do, and even if you do nothing, then you're sort of still on the hook for a bunch of deaths.

And the scientific understanding is evolving, right, Like, we don't understand how is this spread, what works, what doesn't work.

And as we were saying earlier, you need clear policies, right, you can't always convey like, hey, everybody, go read these papers.

Let's discuss.

You know, somebody's going to make a decision like do we close schools or not.

Yeah, those are hard decisions to make, and science informs them.

But in the end it's a political decision.

Right, how do you balance this versus that this risk versus that risk.

Science doesn't make the decisions, it just informs them.

And sometimes science is wrong, right, It's never fully settled and it's always in flux.

So yeah, wow, it's hard to be a public health official.

Oh my gosh.

Yeah, so hard and so important that we are spending this time when there isn't a major pandemic killing a bunch of people, that we try to spend that time helping the public to understand science and trying to build trust.

Yeah, that we then get to benefit from, you know, when something like that happens.

But anyway, so tell us.

About the victory.

Right, So people worked in India.

They pinned down this religious leader to stamp out those last embers was that the end of smallpox.

I believe the last case in nineteen seventy five was a homeless person on a railway platform that they found and they treated and quarantined and it didn't get passed.

And then Ethiopia was the last country to have smallpox.

That a little complicated because there were a lot of nomadic herders, so it was hard to get in touch with, you know, each herd to make sure there hadn't been any cases of smallpox.

So we had a period where no smallpox cases were reported.

We thought we had eradicated it.

We waited for an additional two years where people were hired to like go around the world looking for cases and like go into communities trying to find it.

And after two years of looking hard for smallpox and not finding it, we declared in nineteen eighty that smallpox had been eradicated.

Amazing, yay.

But this wouldn't be an episode run by Kelly if there wasn't something scary at the end.

So one of the difficult things about smallpox is that it looks like chicken pox and monkey pox, and so when you're trying to figure out if you've eradicated it or not.

If a pox case pops up, you want to send a sample of that virus to a lab to confirm, Hey, this is definitely chicken pox, for example, smallpox popping back up again.

And so during this eradication procedure, it was regularly the case that samples of the pox were sent to labs in the Soviet Union and the United States, and they split the case load because it was a lot of work verifying you know, what virus was which.

But at the end of this process, a lab in the United States and a lab in the Soviet Union had lots of different virus samples in their freezers.

Oh I see.

So at the end of this process, the virus had been eradicated in the wild and had been eradicated in human bodies, but it was still existing in labs.

And Kelly at three in the morning as a new mom, where you worried about this escaping from labs and affecting your children.

Not initially, but as I said, in twenty fourteen, they found some smallpox vials that were in a lab in the US that were just in some stinking closet where somebody had forgotten them there.

And at this point we probably don't have immunity anymore, none of us, and so if it got out, it could spread quickly, and it does get out of labs sometimes it does.

Are there documented cases of that?

Yeah, So in nineteen seventy eight there was a woman who was working in a lab above a UK lab that studied smallpox, and smallpox must have gotten into the ventilation system and ended up in her lab and she got smallpox and died, And so we know that sometimes it does get out.

And I think after that the UK was like, you know what, we'll just destroy all of our stores.

But the scientific community has decided to not get rid of all of our samples.

And there's a complicated reason why.

So in nineteen seventy two, a bunch of countries agreed, look, we're not going to try to make biological weapons anymore.

And so nations were supposed to stop doing that kind of research, but the Soviet Union kept doing it, and in particular, they kept doing research on how you could weaponize smallpox.

And there's some reason to believe that they thought the US was doing it too, and so they had to do it to keep up.

But the US wasn't doing it or at least if the US was doing it, that has not become public.

And so the Soviet Union continued to do it.

And so around the time when there was discussions about like, okay, all the labs that still have smallpox, we should destroy it, this news came out that the Soviet Union had been using it for biological weapons.

And now the US didn't want to eradicate THEIRS, because what if a biological weapon made from smallpox does get released?

If you have smallpox in your lab, then you've got a starting point for doing research to figure out how you can, you know, maybe make more vaccines or how you can address this.

And so it ended up being determined that the US didn't want to eradicate theirs, and then the Soviet Union didn't want to eradicate THEIRS.

And then when the Soviet Union fell apart, scientists who had access to the vaccines ended up all over the place, and there was some concern that, you know, a lot of the scientists during the fall of the Soviet Union didn't have enough money to feed their families.

So are they selling it to you know, nations that might like to have smallpox to make their own biological weapons.

And so it is still the case that we have these samples in our freezers and hopefully they never get out a lot of I mean, they're under many layers of security, but they're kept for a variety of reasons.

The bio warfare stuff we talked about.

Also, you know, maybe if monkey pocks jumps to humans in a way where it's even more transmissible than it has been in the past, maybe understanding smallpox could help us with that.

And so there's a bunch of different science related reasons that we've come up with.

But the point is smallpox still exists on this planet, and that keeps Kelly up at night.

So why don't we just keep vaccinating people?

Like, yeah, we eradicated it, but it sure would be nice to be immune.

What's the cost of vaccination?

Yeah, so difficult is with vaccination is another reason why some people argue that we need to keep smallpox around.

So the current vaccine that we have using that cowpox is dangerous for people who are immunocompromised.

So, for example, people with HIV AIDS could die if they got this vaccine.

And so there are folks who argue, like, look, we need to keep smallpox around because we might be able to as you mentioned earlier in the show, maybe we could genetically modify smallpox so that we could create a vaccine that makes people immune to smallpox without killing people who are immunocompromised.

And so, because we don't have a perfect vaccine, maybe you want to keep smallpox around in case you need to do more vaccine research in the future.

To more clearly address your question, you asked, why don't we just vaccinate everybody?

So one you'd have to always vaccinate everybody for a disease that isn't in circulation right now.

That would be incredibly expensive.

And this vaccine is not without risks, And so if you vaccinated everybody, there would be a subset of the population who would die from this vaccine every year, which seems unnecessary at a time when this disease is not spreading in the United States or in the world.

Yeah, yeah, so there really are risks there, and you don't just want to vaccinate people, yeah.

Just for the heck of it.

Although, man, in twenty fourteen, if you had told me I could vaccinate my daughter for smallpox, I might have.

I might have gone for it because I was a little crazy in the middle of the night.

I was talking to a friend who's in the military, and I think he said that he did get vaccinated for smallpox.

And so I think there are some people working in some government job where if you are not immunal compromised, you might still get the vaccine on the off chance that you would be the kind of person who would encounter a bio weapon on the front line.

But this conversation I had was like over a decade ago, So maybe we don't do that anymore.

All right, Well, it's amazing what humanity can do when they come together and get organized and decide that we all have the same goal and we're going to make the sacrifices and used the resources necessary to achieve that goal.

It's incredible.

It is incredible.

And so you know, when I was rereading da Henderson's book, and I also reread School by Jonathan Tucker, And while I was rereading these stories.

I love your pronunciation of that word scurge.

How do you say it?

Scourge?

Scourge?

Oh?

No, is it like three up prions where I'm saying it wrong?

No one of us is all right.

Well, okay, sounds good.

But so, while I was reading those stories, you know, I was, I was getting pretty depressed.

So I was uplifted by the fact that our species came together and cooperated across nations to eradicate this disease that had killed millions of us for thousands of years.

But on the other hand, us AID is not around anymore, and the World Health Organization the United States has pulled out of that.

And I don't want to pretend that the World Health Organization is without problems, because da Henderson complains about the bureaucracy and that organization over and over and over again.

But he was still able to coordinate this effort that brought all the nations of the world together and brought all of our resources together, and the strength of this organization and with this particular person in charge, was able to eradicate this disease.

And you know, I'm worried that we, you know, instead of fixing institutions that have problems in the United States, we're just pulling out of them.

And I worry that the next time we need to coordinate, we are going to be in a less good position to do that.

And so anyway, I was, on the one hand, very proud of our species for eradicating smallpox and a bit scared for our ability to do something like that again in the future.

Well, as scientists, the best we can do is to help people understand how this works, what's going on, what do we know, what do we not know, what are the risks, what are the benefits?

And we hope that that helps people be informed when they make their decisions, policy makers and individuals.

Yep, yep.

But to end on a high note, you know, I do think it's worth sitting and thinking how lucky we are that most of us don't have to worry about tuberculosis or smallpox.

We can be vaccinated for measles and for polio.

There's so many things that would have occupied so much time and worry for parents or you know, anyone, for people living in the past that you know, we we can forget about today.

So many people have never thought about smallpox more than five seconds.

And what a blessing isn't the word I'm looking for.

What's the word I'm looking for?

What a luxury that is?

What a what a mitzvah that is?

What a mitzvah that is?

And so anyway, we are very lucky to live in the time we live in.

Yeah.

And also it's a testament to what humans can accomplish.

Right.

We have changed the nature of life on Earth.

We've removed a big source of suffering and misery.

Yeah, and that tells me that we can do more, We can improve lives.

Science really does help us improve the quality of our life.

Yay science, Yay science.

Let's end on that.

So thank you Toda Anderson for coordinating that massive international project to improve all of our lives, and thank you all for joining us on this historical tour of a human victory.

Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio.

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