An eleven-year-old girl, cholesterol-fed rabbits, a wartime centrifuge, and the receptors that transformed our understanding of heart disease.

In this episode, we trace how scientists uncovered the connection between cholesterol and atherosclerosis. We begin with an 1889 case involving a young girl covered in xanthomas, then follow cholesterol from its discovery in bile to the fatty plaques found inside diseased arteries.

From there, we explore the experiments that showed cholesterol could cause atherosclerosis, the technology that separated HDL from LDL, and the families whose early heart disease revealed the genetics of familial hypercholesterolemia. Finally, we examine the discovery of the LDL receptor and how it transformed our understanding of cholesterol metabolism laying the foundation for modern cholesterol-lowering therapies.

• (00:00:00) - Cholesterol: Xanthomas, Blood, and Bile
• (00:01:07) - The First Case of Familial Hypercholesterolemia
• (00:02:49) - What Is Cholesterol?
• (00:03:54) - From Hardening Arteries to Atherosclerosis
• (00:04:47) - Cholesterol’s Discovery in Bile
• (00:08:04) - Finding Cholesterol in Arterial Plaques
• (00:11:12) - Proving the Connection with Rabbits
• (00:14:25) - High Cholesterol Runs in Families
• (00:15:47) - Cholesterol Is More Than One Thing
• (00:17:37) - Discovering HDL and LDL
• (00:19:01) - Connecting LDL to Heart Disease
• (00:21:41) - The Discovery of the LDL Receptor

A blood transfusion, a horse-drawn carriage, fish scales, and a rare cancer that transformed our understanding of allergies.

In this episode, Dr. Adam J. Brown concludes the asthma series by telling the remarkable story of IgE—the antibody at the center of allergic disease. We begin with a mysterious 1919 case in which a man seemingly developed a horse allergy after a blood transfusion, then follow the pioneering experiments that revealed allergic sensitivity could be transferred through plasma.

From there, we piece together the puzzle of allergy by connecting IgE, mast cells, and histamine. You'll discover how allergen-specific IgE triggers the release of histamine, why this pathway is responsible for many allergic reactions and asthma attacks, and how these discoveries paved the way for anti-IgE therapies like omalizumab—changing the treatment of allergic asthma, chronic hives, food allergies, and more.

• (00:00:00) - Introduction: The Story of IgE
• (00:01:09) - The Man Who Acquired a Horse Allergy
• (00:05:22) - The Fish-Scale Allergy Experiment
• (00:07:00) - The Search for the Mystery Antibody
• (00:09:02) - The Discovery of IgE
• (00:10:36) - A Rare Cancer and Peter Shackford’s Donation
• (00:12:13) - Histamine, Mast Cells, and Paul Ehrlich
• (00:16:18) - Connecting IgE, Mast Cells, and Histamine
• (00:18:23) - How Allergens Trigger Histamine Release
• (00:20:09) - From IgE Receptors to Omalizumab
• (00:22:37) - Why Do We Have IgE and Mast Cells?
• (00:24:33) - Closing Thoughts

Medieval peasants, poisonous rye fungus, racing hearts, and one of the most important inhalers ever invented. In this episode, Dr. Adam J. Brown continues the asthma series with the strange history of beta-2 agonists and albuterol. We begin with ephedra, ephedrine, and early plant-based asthma treatments, then follow the trail through ergot-contaminated rye, Henry Dale’s experiments with ergotamine and adrenaline, and the discovery that the sympathetic nervous system was working through more than one receptor. From there, we trace Raymond Ahlquist’s alpha/beta receptor breakthrough, the rise of epinephrine and isoproterenol as asthma therapies, the asthma death epidemic of the 1960s, and the leap that separated beta-1 from beta-2 receptors. That discovery opened the door to albuterol—an inhaler designed to target the lungs more than the heart, and still one of the most important rescue treatments in asthma.

• (00:00:00) - Introduction
• (00:00:58) - Ephedrine: The Mongolian Asthma Remedy
• (00:02:26) - Ergot: Medieval Pregnant Cows
• (00:04:50) - Henry Dale and the Ergot Mystery
• (00:06:43) - Adrenaline and the Sympathetic System
• (00:08:24) - The Ergotamine-Adrenaline Paradox
• (00:11:10) - Ahlquist Discovers Alpha and Beta Receptors
• (00:12:34) - Early Modern Asthma Treatments
• (00:13:36) - Isoproterenol and the Asthma Death Epidemic
• (00:15:16) - Beta-1 vs Beta-2 Receptors
• (00:15:17) - Albuterol: Modern Rescue Inhaler