One hundred years ago, in 1918, Europe and America were at the height of World War I.

People were moving all over, especially soldiers flocking to the Western Front to fight.

At the beginning of the war’s final year, another enemy would enter the trenches, one that threatened people on and off the battlefield and eventually led to more deaths than all war-related causes combined.

That enemy was the flu.

What made it so deadly?

And 100 years later, could it happen again?

No one knows for sure where the original 1918 flu infection happened.

As the first bout of illnesses cropped up in North America, Europe, and Asia it didn’t kill many people.

But by the Fall of 1918 the disease had grown deadlier.

People displayed classic flu symptoms like nausea, fever, and aches, but many began to develop dark spots on their cheeks, their breathing became difficult, and their faces turned blue from lack of oxygen.

These people caught pneumonia and died from suffocation.

Along the Western Front, rows of dead soldiers piled up, who had just days earlier been young able men.

Because the world was at war, news of these deaths was kept quiet to maintain morale.

Only the Spanish, who had remained neutral in the war, wrote about the frightening numbers of illnesses and deaths, which is why this disease is named for them (such an honor!).

By the time the disease declined in 1919, one third of the world had been infected with the Spanish flu, and between 50 million and 100 million people died– as much as 5% of the world population at the time.

Enough people died in the US that the average lifespan fell by 10 years.

It was a flu more deadly than any we’d seen before or since.

But the flu has been around for a long time.

We see it every year.

What made the 1918 outbreak so bad?

To understand this, we need to shrink down to the nanoscale world.

Influenza is a virus Influenza is a virus, which is essentially a container made to carry genetic information.

These genes are the blueprints for building more virus - using the machinery of your own cells.

Variations in these genetic blueprints determine how deadly a particular virus is.

The virus’ armored shell is made up of two proteins.

One unlocks the door to your cells.

The better it can do this, the more infectious it becomes.

The second helps newly made viruses escape from the cell.

Every flu strain has a name based on different combinations of slightly different H and N proteins.

We now know the 1918 flu was an H1N1 strain, and many Influenza viruses today are a descendant of it, including the 2009 “bird flu”.

When you catch the flu virus, it invades your cells, the viruses reproduce, and infected cells eventually burst.

Your immune system senses this mess, identifies the attacker, and starts building an army of cells that specifically recognize the invader by reading its unique H and N surface proteins.

These recognizable bits are called antigens.

Once you’re better, other cells “remember” that antigen, so you almost never get infected with the exact same flu twice.

But the flu has a few tricks up its sleeve.

Each time it replicates its genes, it makes random mistakes or mutations.

We call this gradual change antigenic drift.

So if, say, an H1N1 strain undergoes enough mutations, the immune system may not recognize it, and it can make you sick again.

This is why you need a new flu shot every year.

But, more extreme changes in flu genes can also occur.

If an unlucky host is infected with two flu viruses at the same time, their genes can shuffle.

Instead of small gradual changes, this can lead to radically new genetic combinations.

Imagine if Nickelback and Limp Bizkit joined forces to make Nickelbizkit.

It would be even more dangerous than the originals.

This kind of shuffle is called an antigenic shift, and it creates flu viruses completely unrecognizable to our immune system.

These are the viruses most likely to cause massive outbreaks like 1918.

To understand if we’re at risk for another super virus emerging today, we need to know exactly what made the 1918 flu so catastrophic.

Today we have better sanitation, vaccines, and antivirals, yet hundreds of thousands of people still die every year from the flu.

But the 1918 flu was different in some very deadly ways, thanks to its unique genetic arrangement.

In the late 1990s, two scientists resurrected the genetic code of the 1918 influenza virus preserved in a body buried in Alaskan permafrost.

Turns out two bits of the 1918 flu were essential for its viral badness.

A deadlier form of the H surface protein helped it enter and kill lung cells more efficiently.

It also carried genes that helped it make copies of itself 50 times faster than modern flus.

But it was really when all of the other pieces of the 1918 virus were put together *with* these two that it became a “super virus” and to be honest, we still don’t have a complete answer as to why.

One answer is more certain: Another deadly flu like 1918 IS possible.

Two general factors determine if a flu will be particularly bad - how well it travels from human to human, and how deadly it is once it gets inside of us.

For example the H5N1 bird flu has a mortality rate of more than 50%, but it can’t spread from human to human, only from birds to humans.

When you get a flu that’s good at both, like 1918, that’s how you get a pandemic.

Say, for example, bird flu mutates so it can be transmitted between humans.

That would be very bad.

It’s true that modern medicine and flu shots have helped in humanity’s war against the flu, but other aspects of our modern culture have put us more at risk for a pandemic.

Humans aren’t the only species that can carry the flu.

But because some of these other versions are similar to human flu, a few changes and they can jump the species barrier.

We have increased contact with livestock today, making these species jumps more likely.

And since we travel so much today, a deadly virus could spread across the globe in hours.

While we don’t know how to predict where a pandemic will start, scientists agree it’s not a question of if, but when.

If a flu like 1918 popped up today, an estimated 100 million people could die world wide.

Can we do anything to be ready?

Containing a pandemic will require global cooperation to stop the spread and treat infected people.

Because traditional vaccines take months to develop, scientists are working on a universal flu vaccine, one that would protect against any strain of the flu, but the task has obviously been difficult because the flu is constantly changing.

These days, the flu feels like an annoying yearly thing.

If you remember to get a shot, maybe it can save you from a few days fever and runny nose.

But flu is a real and honest threat to humanity.

Humans and influenza have been at war for centuries.

Flu infects humans.

Humans develop immunity.

The flu mutates and the process starts again.

Perhaps one day, science will help us leave influenza in the history books.