This video is sponsored by Squarespace.

I don’t want to go all John Green on you guys,  but the history of humanity is full of disease. Even when you pay attention in history class,   though, you usually only hear  about a few headliner events.

You got the Black Death in the 14th  century, the Spanish Flu in 1918… …which actually was not Spanish in origin.  That’s not important right now, though. Pathogens like the influenza virus and Yersinia  Pestis, the species of bacteria responsible for   bubonic plague, have caused many epidemics and  pandemics that you may have never heard about. And that’s kind of inexcusable.

So let’s break down seven of them across history,   and learn why they were every  bit as awful as the famous ones. [♪ INTRO] First, let’s address the difference  between an epidemic and a pandemic. In general, experts use the  word “epidemic” where a certain   geographic area sees an unexpected  increase in cases compared to normal. While “Pandemic” is used for skyrocketing  increase over a broader population and location.

But usually there’s no clearcut threshold for the   exact number of cases that pushes  an outbreak into either category. Public health officials just have to keep an  eye on the typical disease numbers in an area,   and compare what they’re observing now. With that little lesson out of the way, let’s  start with the oldest epidemic on our list,   which features a virus we know all too well.

If you’re like most of our audience,  you were born before the 21st century,   and you’ve already lived through  multiple coronavirus epidemics. But unless you look very, very good for your age,  you definitely did not experience the first one Because our earliest evidence of a coronavirus  epidemic dates to around 23,000 BCE in East Asia. Now of course we do not have  any first-person accounts.

But to explore our ancient  past, scientists can study   our modern genetic code and kinda work backwards. In a study published in 2021, one research  team looked at over 2,500 human genomes   across 26 global populations to look for  evidence of ancient coronavirus epidemics. Specifically, they were looking for  parts of the human genome that code   for certain virus-interacting proteins, or VIPs.

And like that acronym suggests,  VIPs are Very Important Proteins. But not in a good way. For example, some are proteins on the outsides   of our cells that viruses use  to attach to and infect them.

So any evidence of VIP evolution could   suggest some past viral epidemic  caused the proteins to adapt. In other words, people with VIPs that the  viruses couldn’t latch onto as easily were   more likely to not die before passing  their genes to the next generation. For this study, scientists were looking  specifically at VIPs that are known to   interact with coronaviruses…although that does  not mean they only interact with coronavirus.

Hence my use of the word “could”. But based on the genetic evidence, and  some fancy computer models to estimate   when certain mutations must have  originated, the researchers found   significant adaptation in coronavirus  VIPs dating back roughly 900 generations. They also found that most of the  oldest genetic adaptations seem   to have happened in the ancestors  of modern East Asian populations.

Together, the evidence suggests ancient  humans in what is now East Asia probably   experienced a coronavirus epidemic  somewhere around 25,000 years ago. This is… very cool that we can find  evidence for epidemics that happened   thousands of years before we  could even write about them. But learning about the evolutionary  history of humans’ response to   coronavirus can also help us improve  prediction tools for future pandemics.

And we know this was a bad pandemic because  it doesn’t change people’s proteins,   unless a lot of people don’t pass  their genes on because they died. So yeah, I am always in favor of better tools for  predicting and understanding future pandemics. But, genomic signatures are not the only thing that   can tell us about epidemics with  very few contemporary sources.

We can also look at mythology! We’re jumping forward roughly 24,000 years  to the 6th century CE in Wales for this one. A mysterious plague was  sweeping across the country,   leaving horrible recurring  fever and death in its wake.

The disease was known by many names, including  lallwelen in Welsh; pestis flava in Latin;   and the Welsh Yellow Plague, on account of  one characteristic symptom being jaundice. Despite taking place in the same  century as the first official   bubonic plague, the two were caused  by completely different pathogens. Now technically, scientists have not been able   to fully confirm the pathogen  behind the Welsh Yellow Plague.

But based on our writer’s hunt  through the literature, one major   candidate is a species of spiral-shaped  bacteria, called Borrelia recurrentis. This bacteria is carried by lice, and  causes a disease called relapsing fever. Whatever the source, this plague  was so horrible and sudden,   it inspired a mythological yellow monster  called y Fad Felen in Welsh legends.

Perhaps adding to y Fad Felen’s mystique  is how it killed the King of North Wales. According to one admittedly  much later recording of events,   after a poet named Taliesin  prophesied that a strange,   yellow monster would punish him for his  crimes, the king did indeed die of the plague. Due to the great challenge of preserving and  verifying poem-prophesies from the 6th century,   we are not 100% sure that Taliesin  was the author of the prophecy… or that this prophecy was even made back then.

But the legend has been compelling  enough to withstand the centuries. The Yellow Plague also seems  to have shaped human migration. The disease is probably at least one of the major   drivers of a mass exodus out of  Wales to Ireland and Brittany.

If you’ve never heard of Brittany,   it’s now the northwesternmost part  of France, not its own kingdom. But all that plague-inspired immigration  helped Brittany become so powerful,   it didn’t get absorbed by France  for another thousand years. And our next example is another case of disease  shaping local human life for a whole millennium.

Smallpox is probably most  famous for being the only   disease that humans have managed to eradicate. It was a global problem for at  least 3000 years, up until 1980. Smallpox likely came to Japan  through merchants and Buddhist   missionaries in…yet again…the sixth century CE.

And the country’s first recorded  smallpox epidemic started in 735. Proportionally, the death toll of this  epidemic was comparable to the Black Death. Roughly one-third of Japan’s population was lost.

So while it was only in one country, it  was a very big deal for that country. We asked our resident Japan-expert Hiroka if she   had heard of this epidemic before our script  editor pitched this episode…and yes, she had. One interesting characteristic  of this smallpox epidemic is   that 95% of the deaths were in children under 10.

In more modern cases of smallpox outside Japan,   the disease doesn’t seem to  have discriminated so clearly. At the time, managing your  child’s smallpox within the   household became a normal part of Japanese life. People even threw parties to celebrate children’s  recovery as an important coming-of-age milestone.

Good idea. I mean, that’s very sad, but I  hope there was, like, a good cake. Meanwhile, to manage the disease, households  also learned early public health measures.

For example, in more rural areas  where smallpox wasn’t as common,   people implemented isolation  and quarantine measures. You know who also could use some cake? The people stuck in quarantine.

Maybe even more than the people who were finished   with the whole “I might die  from smallpox” thing”... quarantine cake sounds great. Norms like these developed over the centuries,   as dozens of smallpox epidemics  came and went until the mid-1800s. And speaking of diseases that  come back over and over again… When it comes to flu pandemics, the  one from 1918 often gets all the glory.

Which makes sense, given that it killed 50   million people and infected one  fifth of the global population. But the first flu pandemic probably happened   back in 1510, and it spread across  Afroeurasia through trade routes. We actually have first-hand accounts  of the disease, so we know that it came   with the now-familiar symptoms of a hoarse  voice, fever, chills, and a phlegmy cough.

In the 16th century, methods of treating  influenza were pretty ineffective and unpleasant. People still believed in the  four humors theory back then,   which was based on the idea that illness was  caused by an imbalance of fluids in your body. So making people vomit, inducing diarrhea,  and bloodletting were all common treatments.

And that just sounds bad! Thankfully, we now have flu vaccines,  and antivirals, and chicken noodle soup. And speaking of thankful, we are also thankful  to the folks who help us keep our lights on.

Which means it’s time for an ad. Thanks to Squarespace for  supporting this SciShow video! You know Squarespace.

It’s the website place, where you can manage  online stores, payments, emails, and more. Our Director, Hiroka,  uses Squarespace for her website. She even took advantage of the elevated suite of   visual design effects that  fit right into her site.

Squarespace offers flexible templates with  Design Intelligence using AI technology,   so you can have your own  professionally designed website. Plus, they curated videos  on their own YouTube channel   with tutorials to help you through the process. You don’t even have to leave  the site you’re already on!

For a free trial, head to Squarespace.com. And when you’re ready to launch, go to  squarespace.com/SCISHOW to save 10%   off your first purchase of a website or domain. When Spanish conquistadors arrived  in Mexico in the 16th century,   they brought a lot of terrible things with  them, including diseases like smallpox,   which the indigenous population  had never encountered before.

But the deadliest disease around  that time was not smallpox. It was cocoliztli, which translates to  “pestilence” in the Nahuatl language. And while some evidence suggests it  too was brought over from Europe,   there’s not enough to definitely  rule out it being homegrown.

Cocoliztli is regarded as one of the most  devastating epidemics in human history. Within just three years, an epidemic that started  in 1545 killed up to 80% of the indigenous Mexican   population through sudden fever, painful ulcers  all over the body, and excessive bleeding. Death usually came in just a few days.

For a while, scientists weren’t really  sure which pathogen was the culprit. There were a lot of candidates, including  those responsible for typhus, enteric fevers,   measles, and of course, good ol’ fashion plague. But a study published in 2018 suggests something   that probably sounds a lot more  familiar to you: salmonella.

For this research, scientists excavated 29   cocolitzli-era skeletons in Mexico and  isolated DNA samples from the teeth. Which I should clarify does  not have to mean human DNA. Because by sequencing the genomes, and checking  them against known sequences of bacterial DNA,   the researchers were able to identify  the presence of Salmonella paratyphi C.,   which is a strain that causes enteric fever.

It’s not the kind of salmonella that your   friend’s cousin picked up from  eating raw chicken or whatever. But despite this bit of evidence, we’re still not  confident we’ve cracked the code on cocoliztli. According to historical indigenous accounts,   some symptoms don’t completely line  up with the salmonella hypothesis.

For example, there are records of jaundice  and bleeding from various body parts,   and those aren’t completely  consistent with enteric fevers. But the scientists behind the 2018 study  were only looking for DNA evidence,   so that doesn’t rule out any possibility  of non-DNA viruses also being to blame. Or hear me out, maybe it’s not a bacteria or a   virus that’s responsible…like our next epidemic example.

In 1940, the Southwestern  US experienced an epidemic   caused by a fungus called Coccidioides immitis. In general, the disease it causes  is called coccidioidomycosis. But since this particular epidemic happened  in California’s San Joaquin Valley,   the disease behind it was  also called Valley Fever.

Which is a lot easier to say,  so I’m going to be doing that. During World War II, the US military wanted  to train some troops in the San Joaquin Valley,   which if you’ve never been there,  is a dry climate with lots of dust. Since fungi spread especially well in dry areas  that can kick up dust and fungus particles,   scientists already knew that there was  a fairly high risk of Valley Fever.

They also already knew that the  fungus could cause skin lesions,   headaches, chest pain, fever, and night  sweats, depending on how you caught it. In more extreme cases, people  could develop pneumonia and red,   bruise-like bumps all over the skin. Despite the warning, the military decided   that the benefits of the area  outweighed the potential risks.

They went ahead with moving  their soldiers into the Valley. And in response, the local scientists  got to work with public health measures. For example, they had a skin test that  identified if someone ever suffered from   a bout of Valley Fever, even  if they’d already recovered.

And they suspected those people  were unlikely to get reinfected. So when each soldier arrived, he  got screened with a skin test. Anyone who tested negative  would be periodically re-tested.

With this systematic screening,  scientists were also able to   confirm that people whose skin test  was positive did not get reinfected. Fortunately, the more scientists were aware of  Valley Fever, the better they could prevent it. The incidence rate of Valley Fever started  out around 25% among the military recruits,   but with efforts to limit dust exposure,  the rate of new infections dropped by half.

Unfortunately, this wasn’t the only damage  Valley Fever dealt during this epidemic. Because it was also spread through  Japanese internment camps. And while some papers report just 30  cases of Valley Fever in those camps,   we can be pretty sure that the  disease was underreported there.

The Japanese Americans who were incarcerated in  dusty areas were especially vulnerable to Valley   Fever, and did not receive the same public  health screening that the US soldiers had. Similarly, World War II prisoners of war were held   in very dusty and dry military camps in  Arizona…another hotbed for Valley Fever. Many of the prisoners were brought to  Arizona specifically for its dry climate,   because they all had…guess what…tuberculosis!

Oh sorry, is somebody talking about tuberculosis? Having tuberculosis made those prisoners of  war more susceptible to other infections,   and there were at least two  deaths from Valley Fever. We’ve learned a lot about disease prevention  and management over the past century.

But cases like this show how health  resources are not evenly distributed. But to make sure we end on even  more of a downer, let’s look at   a full-blown pandemic you probably have never heard of that is happening right now. When you think about early public health  measures, John Snow’s study of cholera…which   he did in the middle of history’s deadliest  cholera pandemic…might be top of mind.

After all, his groundbreaking work earned him  the title of the “Father of Epidemiology.”   Which might be not as impressive as whatever John Snow did  in George R. R. Martin’s book about the wall up there…  but I know he did some impressive stuff. Why are we talking about Game of Thrones in 2026?

While Snow’s investigation led to the  successful control of cholera in London   in 1854, that was not the last time the  world would suffer a cholera pandemic. In fact, unless the World Health Organization  announces otherwise after we have filmed   this episode, we are currently in the  middle of the seventh cholera pandemic. Cholera is a water-borne disease caused by a  species of bacteria called Vibrio cholerae, and   it’s not just something you can  die of in the Oregon Trail game.

This is a real disease. If you drink water contaminated with cholera,   you could end up with severe watery diarrhea,  which leads to life-threatening dehydration. Even though we’ve known about cholera for  centuries, and we know how to prevent it,   cholera cases are still on the rise.

The US might see only 20 cases a year or  so, but in places like Afghanistan and the   Democratic Republic of the Congo, we’re  looking at tens to hundreds of thousands. The disease still exists in large part because   of the lack of clean water and  proper sanitation facilities. In rural and impoverished communities especially,  not everyone has access to indoor plumbing and   sewage treatment plants that we know are  super important for cholera prevention.

We do have cholera vaccines. And vaccines, as you may have heard,  are great at preventing disease spread. They are what helped us eradicate  smallpox, all those list entries ago.

But there’s been a global cholera  vaccine shortage since 2022. So instead of the two doses a  person needs for full protection,   mass vaccination campaigns can only give out one. While the vaccines do work to prevent cholera,   the single-dose protection only  lasts for about three months.

And as if that weren’t enough, climate  change is adding fuel to this fire. The increase in natural disasters that  come with climate change… like floods,   droughts, and cyclones…devastate communities,  further reducing access to clean water. Like I said, it’s a downer to end on.

But it’s a good reminder that  you don’t just miss major   disease outbreaks because your school’s  history textbooks fail to mention them. You can miss major ones you’re  living through right now,   that will probably get left out  of future history textbooks, too! Kind of makes you feel a little sick, doesn’t it? [♪ OUTRO]