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Epidemiologists are always trying to get one step ahead of the next big outbreak - and often the best clues we have come from outbreaks of the past.

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Adam Brainard, Greg, Alex Hackman. Sam Lutfi, D.A. Noe, الخليفي سلطان, Piya Shedden, KatieMarie Magnone, Scott Satovsky Jr, Charles Southerland, Patrick D. Ashmore, charles george, Kevin Bealer, Chris Peters
The Great Dying
The Justinian Plague
The Antonine Plague
The Plague of Athens
Earliest Known Plague

Image Sources:,_France_1720-1721.jpg
[♪ INTRO].

Epidemiologists—the scientists who track the incidence and spread of diseases—are always on the lookout for the next big outbreak. But predicting the future is tricky.

So, to better understand how epidemics get started and how to counteract them, they often study examples from the past. Deadly diseases have been literally plaguing humanity for as long as we've existed, so there's a lot of material to work with—if you can piece together what happened. And sometimes, they can, even for outbreaks that occurred hundreds or thousands of years ago.

So today, we're going to talk about 6 of human history's most fascinating – and terrifying – ancient outbreaks. When the European colonists aboard the Mayflower arrived in what is now New England, they found an eerie landscape with recently abandoned villages and the bones of thousands of people. They later learned the ghost towns were from a disease called the “Great Dying.” See, Massachusetts and Rhode Island are the homelands of the Wampanoag Nation.

Over 20,000 people were thought to be living there at the turn of the 17th century. But between 1616 and 1619, a mysterious disease devastated these coastal settlements. Reports from the time described symptoms like yellowed skin, fevers, intense nosebleeds, and skin lesions.

And many of these cases were fatal. Estimates of the Wampanoag death toll range from 30% of the population to as high as 90% of it. And lots of diseases have been proposed to explain this outbreak, including smallpox, influenza, and yellow fever.

But none of those seems to quite fit all of the reported symptoms. And that's led epidemiologists to an unconventional suspect: leptospirosis. It's caused by spiral-shaped bacteria that live inside animals, especially rodents, and are spread around when the animals' pee.

A 2010 study noted that the symptoms of the Wampanoag epidemic are similar to some recent leptospirosis outbreaks in Japan and Europe. And the Wampanoag had some habits that might have made them susceptible to picking up the bacteria from contaminated soils or waters, like walking around barefoot and bathing — neither of which were very popular among the Europeans of the time. We can't say for sure that it's leptospirosis though, because although there were plenty of remains in the early 1600s, no bodies from the outbreak have been found recently.

The acidic soils of the region simply aren't very good for preserving the remains of humans or wildlife—they dissolve things too quickly. So even though it's a fairly recent outbreak historically-speaking, scientists haven't been able to run DNA tests to pinpoint the pathogen. And leptospirosis isn't a perfect explanation.

Some scientists have pointed out that these bacteria might not have been able to survive the winters in New England well enough to cause this kind of outbreak. Hopefully, further evidence will help epidemiologists suss out the truth. Because there is some worry that leptospirosis and other tropical diseases may become more common as climate change brings warmer temperatures and more frequent flooding to northern regions.

And if it was leptospirosis, this ancient case could provide valuable insights into how the disease spreads through northern ecosystems. For now, though, the Great Dying will remain a mystery. The 1500s were a rough time for Indigenous Mexicans.

Besides the arrival of European colonists and smallpox, the 16th Century also saw at least three major epidemics of a devastating and mysterious disease known as cocoliztli, a word in the native Nahuatl language meaning “pest.” The very worst of those outbreaks began in 1545. In just three years, this disease killed as many as 15 million people, wiping out as much as 80% of the Indigenous Mexican population. And the repeated outbreaks were devastating.

Numbers plummeted from about 25 million people to just 1 million by the end of the century. Reports by a Spanish physician describe a grim set of symptoms, including fevers, intestinal distress, black tongues, and black urine. And victims usually died within three to four days.

Once again, the identity of the disease has been the subject of debate. A 2002 study likened the symptoms to hemorrhagic fevers—like, the disease caused by hantavirus. Because the most severe cases of cocoliztli occurred in the highlands, and not on the coast when Spanish colonizers landed, the researchers suggested that the pathogen was probably native to Mexico and not introduced.

But a 2018 study examined tooth pulp from 24 bodies from a Mexican cemetery dating to the first cocoliztli epidemic, and they found bacterial DNA belonging to the strain of Salmonella that causes paratyphoid fever. Today, paratyphoid and typhoid fever cause more than 200,000 deaths per year around the globe. And a similar form of Salmonella has been found in the DNA of earlier Europeans in Norway, so the authors suggested cocoliztli was caused by an introduced pathogen.

But it's not an open and shut case. Some scientists have pointed out that the symptoms don't really fit a Salmonella infection. Also, the method used to detect the bacteria wouldn't have spotted an RNA-based virus like hantavirus, and it can only detect pathogens we have DNA sequences for now, as it relies on a global database.

So it could be that the team detected an unrelated Salmonella outbreak, or that it was only a contributor to an epidemic driven by pathogens we haven't found yet. Further studies will be needed to sort this all out. Pinpointing the pathogens in cases like this is especially important because the disease might not be a thing of the past.

The authors of that 2002 study make the horrifying point that the pathogen may not be extinct, but instead lying in wait until the right conditions come around again. In the year 541, during the rule of Roman emperor Justinian I, something went terribly wrong in Constantinople, the capital city of his Byzantine Empire. Residents began to suffer horrible bouts of delusions, fevers, and swelling in their groins and armpits, often leading to death.

By the next year, it's estimated that there were between 5,000 and 10,000 deaths per day in the capital. And this outbreak wasn't just an epidemic. It spread to multiple countries all around the Mediterranean Sea, making it a full-blown pandemic.

It has been named the Justinian Plague, and it's estimated to have killed between 25 and 50 million people, making it one of the worst disease outbreaks in human history. And thanks to ancient DNA research, we actually have a good idea of which pathogen was to blame. It turns out the Justinian Plague was just the plague!

A 2013 study pulled DNA from two bodies in Germany dating to the time of the Justinian. Plague, and found the genetic signature of the bacterium Yersinia pestis—the bacterium responsible for the infamous Black Death. But it wasn't exactly the same as the plague which ravaged 14th century Europe.

DNA studies comparing modern and ancient plagues have found that the Justinian Plague and the. Black Death were caused by two different strains. And yet another different strain caused a third plague pandemic in the 19th and 20th Centuries.

This series of horrifying events has taught epidemiologists never to count out Yersinia pestis. Since the bacteria lives in fleas that hang out on rats, rodent populations can act as reservoirs, holding onto the plague until it's ready for another outbreak. As horrible as all that sounds, these ancient examples might reveal predictable patterns in plague cases.

Which is important because the bacteria are still around infecting people today. And scientists have noticed that all three major plague outbreaks are associated with times of unusually high rainfall, and that these strains of ancient plagues tend to share certain genetic mutations that might have something to do with how well they spread. So more studies of ancient plagues might give us the tools we need to predict the next big outbreak.

Justinian I wasn't the first Roman emperor to see his dominion ruined by disease. A similar outbreak happened under the rule of Marcus Aurelius Antoninus. In the year 165, Roman soldiers returning from Mesopotamia brought back more than war stories.

They probably also carried the pathogen that would cause the Great Pestilence, now known as the Antonine Plague. The symptoms of this disease, as described by the Greek physician Galen, included fever, bloody stool, blistering rashes, and skin pustules. And the pandemic spread to parts of Europe, Asia, and North Africa, ultimately causing the deaths of as many as 10 million people.

As of yet, there are no DNA samples to help pinpoint any pathogens, so all epidemiologists have to go off of are Galen's descriptions—which aren't very detailed. Usually, though, a nasty, deadly disease with a skin rash means one of two things: measles or smallpox. And scientists have actually ruled out measles, because a 2010 study on its evolution found that it's a fairly new problem.

They compared the measles virus to one of its closest relatives, the rinderpest virus, which infects cattle and their relatives. And their evolutionary models suggested that the two didn't split from their common ancestor until around the 11th or 12th century—too late to have caused the Antonine Plague. Of course, smallpox could still explain the rashes and pustules described—so it's the leading guess.

It would be nice to know the disease behind this outbreak for sure, though, since it had such a dramatic impact on the empire. The Roman army is estimated to have experienced a death rate as high as 15%. And some scholars argue that the pandemic was followed by a decline in business and trade across the empire.

Some have even suggested that this period of crisis may have laid the foundations for the eventual fall of the Roma n Empire. If smallpox was really behind this, then that's great news for us though, because Smallpox is now extinct! It was wiped out by the worldwide Smallpox Eradication Program of the 1960s and 70s.

But if it wasn't smallpox, then we should really figure out what it was... in case it breaks out again someday. One of the oldest outbreaks we know of struck Athens, Greece in the summer of 430 BCE. According to reports of the time, the malady started in Africa, but its impact in Greece gave it its name: the Plague of Athens.

The only account of this epidemic is found in the writings of the Greek historian Thucydides. By his description, the residents of Athens were overcome by fevers, redness in the eyes, bloody tongues and throats, ulcers, and more. Over just five years, as many as 100,000 people in the city died of this disease.

That's around 25 percent of the population. Thucydides also describes another side effect of the outbreak: widespread fear, panic, and lawlessness! Like the other outbreaks, many diseases have been accused, but none confirmed.

A 2006 study tested DNA in bodies from a mass burial in Lithuania dating to the year of the epidemic. They were looking for evidence of suspected bacterial agents, including the plague, typhus, tuberculosis, and anthrax. And they didn't find any of those, but they did find DNA which they identified as the strain of Salmonella that causes typhoid fever.

But later re-analysis found that it was only a distant relative of the typhoid bacteria, and that it might actually have been contaminant from the soil, not an infection. A study in 2015 suggested a virus was responsible instead. They argued that the symptoms are a much better match to ebola, but testing for that is tricky.

Ebola can't be identified with a DNA sample because it has none of its own. So we would need to look for the other important genetic molecule: RNA. But RNA breaks down much more quickly than DNA, making it much rarer in the archaeological record.

Even at sites with great preservation conditions, it can be easy to miss. Still, with improving technology and a little bit of luck, we might be able to test for it in ancient remains from Athens. After all, it wasn't too long ago that researchers doubted we'd ever be able to find viral evidence from remains that were more than several hundred years old.

But, a 2018 study found hepatitis B viral DNA in human remains from almost 4,500 years ago! And researchers have pulled viral RNA from ice cores that date back thousands, even hundreds of thousands of years. The technology we use to study ancient DNA and RNA is only getting better as scientists strive to understand human evolution and disease.

So deducing the real culprit of the Plague of Athens may actually be possible… someday. And if it was ebola or a related virus, it could provide unique insights into their epidemics, and maybe even help predict or prevent new outbreaks. Now this last one is so mysterious we're not even sure there was an epidemic at all.

Thousands of years ago, when farming first spread across Europe and Asia, it led to increased populations and newly-advanced civilizations. This included the establishment of mega-settlements in places like Romania and Ukraine. These were cities that could hold more than 10,000 people, which was pretty impressive for the time.

But starting around 4000 to 3000 BCE, they just… disappeared. Mega-settlements apparently stopped being built, and the old ones were abandoned. This time period is sometimes called the Neolithic Decline, as populations across Europe seemed to nosedive - and exactly why this happened isn't clear.

One common hypothesis is that the expanding populations grew too quickly, overexploited the resources in the environment, and then collapsed. It's also been suggested that conflicts broke out between different cultures. But others have wondered if a disease could be to blame—especially since it could also explain why the mega-settlements were abandoned.

And a 2018 study found the first DNA evidence in support of this idea. When the researchers analyzed DNA from two people found in a mass grave in Sweden dating to around 3000 BCE, they found deadly bacterial DNA in one of them—specifically, the DNA of our old friend Yersinia pestis. This is the oldest known strain of the plague, and it suggests this deadly disease was active all the way back then.

And those hugely populated settlements would have been great places for an epidemic to start and to spread. If this really was a plague outbreak, it would be the oldest one known, pre-dating the Justinian. Plague by a good 3,500 years.

But... we'll need more evidence to demonstrate that there was an epidemic, or that an epidemic was involved in the sudden population drop all over. Which mostly means finding more mass graves from the time period. If we can identify a disease, though—the plague, or otherwise—then the Neolithic.

Decline could be added to our growing list of epidemiological case studies. And the pathogen behind it would be especially interesting to examine, as it might be a nemesis that's been following us around for thousands of years. Or it might be one we've already defeated—and even that could teach us a lot about cycles of disease and why some pathogens stand the test of time while others don't.

Delving into our history of deadly diseases may sound a little disturbing, but we should hope that historians and epidemiologists continue to explore these terrifying case studies. Because, every epidemic is an opportunity to find the kinds of patterns that can help us determine the factors — whether they're genetic, environmental, or cultural — which allow major disease to strike over and over. And that, in turn, provides us with clues as to how can we get ahead of them.

So by studying outbreaks of the past, we can maybe learn to predict and mitigate the outbreaks of the future. Thanks for watching this episode of SciShow! And a special thanks as always to all of you who help support what we do, including our.

Channel Members and Patreon Patrons. If you liked learning about pathogens from the past, I suggest checking out our episode on diseases that altered the course of history. [♪ OUTRO].