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In the 14th century, the Black Death spread throughout the old world, wiping out somewhere between a quarter and half of all the people living in Eurasia at the time. And that put the plague right up there with smallpox as one of the deadliest diseases our species has ever faced.

But, of course, nobody gets smallpox any more. Literally nobody: it’s been eradicated. You would think the Black Death is one of those diseases left in the dustbin of history, too.

But the plague is alive and well, and while it’s not causing world-changing epidemics any more, it’s still a problem. It turns out we’re still learning a lot about this infamous bacterium, and the new intel might help scientists determine if it will ever go all medieval on us again. The plague is caused by the bacterium Yersinia pestis.

It evolved from a mild gut bug sometime in the last ten thousand years. And it’s been plaguing us since at least 541 CE, when it picked up a mutated version of a gene called Pla, a protein-cutting enzyme that allowed it to infect more of the body and spread more virulently than its older cousin. Now, there are actually three types of plague.

Bubonic plague is when it infects the lymph nodes, causing them to swell up as painful buboes. If the infection spreads to the bloodstream, it becomes septicemic plague. But the form of most concern to public health professionals is pneumonic plague, which is when it infects the respiratory tract.

It’s more deadly than the other forms, and it can more easily spread from person to person directly because infected people send bacteria-filled droplets into the air when they cough. And that’s a big deal because usually, the bacteria move around thanks to the help of other critters, called vectors. The plague is a zoonotic disease, meaning it can spread between humans and animals.

And while rats are usually blamed for the spread of plague, the actual vectors are biting parasites like fleas, which carry the bacteria in their guts. In fact, a study in January of 2018 suggested that the fleas and lice which spread the Black Death may have mostly been dining on humans rather than frequently jumping between rodents and people. But rodents can get the plague and act as carriers, meaning it can hide in their population while it’s not infecting us, something that definitely did happen back then, and still happens now.

Fortunately, all forms of the plague are treatable with antibiotics. The challenge is catching it in time, since its early symptoms often resemble the flu. And doctors, well, when they see flu-like symptoms, they guess “flu” before they guess “the actual, literal plague.” So could the plague ever mount a Michael Jordan-style comeback?

Well, for people in some parts of the world, “back” is the wrong word. The plague is native to parts of North and South America, Africa, and Asia. And though it isn’t wiping out a third of the world’s population like it used to, it does still cause serious outbreaks in places like Madagascar, and there are a couple thousand cases reported every year.

And that’s in part because of those furry carriers. It’s neither feasible nor desirable to wipe out all the animal reservoirs the plague can hide in. Like rats.

And ferrets. And cute little kitties. And unlike with smallpox, good plague vaccines don’t exist.

At least one promising one is in development, but prior to that, existing vaccines could cause nasty reactions, had to be re-upped frequently, and they didn’t really work very well anyway. A real triple crown. Even today, scientists are still unlocking the plague’s nasty little secrets.

It wasn’t until 2015 that a study published in PLOS Pathogens described how the bacterium could make its way from a tiny, shallow flea bite to your lymph nodes. Since it’s still around, the short answer is yes, the plague could rise again. Luckily, modern hygiene and clinical practices generally keep it in check.

We’re usually able to get anyone who’s coughing up plague-laced sputum off the street before they encounter too many other people. So person-to-person transmission has become blessedly rare. And we don’t tend to interact so much with flea-infested animals.

But the real game-changer has been those antibiotics. And that’s where the potential for a modern outbreak becomes a little more of a reality. See, in 1995, researchers raised red flags over the discovery of strains of the plague that were resistant to some antibiotics, which would make for an extremely deadly outbreak and is therefore a perfectly reasonable thing to raise red flags over.

However, these drug-resistant strains haven’t caused much trouble yet. That’s partially because it actually seems to be difficult for the plague bacterium to acquire antibiotic resistance. Drug resistance is often transmitted among bacteria on small, circular snippets of DNA called plasmids.

Plague bacteria have to pick up these resistance-conferring plasmids from another bacteria, but they just don’t seem to run into resistant bugs that often in nature. And unlike humans, rodent populations don’t frequently encounter antibiotics. So there doesn’t seem to be an evolutionary advantage ensuring that the plague bacteria will hang on to drug resistance even if they do pick it up.

But, if there was to be a global pandemic, it would most likely be from a resistant strain, or from one modified for bioterrorism. There’s actually a really long history of using the plague as a weapon. Armies used to catapult corpses over the walls during sieges to help thin the defenses.

But doctors, scientists, and military personnel have plans in place in case anyone does try to modernize that strategy. And anyone who would even consider such a thing would be violating several international agreements. Short of these two scenarios, a 21st-century Black Death-like epidemic is pretty unlikely.

That doesn’t mean the plague isn’t a problem for the thousands of people who do catch it every year. But fortunately, by developing better vaccines and continuing to study the bacterium responsible, we're working on beating it back for good. Thanks for watching this episode of SciShow!

If you enjoyed learning about the Black Death, you might like our episode about how it and five other diseases totally changed the course of human history. [♪ OUTRO].