Secretly Incredibly Fascinating - Insulin

Episode Date: April 8, 2024

Alex Schmidt and Katie Goldin explore why insulin is secretly incredibly fascinating.Visit http://sifpod.fun/ for research sources and for this week's bonus episode.Come hang out with us on the SIF Discord: https://discord.gg/wbR96nsGg5

Insulin. Known for being medication. Famous for being for diabetes. Nobody thinks much about it, so let's have some fun. Let's find out why insulin is secretly incredibly fascinating. Hey there, folks. Welcome to a whole new podcast episode, a podcast all about why being alive is more interesting than people think it is. My name is Alex Schmidt, and I'm not alone because I'm joined by my co-host, Katie Golden. Katie, what is your relationship to or opinion of insulin? Well, I often get angry at the backstory about insulin. I'm not someone who needs to use insulin. I read about how insulin prices are really high and then I get just so piping hot mad about it. It's not the insulin itself that is at fault here. It is a life-saving substance for people with type 1 and type 2 diabetes. But it is, in my opinion,

should just be free. It should be free, and I'm upset that it's not. Okay. Because when you said you get upset at the backstory, do you mean like that current modern pricing issue in the U.S., or do you mean like the historical? Okay. No, no, no. I mean, I don't know enough about it.

I just know that the inventors of insulin released the patent, made it publicly available. And then like, it should, it should not be patented. Like it should be, in my opinion, it should be a public good. But no, I'm not like mad that they invented insulin. I think that's good. And that's pretty much my relationship to it is I never really think about it. And then I hear about it costing too much once in a while because I'm not diabetic and I don't, it doesn't cross my mind a lot. But many thanks to listeners Skinnerd13 on the Discord who ran a 1 diabetic. So they are excited for other people to think about insulin as much as they do, which is a fun reason. Like, yeah, it's really going on for a lot of people in their day to day. And the rest of us probably don't let it cross our mind that much. I was friends with a girl who had type 1 diabetes in middle school.

I remember being really in awe of her because she would give herself the insulin shots. And it's amazing that we are able to give people medicine in this way that you can kind of just become your own deliverer of medication. Yeah. Yeah, 100%. And this episode, we're going to start from the past and work to the present in modern times. And this is our first episode, as far as I can figure, about a hormone. Insulin is a hormone, so that's fun. And we'll talk about diabetes often. Also, diabetes itself could be a whole separate episode. So we won't hit every amazing story about diabetes. We'll mostly talk about it in relationship to this bodily hormone itself.

Yeah, because when you say insulin, I think about insulin as the injectable medication for diabetes. But yeah, it is just something that is a hormone that everyone has in their bodies to help with processing energy. So it's kind of like, yeah, it just exists, but I think about it in a medical context. And then the other thing we won't talk about much because it's more of a diabetes show topic is a few new medications such as Ozempic, Wegovi, and Monjaro. It turns out those were made for diabetes, but are actually not insulin. They are simulating different hormones that mostly give a feeling of fullness in the stomach. So the one thing to say is I had really presumed those were insulin related and they're not. There's no insulin in those. It's a separate kind of parallel thing.

no insulin in those. It's a separate kind of parallel thing. Yeah, man, there's so much that could be said about like WeGovie and so on, but I just feel like so ill prepared to hop into that discussion. So I'm glad that's not what this episode is about. Yeah, it's just about one little hormone from the pancreas, our friend insulin. Yay! And also relevant to every listener producing it or need to take it as a supplement. So this is for everybody, folks. You need insulin. We all need it. Let's get into some fascinating numbers and statistics. And this week that's in a segment called... Stets it out, stets it out, whoa, whoa, Stets it out, Stets it out.

Nice. Yeah, there we go. That name was submitted by Melodramajestic on the Discord. Great name, Melodramajestic. Are you a Swifty? A Statsy Swifty? Am I a Statsy Swifty? I guess so.

This is not the first Taylor Swift song. I guess I'm going that way. Yeah. She also, she has a really quite heartbreaking song called So It Goes. And that is a phrase made famous by Kurt Vonnegut. So I was excited to find that out the other day. That's pretty cool. Yeah.

Yeah. Yeah. I have nothing against Taylor Swift. Oh, yeah. Yeah. I'd like to state that for the record. And our first number this week, our number is two, because there are, in a very general way, two functions of the human pancreas. There's two broad jobs of that organ that I never think about.

I just let it run in there. You can have a pancreas fight if you're in the OR, throwing around pancreases, it's really messy. And the name feels like a comedy word to me. It's one of the funnier organ names, just for some reason. I don't know. Yeah. I'm imagining sort of a brownish red colored floppy, sloppity organ. Yeah, I believe it's a little more yellow, but it's kind of that broad shade of color. Yeah, right. And it's very bumpy all over itself. I'm Googling a pancreas right now.

Yeah, everybody do this. Let's all get pancreas on our phones, you know, let's check it out. Okay, no, these are just diagrams. I want real human pancreas on our phones, you know? Let's check it out. Okay, no, these are just diagrams. I want real human pancreas. Not the eBay listings. Oh no. Ew. Not gonna lie, it looks a little bit sausage-like and I don't want to eat it, but a little bit like a sausage. Just a little bit. Ironically, one of its functions is to help you eat stuff because... Yeah, like a sausage. Just a little bit. Ironically, one of its functions is to help you eat stuff because... Yeah, like a sausage.

Right. Sausages all the way down. Yeah. One main function is that the pancreas releases enzymes that help with digestion. It helps you break down food. And then the other main function is that it makes a set of hormones. The hormones go straight into the bloodstream and regulate bodily functions. And one of the main ones is a hormone called insulin. And insulin is an essential hormone, according to the Cleveland Clinic. You have to have it. And it allows your body to turn glucose into energy. One metaphor I

saw is that it's like a key that goes into a lock to allow glucose into the door of your cells to power your cells. Yeah. In terms of cellular biology, a general thing is that anytime you have like an interaction between a cell and glucose or protein or whatever, it is a physical one thing bonking into the other, unlocking a thing. Yeah. You know, like it's a Rube Goldberg machine on a microscopic level.

And so insulin, like you said, it's like this key that helps unlock, it facilitates this interaction between the cell and like sugars and stuff such that they can go in the cell and make stuff happen. Exactly. And before researching, if somebody had forced me to describe insulin, I would have guessed it's some kind of sugar. But it's a hormone that facilitates sugar to do stuff. Exactly, yes.

And it's also, in a super technical level, it actually decreases the amount of sugar in your bloodstream. Because what insulin does is it allows the glucose in your bloodstream to go into cells and be used by cells. Yes. And so if you don't have insulin, that means sugar builds up in your blood and leads to high blood sugar, leads to diabetes. On its own, that could lead to your death if it's just completely unmanaged and undealt with. Yeah. And we're not really talking about added sugar to food. If you're like, oh, well, if sugar is good for me, I should have some packets of white sugar. You know, sugar is found in everything.

It's found in apples and broccoli. You don't need to add sugar to food because food already has sugar, generally speaking. Yeah, I like that we did a caffeine episode recently on that topic because it was interesting to learn that caffeine is a totally optional drug, but sugar is not optional. And I have a dependence on added sugar, but I also need there to be sugar and, like you said, broccoli and other things where I don't think of them as sugary. Back on the topic of insulin, yeah, it's interesting. When we eat food, it's hard to imagine all the tiny processes that happen among our cells that is breaking down this food into usable parts. Like, you know, it's not just like one food molecule, like a cell eats and goes, mmm, yummy food.

You know, it's like broken down into all these different components. There are proteins, there are lipids, there are water, you know, all of these things. There are proteins, there are lipids, there are water, you know, all of these things. And then there are these chemical reactions that happen outside your cell, on the surface of the cell and within the cell. Those chemical reactions just sort of boil down to essentially physical interactions between molecules bonking into each other and causing structural changes or reactions. And there's so much stuff going on there. It's like a constant, it's a constant party inside, inside our bodies. It is like, it turns out insulin is not even the only hormone from the pancreas related to blood sugar. There's another hormone called glucagon,

which raises your blood sugar. Like the pancreas is just doing a lot of different versions of that party to make the blood sugar level in your blood sugar. The pancreas is just doing a lot of different versions of that party to make the blood sugar level in your body correct. Does glucagon interfere with the uptake of sugar or something like that? How does it raise the level of blood sugar? It's pretty much that. The Cleveland Clinic says glucagon triggers your liver to convert stored glucose into a usable form. And it can also prevent your liver from taking in and storing glucose so that more of it stays in your blood. And it can also help your body make glucose from other sources such as amino acids. So it's another whole lever your pancreas can pull is to make this glucagon stuff. Yeah. whole lever your pancreas can pull is to make this glucagon stuff. And I had never heard that word in my whole life, but it is related to the word insulin that I had heard. And it's just interesting how much of this we pick up in our day to day. The next number here is 422 million. 422 million, that's a World Health Organization estimate of how many people have a form of

diabetes in the world. And that's including both type 1 and type 2? It is, yeah. And quick version since it's not our main topic, type 1 diabetes is a condition where the pancreas produces little or no insulin. It's usually diagnosed in childhood. Sometimes it's called juvenile diabetes. And then type 2 diabetes is more often diagnosed in adulthood. And that's when you had a pancreas making insulin, but your body has developed a resistance to using that insulin over time or has stopped making enough insulin. Something has developed over time. Right. stopped making enough insulin. Something has developed over time. Another number is about 37 million Americans have type 2 diabetes on its own. So that's about 1 in 10 people in the United States just with type 2. Another population has type 1. This is a very common situation

in people's lives and in your community. And like we said, you have to have insulin in your body, no matter who you are. So it's very important that we provide it to people. Yeah, if you think you're too rich to need insulin, think again. Yeah, you can't eat enough bull testicles out of having to have insulin. Thanks, pancreas. Yeah, what a good organ.

Who's a good organ? Who's a good organ? Who's a good organ? You do a good job. The pancreas, again, it does these two things, enzymes for digestion and hormones for your blood sugar and other processes. And there's a lot of astounding medical history around us understanding that. And we're going to make that a mini takeaway number one. Scientists discovered the pancreas and discovered diabetes many centuries before they understood insulin. It turns out we've known about insulin for less than 200 years.

Well, pancreas big, insulin small. So it makes sense that we would discover the pancreas before insulin. And also that we would maybe discover diabetes before insulin, because diabetes is like a disease that has physical effects on the body. And so it's like we would be able to observe these things before we have the ability to identify the insulin hormone exactly yeah yeah those things have been with us for all of people being people and and the pancreas is a large organ like as yeah as people just saw the insides of humans they said hey what's that like it's's the sausage doing in them? I'm going to taste it. Now I'm hungry for sausage, but I guess I'm bad all the time. That's a latent state.

That's sort of a Schmidt affect. Yeah, oompa music starts playing in my soul when I think about sausage. It's really a thing. A little alarmed that it's in the context of a human organ, but okay. But yeah, so with both these things we've known about for a long time, starting with diabetes, then going to the pancreas, there's still numbers in this mini takeaway. The next number is 3,500 years ago. And 3,500 years ago is a possible earliest recorded observation of diabetes that we still have evidence of and the writing of. And it's cool. It's written on ancient Egyptian papyrus. And this is the American Chemical Society is the

source. They say a physician named Hesi Ra used papyrus to write about a condition of frequent urination and a few other symptoms. And it may or may not be a description of diabetes. One diabetic symptom can be that the kidneys are not filtering enough excess glucose. And then there's more sugary fluids in your urine and more urination. Yeah. And so if your urine tastes sweet, it could be diabetes. Yeah, turns out. Just test your urine every day. Taste a little bit of urine just to check to make sure you don't do that. I'm joking. It's a joke. Because I did think that ancient doctors would do a lot of pee-pee tasting because before we had like laboratory analysis where you can like, you know, kind of test urine for various things.

You can do a test of urine for signs of diabetes without having to taste it. But, you know, back before that, you could have a doctor just, you know, taste a little bit of that pee-pee. Yeah, exactly. And one of the recorded examples is 1675 is the year, AD, 1675. That's when a British scientist named Thomas Willis started testing the urine of some of his patients. And when he tasted it, he discovered a connection between patients with sweet-tasting urine and patients with diabetes symptoms. And he coined the name diabetes mellitus because mellitus means honeyed. And he was like, if you have honeyed urine,

you probably have this thing we're beginning to call diabetes. Did he ever make sort of like cocktails out of his like patients pee pee? Like, you know, like, you know, just kind of have different vintage patient pee pee. It would be very British if he did. We'll link about British people like eating mummies and stuff. They did a lot of that back in the imperial day. It's like people jerky.

Sounds good. Sounds good to me. Flipping to the pancreas itself here, the history of medical understanding of this is really weird because it took until the 1600s for European scientists to begin to accurately identify any of what the pancreas does. The 1600s, they started to get a few correct guesses going about it. Before that, they just kind of said it's in the body. It seems like it'd be hard with the pancreas, right? Because it's producing hormones. With the heart, you can kind of see it moving around, pumping blood. There's kind of a more direct connection there. Lungs too, like, you know,

it seems like a lot easier to kind of see the physics of like the heart and the lungs and even the blood vessels, right? Like you start to get a sense of that. Even things like, you know, gonads or even the brain, right? Because like if you have like a head injury and it affects your behavior, it could be like, huh, that's interesting. But like with the pancreas, right? Like how do you determine what these weird little organs, or not even that little, but just weird organs that are doing stuff on a scale where it's like, we don't even know insulin exists. We don't know what it does, let alone that it's there. So how would you know what the pancreas does?

How would you even guess? Exactly. Yeah. Enzymes and hormones are not very visible. And so they saw this big organ with no obvious purpose. And Greek and Roman people tended to guess it was padding, like it was packing peanuts or something, like just protecting the important stuff. Yeah, packing peanuts. It does weird me out how like after surgery and stuff, like when they kind of have to remove stuff to get at the stuff that they're doing the surgery on, they just kind of like, you know, in a doctorly way, kind of put stuff back in, but it's not like there's any like reassembly that's too precise. It's just like, kind of like put it in the general location and, you know, and then like your intestines,

like after surgery, sometimes like, you know, your your intestines will just settle back in after you're moving around for a bit. And it's just so weird. It's like you'd think there'd be a much more formal like IKEA level reconfiguration of your organs. But no, it's just kind of like, well, this sort of is in this area. Your intestines kind of get piled up in this area. And, you know, bada bing, bada boom, it's done. Rez, it's a little less precise than the weird electrical board game Operation. A little bit less.

Like, yeah, you know, it can go in there. If you hit the sides, it's all right. Yeah, there's not really like a slot for your pancreas to go in. Yeah, and the Greek philosopher Aristotle, he thought the pancreas was a shield for major blood vessels. And the Roman doctor Galen guessed that it might physically cushion the stomach. It's just kind of helping with like if you get hit. Like a pillow, a pillow for your tummy. Yeah, and the ancient Greeks named it, they coined the name pancreas, but it just comes from words that mean all flesh and probably referred to the uniform physical appearance of it. Like it's just that same kind of bumpy, sausagey vibe across the whole thing.

Well, all right. So that's where the name comes from is they just said, you know, it's fleshy. That's what we know. Man, they weren't very creative. It would have been cool to call it like the snake organ or like the sausage thing, but yeah, all right. Just like, yeah, it's fleshy. Seems like that describes a lot of stuff, but all right. I am. I'm just realizing from my doc that the next scientist here is German. So great. He should have called it stomachwurst or something, but he didn't get to it. The next scientist here is German. So great. He should have called it stomachwurst or

something, but he didn't get to it. The next scientist, 1642 is the year. So pretty close to now historically. An anatomist named Johann Wirsung, he discovered a duct leading from the pancreas to the intestines. This is one of the first real medical discoveries about the pancreas is that just a few hundred years ago, they figured out it's connected to the intestines mechanically. It was news. They were like, holy cow, a hole. We have a lead. He decided to publish this, but science was so weird in 1642, he didn't publish it on paper. He hired an engraver to make copper plates depicting the ducts and then shipped the plates to various other leading anatomists.

Huh. Was the idea that paper was just too flammable or why the copper plates? I think it was weird even then. Maybe his buddy was an engraver and needed work or something. They were printing stuff on paper at that point. It was weird even for them. Yeah. So then these 1600 scientists said, we know more about the intestines than the pancreas. Maybe this relates to digestion. And they proceeded to make actual discoveries about just one of those two functions we described, the enzymes for digestion part. They started to figure

out, like they extracted fluid from a pancreas and put it on foods and saw that it broke them down. Ah, there you go. And then more than 200 years later, 1869 is our next number. That's when a German medical student named Paul Langerhans noticed that the pancreas contains a distinctive type of cell. Okay, that's why they're called Langerhans cells. Yeah. Oh, it's cool you know. Yeah. I'd never heard of him. I heard about him like, I don't know, it's been like 10 years. I used to work for a company where we would make medical educational materials, so like textbooks and e-learning modules.

That's great. Langerhans cells. I think maybe it has something to do with insulin production. That's the thing, like Langerhans found these and said, maybe this has something to do with other pancreatic functions. And that's the main things he could figure out. It turns out these are patches of endocrine tissue that make insulin. Ah, okay. And so 1869 is when we began to see the body part at all that makes insulin, like within the pancreas.

Less than 200 years ago, we said, there it is. That's how recent these discoveries are. Yeah, it takes a while. Also, his finding of this is where we get the name of insulin, because they describe these as islands, and they're sometimes called islets of Langerhans. And the Latin words for islands are insular and so on. And so insulin comes from an island name in Latin. That's why it's called that. No man is an island, but a Langerhans cell kind of is an island. The other amazing medical history thing here is takeaway number two. The key experiment that brought insulin to patients came from Canadian scientists and from heroic dogs.

Oh, no. Oh, no. Why were the dogs heroes? Because of their sacrifice and experiments. Yeah. Oh. Yeah, I'm sorry. That was at the beginning when you were like, I object to the background of insulin. I was wondering, like, is it the dog thing? But this might be news. No, it's that it's now it's that we're

killing people by making it too expensive when the people who made it explicitly did not want that to happen. I'm sad for the dogs. I do think it's, oh, man, poor puppies. But I'm glad insulin exists because people really need it. And I think it has overall reduced the amount of suffering in the world. But man, look at this puppy. He's so sad. I'm looking at a picture and I can only assume these guys are insulin researchers. And there's this dog who looks very askance.

He's like, wait, we're doing what now? I don't want to be a hero. I just want some sausage. We have a bunch of sources here and some of them are the Canadian Encyclopedia and a Canadian Heritage Minute. It turns out that until the 1920s, the disease of diabetes was essentially a death sentence for many patients. Yeah. Untreated, it's really terrible. Yeah, because before then, we did not have insulin available as medication. It was just a hormone, and some people and then the people who didn't have it were often told by a doctor, you have diabetes and you're going to die. And there are things we can do to like prolong your life, but that's it. Yeah. Yeah. And so it turns

out that the scientists who made the key last leap to make insulin a pharmaceutical did experiments on dogs that are a huge bummer, but were necessary and heroic by the dogs, even though they didn't choose it, to make this a medication and save millions of human lives in the past and present and future. Yeah. I mean, you know, I really love dogs, and I would have preferred they used like a less affable animal. I mean, I love all animals. Let's be clear. But, you know, like if they had been able to do these tests on, say, mosquitoes instead of dogs, that would have been better.

Obviously, that's not. They didn't just choose dogs because they're being mean. I'm especially sensitive to this today because my dog, Cookie, has diarrhea. She's getting better. She's feeling a lot better today. Yeah, but she has some diarrhea and I've been making her mashed tatoes and white rice for her tummy because she's had a tummy ache and like giving her belly, like very gentle belly massages to help with a digestion so i've been really like coddling and taking care of cookie uh for her diarrhea and so i'm like like yeah so i'm just like the idea of a sick dog makes me feel very emotional right now i'm fine though though. I'm cool. But yeah, Cookie's doing good today.

She's very hungry for mashed potatoes. Oh, and also with this story, in particular, a key Canadian scientist here named Frederick Banting, he apparently grew up on a farm, was hugely a dog person. And it seems like the scientists who chose dogs for this, they partly chose them because they love dogs, are very good with dogs. Banting was conflicted and heartbroken throughout this experience. And it was rough on everybody, but it was with the knowledge that they were in particular saving children's lives. Sorry. Was it rough? Oh, no. Why did I pick that? Was it rough? Alex.

I look, it starts here. It's, this is how we cope. This is, well, this is specifically how I cope. No, I don't think these like, yeah, it's, I, I have very complicated feelings about animal research. I think that it is justified when it's going to save so many people's lives and save so many people from suffering. Like, obviously, I think that we should do everything we can to spare animals from suffering as well in laboratory settings. But, you know, I think that the, I'm sure that the researchers that were working on this were not just like psychopaths who were mean to dogs, like, and that must've been tough. Yeah, the key scientists here,

there's one more guy in Germany. His name's Oskar Minkowski. He was born in Russia and Lithuania and then moved to Germany, partly because of how Russia was. And he became a leading researcher on diabetes. In 1889, he published findings from a set of experiments on diabetes. In 1889, he published findings from a set of experiments on dogs. And they did groundbreaking work indicating the relationship of the pancreas to diabetes. And tragically,

the experiment was remove a pancreas from a dog and see what happens. And what happened is the dogs got diabetes immediately and then died of it. Yeah. And so, you know, tragic and such a necessary building block for how science worked at that time. Like, that's just how they could figure it out. If I could go back in time, I would remove the pancreas from baby Hitler instead. Just getting in a time machine with extremely specific tools. That doesn't look good. I don't like it. Time for some baby Hitler surgery.

But yeah, and then in 1920, there was a orthopedic surgeon in Ontario, Canada named Frederick Banting, who was not a researcher and was not really a diabetes expert. But Banting was going to give a medical school lecture. He just learned as much about diabetes as he could. And then he had a guess that they could expand on those dog experiments. What they could do is they'd remove the pancreas of one dog, but then they would, this is hard, but basically tie off the pancreas of a second dog within its body. And so whatever a pancreas is producing would get like concentrated in that pancreas and then take an extract of that, inject it into the first dog and see if that relieved its diabetes and kept it going was his idea. And this idea doesn't totally biologically work, but it got them on the path.

Yeah, it's like not a terrible idea for the time period, but man, saw level like, you know, medicine. Just like, what if we create and turn an organ into a balloon and take the juices out and use it on the other dog? Yeah. Yeah. Frederick Banting gets so passionate about this experiment, he starts doing it for no pay and with no funding. He just goes to a university. He's able to get one volunteer college student to help, a guy named Charles Best. Banting and Best start doing these dog experiments. They eventually get the help of an actual professor named J.J.R. MacLeod and also a biochemist named James Collip. As they did this set of experiments, luckily J.J.R. MacLeod,

who knew more about all this stuff, said, hey, you could kind of do the same experiment with discarded pancreases from cows and pigs and other animals that were eating and turning into parts in slaughterhouses. And I know that's grisly, but they realized, oh, part of this dog experiment, we could use less dogs. Let's immediately switch to that approach. They found better ways as they went. And across experiments, they start to get more and more pure pancreas extracts and better approaches to injecting them into the dogs. And they start being able to make dogs live without pancreases for many days in a row. The most successful dog was a dog they named Marjorie who lasted more than two

months and maybe could have kept going. They just decided they didn't have enough pancreas extract and had to stop. But thanks to these experiments, they were able to do an injection in a human. And they did that in January of 1922. The world was full of human children just dying of type 1 diabetes. And so they found a 14-year-old named Leonard Thompson, injected him with a pancreatic extract that immediately made him feel better. And from there, the world said, we've found a way to make this not a death sentence anymore. That Canadian team won the 1923 Nobel Prize for this insight. And they gave away the idea and drug companies started making what became called insulin for diabetes patients.

It's so amazing. Just like going from like these weird theories of like, maybe this is what it does. Look at these weird cells. And like, and then finally getting to the point of like, okay, this juice is going inside this kid with diabetes and it worked. It's so incredible. Yeah. Just fantastic. Yeah. And they were very world-minded about it.

They started partnering with a drug company called Eli Lilly to manufacture it, but it wasn't made exclusive to those guys. They just teamed up with business because that would make more of this sooner, faster. And the Nobel Prize money went to just two of the guys, and then they shared their prize money with the other two guys. And it was a very positive group of people. And they made this big change for everybody. Yeah. No, I mean, I think they did an incredible job. I'm still mad, though, because what they clearly wanted was to make this producible and easily accessible to save people's lives. through the market forces, unrestrained market forces and patents and stuff, like it's become something that is expensive in a way that it does not need to be that expensive. It can be produced very cheaply. Yeah. And we've done our numbers and two takeaways. We have a couple more takeaways

about how insulin is made today because it's not animal parts anymore, which is great news. But we'll get into all that after a short break. So stick around for Modern Insulin. I'm Jesse Thorne. I just don't want to leave a mess. This week on Bullseye, Dan Aykroyd talks to me about the Blues Brothers, Ghostbusters, and his very detailed plans about how he'll spend his afterlife. I think I'm going to roam in a few places, yes. I'm going to manifest and roam. All that and more on the next Bullseye from MaximumFun.org and NPR. JV Club with Janet Varney is part of the curriculum for the school year. Learning about the teenage years of such guests as Alison Brie, Vicki Peterson, John Hodgman, and so many more is a valuable and enriching experience, one you have no choice but to embrace, because yes, listening is mandatory. The JV Club with Janet Varney is available every Thursday on Maximum Fun or wherever you get your podcasts.

Thank you. And remember, no running in the halls. And we're back with the rest of the takeaways about insulin, which is made very differently from those old Canadian experiments. The next one is takeaway number three. and experiments. The next one is takeaway number three. In the 1980s, we stopped making insulin out of animal pancreases and started making it by modifying microorganism DNA. Cool. It turns out the way we make it is amazing. I had never even thought about it at all, but it's a lot less grisly than the 1920s and it's really advanced and cool.

Yeah. I mean, it's good that we're not just like chugging Capri Sun pancreases in order to treat diabetes these days. There's a picture, and I didn't send it to you, but there's a picture that the Smithsonian has of like an Eli Lilly facility in the 1920s making insulin. And it's like the comedy picture. Like it's a guy pushing a pile of pancreases into a grinder. It's ridiculous. It was that joke about the turn of the century until we got a better version going. century until we got a better version going. Yeah. It is really amazing how a lot of these, like the more modern versions of drugs are made. And like you said, like modifying DNA, it's incredible. Yeah. And when we first got insulin going for people, companies like Eli Lilly, which by the way, is a guy's name that was a Union Army officer who started a drug company that mainly made quinine for malaria first. But they became a big manufacturer of insulin by just sourcing pancreases from animals that we eat, like pigs and cattle. And that was how we did it from the 1920s until the 1970s. At the same time, people notice,

hey, there are more and more diabetes patients, mainly because they're not just dying. And also modern American diets were maybe contributing to some more type two cases. And then people said, will we run out of animal parts to meet this need? Like apparently as of 1981, they needed glands from more than 31,000 animals to make insulin for 1,000 humans for one year. Also in the late 1970s, the U.S. had some economic shocks and the price of meat varied a lot. And so the drug industry was concerned about getting enough parts from the meat industry, even though you wouldn't know those are linked together to make insulin. It's a very surprising situation that developed. Yeah, it's like there must be a more efficient way to create insulin

than just creating smoothies out of countless cow pancreases. Yeah, and we finally found it in the early 1980s. Like in a lot of listeners' lifetimes, scientists figured out a way to make insulin from recombinant DNA, which is hard to describe. But the super short version is scientists isolate and extract the polypeptide chains that make up the gene of human insulin. And basically, they take a piece of this gene and insert it into a kind of bacteria. And then they use that to genetically program the bacteria to produce a bunch of insulin.

They can also do this with yeast and with a few other microorganisms. And so now we essentially get insulin out of big vats. Yeah. Use DNA and a scientific method to make microorganisms belch out a bunch of this insulin. Yeah. I had no idea any of this process happened at all. First the cows and now vats of microorganisms. And also this is a huge deal for understanding the price of insulin over time. Because when we were making it out of cows, you can see how that would be expensive.

Maybe it deserves subsidizing. But a whole cow for a little bit of insulin plus beef is one price point. And now we just need to build infrastructure of vats, essentially, and make enough buildings and hire enough people. And it's detached from our meat supply chain today. Yes. Yeah. Like the energy that goes into growing a cow to maturity is so much compared to the energy required to feed like yeast or bacteria to produce insulin in a vat. It's just way, way more efficient.

Kind of like making beer. And yeah, the FDA in the US, they approved this in 1982. So we've only been doing it in that way that long. And also there's a huge range, too many to name, of different makes and models of insulin. There's a rapid acting kind. In 2006, the FDA approved the first insulin you can inhale rather than injecting. There's also a lot of different versions of an insulin pump. And so there's constant R&D on the drug itself and the delivery system for Americans and other people too. That's just an ongoing,

amazing scientific process. Yeah. Because it is nice to be able to have other methods of delivery for insulin because even though a lot of people are able to give themselves shots every day, that's not an easy thing to do. Yeah, and related to that, we have two more fast takeaways for the main show. The next one is takeaway number four. takeaway number four. Insulin prices might be surprisingly important in the next U.S. presidential election. It turns out that might be a huge thing here in 2024. Yeah, this is the thing that upsets me. I mean, obviously the dogs upsets me as well. But to me, that's more morally understandable. But yeah, it's the fact that insulin is too expensive. Yeah. And the price thing, it's being made a huge issue by both of the candidates. And one of them is current President Joe Biden. In 2022, he and Congress passed a law called the Inflation Reduction Act. And that law touches on all kinds of parts of life. But one of them is that it capped the

out-of-pocket cost of insulin at $35 per month for people on Medicare. And I know that was a lot of policy and may be boring, but the point is that they made it so insulin can't cost more than $35 per month if you're on Medicare. And that only took effect at the start of 2024. So that's news most people haven't heard. That was definitely, though, caused by that one person who pretended to be Eli. Remember when Twitter changed its verification system where anyone could be verified and someone pretended to be Eli Lilly and tweeted out that they're making insulin free. And that forced Eli Lilly to be like, we're not we're not doing that. But then it made it into this big issue. And I think Eli Lilly even like committed to like lowering prices., and then like, yeah, I'm kind of joking being tongue in cheek. I don't actually have any evidence that this is directly linked to why it became part of, uh, you know, uh, this, uh, policy, but it is funny. Yeah. We'll link about that. Cause that's another thing. There are three main companies,

including Eli Lilly that make most of the insulin in the US, and they have variously promised to now or later do a similar $35 cap, partly driven by the very, very good website x.com that works really well, just being exploited to make a fake Eli Lilly post that says it's free now. That's amazing. that says it's free now. That's amazing. That may have been the most morally righteous troll post in the history of the internet. Yeah. But since then, and this may become more and more apparent as the election goes on, the Joe Biden campaign has done a lot to feature his concrete steps that have made Medicare patients have cheaper insulin, and then a follow-up promise of, especially if we can get reelected and get congressional majorities, we Democrats will make that $35 insulin cap a thing for everybody,

is the promise coming from. I shouldn't have used we because I'm not part of that administration, but that administration, but like that administration, that's what they're saying about themselves. You're not part of the Biden administration? You're not riding with Biden? I'm the secretary of funny podcast goofs. I admit it. I'm in the cabinet.

The S-F-P-G, secretary of funny podcast goofs. Have a little seal. It's good. Nice. Good job. You got there. You got there. Thank you. So what's the, is there like opposition to this other than like potentially from like drug manufacturers? Because like it seems like. Yeah.

I don't know what Trump's position on this. Is he going like, no, I'll make insulin more expensive. Perfect question, because there is a roundabout and probably effective way this is being argued against. Because the thing is, this change to Medicare, it was plugged into a law called the Inflation Reduction Act, right? It's not named the Cheaper Insulin Act. And it's extraordinarily big as a law. Like there is a lot more to it than insulin. It's fair to describe it as other things. Right, right. And what's happened is apparently voters don't know this insulin stuff is in that law or that this change happened at all. that have found that most voters, including people above 65 years old who might be on Medicare,

most voters have no idea this change happened at all, let alone that it's from the Biden administration and a primarily Democratic-pushing Congress. And so the scuttlebutt around the Biden camp in the election is, how do we tell anybody about this? And let's have Joe talk about it in all the speeches whenever possible. So it's going to come up a lot, this topic of our podcast. Listen, Corn Knuckle, I got you some news here about that ding-dang insulin that you like to suck up so much. Now you no longer have to stick a straw in a cow pancreas and crush that back like a Capri Sun.

We can give you your insulin in many a deliverable form. And we are committed to making this less than $39.99. That's $39.99 a month. Call now. And I'm always glad when he brings up Corn Knuckle because he was my predecessor as the secretary of Funny Podcast Goofs. I know him really well. We hang out at Camp David. He's great. It's a diminutive form of corn pop. And the other political situation with this insulin change is the idea pulls extremely well, apparently. It just is an idea everybody's into.

Well, yeah, nobody wants to die because they can't afford insulin. I mean, come on. But then the thing is, MIT Technology Review did a piece about this just a few weeks ago. They talked to a group of advisors to Republican candidate Donald Trump. And apparently in public and private, the Trump camp is saying one of our main things, maybe our main policy goal is to run against the Inflation Reduction Act. And to say this is a hugely overspending and foolish law. And the main way they're framing it, which is not totally unfair, is that they're focusing on the climate part of the law, the environmentalism part of the law. Like that is part of it. And so that's the part they're focusing on. Basically, the way this debate might go is it might be one side saying,

repeal the law that partly involves insulin without ever bringing up insulin. And then the Democratic side might be out here saying, everyone needs to know my economy and environment law is also insulin. That might be the way this debate goes over the next several months. Man, please keep insulin affordable. I remember the story of this guy who was doing a GoFundMe for his insulin, and he didn't reach the amount, and he died. And that's super messed up. That should not exist in our society.

There's no excuse for that. It is a substance that we could choose to subsidize the cost of for everyone. Yes. Because we just need to build vats of microorganisms and then bottle it, distribute it. Yes. So it's an option. Yeah. There is no reason that people need to suffer in terms of not having access to insulin.

And so I'm not going to tell you what to think in terms of politics. But for me, it's just like choosing the path where it is less likely that people will not be able to afford life-saving medicine that is cheap and easy to make. There's a whole nother US thing for our final quick takeaway of the main show, because takeaway number five. In the last decade, there's been an underground ring of Americans hacking insulin pumps. Oh, my God. That's cool as heck. It turns out there is a mainly through the Internet network of Americans who have been hacking insulin pumps

to do things that were not yet FDA approved. This sounds cool. Is it cool? Because this sounds cyberpunk and I love it. I'm hoping this isn't like something where they're hacking insulin pumps to like shoot bullets at people. This ties into the previous takeaway because it's about cost. And then unlike the previous takeaway, I am much more conflicted about this story and about where we should go with it. Because especially right now as we tape, the FDA and companies are mostly solving what these people were trying to fix for themselves.

Right. There is a cybersecurity element to it that is like compelling in both directions. Oh, like could you hack someone else's pump and then like hurt them or something? Is that the idea? Yes. To be fair, I don't think hurting other people is awesome. It's just that when you dangle some cyberpunk red meat in front of me, I'm going to salivate. But I am not in favor of using your cool cyberpunk biohacking skills to harm others.

And I think the people doing this for themselves are just doing it because they want that good thing in their lives. The gist of what's happening here is that starting around 2014, some Americans figured out that there was one specific model of insulin pump, which was an obsolete and discontinued model of insulin pump, they figured out that it had a security flaw where you can reprogram it to interact with other technology to be what's known as an artificial pancreas. What? Which is a thing that we are now in a secure and normal way building for people lately and through the FDA and through the regular way. What exactly does it mean to make like an artificial pancreas? Like they are using other sort of biometrics to basically tell their insulin pump like

when it should be making insulin or something. Like what is the improvement here from a basic insulin pump to this like upgraded insulin pump? Yeah, the improvement is basically networking existing technology and writing software. What's described as an artificial pancreas is combining a set of existing technology. It's a continuous blood glucose monitor. It's a machine that tracks your blood glucose. Right. And then you have an insulin pump machine

and a computerized control system for it. And so lately the FDA and actual companies have developed a machine that combines all these purposes. And it feels like an artificial pancreas because the machine checks your blood glucose and automatically supplies you with insulin. And for decades, people with diabetes have tracked their own glucose with sticking themselves and then injecting themselves with insulin. And so if you can just have a machine passively do that for you, that's really nice. It's the same health situation, but it's nicer. It's less labor and sticking yourself. Man, human beings are so cool. It's just like, man, my pancreas isn't working right. I'm just going to make myself a new one out of parts. There's no way I am equipped to say that this

is safe, but I am equipped to say that it is really cool that people have individually been tinkering with this. That's really cool. And I hope they're all safe and everything's okay. We're not doctors. And I would say people shouldn't do this because there's official ways now that are technologically secure. Okay. That's fair enough. But when the official ways started rolling out, they were expensive.

But when the official ways started rolling out, they were expensive. The first approved one was in 2018, and it costed around $7,000 before insurance. Oof. Before that in 2014, here's what people did. In 2014, and word spread about this online, people said, hey, one specific model of old insulin pump. Here is a set of open source software and a set of instructions for you to hack it. I see. And by hacking it, you could use that machine, you could reprogram it to talk to a blood glucose

monitor and do artificial pancreas stuff for you. But that meant you needed to get this pump without permission, use it in a way it's not regulated and labeled to be used for. I'd say, yeah. But people chose that for the better life experience. They were like, great, I can do this. And it's also, it doesn't cost $7,000 to get one of these off Craigslist or something and then reprogram it. Right. Yeah. Cause then I can see what the risk would be, right? Like if, if it's not done correctly, you could be, you do not want to overdose yourself with insulin or have it not go off at the right time. So like if it's not quite right, then you could actually get seriously hurt. So now I, I, I totally see the problem then with that.

actually get seriously hurt. So no, I totally see the problem then with that. Exactly. Yeah. For one thing, you are DIYing a hormone that keeps you alive. So you could just mess that up. Yeah. And then the other thing is this whole thing they figured out is due to one security flaw in one model of pump. And then in 2018, two cybersecurity experts, they presented at a conference that was called a Black Hat Conference. They're coming from a good moral place, but they went to this conference. Wait, I'm confused. I thought black hats were bad and white hats were good, though, in the sort of computer wizard realm. Yeah, I think they should have called this

white hat. I think it's like a conference for people to demonstrate what a Black Hat hacker could do, which is just White Hat to me. But Wired.com described it as a Black Hat hacking conference. So that's what they say. I get it. I get it. Black magic sounds cool. Right. Darth Vader vibes. Everyone wants to be in Slytherin. I get it.

Yeah. Yeah. And so they went to this conference and they said, hey, here's a device we made and you can use it to take over the insulin pump. That want the manufacturer of it to fully recall these. They want the FDA to fast track the real secure version of this. They were like, we built this to prove that we need immediate action on a better version of this that's subsidized and built right and taking this like DIY version out of the world. Man, I have so many conflicting feelings about this. And nobody should listen to me because I'm dumb. Yes, like maybe like pointing out this feature, right? Like that you can hack these and there's a security flaw.

So you could like hack into someone else's insulin pump. Like maybe there's a good effect of that, but also like maybe like a bad person never would have thought or figured out how to do that if you hadn't pointed it out. You know what I mean? Like, I don't, you're making it easier for someone to do it, but also you're pointing out that this could be done. And so people be careful. So, God, I don't know. I don't know whether that was the right thing to do or not. When people figured out this security flaw thing, there's basically like an Alfred Hitchcock movie premise in there, right?

Like you could hack somebody's pump and hold them ransom and make them do whatever you want them to do, you know? It's a wild cyberpunk-y situation. And so I'm glad that we're developing a security-patched, correctly built-on-purpose version of this good technology. But that's just been going on in the late 2010s and in the last couple of years, and nobody knows outside the diabetic community. And in the last couple of years, and nobody knows outside the diabetic community. But I can't blame, like, there's no way I can blame people who are diabetic for doing these hacks, right? Because like, if there's a need for it, and it's like prohibitively expensive to get the above the table version, I can't like blame people for being, you know, quote unquote, irresponsible for wanting to, you know, get this technology faster.

My sense is that we could probably make things if we like really just devoted a lot of like funding towards this where it's like we are publicly subsidizing this, then I think we could come out with this technology faster and make it cheaper faster. But, you know, so, yeah, I just hope everyone is staying safe when it comes to these these tricked up insulin pumps. Yeah. So so hang in there, folks. And what a. Yeah, I truly find it stiff. I don't know. There's darkness in the politics and stuff, but like, boy, what a world. It's really interesting. If someone offers to pimp your insulin pump, just be careful, you know? Exercise caution.

Do diligence. Dog, I heard you like insulin, so I made you an insulin pump. And that's just it. Like, it's like, well, that makes sense. Yeah, great. That was surprisingly reasonable exhibit, the host of Pimp My Ride. That is what it's for. Yes.

Hey, folks, that's the main episode for this week. Welcome to the outro with fun features for you, such as help remembering this episode with a run back through the big takeaways. Takeaway number one, scientists discovered the pancreas and discovered diabetes many centuries before they understood insulin. Takeaway number two, the key experiment that brought insulin to patients came from Canadian scientists and from heroic dogs. Takeaway number three, in the 1980s, we stopped making insulin out of discarded animal pancreases and started making it by modifying microorganism DNA.

Takeaway number four, insulin prices might be a central argument in the 2024 presidential election. Takeaway number five. In the last decade, some American diabetics turned an outmoded insulin pump into an artificial pancreas through hacking. Those are the takeaways. Also, I said that's the main episode because there is more secretly incredibly fascinating stuff available to you right now if you support this show at MaximumFun.org. Members are the reason this podcast exists. So members get a bonus show every week where we explore one obviously incredibly fascinating story related to the main episode. This week's

bonus topic is three astounding studies of insulin in wild animals, including bears. We'll talk about bear insulin. Visit sifpod.fun for that bonus show, for a library of almost 16 dozen other secretly incredibly fascinating bonus shows, and a catalog of all sorts of MaxFun bonus shows. It's special audio. It's just for members. Thank you to everybody who backs this podcast operation. Additional fun things, check out our research sources on this episode's page at MaximumFun.org. Key sources this week include a lot of medical resources from the Cleveland Clinic, the World Health Organization, the U.S. National Institutes of Health,

and also digital and historical material from the Canadian Encyclopedia, National Geographic, the American Chemical Society, the Smithsonian, and more. That page also features resources such as native-land.ca. I'm using those to acknowledge that I recorded this in Lenapehoking, the traditional land of the Munsee Lenape people and the Wappinger people, as well as the Mohican people, Skadigok people, and others. Also, Katie taped this in the country of Italy, and I want to acknowledge that in my location, in many other locations in the Americas and elsewhere, Native people are very much still here. That feels worth doing on each episode, and join the free SIF Discord, where we're sharing stories and resources about Native people and life. there is a link in this episode's description to join that Discord. We're also talking about this episode on the Discord. And hey, would you

like a tip on another episode? Because each week I'm finding you something randomly incredibly fascinating by running all the past episode numbers through a random number generator. This week's pick is episode 135. That's an episode about duct tape. Fun fact there, a lot of airline passengers look out the window of the plane and mistakenly think that the wings of their plane are held together with duct tape. That's a myth. In actuality, the wings are held together with a different kind of tape that is fine, except when it isn't sometimes. So I recommend that episode. I also recommend my co-host Katie Golden's weekly podcast, Creature Feature, about animals, science, and more.

Our theme music is Unbroken Unshaven by the Budos Band. Our show logo is by artist Burton Durand. Special thanks to Chris Souza for audio mastering on this episode. Special thanks to the Beacon Music Factory for taping support. Extra, extra special thanks go to our members, and thank you to all our listeners. I am thrilled to say we will be back next week with more secretly

incredibly fascinating So how about that? Talk to you then. maximum fun a worker-owned network of artists own shows supported directly by you