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Stefan: Infectious diseases have had some pretty major impacts on human history, and that's putting it mildly.  Take the Black Death of the middle ages, which wiped out more than 1/3 of of the population of Europe, or smallpox, which hitched a ride to the Americas on ships and decimated native peoples.  We've been haunted by microbial enemies, but sometimes, our drive to understand them has laid the foundations of modern science, so here are six of history's most devastating diseases and how they affected us in some pretty big ways. 

We'll start our list with plague, caused by the bacteria Yersinia pestis.  It's transmitted to people when they're bitten by fleas carried by rodents.  Most famous for the 14th century outbreak called the Black Death, plague bacteria actually caused three different forms of the disease.  You've probably heard of the most common one, bubonic plague.  It's when these bacteria target the lymphatic system, which helps protect your body from junk like toxins.  Between two and six days later, infected victims get a high fever, headaches, and vomiting, plus they get swollen lymph nodes called buboes, which give the plague its name. 

Bubonic plague causes plenty of damage on its own, but if it's left untreated, it can develop into another form, though these kinds can also occur on their own.  If the bacteria infect the bloodstream, it's called septicemic plague.  They can cause clots that keep blood from reaching tissues which turn black as they die, or if the microbes infect the lungs, it's called pneumonic plague.  This can lead to bloody coughs and rapid death and lets people transmit the plague through tiny droplets in the air.

Today, all forms of plague can be treated using antibiotics, but they used to kill half of more of infected patients, which had some huge effects on society.  The first confirmed plague epidemic was called the Justinian plague.  It swept through the Roman empire starting in 541 CE and contributed to its fall.  In the Roman capital of Constantinople, it's estimated that upwards of 5,000 people per day were killed at its peak.  The second big wave reached Europe in 1347, when merchant ships arrived in Italy full of sick sailors.  The Black Death swept through the continent in just a few years, and during that time, it's estimated that a quarter to half of all Europeans died, some 25 million people.

Over the next couple centuries, Plague kept cropping up, and the first quarantines were implemented.  At the time, it was thought that infectious diseases were transmitted by bad air, so officials tried to isolate sick people and those traveling from places that had an outbreak to prevent more deaths, and even though the science was wrong, quarantines helped prevent the spread of pneumonic plague between people and control the rats with fleas that carried plague bacteria.  The last huge wave of outbreaks began in 1894 in rural China, sweeping through Asia and Australia, and finally after a few decades, scientists discovered the bacteria and carriers behind it all, which let us start squashing out this disease.

Smallpox was also a major cause of death in the past and killed nearly 30% of all people who had it.  It's a disease caused by the variola virus, which starts with high fever and headache.  Then, small bumps full of infectious fluid appear all over.  Those are the pox, and in survivors, they eventually scab and turn into scars.  Humans infected each other through tiny droplets coughed or sneezed through the air, but in a super gross twist, the pox fluids and crusty scabs got all over clothes and blankets and could infect new hosts, too.

Now, smallpox was devastating for lots of human history, but it hit especially hard when colonists from Europe invaded the Americas. The native populations had immune systems that were adapted to fight off local diseases, not foreign ones.  So the variola virus infected and killed huge numbers of them.  Overall, diseases like smallpox may have caused the death of up to 90% of the native American population.  Smallpox likely helped the Spanish conquer the Aztec empire, too.

Though it's not nearly on the same scale, the European colonists were also hurt by the disease.  Like, some estimates think that George Washington lost more troops to the smallpox epidemic of 1775-1782 than in battle during the Revolutionary War.  Casualty rates got a little better after an army-wide variolation or intentionally infecting people with a bit of gunk from a patient's scabs to hopefully help them build immunity.  Exposing people to the virus in a controlled way ended up being safer than normal, but they still suffer from some symptoms and there was a risk of death.

Later, doctors tried to make it less dangerous by using people or animals infected with cowpox, a less harmful cousin of smallpox caused by the (?~4:11) virus.  This process was called vaccination and led to the eradication of smallpox and to all the vaccines we rely on today.

Speaking of diseases that crossed oceans, let's talk about syphilis.  Scientists think this sexually transmitted bacterial infection may have made its way to Europe in colonists returning from the Americas.  It's caused by Treponema pallidum bacteria and the initial symptoms aren't fun: rashes, fever, sores, headaches, and muscle pain.  It's transmitted by direct contact with the sores or passed down from an infected mother to her child.  After a few weeks or month, though, the rashes and sores disappear and the disease goes into a latent stage where it can be detected in a blood test, but it doesn't cause any symptoms, and in up to a third of untreated cases, the disease comes roaring back to cause dementia, dysfunction of multiple organs, lots of pain, and death.

The first recorded outbreak of syphilis began in 1495, after a victory celebration by the French army with infected sex workers, so the people of the time started to call it the French disease, and it was pretty deadly, possibly because the disease was new to Europe and people didn't have any immune resistance to it. It's hard to say how many people syphilis killed because we didn't have any medical records that tracked cause of death, not to mention, sexually transmitted infections were considered shameful, so many people tried to hide them or pass them off as other things like leprosy.

What we do know is that the disease ravaged the world until one of the first antibiotics ever developed put an end to it.  Around the turn of the 20th century, the immunologist Dr. Paul Ehrlich had discovered that certain dyes only bonded to specific types of cells in his lab.  This finding led him to believe that certain compounds could target disease-causing agents like bacteria without attacking healthy tissues, a treatment that would later be called chemotherapy.  Using a systematic screening process, Ehrlich found a chemical that he developed into an anti-syphilitic drug called Salvarsan.  It quickly became the most prescribed drug in the world and the process that led to its discovery earned Ehrlich the Nobel Prize in Physiology or Medicine in 1908.

Caused by a bacterium called Vibrio cholerae, cholera is a severe gastrointestinal disease that causes vomiting and diarrhea.  As soon as 12 hours after infection, these bacteria produce toxins that bind to small intestine enzymes that control water secretion from the rest of the body.  Specifically, the toxin makes these enzymes flood the intestines with water, and that leads to dehydration so severe that it's deadly.  There were reports of similar sounding diseases in India as early as 1000 CE, but cholera didn't become a global problem until the 19th century, when widespread traits started happening.

Cholera caused a lot of fear wherever it went, and even today it's a public health problem with estimated millions of cases a year and 100,000 deaths.  Nowadays, we know that cholera is spread through drinking water that's been contaminated by infected poop particles, but when it hit England in the 1830s, medicine was ruled by the idea that disease, whether it's Black Plague or cholera, was caused by bad air from corpses, impure people, or even from swamps.  So in 1854 when a doctor named John Snow traced almost every victim of a cholera outbreak in London to a single water pump, nobody really believed him.  Town officials removed the pump's handle, which kept people from drinking that water to humor him, and new cases of cholera dropped off sharply, but people still didn't buy his ideas until a local minister set out to prove him wrong, and that failed spectacularly.  His report actually ended up tracing the outbreak to a dirty diaper from a baby who'd contracted cholera outside of London.  Dr. Snow's revolutionary methods to track infection patterns and find the source of an outbreak is why he's considered one of the fathers of modern epidemiology.  So it turns this John Snow might have known something after all.

Mosquitoes are a well-known pest when it comes to spreading disease and yellow fever is no exception.  It's a viral infection and most people infected with flavivirus experience symptoms like fever, chills, aches, fatigue, and vomiting.  An unlucky 15% or so of patients have it much worse, with bleeding, jaundice, and multi-organ failure, which can lead to death.  Today, we have a vaccine for yellow fever, but that wasn't the case in the 1880s when the French started building the Panama Canal.  We knew that yellow fever was a thing, but not how it was transmitted, so we couldn't stop people from getting sick.  

More than 20,000 workers died of either yellow fever or malaria or a fun combination of both, so the French quit construction in 1889.  It wasn't until the 1900s that we discovered mosquitoes were the culprit and the US was able to fight the disease and finish the canal.  They drained pools of water near towns and houses, which is where mosquitoes lay their eggs, and they covered water that they couldn't drain with films of oil to smother the larva that had already hatched, and they dumped pesticides everywhere else, trying to kill all the mosquitoes they could find.

The last disease in our list is a bit different from the others.  It's not transmitted, it's inherited, and that's why it used to be called the royal disease.  Hemophilia is a disorder that makes it hard to form blood clots, causing victims to bleed out from minor wounds that would normally seal up.  Humans have 20 different proteins that help form blood clots, but hemophilia is caused by problems in just two, and both of the genes involved are on the X chromosome.  

Humans have 22 pairs of non-sex chromosomes, so you have two copies of each gene, plus a 23rd pair that's usually either XX or XY, and you get half of your genes from each parent.  For a dominant trait, you just need one of your two genes to express the trait, like having a widow's peak.  Recessive traits, on the other hand, need two copies to be expressed, so people can have only one copy, not express the trait, and still pass it on to their kids.  They're called carriers.  

Now, recessive traits on sex chromosomes can work a little differently, because they're not necessarily identical.  People who are XY don't have a backup copy of either set of genes, so recessive diseases caused by genes on the X chromosome just get expressed, and that's exactly what happened with hemophilia.  Historically, to try and remain purebloods, the royal families of Europe were notorious for incest, and two related people have a higher chance of both being carriers for the same recessive trait, because they share more genes than un-related people.

Queen Victoria of England was a carrier for hemophilia, and one son and three grandsons bled out from minor injuries by early adulthood.  The most famous of her dangerously bleeding descendents was the Russian prince Alexei Romanov.  

The Romanov family kept their only heir's sickness a secret, not wanting to appear weak, and they put their trust in the so-called magical healing abilities of Siberian Grigori Rasputin.  The perceived influence Rasputin had over the royal family led to tension with the general public and may have hastened the execution of the royal family in 1918 during the Russian Revolution.  So maybe recessive disorders are why the Lannisters and Targaryens are so messed up.  The perceived influence Rasputin had over the royal family led to tension with the general public and may have hastened the execution of the royal family in 1918 during the Russian Revolution.  

So history is shaped by lots of forces, especially things like human health.  These six diseases caused widespread death, changed societies, and revolutionized what we know about medicine in ways that still impact us today.  

Thanks for watching this episode of SciShow, which is produced by Complexly, a group of people who believe the more we learn, the better we get at being humans.  If you want to learn more about human health, check out one of our sister channels, Healthcare Triage, at Youtube.com/HealthcareTriage.

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