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The Very First Vaccine

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The Very First Vaccine

The Very First Vaccine

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You hear this a lot. The economy cannot go back to normal until there's a coronavirus vaccine. It's the highest-stake thing science is trying to solve right now. More than 90 different vaccines are being developed by companies and universities. But before we put all of our hopes on a worldwide coronavirus vaccine, let's look at the history.

Vaccines are difficult to pull off. If you think about it, we've only made vaccines for so many things. There's, like, 22 diseases that we have vaccines for in the U.S. We have it for the measles, mumps and rubella, polio, hepatitis A, hepatitis B, but we don't have a vaccine for hepatitis C or for HIV or malaria or West Nile or Zika or a bunch of others. Some viruses, there is no vaccine for them yet. Sometimes there's just a treatment, a drug, something to treat a virus once we have it but not prevent us from getting it the way a vaccine does.

A vaccine, super simply, is just exposing yourself to a little bit of the bad thing so that your body can create an immune response that protects you in the future. But when did we first get the idea to do that? Like, how did it occur to us to inject ourselves with something that can kill us in order to save us?

Hello, and welcome to PLANET MONEY. I'm Sarah Gonzalez. Today on the show, we trace the history of the very first vaccine. It was for smallpox. We follow it from ancient Greece to Imperial China and eventually England. This 2,000-year story shows you the kind of patience and risk-taking and coincidences you need to create a medical breakthrough. Also, it's just a really great story involving a royal experiment, a nose pipe, milkmaids and a beautiful European lady out for revenge.


GONZALEZ: All right. As long as humans have been around, humans have been getting sick and dying. But this other thing has also been true. Some humans have been getting sick and not dying, and people notice, like, since almost the beginning of time. Josefa Steinhauer is a molecular biologist at Yeshiva University in New York City, and she says people have always recognized that some people survived sicknesses.

JOSEFA STEINHAUER: In 430 B.C.E., Thucydides wrote about a plague in Athens in ancient Greece that killed many people.

GONZALEZ: I've never heard of her - him.


GONZALEZ: Him. What did he do?

STEINHAUER: He's an ancient Athenian. He's prominent in ancient Greek society.

GONZALEZ: OK, so he was just some guy.

STEINHAUER: (Laughter) I guess he's a historian.

GONZALEZ: Thucydides is more like the Greek pronunciation. You may have learned it as Thucydides, famous historian who thought to write about this plague in ancient Greece.

STEINHAUER: And he noted that the few individuals who recovered from the disease could tend to the sick without becoming reinfected.

GONZALEZ: People who survived the disease could care for other people who had the disease and not get sick again - immunity. People knew this was a thing since at least 430 B.C. just by seeing it happen in the world.

STEINHAUER: So the idea that you could be exposed to a bad thing, survive and then be immune to this bad thing was known throughout the history of civilization.

GONZALEZ: Josefa Steinhauer has spent most of her career studying biology. But recently, she started looking into the history side of the field.

STEINHAUER: So a few years ago, I was recruited to teach a science for nonscientists course.

GONZALEZ: Oh, that's what I need.

STEINHAUER: (Laughter).

GONZALEZ: Great laugh. So Josefa taught this science for nonscientists lesson on vaccines, on the first vaccine. And then she performed it at a bar recently for this thing called Nerd Night, a bunch of nerds at a bar learning things, including me. It was one of the last things I did before the coronavirus hit. And I brought Josefa into the studio after for an interview.

OK, so back to ancient times. Humanity had figured out this immunity thing. They didn't know how or why it would happen, but they knew it would happen. Some people just wouldn't get sick again. And there was this one virus that's probably what Thucydides, Thucydides was talking about - smallpox. Josefa says it afflicted pretty much all ancient civilizations.

STEINHAUER: Yeah. We're talking, like, Egyptians and ancient Indian civilizations, ancient Chinese civilizations.

GONZALEZ: And smallpox stuck around for thousands of years. European explorers brought it to the Americas.

STEINHAUER: It's thought to have contributed to the decline of the Aztec and Incan empires in Central and South America.

GONZALEZ: Feared all over the world, killed many millions - 30% of those who got it.

STEINHAUER: It looks like chicken pox.

GONZALEZ: Oh, like little tiny bumps.


GONZALEZ: But like, all over your face and arms - bad, just covered. People weren't even recognizable. And if you survived, it left its scars on you forever. Here's a quote about it.

STEINHAUER: "Turning the babe into a changeling at which the mother shuddered and making the eyes and cheeks of the betrothed maiden objects of horror to the lover."

(Singing) Dun, dun, dun.

GONZALEZ: (Singing) Dun, dun, dun.

And people had been thinking about this immunity thing - this thing that could protect your beautiful face and your life, wondering about it. And finally, somewhere in the Middle Ages, there was a breakthrough in China. The Chinese were like, OK, we've known for so long now that some people who get smallpox and survive it don't get it again. They're immune. And they were like, what if we could manufacture immunity - artificially cause it? And how they chose to do it - I'm just going to give you a little warning - it's a little gross.

STEINHAUER: So they're going to collect scabs from a person with a mild case.

GONZALEZ: Like, open up the scabs on someone ripe with smallpox.

STEINHAUER: So you could theoretically collect them once they're already dry, but that wouldn't give you the pus that you need. You need live virus that's present in the pus. Pus is the active component here.

GONZALEZ: Active ingredient...

STEINHAUER: (Laughter) Yeah.

GONZALEZ: ...Pus. OK. Right. OK.

STEINHAUER: So you're collecting these pustules from the individual with smallpox, and you're allowing them to dry. Then you're going to ground them up into a powder.

GONZALEZ: Like, in a bowl of some sort.

STEINHAUER: Mortar and pestle maybe.

GONZALEZ: Mortar - OK.

STEINHAUER: Then you're going to ground them up, wrap them in cotton, pack the material into a pipe.

GONZALEZ: Like, pack the pus scab cotton wad into a long pipe.

STEINHAUER: And Sarah...

GONZALEZ: Shot it up their nose?

STEINHAUER: (Laughter) Puffed it up the patient's nose.

GONZALEZ: Just shoot some smallpox plagues up your nose, little bump of smallpox (sniffing). Let it get all up in there. Is that, like - it's weird to think, we don't want you to have smallpox, and so in order to prevent you from having smallpox, we're going to give you a little bit of smallpox. But that's what it is.

STEINHAUER: So this is actually one of the rationales that was used by anti-vaxxers, was that it was seen as very unnatural to be deliberately infecting people with a deadly disease.

GONZALEZ: I know. I'm coming across as an anti-vaxxer. That's not what I'm trying...

STEINHAUER: It's a very logical thing to think that this is dangerous.

GONZALEZ: And yet we did it. And somewhere along the way, they learned that this works.

STEINHAUER: Yeah. I mean, it doesn't work perfectly. But the death rate amongst those who have been treated is much lower.

GONZALEZ: What was happening was that, yes, patients were getting a whiff of smallpox. But this smallpox powder sprinkling thing led to a weaker form of the disease and, therefore, a lower fatality rate than people who naturally became infected with smallpox - like, who got it out in the real world.

Is this our first vaccine?

STEINHAUER: Yeah, I guess so.

GONZALEZ: OK. So first vaccine, Middle Ages in China.


GONZALEZ: Thank you, China.

STEINHAUER: (Laughter).

GONZALEZ: But we didn't have that word yet - vaccine. It was called insufflation and inoculation and variolation. And the process wasn't widely used. Knowledge about variolation and manufacturing immunity had to spread from person to person, just like the virus itself. And the knowledge spread along the Silk Road, these trade routes through China and India and Turkey.

STEINHAUER: So you have traders and merchants traveling the Silk Road, and they're also exchanging knowledge between these communities.

GONZALEZ: We're, like, in the 1670s, early 1700s now. And merchants in Turkey are like, have you heard what they're doing in the East?

STEINHAUER: Like, oh, smallpox is a problem in your community. Well, I hear that in China...

GONZALEZ: And along the way, the technique had been getting refined, improved because the nose pipe puff method had at least one big drawback - doctors had to blow smallpox up someone's nose using a pipe. Like, the doctor's mouth is on this end of the pipe, smallpox cotton on that end of the pipe - not super hygienic, not super great. And by the time inoculation got to Turkey, there was a less delicate approach. Now the method was to dip a needle in some smallpox pus and then scrape the wet needle across someone's arm - but not like gently sweeping across, much less pleasant.

STEINHAUER: I mean, if I were doing it, I would make small scratches on the surface. But it sounds like some doctors were making very large cuts in their patients (laughter).

GONZALEZ: Like, long or deep?



STEINHAUER: Actually, I think I have a picture.

GONZALEZ: Yeah, show me a picture. Oh.

STEINHAUER: There are five enormous gashes in the arm of this patient.

GONZALEZ: Like, these huge, T-shaped, swollen, bulby, deep-red gashes all over your arm. But it could protect you from smallpox. So it was so worth it to people. And this procedure, passed on by traders, was spreading around the world. But it wasn't reaching everyone. It wasn't going to eradicate smallpox. That would take one very open-minded woman who saw the potential, Lady Mary Wortley Montagu. Lady Mary's husband is the British ambassador to Turkey. And she visits the country somewhere around 1717. And she sees this laceration arm cut technique being done in Turkey - Silk Road. And Lady Mary Montagu is like, wow.

STEINHAUER: This is very personal for her because she herself is infected with smallpox. She survives. But she was very famous for being beautiful before smallpox, and smallpox ravages her beauty, destroys her face. She's covered in pockmarks for the rest of her life.

GONZALEZ: She lost her eyelashes. It was awful for her. Beauty was a pretty big deal at the time.

STEINHAUER: Yeah, I guess if you were a woman, it was your main economic collateral, right (laughter)?


STEINHAUER: You got to get a rich husband.

GONZALEZ: So Lady Mary Montagu becomes a huge proponent of this gashes on your arm method. She goes back to Britain like, we got to get on this. But Britain is, you know, hesitant.

STEINHAUER: Because, like you said before, it's scary to expose uninfected people with this very dangerous, deadly illness.

GONZALEZ: But eventually the king, George I - he hears about this. And he agrees to do something pretty unheard of at the time - sponsor a clinical trial to see if it's safe.

STEINHAUER: They did a trial run. Who should they use as their trial guinea pigs?


STEINHAUER: (Laughter).

GONZALEZ: For people?

STEINHAUER: That's a good one. What about people on death row who were probably poor?

GONZALEZ: Yeah. They sprinkle smallpox into the cuts of six death row inmates at Newgate Prison in 1721. And the terms of this clinical trial are a little weird. If you die, you were gonna die anyway.

STEINHAUER: Yeah, exactly. If you die, well, that's one less hanging we have to perform.

GONZALEZ: But if they survived, the king would pardon them, set them free. This was called the Royal Experiment.

Like, official...

STEINHAUER: The Royal Experiment.

GONZALEZ: I imagine there's been many royal experiments? No?

STEINHAUER: I don't think so.

GONZALEZ: OK. This is, like, the Royal Experiment.



STEINHAUER: This is the one.


GONZALEZ: All six prisoners agreed to the smallpox exposure. All six survived. All six were released. And just to emphasize, it's believed that all six became immune. And then they try it again, this time on 11 children, including five orphans. So it was babies. But they all survived. And the Royal Experiment is declared a success. So all the royals signed up. Like, give me some of that smallpox cut thing. By 1746, there's an official smallpox inoculation hospital. It's being done in the new world, too, in the colonies. And as the practice becomes more widespread and popular, it also becomes more of an elaborate procedure. It becomes, like, a luxury good, a way for the rich to not catch the diseases of the masses. And like any luxury good, doctors start to add on bells and whistles.

STEINHAUER: There was this whole litany of terrible things that they would do to their patients to, quote-unquote, "prepare" them for variolation. They would starve them. They weren't allowed to eat for a few weeks. They would give them ipecac or other chemicals that would make them nauseous and vomit. This is, like, torturing these patients before they variolate them.

GONZALEZ: This whole weeks-long torture process - it wasn't necessary, but it was lucrative for doctors. Rich people would pay a lot for the promise of immunity. And patients were becoming immune to smallpox. There was just this little caveat, though.

STEINHAUER: You're exposing people to smallpox, which is very deadly. So a handful of people, a small proportion of people who are exposed to smallpox by this variolation method die from the disease. Or even worse, they are carriers of smallpox, and they're transmitting the disease. So they're starting a new epidemic.

GONZALEZ: What was needed to truly create a safer vaccine was an entirely new way of looking at the problem, say, through the eyes of a cow or a milkmaid - after the break.


GONZALEZ: All right. So there's this kind of scary and expensive way to protect yourself from smallpox. And it might have stayed that way if it weren't for this one strange coincidence. It's the late 1700s, rural England. And dairy farmers and milkmaids have been noticing that cows would sometimes get these pustules on their udders that kind of looked like smallpox.

So these cows have, like, pus balls on their udders?

STEINHAUER: (Laughter) Let's call them pocks.



GONZALEZ: Pus balls sounds horrible.


GONZALEZ: But they're, like, pus bumps, like smallpox.

STEINHAUER: Like pimples, yeah.

GONZALEZ: Like pimples. It was cowpox.

STEINHAUER: But this so-called cowpox was much milder. The cows didn't die from it.

GONZALEZ: Cows didn't die from cowpox. And milkmaids who, you know, touched these cow pocks - they sometimes got cowpox on their hands from milking the cows. And it was kind of this old wives' tale type thing. But people noticed that milkmaids who got cow pox wouldn't get smallpox when an outbreak came around. So people were like get me near a cowpox cow, like this one farmer, Benjamin Jesty. He was known for shoving a little cow pus into humans.

STEINHAUER: It's really smart, right? I mean, people knew - people already knew that if you worked with cows and acquired cowpox, you would be immune to smallpox. So why not try to do it ourselves?

GONZALEZ: I wouldn't have survived in the early days.

STEINHAUER: (Laughter).

GONZALEZ: I already know I'm not experimental enough.

Human bodies don't love having little bits of cow anything in them. So there were these negative reactions. People almost lost limbs over this.

STEINHAUER: And here's where we meet the protagonist of our story, Edward Jenner.

GONZALEZ: Coming in a little late to the story for a protagonist, but we're going to go with it. Edward Jenner was a physician in England. He went to all the good schools. But he was from a rural town. And Jenner was like, you guys are having these negative reactions because cowpox pus is going straight from a cow into a human. He has the idea to take cowpox pus from a milkmaid who got cowpox from milking cows. He's like, we're going to do a human-to-human transfer.

STEINHAUER: It's cowpox, but he takes it from a human host.

GONZALEZ: From a human host.


GONZALEZ: OK. So the milkmaid has...


GONZALEZ: ...Some cow pus on her, in her.

STEINHAUER: Her name is Sarah Nelmes.

GONZALEZ: Oh, we know her name?


GONZALEZ: Sarah Nelmes.

STEINHAUER: Yeah, Sarah Nelmes. So in 1796, he takes some cowpox pus from Sarah Nelmes, from her hand.

GONZALEZ: A milkmaid.

STEINHAUER: A milkmaid. And he scrapes it on to an 8-year-old year old boy in the neighborhood named James Phipps. I think he was the gardener's son (laughter).

GONZALEZ: So a very, very clinical experiment.

STEINHAUER: Also not particularly ethical.

GONZALEZ: Just like, give me your arm, James the gardener's son. Here's some milkmaid pus. And then about two months later, he exposed the kid to fresh smallpox. And the kid didn't get smallpox. It worked. This was huge. And it was super safe 'cause you can't really die from cowpox. It's a mild disease. And the cowpox made the boy immune to smallpox, which you can die of. So Jenner publishes a paper.

STEINHAUER: And he coins the name variola vaccina, for the Latin word for cow, which is vacca. And his inoculation process he calls vaccination.

GONZALEZ: So that's where we get vaccines?

STEINHAUER: Yes, from cows.

STEINHAUER: They all mean cows?

STEINHAUER: (Laughter).

GONZALEZ: Vacca - cow. Vaccina - vaccine - so good. And now we call all vaccines vaccines, even if they have nothing to do with cows, because of Edward Jenner. His vaccine is the one that took off. And it spread around the whole world, though the formula did evolve as the science got better. Now, even back then, there were some early anti-vaxxers. People thought that injecting a cow virus from a milkmaid would, like, contaminate you and make cow parts grow out of your body or something like that. It didn't. And the last person on earth to get smallpox naturally was in Somalia in 1977. They were quarantined. And in 1980, the World Health Assembly declared smallpox eradicated. Almost 200 years after Jenner's vaccine, smallpox was gone.


GONZALEZ: Today's show was produced by James Sneed and Liza Yeager. Alex Goldmark is our supervising producer. And Bryant Urstadt is the editor of the show. Robert Smith edited this episode. Fact checking this episode has been bananas. So thank you to Greta Pittenger and Julia Wohl (ph) for all of the history fact-checks. And thank you to Maddie Sofia for some of the science medical fact checks. If you like this episode, rate us. Tell a friend about us. It really helps us out. We're also on Instagram, Facebook, Twitter and now TikTok. Yes, we are on TikTok. We have some pretty on-brand videos for you there. I'm Sarah Gonzalez. This is NPR. Thanks for listening.

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