for twelve straight hours Straight? Single-celled organisms. AKA microbes, germs, the tiny machines

that allow us to digest—and can kill us. “What is life?” Turns out, life is relentless,

everywhere on earth!

[Intro Music Plays]

Microbes are invisible: they're single cells.

So to understand microbes—that is, to do microbiology—scientists first needed to

study cells.

German botanist Matthias Schleiden and physiologist Theodor Schwann

proposed a modern cell theory around 1837: every living thing

is made up of one or more cells. So the cell was the fundamental unit of life, the thing

that gives structure to all forms of life. Amazingly, Schleiden—who studied plants—and

Schwann—who studied animals—both noticed tiny dots in the middles of the cells they

looked at under their microscopes. These nuclei must somehow be important to all life, they figured—correctly.

Darwin's chief public defender, Thomas Henry

Huxley, also wrote a article called “The Cell–Theory” in 1853.

Where the Germans were cataloging different microscopic forms, Huxley proposed a mechanistic

model: cells are little factories with different parts that have different functions. Their

functions make the parts add up into an organic whole.

Not every scientist believed cell theory right away, but many came around, as microscope-enabled

evidence mounted.

And yet, being able to observe single-celled organisms didn't immediately lead scientists

to connect them to disease. In fact, medicine in the early 1800s mostly

worked the way it had hundreds or even a thousand years earlier. It was still all about liquids

called humors. But some diseases were understood differently.

These were caused by a kind of invisible badness in the environment called a miasma.

According to miasma theory, diseases were caused by foul-smelling airs that came from

rotting meats, swamps, and other putrefying sources.

Before you knock it, think about it: this theory mostly works. Dangerous microbes grow

on smelly, dirty stuff. The smell is a byproduct of the microbes' eating organic matter.

But even today, we can't see these microbes without instruments. So following our unaided

senses is still smart: don't eat gross trash!

Sniff the turkey before you eat it. And then, just eat it anyway like I did this morning.

By the mid-1800s, however, a few scientific rebels were pushing a germ theory of disease. This holds that germs, or pathogenic microorganisms,

cause infectious diseases. [Snow]

Around this time, a nasty germ called Vibrio cholerae provided

an opportunity to test the theory out.h Cholera had ravaged England since the germ

started to travel widely out of south Asia in the early 1800s, hitching rides on the

expanding armada of merchant ships. Empire had all kinds of unpredicted downsides.

In 1854, a bad cholera epidemic hit Broad Street in the Soho neighborhood of London,

killing over six hundred people. One doctor named John Snow had a hunch about what was

going on. Snow created a map of the outbreak and noted

that the cases seemed to cluster around one public well. He hypothesized that cholera

microbes were rapidly multiplying in its water. So he convinced the Soho council to remove

the well's pump handle. People went elsewhere for water, and the cholera infections decreased.

John Snow became a hero! Saving Lives! Even though, it turned out, the outbreak was already in decline when

he removed the handle. Thus proving that some John Snows, do know

somethings.

Snow's quick thinking didn't really prove germ theory. For germs to replace miasmas

in their minds, scientists would require a better model of what germs are, and how they

behave. For that, we turn to one of the first experimental

microbiologists and a dude whose name you probably should know from milk labels: Louis Pasteur

Born in France in 1822—the same year as

Galton—Pasteur was a chemist, not a physician. But he is known for his work on germs and

health. Pasteur is credited as the co-founder of microbiology

and the founder of modern zymology, the science of fermentation. Fermentation

is the biological and chemical process needed to make beer, wine, yogurt, cheese, bread,

and many other foods. ThoughtBubble, show us what that means.

Chemically, fermentation is the conversion of sugar molecules into ethanol, or alcohol,

and carbon dioxide. In food, this usually happens thanks to bacteria

or yeast. Looking good, Saccharomyces! Pasteur first connected yeast to the fermentation

of wine in 1857. He observed that microscopic yeast on grape skins makes grape juice ferment

into wine. If you sterilize the skins, killing the yeast, fermentation won't happen.

Pasteur even made the the analogy that the microbes growing in wine and beer were similar

to the microbes causing diseases in humans and animals. He hypothesized that microbes

are everywhere and must be responsible for all kinds of phenomena, like making food spoil.

So in 1865, he patented a process in which liquids such as milk were heated to a temperature

between sixty and one hundred degrees Celsius in order to kill microbes. This became known

as pasteurization. It may sound kinda simple, but this was revolutionary!

Earlier, Nicolas Appert had invented canning to make foods safe, so Napoleon could fight

wars for longer. But Pasteur's method used a lower temperature, thus preserving tastes

and textures. Related to this idea of killing bad germs,

Pasteur also helped develop hygienic medical practices, along with British surgeon Joseph

Lister. No germs in the operating room! Most importantly for the history of biology,

Pasteur got tangled up in a debate with a fellow scientist named Félix Pouchet

who believed that living things spawn naturally from certain environments. This widely held

belief was called spontaneous generation.

Pasteur, based on his observations of grapes, reasoned that living things can only grow

from other living things. So he created an ingenious experiment to prove the theory of

biogenesis, or life from life. Pasteur showed that no germs would grow in

sealed, sterilized long-necked flasks full of beef broth. But in sterilized but open

flasks, microbes would eventually show up.

Thanks Thoughtbubble. After proving biogenesis, in the 1870s, Pasteur worked on immunology

and vaccination. Pasteur's work with the rabies and anthrax microbes supported the

germ theory and its use in medicine: if you could identify a microorganism, you could

give someone a weakened version of it, or vaccine, and the patient taking the vaccine

would develop immunity to the real bug. And in 1879, Pasteur developed the first lab-manufactured

vaccine, for chicken cholera. It was around this time that germ theory was

finally widely accepted, in part due to Pasteur's work.

But Pasteur's ethics were questionable: when rabies vaccines for humans rolled out,

Pasteur kept his data on their effectiveness secret. He even kept secret mortality data,

or how many people his vaccines didn't help. So unlike today, in Pasteur's time, it wasn't

necessarily a norm that useful medical research should be shared publicly.

But Pasteur was not the only notable germ

wrangler. Born in 1843, the German physician Robert Koch painstakingly worked

at a microscope to definitively establish the germ concept of disease.

He identified different microbes, becoming the leader of a large research team in Berlin.

They founded the discipline of bacteriology, or the study of bacteria, particularly in

relation to human health. In the late 1880s and '90s, Koch and his

team traveled into areas experiencing epidemics, including India and Egypt, to identify the

microbes causing diseases there. By ID-ing these microorganisms, they hoped to create

vaccines. First, Koch proved that the anthrax germ causes

anthrax-the-disease. Later, he identified the bacterium that causes tuberculosis or

TB, which was a very widespread disease. Koch also characterized cholera, vindicating

the work of John Snow by showing that the bacterium lives naturally in the small intestine

of humans. Snow wasn't just high on ether: he'd correctly guessed how cholera spreads!

Eventually, Koch's team contributed to the identification of the germs that causes diphtheria,

typhoid, pneumonia, gonorrhea, meningitis, whooping cough, tetanus, plague, leprosy,

and syphilis. …I would not want to borrow this dude's

lucky microscope!

It's been through a lot!

Through this work, Koch developed the four postulates or steps for identifying infectious

diseases. One, the microorganism must always be present,

in every case of the disease.

Two, the germ must be able to be isolated from a host containing the disease and grown

in a lab, in a “culture.” Three, samples taken from the culture must

cause the same disease when introduced into a healthy model animal like a mouse.

Four, the germ must be isolated from that new animal, meaning it is the same organism

that caused the disease in the original host.

So structure matters: in all infections, germs grow out of hand, throwing the body out of

whack and causing inflammation. These bad germs, or pathogens, develop and live within

us, and can kill us. But with Pasteur's vaccines and Koch's

scientific method of ID-ing bacteria, humans could now develop medicines to fight jerk-sauce

germs. Go team us!

Back in the world of multicellular organisms, another scientist at the intersection of biology

and medicine was exploring the structure of living things.

In 1892, German-American physiologist Jacques Loeb began his experiments

on embryonic development, or how organisms grow from single-celled embryos into whatever

they're supposed to look like. So he started dunking sea urchin embryos into

different salt solutions. And, in 1899, he got one to give birth… just from being salty!

Loeb's artificial parthenogenesis, or birth from the self, was mega-astounding news. It

raised basic questions, such as what is sex? Could a human one day give birth by herself…

or him-self? Causing sea urchins to give virgin births made Loeb a celebrity.

But for the history of biology, it was revolutionary that Loeb's sense of scientific understanding

of life was tied to his ability to control it. His work with sea urchins can be seen

as an early form of bioengineering, or treating cells and tissues as machine-parts to be used

constructively by a human designer. Loeb's notable students included the behavioral

psychologists, B. F. Skinner and J. B. Watson, and a creator of birth control, Gregory Pincus.

Biology, like other scientific disciplines, shows a historical arc from observations to

experiments, and from less control to more. From the mid-1800s to the early 1900s, scientists

moved from mostly believing that living things spontaneously appear out of nowhere to controlling

fermentation on a massive scale. Cheers to that!

Next time—we'll add the missing mechanism to this crazy Rube Goldberg machine we call

biology: it's time for a monk named Mendel to accidentally figure out genetic variation—in

mice, men, and peas. Crash Course History of Science is filmed

in the Dr. Cheryl C. Kinney studio in Missoula, Montana and it's made with the help of all

this nice people and our animation team is Thought Cafe.

Crash Course is a Complexly production. If you wanna keep imagining the world complexly

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