How To End A Pandemic
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I will not stop until he is destroyed. Every soul is in peril. Shall we begin? The Lord of the Rings. The Rings of Power. New season, August 29th. Only on Prime Video. In 1980, the World Health Organisation announced a landmark in the history of public health. Smallpox had been eradicated.

Two years had passed since the last case of smallpox, a disease that killed three in ten of those it infected and scarred or blinded many more. After waiting for a while to be sure smallpox was truly gone, the WHO made it official. Decades later, a physician in Oklahoma City saw a patient complaining of fever and mouth ulcers.

It's not surprising she didn't think of smallpox as a possible explanation. But then came another patient, and another, in surgeries and emergency rooms across Oklahoma City. What was going on? Specialists were called in from the Centers for Disease Control and Prevention. They confirmed the shocking news: smallpox was back. And not just in Oklahoma. Reports started coming in from Philadelphia and Atlanta.

Investigators figured out that in each of the three cities, all the smallpox patients had been at the same mall at the same time several days earlier. What had happened was all too clear. It was a deliberate, synchronised, terrorist attack. The variola virus which causes smallpox is highly contagious even before it develops into the distinctive disfiguring rash.

pustules filled with thick, opaque fluid that cover the body. Just six days after the Oklahoma news, there are 2,000 cases. Authorities are trying desperately to trace all their contacts. A vaccine will work if you administer it soon after exposure, but things aren't looking good. The virus has spread to 15 states and Canada, Mexico and the United Kingdom.

If you're wondering when this was and why you don't remember, it happened in 2001. And you don't remember? Because what I've just described was a simulation, Operation Dark Winter, a training exercise to see how decision-makers would respond. All the events I've described took place only in the training scenario. The smallpox bioterrorism attack didn't happen.

But it was no game. Operation Dark Winter took a lot of effort to research and prepare. Some very senior people gave it their time. It wasn't for fun. The organisers wanted to learn about a threat they took very seriously. So perhaps I should say, the smallpox bioterrorism attack hasn't happened yet. I'm Tim Harford, and you're listening to Cautionary Tales. CAUTIONARY TALES

In 1666, smallpox came to Boston, Massachusetts. It wasn't too bad this time, just a few dozen died. The next epidemic, in 1677, was worse. A teenage Bostonian called Cotton Mather described the scene at burial sites. Corpses following each other, close at their heels.

Smallpox came again in 1689. Mather was then a well-known Puritan minister, about to unwisely fan the flames of hysteria in the notorious Salem witch trials. He would lose many people's respect in the process. In a smallpox outbreak in 1702,

The Boston authorities limited the tolling of bells to make it less appallingly obvious how many people were dying. And with smallpox returning every 10 or 15 years, another outbreak was evidently just a matter of time. By 1715, Cotton Mather, now in his 50s, was wondering when the next one would come. He'd been working hard to redeem his reputation as a man of science.

He'd been admitted to the Royal Society in London. No mean feat. His letters to the society covered subjects from hummingbirds to rainbows. He'd just sent them his observations on measles, which one historian has called a classic of early American medicine. On slavery, Mather wasn't quite so far ahead of his time. He was a slave owner himself, and even received a slave as a gift from his congregation.

He renamed this enslaved man, "Wanissimus", a biblical name. Thinking one day about the overdue smallpox epidemic, he asked Wanissimus if he'd ever had the disease. "Yes and no," Wanissimus replied. As a child in Africa, he'd had a kind of operation. He explained to Mother what it involved: "You take fluid from a smallpox blister, you cut the arm of a healthy person, and you put in a drop of the fluid.

After a few days, they'd get ill, but usually not too badly. And then, they never got smallpox again. Onesimus showed Mather the scar on his arm. Mather would later interview other Africans around Boston, contemptuously grumbling about the way they told their story. But for all his racism, there was one fact Mather was willing to hear. Inoculation was widely practised in West Africa.

The next year passed with still no epidemic. Mather eagerly took delivery of the Royal Society's latest volume of Philosophical Transactions, looking forward to seeing his thoughts in print. But it was another article that caught his eye. It was written by a Greek physician in Turkey. An account or history of the procuring of the smallpox by incision or inoculation, as it has for some time been practised at Constantinople.

Mather realised that this was just what Onesimus had described. Not only did they know about inoculation in West Africa, they knew about it in Turkey too. But it just hadn't got to Western Europe or America yet. Mather was electrified. When the next smallpox epidemic hit, he could save the city. That happened five years later. Stephen Cost tells the story in his book, The Fever of 1721.

Infected sailors came on a ship from Barbados. Attempts to quarantine the early cases failed. The disease started to spread. This was Mather's moment. He wrote to every doctor in Boston, explaining what he'd learned about inoculation and urging them to experiment. But they all had the same reaction. Copy the Africans and deliberately give people smallpox. Mather had lost his mind.

Actually, not quite all. There was one doctor willing to listen. Zabdiel Boylston. 42 years old, a surgeon whose face bore the scars of his own battle with smallpox as a younger man. And perhaps Mather's idea didn't sound quite so strange to Boylston, because Boylston's scars were the result of deliberately exposing himself to the disease. To work as a doctor, he'd have to become immune sooner or later. Might as well get it over with.

He'd crossed his fingers for a quick recovery. He nearly died. Boylston's father was also a physician and travelled widely and learned from the indigenous people he met. Boylston's father took their remedies seriously and so did Boylston. So while other doctors scorned the notion that African slaves or Greek old women could possibly have anything useful to say, Boylston did not. Inoculation seemed worth trying.

he decided to inoculate his slaves, a father and two-year-old son, Jack and little Jackie. Experimenting on enslaved people makes us gasp with horror today, but of course that's not what scandalised the Bostonians of three centuries ago. No, what horrified them was that Boylston also inoculated Thomas, his six-year-old son.

After all, Boylston reasoned, he'd soon be seeing lots of smallpox patients. It seemed unlikely that young Thomas could escape being exposed. If inoculation might give him a milder case, why not give it a go? Boylston took fluid from a patient's blisters and hurried home. He sliced into his son's arm and inserted a drop of the fluid. And he waited.

The citizens of Boston were appalled, both at Boylston's seeming recklessness and at Mather for putting him up to it. Both men were unnerved by this horrid clamour, as Mather put it. Boylston was even more unnerved when Thomas developed a high fever that stubbornly refused to subside. Jack was hardly affected. Young Jackie had only a mild fever, but Thomas was delirious. Boylston sat anxiously by his son's bed.

But eventually, the fever broke. Thomas came out in pustules, but not many. And soon, he felt absolutely fine. But if Boylston expected this news to mollify the citizens of Boston, he was in for a disappointment. The town's most eminent doctor called inoculation wicked and criminal. And Boylston, a quack.

The New England Courant carried screed after screed attacking the doubtful and dangerous practice. And, well, it was dangerous. Inoculis became contagious. Some got very ill indeed, but not everyone was yelling abuse at Boylston in the street. A few approached him quietly. First a trickle, then a steady stream.

Boylston inoculated anyone who asked. He kept careful notes of every case. In October 1721, Boston's outbreak reached its peak. 400 people died that month, from a population of only 12,000. New clients started to arrive from nearby towns where the epidemic was just taking hold. Cotton Mather invited his nephew to come and stay with him for a Boylston inoculation.

Bostonians who'd managed to avoid the smallpox were incensed. Just as their own outbreak finally seemed to be waning, the last thing they wanted was an influx of visitors who might set it off again. One disgruntled citizen decided to act. He or she, they were never identified, composed a note addressed to Cotton Mather. "'You dog,' it read. "'Damn you. I will inoculate you with this, with a pox to you.'

This person also made a bomb. A ball of iron containing turpentine and gunpowder. At 3 o'clock in the morning, they took the note and the bomb and made their way to Cotton Mather's house. And they lobbed the bomb at his window. AI might be the most important new computer technology ever. It's storming every industry and literally billions of dollars are being invested. So, buckle up.

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We left Operation Dark Winter with an imagined terrorist attack spreading smallpox fast. Let's check back on the scenario. It's not going well. 13 days into the simulated epidemic, there are now 16,000 cases in 25 states. It's no longer feasible to identify all the contacts. And vaccines, anyway, are running out. There are only 12 million in stock. It's nowhere near enough.

Factories are making new ones, but they're at least four weeks away. Until then, there's only social distancing. If that doesn't work, the experts warn of a million deaths. This terrifying training exercise did exactly what the team behind Dark Winter had hoped it would. It startled decision-makers into action. We heard in an earlier episode that warnings aren't always heeded, but in one important respect, this one was.

Now the US has 300 million smallpox vaccine doses. It should be much better prepared in case dark winter ever happens. But hold on. If smallpox was eradicated in 1980, how could the scenario in dark winter happen? There are alas a few possibilities. Samples of smallpox still exist in two ultra-secure facilities, one in America, one in Russia.

But nowhere, of course, can be completely secure. For years, the World Health Organization has debated destroying these remaining stocks of smallpox. And you might wonder why there's still room for debate. Why take chances? One problem is that more smallpox might exist unofficially somewhere else. A few years ago, employees of the US National Institutes of Health were clearing out a long-forgotten storeroom when they came across some cardboard boxes.

Inside were vials, packed in white cotton, with faded labels. Just one word was legible: variola. It was freeze-dried smallpox virus, from the 1950s, still quite capable of infecting someone. The vials were safely destroyed. "A problem in inventory control," came the embarrassed explanation. Who knows if there are undiscovered inventory problems elsewhere?

There was certainly plenty of smallpox around at the end of the Cold War. The Soviet Union made up to 100 tonnes a year for specially designed biological weapons. Thankfully, they were never used. Still, when the Soviet Union collapsed, was all that smallpox carefully accounted for? We can't be sure. And now it's becoming easier and cheaper to make all kinds of pathogens in the lab.

In 2017, researchers caused a stir by synthesising the horsepox virus. Harmless to humans, but closely related to smallpox. The same year, Bill Gates warned that the next epidemic could be a terrorist. Using genetic engineering to create a synthetic version of the smallpox virus. Bill Gates. He's been right before.

And if smallpox might come back, the argument goes, we should keep researching it. Medical knowledge is advancing all the time and we want better vaccines. The current one's not safe for pregnant women or cancer survivors. It's a little risky for everyone else. Destroy those remaining smallpox samples and research gets trickier. It's a conundrum. There's no easy answer. Back in Boston.

1721. At three o'clock in the morning, a bomb has been hurled at the window of the unsuspecting household of Cotton Mather. But the window at which the bomb is aimed has an iron casement. The bomb hits it, and that knocks out the fuse, which fizzles and dies without igniting the turpentine and gunpowder. Instead, it's a bomb that's been hurled at the window of the unsuspecting household of Cotton Mather.

The iron ball thuds harmlessly to the floor, next to a bed containing Cotton Mather's startled nephew. So Mather survived to write to his friends at the Royal Society in London, describing the inoculation efforts at Dr Boylston. London was in the midst of its own smallpox outbreak and its own dispute about inoculation. They'd seen, of course, the same account as Mather in the philosophical transactions, describing the customs in Constantinople,

What's more, Lady Mary Wortley Montague had actually lived in Constantinople, had her own children inoculated, and now she was back in London urging others to do the same. Few were ready to listen. Lady Mary was not a doctor. She was also not a man. But she was determined, and she was friends with Princess Caroline, wife of the future King George II.

They persuaded the current king to sanction a few experiments on prisoners and orphans. Medical ethics have evolved a bit since then. The results were promising, but small scale. Cotton Mather's report from Boston was perfectly timed to strengthen the case. Five days after his letter was read to the Royal Society, Princess Caroline had her daughters inoculated too.

The Royal Society invited Boylston to London to discuss his work. 282 people had been inoculated in the Boston area. Six had died. The Society advertised for doctors in England to send in their accounts, added up the numbers, and they were remarkably similar. A death rate from inoculation of a little over 2%. That's not a trivial risk, but it was vastly lower than the death rate from smallpox itself.

For the 1720s all this was groundbreaking stuff. The first known example of statistics being used to evaluate what was effectively a clinical trial. So the practice spread. Even the top Boston doctor, who'd said it was "wicked and criminal", grudgingly started to inoculate his patients.

At the end of the 18th century, there was a breakthrough in safety. An English doctor named Edward Jenner had noticed that having cowpox made you immune to smallpox. And cowpox was a far less dangerous disease. Jenner thought, if he inoculated someone with cowpox, wouldn't that make them immune to smallpox too? It did. And unlike the traditional inoculation, it didn't have a 2% chance of killing you.

The Latin for cow is vacca, hence the term vaccine. Jenner knew he'd made a big discovery. The vaccine, he said, could extirpate smallpox from the earth. That was optimistic. But in 1967, the World Health Organization raised funds for a 10-year program to make it happen. There were still over 10 million cases a year in countries where mass vaccination was a challenge.

So the smallpox eradication programme's first task was to get vaccines into those hard-to-reach places. And then, when cases were few enough, to send a team to every new smallpox case and track every contact until the virus, at last, had nobody left to infect. The end of smallpox is one of humankind's greatest achievements. I started this mini-series of COVID-themed tales with a confession.

I hadn't seen the current crisis coming. I interviewed an epidemiologist back in February 2020 who told me the pandemic was on its way, that the death rate might be 1% or maybe half, that most of the world might get it. I believed her. And I never imagined that it might lead to the shutting down of societies and a deep economic recession. Perhaps I shouldn't be too hard on myself.

Perhaps it wasn't really obvious. Back in 2001, the organisers of Operation Dark Winter had been interested to explore how far decision-makers would be willing to go. Among the uncertainties, should national travel restrictions be imposed? How can disease containment best be balanced against economic disruption and the protection of civil liberties? And this was smallpox.

So, no, it really wasn't obvious what price we'd be willing to pay to contain a virus like the one that causes COVID-19. It turns out that price is high. That's a new data point, and it's an interesting one for rogue states and terrorists, say experts like Ellen Lapeson, the former vice chair of the US National Intelligence Council. They will have learned, she writes, that nothing is more destructive to the modern liberal order...

than a biological agent. They'll have learned that to bring societies and economies to a crunching halt, you don't need a pathogen that's as dangerous as smallpox. You don't even need one that's as dangerous as a smallpox inoculation. I asked in an earlier episode, what if COVID-19 is the warning? And to be more specific, what if it's a warning that the next pandemic might not be an accident? But let's not get ahead of ourselves.

First, we've got to get on top of this pandemic. And here, the story of smallpox is both cautionary and inspiring. It shows that humans can beat diseases. And how? By following the example of Zabdiel Boylston and Mary Wortley Montague. An openness to new thinking, no matter its source. A willingness to take risks. The determination to collect good data. And the courage to follow where the data lead, even as people panic around you.

And then by learning from the WHO's smallpox eradication programme, sheer logistical effort to roll out the solutions to the places where they're needed most. But it also shows something else, that victory over disease can't be final. Even when we think we've won, we can never afford to relax.

This was the final episode of this mini-season of Cautionary Tales. Thank you so much for listening. I'll be back later this year with more, so please stay tuned, leave a review, and tell your friends. This episode of Cautionary Tales owes a debt to Stephen Coss's book, The Fever of 1721, Ibram X. Kendi's book, Stamped from the Beginning, and an article about Dark Winter, written by Tara O'Toole, Michael Mayer, and Thomas Inglesby.

For a full list of our sources, please see the show notes at timharford.com.

Cautionary Tales is written and presented by me, Tim Harford, with help from Andrew Wright. The show was produced by Ryan Dilley with support from Pete Norton. The music, sound design and mixing are the work of Pascal Wise. The scripts were edited by Julia Barton. Special thanks to Mia LaBelle, Carly Migliori, Heather Fane, Maya Koenig, Jacob Weisberg and Malcolm Gladwell. Cautionary Tales is a Pushkin Industries production.

So I have some big news for vegans and vegetarians everywhere. It's Hellman's plant-based mayo spread and dressing. Made for people with a plant-based diet or anyone really who wants to enjoy the great taste of Hellman's real without the eggs. Hellman's plant-based is perfect for sandwiches, salads, veggie burgers, or any of your family favorites.

To celebrate, Hellman's is sharing some easy, delicious plant-based recipes at hellmans.com. Hellman's Plant-Based Mayo Spread and Dressing. Same great taste, plant-based.

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