The Tim Ferriss Show - #842: The Story Behind EpiPen, The Rise of Food Allergies, and What Doctors Got Wrong

Episode Date: December 30, 2025

This time around, we have an experimental format, featuring the first episode of a brand-new podcast launching next week, Drug Story. I rarely feature episodes from other shows, but I think this one is well worth your time. It changed how I think about allergies, especially as someone who carries an EpiPen and has wondered: why on earth have food allergies seemed to skyrocket in the last few decades?Drug Story is a podcast that tells the story of the disease business, one drug at a time. Each episode explores one disease and one drug, and it kicks off with EpiPen and food allergies. A quick teaser: What if I told you that a well-meaning medical recommendation may have caused millions of kids to develop food allergies?Make sure to subscribe to Drug Story on Apple Podcasts, Spotify, or wherever you get your podcasts. You can also simply go to DrugStory.co and learn more.The host is Thomas Goetz. He is a senior impact fellow at the University of California Berkeley School of Public Health, and much earlier, Thomas was the executive editor at WIRED, which he led to a dozen National Magazine Awards from 2001 to 2013. His writing has been repeatedly selected for the Best American Science Writing and Best Technology Writing anthologies.P.S. To help you kick off 2026, I recommend checking out Henry Shukman, a past podcast guest and one of the few in the world authorized to teach Sanbo Zen. Henry’s app, The Way, has changed my life. I’ve been using it daily, often twice a day, and it’s lowered my anxiety more than I thought possible. For 30 free sessions, just visit thewayapp.com/tim No credit card required.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Hello, boys and girls, ladies and germs. This is Tim Ferriss. Welcome to another episode of the Tim Ferriss show, my last of 2025. This time around, we have an experimental format, which I do very rarely, but this one features the first episode of a brand new podcast launching next week called Drug Story. Why would I do this? I rarely feature episodes from other shows, but every once in a blue moon, I highlight something because I think it's well worth your time. time. This one came over the transom to me. It changed how I think about allergies. And I say that as someone who carries an EpiPen and has wondered why on earth have food allergies seem to skyrocket in the last few decades. And what a wild rom. I learned a ton. Drug Story is a podcast that tells the story of the disease business one drug at a time. Each episode explores one disease and one drug and it kicks off with EpiPen and food allergies. A quick teaser, what if I told you that a well-meaning medical recommendation may have caused millions of kids to develop food allergies? Yes, that and more in this episode. So make sure to

subscribe to Drug Story on Apple Podcasts, Spotify, or wherever you get your fine podcasts, you can also go to Drugstory.com and learn more. The host is someone I've known for a long time, Thomas Gets, G-O-E-T-Z. He is many things, but among others, he is a senior impact fellow at the University of California, Berkeley, School of Public Health. And much before that, Thomas was the executive editor at Wired. That's how we connected, which he led to a dozen national magazine awards from 2001 to 2013. His writing has been repeatedly selected for the best American science writing and best technology writing anthologies. He's also written bestselling books and much more. One quick PS before you go and jump into this episode, which I think you're really going to enjoy, to help

kickoff 2026, check out Henry Shookman, S-H-U-K-M-A-N. He's a past podcast guest, incredible, and one of the few in the world authorized to teach Sambo Zen. He is a master, and Henry's app, the way, has changed my life. I've been using it daily, often twice a day, hundreds upon hundreds of sessions, and it's lowered my anxiety more than I thought possible. And that's something that I saw within, I would say, 10 to 14 days. You can get 30 free session, no credit card required, just visit the way app.com slash tim. That's the way, W-A-Y, app app, A-P-P-com, the way app.com slash tim.

And I highly encourage you to check it out. Man, oh, man, it's been a game changer. And now, without further ado, here's Thomas with the wild story of EpiPen and the rise of food allergies. So the current foods I'm allergic to are milk. egg, wheat, peanuts, tree nuts, oat, mustard, barley, and fish. Got it.

I've never actually had an allergic reaction to barley itself, specifically, mainly due to the fact that I'm not of legal drinking age. Right. I forgot about beer. There's definitely barley and beer. I'd like you to meet Alex. My name is Alexander Hajou. I'm 19 years old.

I live in New York City, and I'm in this interview because of the shoot. amount of food allergies, I have. Alex has lived his whole life with food allergies. And that means his life has been a little bit different in some surprising ways. Here's an example. I've never eaten a single food from any restaurant ever in my life. I always bring my own food. I typically just ask for an empty plate.

A lot of places, when I tell them I have allergies, often say, like, listen, what are your allergies? Maybe we can try to accommodate for you. I show them the list, and the answer always ends up being, I'm sorry, I don't think we can do all of the eats, never mind. So, no restaurants, or no restaurant food, at least. Alex has a particularly severe set of food allergies, but he's not alone. He's one of many kids born in recent decades who have severe food allergies, allergies that force him to scrutinize every single thing he eats.

But even though Alex is super careful and always watchful, sometimes something happens. This was about two years ago. Previously to this, tuna showed up low on my blood test. It didn't show up on the skin test at all. I had an oral exam for tuna and nothing came up. So the allerges cleared me and said to just take it easy because I still had an allergy to other fish. So I'd have like small amounts of tuna increasing them a little bit every time I had it.

This was, I believe, my eight or ninth time having tuna, and I had the meal at home before I went to tennis practice. I get to the court, and I start playing after about 10 minutes in the warm up, I'm feeling like, man, my wrist's really hurting. I don't think I can play with this. And I also noticed that, like, I was breathing really hard, and my face felt like it was burning a little. But I wrote that off as it was my asthma acting up because I was playing tennis. Then I call my dad down from the upper level. And I tell him, hey, dad, my wrist hurts. I don't think I'm going to be able to play.

And dad asks me, like, is it that bad that you're crying? I was like, what do you mean? I wasn't crying. I'm fine. And he says, you look really bad. So they know they need to leave. Alex takes some Benadryl, but it does nothing. Alex's face continues to swell.

So I tell that, like, I'm going to do the EpiPen. I reach into my tennis bag. I pull out my emergency pack. Pull out the EpiPen. I want to say you inject yourself in the thigh with the needle, but it's more like you really want to, like, smack yourself with it sometimes. At least that's what I do, because it always helps me get over the hesitation of doing it, the needle's just so big.

Like, that thing is huge. Yeah. So I hit myself with it. I count to 10 shortly after the EpiPen. The symptoms, I could feel them like immediately going down. My face, I could feel it was really swollen. And it already started to feel like a little lighter, a little cooler. At the hospital, they give him a shot of epinephrine.

That's the same drug that's in the EpiPen. And they watch him for a few hours. And he's, long story short, he's fine. It's just another day in the life of someone with a food allergy, or in Alex's case, nine food allergies. This is drug story. I'm Thomas Getz. On each episode of drug story, we explore the history and economics of one drug, one prescription medicine. We tell each story in three parts, diagnosis, prescription, and side effects. Today's drug is the EpiPen.

EpiPen is an odd drug because it's not really even a drug. EpiPen is a delivery device for a drug, or what the FDA, that's the Food and Drug Administration, what the FDA calls a drug device combination. That means the product is both a drug and a machine that delivers the drug into the body. This can be an inhaler or a nasal spray or in the case of the EpiPen, an auto-injector that delivers a precise dose of the drug into the body through a needle. One stab, one dose. The drug inside an EpiPen is a synthetic hormone called epinephrine, which is also known as adrenaline. You've probably heard of adrenaline. It's a naturally

occurring substance in the human body, but it is also a chemically synthesized drug that was first patented and sold way, way back in 1903. Then, more than 100 years later, EpiPen became one of the most controversial drugs in America. And one of the biggest blockbusters. The story of EpiPen is also a story of unintended consequences and unexpected discoveries, one that goes from the Azores, some islands in the middle of the Pacific Ocean, to Sweden, the home of the Nobel Prize, to Israel. Today, EpiPens are in schools, they're in malls, they're on airplanes, they may even be in your backpack or purse or glove compartment just in case.

And there's also the biggest unintended consequence of all. It turns out that for many of the millions of people like Alex who live with food allergies and the risk of anaphylaxis, well, their condition may in fact be the result of one of the biggest blunders, of the past century of medicine and public health. Here's part one, the diagnosis. Anaphylaxis is a big, ugly medical word. It means a severe allergic reaction, so severe that it can be fatal. It's the underlying condition that the EpiPen attempts to solve.

And to understand anaphylaxis, we need to go back to its discovery. Let's take a trip to 1901 on the shores of the Mediterranean Sea in the tiny kingdom of Monaco. Monaco is on the Riviera, surrounded by France. It's known today for the Monaco Grand Prix car race

and for gambling and James Bond and generally for being a good place to be super rich. And for more than 700 years, Monaco has been ruled by the Monaco royal family, officially known as the House of Grimaldi. In 1901, the head of the royal family was Prince Albert of Monaco. Being a prince, Albert owned several yachts, ships, really. One was almost the size of a football field.

Prince Albert considered himself something of an explorer. He was interested in making maps and observing the weather in a biology. he would invite scientists to join him on his voyages, and they would catalog the animals they saw, both on land and water. One creature stood out. It was transparent, a sort of jellyfish, with a fluke standing out of the water

that resembled a Portuguese sailing ship. So it was called a Portuguese man-of-war. But as delicate and gentle as they looked, these creatures could also be quite dangerous. Fishermen and sailors reaching into the... the water, sometimes even swimmers, frolicking in the French Riviera, they had long known that if you brushed against these animals, you would suffer these horrible stings. The stings were intensely painful. They could linger for hours. Sometimes they could even be fatal.

These creatures are what we now know as Fasalia Fesalis. They have long tentacles that will ensnare a fish, zap it with venom to paralyze it, and they have long tentacles. They will ensnacle it, and they then reel it in. And since they don't have teeth, the Manawar injects the fish with chemicals and it liquefies it so then they can absorb it. This is a crazy process. There's this cool video on YouTube from Blue Planet. It's totally worth a click. Anyway, for humans, the risk wasn't getting eaten alive. It's just going to hurt like hell. Prince Albert was fascinated by these animals and by the strange poison they contained. So he invited two French scientists, Paul Portier and Charles Ryshe, to join him on an expedition to study them. On July 5th, 1901, they set off from the port

in Monaco and sailed to the Azores, islands about a thousand miles off the coast of Portugal. It was in the Azores that they found a large colony of Fesalia Fassalis, enough so that they very carefully harvested them out of the ocean. Then on the ship, they began a series of experiments on these animals that they had brought along for the purpose. Frogs and pigeons and even the proverbial guinea pigs. First, Portier and Richet extracted some poison from the tentacles of the creature. Then they injected some of the serum into the animals. Their hunch, their hypothesis, was that this first dose would create an immune response and that the animals would be protected from the poison with a second exposure.

Basically, that one dose would give a creature immunity from future stinks. This would be especially helpful to beachgoers back in Monaco on the Riviera. But what they found was the opposite. Cordier would later recall the moment. And this is an actor, by the way. We don't have tape from 1901. It was then that we noticed with surprise that the results were not those we expected.

No. the animals were not immunized. Certain ones seemed sensitized. The effect appeared so unforeseen in paradoxical that Dr. Rochet asked me if I had not mixed the animals in the two theories, those vaccinated, and the controls. But he had not. In fact, they had primed the animal's immune systems to be super sensitive to the poison, such that when even a small second dose was administered, it could provoke a fatal reaction

in the animal. When they returned to Monaco, Portier and Rischet began more experiments under more controlled circumstances. This time, they moved on to dogs, yes? Sadly, they used dogs, and the results were striking. Portier described what was happening when they exposed one dog to that second dose of man-of-war poison. The dog was in perfect health. Careful, active, the coat was shiny. On this day at 2 p.m., it was in.

Injected, immediately produced vomiting, defecation, trembling of front legs. The dog fell on their side, lost consciousness, and in one half hour, was dead. Portier and Rochay called this phenomenon anaphylaxis, meaning anti-protection. It was the first recorded observation of an intense allergic reaction, where a sensitivity to a substance would increase on a further exposure. This was a great discovery, and a few years later, on December 11, 1913, at the Grand Hotel in Stockholm, Sweden, Charles Rochet was awarded the Nobel Prize for the discovery. At the banquet, Rishay delivered his Nobel lecture, where he mentioned in passing what he called elementary anaphylaxis.

That is, an allergic reaction caused by eating. Here's what he said. It has a long been known that some people are sensitive to sheep or to sheds or to to produce, to fish, to shell fish, to eggs, or even to milk. Now, the symptoms to be seen in such individuals and ingesting such and such foods are analogous to the effects of anaphylaxis. Acute stomach pains, vomiting, diarrhea, colic, erythema, orthocharya, etching, and sometimes cardiac troubles can be there.

We know that these are anaphylactic phenomena. This has become a pathological commonplace. It was a commonplace, but still something of a mystery. In fact, there had been occasional observations of bad reactions to certain foods for centuries. In 450 BC, Hippocrates mentioned asthma, which means panting in Greek, and its association with certain foods. In about 55 BC, the Roman philosopher Lucretius Cato, he famously stated that what is food for some may be fierce poison for others. Even with the emergence of modern medicine in the 20th century, food allergies were a curiosity

and poorly understood. In part, this is because it was so hard to nail down cause and effect. Skin tests were developed in the early years of the 20th century, but they were unreliable, and they often produced false positives and false negatives. And food allergies themselves were still relatively uncommon, enough so that in not 1964, the Journal of the American Medical Association, JAMA, it found it noteworthy that a 32-year-old man had been admitted to the emergency room of the Jewish hospital in Brooklyn, complaining of, quote, itching and tearing of the eyes,

swelling of the eyelids, itching of the roof of the mouth, profuse sweating, and tightness of the chest with noisy breathing. The patient stated that he had eaten two slices of peeled mango. This JAMA report concluded, true anaphylactic reactions related to food intake are rarely encountered but are known to occur. So what is actually happening here? How do we get from the curious case of a peeled mango

to lots of people like Alex who manage their list of severe allergies in everyday life? Well, the immune system is notoriously complex. But basically, what's happening is that for some people, the body reacts to certain proteins and certain foods as if they're poisons and the immune system mounts a full-on defense as a result. Thinking that food is poison,

the body slows down and swells up in an attempt to limit the body from absorbing this supposed poison. This is the allergic reaction that can lead to anaphylaxis. If you think about it, the immune system very early on in life, even in utero when the baby is in the womb, needs to learn what is friend and what is foe. Otherwise, the immune system has a potential to attack all proteins, including its own. This is Dr. Gideon Lack. He's a professor of pediatric allergy

at King's College London. His whole career has been dedicated to understanding food allergies, why they happen, who they happen to, and how to prevent them. He's pretty much the hero of this episode. During embryological development, all one's own body proteins and tissues are presented to the immune system so the immune system doesn't attack itself. That's a process called tolerance. And the same has to happen after birth to foods, because otherwise the immune system who would attack any foods, and the process of doing that is early introduction to foods into the baby's dodge. And when you don't expose a baby to foods early,

and this, it turns out, is key. The immune system can be unprepared when they do come along. And that is what we call an allergic reaction. And a severe reaction is anaphylaxis. Today, of course, anaphylactic reactions to food are much more common. Odds are you have a family member with a food allergy, or you may have one yourself. As of 2024, about 10% of adults in the U.S.

six and ten percent of children are estimated to have a food allergy. That's a huge change over the past 50 years. When I was in medical school, 1978, 85, so we saw one child admitted for asthma and we were called to listen to his chest as a sort of teaching case. This was not an unheard of phenomenon, but pretty unusual in those days. And food allergies, I'd never heard of. It wasn't on the medical school curriculum. Then when I did my residency in New York, in the Bronx, one of the hospitals I worked at, I was struck and horrified to see a teenager come in anaphylactic shock, well, bronch spasm, and then ventric cardiac arrest and died and was really completely irreversible.

I always struck me. Over the next few years, Dr. Lack saw a lot more cases of food allergies and a lot more often. And started to see, hey, we're seeing peanut and food allergies, not just in tertiary specialty centers for pediatric allergy, but we're seeing them in the community and literally saw the numbers grow before my eyes without needing to do epidemiology and just become, a more and more apparent problem over about a five-year period. What Dr. Lack saw in Bristol was happening across England, across the United States and in many other Western countries. The 1980s and 90s saw the beginning of a worldwide epidemic of food allergies, especially in children. Peanuts were the first main concern, but soon other

potentially worrisome foods were added to the list. Eggs, shellfish, milk, fish, fish, tree nuts, wheat, soybeans. These are the so-called big-eight allergens. They account for 90% of all food allergies. Where in the 1970s, maybe 1% of kids had food allergies. By 1995, it was estimated that 5% had some sort of food allergy. So what happened? What was the cause?

Like a lot of things in health and science, there were several things going on at once. You work? Bath time. I have a surprise for you. Where's that little scamp? Is it a rocket? You can't see it. Not until you get into that tub.

It's a horse. It is not. It's Mr. Bubble. And he'll get you so clean, your mother won't know you. Knowing my mommy's hair looks so shiny and healthy, she's been using my shampoo, Johnson's baby shampoo.

You're pure, you're natural, you're one of a kind. You're my ivory, baby. Part of the story was that things were a lot cleaner than they used to be. And not entirely in a good way. This is the so-called hygiene hypothesis. It suggests that with the rise of consumer cleaning products and spick and span households, people were just not exposed to as much as they used to be.

And our immune systems were less robust than they once were. Basically, the lack of exposure makes us more vulnerable when something new, say, an unexpected protein comes along. And our body's immune system mistakes this new, benign protein for something poisonous or harmful. And that's an allergy. This may be especially true for babies, who often get daily baths that are actually washing away natural oils from the skin and protects them. So ironically, more hygiene means less immune tolerance. This idea of the hygiene hypothesis didn't come along until 1989, when it was first suggested as an explanation for the rise in Haysen,

fever and eczema and asthma, all allergic conditions like food allergies. By that time, of course, the food allergy epidemic was well on its way, and it was generating a lot of concern among parents and pediatricians alike. And it seemed reasonable, sensible even, that the best course of action was to avoid things that could prompt an allergic reaction. This is what's called the precautionary principle. This is an idea that has been around for hundreds of years, but it was a reasonable. really codified into medicine in the 1990s.

You can think of it as an ethical framework for decision-making that boils down to better safe than sorry. In 2000, the American Academy of Pediatrics, the AAP, for short, they issued new guidance for parents. They called it the one, two, three rule. Don't feed your baby dairy or milk until age one, wait until age two to introduce eggs, and don't introduce peanuts or seafood until age...

Three, the idea was to minimize exposure when children were very young, and their immune system was not developed enough, supposedly, to tolerate these foods. The only problem was this recommendation wasn't based in science. It was based on the precautionary principle. With more children allergic to foods, it seemed sensible to delay the introduction of those foods to children, and it turns out that scientifically, biologically, this was exactly the wrong. advice. What the AAP had done was to unintentionally create a feedback loop. As more children avoided foods at an early age, more children would be sensitized to those foods later,

and more children would be diagnosed with food allergies. And that rise in food allergies created more concerns and more fears about the foods, which led to more avoidance, less exposure, and yes, more allergies. But it seemed like good advice, because so many kids were getting food allergies. And it seemed like common sense, avoid possible allergens at all costs. Peanuts were prohibited in schools, they were banned by some airlines, and cases continued to climb. And so then, in 2005, Dr. Gideon Lack is in Tel Aviv, Israel, giving a lecture on peanut allergies. Reports about peanut allergies started to come out in the scientific

in the clinical literature, but they apparently weren't seen very much of it there. And my opening question when I started to give my talk was, how many of you have seen a child with peanut allergy in the last year? Two or three, suddenly less than a handful of people put up their hands, whereas at the time in the UK, every pediatrician would have put up their hand. So I thought this is strange. It turned out that in Israel, infants are often fed a snack. called Bomba. They look like Cheetos, but they're peanut-flavored. Kids teeth on these puffs at a really

early age, like four or five months old. And when Dr. Lack learned about this, he thought he should research it. So he got some colleagues involved and started a study. They decided to research how frequently peanut allergies happened in Israeli children compared to children in the UK. And they chose to look specifically at Jewish children so that the genetic backgrounds would be more similar. If there were any differences, it would be less likely to be a genetic explanation. We got our responses and found out that the rate of peanut allergy in the UK children was about 2%, which was about 10-fold higher than in the Israeli school children, where peanut allergy was virtually not being seen. The few cases of peanut allergy in that study were derived largely from children

who were born outside Israel and developed their peanut allergy prior to being in Israel. The results were published in 2008. It showed that children in Israel had a much lower rate of peanut allergies. Now, mind you, this was an observational study, meaning that the researchers tracked two different populations over time.

It's a good way to do research in public health where there are lots of real-life variables and messiness, but ultimately it really doesn't tell you anything about the causes of any differences. Was the difference explained by those bomb-puffs? Maybe, but it could also be caused by the water or by something else in their diets or environments. The study suggested an association,

but it did not prove anything. Meanwhile, the recommendations from officials didn't really change, and certainly clinical practice what parents were being told to do by their pediatricians, that did not really change. the precautionary principle still held sway. And food allergy rates, they continue to rise. And just remember, the fear here, it's very real. In 2001, the Journal of the American Medical Association estimated that between 500 and 1,000 people die every year in the U.S. from anaphylaxis.

Thankfully, there was something that could help. Should a child or an adult accidentally or inadvertently consume a food they're allergic to, this was a simple device called the epipen. It administered a small but effective dose of epinephrine with a simple stab. The trick was to make sure there was an epipen at hand at that moment of need. We'll dig into that after the break. To set the scene, we're going to run a commercial, but it's not an advertisement for drug story. This was a commercial that Myelin Pharmaceuticals, a maker, of EpiPen that they ran in 2016. You'll notice that it doesn't actually mention the EpiPen, not even once.

That's because it's what the FDA called a disease awareness ad, which means the ad discusses the condition to raise awareness, but it doesn't make any claims about any one specific product or drug. And again, we can't emphasize enough. This commercial is not an advertisement on Drug Story. Look at your face and your hands. It's still getting worse. Is it your allergy?

There were a penis in the brownies, right? Peanut butter. Oh no, I forgot. What? She asked you. Call my one once. Oh, sorry. Okay, okay.

Every six minutes, life-threatening food allergies send someone to the hospital. Always avoid your allergens and talk to your doctor about a prescription treatment you should carry for severe reactions. Learn more at faceyourrisk.com. This is part two, the prescription. So in part one, we heard about the discovery of anaphylaxis, a severe, potentially deadly, allergic reaction, and the surprising rise of food allergies in 1990s and early 2000s. But what about the treatment? What could treat an anaphylactic reaction before it turns fatal? For that, let's go back.

125 years, 1900. It was actually just a few months before Prince Albert and George Rischet and Paul Portier set off on their voyage to the Azores. and we're going to Philadelphia, Pennsylvania. There, we meet Solomon Salas Cohen. He was a prominent local doctor who was asked to help treat a 22-year-old patient who was wracked with asthma. This poor woman, she was constantly short of breath

with occasional asthma attacks that would have her coughing for hours. She sounded miserable. Dr. Solis tried a few things, and then he gave her an extract of the adrenal gland, known as adrenaline, and sold in tablets. He gradually up the dosage to 18 tablets a day. And at that dosage, something seemed to work.

Her breathing improved, the spasms stopped. Soon, she was able to go outside and breathe normally. Dr. Solis-Cohen tried adrenaline on several other patients also with severe allergies, typically asthma or hay fever, with similar results. Some required just a pill or two a day. Time and again, it worked with great success. There was one caveat. The tablets were simply an extract of the adrenal gland of animals.

They hadn't been purified to just be the active ingredient. In fact, there was no real understanding of what that active ingredient may be. The result, the good doctor noted, was that, quote, The preparation could give rise to diarrhea with offensive discharges. If we could have the active agent alone, our therapy would be much more definite. Well, okay. This wouldn't be the last time that diarrhea, would be noted as the side effect of a drug.

But give the doctor credit, his experiments were the first known clinical use of adrenaline to treat allergies. And Dr. Solis-Cohen's wish for a more purified preparation, that would soon be granted. Within a couple of years, adrenaline would be chemically isolated and patented. In its synthetic form, it is called epinephrine. But again, it's basically the same thing as adrenaline. Goodbye, animal extracts.

Hello, industrial manufacturing. So, how does epinephrine actually work to control an allergic reaction? Well, remember that the body reacts to an allergen as if it were a poison. It releases histamine, which tightens airways and slows down the heart. They're swelling, difficulty breathing. In worst case, the body slows down so much that people stop breathing, where they go into shock, or they're effectively paralyzed. This is how people die of anaphylaxis.

Well, epinephrine, it does just the opposite. It causes the heart rate to increase. Circulation to increase, and inflammation goes down. It also makes people anxious and excited. Remember, it's just synthetic adrenaline. But the important thing is it works very well to stop anaphylaxis and to prevent anaphylactic shock. By 1918, an injection of epinephrine was specifically recommended for use by doctors and

pharmacist to treat anaphylactic shock, and it was cheap to make. But there was relatively limited demand. By the 1940s and 1950s, other drugs had been discovered that treated asthma, including ephedrin, an isoprenelene, and even cigarettes laced with belladonna. Yes, they actually once prescribed poison cigarettes for asthma. For many people, though, these worked better, and they were easier to tolerate than epinephrine injections. But another use case for epinephrine emerged in these years, the years after World War II during the so-called Cold War. The United States was concerned about reports

that the Soviet Union was developing a new kind of nerve gas that could be used on battlefields. They brought in an engineer named Sheldon Kaplan. He had just the right qualifications. He had recently worked for NASA, developing emergency medical kits for the Apollo missions. Kaplan invented something called the combo pen. It was meant for military troops to administer an antidote to nerve gas in the field.

Soon, Kaplan realized that his invention also had application for consumers with allergies. Instead of filling the pen with nerve gas antidote, it could be filled with epinephrine for the emergency treatment of anaphylaxis. Kaplan and Survival Technology Inc., that was the name of the company that hired him, they were awarded a patent for his invention in 1977 and the EpiPen was approved by the FDA as a drug device combination in 1987. For years, the EpiPen wasn't actually used very much.

It wasn't until 1990 that the New York Times first mentioned the device and a story that mentioned how a Brown University student with a peanut allergy had died a few years earlier after eating chili that had peanut butter in it. And the EpiPen did make a big difference for a lot of people with food allergies. It saved a lot of lives. So eight years old, going camping in Huntsville State Park, which is this really beautiful, lush piney woods forest north of Houston. This is Lauren.

My name is Lauren Gilmer. I am 33 years old. I currently live in Nashville, Tennessee. So I went to the nature center, looked around, and right outside of the nature center, they had a collection of bird feeders, poisted up a plint style with a pole in the center. And I wanted to see if there were any birds and climbed up, looked inside, put my hands on the edge of it, didn't see anything, popped down, walked with my family to the trailhead, bent over a water fountain, took a drink. And when I straightened back up, I had a sneezing fit, which sounds kind of silly. But when I say sneezing fit. I sneezed maybe for a minute and a half straight. I couldn't stop sneezing. And my mom was

bewildered. I straightened up and looked at her probably to try and gain some perspective like, is this normal? My mom realized, okay, we should probably pull out the big guns. At this point, I had developed hives on my neck, like the capillary rich areas, the backs of my hands on the tops of my feet. I was extremely itchy. I could feel my face swelling and it was getting harder to see, harder to breathe. Oh my God. And this is all in like 10 minutes after the bird feeder or how long? Yeah, a max of 10 minutes, I would say. And my mom looked at me and was like, your lips are turning blue. And I knew what that meant because I'd had anaphylactic reactions in the past. And I said out loud, I think I need my shot. I was having a really hard time breathing. And I felt this

this panic rising up in me as it became harder and harder to breathe. And even for someone that had had asthma attacks and for whom that was a pretty normal aspect of life, I mean, this was an entirely different level of air hunger. So her mom busts out the Epipan and jams it into Lauren's leg. I remember not even feeling the needle because I was kind of out of it at that point and focused on breathing. And you're eight years old. Yeah. And there is a small hospital in Huntsville, but it was like, I want to say, 20 minutes away. So without the EpiPen, I doubt if I would have made it there. And once I arrived, I needed more epinephrine. Stories like Lawrence were becoming more and more common. And the EpiPen was in more and more homes and cars and schools. The EpiPen was turning into a very good business. From 2003 to 2007, revenue from EpiPen grew by nearly 50%, with sales at around $200 million a year.

That sounds like a lot of money, and it was, but it's still puny compared to massive blockbuster drugs like Lipitor, which made $16 billion in 2005. And then, in 2007, Mylan Pharmaceuticals spent almost $7 billion to acquire EpiPen. Now things were getting interesting. This quiet little drug delivery product made for emergencies would become a very big and very controversial thing. That's coming up. But first, a commercial.

One more gem from the advertising archives. An ad for EpiPen from 2013. He's ready for an adventure. You're just hoping his food allergies aren't a part of it, which is why there's a plan for wherever he goes. Avoid allergens first. Carry EpiPen always. EpiPen auto-injectors are for the emergency treatment

of life-threatening allergic reactions, anaphylaxis, and for people who are at increased risk for these reactions. Epipan is intended for immediate administration as emergency supportive therapy only. Seek emergency medical treatment immediately after use. Epipen is injected into the outer thigh. Do not inject into your vein, buttock, hands or feet.

Use with caution if you have heart disease or are taking medicines that cause heart-related symptoms. Side effects may include faster, irregular, or pounding heartbeat, sweating, nausea, and vomiting, difficulty breathing, paleness, dizziness, weakness, or shigginess, headache, nervousness, or anxiety. If you have high blood pressure, overactive thyroid, Parkinson's disease,

diabetes or heart disease, these side effects may be more severe or last longer. Have a plan for life-threatening allergies wherever they go. Ask your healthcare professional about EpiPen and visit EpiPen.com for more information. This is part three, side effects. In 2007, EpiPen was a quiet but reliable moneymaker. It brought in $200 million a year. But after Mylan acquired the rights to the EpiPen that year, the company well, it began to raise the price.

Over the next five years, the price of EpiPen more than doubled, from about $109 each to about $230 in 2013. And all the while, even as prices climbed, people kept buying the devices for a couple reasons. First, the epinephrine inside the EpiPen, well, it had an expiration date on it. They generally are good for one year. And second, Mylan began to spend a lot more money,

on lobbying to Congress and States, with great success. In 2010, the FDA adjusted its guidance to allow two EpiPen devices to be sold in a package instead of one. The idea made sense in theory. Sometimes one EpiPen wasn't enough, so a second dose would be needed to avoid anaphylaxis. It happened rarely, but just like that, parents were now buying two packs instead of single epipans. States started passing laws requiring public schools to have epipans on hand. At the same time, Milin began to create training programs at schools, where they would instruct teachers and nurses free of charge on how to administer the EpiPen.

So they were getting trained on the EpiPen devices. Now, there was an alternative device, the Adrenoclick, and that was even cheaper. But it worked a little differently than the EpiPen. And since teachers and nurses weren't trained on those devices, schools required parents to purchase EpiPens. This is what economists call lock-in. And if that wasn't enough, in 2012, Mylan started its EpiPen for Schools program, providing free and discounted EpiPens to schools that agreed not to purchase competing products.

That's even more lock-in, a captive market. And still, prices continued to climb. By 2016, a pack of two EpiPen devices had a list price of over $600. For $300 a piece, That's more than three times in less than a decade. Annual sales now topped $1 billion. It was officially a blockbuster drug, more than a century after epinephrine was first synthesized.

But by now, people had noticed. The soaring cost of prescription drugs had become a national scandal. And Mylan found itself standing out as a prime example of pharma greed. The company had been just, so consistent in raising prices, and so good at playing the game. The headlines, news reports, they were full of outrage, and sometimes tragic stories of parents who were now unable to afford the EpiPen for their children. As the furor grew in August 2016,

Mylan tried to diffuse the controversy by announcing that it would begin offering a generic version of EpiPen at half the price. Now $300 for a two-pack instead of $600. But that gesture didn't quell the outrage. On September 21st, 2016, the CEO of Mylan, Heather Bresh, found herself in front of the U.S. Congress, testifying before a House committee investigating drug prices. Do you think you were charging too much at 600? Sir, we believe it was a fair price, and we've just now lowered that price by half. Why'd you lower it by half if you thought it was fair?

If you thought it was fair, leave it where it's... that. Because we wanted to make sure we're addressing the patients out there that are facing higher out-of-pocket cost and paying the wholesale acquisition cost, which was not intended. The system wasn't intended for people to pay the wholesale acquisition cost. And that's what's happening at an alarmingly rising rate, which is we took the unprecedented step of putting the generic in to sidestep that and be able to lower the cost. You're doing everyone a favor by charging three times what you acquired the drug for is a generic. You're trying to make us feel good about that. I just don't. I mean, I'm not buying your argument. Do you have a guilty conscience about

any of this? Over that period of time, putting it in public places, giving free 700,000 free epipens to 66,000 schools, and wanting to get into all of the public schools across America. Well, if it costs 20 bucks, they could afford to buy their own. You wouldn't have to give them to them. But instead, you chose to jack the prices up and then somehow make everyone want to feel good about you by saying how much you do. So patients could get a two-pack of the official EpiPen for $600, or a generic version, basically the same thing, but not called EpiPen, for $300. And sure enough, over the next few months, more people started to fill their prescriptions for the generic version rather than the full-price EpiPen. Although here's the thing, because of the odd economics of drug prices,

even the generic version would still earn the company massive amounts of profit per device. By some calculations, almost the same amount of profit, as it turns out. Okay, so price is still high, rates of allergies still high, and still the official guidance to pediatricians told parents avoid feeding peanuts to young babies, avoid foods that are potentially allergic. Here's where Gideon Lack re-enters our story. You'll recall that back in 2008, he published his observational study that suggested a link between early peanut exposure and no allergies. Or the opposite, a lack of exposure and a higher rate of peanut allergies. But that study, it didn't change the mainstream practice or recommendations by doctors.

It wasn't strong enough evidence to meaningfully shift the guidelines, or to shift what most pediatricians were telling parents. To actually prove that early exposure is beneficial and not, in fact, dangerous, well, to prove that, well, you would need the gold standard of evidence. And that would be a randomized control trial. or an RCT. In an RCT, you would take a group of children and randomly assign them to one of two groups.

Some of them would be given a treatment, in this case, early exposure to peanuts. And others would be given the placebo, a fake supplement with no potential allergens. And the study should be what's called double-blind. Neither the children or parents or the researchers would know who was in which group to avoid bias. And then several years would have to go by,

then several years later, you'd see if there's a difference in allergy rates. But all that would take years. Dr. Lack and his colleagues started this other study. They called it the learning early about peanut allergy, or the Leap study. They recruited 640 children between 4 and 11 months old, and the plan was to carefully expose half of them to peanuts regularly and consistently until they turn 5, and then to compare the rates of allergies between the two groups of children. Talking to Dr. Lack, though, I was curious.

How exactly did they convince 640 parents to enroll their babies in this study? A lot of resources went into screening and talking to the families and explaining to the parents what the situation was. People respond to data and common sense and realized that the guidelines were not working and that there was a significant chance that by doing nothing, their baby would develop peanut allergy anyway, here was the possibility of an intervention that would actually reduce peanut allergy. And so five years of careful experiment go by, and finally they have their results.

It was published in the New England Journal of Medicine, the most prestigious journal in medicine, in February 2015. Here's what it found. At five years of age, the rate of allergy, in the children who had avoided peanuts was nearly 14%, about what it was in the general population. But in the group that had been consistently consuming peanuts since those first few months,

the rate of allergies was just 1.9%. 1.9% compared to 14%. That's a huge difference. Exposing babies early, as early as four months, was clearly and profoundly beneficial. This prevented food allergies. Well, I was really astonished that it would be that high.

We were powered statistically, I believe, to look for a 50% reduction, not an 86% reduction in the rate of allergies. So that's at a level of very successful vaccines in terms of protection. It was a massive finding. And of course, it directly contradicted the prevailing guidelines at the time. But the evidence was solid. And within two years, in 2017, the National Institute of Allergy and Infectious Diseases announced a new recommendation.

Instead of avoiding exposure, the new guidance was to expose children to peanuts and other potentially allergic foods early and often. When you give by mouth, expose it through the gastrointestinal tract, an antigen early on before the child's immune system is fully developed. that you, what we call, tolerize the child to not make a bad response against the peanuts. They become, quote, tolerant to the peanut.

That voice might be familiar. That was Dr. Anthony Fauci. Yes, that same Dr. Fauci, announcing the new recommendation. So there we have it. After generation of children had been raised with exactly the wrong recommendation, we finally had a new,

evidence-based recommendation to expose children early and often. That would be the best way to avoid food allergies later in life. This was quite the U-turn. But Dr. Lack, he's fairly modest about his discovery. You know, that famous line, there's nothing to fear but fear itself, which couldn't be more appropriate in the case of food allergy, where your fear of your baby developing the disease leads to avoiding the food, leads to causing the baby to have the disease.

disease. And I'm doing that way of thinking is very difficult. Yeah. It's just striking to me that it was the kind of medical establishment. I mean, it was the official recommendation of NHS and NIH that avoidance was the best course of action. And that in some ways ended up, well, I guess it goes to causality. But it certainly ended up, if not creating the epidemic of food allergies, exacerbating the epidemic. Look, we don't hold all the answers, and very often we get it wrong before we get it right, and I got it wrong. If I were to criticize my colleagues, I would equally have to criticize myself, and people change their minds.

I think it's important to change one's mind when new evidence comes about. So is that all it took? New science, new recommendation, and presto, no more food allergies. Well, not quite. In fact, despite the change in guidance, food allergies are not going down. Even after the guidance shifted in 2017, rates of food allergies among children have continued to increase, and they have also increased in adults as well, which is confounding, but maybe not too surprising. When you think about it, there's probably a couple things still going on.

First, many parents are probably just still not okay with the idea of exposing their their babies to these foods in those early months and years. The precautionary principle is still holding us back. What's more, the belief in hygiene and sterility, it hasn't gone away. Many parents are probably still bathing their infants too much. And so food allergies and other sensitivities, they're still common and prevalent, meaning there is still a very big market for the EpiPen. And the EpiPen is still a huge moneymaker. In 2023, the EpiPen and the generic, they brought in nearly $2 billion in revenue. Yes, that's double the amount from 2016.

And the price of a two-pack, it's now about $700. That's 15% higher than when the Mylan CEO was called in to testify in front of Congress. Since the controversy and congressional hearings back in 2016, there have been many efforts to control drug prices. Price controls, more generic competition, and lots and lots of talk in Washington. But nothing has changed the direction of prices. Nothing has really stuck.

Drug pricing is a very confusing, very convoluted subject, and it's one we will return to again in other episodes. But the bottom line is, manufacturers have huge leeway to set prices as they see fit, and the U.S. government has shown very little appetite for stepping in with price controls. So many drugs stay expensive, and people still want and need those drugs.

And so the cost of health care, it creeps a little higher every year. And for many people, that means deciding between medicines they need and the other things they need, like clothes, or food, or school. This is still a very, very big problem. Oh, and in 2019, Myelin Pharmaceuticals announced that it was merging with a unit of Pfizer and would become a new company called Theatris. a name that must have been designed just to be easy to forget. Theatris.

Meanwhile, for all those millions of people who still suffer with food allergies, there are some signs of hope. Maybe this idea of exposure could be used to help people who already have an allergy. Dr. Lack explains. While the lead trial was being constructed, designed, carried out, people also started to explore the notion that, well, if you have a food allergy, you're told to avoid the food, and we still give that that advice, that's correct. But maybe low-level regular supervised exposure in an allergic child might be a better thing

than avoidance, and we're now at a phase where we do have new products to treat peanut allergy, but also people are doing this to multiple food allergies, starting at milligram quantities of food protein, tiny amounts and increasing it, and showing that you don't reverse or cure the disease, but you get these children to be able to tolerate significant amounts. This is called allergen immunotherapy, or exposure therapy. It can work wonders. In fact, in 2020, the FDA approved a prescription treatment for people with food allergies, a product called palvorzia, which exposes people with peanut allergies to tiny amounts of protein,

with some proven benefit in reducing the risk of anaphylaxis. And for new parents, there are foods, besides, you know, plain old peanut butter, that are designed to help them introduce peanuts and other potential allergens into the diet early. One of them, Mission Mighty Me, is from a company co-founded by none other than Dr. Gideon Black. Drug Story was created, written, and hosted by me, Thomas Gatz. Molly Warner is our research director. From reasonable volume, Rachel Swayby produced and sound design this episode,

with assistance from Audrey No. Elise Hugh was the editor. Mark Bush is our engineer. Voice acting by Colin Borden. Drug Story was produced with support from the University of California, Berkeley, School of Public Special thanks to Claudia Williams and Dean Michael Liu. Thanks also to Alexander Hajou, Lauren Gilmer, and Dr. Gideon Lack. For an annotated list of our sources for this episode, visit drugstory.co.

Drugstory is an independent production. There's no tech company or big media conglomerate behind us. If you would like to support our work, contact us at drugstory.co. You can also subscribe to our substack there, and be notified when new episodes come out. And if you like this episode, please tell your friends, rate us on Apple or Spotify. The more people who download and like Drug Story, the closer we get to doing a season two. Seriously, help us spread the word.

Next up on Drug Story, we're going to look at Lipitor and heart disease and ask if millions of people are taking a drug every day for the rest of their lives with no real benefit. We'll see you next time. Listening to this episode of drug story may cause you to feel itchy, dizzy, woozy, or even a bit weezy. We advise you to watch what you eat, take your medicine as prescribed, and avoid exposure to people who don't appreciate who you are and why you are so awesome. Thank you.