On August 22, 1643, the  anatomist Johann Wirsung was talking with a few of his neighbors  outside his home in Padua, Italy.

When suddenly… BANG! The professional corpse dissector was murdered… bleeding out from a gunshot wound.

But who killed him? And why? Poor old Wirsung certainly had enemies.

Professional rivals of sorts. They all studied an unassuming  organ in the human body: the pancreas. Today, the pancreas might be best  known for a hormone it produces: insulin.

Or the disease you get when it  doesn’t produce enough insulin: diabetes. Wirsung didn’t know anything about that. Nor did anyone else.

But he had a hunch it did more than what most people thought at the time. That may have been the thing that got him killed. And the weird thing is, that was just the beginning of the violence  inspired by the pancreas. [♪INTRO] The pancreas is about the size of your hand, and sits behind your stomach.

The ancient Greeks knew it was  there, but had no idea what it did. The works of Aristotle,  Herophilus, and Rufus of Ephesus… all ancient Greek physicians working between 400 BCE and 100 CE make brief mention of the organ. But apparently they didn’t think much of it.

The name itself simply means “all flesh”. Not long after, the famous  Greek and Roman physician Galen proposed an actual  purpose for this blob of flesh. He said, maybe it’s there to fill  the space between the other organs, and protect the veins and nerves.

In other words, a bit of bubble wrap that pads and props up all the important  stuff while you walk around. Which was definitely wrong, but the idea stuck around for more than a millennium. Eventually, the Renaissance arrived.

In the 1500s, physician Andreas Vesalius published detailed diagrams of the pancreas. He said it looked like a big gland. And glands are defined by secreting stuff.

Like sweat glands, for example. But ultimately, he agreed with Galen that it was probably just there for support. Meanwhile, Gabriel Fallopius, of  fallopian tube fame, disagreed.

Because four-legged animals also have pancreases. And based on where the pancreas  sits behind the stomach, it is doing nothing to  support any of their organs. But despite pointing this  out, Galen’s idea persisted.

Now Vesalius, Fallopius, and many other Renaissance-era physicians worked in Padua. For centuries, the Italian city  was known for its friendliness to cutting-edge research, including  the dissection of cadavers. And I’m talking public dissections,  completed not just in lecture halls, but modular, portable theaters that  you could set up in courtyards, or even in professors’ homes.

These dissections were so popular, permanent theaters were built so  everyone could get a good view. Padua has the world’s first  permanent anatomical theater, completed in 1595. It’s still  there, and they offer tours!

So it’s no wonder that aspiring  physicians from across Europe traveled to Padua to make a name for  themselves. Including Johann Wirsung. In March of 1642, a year before the assassination, Wirsung and two students dissected a pancreas from an executed criminal.

But instead of reaffirming this  was just a lump of all-flesh, Wirsung found a duct that  led toward the intestines. This big, gland-shaped thing actually had a path to secrete stuff into another organ! To stake his claim for this discovery,  he had sketches of the organ and its duct engraved and sent  to other leading physicians.

You could even call them…”unsolicited duct pics”. But Wirsung never had the chance  to present his work publicly. That fateful August evening,  three assassins stalked him through the streets of Padua  and shot him outside his home.

A neighbor saw it all go down, and Wirsung shouted one name as he bled out: Cambier! That’s Belgian doctor Jacobus Cambier, his relative Nicaise Cambier,  and an unknown medical student. According to one Wirsung biography,  Dr.

Cambier shot Wirsung, quote, “for personal reasons of hatred”. Or I guess the Italian quote of  “personal reasons of hatred.” But the conspiracy might go even further. Remember how Wirsung wasn’t alone when he dissected that criminal’s pancreas?

One of the students with him, Maurice Hoffman, claimed that he’d shown Wirsung an equivalent duct inside a rooster pancreas ahead of time. Recipients of Wirsung’s duct images  wanted to call it Wirsung’s duct; Hoffman wanted it named for himself. So, maybe, Hoffman paid the Cambiers to kill Wirsung out of professional jealousy.

The world may never know exactly  why Wirsung was assassinated, but there was still a lot  to learn about the pancreas… for anyone willing to take the risk. Fast forward to the 1800s, when people started applying the scientific method to medicine. Prior to that point in history,  physicians were focused on structure and anatomy.

Which  explains all the dissections. But in the 1800s, researchers finally  started running experiments to understand how the body works,  creating the field of physiology. And in France, big-deal  physiologist Claude Bernard showed that the stomach is not  the end-all be-all of digestion.

His experiments in the  1850s showed that pancreatic secretions are key for digesting  both fats and starches. A few years later, this time in Germany, Paul Langerhans put the  pancreas under a microscope to find out where all these  secretions were coming from. He saw the duct of Wirsung and,  clustered around that duct, some berry-shaped cells  producing digestive juices.

He also saw another type of cell,  each isolated from one another, which together resembled  a bunch of little islands. Today, we call the berry-like cells acinar cells, from the Latin for “berry”, and the  island-like cells islets of Langerhans. Presumably, no one tried to kill  him over a disputed discovery.

Don’t worry, there’s still more violence to come. In the 1890s, researchers  began to connect the pancreas, specifically the islet cells, with diabetes. Today, over 800 million people  have diabetes around the world, including over 38 million  people in the United States.

About 9 million people worldwide,  and just under 2 million in the US, have type 1 diabetes. Which is  what we’re going to focus on. Scientists don’t know exactly what causes type 1 diabetes, or how to prevent it.

But it tends to start in childhood, and if you have access to  and can afford health care, it’s a manageable, chronic disease. If you were born before the 1920s, though, your outlook was a lot more dire. The key problem with diabetes  is how the body uses sugar.

People with the disease can  experience very high blood sugar, high blood acids from  breaking down fats for energy, or very low blood sugar. All of these  can put that person into a coma. The only treatment available to prevent these crises was an extremely restrictive diet, with low calories and low carbs.

So, when someone was diagnosed with diabetes, they lived for less than a decade, on average. There had to be a better way. And thanks to that early pancreas research, doctors of the early 20th century  knew where to start looking.

Research teams around the world  were asking questions like: How does the pancreas usually work  so people don’t have diabetes? What do the islet cells produce that’s different from the digestive juices we already know about? And can we purify that useful  thing and treat diabetes with it?

The first world war threw a massive  wrench into some of that research. Some projects in Germany  and the US never recovered, despite some initial promising results. But the most successful story  comes to us courtesy of Canada.

In 1920, Dr. Fred Banting left his  struggling surgery practice and took a medical demonstrator job at  the University of Western Ontario, teaching students practical, clinical skills. In other words, he wasn’t  really a scientific researcher, and didn’t have experience running experiments.

But that year, he read a  research article about people who had clogged pancreas ducts  and later developed diabetes. And that gave him an idea  for an experiment of his own. He brought it to senior  professor John Macleod at the University of Toronto, a leading  researcher in sugar metabolism.

What if, Banting asked, we could surgically block the pancreatic ducts in dogs? That would kill the acinar cells, and stop them from making digestive juices. He would then be free to study exactly what the islet cells were secreting.

Macleod was not impressed, but  he said, sure, give it a try. And he assigned one of his  students, Charles Best, to help. Just a warning if you’re kind  of sensitive to this stuff: The following research gets a  little graphic with the dogs.

Banting and Best started  their experiments in 1921, and they went something like this. First, get two dogs. One of them  has its Wirsung duct blocked so its pancreas can’t make  digestive juices anymore, but it still has functioning islet cells.

The other dog has its pancreas removed. If it survives the operation, it  will eventually develop diabetes, which you can measure from  its high blood sugar levels. Then, if things weren’t already bleak enough, you kill the first dog, remove  the pancreas, and grind it up.

Inject the resulting extract into Dog 2, and measure its blood sugar again. If the extract works, that  dog’s blood sugar will go down. Now, if it wasn’t already obvious,  this was a brutal process.

Not only were these guys doing  really difficult surgery on dogs, they were also working in an unsanitary, un-air-conditioned space in the middle of summer. Definitely not a proper operating room. Dogs died from complications and infections, which Banting felt genuinely bad about.

But if they could find a  reliable treatment for diabetes, it could be worth it. And they quickly learned  they were on the right track. In dog after diabetic dog, the extract from an islet-cell-only pancreas lowered  their rising blood sugar.

They named this extract isletin,  but their work wasn’t done. That fall, Best and Banting  brought their results to Macleod, who finally agreed they were onto something. He brought on another member  of the team, a biochemist named James Collip, to help  purify the islet cell secretion.

The team found that calf pancreases  can create more of the secretion, and therefore make a stronger treatment. They also studied its effect  in rabbits to understand how well their new purification  techniques were working. Then, in January 1922, the team  was ready to test their new treatment on the first  human subject with diabetes: a 14-year-old boy named Leonard Thompson.

He was semi-comatose, frequently in the hospital, and weighed just 65 pounds  because of his severe diet. The research team’s first attempt  at treatment didn’t quite work. But with stronger injections,  improved by Collip, the teen woke up, his health improved, and he soon returned home.

Diabetes was no longer a death sentence. But it wouldn’t be pancreas  research without a fight. In one corner, Banting wanted to  get this islet cell extract to as many patients as possible, he  just needed Collip’s procedure.

In the other corner, Collip said, hang on. You can’t do that, this is my  extract, my purification procedure. He refused to share.

Banting accused Collip of maintaining bad records on purpose, to protect his secret recipe and patent the extract himself. Ding ding: Banting went to Collip’s lab, threw him in a chair by his  overcoat, and nearly throttled him. Luckily, Best stepped in and split up the fight.

So Wirsung remains our only murder this episode. With an uneasy truce in place,  the team licensed the extract and purification technique to their university, which partnered with the  pharmaceutical company Eli Lilly to mass produce the treatment  we now know as insulin. In 1923, the Nobel Prize in  Medicine was awarded to Banting… and Macleod.

Enter, the second round of fighting. Although as far as we know it  didn’t descend into fisticuffs. Banting wanted to share the prize with Best, who had been alongside him,  elbow-deep in dog pancreases.

From his perspective, Macleod  not only doubted the work from the get-go, he withheld resources and kept his distance until it seemed successful. But to Macleod’s credit,  he gave the team legitimacy in the cutthroat world of academic research. He knew how to present these  important results to colleagues, and stepped in when Banting froze up  at a major scientific conference.

Technically, the Nobel Prize  can be split among three people, so maybe Best could have gotten a slice. But that would still leave  out one member of their team. So Banting split his share of the prize with Best.

In return, Macleod split his share with Collip. But the drama wasn’t over, yet. There was still more academic  jockeying as researchers around the world claimed that they  provided pieces of the puzzle that led to Best and Banting’s  results and the Nobel Prize.

And the full story of the team’s  interpersonal conflicts was kept quiet until the 1970s,  after all four of them had died. Still, other researchers could  take their work and run with it. Over the next few decades, scientists  figured out that insulin is just one protein, figured out the building  blocks that this protein is made of, and decoded the DNA sequence behind it.

Initially, this allowed pharmaceutical companies to better isolate insulin from animal pancreases. And in 1978, they genetically  engineered bacteria with that DNA sequence so they’d secrete the  human version of the insulin for us. Because it should come as no surprise that human insulin works better for  humans than cow insulin does!

Major improvements have also  been made to the equipment that people use to monitor  and manage their diabetes. And insulin itself has been  modified into a suite of different medications that work in different  ways, like fast-acting or slow-acting versions, depending  on what a person needs. Millions of lives have been saved  thanks to all of these achievements.

But on the flipside, this kind of  incremental progress also means that all of these drugs and technologies  are still protected by patents, making them unaffordable and  inaccessible to many who need them. So there’s work to do to get this live-saving treatment to people who need it. But we can also remember just how far we’ve come, and the sacrifices that got us here.

So pour one out for Johann Wirsung  and some very, very good dogs. [♪OUTRO]