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

Transcript from https://podmenti.com/t/bf909149b1e2414b

Hello, boys and girls, ladies and germs, this is Tim Ferris. Welcome to another episode of the Tim Ferris 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. 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 seemed to skyrocket in the last few years.
Decades.
And what a wild rob. 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.co and learn more. The host is someone I've known for a long time, Thomas Getz, 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 best selling 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 you kick off 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 Sambozen. 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 sessions
No credit card required. Just visit the wayapp.com slash Tim. That's the way W A Y app.
APP.com, the wayapp.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
R
Milk.
Egg.
Wheat?
Peanuts.
Tree nuts.
Out.
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's Alexander Haju. I'm nineteen years old. I live in New York City.
And I'm in this interview.
Because of the sheer 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.
Yeah.
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 all always ends up being
I'm sorry, I don't think we can do all of these, 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 is about
Two years ago.
Previously to this
Tuna showed up low on my blood test?
It didn't show up on the skin tests at all.
I had an oral exam for Tuna.
And
Nothing came up, so the how just cleared me.
And said to just take it easy because I still had an allergy to other fish.
So it has 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 ten minutes into 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 gonna be able to play.
And Dad asks me like
Із да бать да тюрг?
I was like
What do you mean, I'm I wasn't crying, I'm fine?
And he says you look really bad.
So they know they need to leave.
Alex takes some penadrill.
But it does nothing.
Alex's face.
continues to swell.
So
I tell dad like I'm gonna do the epi pen.
I reach into m my tennis bag, I pull out my emergency pack.
Pull out the epi pen.
I want to say you inject yourself into thigh.
With the needle.
But it's more like you really want to like smack yourself with it sometimes.
Uh-huh.
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 ten.
Shortly after the epi pen.
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 epi pen.
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 epi pen.
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 epi pen.
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
А кемикли снтесиз дроб.
That was first patented and sold way back.
In Nineteen O three.
That
More than one hundred years later.
ЕпіПен беким вона в моз контровершіal 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.
Epi pens 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.
Та формані а мільїспі Алекс.
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 nineteen oh one.
On the shores of the Mediterranean Sea.

Of Monaco.
Monaco is on the Riviera.
Surrounded by France.
It's known today.
For the Monaco Grand Prix car race.
for gambling and James Bond and generally for being a good place.
To be super
Rich.
For more than seven hundred years.
Monaco has been ruled by the Monaco royal family.
Officially known.
As the house
of Grimaldi.
In nineteen oh one.
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 a biology.
He would invite scientists to join him on his voyages.
And they would catalogue 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 man of war.
But as delicate and gentle as they look.
These creatures could also be quite dangerous.
Fishermen and sailors reaching into the water, sometimes even swimmers frolicing 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
Or what we now know.
As Fasalia Fasalis.
They have long tentacles that will ensnare a fish.
Zap it with venom.
To paralyze it.
And then we live in.
And since they don't have teeth.
The manower 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 we invited two French scientists.
Paul Portier.
And Charles Richet.
To join him on an expedition to study them.
On July fifth, nineteen oh one.
They set off from the port in Monaco.
And sail 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 Fasalia Fasalis.
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.

Frogs and pigeons.
And even the proverbial guinea pigs.
First.
Cordier and Richet.
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 immun 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 eighteen oh one.
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 uh sensitized. The effect appeared so unforeseen and paradoxical that doctor Roche asked me if I had no mixed the animals into two series, 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.
Само івен а сма сек досвої аміністр.
It could provoke a fatal reaction.
In the animal.
When they returned to Monaco.
Poi and Roche began more experiments under more controlled circumstances.
This time they moved on to dogs, yes.
Sadly, they use dogs.
And the results were striking.
Pornier described what was happening when they exposed one dog to that second dose of manow or poison.
Zidog was in.
Perfect hills.
Cheerful, active, the coat was shiny.
On this day at two PM it was injected.
immediately produced vomiting.
Defecation.
Trembling of front legs.
The dog fell on their side, lost consciousness, and in one half hour
was dead.
Poirier and Rochet 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 eleventh, Nineteen Thirteen.
At the Grand Hotel in Stockholm, Sweden.
Charles Rashe was awarded the Nobel Prize.
For the discovery.
At the banquet.
Rachet delivered his Nobel Lecture.
Where he mentioned in passing.
What he called
Elementary analysis.
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 sheets or to stubborees, to fish, or to shellfish, or to eggs or even to milk.
Now the symptoms to be seen in such individuals on ingesting such and such foods are analogous to the effects of anaphylaxis.
A cute stomach pains, vomiting, diarrhea, coli.
Alphema.
Or to carry ya.
Selfie itching, and sometimes.
Cal their troubles and be there.
We know that these are
An ephalactic
Phenomenal.
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 four fifty BC.
Hippocrates mentioned asthma.
Which means panting in Greek.
And its association with certain foods.
In about fifty five B C.
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 twentieth 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 twentieth 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 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 immun system bounce a full on defense as 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.
А то зустрі.
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.
Um
One's own body proteins and tissues.
A presentage
to the immun system
So the immune system doesn't
attack itself.
That's a process called tolerance.
Um
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 dark.
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.
Anaphylactric 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 twenty twenty four, about ten percent of adults in the US and between six and ten percent of children.
Are estimated to have a food allergy.
That's a huge change.
Over the past fifty years.
When I was in
Medical school, nineteen
Seventy eight to eighty five.
Time we saw
One child admitted for asthma.
And we'll
call to listen to his chest as a sort of teaching.
Case.
This was
Not an unheard of phenomenal.
But pretty unusual in those days. And
Two dialogy I've 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
The
A teenager coming in anaphylactic.
Shock.
Uh well
And then
Panicardia arrest and
Died.
And
Was really
Completely irreversible.
It always struck me.
Over the next few years, Doctor Lack saw a lot more cases of food allergies.
And a lot more often.
And started to see hey.
Was seeing peanuts and food allergies not just
And
Tree.
specialty centres.
or pediatric allergy but we're seeing them in
The community.
And
Literally sold.
The numbers grow before my eyes.
Without needing to do
epidemiology and just become a a more and more apparent problem.
Right.
But Doctor Lac saw in Bristol.
Was happening across England.
Кросс, Униді Стать і манила Western countries.
The nineteen eighties 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.
So it means.
These are the so called
Big eight allergens.
They account for ninety percent.
Of all food allergies.
We are in the Night Seventies.
Maybe one percent of kids had food allergies.
But Night Nighty Five.
It was estimated that five percent 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.
Is it a rocket?
Oh you can't see it.
It's a horse. It is not. It's Mr. Bobble, and it'll get you so close.
Your mother won't know you. Knowing my mommy's here look so shiny and healthy.
She's been using my shampoo. Johnson's baby shampoo. What a kind.


With Ivory. 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 ban 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.
It's a 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.
We often get daily baths that are actually washing away natural oils from the skin.
That protects them.
So ironically.
More hygiene means
Less immune tolerance.
This idea of the hygiene hypothesis.
didn't come along until nineteen eighty nine.
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 nineteen nineties.
You can think of it as an ethical framework for decision making that boils down to
Better safe than sorry.
In two thousand
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 of the
Was to minimize exposure.
When children were very young.
And their immune system.
Was not developed enough, supposedly.
To tolerate these foods.
Mm.
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 seems 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 two tausend five
Doctor Gideon Lack.
Is in Tel Aviv, Israel.
Giving a lecture.
On peanut allergies.
Reports about peanut allergies started to come out.
In the scientific and the clinical literature.
But they apparently won't seen very much of it there.
Um
My opening question
when I started to give my talk was how many of you have seen a
childhood penis allergy in the last year.
Two or three, suddenly less than a handful of people.
Put up their hands.
Where's at the time in the ЮK.
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 Bamba.
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 Doctor Lack learned about this
He thought.
You 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 are any differences
it would be less likely to be a genetic explanation.
We
of our sponsors and found out that the rate of peanut allergy
In
The UK Jewish children was about two percent.
Which was about tenfold higher.
Then in
The Israeli school children.
where peanut allergy was virtually not being seen.
A few cases of peanut allergy.
in that study were derived largely
From children who were born outside Israel.
And
develop their peanut as a G
prior to being in Israel.
The results were published in two thousand eight.
It showed that children in Israel had a much lower rate than
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 two thousand one.
The journal of the American Medical Association estimated that between five hundred and one thousand 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
Yeah, be back.
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 drugstory.
This was a commercial that Mylen Pharmaceuticals
Make or be pen.
That they ran in twenty sixteen.
You'll notice that it doesn't actually mention the epipad.
Not even once.
That's because it's what the FTA 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 drugstore.
Look at your face!
And your hands.
It's still getting worse. Is it your allergy?
You're pizza!
Right?
Peanut butter. Oh no, I forgot. What'd she ask you? So 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 the nineteen nineties and early two thousands.
But what about the treatment?
What could treat an anaphylactic reaction before it turns fatal?
For that, let's go back.
Hundred twenty five years, nineteen hundred.
Actually, just a few months before Prince Albert.
And George Rachet and Paul Portier set off on their voyage to the Azores.
And we're going to Philadelphia, Pennsylvania.
There.
We meet Solomon Solas Cohen.
He was a prominent local doctor.
who was asked to help treat a twenty two year old patient.
It 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.
doctor 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.
Тю ейтін таблиць а дай.
And at that dosage.
Something seemed to work.
Her breathing improved, the spasm stopped.
Soon she was able to go outside.
and breathe normally.
Doctor Solis Cohen.
Fight 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 dream 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
Or the first known clinical use of adrenaline to treat allergies.
Doctor 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 do 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.
There's swelling, difficulty breathing.
Worst case.
The body slows down so much that people stop breathing.
They go into shock.
But 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 pharmacists to treat anaphylactic shock.
And it was cheap to make.
but there was relatively limited demand.
А за наті фортіс і найтінфитіс.
Other drugs had been discovered that treated asthma.
Including ephedrin, an isoprenaline.
And even cigarettes laced with belladonna.
Yes.
They actually once prescribed poison cigarettes.
For asthma.
For many people though, these work better.
And they were easier to tolerate than epinephrine injections.
But another use case for epinephrine emerged in these years.
Years after World War Two, during the so called Cold War.
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 Keplin 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 nineteen seventy seven.
And the EpiPen was approved by the FTA as a drug device combination.
In nineteen eighty seven.
For years the EpiPen wasn't actually used very much.
It wasn't until nineteen ninety 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's 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'm
thirty three 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.
Poist it up.
plint style with a pole in the center.
And I wanted to see w if there were any birds.
And
climbed up, looked inside, put my hands on the edge of it, didn't see anything.
Pop 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.
Realize 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 and this is all in like
Ten minutes after the
bird feeder or how long? Yeah, a max of ten 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

panic rising up in me as it became harder and harder to breathe. And even for someone
That
It had
asthma attacks and for him that was
a pretty normal aspect of life. I mean this was an entirely different level uh
Air hunger.
So her mom busts out the Ebi Pen.
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 wanna say twenty minutes away. So
without the epi pen.
I doubt if I would have made it there. And once I arrived, I needed more epinephrine.
Stories like Lauren's were becoming more and more common.
And the epi pen.
was in more and more homes and cars and schools.
The epipen was turning into a very good business.
From two thousand three to two thousand seven, revenue from EpiPen.
grew by nearly fifty percent.
With sales at around two hundred million dollars a year.
That sounds like a lot of money, and it was.
But it's still puny compared to massive blockbuster drugs like Libator.
Which made sixteen billion dollars in two thousand five.
And then in two thousand seven.
Myland Pharmaceuticals spent almost seven billion dollars 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 twenty thirteen.
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 auto injectors 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, 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, palness, 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 EpiPen.com for more information.
This is part three.
Side effects.
In two thousand seven
EpiPen was a quiet

It brought in two hundred million dollars a year.
But after Milan 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 two hundred and thirty dollars.
twenty thirteen.
And all the while, even as prices climbed.
People kept buying the devices.
For a couple reasons.
First the epinephrine inside the epipan.
Well it had an expiration date on it.
They generally are good for one year.
Second
Mylan began to spend a lot more money.
On lobbying to Congress and States.
With great success.
In twenty ten, 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 epi packs.
States started passing laws requiring public schools to have epi pen's on hand.
А та сам тайм.
Mylen 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.
На терпані alternative девайс.

Adrenalike.
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 epi pets.
This is what economists call
Lock in.
And if that wasn't enough.
In twenty twelve, myland started its Epipen for schools program.
Providing free and discounted debents 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 three hundred dollars apiece.
That's more than three times.
in less than a decade.
Annual sales now topped.
One billion dollars.
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 Milan 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 parents who were now unable to afford the epi pen for their children.
As the fear grew in August twenty sixteen.
Milan tried to defuse the controversy by announcing that it would begin offering a generic version of EpiPen at half the price.
Now three hundred dollars for a two pack.
Instead of six hundred dollars.
But that gesture.
Didn't quell the outrage.
On September twenty first, twenty sixteen.
The CEO of Milan.
Heather Brush.
found herself in front of the US Congress.
Testifying before a house committee.
Investigat drug prices.
Do you think you were charging too much at six hundred?
Sir, the 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 leave it where it's at.
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.
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 the You're doing everyone a favor by charging three times what you acquire 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.
And conscience about any of this? Over that period of time.
Putting it in public places, giving free seven hundred thousand free EpiPens to sixty six thousand schools and wanting to get it into all of the public schools across America.
Well, if it costs twenty 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 feel 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 six hundred dollars.
Or a generic version, basically the same thing, but not called the EpiPen.
For three hundred dollars.
And sure enough.
Over the next few months, more people started to fill their prescriptions for the generic version rather than the full price epi pen.
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 two thousand eight he published his observational study.
That suggested a link between early penite 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.
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 R C T.
In an R C T 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.
Doctor Lack and his colleagues started this other study.
They called it the learning early about peanut allergy.
Or the leap study.
They recruited six hundred and forty children.
between four and eleven months old
And the plan was to carefully expose half of them to peanuts regularly and consistently until they turn five.
And then to compare the rates of allergies between the two groups of children.
Talking to Doctor Lack, though, I was curious.
How exactly did they convince six hundred and forty 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
Realised that
The guidelines were not working.
And the
There was a significant chance that by doing nothing
the baby would develop peanut allergy anyway.
Here was the possibility of an intervention.
that would actually reduce theme nuts energy.
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 twenty fifteen.
Here's what it found at five years of age.
the rate of allergies in the children who had avoided peanuts was nearly fourteen percent.
about what it was in the general population.
But in the group that have been consistently consuming peanuts since those first few months.
The rate of allergies was just one point nine percent.
One point nine percent compared to fourteen percent.
That's a huge difference.
Exposing babies early.
As early as four months was clearly and profoundly beneficial.
This prevented
Food allergies.
Well
astonished that it would be that high.
We were powered statistically, I believe.
to look for a
fifty percent reduction, not an eighty six percent reduction.
In the right of
Allergy. So
That's at the 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 twenty seventeen, 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 track.
An antigen early on.
Before the child's іму систем і фулі девеп.
That you what we call toleraize the child to not.
Make a bad response against the peanut become quot.
Tolerant to the peanut.
That voice might be familiar.
That was Doctor Anthony Fauci.
Yes.
That same Doctor Fauci.
Announcing the new recommendation.
So there we have it.
After generation of children have 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.
Doctor Lack?
He's fairly modest about his discovery.
You know, that famous line there's nothing
To fair but fair itself, which couldn't be more appropriate in the case of
Food allergy.
Well your fear of
Your baby developing the disease.
leads to avoiding the food, leads to causing the baby to have the 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 goes to causality, but it certainly ended up, if not creating the epidemic of food allergies, exacerbating
The epidemic.
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.
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 twenty seventy.
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 epi pen.
Is still
A huge.
Moneymaker.
In twenty twenty three, the epi pen and the generic.
They brought in nearly two billion dollars in revenue.
Yes.
That's
Double the amount from twenty sixteen.
And the price of a two pack.
It's now.
About seven hundred dollars.
That's fifteen percent higher.
And when the Milan CEO was called in to testify in front of Congress.
S controversy and congressional hearings back in twenty sixty.
There 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 episode.
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 twenty nineteen.
My Lin Pharmaceuticals announced.
That it was merging with a unit of Pfizer.
And will become a new company called
Theatre.
A name.
That must have been designed.
Just to be easy to forget.
Theatre.
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.
doctor Lack explains.
While the lead
Charles 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 get 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
P not 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 twenty twenty
The FDA approved a prescription treatment for people with food allergies.
A product called Palvorsia.
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.

by none other than Dr. Gideon Black.
Drug Story was created, written, and hosted by me, Thomas Getz.
Molly Warner is our research director.
From reasonable volume, Rachel Sway produced and sound designed this episode with assistance from Audre No.
Elise Hugh was the editor.
Mark Bush.
is our engineer.
Voice acting by Colin Orton.
Drugs are eight 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 Hajou.
Lauren Gilmer.
and Dr. Gideon Black.
For an annotated list of our sources for this episode.
visit drugstory daт CO
Drugstory is an independent production. There's no tech company or big media conglomerate behind us.
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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.
Лишеньки друг сторію ті філ і.
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.