Name: The (Second) Deadliest Virus
Uploaded: 2026-01-22T17:01:04.000Z
Duration: 11 min 9 s
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Few of the monsters that evolution created have been so successful at hurting us as the variola virus responsible for smallpox.

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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 3,000 years.

1,300 years ago, smallpox killed up to a third of Japan's population.

By the 1600s, 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.

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.

Variola is highly infectious and catches a ride in small droplets.

Immediately, it begins to infect the cells that line your throat and starts killing them to cause chaos.

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

Variola infects a crucial cell of your immune system, your dendritic cells, intelligent cells that gather information and 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.

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.

Millions of viruses use the lymphatic highway to spill into your blood and organs, infecting your whole body.

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 and but also quickly activating millions of antivirus weapons.

But variola is able to deactivate interferons, which stuns the antivirus 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 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

Normally an efficient killer of invaders great and small, it's not very effective against smallpox.

And even worse, neutrophils fight by vomiting deadly chemicals, which kills even more of your cells.

On top of that, they order inflammation fluids streaming from your blood vessels into your tissue, all over your body.

As first millions, then billions of your cells die.

You get a rash that only gets worse and worse.

Pus and cellular junk fills it up as your body swells up with hundreds of lesions all over your skin and inside, even on your organs, all filled with billions of variola viruses.

Now the critical phase begins as you fight for survival.

Thousands of battlegrounds drain your blood of fluid that streams into your tissue and organs.

Blood clotting appears all over your body, While floods of toxins from dead cells build up and can cause organs to fail.

Your lungs fill up with fluid, making it harder and harder to breathe.

Either your immune system wrestles back control.

Heavy weapons have been dispatched, killing infected cells, cleaning up the thousands of infections one by one, Killing variola wherever it can be found so you can slowly begin to recover.

The immune system will forever remember variola, making you immune forever.

Or you die, overwhelmed by the infection and your immune system's panicked reaction to the body wide infection.

About a third of people who contract smallpox don't survive.

And if you survive, you're very likely branded by scars and may even lose your eyesight or hearing.

For thousands of years, this terrible disease ravaged the world, leaving Death and destruction traumatized and maimed survivors.

Smallpox is one of the worst diseases humanity has ever known.

A murderous family destroying, life ruining monster.

There was nothing you could do for the infected.

But people noticed that if you survived, you were immune.

So out of desperation, they came up with the dangerous practice of variolation.

Take scabs from an infected person that had a mild case of smallpox, let them dry out and grind them to a fine powder.

Then blow the powder up the nostril of a patient or scratch their skin with it.

If things went well, they only got a mild version of smallpox and gained immunity against the disease.

Variolation probably worked because it introduced variola in a part of the body the virus wasn't prepared for, disabling most of its nasty tricks.

And because the inoculation was left to dry out, that damaged the virus so it couldn't cause the full disease.

Unfortunately, 2 to 3% of all patients still died because they got the smallpox or suffered other diseases as a result of treatment.

Still, smallpox was such a horrible and to some degree unavoidable disease that people took the risk for themselves and their children.

Variolation spread around the globe, while variola continued to kill millions.

A victory over the virus only became a real possibility when scientists realized that it wasn't necessary to variolate with the real smallpox disease, but

much safer to use material from cowpox, a variant that affected surprise cows.

And only a few years later, this led to one of humankind's most outstanding achievements.

Instead of using the real virus to train the immune system, use a related virus, cowpox, that was only mild, but

Countless individuals fighting the monster where they could, delivering vaccines to the most remote places on earth.

All the while, the disease ravaged on, killing over 300 million people in the 20th century alone.

In 1966, the World Health Organization decided that humanity had to come together in a final major effort.

A global smallpox news network based on residents in hotspots was created, tackling local outbreaks of the virus.

Cases were encircled, vaccines given, preventing further spread.

Smallpox only infects humans, so if we stopped the human transmission chain, we would starve the virus.

The last naturally occurring infection was in 1977.

And 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 mothers or brothers or uncles or cousins.

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The (Second) Deadliest Virus

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