Drug Story

Today we’re sharing an episode of Cautionary Tales, by Tim Harford.
This show concerns Lydia Pinkham’s Vegetable Compound - one of the most popular patent medicines of the late 19th century. Mrs. Pinkham’s compound was sold as a “women’s tonic,” ideal for menopause or menstrual pain. The package promised big: "It cures bloating, headaches, nervous prostration, general debility, sleeplessness, depression, and indigestion.”
But did it, really? No, it did not. Lydia Pinkham’s compound was the epitome of a cure-all that cured nothing, a secret concoction of herbs and roots and other ambiguous ingredients that promised tremendous benefits without any evidence whatsoever. 
Eventually, it was outrage over patent medicines like Mrs. Pinkham’s that turned into the creation of the FDA, and the evidence-based medicine we have today. 
Back next week with a new episode of DRUG STORY!


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20 years ago, pharmacogenomics was all the buzz: matching specific drugs to our personal DNA was supposed to transform medicine and human health.
But here we are 20 years later, and much of that excitement has fizzled. Very few doctors are actually tailoring their treatments to individual patient DNA in the clinic.
In this special episode, I talk with Dr. Eric Topol, author of the new book Super Agers, about the promise of pharmacogenomics and the new frontiers of medicine. We talk about how he has always put science first - he shares the story of Vioxx, a pain reliever that he was early to see carried massive risks. Eric put his career on the line to let the world know about the problems.


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Ever heard of neurasthenia, aka Americanitis? It was the first epidemic of the 20th century - and it's number one symptom was insomnia.
It may have just been the electricity.
In this episode of Drug Story, we step into that sweet oblivion called sleep, and that infernal torment called insomnia. We visit hustle culture, where sleep is just an obstacle to crushing it.
And we learn about Ambien: the most popular sleeping pill ever invented. Until women started showing up in emergency rooms with amnesia...
Sources for this episode
[1] NEURASTHENIA, DEGENERACY, AND MOBILE ORGANS (1906) The British Medical Journal: Neurasthenia is defined by a state of "nervous exhaustion" and can include physical symptoms like head or spinal pain, insomnia, and constipation, along with mental depression.
[2] Neurasthenia and a Modernizing America (2003) JAMA: Introduces neurasthenia after the Civil War as a nervous-energy disorder; the term declined in use after the 1930s.
[3] ‘Americanitis’: The Disease of Living Too Fast (2016) The Atlantic: Frames neurasthenia as a disease of living too fast in industrializing America.
[4] Insomnia and the late nineteenth-century insomniac: the case of Albert Kimball (2020) Interface Focus:The identity of the “insomniac” emerged alongside industrial-era stress and the concept of neurasthenia.
[5] A short history of insomnia and how we became obsessed with sleep (2023) The Conversation: Industrialization increased insomnia rates through artificial lighting, work shifts, and societal change.
[6] The Pathophysiology of Insomnia (2015) Contemporary Reviews In Sleep Medicine: Insomnia can be influenced by genetics, cellular and physiological mechanisms, and sleep behaviors.
[7] Insomnia: a cultural history (2018) The Lancet: Contrasts pre-industrial ritualized sleep with modern increases in chronic insomnia.
[8] Phenome-wide Analysis of Diseases in Relation to Objectively Measured Sleep Traits and Comparison with Subjective Sleep Traits in 88,461 Adults (2025) Health Data Science: In a research study, poor sleep quality was associated with increased risk for 172 different diseases including Parkinson's disease and type 2 diabetes.
[9] A Short History of Sleeping Pills (2018) Sleep Review: The history of treatments for insomnia covering alcohol, opiates, barbiturates, benzodiazepines, and “Z drugs” like Ambien.
[10] The Evolution and Development of Insomnia Pharmacotherapies (2007) Journal of Clinical Sleep Medicine: History of pharmacological treatment for insomnia: from older, less safe options like barbiturates to the current generation of medications with improved safety profile.
[11] The Big Sleep (2013) The New Yorker: In 1973, Jean-Pierre Kaplan began work on a new class of sleeping pills at Synthélabo, leading to zolpidem’s development.
[12] Critics say drug ads should be a wake-up call (2006) Star News: Critics link increased use of Ambien and Lunesta to aggressive advertising campaigns.
[13] Evaluation of the long term efficacy and safety of zolpidem-MR 12.5 mg compared to placebo, when both are administered over a long term period “as needed”, in patients with chronic primary insomnia (2008) Sanofi-Aventis: Summary of Phase III clinical trial investigating the long-term efficacy and safety of the extended-release sleep medication, zolpidem.
[14] Emergency Department Visits for Adverse Reactions Involving the Insomnia Medication Zolpidem (2013) SAMHSA: There was a 220% increase in emergency department visits related to adverse reactions from the sleep medication zolpidem between 2005 and 2010
[15] FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR (2013) The U.S. Food and Drug Administration: FDA recommended lower doses and advised avoiding driving the day after using Ambien CR.
[16] FDA adds Boxed Warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines (2019) The U.S. Food and Drug Administration: The official safety communication from the FDA announcing a Boxed Warning for specific prescription insomnia medications, including eszopiclone, zaleplon, and zolpidem, due to reports of dangerous side effects.
[17] Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem (2009) Journal of Clinical Sleep Medicine: PET scans and literature review on zolpidem’s association with abnormal sleep behaviors.
[18] Zolpidem and Driving Impairment — Identifying Persons at Risk (2013) New England Journal of Medicine: Examines risks of zolpidem, including sleepwalking, sleep-related eating disorder, and sleep-driving.


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Pain is probably the oldest problem in medicine. It’s the way our bodies tell us that something is wrong here.
But pain has long been considered a symptom. So when medicine can’t find what’s wrong, or when medicine can’t fix the pain, well, that’s usually the end of the story. And that’s left a lot of people with chronic pain suffering in silence.
In this episode, we learn why pain is one of the great mysteries of medicine - one of the most challenging conditions to diagnose, to measure, and to treat successfully.
We explore why the worthy effort to bring pain into the light inadvertently created what may be the most devastating social crisis (ahem, opioid epidemic) of the last century.
And we look at a new pain medicine - Journavx - which is not approved for chronic pain (yet) but has a lot of people hoping for a path to peace without addiction.
Sources for this episode
[1]  "Wrestling With Pain:" John J. Bonica, MD. Autobiography (1987) The International Symposium on Pain Analgesia: Dr. John J. Bonica recounts his life as a "wrestling match" against medical indifference to establish the multidisciplinary approach to pain therapy. 
[2] Oral History Interview with John J. Bonica (1993) John C. Liebeskind History of Pain Collection: John Bonica is widely regarded as the founding father of pain management.
[3] International Symposium on Pain (1974) Raven Press: Proceedings from the first major international meeting on pain research and management.
[4] Individual Differences in Pain: Understanding the Mosaic that Makes Pain Personal (2017) PAIN: Explains how biological, psychological, and social factors shape personal pain experiences.
[5] Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice (2021) Journal of Pain Research: "Chronic pain" is a semantically inaccurate and potentially misleading clinical label because it overemphasizes duration while failing to account for biopsychosocial factors.
[6] Prevalence of Depression and Anxiety in Chronic Pain (2025) JAMA: Systematic review and meta-analysis showing high rates of depression and anxiety among adults with chronic pain.
[7]  Improving Outcomes of Analgesic Treatment: Is Education Enough? (1990) Annals of Internal Medicine: The persistent undertreatment of pain is rooted in a historical medical focus on physical lesions over subjective symptoms. 
[8]  Pain as the 5th Vital Sign Toolkit (2000) The Veterans Health Administration: A comprehensive guide developed by the Veterans Health Administration (VHA) to institutionalize a standardized, system-wide approach to managing patient discomfort.
[9] A Capsule History of Pain Management (2003) JAMA: Historical overview of approaches to managing pain, from ancient remedies to modern treatments.
[10] Bridging Old and New in Pain Medicine: An Historical Review (2023) Cureus: Historical review linking traditional pain remedies with modern medical practices.
[11] The Opioid Epidemic: It’s Time to Place Blame Where It Belongs (2017) The Journal of the Missouri State Medical Association: Dr. Ronald Hirsch argues that the opioid crisis was driven by a network of "co-conspirators" including pharmaceutical companies, medical oversight organizations, and government agencies.
[12] The 5th Vital Sign and America’s Painkiller Epidemic (2016) The University of Arizona Health Sciences: The institutionalization of pain management led to a surge in prescription drug abuse and overdose deaths. 
[13]  The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy (2008) The American Journal of Public Health: Oxycotin’s commercial success was driven by predatory marketing tactics, such as targeting high-volume prescribers and systematically understating the risk of addiction.
[14]  The fifth vital sign: A complex story of politics and patient care (2016) Cleveland Clinic Journal of Medicine: Aggressive marketing and institutional mandates minimized the perceived risks of addiction, leading to the current opioid epidemic.
[15] The Pain and Opioid Epidemics: Policy and Vital Signs (2016) JAMA Health Forum: The historical movement to treat pain as a fifth vital sign inadvertently fueled a massive increase in narcotic prescriptions.
[16] Addiction Rare in Patients Treated with Narcotics (1980) The New England Journal of Medicine: a 1980 letter to the editor of the New England Journal of Medicine covers the low incidence of narcotic addiction in medical settings.  
[17] Remove Pain as 5th Vital Sign, AMA Urged (2016) Medpage Today: Medical professionals at an American Medical Association met to advocate for the removal of pain as a "fifth vital sign".
[18] FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain (2025) US Food & Drug Administration: FDA announcement of approval for a new, non-opioid treatment for moderate to severe acute pain.
[19] F.D.A. Approves Drug to Treat Pain Without Opioid Effects (2025) The New York Times: The FDA approved a non-opioid painkiller developed by Vertex.
[20] What Is Journavx, the New Opioid-Free Painkiller from Vertex? (2025) Scientific American: Journavx functions by blocking sodium ion channels to stop pain signals before they reach the central nervous system, offering a mechanism entirely different from traditional treatments.
[21] Painkillers without the addiction? The new wave of non-opioid pain relief (2025) Guaridian:  The pharmaceutical industry is shifting toward developing non-opioid pain relief to address the devastating global addiction crisis.
[22] An SCN9A channelopathy causes congenital inability to experience pain (2006) Nature: Discovery that mutations in the SCN9A gene cause congenital inability to experience pain.
[23] Chronic Pain Is a Hidden Epidemic. It’s Time for a Revolution. (2025) The New York Times Magazine: Opinion piece calling for a revolution in how chronic pain is addressed in society.


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The idea of drug patents makes a lot of sense: The company that put the effort and resources into developing the medicine is the first to reap the benefits. That company gets a limited monopoly for 20 years, when it is the only company allowed to manufacture and sell that drug.
The deal is that after that patent expires, other companies can manufacture and sell the drug, too. The drug goes “generic.” Typically that means lower prices for patients - more people benefit. That’s how the system is supposed to work. 
But that system relies a lot on good faith - and many pharma companies have gotten very good at finding ways to extend that 20 years, making small tweaks to a drug to extend their monopoly for years.
Today, I hand Drug Story over to the excellent journalist Dan Weissmann, host of the NPR podcast An Arm and A Leg. In this episode of An Arm and a Leg, Dan talks with John Green - author of the new book, Everything is Tuberculosis. Green explains a very effective drug for TB was kept under patent protection for years, making it too expensive to treat millions of people with tuberculosis, leading to thousands of unnecessary deaths worldwide.


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