Discover how modern medicine was built. This podcast explores the careful, often overlooked history of how doctors and scientists identified diseases, uncovered their secrets in the lab, and developed treatments that transformed lives. Join us to appreciate the work behind the medicines we rely on today.
Cholesterol: Schizophrenia and Water Filters The Story of Niacin & Cholestyramine
A failed schizophrenia treatment, a vitamin given in massive doses, radioactive rats, and a water-filter resin that became one of the first drugs used to lower cholesterol.
In this episode, we trace the strange early history of cholesterol-lowering therapy through niacin and cholestyramine. We begin in a Saskatchewan psychiatric hospital, where researchers experimenting with high-dose niacin as a treatment for schizophrenia stumbled onto an unexpected effect: cholesterol levels fell. That observation helped launch niacin into cardiovascular medicine and eventually contributed to some of the earliest evidence that lowering cholesterol could reduce the risk of heart attack.
From there, we follow radioactive cholesterol through laboratory rats as scientists worked out how the body eliminates—and then reabsorbs—cholesterol through the liver, bile, and intestines. That discovery opened the door to an entirely different approach: preventing bile acids from being recycled.
The solution came from an unlikely place: ion-exchange resins already used in water treatment. Cholestyramine could trap bile acids inside the intestine and force the body to use more cholesterol to replace them. Together, niacin and cholestyramine helped establish a revolutionary idea that cholesterol wasn't just associated with heart disease, but could be deliberately lowered to reduce cardiovascular risk—setting the stage for the statin era that followed.
3 Sept 2026
Cholesterol: Xanthomas, Blood, & Bile Linking Cholesterol to Heart Disease
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.
27 Jul 2026
Asthma: Horses, Fish Scale, IgE - The Story of Elucidating the Mechanism of Allergies
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.
23 Jun 2026
Asthma: From Medieval Pregnant Cows to Albuterol - The Discovery of Beta Agonists
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.
16 May 2026
Asthma: Dreams of Anticholinergics
Asthma treatment wasn’t always built around inhalers. It once came from poisonous plants, smoke, and a mysterious dream. In this episode, we explore the strange history of anticholinergics, tracing the path from Jimsonweed and belladonna to atropine, acetylcholine, and Otto Loewi’s discovery of “Vagusstoff.” We follow how Loewi’s frog-heart experiment helped prove that nerves communicate through chemical messengers, and how Henry Dale’s work connected those discoveries to the vagus nerve and airway constriction. We examine why early plant-based asthma remedies could open the airways while also causing dangerous side effects, and how that understanding eventually led to modern anticholinergic therapy. This episode reveals how a dream, a frog heart, and a toxic smoke helped shape the pharmacology of asthma.
11 Apr 2026
Asthma: From the Greeks to Albuterol How Science Unraveled the Airways
Asthma wasn’t always a diagnosis—it was once just a word for breathlessness. In this episode, we explore how asthma evolved from a nonspecific symptom into a defined disease of the small airways. From early descriptions in Greek medicine to the pathologic insights of Morgagni and the mechanistic thinking of Henry Hyde Salter, we follow the key discoveries that shaped our understanding of asthma. We examine how airway inflammation, bronchospasm, mucus plugging, and allergic responses were gradually identified as central features of the disease. This episode sets the stage for understanding the modern pathophysiology of asthma and the therapies that followed.
12 Mar 2026
Breaking the RAAS Cycle: ACE Inhibition in Heart and Kidney Disease
From the discovery of a mysterious blood-pressure–lowering effect in the venom of a Brazilian pit viper to the development of the first ACE inhibitor, we trace how scientists transformed a deadly toxin into lifesaving medicine. We follow the work that identified bradykinin-potentiating peptides in snake venom and revealed that angiotensin-converting enzyme could be blocked—leading to the creation of captopril and later drugs such as enalapril and lisinopril. Along the way, landmark experiments and clinical trials showed that ACE inhibitors do far more than lower blood pressure, reshaping the treatment of heart failure and chronic kidney disease by targeting maladaptive activation of the renin–angiotensin–aldosterone system.
11 Feb 2026
ACE Inhibitors, RAAS Physiology, and Snake Venom: Renin, Angiotensin, and Kidney Blood Pressure Control
From grinding up kidneys and injecting the extracts into animals to the famous Goldblatt clamp experiment, we trace decades of bold science that uncovered the body's most elaborate blood pressure system piece by piece. In part one of a two-part story, we follow the kidney's rise from simple filter to master regulator — through the discovery of renin, the bitter 17-year naming rivalry between Buenos Aires and Cleveland, and the identification of the enzyme that activates it all. Along the way, we encounter a Brazilian pit viper whose venom holds a molecular clue to one of modern medicine's greatest breakthroughs.
13 Jan 2026
Mercury, the First Antibiotic, and the Birth of Thiazide Diuretics
From mercury injections in early syphilis and heart failure patients to the discovery of carbonic anhydrase and the rise of sulfa drugs, we follow how physicians first learned to manipulate fluid balance. We also explore the development of acetazolamide and the eventual breakthrough of thiazide diuretics—revealing how observation and experimentation reshaped the treatment of heart failure and high blood pressure.
20 Dec 2025
Muscle Poisons, Malaria, and Hydralazine Roots: The First Pharmacological Options For Hypertension
Dive into the first real medications used to treat dangerously high blood pressure. From muscle poisons and anti-malarials to a plant root used for centuries, we trace how hydralazine and reserpine emerged as early antihypertensive therapies. We also explore the landmark VA Cooperative Study, which proved that lowering blood pressure could prevent strokes, heart failure, and kidney damage—and began changing modern medicine.
1 Dec 2025
Blood, Salt and Sympathectomies: Early Interventions and Blood Pressure Management
Before thiazides and ACE inhibitors, clinicians relied on bleeding, low-salt diets, metabolic experiments, and even nerve-cutting surgeries to manage dangerous blood pressure. This episode explains how these early interventions—and key discoveries about volume, salt, and baroreceptors—shaped our understanding of hypertension and paved the way for pharmacologic breakthroughs.
28 Nov 2025
Animal Cruelty, Obliterating Arteries, and Insurance Actuaries: How Medicine Recognized the Dangers of Hypertension
We trace the origins of how medicine first understood and measured blood pressure. From early fluid-pressure experiments and invasive animal studies to the invention of the modern blood-pressure cuff, we follow the slow realization that chronically elevated blood pressure is dangerous. We also explore the long-standing debate surrounding "essential hypertension" and how research—from Janeway's observations to insurance-company data and the Framingham Study—ultimately shifted medical practice toward active treatment.
9 Aug 2025
Trailer: Introducing Mechanism of Action
Hosted by Dr. Adam Brown, a rheumatologist with a deep passion for medical history, Mechanism of Action invites you on a journey through the hidden chapters of modern medicine. From the first whispers of mysterious illnesses to the lab discoveries that revolutionized treatment, this show uncovers the fascinating stories behind the drugs we depend on.
Reach and audience
Public platform figures. Ratings count people who left a rating, not total listeners.
Apple Podcasts (US)
5.0 / 5
11 ratings
Contact Mechanism of Action
Guest appearances
Does not typically book guests
Based on episode analysis; this does not confirm that the show is currently accepting guests.
Pod Engine is an independent podcast discovery and analytics service and is not affiliated with or endorsed by this podcast. Artwork and show content belong to their owners. Full legal notice.
Explore this show Podcast research with Pod Engine
