By now, you’re probably used to ‘flu season’ coming around every year.

These days, you can often avoid getting sick through vaccines, washing your hands, andavoiding sneezing co-workers. So while influenza can be dangerous, for most people it’s just another part of winter.

But a hundred years ago, at the start of 1918, the normal flu season took a backseat to whatbecame the deadliest outbreak in history: a global influenza pandemic that killed anywherebetween 50 and 100 million people. Today, it’s called “the mother of all pandemics”, and scientists think they’vefigured out what made it so deadly.[♪INTRO]Epidemiologists still aren’t sure where this killer flu originated. Some say it started in China, while others point to early cases from a military trainingbase in Kansas.

But eventually, thanks to the war and global trade routes, it spread around the world andbecame known as — of all things — the Spanish flu. See, in 1918, a lot of the world was busy finishing World War I, and many countrieswere heavily censoring their news. Anything that might hurt morale — like a deadly, fast-moving plague, for example — waskept from the media.

But Spain, which wasn’t involved in the war, had no problem reporting the outbreak. So, people started calling it the Spanish Flu, since it seemed to have emerged therefirst — if only according to the news. Regardless of where it started, this flu was so devastating that some people believed itwas biological warfare.

Some estimates say that one-third of the world population was infected, and that more than2.5% of people died from it, often through complications like pneumonia — includingmillions of 20- to 40-year-olds, who are usually the least vulnerable. A normal flu, meanwhile, is fatal in less than 0.1% of cases. To know why it was so dangerous, it helps to know a bit about the flu virus itself.

There are four subtypes of the influenza virus, called influenzae A-D, with influenza A beingthe main kind that causes pandemics. Those viruses are categorized by two surface proteins: hemagglutinin, which comes in 18varieties, and neuraminidase, which comes in 11. They give flu strains names like 1918’s “H1N1”, although there can still be variationsamong viruses with the same name.

Your immune system builds antibodies that recognize all these proteins and protect youfrom multiple infections — but unfortunately, the influenza virus mutates so quickly thatyour body doesn’t always recognize it. Most mutations are small — enough that your body will probably still be able to defenditself. These tiny changes are called antigenic drifts.

But the 1918 flu virus underwent a much bigger change — called an antigenic shift — thatleft people vulnerable. These big mutations result in viruses with very different or entirely new combinationsof surface proteins, and they’re different enough that most people have little or nonatural immunity. Changes like these are what cause flu pandemics.

Now, even though the virus changes all the time, scientists think that the first fluyou encounter may have a life-long effect on the way your body fights new infections. They call this idea the antigenic imprinting — or the “doctrine of original antigenicsin”. Really.

It says that your immune system seems to remember your first influenza infection and will tryto fight later flus using the same antibodies. So if you caught an H3-type flu as a child, you’re better able to protect yourself againstother H3 flu viruses, even if some of its other proteins have changed. But you probably wouldn’t do as well against, say, an H1-type virus.

Which is exactly what happened 100 years ago. And it’s one reason why 20- to 40-year-olds were so likely to die during this outbreak,even though they’re usually the least affected. When they were younger, the so-called “Russian Flu” was the dominant strain — and thatwas probably the H3N8 variant.

Then, around 1900, the H1-type virus became dominant. And sometime right before 1918, another shift created the H1N1 strain that caused the pandemicand left young adults with almost no immunity. Meanwhile, people older than 40 may have experienced an H1-type virus in their childhood, so theyalready had some protection against this new version.

On top of that, young adults also have especially strong immune systems, which actually workedagainst them and caused a lot of people to die quickly after showing symptoms. These rapid deaths were likely caused by cytokine storms, which is an immune system responseso intense it damages a patient’s tissues. And the stronger your immune system, the more damage a cytokine storm can do.

So, 1918 was not a great time to be a young person. After racing across the world, the deadly pandemic seemed to burn itself out after ayear or so. Researchers think that, since so many people were infected in the first outbreak, enoughof the population gained immunity to prevent further chaos.

The virus also probably mutated to a less deadly form — though, in general, scientistsaren't certain what magical combination of mutations makes a flu more or less deadly. Either way, we don’t need to worry specifically about the Spanish flu these days. Many of today’s H1 viruses are actually descended from that 1918 virus — which ispartially why it’s called “the mother of all pandemics” — so most people havesome H1 immunity.

But if there’s ever another big antigenic shift, that could be a problem — becauseit could definitely happen and might even cause another pandemic. To protect us from that possibility — and the rest of the flus — scientists are workingon a universal vaccine. There are several in development right now that target parts of the virus that are thesame across all variants.

And if any of them work, it could someday mean that one vaccine would protect you fromevery flu season. So even though it’s possible, hopefully we’ll never experience another pandemiclike the Spanish flu again. Thanks for watching this episode of SciShow, and a special thanks to our patrons on Patreonwho help us make episodes like this.

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