What is anaphylaxis and its discovery

Epipen is an exquisitely engineered, expertly marketed, totally modern drug. And it’s an amazing success story, especially if you count success through dollars - Epipen sales rose from $200 million in 2007 to $1 billion a year in 2015 to more than $2 billion in 2023. Epipen is what they call in the pharma business, a blockbuster.

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 Atlantic Ocean, to Sweden, the home of the Nobel Prize, to Vietnam, during the Vietnam War.

This story also lands very close to home. 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. So in this episode, we’ll learn all about that.

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 - their condition may in fact be the result of one of the biggest blunders of the past century of medicine and public health.

Sources for this episode

[1] A Mighty Pen (2013) Science History Institute Museum and Library: In the 1970s, inventor Sheldon Kaplan developed an epinephrine autoinjector in response to the need for rapid, self-administered injections to treat anaphylactic shock.

[2] Auvi-Q Versus EpiPen: Preferences of Adults, Caregivers, and Children (2013) The Journal of Allergy and Clinical Immunology: This study evaluates preference for the Auvi-Q epinephrine autoinjector over the EpiPen among adults, caregivers, and children.

[3] Epinephrine Administered in Anaphylaxis: The Evolution of 0.3 mg Dosage (2023) Therapeutic Advances in Allergy and Rhinology: Anaphylaxis was first formally discovered by French scientists Charles Richet and Paul Portier in experiments with dogs. They found that dogs became more sensitive, rather than less sensitive, to a toxin after an initial small dose.

[4] Northeastern alumnus the genius behind life-saving EpiPen (2016) Northeastern Global News: Sheldon Kaplan reengineered a Cold War-era device, the ComboPen, that delivered a nerve agent antidote, into a device that delivered epinephrine. The new device, EpiPen, was patented under Kaplan’s name in 1977.

[5] Body and Mind; Backward Protection (1989) New York Magazine: Anaphylaxis is a biological mechanism where the immune system provides misguided “backwards protection” by overreacting to allergens such as nuts, penicillin, or insect stings.

[6] The Use of Adrenal Substance In the Treatment of Asthma (1900) Journal of the American Medical Association: Early research by Dr. Solomon Solis-Cohen showed that using extracts from animal adrenal glands could significantly relieve asthma symptoms by strengthening blood vessels and reducing swelling in the airways.

[7] The Allergy Epidemics: 1870–2010 (2015) The Journal of Allergy and Clinical Immunology: The rise in allergies over the past 150 years can be attributed to advances in hygiene and lifestyle changes, such as increased sedentary indoor lifestyles.

[8] History of food allergy and where we are today (2024) World Allergy Organization Journal: Once poorly understood, food allergies are now managed through strategies beyond avoidance, including immunotherapy, biologic treatments, and early allergen introduction for prevention.

[9] How Marketing Turned the EpiPen Into a 20 Billion-Dollar Business (2015) Bloomberg Businessweek: Mylan Pharmaceuticals, the manufacturer of EpiPen, ran marketing campaigns emphasizing the dangers of food allergies and lobbied lawmakers to place EpiPens in schools and public venues. As a result, the EpiPen became a $1 billion-per-year product, and its price increased by 400% after Mylan acquired it in 2007.

[10] Epinephrine: a short history (2015) The Lancet Respiratory Medicine: In 1894, the English physician George Oliver and the English physiologist Edward Schafer discovered the physiological effects of adrenal medulla extract. In 1899, American biochemist John Jacob Abel successfully purified the extract’s active ingredient and named it epinephrine. It was then synthesized in ampules by Parke-Davis & Company in 1909.

[11] The ancestry of allergy: Being an account of the original experimental induction of hypersensitivity recognizing the contribution of Paul Portier (1985) The Journal of Allergy and Clinical Immunology: In 1902, Paul Portier and Charles Richet discovered anaphylaxis after observing that a second, weak injection of sea anemone toxin caused fatal hypersensitivity in dogs rather than the expected immunity.

[12] Feed Your Kids Peanuts, Early and Often, New Guidelines Urge (2017) The New York Times: The National Institute of Allergy and Infectious Diseases shifted its approach to child nutrition in 2017 by recommending that parents introduce peanut-based foods to infants as early as four to six months of age.

[13] Portier, Richet, and the discovery of anaphylaxis: A centennial (2002) The Journal of Allergy and Clinical Immunology: Paul Portier and Charles Richet discovered anaphylaxis while investigating the toxins of marine life aboard the yacht of Prince Albert of Monaco in 1901.

[14] The Prevalence of Chronic Respiratory Disease in the Industrial Era The United States, 1895–1910 (2003) National Bureau of Economic Research: Chronic respiratory disease prevalence rose in the United States between 1895 and 1910 due to rapid urbanization, industrial pollution, and the emergence of cigarettes.

[15] Shock Reaction Following Ingestion of Mango (1965) Journal of the American Medical Association: A case study on an anaphylactic-like response to mango helped establish early clinical understanding of food-induced anaphylaxis.

[16] Slow Epinephrine In the Treatment of Chronic Asthma (1939) The Journal of Allergy: This 1938 study shows that mixing epinephrine with peanut oil allows the body to absorb the medicine more slowly than the standard water-based version. By delaying absorption, patients can reduce the frequency of injections.