Few of the monsters that evolution created have been so successful at hurting us as the variola virus, responsible for smallpox. The carnage it caused was so terrible and merciless that it compelled humankind, for the first time, to act truly globally. It was one of the greatest wins of our species over the ancient powers of nature, all made possible by… cows.

Variola is a virus, a tiny machine that only seeks to reproduce itself. Evidence of it has been found in Egyptian mummies and in writing from India and China as old as 3000 years. 1300 years ago smallpox killed up to a third of Japan’s population. By the sixteen hundreds, it was one of the major causes of death worldwide. In late 18th century Europe, it killed 400,000 a year. Every third person who went blind did so because of this virus. Even in the 20th century, a hot second ago in history, it still killed at least 300 million people. Smallpox is an abusive monster that returns over and over and over again, killing, maiming, and disrupting societies.

How could variola be so incredibly deadly for so long and how could we have forgotten its horror so quickly? In 2023, there are only two laboratories left where the living virus is officially stored for research: in Koltsovo, Russia and in Atlanta, USA. Which is certainly a good idea because what could possibly go wrong?

Let’s say that through an unfortunate series of events the virus got out and you got infected. What would happen to you? How Smallpox Kills Variola is highly infectious and catches a ride in small droplets you breathe in. Immediately it begins to infect the cells that line your throat and starts killing them to cause chaos. Why? To trick your body into giving it a lift. Whenever cells in your body die a violent death, your immune cells immediately stream to the site of infection to help out. In this case that backfires horribly. As immune cells begin cleaning up dead cells, eating viruses and killing infected cells, variola infects a crucial cell of your immune system: Your Dendritic cells, intelligence cells that gather information and leave the battlefield to get help.

They enter your lymphatic system, a highway network that spans your entire body and connects hundreds of immune bases. In these bases your heavy defenses are activated and should be the last place an enemy would want to invade, but Variola wants to get here. For about 12 days, the virus quietly infects civilian and immune cells, jumping from cell to cell infecting more and more of them. At some point a critical threshold is reached and variola starts its attack for real. Millions of viruses use the lymphatic highway to spill into your blood and organs, infecting your whole body. Suddenly variola is everywhere. But despite this global attack, your adaptive immune system is struggling to wake up. Your immune cells look for and use critical transmitters called interferons to mobilize the body against viruses. Interferons, as the name suggests, interfere – significantly slowing down virus infections but also quickly activating millions of anti virus weapons.

But Variola is able to deactivate interferons, which stuns the anti virus side of your defense system. Other systems would usually help - like the complement system, a sort of mobile minefield that can destroy viruses but variola also manages to shut this down too. And so, with little resistance variola spreads everywhere and infects billions of your cells all over your body. Among the infected are your capillaries, the smallest blood vessels in your body, which die in great numbers. All this death activates an immune cell that you really don’t need right now but that is attracted by death: The Neutrophil. Normally an efficient killer of invaders great and small, it is not very effective against smallpox. And even worse, Neutrophils fight by vomiting deadly chemicals, which kills even more of your cells. In 1980, the campaign was declared successful:  Smallpox was eradicated from the face of the earth.

Smallpox is one of the worst diseases humanity has ever known, leaving death and destruction in its wake. In order to gain immunity, people resorted to a dangerous practice known as variolation, which involved taking scabs from an infected person and introducing them into the body of a patient. This was risky, as 2-3% of patients still died as a result of the treatment.

In the late 18th century, scientists realized that it was not necessary to use the real smallpox virus for treatment, and instead opted to use material from cowpox, a milder virus that still gave immunity. This led to the development of vaccinations, and in 1966, the World Health Organization launched a global campaign to eradicate smallpox. In 1980, the campaign was declared successful, and smallpox was eradicated from the face of the earth. Smallpox only infects humans, so if we stopped the human transmission chain, we would starve the virus. In 1980, just shy of 200 years since the first vaccine was used, Smallpox was declared eradicated. Variola, the scourge of humanity, was dead. No more children would be killed by it, no more mothers or brothers or uncles or cousins. It is hard to convey to people around today what an incredible win this was; one of the cruelest, most dangerous monsters that has hunted us for literally millenia was slain, by us, apes with pointy needles.

Today we live in a time of enlightenment; none of us alive today are haunted by the specter of smallpox. This light is not natural; it was set in the sky by the sheer will of humankind wanting to be safe from the monsters haunting us. But because we live without them, we forget that they ever existed and that they are real; that the diseases might reawaken, or new ones might be brewing in jungles, wet markets or laboratories, ready to strike us once more. We forget what an incredible gift vaccines are and how hard we had to battle to get them.

We are still protected by the light but it is cooling each and every day, and we owe it to those who will come after us to make sure it doesn’t go out. We killed one monster. We can do it again.

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