How Studying Bacteria Almost Kept Us From Discovering the Flu

{♫Intro♫} If you’re coughing, sneezing, or starting
to feel under the weather, you might blame a virus, or possibly a bacterium. Which is not something humans have known to
do for very long. Around 400 B.C.E., doctors might have blamed
an imbalance of the four vital humors for your illness. Around the 1700s, they might have pointed
to an invisible, disease-carrying fog instead. Today, we know pathogens — viruses, bacteria,
and certain other microbes — are responsible for many diseases. But linking specific diseases to the microbes
that cause them has been surprisingly tricky. In 1882, a scientist named Robert Koch demonstrated
that the bacterium Mycobacterium tuberculosis causes tuberculosis. And in 1890, he also published a framework
for future scientists to make similar discoveries. He created a checklist for researchers to
reference any time they’re trying to link a pathogen to a disease. The steps are as follows. First, researchers had to be able to find
the pathogen in sick organisms, but not healthy ones. Second, it could be grown in pure culture
— which means that a sample of the microbe could be taken from a sick organism, and then
the microbe could grow independently in a 19th century version of the petri dish. Third, if they exposed a healthy organism
to the stuff that they grew in step two, that organism would get sick with the same disease. Finally, though this step is sometimes considered
optional, the same microbe that was isolated in step one must be found again in the organism
made sick in step three. These steps are now known as Koch’s Postulates. The idea is that if the microbe meets all
of the postulates, then you know it’s the cause of the disease. Unfortunately, his postulates had a few problems. Take postulate one. Tuberculosis can actually be found in healthy
individuals — that’s called latent tuberculosis — so it doesn’t meet Koch’s first postulate. This situation just didn’t show up in his
experiments, which were done in guinea pigs. Postulate three isn’t perfect either. Assuming that any healthy organism exposed
to a pathogen will get sick ignores differences in immune systems. A healthy organism might be able to fight
off the infection or might already be immune to the disease. But it was the second postulate that caused
the most confusion. Something grown in “pure culture” has
to be the only living thing in the dish, and many pathogens just can’t grow independently
like that. Viruses, for example, reproduce by hijacking
molecular machinery in the cells of the organism they’re infecting. Meaning you can’t grow them in a dish by
themselves. But bacteria often grow in a dish just fine. Because postulate two required the thing to
grow in culture, researchers at the turn of the twentieth century would almost exclusively
blame bacteria for the diseases they were studying, which resulted in some false accusations. Malaria, which is actually caused by blood-infecting
parasites, was blamed on a bacterium from Italian marshes in the 1880s, which they named
Bacillus malariae. Canine distemper, a sometimes deadly disease
in dogs that causes symptoms like fever and vomiting, was linked to a series of different
bacteria before it was finally proven to be a virus in the 1920s. And the familiar virus influenza, or the flu,
was misidentified as a bacterium in eighteen ninety-two, by a colleague of Koch’s. The bacterium came to be known as Haemophilus
influenzae. To study the flu, researchers needed samples
of spit and snot from people with obvious symptoms. But one thing that made influenza hard to
study was that, even though the flu usually reaches a peak in winter, the only time that
scientists could reliably find large numbers of flu-ridden folks at the same time was during
a pandemic. And those could be decades apart. So the first chance scientists had to check
the results from 1892 was during the next influenza pandemic… in 1918. Researchers were unable to replicate those
initial results. But it wasn’t clear at the time if it was
because of poorly controlled studies in the chaos of one of the worst pandemics in recent
history and the end of World War I, or if they were just… wrong. A vaccine was developed in New York based
on Haemophilus, just in case. There was at least one study around that time
that managed to find evidence of the right answer: influenza is a virus. It took until 1933 and another influenza pandemic
for scientists to prove without a doubt that the flu is caused by a virus, thanks to the
introduction of ferrets as a model organism. Ferrets were the only small mammals they could
find that actually get the flu and show symptoms similar to ours. So it seems like Koch’s Postulates, especially
the second, really hindered research into any disease that didn’t have a bacterium
behind it. Does that mean they’re useless? Not at all. Since the 1880s, scientists have tweaked Koch’s
postulates over time to match modern understandings of pathogens. Today, the focus isn’t just on microbes,
but on their genes. Using genetic sequencing, scientists can gather
information about all of the nucleic acids in a sample, whether DNA or RNA, and then
use a modified version of Koch’s postulates to figure out which genes are most associated
with disease symptoms. For example, in 1996 scientists at Stanford
came up with a new set of postulates with seven gene-centric points. By using gene sequencing, scientists can find
pathogens that haven’t been isolated and identified before. And there’s no need to culture them. Koch’s postulates provided a solid foundation
for researchers to begin linking diseases to their sources. Sure, there were a few mistakes, but they
provided a rigorous, testable basis for understanding disease. Even if we had to come along and make some
changes later. And even if some ferrets had to get the sniffles. Thanks for watching this episode of SciShow,
and thanks to our supporters on Patreon for making what we do possible. If you want to join them and help us, while
also getting some cool benefits, check out {♫Outro♫}

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