Thread by @jasoncrawford

Smallpox was one of the worst diseases humanity has ever faced—and also the only human disease we have ever eradicated. It was also the first disease with a vaccine.

You may think you know the story of vaccines—Edward Jenner and the milkmaids.

But the milkmaid story is a lie.

And “vaccine” in that era wasn't what we think of today: a little shot in the arm with almost no side effects. Jenner used a live virus. Vaccination was literally giving the patient cowpox.

But vaccination wasn't even the first procedure to deliberately inject a disease—

Before Jenner, doctors would deliberately infect patients with *smallpox itself*, a practice called inoculation. Getting the disease once granted lifetime immunity—and it was milder and safer than catching smallpox naturally.

Smallpox was extremely common, especially in big cities, so this was a good deal. It was a terrible disease, causing a rash of pustules all over the body that would last for a couple of weeks, and killing up to a third of those who caught it. Many of its victims were children.

Why was inoculation less deadly? No one knew. (The best modern theory is that your body has a better immune response if the virus enters through the skin, rather than through the respiratory system.)

Inoculation was a folk practice established in China, India, parts of the Middle East, parts of Africa, and parts of Wales, where it was called “buying the pox”. But it wasn't used widely enough to stop epidemics. And it wasn't widely known in the West.

When inoculation was introduced in England and Boston in 1721, it was highly controversial (some things never change). The Rev. Edmund Massey gave a whole sermon against it, claiming it defied Providence; the Puritan minister Cotton Mather was a strong advocate for it.

The case was settled with data. Physicians in Britain and America collected stats on smallpox cases and inoculations, and how many died of each. These were published by James Jurin, secretary of the Royal Society, the premiere science institution of the day.

This sounds obvious today but it was cutting-edge at the time! No one had done clinical trials or quantitative epidemiology. Medicine was dominated by tradition and authority.

The results: smallpox killed ~17%; inoculation < 2%

A medical procedure with a 2% death rate would be considered wildly unsafe today. (!) But when it's ~10x safer than the likely alternative, it makes sense. And when people understood the facts they eagerly got inoculated.

Inoculation became a booming business; “inoculation houses” were opened where you could rest & quarantine while going through the (mild) symptoms. One family, the Suttons, opened a chain of houses and even an international franchise. (MacSmallpox?)

Whole populations of the countryside would get inoculated (especially in epidemics). And when this happened, the inoculators noticed something:

Some people were already immune.

No one knew why until the case of a farmer in 1768 who did not respond to inoculation. He swore he hadn't had smallpox before, but mentioned he *had* suffered from *cowpox*.

Aha! It turned out that cowpox *also* granted immunity to smallpox.

The doctor who discovered this, John Fewster, reported it to a local medical society and didn't pursue it further. And nothing was made of it for decades.

But Edward Jenner, then a young apprentice, heard about it and saw an opportunity.

The problem with inoculation was that it was *still smallpox*. There was a small risk of death (by this time reduced to < 0.2%), and the patient was still contagious—and if they passed the disease on it was the full, vicious form. So inoculation risked starting epidemics.

But cowpox was never deadly, and couldn't spread smallpox. This was Jenner's innovation—substitute cowpox for smallpox in the inoculation procedure.

Smallpox was “variola” in Latin, so Jenner called cowpox “variolae vaccinae”—smallpox of the cow—and his technique *vaccination*.

Why didn't Fewster do this decades before? Largely because he thought cowpox didn't *always* give smallpox immunity. Jenner discovered that not everything that looks like cowpox actually *is*, and how to tell the difference. Actual cowpox does confer immunity.

(And the story of the milkmaids? A fabrication by Jenner’s first biographer, possibly an attempt to bolster his reputation by erasing any prior art.)

Vaccination—even safer and milder than variolation—spread even further, and smallpox was beat back. Incremental improvements over the next 150 years made vaccines safer & easier to store and transport. The most important was the introduction of freeze-dried vaccine in the 1950s.

By 1966, smallpox had been eliminated from most of the developed world, and was endemic only in Africa, the Middle East, South and Southeast Asia, and Brazil. In this year the WHO launched a program to eradicate it completely.

Many—including, amazingly, the WHO director-general—thought eradication was impossible. In part that was because they assumed it would require vaccinating almost everyone on earth.

D. A. Henderson, who led the effort, found another way.

Instead of mass vaccination, Henderson established “surveillance and containment”—build a network of people on the ground who can diagnose cases and sound the alarm, then rush to the scene and vaccinate everyone who came in contact with the person, forming a defensive perimeter.

They were helped by the invention of the bifurcated needle, a small metal pin with a double point. It was simple, cheap, easy to use, required no electricity—and used 1/4 the vaccine of a normal applicator, stretching out the supplies to 4x the dosage.

Smallpox made its last stand in Somalia in 1977, infecting a 23-year-old cook named Ali Maow Maalin—the last endemic case of smallpox in human history.

He lived.

Afterward Henderson awarded his staff a certificate and lapel badge inducting them into the “Order of the Bifurcated Needle”, with the needle's point bent into a ring to signify 0, for Target Zero—their goal.

Smallpox was gone, just over 250 years after inoculation was introduced to the West. Before that, it had been around for thousands of years, and inoculation had existed as a folk practice for centuries.

What happened? Here are some factors:

1. The idea of progress. 18th-century Europe believed that progress was possible & desirable, even in medicine. They actively looked for advances and imported new ideas. In part this is the legacy of Francis Bacon and his quest for “useful knowledge”.

2. Secularism/humanism. Some cultures rejected inoculation because it defied the will of God. To accept it you have to believe in human agency and care about human life. You have to be willing to take matters into your own hands and defy fate.

3. Communication. Inoculation was practiced in 10th-century China but was kept a secret rite (!), not made more public until the 1500s. In 18th-century Europe there were hubs of information like the Royal Society and a culture of openly sharing knowledge and innovations.

4. Science. Inoculation was controversial, for understandable reasons. In the West, the case was proved with data. The scientific method also drove incremental improvements in the technique and breakthroughs like Jenner's vaccine.

5. Capitalism. Inoculation was a *business*. Inoculators competed with each other, driving down prices and sending them in search of new markets. Advertising educated the public about the benefits of inoculation and how easy and painless it could be.

6. Momentum. The Industrial Revolution was a massive feedback loop that fed on itself, progress begetting progress. Electronic communications, airplanes and motor vehicles, mass manufacturing, refrigeration and freeze-drying, and modern science were all crucial to eradication.

Smallpox was the first to be eradicated, but it doesn't have to be the last. Other diseases will be harder though. Polio has taken over 30 years and isn't gone. Tuberculosis has a long latency period. Yellow fever has an animal reservoir. Malaria and HIV don't even have vaccines.

But as @DavidDeutschOxf says, anything not forbidden by the laws of nature is achievable, given the right knowledge. No law of physics says diseases must exist. If human progress continues, I believe humanity will see the end of disease.

Many more details in my full blog post at @rootsofprogress: rootsofprogress.org/smallpox-and-v…