This episode of Drug Story is hosted by Thomas Goetz, Senior Impact Fellow at the University of California Berkeley and former executive editor at Wired magazine. The show explores the history and economics of prescription medicines, examining one drug per episode through the lens of disease, business, and unintended consequences.

The episode features Alexander Haju, a 19-year-old New Yorker living with nine severe food allergies who has never eaten restaurant food, and Dr. Gideon Lack, professor of pediatric allergy at King's College London, whose research revolutionized food allergy prevention. Lauren Gilmer, now 33, shares her childhood anaphylactic emergency that required an EpiPen to save her life.

The narrative traces the discovery of anaphylaxis in 1901 Monaco through Prince Albert's scientific expeditions, the development of epinephrine as a treatment, and the invention of the EpiPen auto-injector by NASA engineer Sheldon Kaplan in 1977. The story culminates in the controversial price increases by Mylan Pharmaceuticals and the groundbreaking 2015 LEAP study that overturned decades of medical guidance.

Central to the episode is the revelation that well-intentioned medical recommendations to avoid allergens in early childhood may have caused millions of children to develop food allergies, representing one of modern medicine's most significant unintended consequences.

The Discovery of Anaphylaxis in Monaco Waters

In 1901, Prince Albert of Monaco invited French scientists Paul Poitier and Charles Richet aboard his yacht to study Portuguese Man-of-war jellyfish, whose stings caused intense pain and occasional fatalities. The scientists extracted venom and injected it into experimental animals including frogs, pigeons, and guinea pigs.

"Immediately produced vomiting, defecation, trembling of front legs. The dog fell on the side, lost consciousness, and in one half hour was dead" - Poitier describing a dog's reaction to a second dose of man-of-war venom. The scientists discovered that initial exposure sensitized rather than immunized animals, making subsequent exposures potentially fatal.

Richet coined the term "anaphylaxis" meaning "anti-protection" and received the 1913 Nobel Prize for the discovery. In his Nobel lecture, he noted that "acute stomach pains, vomiting, diarrhea, colic, erythema, urticaria, severe itching" from certain foods were "analogous to the effects of anaphylaxis."

Historical records show food allergies were documented as early as 450 BC when Hippocrates mentioned asthma's association with certain foods, and 55 BC when Roman philosopher Lucretius Cato wrote "one man's meat is another man's poison." However, food allergies remained poorly understood curiosities through the early 20th century.

The Hygiene Hypothesis and Rising Allergy Rates

"When I was in medical school, 1978-85, we saw one child admitted for asthma as a sort of teaching case. This was not an unheard of phenomenon, but pretty unusual" - Dr. Gideon Lack. By his residency in the Bronx, he witnessed a teenager die from anaphylactic shock, marking the beginning of a visible epidemic.

The hygiene hypothesis, first proposed in 1989, suggests that increased use of consumer cleaning products and overly sanitized households reduced immune system exposure to environmental factors. Daily baby baths were washing away natural protective oils, ironically making immune systems less robust and more prone to allergic reactions.

Food allergy rates exploded from approximately 1% of children in the 1970s to 5% by 1995, with the trend accelerating through the 2000s. As of 2024, about 10% of adults and between 8-10% of children in the U.S. have food allergies, representing a tenfold increase over 50 years.

The "big eight" allergens - peanuts, eggs, shellfish, milk, fish, tree nuts, wheat, and soybeans - account for 90% of all food allergies. Peanuts emerged as the first major concern in the 1980s and 1990s, leading to widespread bans in schools and on airlines.

The Precautionary Principle Backfires Catastrophically

In 2000, the American Academy of Pediatrics issued the "1-2-3 rule" guidance: avoid dairy until age one, eggs until age two, and peanuts/seafood until age three. This recommendation was based on the precautionary principle of "better safe than sorry" rather than scientific evidence.

"The idea was to minimize exposure when children were very young, and their immune system was not developed enough, supposedly, to tolerate these foods" - Host. The guidance created a devastating feedback loop where avoiding foods at early ages sensitized more children to those foods later, driving allergy rates even higher.

Dr. Lack's 2008 observational study compared Jewish children in the UK versus Israel, finding UK children had 2% peanut allergy rates - tenfold higher than Israeli children who consumed bamba (peanut-flavored puffs) starting at 4-5 months old. However, this observation alone couldn't change medical practice.

"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" - Dr. Lack on the tragic irony of avoidance recommendations.

The LEAP Study Overturns Decades of Medical Guidance

The Learning Early About Peanut Allergy (LEAP) study recruited 640 children aged 4-11 months for a randomized controlled trial. Half were regularly exposed to peanuts until age five, while the control group avoided peanuts following standard guidance at the time.

"I was really astonished that it would be that high. We were powered statistically to look for a 50% reduction, not an 86% reduction in the rate of allergies. That's at a level of very successful vaccines" - Dr. Lack on the February 2015 results published in the New England Journal of Medicine.

At five years old, children who avoided peanuts had 14% allergy rates - matching general population levels. Children with early consistent peanut exposure had just 1.9% allergy rates, representing an 86% reduction and protection comparable to highly effective vaccines.

In 2017, Dr. Anthony Fauci announced new National Institute of Health guidance reversing the 2000 recommendations: "When you give by mouth, expose through the gastrointestinal tract, an antigen early on before the child's immune system is fully developed, you tolerize the child."

Despite the 2017 guidance change, food allergy rates have continued increasing in both children and adults. Many parents remain uncomfortable with early exposure, the precautionary principle persists culturally, and excessive infant bathing continues to compromise natural skin protection.

From Nerve Gas Antidote to Life-Saving Auto-Injector

In 1900, Philadelphia doctor Solomon Solas Cohen treated a 22-year-old asthma patient with adrenal gland extract tablets, gradually increasing dosage to 18 tablets daily. Her breathing improved dramatically, marking the first clinical use of adrenaline for allergies, though the extract caused "diarrhea with offensive discharges."

Within two years, adrenaline was chemically isolated and patented in synthetic form as epinephrine. By 1918, epinephrine injections were specifically recommended for anaphylactic shock treatment. The drug works by increasing heart rate and circulation while reducing inflammation - the opposite of an allergic reaction's effects.

During the Cold War, the U.S. military hired NASA engineer Sheldon Kaplan to develop emergency medical solutions for nerve gas exposure. Kaplan invented the "combo pen" for troops to self-administer antidotes in the field, which he realized could be adapted for epinephrine delivery.

Kaplan and Survival Technology Inc. received a patent for the auto-injector in 1977, and the EpiPen was FDA-approved as a drug-device combination in 1987. The device wasn't widely used until the 1990s when food allergy rates began climbing dramatically.

Lauren Gilmer's story illustrates the EpiPen's life-saving capability: at age eight, she suffered anaphylaxis from touching bird feeders at a state park. "I remember not even feeling the needle because I was kind of out of it at that point and focused on breathing... without the EpiPen, I doubt if I would have made it" to the hospital 20 minutes away.

Mylan's Price Gouging and Congressional Reckoning

When Mylan Pharmaceuticals acquired EpiPen rights in 2007 for nearly $7 billion, annual sales were around $200 million. The company immediately began raising prices, more than doubling the cost from $109 per device to $230 by 2012.

In 2010, the FDA changed guidance to allow two-device packages, effectively doubling purchases since sometimes one dose isn't enough to prevent anaphylaxis. Mylan simultaneously lobbied states to require EpiPens in schools and created free training programs that taught teachers and nurses exclusively on EpiPen devices.

The training created "lock-in" - schools required parents to purchase EpiPens rather than cheaper alternatives like Adrenaclick because staff weren't trained on other devices. Mylan launched the EpiPen4Schools program in 2012, further cementing market dominance through institutional requirements.

By 2016, a two-pack cost over $600 - more than triple the 2007 price - with annual sales topping $1 billion, making it an official blockbuster drug. The price increases sparked national outrage as parents shared stories of being unable to afford life-saving medication for their children.

"Do you think you were charging too much at $600?" "Sir, we believe it was a fair price, and we've just now lowered that price by half." "Why'd you lower it by half if you thought it was fair?" - Congressional testimony exchange with Mylan CEO in September 2016, where she defended the pricing as necessary for school distribution programs.

Despite congressional hearings and public outcry, EpiPen prices continued rising. By 2023, a two-pack cost approximately $700 - 15% higher than the 2016 scandal price - with annual revenue reaching nearly $2 billion. Mylan merged with Pfizer in 2019 to become Viatris, and U.S. drug pricing remains largely unregulated.

Living with Severe Food Allergies in Modern America

Alexander Haju, 19, lives with nine food allergies and has never eaten restaurant food in his life. "I always bring my own food. I typically just ask for an empty plate. 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."

During his eighth or ninth time eating tuna - previously cleared by his allergist through blood tests, skin tests, and oral examination - Alex experienced anaphylaxis at tennis practice. "My wrist's really hurting... I was breathing really hard and my face" began swelling. His father noticed he looked like he was crying.

"The needle's just so big, like that thing is huge. I hit myself with it. I count to 10 shortly after the EpiPen. The symptoms, I could feel them like immediately going down" - Alex describing self-administering the auto-injector. He was then taken to the hospital for additional epinephrine and observation.

New treatments offer hope: the FDA approved Palforzia in 2020, a prescription allergen immunotherapy that exposes peanut allergy patients to tiny amounts of protein with proven benefit. Dr. Lack co-founded Mission Mighty Me, a company creating foods designed to introduce allergens early in infant diets.

"If you give by mouth, expose it through the gastrointestinal tract, an antigen early on before the child's immune system is fully developed, you tolerize the child to not" develop allergies - Dr. Fauci explaining the biological mechanism behind early exposure's protective effect.