The EpiPen and Food Allergies (from Drug Story)

Dan: Hey there. With today’s story, we’re switching things up a little bit, but first I wanna ask your help. Can you take a couple minutes to help us make an arm and a leg better by. Taking a quick survey to help us understand what’s working for you and what you’d like to see and hear more of or less, just go to armanda leg show.com/survey.

That’s armanda leg show.com/survey. There’s a link wherever you’re listening. You could go ahead and click it right now and then it’ll be there when you’re done listening. Now on to today’s special. I’m excited to share an episode from a new podcast called Drug Story. The host Thomas Goetz describes himself as a science journalist and public health nerd.

So each episode dives deep into the story of a single drug and what it reveals about the business of health. And disease. So we are sharing his story about the EpiPen, which is a Divis. We’ll find in classrooms on airplanes and glove compartments everywhere, because the EpiPen can be a literal lifesaver for people with severe allergies.

And of course, the EpiPen is also a symbol of drug company profiteering, which is why I’m so pleased to bring you this particular episode of Drug Story.

Briefly. In 2007, a company called Myelin Pharmaceuticals took over the EpiPen. It had been around for a while, and they did two things. First, they dramatically expanded their market and their market share through lobbying campaigns focused on lawmakers and regulators and even school districts. And second.

They jacked up the price trick, bolded, actually, you’ll hear all about it. You’ll also hear all about the history and the science here. The drug inside the EpiPen was developed more than a hundred years ago and in the last couple of decades. Researchers have learned a ton about how to prevent the kind of severe food allergies that make EpiPens necessary for so many people.

Thomas Getz, public health nerd, just like he says, does a great job telling the whole story. We will be back with new episodes of an arm and a leg in a few weeks to then enjoy drug story, EpiPen and food allergies. Oh. And, uh, thanks for taking a minute to fill out our survey. You could even win a prize.

That’s armanda leg show.com/survey. Okay, here’s drug story.

Alexander Haiju: So the current foods I’m allergic to are milk, egg, wheat, peanuts, tree nuts, oat mustard, barley and fish. 

Thomas Goetz, host: Got it. 

Alexander Haiju: 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. 

Thomas Goetz, host: Right. I forgot about beer. There’s definitely barley and beer.

I’d like you to meet Alex. 

Alexander Haiju: My name’s Alexander Haji. I’m 19 years old. I live in New York City and I’m in this interview because of the sheer amount of food allergies I have. 

Thomas Goetz, host: Alex has lived his whole life with food allergies. That means his life has been a little bit different in some surprising ways.

Here’s an example. 

Alexander Haiju: 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 these. It’s never mind. 

Thomas Goetz, host: 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.

Even though Alex is super careful and always watchful, sometimes something happens. 

Alexander Haiju: This is 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 allergist cleared me and said to just take it easy because I still had an allergy to other fish, so I would have like small amounts of tuna increasing them a little bit every time I had it.

This was, I believe, my eighth 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 warmup, I’m feeling like, man, my wrists 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. 

Young girl: Mm-hmm. 

Alexander Haiju: And I tell him, Hey dad, my wrist hurts. I don’t think I’m gonna 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’m, I wasn’t crying. I’m fine. And he says, you look really bad.

Thomas Goetz, host: So they know they need to leave. Alex takes some Benadryl, but it does nothing. Alex’s face continues to swell, 

Alexander Haiju: so I tell dad like, I’m gonna 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 into thigh. With the needle, but it’s more like you really wanna like smack yourself with it sometimes.

Thomas Goetz, host: Mm-hmm. 

Alexander Haiju: 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. 

Thomas Goetz, host: Yeah. 

Alexander Haiju: 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.

It already started to feel like a little lighter, a little cooler. 

Thomas Goetz, host: 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. 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 autoinjector 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 and 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, and in biology, he would invite scientists to join him on his voyages and they would catalog the animals they saw both on land and in 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 Mana War. But as delicate and gentle as they looked, these creatures could also be quite dangerous. Fishermen and sailors reaching into 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 Lia Fas. They have long tentacles that will ensnare a fish, zap it with venom to paralyze it, and then reel it in. And since they don’t have teeth, the manir injects the fish with chemicals and it liquefies it, so then they can absorb it.

This is a crazy process. There’s, 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 Porter and Charles Che, 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 fa fas 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 Poitier and riche extracted some poison from the tentacles of the creature. Then they injected some of the serum into the animals. Their hunch, their, 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. 

Doctor:: It was then that we noticed with surprise that their 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. Rashe asked me if I had not mixed the animals into series, so was vaccinated and the controls, 

Thomas Goetz, host: 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, Poitier and Riche 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 or poison. 

Doctor:: The dog was in perfect health, cheerful active.

The coat was shiny on this day at 2:00 PM It was injected, immediately produced a vomiting, defecation, trembling of front legs. The dog fell on the side, lost consciousness, and in one half hour was dead. 

Thomas Goetz, host: Porter and Rashe called this phenomenon. 

Doctor:: Anaphylaxis 

Thomas Goetz, host: 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 11th, 1913, at the Grand Hotel in Stockholm, Sweden, Charles Che was awarded the Nobel Prize for the discovery at the banquet. Che delivered his Nobel lecture. Where he mentioned in passing what he called 

Doctor:: elementary phylaxis, 

Thomas Goetz, host: that is an allergic reaction caused by eating.

Here’s what he said. 

Doctor:: It has a long been known that some people are sensitive to she or to stop trees or to fish. Shout to shellfish, short eggs, or even to milk. Now these symptoms to be seen in such individuals only suggesting such and such foods are analogous to the effects of anaphylaxis. Your stomach pains, vomiting, diarrhea, colleague erythema or aria itching and sometimes cardiac troubles and be there.

We know that these are anaphylactic phenomena. This has become a pathological commonplace. 

Thomas Goetz, host: It was a common place. But still something of a mystery. In fact, there had been occasional observations of bad reactions to certain foods for centuries. In four 50 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 1964, the Journal of the American Medical Association, jama, it found it noteworthy that a 3-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. A patient stated that he had eaten 

Doctor:: two slices of peeled mango. 

Thomas Goetz, host: This jamer 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 appealed mango to lots of people like Alex, who manage their list of severe allergies in everyday life? Well, the immune system is notoriously complex. Basically what’s happening is that for some people, the body reacts to certain proteins in certain foods as if they’re poisons, and the immune system mounts a fall 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. 

Dr. Gideon Lack: If you think about it, the immune system, very early on. 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. 

Thomas Goetz, host: 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. 

Dr. Gideon Lack: 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. 

Thomas Goetz, host: 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 US and between six and 10% of children are estimated to have a food allergy. That’s a huge change over the past 50 years.

Dr. Gideon Lack: When I was in medical school, 19 78, 85, so I only saw one child admitted for asthma. We will hold 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 allergy 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 in anaphylactic shock, uh, well bronch spasm, and then anti cardiac arrest and died and was really completely irreversible.

It always struck me. 

Thomas Goetz, host: Over the next few years, Dr. Lax saw a lot more cases of food allergies and a lot more often 

Dr. Gideon Lack: and started to see, hey, we’re seeing peanut and food allergies not just in tertiary specialty centers or pediatric allergy, but we’re seeing them in the community and literally saw the numbers grow before my eyes without needing to do.

Epidemiology had just become a more and more apparent problem, 

Thomas Goetz, host: right 

Dr. Gideon Lack: over about a five year period, 

Thomas Goetz, host: what Dr. Lax saw in Bristol was happening across England, across the United States and in many other Western countries. The 1980s and nineties 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, tree, nuts, wheat, soybeans. These are the so-called Big eight allergens. They account for 90% of all food allergies we’re 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 

Commercial actor: You work bath time, grandma has a surprise for you. Where’s that little scam? 

Young girl: Is it a rocket? But 

Commercial actor: you can’t see it. Not until you get in the bathtub.

Young girl: It’s a whore. 

Commercial actor: It’s not. It’s Mr. Bubble, and he’ll get you so clean. Your mother won’t know 

Young girl: you. No, my mommy’s hair looks so shiny and healthy. She’s been using my shampoo. Johnson’s baby shampoo. 

Singer: You pew, you natural, you one of a kind, you’re my iry baby. 

Thomas Goetz, host: Part of the story was that things were a lot cleaner than they used to be.

Baby, your skin with 

Singer: ivory 

Thomas Goetz, host: 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 spic 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 that protects ’em.

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 hay 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 was 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 A A P for short, they issued new guidance for parents. They called it the 1, 2, 3 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. 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 a a P 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.

Dr. Gideon Lack: Reports about peanut allergies started to come out in the scientific and the clinical literature, but they apparently weren’t seeing 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’ve put up their hands. So I thought, this is strange. 

Thomas Goetz, host: 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. 

Dr. Gideon Lack: We got our responses and found out that the rate of peanut allergy in the UK Jewish children was about 2%, which was about tenfold higher than in the Israeli schoolchildren 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. 

Thomas Goetz, host: 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 track 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 Bomba 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, and just remember the fear here. It’s very real in 2001. The Journal of the American Medical Association estimated that between 501,000 people die every year in the US 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 gonna run a commercial. But it’s not an advertisement for drug story. This was a commercial that Myelin Pharmaceuticals, the 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. 

Commercial actor: Look at your face and your hands. 

Thomas Goetz, host: It’s still getting worse. 

Commercial actor: Is it your allergy? The word penis in the brownies, right? Peanut butter. Oh no. I forgot what she asked you. Call 9 1 1. So sorry. 

Voiceover: Hey. Okay. Every six minutes, life-threatening food allergies sends 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@faceyourrisk.com. 

Thomas Goetz, host: This is part two, the prescription. So in part one, we heard about the discovery of anaphylaxis, a severe, potentially deadly allergic reaction, and a surprising rise of food allergies in 1990s and early two thousands.

What about the treatment? What could treat an anaphylactic reaction before it turns fatal? For that, let’s go back 125 years, 1900. It’s actually just a few months before Prince Albert and George Riche and Paul Porter set off in 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 racked 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 adrenaline gland known as adrenaline and sold in tablets.

He gradually upped the dosage to 18 tablets a day. And at that dosage, something seemed to work. Her breathing improved, the spasm 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 pillar, 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. 

Doctor:: 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. 

Thomas Goetz, host: 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, their swelling, difficulty breathing.

Worst case, the body slows down so much that people stop breathing or 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. 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 pharmacists 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 ephedrine and isoprene and even cigarettes laced with Bella Donna, 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. 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 an 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, 

Lauren Gilmer: so eight years old going camping in Huntsville State Park, which is this really beautiful lush Piney Woods Forest north of Houston. 

Thomas Goetz, host: This is Lauren. 

Lauren Gilmer: 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, hoisted up a plinth style with a pull 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 trail head, 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. 

Thomas Goetz, host: Oh my God. And, and this is all in like 10 minutes after the bird feeder, or how long? 

Lauren Gilmer: 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. 

Thomas Goetz, host: So her mom busts out the EpiPen and jams it into Lauren’s leg. 

Lauren Gilmer: I remember not even feeling the needle because I was kind of out of it at that point and focused on breathing. 

Alexander Haiju: And 

Thomas Goetz, host: you’re eight years old? 

Lauren Gilmer: Yeah. And there is a small hospital in Huntsville, but it was like, I wanna say 20 minutes away.

So without the EpiPen, I doubt if I would’ve made it there. And once I arrived, I needed more epinephrine 

Thomas Goetz, host: Stories like Lauren’s were becoming more and more common. 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 still puny compared to massive blockbuster drugs like Lipitor, which made $16 billion in 2005, and then in 2007. Myelin 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. 

Voiceover: He’s ready for an adventure. You, 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 autoinjectors are for the emergency treatment of life-threatening allergic reactions, anaphylaxis, and for people who are at increased risk for these reactions.

EpiPen 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, but. 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 shakiness 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.

Thomas Goetz, host: This is part three side effects. In 2007, EpiPen was a quiet but reliable money maker. It brought in $200 million a year, but after Myelin 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, while it had an expiration date on it, they generally are good for one year and second. Myelin 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 EpiPens, states started passing laws requiring public schools to have EpiPens on hand. At the same time, Milan 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 adrenaclick, and that was even cheaper, but it worked a little differently than the EpiPen. And since teachers or 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 or $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 or that 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 fewer grew. In August, 2016, Milan 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. That gesture didn’t quell the outrage. On September 21st, 2016, the CEO of Mylan Heather Brush found herself in front of the US Congress testifying before a house committee investigating drug prices. 

Heather Bresch: The 

Lawmaker: six, do you think you were charging too much at 600, 

Heather Bresch: sir? The, we believe it was a fair price, and we’ve just now lowered that price by half.

Lawmaker: Why’d you lower it by half? If you thought it was fair, if you thought it was fair, leave it. Leave it where it’s at. 

Heather Bresch: 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 of, you’re 

Lawmaker: doing everyone a favor by charging three times what you acquired the drug for. As a generic. You’re trying to make us feel good about that. I just don’t, I mean, I’m not buying your argument.

Heather Bresch: And sir, do 

Lawmaker: you have guilty, have a guilty conscience about any of this 

Heather Bresch: over that period of time? Putting it in public places, giving free 700,000 free EpiPens to 66,000 schools and wanting to get it into all of the public schools across America. 

Lawmaker: Well, if it costs 20 bucks, they could afford to buy their own.

You wouldn’t have to give them to ’em, but instead, you chose to jack the prices up and then somehow feel, make everyone want to feel good about you by saying how much you do. 

Thomas Goetz, host: 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 prices still high. Rates of allergies still high. Still the official guidance to pediatricians told parents, avoid feeding peanuts to young babies, avoid foods that are potentially allergic. Here’s where Gideon La Reenters 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. 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 was 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 and 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 four and 11 months old, and the plan was to carefully expose half of them to peanuts regularly and consistently until they turned five. 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? 

Dr. Gideon Lack: 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 realize 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 a possibility of an intervention that would actually reduce peanut allergy. 

Thomas Goetz, host: 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 allergies 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? 

Dr. Gideon Lack: Well, it 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, very successful vaccines in terms of protection.

Thomas Goetz, host: It was a massive finding. 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.

Anthony Fauci: 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 tolerant to the peanut. 

Thomas Goetz, host: 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. 

Dr. Gideon Lack: 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 and undo that way of thinking is very difficult. 

Thomas Goetz, host: 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 goes to causality, but it certainly ended up, if not creating the epidemic of food allergies exacerbating the epidemic.

Dr. Gideon Lack: Look, uh. We don’t hold all the answers, and very often we get it wrong before we get it right, and I got it wrong. You know, 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.

Thomas Goetz, host: 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 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 money maker. 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 Milan 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, another episodes. But the bottom line is manufacturers have huge leeway to set prices as they see fit. And the US 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 healthcare, 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 Fiat. A name that must have been designed just to be easy to forget fiat. 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 

Dr. Gideon Lack: while the LEAP 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 allergy, 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.

Thomas Goetz, host: 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 palor, which exposes people with peanut allergies to tiny amounts of protein. 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 Lack

drug. Story was created, written and hosted by me, Thomas Getz. Molly Warner is our research director. From Reasonable volume. Rachel Schwabe produced and sound designed this episode with assistance from Audrey. No, Elise Hugh was the editor. Mark Bush is our engineer voice acting by Colin Orden. Drug story was produced with support from the University of California Berkeley School of Public Health.

Special thanks to Claudia Williams and Dean Michael Lu. Thanks also to Alexander Haji, Lauren Gilmer and Dr. Gideon Lack for an annotated list of our sources. For this episode, visit, drug story.co. Drug story 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@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.

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Listening to this episode of Drug Story may cause you to feel itchy, dizzy, woozy. Or even a bit wheezy. 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.