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On August 22, 1643, the
anatomist Johann Wirsung was
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talking with a few of his neighbors
outside his home in Padua, Italy.
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When suddenly…
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BANG!
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The professional corpse dissector was murdered…
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bleeding out from a gunshot wound.
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But who killed him? And why?
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Poor old Wirsung certainly had enemies.
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Professional rivals of sorts.
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They all studied an unassuming
organ in the human body:
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the pancreas.
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Today, the pancreas might be best
known for a hormone it produces:
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insulin.
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Or the disease you get when it
doesn’t produce enough insulin:
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diabetes.
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Wirsung didn’t know anything about that.
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Nor did anyone else.
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But he had a hunch it did more than what
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most people thought at the time.
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That may have been the thing that got him killed.
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And the weird thing is, that was just the
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beginning of the violence
inspired by the pancreas.
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[♪INTRO]
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The pancreas is about the size of your hand,
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and sits behind your stomach.
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The ancient Greeks knew it was
there, but had no idea what it did.
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The works of Aristotle,
Herophilus, and Rufus of Ephesus…
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all ancient Greek physicians working
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between 400 BCE and 100 CE
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make brief mention of the organ.
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But apparently they didn’t think much of it.
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The name itself simply means “all flesh”.
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Not long after, the famous
Greek and Roman physician
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Galen proposed an actual
purpose for this blob of flesh.
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He said, maybe it’s there to fill
the space between the other organs,
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and protect the veins and nerves.
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In other words, a bit of bubble wrap that pads
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and props up all the important
stuff while you walk around.
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Which was definitely wrong, but the idea
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stuck around for more than a millennium.
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Eventually, the Renaissance arrived.
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In the 1500s, physician Andreas Vesalius
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published detailed diagrams of the pancreas.
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He said it looked like a big gland.
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And glands are defined by secreting stuff.
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Like sweat glands, for example.
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But ultimately, he agreed with Galen
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that it was probably just there for support.
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Meanwhile, Gabriel Fallopius, of
fallopian tube fame, disagreed.
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Because four-legged animals also have pancreases.
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And based on where the pancreas
sits behind the stomach,
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it is doing nothing to
support any of their organs.
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But despite pointing this
out, Galen’s idea persisted.
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Now Vesalius, Fallopius, and many other
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Renaissance-era physicians worked in Padua.
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For centuries, the Italian city
was known for its friendliness
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to cutting-edge research, including
the dissection of cadavers.
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And I’m talking public dissections,
completed not just in lecture halls,
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but modular, portable theaters that
you could set up in courtyards,
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or even in professors’ homes.
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These dissections were so popular,
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permanent theaters were built so
everyone could get a good view.
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Padua has the world’s first
permanent anatomical theater,
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completed in 1595. It’s still
there, and they offer tours!
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So it’s no wonder that aspiring
physicians from across Europe traveled
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to Padua to make a name for
themselves. Including Johann Wirsung.
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In March of 1642, a year before the assassination,
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Wirsung and two students dissected
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a pancreas from an executed criminal.
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But instead of reaffirming this
was just a lump of all-flesh,
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Wirsung found a duct that
led toward the intestines.
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This big, gland-shaped thing actually
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had a path to secrete stuff into another organ!
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To stake his claim for this discovery,
he had sketches of the organ
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and its duct engraved and sent
to other leading physicians.
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You could even call them…”unsolicited duct pics”.
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But Wirsung never had the chance
to present his work publicly.
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That fateful August evening,
three assassins stalked him
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through the streets of Padua
and shot him outside his home.
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A neighbor saw it all go down,
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and Wirsung shouted one name as he bled out:
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Cambier!
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That’s Belgian doctor Jacobus Cambier,
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his relative Nicaise Cambier,
and an unknown medical student.
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According to one Wirsung biography,
Dr. Cambier shot Wirsung, quote,
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“for personal reasons of hatred”.
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Or I guess the Italian quote of
“personal reasons of hatred.”
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But the conspiracy might go even further.
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Remember how Wirsung wasn’t alone
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when he dissected that criminal’s pancreas?
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One of the students with him, Maurice Hoffman,
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claimed that he’d shown Wirsung an equivalent
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duct inside a rooster pancreas ahead of time.
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Recipients of Wirsung’s duct images
wanted to call it Wirsung’s duct;
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Hoffman wanted it named for himself.
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So, maybe, Hoffman paid the Cambiers
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to kill Wirsung out of professional jealousy.
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The world may never know exactly
why Wirsung was assassinated,
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but there was still a lot
to learn about the pancreas…
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for anyone willing to take the risk.
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Fast forward to the 1800s, when people started
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applying the scientific method to medicine.
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Prior to that point in history,
physicians were focused
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on structure and anatomy. Which
explains all the dissections.
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But in the 1800s, researchers finally
started running experiments to
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understand how the body works,
creating the field of physiology.
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And in France, big-deal
physiologist Claude Bernard
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showed that the stomach is not
the end-all be-all of digestion.
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His experiments in the
1850s showed that pancreatic
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secretions are key for digesting
both fats and starches.
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A few years later, this time in Germany,
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Paul Langerhans put the
pancreas under a microscope
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to find out where all these
secretions were coming from.
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He saw the duct of Wirsung and,
clustered around that duct,
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some berry-shaped cells
producing digestive juices.
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He also saw another type of cell,
each isolated from one another,
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which together resembled
a bunch of little islands.
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Today, we call the berry-like cells acinar cells,
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from the Latin for “berry”, and the
island-like cells islets of Langerhans.
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Presumably, no one tried to kill
him over a disputed discovery.
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Don’t worry, there’s still more violence to come.
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In the 1890s, researchers
began to connect the pancreas,
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specifically the islet cells, with diabetes.
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Today, over 800 million people
have diabetes around the world,
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including over 38 million
people in the United States.
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About 9 million people worldwide,
and just under 2 million in the US,
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have type 1 diabetes. Which is
what we’re going to focus on.
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Scientists don’t know exactly what causes
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type 1 diabetes, or how to prevent it.
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But it tends to start in childhood,
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and if you have access to
and can afford health care,
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it’s a manageable, chronic disease.
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If you were born before the 1920s, though,
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your outlook was a lot more dire.
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The key problem with diabetes
is how the body uses sugar.
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People with the disease can
experience very high blood sugar,
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high blood acids from
breaking down fats for energy,
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or very low blood sugar. All of these
can put that person into a coma.
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The only treatment available to prevent
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these crises was an extremely restrictive diet,
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with low calories and low carbs.
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So, when someone was diagnosed with diabetes,
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they lived for less than a decade, on average.
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There had to be a better way.
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And thanks to that early pancreas research,
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doctors of the early 20th century
knew where to start looking.
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Research teams around the world
were asking questions like:
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How does the pancreas usually work
so people don’t have diabetes?
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What do the islet cells produce that’s different
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from the digestive juices we already know about?
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And can we purify that useful
thing and treat diabetes with it?
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The first world war threw a massive
wrench into some of that research.
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Some projects in Germany
and the US never recovered,
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despite some initial promising results.
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But the most successful story
comes to us courtesy of Canada.
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In 1920, Dr. Fred Banting left his
struggling surgery practice and
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took a medical demonstrator job at
the University of Western Ontario,
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teaching students practical, clinical skills.
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In other words, he wasn’t
really a scientific researcher,
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and didn’t have experience running experiments.
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But that year, he read a
research article about people
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who had clogged pancreas ducts
and later developed diabetes.
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And that gave him an idea
for an experiment of his own.
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He brought it to senior
professor John Macleod at the
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University of Toronto, a leading
researcher in sugar metabolism.
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What if, Banting asked, we could surgically
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block the pancreatic ducts in dogs?
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That would kill the acinar cells,
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and stop them from making digestive juices.
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He would then be free to study exactly
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what the islet cells were secreting.
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Macleod was not impressed, but
he said, sure, give it a try.
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And he assigned one of his
students, Charles Best, to help.
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Just a warning if you’re kind
of sensitive to this stuff:
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The following research gets a
little graphic with the dogs.
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Banting and Best started
their experiments in 1921,
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and they went something like this.
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First, get two dogs. One of them
has its Wirsung duct blocked
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so its pancreas can’t make
digestive juices anymore,
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but it still has functioning islet cells.
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The other dog has its pancreas removed.
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If it survives the operation, it
will eventually develop diabetes,
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which you can measure from
its high blood sugar levels.
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Then, if things weren’t already bleak enough,
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you kill the first dog, remove
the pancreas, and grind it up.
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Inject the resulting extract into Dog 2,
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and measure its blood sugar again.
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If the extract works, that
dog’s blood sugar will go down.
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Now, if it wasn’t already obvious,
this was a brutal process.
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Not only were these guys doing
really difficult surgery on dogs,
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they were also working in an unsanitary,
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un-air-conditioned space in the middle of summer.
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Definitely not a proper operating room.
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Dogs died from complications and infections,
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which Banting felt genuinely bad about.
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But if they could find a
reliable treatment for diabetes,
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it could be worth it.
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And they quickly learned
they were on the right track.
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In dog after diabetic dog, the extract from an
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islet-cell-only pancreas lowered
their rising blood sugar.
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They named this extract isletin,
but their work wasn’t done.
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That fall, Best and Banting
brought their results to Macleod,
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who finally agreed they were onto something.
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He brought on another member
of the team, a biochemist
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named James Collip, to help
purify the islet cell secretion.
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The team found that calf pancreases
can create more of the secretion,
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and therefore make a stronger treatment.
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They also studied its effect
in rabbits to understand
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how well their new purification
techniques were working.
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Then, in January 1922, the team
was ready to test their new
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treatment on the first
human subject with diabetes:
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a 14-year-old boy named Leonard Thompson.
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He was semi-comatose, frequently in the hospital,
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and weighed just 65 pounds
because of his severe diet.
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The research team’s first attempt
at treatment didn’t quite work.
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But with stronger injections,
improved by Collip, the teen woke up,
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his health improved, and he soon returned home.
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Diabetes was no longer a death sentence.
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But it wouldn’t be pancreas
research without a fight.
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In one corner, Banting wanted to
get this islet cell extract to as
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many patients as possible, he
just needed Collip’s procedure.
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In the other corner, Collip said, hang on.
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You can’t do that, this is my
extract, my purification procedure.
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He refused to share. Banting accused Collip of
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maintaining bad records on purpose, to protect his
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secret recipe and patent the extract himself.
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Ding ding: Banting went to Collip’s lab,
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threw him in a chair by his
overcoat, and nearly throttled him.
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Luckily, Best stepped in and split up the fight.
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So Wirsung remains our only murder this episode.
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With an uneasy truce in place,
the team licensed the extract
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and purification technique to their university,
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which partnered with the
pharmaceutical company Eli Lilly
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to mass produce the treatment
we now know as insulin.
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In 1923, the Nobel Prize in
Medicine was awarded to Banting…
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and Macleod.
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Enter, the second round of fighting.
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Although as far as we know it
didn’t descend into fisticuffs.
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Banting wanted to share the prize with Best,
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who had been alongside him,
elbow-deep in dog pancreases.
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From his perspective, Macleod
not only doubted the work
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from the get-go, he withheld resources
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and kept his distance until it seemed successful.
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But to Macleod’s credit,
he gave the team legitimacy
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in the cutthroat world of academic research.
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He knew how to present these
important results to colleagues, and
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stepped in when Banting froze up
at a major scientific conference.
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Technically, the Nobel Prize
can be split among three people,
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so maybe Best could have gotten a slice.
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But that would still leave
out one member of their team.
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So Banting split his share of the prize with Best.
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In return, Macleod split his share with Collip.
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But the drama wasn’t over, yet.
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There was still more academic
jockeying as researchers around
00:12:35
the world claimed that they
provided pieces of the puzzle that
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led to Best and Banting’s
results and the Nobel Prize.
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And the full story of the team’s
interpersonal conflicts was
00:12:44
kept quiet until the 1970s,
after all four of them had died.
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Still, other researchers could
take their work and run with it.
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Over the next few decades, scientists
figured out that insulin is just
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one protein, figured out the building
blocks that this protein is made of,
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and decoded the DNA sequence behind it.
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Initially, this allowed pharmaceutical companies
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to better isolate insulin from animal pancreases.
00:13:06
And in 1978, they genetically
engineered bacteria with that DNA
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sequence so they’d secrete the
human version of the insulin for us.
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Because it should come as no surprise that human
00:13:17
insulin works better for
humans than cow insulin does!
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Major improvements have also
been made to the equipment
00:13:22
that people use to monitor
and manage their diabetes.
00:13:25
And insulin itself has been
modified into a suite of different
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medications that work in different
ways, like fast-acting or
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slow-acting versions, depending
on what a person needs.
00:13:36
Millions of lives have been saved
thanks to all of these achievements.
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But on the flipside, this kind of
incremental progress also means that
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all of these drugs and technologies
are still protected by patents,
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making them unaffordable and
inaccessible to many who need them.
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So there’s work to do to get this live-saving
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treatment to people who need it.
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But we can also remember just how far we’ve come,
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and the sacrifices that got us here.
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So pour one out for Johann Wirsung
and some very, very good dogs.
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[♪OUTRO]
