pplpod

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People take aspirin somewhere between 50 and 120 billion times a year, yet for most of its commercial life no one knew how it worked. This episode traces it from willow bark and meadowsweet, recorded on Sumerian clay tablets and in the Ebers Papyrus and prescribed as a tea by Hippocrates, to the Reverend Edward Stone, who in 1763 tasted bitter willow bark, dried it for feverish parishioners, and reported to the Royal Society. Charles Gerhardt first synthesized acetylsalicylic acid in 1853, and in 1897 Bayer produced a stable, more tolerable form, with credit disputed between Felix Hoffmann and Arthur Eichengrün.

Bayer launched the name Aspirin in 1899, then lost the trademark in the United States and other countries after World War I. In 1971 John Vane showed that aspirin blocks prostaglandins and thromboxanes, work that earned the 1982 Nobel Prize. It does so by permanently disabling the COX enzyme, a process called suicide inhibition, which matters because platelets have no nucleus and cannot replace it. The episode covers Reye's syndrome, why chronic overdose carries a 25 percent mortality rate against about 2 percent for acute overdose, the 2022 task force reversal, and a March 2025 Nature study on cancer.

• How the name combines acetyl, Spirsäure from meadowsweet, and a standard drug suffix
• Why Canadian generics must be sold as ASA instead of aspirin
• The vinegar smell that signals aspirin breaking down through hydrolysis
• How salicylate swings blood chemistry from respiratory alkalosis to metabolic acidosis
• Hijacked platelets using thromboxane A2 to hide metastasizing cancer cells from T cells

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Before the 1840s, surgery meant being strapped to a table and feeling every cut, and many doctors believed pain kept a patient's vital force alive. Horace Wells, born in 1815 to a wealthy New England family, opened a successful dental practice in Hartford, Connecticut, in 1836 and wrote a booklet at 23 urging less sugar, daily brushing, and saving children's baby teeth. In December 1844 he watched a laughing gas show in which a volunteer gashed his legs on a bench without noticing. The next day Wells inhaled nitrous oxide himself and had a wisdom tooth pulled without pain.

In early 1845 he demonstrated the gas at Massachusetts General Hospital in Boston, assisted by his former student William Morton. The patient groaned, the audience called Wells a fraud, and he left in disgrace, though the patient later said he felt no pain. In 1846 Morton succeeded with ether and tried to patent it as his own discovery. Wells spiraled, experimented on himself with ether and chloroform in New York, and on his 33rd birthday, January 21, 1848, threw acid on two women. He took his own life in the Tombs prison days after the Paris medical society had voted to recognize him as the pioneer of anesthesia.

• The traveling tooth pullers at his family's inn who first drew him to dentistry
• How nitrous oxide inhibits NMDA receptors involved in pain signaling
• Why the Boston patient, a heavy drinker, likely needed a larger dose
• The chloroform he inhaled before his death and the letters he wrote to his family
• Posthumous recognition by American medical and dental associations over Morton

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In alien hand syndrome, one hand, most often the left, carries out purposeful actions its owner never chose: snatching a cigarette from the mouth, or unbuttoning a shirt as fast as the other hand buttons it. This episode separates the condition, also called Dr. Strangelove syndrome, from twitches and reflexes and explains intermanual conflict, where the hands work against each other. Patients still feel the limb as their own but lose the sense of agency, and many give it a name. One patient described by Rochelle Doody and Joseph Jankovic called hers Baby Joseph and scolded it like a mischievous infant.

The mechanism centers on the efference copy, the internal memo that tells the brain a movement was self-generated. When it fails, the brain reads the hand's actions as caused by an outside force. The episode covers three variants: the callosal type seen after the corpus callosum is cut to treat epilepsy, the frontal type with compulsive grasping that Derek Denny-Brown described as positive tropism, and the posterior type in which the hand recoils and levitates. It ends with the workarounds patients use and the recovery that neuroplasticity can bring.

• Other names patients have given their hands, from Cheeky to the monster from the moon
• Tonic grasping, where patients must pry the fingers off objects with their other hand
• How approach and withdrawal systems in the brain normally hold each other in check
• Canes, oven mitts, and biofeedback alarms used to keep a rogue hand occupied
• Why one-sided stroke cases often improve significantly within a year

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Alice in Wonderland syndrome makes a person's own hands look like a toddler's, stretches a nearby wall into the distance, and turns the hum of a refrigerator deafening, all while the person knows none of it is real. This episode walks through the distortions: micropsia and macropsia, objects looming close or receding far away, the feeling of body parts growing or shrinking, depersonalization, derealization, and a broken sense of time and speed. Brain scans point to the temporo-parieto-occipital junction, where visual and body-position signals merge, showing abnormal electrical activity and reduced blood flow during episodes.

In more than half of cases the trigger is unknown. In children, the documented causes are mostly infections such as Epstein-Barr virus, influenza A, chickenpox, coxsackievirus, and Zika; in adults, migraines dominate, with about 1 in 10 chronic migraine sufferers reporting symptoms. The name comes from British psychiatrist John Todd, who in 1955 argued that Lewis Carroll drew Alice's transformations from his own migraine auras. The episode weighs that theory against the mushroom theory and explains why the condition still has no code in the DSM-5 or ICD-10.

• Cortical spreading depression, the slow electrical wave behind migraine aura, explained
• Carroll's diary references to bilious headaches and his 1856 visit to ophthalmologist William Bowman
• The 1909 coinage of Lilliputian hallucinations after Gulliver's Travels
• Why frightened children often hide symptoms and how doctors use their drawings as clues
• Episodes lasting minutes to an hour and fading once the underlying cause is treated

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As a boy in Luton, Alec Jeffreys dissected a dead cat from his paper route on the family dining table, made explosions with a modified chemistry set, and was left with a sulfuric acid scar on his chin that he still hides under his beard. Born in Oxford in 1950, he earned first class honors in biochemistry at Merton College, Oxford, and moved to the University of Leicester in 1977. On September 10, 1984, while studying an X-ray film of DNA from his lab technician's family, he saw both shared patterns and differences, and within about 30 minutes grasped that minisatellite regions could identify individuals like a barcode.

The first real case in 1985 was an immigration dispute in which his test proved a British boy of Ghanaian family was his mother's son. Then came the Narborough murders of Lynda Mann and Dawn Ashworth: the DNA cleared Richard Buckland, a teenager who had confessed to one killing, and led to the conviction of Colin Pitchfork. In 1992 Jeffreys' team confirmed the remains of Josef Mengele using DNA from his mother and son. The episode ends with the shift to PCR and STR profiling, the UK National DNA Database launched in 1995, and Jeffreys' objection to storing the profiles of people who were never convicted.

• The Victorian brass microscope from his father that started his bumblebee dissections
• How radioactive probes turned minisatellites into dark bands on X-ray film
• Why his Leicester lab was the only place doing DNA fingerprinting until 1987
• About 5.6 million people held on the UK database by 2020, arrested or not
• His proposal for a universal database run by an independent third party and searched only by warrant

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Adrenaline is the hormone behind the parent who lifts a car off a trapped person and the skydiver chasing a rush. This episode explains where it comes from: more than 90 percent of circulating adrenaline is made in the adrenal medulla on top of the kidneys, with a small amount produced by neurons in the medulla oblongata. As a non-selective agonist, it acts like a master key on alpha-1, alpha-2, beta-1, beta-2, and beta-3 receptors, dilating pupils, opening airways, speeding the heart, breaking down fat, and flooding the blood with glucose from the liver, while squeezing vessels in the limbs to keep pressure up in the heart and brain.

The story then turns to memory and medicine. In fear film experiments, subjects given adrenaline showed more fear and later recalled the films more negatively, an effect that did not appear with funny or anger-inducing films. Because adrenaline does not easily cross the blood-brain barrier, it works through peripheral receptors, which the beta blocker sotalol was shown to block. The episode closes with the naming feud: John Jacob Abel's 1897 extract called epinephrine, Jokichi Takamine's purified version trademarked as Adrenalin by Parke-Davis, and the transatlantic split that still exists today.

• Why vasoconstriction in the arms and legs raises coronary and cerebral perfusion pressure
• Retrograde enhancement of long-term memory and its link to post-traumatic stress disorder
• Resting levels under 10 nanograms per liter versus 10,000 to 100,000 during cardiac care
• Uses in anaphylaxis, cardiac arrest, severe asthma, croup, and open angle glaucoma
• Friedrich Stolz's 1904 synthesis and why American doctors still speak of adrenergic receptors

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The psychologist who proved that affection is a biological need said he never loved the monkeys he studied. Born Harry Israel in Fairfield, Iowa, in 1905, Harlow switched from English to psychology at Stanford and took the name Harlow on the advice of mentor Lewis Terman. Denied lab space at the University of Wisconsin, he and his students renovated a vacant building into a primate lab. At a time when behaviorists said infants bonded only for food and doctors warned against touching babies, his nursery raised monkeys clung desperately to cloth diapers.

His surrogate experiment offered infant rhesus macaques a wire mother with milk and a cloth mother with none. They spent up to 18 hours a day on the cloth mother, used her as a secure base, and he called the result contact comfort in his 1958 address The Nature of Love. After his wife Margaret died of cancer in 1971, Harlow sank into depression and turned to isolation chambers he called the pit of despair, keeping some infants alone for up to two years. The backlash fed the American animal liberation movement.

• Learning sets, his early finding that monkeys learn how to learn
• The drumming teddy bear fear test and the cloth mother as a secure base
• Chronic diarrhea in wire mother infants that drank as much milk
• Peer therapy that paired isolated monkeys with younger, gentler ones
• Student Stephen Suomi's nightmares and William Mason's account of Harlow's mindset

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In 1863 Charles Sherwood Stratton, two feet eleven inches tall, stood on a grand piano at New York's Metropolitan Hotel greeting about 10,000 wedding guests before visiting Abraham Lincoln at the White House. This episode follows Stratton, born in Bridgeport, Connecticut, in 1838, a healthy baby who stopped growing at six months, a condition now attributed to pituitary dwarfism. P.T. Barnum signed a contract with his parents, trained the four year old to sing, mime, and banter, and named him General Tom Thumb, dressing him as Napoleon.

A European tour beginning in 1844 brought performances for Queen Victoria, and by about age seven Stratton was starring in full length plays reviewed for his timing and diction. He moved to a share of box office receipts, bought a mansion, an island estate, and a steam yacht, and became a Freemason in 1862. When Barnum faced bankruptcy, Stratton lent him money and became his partner. He married Lavinia Warren, survived the 1883 Newhall House fire in Milwaukee, and died of a stroke six months later at 45.

• Why doctors in the 1840s had no way to explain his condition
• Starring roles in Hop o' My Thumb and The Seven League Boots
• A 1847 collection for Irish famine relief organized aboard ship
• Manager Sylvester Bleeker carrying the couple to safety from the hotel fire
• A funeral of more than 20,000 people and the life size statue Barnum placed on his grave

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Joseph Priestley first made nitrous oxide in 1772 and called it dephlogisticated nitrous air. In 1794 Thomas Beddoes and James Watt built a machine to produce it, and in 1800 Humphry Davy found it dulled the pain of an erupting wisdom tooth, suggested it for surgery, and named it laughing gas. Fashionable laughing gas parties followed, and more than 40 years passed before dentist Horace Wells used it for an extraction in 1844, only to be mocked when a patient cried out at Massachusetts General Hospital. Gardner Quincy Colton later used it on tens of thousands of patients without a fatality.

This episode explains how the gas acts on NMDA, GABA, and opioid pathways and why it leaves the body so quickly. Above about 300 degrees Celsius it becomes a powerful oxidizer, which powered the Luftwaffe's GM-1 system, drag racing, and SpaceShipOne. As food additive E942 it whips cream, and as a cheap party drug it causes hypoxia and B12 related nerve damage. It is also the third most important greenhouse gas, 273 times as potent as carbon dioxide, and a leading cause of ozone loss.

• Joseph Clover's 1876 inhaler that moved patients from nitrous oxide to ether
• Why racing nitrous is laced with sulfur dioxide
• Adiabatic heating and how a contaminated line can detonate a tank
• The 2024 galaxy gas trend and why canisters hold no oxygen
• How fertilized soil microbes drive the human share of emissions

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In 1824 Scottish merchant Robert Hunter saw what he took for a strange creature in a river in Siam and found two teenage boys joined at the chest. Chang and Eng, born in 1811 to a family of Chinese descent, were brought to the United States in 1829 by Hunter and sea captain Abel Coffin, under a contract the twins later said paid only $500. This episode follows their early tours in costume, invasive exams including phrenology, arrests after defending themselves in Massachusetts and fleeing a riot in Alabama, and the penny pinching management of Susan Coffin.

At 21 they broke away, dressed in tailored suits, ran their own shows, and grew wealthy. In 1839 they settled in North Carolina, became citizens despite a federal law limiting citizenship to free white persons, took the surname Bunker, married sisters Adelaide and Sarah Yates, and had 21 children. They also enslaved as many as 18 people. The Civil War wiped out their Confederate investments, Chang suffered a stroke in 1870, and in January 1874 Eng died about two hours after his brother.

• How the twins split time between two households every three days
• Their brief 1860 contract with P.T. Barnum, a business rival, not their creator
• Northern newspapers that turned their bodies into a fictional allegory about secession
• Dr. William Pancoast's finding that Eng died of fright and the competing blood loss theory
• A record lifespan of 62 years and more than 1,500 descendants