Germs-- we're all familiar with these little creepy crawlies that are invisible to the naked eye but can make us really sick.

But humanity didn't always know about these tiny microbes, viruses, and bacteria, commonly all grouped together as pathogens.

So what was the path to discovery that led us to realizing that tiny specimen even existed?

And what did we believe before and after the germ theory of disease was considered the norm?

Well, today on "Origin of Everything," we're gonna take a stroll down memory or history lane to look back on all the twists and turns that led to the first germ discoveries of the 19th and 20th centuries, and how these new revelations revolutionized the medical profession.

[upbeat music] So, what were some of the working theories of disease before we knew what actually makes us sick?

Well, hang on to your hats because some of these theories are gonna sound positively medieval, or ancient historical at the very least.

NPR's "Goats and Soda" does an interesting job of tracing the history of humans and disease.

In short, they note that early humans lived in forager and hunter societies, where they were migrating and living further apart.

As a result, though they were often exposed to disease from interacting with the animals they hunted for food, it was harder for these diseases to spread from human to human.

But with the rise of the domestication of animals and agriculture, humans began to settle down in fixed locations for long periods of time.

This led to the development of towns and cities where diseases could spread from person to person more rapidly.

But rather than deducing that living in close proximity to wild animals and other dirty humans may not be such a hot thing, they attributed it to the rise of "bad air."

One of the oldest and most commonly-held beliefs about the spread of disease was a practice known as miasma theory.

Miasma theory stated that disease was spread by miasmas, an outdated word that essentially means "bad air," or night air.

Miasmas were thought to emanate from foul-smelling and unsanitary living conditions like human waste-- yuck-- dirty water, and rotting food.

The thought went that these gross conditions gave rise to miasmas that went on to cause major illnesses, like cholera, malaria, and the plague, AKA black death.

And although this bad-air belief may seem odd to us today, it had a strangely long staying power.

The roots of miasma theory date back to ancient Greece, China, and Rome, and continued to be the prevalent theory of disease until the mid 19th century.

That's literally hundreds of years believing that disease most likely came from one place.

We now know that things like unclean water, interacting with human waste, and unsanitary living conditions can contribute to disease.

But we also know it's not from big clouds of bad air roaming through the streets.

However, there is historical evidence that other schools of thought existed, and these range from blaming illnesses on witchcraft to exposure to demons and devils.

Some also posit that certain religious rituals and rites, like hand washing, may have shown an early understanding of how illness spreads.

But those theories were less about disease and science and stem more from personally and culturally-held views.

Battling disease prior to the germ theory of disease's emergence in the 19th century was also equally misguided.

People resorted to drilling holes in people's head, bloodletting and leaching, arsenic, incantations, and a host of balms and salves that could work, but could also kill a person faster than the pathogens would.

But big changes came on the scene in the mid 19th century.

Scientists were having doubts regarding the not-totally-logical theories about disease spread, so they did what all good scientists do.

They conducted experiments.

Three important experimenters helped develop germ theory.

The first was French scientist Louis Pasteur, who in the mid-1800s demonstrated how yeast could cause fermentation.

This led to the invention of pasteurization, as you all know from your middle school science classes.

But it also led to an understanding that fermentation was a biological process involving living organisms.

The second was one of Pasteur's contemporaries, German physician Robert Koch, who believed that a microscopic organism was responsible for anthrax.

After much research, he saw the microbe Bacillus anthracis with his microscope, proving that a germ could cause a disease.

The third important contributor to germ theory was British physician Joseph Lister, who read Pasteur's research and conducted an experiment of his own, disinfecting bandages, medical instruments, and spaces where patients were seen.

He also began washing his hands.

These methods, of course, helped to keep patients healthier, and other doctors and researchers took note.

By the way, if you're interested in more about the history of hand washing, we have a video on that right here on our channel.

It'd be impossible to overstate the importance of the work of Pasteur, Koch, and Lister, and their contemporaries to the medical field.

The understanding that germs, primarily bacteria, viruses, fungi, and protozoa, are responsible for the spread of many diseases led to a massive acceleration in researchers identifying specific disease causes, preventers, and treatments.

And like the researchers before them, this new wave of scientists found inspiration in each other's work.

One scientist who piggybacked off of their findings was a physician named Patrick Manson.

In 1878, he demonstrated for the first time that insects can host germ-carrying parasites that cause diseases in humans.

His research then inspired a colleague, Dr. Ronald Ross, who discovered that mosquitoes were the ones spreading malaria to humans.

These were hugely important findings.

Now that people understood that they could get sick from insects, it was possible to mitigate epidemics of those diseases and start to work on cures.

Another disease that was causing major issues at the time was syphilis.

Syphilis had emerged in deadly outbreaks in Europe since at least the 1490s.

Famous philosopher Erasmus once called it, "The most destructive of all diseases."

In the early 20th century, two researchers, Paul Ehrlich and Sahachiro Hata, tested more than 900 chemical compounds on mice before they made their discovery.

Compound number 606 could kill the microbe responsible for syphilis.

This led to the release of the drug Salvarsan.

One of the researchers who immediately began giving Salvarsan to patients by inserting it into their veins-- a rare way of administering medicine at the time-- was physician Alexander Fleming.

That's right, the invention of Salvarsan led to Fleming's greatest discovery, penicillin, in 1928.

Being able to kill bacteria with antibiotics changed the world.

During the early 1900s, pneumonia had a reported 30% to 40% fatality rate.

And in a 2010 analysis of over one million elderly patients hospitalized in the U.S. with pneumonia, the mortality rate was 11% within 30 days of admissions.

And that's just one example of the positive consequences.

People can now take penicillin for a wide range of bacterial infections, but one of the disease-causing germs remained more mysterious-- the virus, which is perhaps surprising, considering molecular genetic researcher Lotti Tajouri has put it, "Viruses are the most common biological entities on Earth."

They're literally everywhere, including the one we're facing now, SARS-CoV-2, the virus behind COVID-19.

But viruses are smaller than bacteria and protozoa, so it wasn't until the early 1940s that we got clear photographs of them.

Most early discoveries regarding viruses actually came from botanists trying to better comprehend a virus that was going after tobacco plants.

The word "virus" was coined by a microbiologist studying that phenomenon who named it after the Latin term for "venom."

Though there were a few vaccines for viruses before the 20th century, that's the century that virus vaccines exploded.

Influenza got an effective vaccine in the 1940s.

One of the men responsible for its creation, physician and researcher Jonas Salk, went on to announce that he'd created a polio vaccine in 1953, a year after a polio epidemic in which 58,000 new diagnoses were reported in the U.S. A measles vaccine was released in 1963.

Up until that time, 48,000 Americans had been hospitalized with measles every year.

In 1964, there was a rubella epidemic in which 12.5 million Americans contracted the disease.

That same year, physician and researcher Stanley Plotkin developed the rubella vaccine.

It was a golden age.

In 1972, the "Natural History of Infectious Disease" textbook boldly claimed, "The most likely forecast "about the future of infectious disease is "that it will be very dull.

"There may be some wholly unexpected emergence "of a new and dangerous infectious disease, but nothing of the sort that has marked the last 50 years."

And indeed, humanity would continue to face pandemics, including the AIDS pandemic, as well as one that we're facing now, the COVID-19 pandemic.

Even though we continue to face new challenges, we can look back with hope on all of this progress.

Scientists figured out the genetic sequence of COVID-19, and just 63 days later, vaccines were being tested on people.

Director of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci, called that record pace.

And none other than 87-year-old Stanley Plotkin, the inventor of the rubella vaccine, is currently consulting for six companies that are working on coronavirus vaccines.

So, we continue to see the benefits of collective learning, dating all the way back to the original conceivers of germ theory, and who knows what problems this data we're now will help to solve in the future.