The dramatic race to discover Insulin

Looksmaxxing, weight loss, and muscle building have fueled a massive craze for injectable peptides. Some natural and some synthetic. These injectables have unleashed a multi-billion-dollar gray-market industry online and a high-stakes frontier for the pharmaceutical industry. Today, we reach back to the quest to manufacture the first peptide-based medicine: Insulin. Guests: Alison Li, historian of science and medicine, author of J. B. Collip and the Development of Medical Research in Canada: Extracts and Enterprise Grant Maltman, curator of Banting House National Historic Site Support public media with NPR+ and enjoy perks for over 25 podcasts like this one. This show’s perks include sponsor-free listening. Learn more at plus.npr.org http://plus.npr.org/. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

• 0:00Speaker 00

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• 0:19Speaker 01

  December 2nd, 1921.

• 0:23Speaker 01

  Leonard Thompson, a 14-year-old Canadian boy, checks in to Toronto General Hospital. He's in critical condition.

• 0:32Speaker 02

  He was completely apathetic because he was so starved and so ill. His hair was falling out, his eye sockets were dark, and he had this sort of distended stomach.

• 0:46Speaker 01

  His parents are looking for glimmers of hope. Leonard lies in his bed, day after day, listless. He's no longer the boy he was just two years before, then a perfectly healthy kid.

• 1:01Speaker 02

  One day, he started wetting his bed, and he developed swollen ankles. And his parents took him to a doctor. And a few weeks later, developed sugar in his urine. And that was the absolute sign that he had developed diabetes.

• 1:22Speaker 01

  Leonard's situation is grim. He weighs just 65 pounds. His thin breath, almost a whisper, smells like acetone, almost like paint thinner. He's drifting in and out of sleep, and he's on a strict diet, borderline starving.

• 1:40Speaker 02

  450 calories. He was allowed 50 grams of lean meat and just like 100 grams of carbs.

• 1:49Speaker 01

  The doctor's secretary takes one look at him and says, I've never seen a living creature as thin as he was.

• 1:56Speaker 02

  He was on the verge of death.

• 1:59Speaker 02

  Everyone on the floor knew that he was doomed.

• 2:03Speaker 01

  And while Leonard's family waits for the worst to come, four unlikely people come together at the right time to make a discovery.

• 2:13Speaker 03

  Here we are 105, 106 years later. We still have a doctor giving a newly diagnosed patient an injection of this elixir, this insulin that changed the world all those years ago.

• 2:24Speaker 01

  A lifesaving treatment that beat a race against death.

• 2:28Speaker 03

  If you're living with type 1 diabetes, you need them to win that race. Because if you have diabetes in 1920, 21, you don't have three to five years to wait.

• 2:41Speaker 01

  I'm Randa Abdel Fattah, and you're listening to Throughline from NPR.

• 2:47Speaker 01

  Looks maxing, weight loss, muscle building, all these things have been driving a massive craze for a few years now. Injectable peptides, some natural and some synthetic. They promise wellness, beauty, and even longevity. A peptide is a basic building block in our body, and some act as powerful hormones regulating key functions, like GLP-1 drugs, that have been life-changing for millions of people. These injectables have unleashed a multi-billion-dollar gray market industry online, helped by the FDA, that's looking to loosen restrictions on unapproved, untested peptides.

• 3:30Speaker 01

  So today, we're reaching back a century to the murky and surprising story about the mad dash to manufacture the OG peptide-based medicine: insulin. It's a story rife with personal grudges, trial and error, and many, many dogs. Stay with us.

• 3:55Speaker 04

  Hi, this is Claire Poprocky calling from Madison, Wisconsin. I'm a longtime listener, first-time caller. You're listening to Throughline from NPR.

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  This message comes from Capella University. That spark you feel? That's your drive for more. Capella University's FlexPath learning format lets you earn your degree at your pace without putting life on pause. Learn more at capella.edu.

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  This message comes from Bowlin Branch. Change the way you sleep with soft, 100% organic cotton sheets from Bowlin Branch, designed to help you fall asleep faster, with airy blankets, cloud-like duvets, and breathable sheets. Experience pure comfort on night one and feel your sheets get softer with every wash. Discover the difference with 15% off your first order at bowlinbranch.com with code NPR. Exclusions apply. See site for details.

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  Support for this podcast and the following message come from the Southern Environmental Law Center. No one voted for a dirty air. No one voted for polluted water. That's why S E L C is fighting back to defend the healthy environment everyone depends on, just as they've done for 40 years. Because clean air, clean water, and a healthy climate aren't political, they're fundamental. Learn more at selc.org.

• 5:42Speaker 01

  Part one, 25 words.

• 5:46Speaker 01

  It's summer 1920, a little over a year before Leonard Thompson will find himself in that hospital ward. A young general surgeon has just opened a private practice in a little house in London, Ontario, Canada, Fredrick Banting.

• 6:02Speaker 03

  I think the best way to describe it would be a reluctant hero. This is someone on his own who was uncomfortable in his own skin sometimes.

• 6:13Speaker 01

  This is Grant Maltman.

• 6:14Speaker 03

  I'm the curator at Banning House National Historic Site of Canada, and I'm in London, Ontario.

• 6:19Speaker 01

  Born to hardworking farmers, methodists, the youngest of five, Fred Banting was a shy kid growing up, prone to insecurity. He's tall, almost six feet, and he wasn't a great student. One former high school principal said of him.

• 6:35Speaker 03

  Not a student on whom he thought fame would ever settle.

• 6:39Speaker 03

  This is someone who did fail a lot.

• 6:42Speaker 01

  Academically, he goes on to struggle at university.

• 6:46Speaker 03

  He didn't have a passing grade, so you can say he failed his first year.

• 6:49Speaker 01

  So Banting leaves his liberal arts studies and enters the field of medicine. But as fate would have it, his medical studies get cut short because of World War I. He's sent into combat as a doctor with what Banting would describe as very deficient medical training.

• 7:08Speaker 03

  He comes back from the first war, a national war hero, can't get a job in Toronto.

• 7:13Speaker 01

  So instead, he moves to London, Ontario, and opens up a private practice.

• 7:18Speaker 03

  And then he does everything wrong here.

• 7:21Speaker 03

  His location isn't great. It wasn't a high-traffic area. You could advertise by putting your front name up front, beautiful silver maple up front, so you can't see the sign. Phone book's a good way to go, but it came out in April, and he doesn't move to London.

• 7:36Speaker 01

  So he's not in the phone book?

• 7:37Speaker 03

  No, he's not in the phone book, yeah, because he doesn't move here until June. So he's literally 0 for 4.

• 7:43Speaker 01

  For months and months, Fred Banting struggles to make money. Six days a week, he remains open, but not a single patient arrives.

• 7:52Speaker 03

  And when he opens the door on July 1st, his first patient doesn't arrive until 28 days later.

• 7:59Speaker 01

  Patient number one is an alcoholic.

• 8:01Speaker 03

  In Ontario in 1920, we're still under the Prohibition Act. So the only place you're getting alcohol is from your doctor, you know, that shot for medicinal person.

• 8:10Speaker 01

  So he came for the alcohol.

• 8:12Speaker 03

  Yeah, he was an honest soldier, and he wanted to give his men a drink. I wrote him this, I thought myself rather good at the barkeeping business today, so I wrote him the prescription, felt good about it.

• 8:22Speaker 01

  So he gave him the alcohol?

• 8:25Speaker 03

  Yeah, great Canadian hero, starts off as a legal alcohol sales.

• 8:30Speaker 01

  He's a bootlegger, kind of.

• 8:33Speaker 03

  Yeah, yeah, exactly.

• 8:38Speaker 01

  Banting is super broke, in debt for medical school. To de-stress, he paints and tries to sell his art, cooks his meals on a Bunsen burner, rents out rooms in his home. Down on his luck, he finally gets a win.

• 8:53Speaker 03

  This wonderful opportunity arises.

• 8:56Speaker 01

  He finds a part-time job teaching at a local university.

• 8:59Speaker 03

  We need instructors in surgery, physiology, and anatomy. Pick me, I'll do all three. And why? It's $2 an hour. So he does three labs in that first week of the fall session. He will equal his entire July income.

• 9:15Speaker 01

  Banting is someone who likes being in the lab with his sleeves rolled up. Actually, he takes it even further.

• 9:22Speaker 03

  He's always in short sleeves because he cut the sleeves off. He liked having bare arms and working. All his lab coats were always short-sleeved.

• 9:32Speaker 01

  By now, it's October of 1920. The failed clinician gets an assignment from a colleague.

• 9:38Speaker 03

  I need you to do a lecture on diabetes and carbohydrate metabolism. And you can't do much of a lecture on four sentences. He's never treated a patient with diabetes. So he goes to the medical school, he reads everything he can, and prepares his lecture.

• 9:57Speaker 01

  It's worth noting, up to this point, the medical community only knew a little about diabetes. A lot was still a mystery.

• 10:06Speaker 03

  The first recording of the diabetes condition was 1552 B.C. in ancient Egypt. It's the Ebers Papyrus, it's the oldest surviving medical text. And it translated a couple of different ways, but sort of the one more accepted is it's a prescription for someone who has sweet-smelling urine. So we think that's the first recording of the diabetes condition.

• 10:30Speaker 01

  In the late 1800s, scientists had figured out that the pancreas was involved, and progress was being made. But a big puzzle remained. How to extract the essential substance from a healthy pancreas? So it might be given to diabetics who couldn't produce it on their own. There was no cure. The only treatment, a starvation diet. And that extended life by only a few years at most. Banting brings the scientific literature home, and he crams into the night, poring over a stack of medical journals. In the bathtub before going to bed, an article catches his eye.

• 11:07Speaker 03

  An article on diabetes research.

• 11:09Speaker 01

  From the upcoming issue of the journal Surgery, Gynecology, and Obstetrics.

• 11:14Speaker 03

  So he reads the article, turns out the light. And we're fortunate to have his own words. You know, it was one of those nights when I was restless and could not sleep. I was trying to figure out ways to get away from my debt and my worry. The lecturer and the article then began chasing each other in my mind. At 2:00 a.m., they came together and gave me the idea. I got up, I wrote down, I couldn't stop thinking about it.

• 11:37Speaker 01

  He grabs a piece of paper and scribbles down 25 words.

• 11:41Speaker 03

  Diabetes ligate pancreatic ducts of a dog. Keep dogs alive to the cinni degenerate, leaving glycosuria. Try to relieve glycosuria. I'm almost having a brain cramp on the last five words. We treat internal secretion of these to relieve glycosuria.

• 12:02Speaker 01

  Wow, that is not what comes to me in the middle of the night.

• 12:05Speaker 03

  No, it doesn't. You know, this is, oh, I'll remember this in the morning type of thing as we all go through.

• 12:13Speaker 01

  Turns out, even for a Banting scholar, it's hard to remember all the words. What's key here? Pancreatic cells, or Ilets, ducts of a dog, secretion, one grant left out, try to isolate, and keep dogs alive. And with that fever dream, Banting is convinced he's found a way to successfully extract the key substance from the pancreas that could lead to a treatment for diabetes.

• 12:46Speaker 01

  The very next morning, Banting brings the jumble of words to a colleague where he's teaching.

• 12:51Speaker 03

  Look, I think I've got something.

• 12:55Speaker 01

  No luck. They send him away. Surely someone had already tried this, the professor suggests. Struggling to make a dime and still eating meals off that Bunsen burner, a week later, convinced by his clarion dream, Fred Banting travels to his alma mater, the University of Toronto, and makes an appointment to speak with J.J.R. MacLeod, this hotshot, internationally-known physiologist, who has also studied diabetes for over a decade.

• 13:26Speaker 01

  What do we know about Banting's first impression of MacLeod?

• 13:29Speaker 03

  Oh, this is, yeah, it doesn't go well. You have MacLeod, this, you know, well-respected scholar in this field. Forty years he's been working. And Banting's not only a clinician, but he's a failing clinician. So you think of that academic world, you know, and it's not a bottom-up world. This is top-down during this period, and rightfully so. It'd be something akin today of you or I showing up at Harvard and meeting a professor and say, oh, I did my research last night, you know?

• 14:02Speaker 01

  I read an article.

• 14:02Speaker 03

  Yeah, I read an article, I Googled, right? And that's what, he's only read four or five articles from MacLeod.

• 14:09Speaker 01

  It's incredible.

• 14:09Speaker 03

  The fact that MacLeod offers the courtesy of taking this meeting,

• 14:12Speaker 01

  Right, yeah.

• 14:13Speaker 03

  you know, is in itself somewhat ridiculous that that happened. And Banting, this is a new feel to him, you know? And MacLeod, you know, you've barely done any research. This idea of yours isn't entirely new. It's a twist because it's a surgical approach. But the best experts in the world have, you know, pretty much dismissed this.

• 14:38Speaker 01

  Well, what was his pitch exactly to MacLeod?

• 14:41Speaker 03

  Well, it said 25 words. And that's the thing, it's not a 100-page proposal. And in today's standards, it's a post-it note. He wanted to get support from a text or a post-it note.

• 14:55Speaker 01

  Banting's own account of this pitch meeting is a real downer.

• 14:59Speaker 03

  MacLeod doesn't believe in me.

• 15:02Speaker 01

  Banting was asking someone to take a chance on a rookie scientist. MacLeod's got an appropriate level of skepticism.

• 15:09Speaker 03

  Do you know how many real scientists we've turned down? You know, it was, it was years ago, I had a visiting professor come through, and it seems to be in his, in his mind that MacLeod had already debunked one of these internal secretion theories a few weeks prior to this meeting. Even 20 years later, you get, when you read his writings, you can still see, you could, you could hear the anger in his writing towards MacLeod. You know, he doesn't believe in me, so forget it. And the meeting ends, and Banting returns home, and he's, you know, he's mad at MacLeod, angry with MacLeod.

• 15:47Speaker 01

  A few days later, to Banting's surprise, MacLeod gives him the green light to try out this experiment. Why the change of heart?

• 15:56Speaker 03

  The only reason that MacLeod was even going to give Banting the time of day was that he could do this research and fail and publish, and then no one would go down this route.

• 16:05Speaker 01

  Plus, it helped that Banting was willing to work for free. So MacLeod tells him.

• 16:10Speaker 03

  You can work next year. I've got a couple of graduate students who are going to need jobs.

• 16:15Speaker 01

  They strike a deal. Banting can start work the following May with a first-year grad student named Charlie Best.

• 16:23Speaker 03

  You have a graduate student in biochemistry being led by a clinician with no real scientific method of studying, you know, research, what have you.

• 16:35Speaker 01

  And the two-month summer would begin with a hunt. That's in a minute.

• 16:45Speaker 06

  Hi, this is Neville from Kitchener, Ontario, Canada. I used to live in Northern Virginia, but I still continue to listen to Throughline and support it through NPR. Storytelling is so well-made. What makes it great, it is well-produced and researched. You are listening to Throughline from NPR, the best podcast anywhere.

• 17:04Speaker 05

  Stay tuned for the following announcements and messages from our sponsors.

• 17:08Speaker 01

  This message comes from Capella University. That spark you feel? That's your drive for more. Capella University's FlexPath learning format lets you earn your degree at your pace without putting life on pause. Learn more at capella.edu.

• 17:23Speaker 05

  This message comes from Bowlin Branch. Change the way you sleep with soft, 100% organic cotton bedding from Bowlin Branch. Designed to help you fall asleep faster and never sleep hot while wrapped in luxurious comfort, airy blankets, cloud-like duvets, and breathable sheets. Experience pure comfort and feel your bedding get softer with every wash. Discover the difference with 15% off your first order at bowlinbranch.com with code NPR. Exclusions apply. See site for details. Support for this podcast and the following message come from the Southern Environmental Law Center. No one voted for a dirty air. No one voted for polluted water. That's why S E L C is fighting back to defend the healthy environment

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  everyone depends on, just as they've done for 40 years. Because clean air, clean water, and a healthy climate aren't political, they're fundamental. Learn more at selc.org.

• 18:19Speaker 01

  Part Two, The Discovery.

• 18:30Speaker 01

  Before Fred Banting and his newly recruited grad student Charlie Best could study the dogs and deliver on Banting's idea, first, they had to capture them.

• 18:41Speaker 03

  There's a story of Banting and Best going down an alley with 12 leashes, and they come out with 13 dogs, and Banting's no longer wearing a tie.

• 18:50Speaker 01

  That tie was wrapped around a dog's neck, a makeshift leash. The men run down the streets of Toronto, rounding up these unlucky four-legged test subjects. They need a lot of them, so they can remove their pancreas, inducing diabetes. And you might be wondering, why dogs? Well, years earlier, German researchers had accidentally figured something out.

• 19:14Speaker 03

  They took the pancreas out, and the dog developed diabetes. They knew that connection was dogs were a good size to work with.

• 19:23Speaker 01

  Professor MacLeod had clued them into that connection before leaving for a vacation in Scotland for the summer. His priority before leaving town: teach them how to operate on dogs. And then he leaves. But he keeps tabs on their progress throughout the summer by letter.

• 19:41Speaker 01

  So after they've captured enough dogs, they start running experiments, going down dead end after dead end.

• 19:48Speaker 03

  Lots of struggles. They go through a number of dogs, trying to figure out how to do this.

• 19:54Speaker 01

  They tested the dog's urine, the dog's blood. They operated on so many. Dog 387, dog 388, 389, 340, on and on.

• 20:05Speaker 03

  Banting wasn't an evil dog scientist. This is someone who got visibly upset when the dogs passed during these experiments.

• 20:13Speaker 01

  Their dingy lab is smelly. They're holed up in a tiny room next to the dogs' quarters, under a tin roof. They have to clean the dogs' cages themselves. They work in sweat and dirt. It's hot, the dead of summer. Some of the dogs stay alive, some don't.

• 20:31Speaker 03

  They're plugging away, and they come to this July 30th. They have dog 410.

• 20:37Speaker 01

  A white, short-haired mongrel terrier. Banting and Best extract a substance from dog 391's pancreas to concoct a solution that's injected into mighty 410. They wait a couple of hours.

• 20:52Speaker 03

  And her blood glucose starts to drop.

• 20:55Speaker 01

  Eureka. That extract, mixed with a cocktail of water and salts, worked magic. It controlled her blood sugar, and the mighty terrier 410 stabilized, at least for a day, before going into a coma and then dying.

• 21:14Speaker 01

  Nonetheless, the men had done something no one had ever documented before. They had successfully extracted pancreatic cells and added them to a solution that seemed to work. But the solution wasn't perfect. It was very sludgy, not purified.

• 21:32Speaker 03

  It's like taking a glass of water from the Hudson River and a glass of water from a Brita filter. Both are water, and one's gonna have a lot of junk in it. That's what they have. But it seemed to put them on this right track.

• 21:45Speaker 01

  At last, they were on to something. Best wrote to MacLeod. The extract seemed to have a market effect.

• 21:53Speaker 03

  We think we've got something.

• 21:57Speaker 01

  When MacLeod hears about it, he's a little less enthusiastic. You might even say skeptical.

• 22:04Speaker 03

  MacLeod's research methodology is a little weak.

• 22:07Speaker 01

  And tells them there has to be no possibility of mistake. MacLeod wants to bring more critical thinking to their work, more rigid controls. Banting gets agitated. He wants a salary, a better room to work in, an assistant to look after dogs. MacLeod can't offer that. It's tense. Banting says that if the University of Toronto doesn't think the research he's doing is important, he'll take it someplace else. MacLeod's reply: As far as you are concerned, I am the University of Toronto. But eventually, MacLeod relends to Banting. The men can continue their work. He isn't about to pat Banting on the back,

• 22:51Speaker 01

  but he can see they were on to something, maybe something big. This time, they plan to refine the purification process. They need to make it more potent.

• 23:01Speaker 03

  Okay, we're gonna redo the experiments.

• 23:03Speaker 01

  And we should note, they're using questionable methods to test the serum's effectiveness.

• 23:08Speaker 03

  They're testing on themselves. Okay, we didn't die. I'll try a spoonful. You know, how are we gonna deliver this extract? And how are we gonna get more?

• 23:18Speaker 01

  You say they were testing on themselves?

• 23:20Speaker 03

  Yeah, they're just to make sure. Yeah, it was something not uncommon for Banting.

• 23:25Speaker 01

  That seems risky.

• 23:26Speaker 03

  Yeah, yeah. Again, bull in a china shop is a way to describe him sometimes.

• 23:31Speaker 01

  They are desperate to crack the hardest part of this puzzle.

• 23:35Speaker 03

  How do we make the leap to humans?

• 23:39Speaker 01

  How can they concoct a serum that's purified enough to test on a human?

• 23:46Speaker 01

  As the end of 1921 approaches, MacLeod says it's time to bring in a more experienced teammate.

• 23:53Speaker 03

  We need to bring a better expert in.

• 23:55Speaker 01

  Dr. James Bertram Collop, a renowned researcher and endocrinologist.

• 24:00Speaker 03

  December is when JB Collop, Dr. Collop, joins the team. He's our first Canadian-born professor of biochemistry. He's this person that can get us over the finish line.

• 24:13Speaker 02

  He was a very astute biochemist.

• 24:16Speaker 01

  This is Alison Lee.

• 24:18Speaker 02

  I'm a historian of science and medicine, and I'm the author of a biography of James Bertram Collop. He had learned some of the latest methods in measuring blood sugar.

• 24:31Speaker 01

  Banting had actually wanted the biochemist to join the team months earlier. But now he wondered if he was really needed, worrying that this renowned researcher might Bigfoot him and get all the glory.

• 24:43Speaker 03

  Banting sees his experiments being taken away from him. The collaborative process, in his mind, is me and Charlie. And whereas MacLeod is seeing the bigger picture and realize we have to bring in somebody else, because we're on the cusp of something.

• 24:59Speaker 01

  The cusp of a major breakthrough, producing a solution fit for humans. And they know they're close. The stakes could not be higher. Tensions are flaring, and it exacerbates feelings in the lab. Who will discover the solution first?

• 25:17Speaker 03

  They are butting heads, and they're not making it easy on each other, if we put it that way.

• 25:28Speaker 01

  The new year arrives, 1922. The men are in separate labs now. Banting and Best in one, MacLeod and Collop in another.

• 25:38Speaker 03

  It's a team, but they're sort of working in a separate, two different labs, sort of thing, sharing information.

• 25:46Speaker 01

  Banting and Best struggle with their extracts. Collop's experiments are going smoothly. He makes his own extract, improving on Best and Banting's approach. The team thus far had used the serum on dogs and tested on themselves. It was time to make the leap to someone who had diabetes. Enter 14-year-old Leonard Thompson, who was languishing in a bed at Toronto General Hospital, not far from the men's lab. Without treatment, he would soon die. Banting and Best approach MacLeod. They want to help Leonard with their extract, to be the first to ever successfully treat a human.

• 26:28Speaker 03

  They convince him, without Collop's knowledge, that we've got something. It's kind of nasty. Banting can't get hospital privileges in Toronto for this. Because, you know, and I think it's legitimate. He wasn't in private practice at this point.

• 26:44Speaker 01

  But the men plead with MacLeod.

• 26:46Speaker 03

  We have someone we know is dying, a couple of blocks away, and we might have something here.

• 26:52Speaker 02

  It was really because he was on the verge of death, and they really felt that it was worth a try.

• 27:00Speaker 01

  Banting goes behind the back of their more experienced colleague, Dr. Collop, to convince MacLeod to approach Leonard's parents.

• 27:09Speaker 03

  They go over to Toronto General Hospital and speak with Mr. Thompson. I can imagine what the conversation was like. It was just like, you know, your son's not long for this world. I've got two guys in the hallway here who have something that they think is gonna work. Can we use your son for this experiment? You know, you think of it today. I mean, no ethics, or, you know, double-blind trial. It's someone who's breathing, who's not going to live much longer.

• 27:38Speaker 01

  On January 11, 1922, Banting and Best, without Collop, bring a syringe filled with a thick brown solution they call Ilotin to Leonard's medical team at the hospital.

• 27:52Speaker 02

  His doctor agreed to give that a try, and Leonard's father, Harry Thompson, agreed to let them try Banting's serum on Leonard. And so he was injected with 15 cc's. And you can imagine Harry Thompson sitting by his son's bedside, watching this poor boy who was emaciated.

• 28:20Speaker 03

  There's still too many impurities, and it leaves this sterile abscess at the point of injection.

• 28:25Speaker 02

  And so in the chart, it said no clinical benefit was evidenced.

• 28:32Speaker 01

  When the experienced biochemist, Dr. Collop, hears about this failed attempt...

• 28:37Speaker 03

  She's outraged. I thought, we're a team, even though we're working separately. And so he just doubles down. You know, he says he pulled a Banting.

• 28:46Speaker 01

  Now, Dr. Collop needs to beat the clock. himself. For a few days, he works late in the lab, motivated to crack the purification problem and offer something to the Thompson family much better than that brown sludge.

• 29:00Speaker 02

  And by adjusting levels of alcohol, he suddenly saw this sort of white substance precipitate out of the solution.

• 29:11Speaker 01

  A substance he dubs colip'silin. With the purified, clear serum in hand, MacLeod persuades Leonard's family to try another shot. So on January 23rd, 1922.

• 29:25Speaker 03

  Again, knock on the door, you know, Mr. Thompson, you know, it's a hate to oversimplify it, but it just makes the story that much more fantastical. I've got this guy in the hallway who's got something.

• 29:36Speaker 02

  11 that morning, his doctor injected Leonard with some of this extract. The results were just strikingly positive.

• 29:48Speaker 01

  The boy's blood sugar drops. His eyes flutter open.

• 29:52Speaker 02

  They immediately noticed that Leonard felt better. He looked brighter and stronger and more energetic. He immediately felt better. This was clearly the first successful use of the substance insulin.

• 30:10Speaker 03

  Almost six months to the day for that first test on that dog. We have now successfully translated that into a successful human test. It was a race against death that they beat.

• 30:25Speaker 01

  Leonard Thompson would survive. The first patient who was successfully treated with insulin. The four men had done it.

• 30:35Speaker 03

  And then, oops.

• 30:38Speaker 01

  They'd done it once, but now they couldn't figure out how to make another batch of this lifesaving cure. And pretty soon, a lot of people were going to want it. That's coming up.

• 30:55Speaker 02

  This is Carrie calling from Mexico. Thank you for continuing my education in a way that actually sticks with me. You're listening to Throughline from NPR.

• 31:05Speaker 00

  Stay tuned for the following announcements and messages from our sponsors. This message comes from Capella University. That spark you feel? That's your drive for more. Capella University's FlexPath learning format lets you earn your degree at your pace without putting life on pause. Learn more at capella.edu. This message comes from Bowlin Branch. Change the way you sleep with soft, 100% organic cotton sheets from Bowlin Branch, designed to help you fall asleep faster. With airy blankets, cloud-like duvets, and breathable sheets, experience pure comfort on night one and feel your sheets get softer with every wash. Discover the difference with 15% off your first order at bowlinbranch.com with code NPR.

• 31:50Speaker 00

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• 31:53Speaker 05

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• 32:19Speaker 04

  Part three, replication.

• 32:23Speaker 01

  News of insulin's lifesaving treatment wasn't blockbuster at first. In fact, the news reports only trickled in. The local paper headline, Toronto Doctors on Track of Diabetes Cure. It takes time for news to trickle out about this amazing discovery. But when it catches on several months later, it's big.

• 32:47Speaker 01

  Serum Proves Boom in Fighting Diabetes, from the New York Times. The medical establishment is astonished by Banting Best, MacLeod, and Colip's work.

• 32:58Speaker 02

  They would see people come out of diabetic comas. And the language they used was the language of resurrection.

• 33:10Speaker 02

  One of the most famous researchers sort of used the language of the Bible. He said it was like prophet Ezekiel talking about seeing a valley of dry bones come to life.

• 33:27Speaker 02

  Because they had seen these children

• 33:31Speaker 02

  were really on the verge of death, suddenly being brought back to life and to be able to expect to live longer lives because of that. And so I think very early on, people who really understood diabetes really felt it was almost like a miracle.

• 33:54Speaker 01

  A miracle that conjures a pilgrimage. Soon people flood to Toronto for human trials to help reproduce the solution. At first, it's known as Colip's extract, which enrages Banting. It's a harried, rushed process. The doctors are like short-order cooks.

• 34:11Speaker 03

  Call referred to as it was bathtub chemistry.

• 34:14Speaker 01

  To keep up with the demand, the team first partners with another Canadian lab. They get a $5,000 advance to expand the extraction from lots of animal pancreases. And they also patent their discovery. When they do, the internal squabbling over naming rights ends. They decide an insulin, a scientific name that circulated years earlier by a Belgian scientist.

• 34:43Speaker 02

  The patent was taken out in the names of Banting, Best, and Colip. And what they did was they sold the patent to the University of Toronto for $1.

• 34:55Speaker 03

  For that nominal dollar each fee to make it available for the world.

• 35:02Speaker 02

  They really felt it was wrong for them to personally profit from it. And instead, they had the university hold the patent and then license it out to reliable manufacturers. The whole idea was that they wanted to make insulin available at a low cost to everyone who needed it around the world. And they wanted to prevent any manufacturers from monopolizing it.

• 35:34Speaker 01

  And within the year, they need to turbocharge the operation. Demand is skyrocketing. So they make a deal with the pharmaceutical company Eli Lilly. By October 1923, the Nobel Prize Committee takes notice.

• 35:50Speaker 03

  And the wording is fantastic. The professorial staff at the Caroline Institute has considered the work of Banting and MacLeod to be of such importance theoretically. So there's MacLeod's 40 years. And practically, Banting taking it from the beaker to the bedside that we resolve to jointly award them this great distinction.

• 36:11Speaker 01

  A glaring omission from the announcement and the team's award, Charlie Best and Dr. James Colip.

• 36:18Speaker 03

  And Banting is outraged.

• 36:22Speaker 01

  Banting sends a telegram to Charlie Best, who was giving a lecture at Harvard.

• 36:27Speaker 03

  Charlie, I'm hurt Nobel Committee won't recognize you. To you I ascribe half my prize money, Fred. So Banting, this great man for this discovery, now is giving half his prize money away. How can you not elevate this man's status?

• 36:45Speaker 03

  MacLeod gets blindsided by this.

• 36:48Speaker 01

  And when asked, he tells a reporter that he needs a few days to figure out what he'll do with his share of the prize money. Eventually, he telegraphs Colip, some say reluctantly.

• 37:00Speaker 03

  He releases a statement to the press. I spoke with Dr. Colip. He's agreed to take half my money.

• 37:09Speaker 01

  After the prize announcement, the four men went their separate ways. Charlie Best finished his graduate degree at the University of Toronto and went on to serve as the head of the physiology department there. MacLeod left Canada for a new university position in Scotland. Colip, the brilliant mind who made victory possible in the final week, was forgotten to history until recently. And Fred Banting, he became a national hero. The man once consumed by failure became the face of the drug before pioneering aviation medicine during World War II. Banting and Colip, the man forgotten to time, eventually did make up. Before setting off for a research mission in Britain,

• 37:53Speaker 01

  Banting and Colip met up.

• 37:56Speaker 02

  The last friend to see him before he went on that trip was Colip. Colip and he had a dinner together. Colip gave him a warm pair of gloves to wear on the plane.

• 38:07Speaker 01

  Banting would never live to tell the story. Shortly after takeoff on February 20th, 1941, the bomber he boarded crashed in eastern Newfoundland. Just 49 years old, he died with those gloves gifted to him from the man he once worried might steal his glory.

• 38:29Speaker 01

  Before he died, Banting got to see so many lives changed, including Leonard Thompson, who lived 13 more years after that first successful dose of insulin. Millions more have been saved since.

• 38:43Speaker 03

  He received letters from around the world.

• 38:47Speaker 03

  Dear Dr. Banting, I'm a fat boy now and I feel fine. I can even climb a tree. I hope you're well. Four-year-old girl. My mommy says this is the greatest Christmas ever. Thank you for your gift. Dear Dr. Banting, this is the site of the greatest moment for Alzheimer's type 1. My daughter diagnosed last week at age 2 deserved to live.

• 39:09Speaker 03

  Dear Dr. Banting, this is my 17th anniversary. I came to let you know I'm alive and doing well. I look forward to seeing you again next World Diabetes Day. We have almost 4,000 of these letters in our collection now, written in 13 different languages.

• 39:30Speaker 03

  You know, as a public historian, it doesn't get any better than that. These are people writing to a dead man.

• 39:38Speaker 01

  It's remarkable to think. That as Leonard lay starving and dying, his father and mother made a remarkable choice to place hope in an injection of an untested serum, a concoction that was imagined in a dream just a year earlier and reproduced with suspect methods by a failed surgeon who had never studied diabetes. Had the Thompsons known any of the twists and turns that led up to that first injection? Who knows what they might have decided?

• 40:24Speaker 01

  And that's it for this week's show. I'm Randa Abdel Fattah. Throughline was created by me and Ramtin Arablouei. This episode was produced by me and

• 40:34Speaker 04

  Amy Padula. Julia Redpath. Molly Marcello. Sarah Wyman. Lou Olkowski. Lyanna Simstrom. Irene Noguchi.

• 40:45Speaker 01

  Fact checking for this episode was done by Kevin Vogel. You can read more about this story in the book, The Discovery of Insulin by Michael Bliss. Thanks also to Johan Nystergi, Josie Gettle, Jeff Leon, and Scott Hensley. This episode was mixed by Jimmy Keely. Music for this episode was composed by Ramtin and his band, Drop Electric. And finally, if you have an idea or liked something you heard on the show, please write us at [email protected]. Also, make sure to follow us on Apple, Spotify, or the NPR app. That way, you'll never miss an episode. Thanks for listening.

• 41:26Speaker 05

  Stay tuned for the following announcements and messages from our sponsors.

• 41:30Speaker 00

  This message comes from Bowlin Branch. Change the way you sleep with soft, 100% organic cotton sheets from Bowlin Branch, designed to help you fall asleep faster with airy blankets, cloud-like duvets, and breathable sheets. Experience pure comfort on night one and feel your sheets get softer with every wash. Discover the difference with 15% off your first order at bowlinbranch.com with code NPR. Exclusions apply. See site for details. This message comes from Whole Foods Market. Fall tastes better with better ingredients from Whole Foods Market. No added growth hormones or antibiotics in their meat department means slow-braise short ribs are even more satisfying. All seafood is wild-caught, like they're vibrant sockeye salmon

• 42:14Speaker 00

  or verified responsibly farmed. And all sweets, including fall-themed cookies, are made without high-fructose corn syrup. Spice up fall at Whole Foods Market.