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Deep in the center of your brain sits a rice-sized, pine cone shaped organ that once looked up at the prehistoric sky. This episode follows the pineal gland from ancient medicine to modern chronobiology. Herophilus imagined it as a valve controlling the flow of vital spirits, or pneuma, through the brain's ventricles. Galen, who called it konarion, argued it could not move and so was just a support for blood vessels. In the 17th century René Descartes noticed it was the brain's only unpaired structure and named it the principal seat of the soul, and later Madame Blavatsky linked it to the third eye. Biology turned out stranger than mysticism. The pineal gland began as a light-sensing organ, and in some frogs, lizards and the tuatara of New Zealand it still forms a parietal eye with a cornea, lens and retina. In 1958 Yale dermatologist Aaron B. Lerner, chasing a skin disease cure, isolated melatonin. The episode traces the looping nerve route that tells the gland when it is dark, and why this barely protected organ slowly calcifies. H.P. Lovecraft's story From Beyond imagined a machine that stimulates the pineal gland to reveal other dimensions Fossil Devonian fishes show two holes in the skull, evidence of paired eyes that fused into one structure A 1917 finding that cow pineal extract lightened frog skin set Lerner on the path to melatonin The signal runs from the retina to the suprachiasmatic nucleus, down through the spinal cord and superior cervical ganglia, and back up Brain sand, or corpora arenacea, shows on skull X-rays and is estimated in about 40 percent of Americans by age 17

The human genome has roughly 20,000 to 25,000 genes, but the gut microbiome carries about 100 times more, making you genetically about 1 percent human. This episode tours the 10 to 100 trillion microbes inside you, which make up as much as 55 percent of the dry mass of stool. The stomach is nearly sterile acid, though Helicobacter pylori survives by wrapping itself in ammonia. The colon holds the densest microbial community ever studied, with 300 to 1,000 species, yet about 99 percent of gut bacteria come from 30 or 40 species, almost all strict anaerobes that die in oxygen. These microbes ferment fibers we cannot digest into short chain fatty acids. Butyric acid supplies about 70 percent of the energy for cells lining the colon, and the gut flora also makes B vitamins and vitamin K. Acting like an endocrine organ, it influences how calories are stored. The episode covers dysbiosis in inflammatory bowel disease, the gut-brain axis along the vagus nerve, gut yeasts, how a microbiome forms by about age two, and how industrial diets and antibiotics are thinning its diversity. Germ-free rodents needed 30 percent more calories to keep the same body weight as normal rodents In inflamed guts, oxygen seeps in, beneficial anaerobes die and Proteobacteria multiply Over 90 percent of the body's serotonin is produced in the gut Gut bacteria in Malawian and Amerindian communities carry different enzyme toolkits than those of people in the United States A 2018 proposal for a global biobank to preserve stool samples from non-industrialized populations

Around 1800, French orphan Martin Fugate settled along Troublesome Creek near Hazard, Kentucky, and married Elizabeth Smith. Both unknowingly carried a rare recessive gene for methemoglobinemia, and four of their seven children were born with vivid blue skin. In a valley cut off from roads and railroads, descendants married into the local Combs, Ritchie and Smith families, and the trait resurfaced for generations. Yet many of the blue Fugates farmed, raised families and lived into their 80s and 90s, because their partial enzyme deficiency kept the condition at a steady, low level. The episode explains the chemistry: iron in hemoglobin oxidizes from the ferrous to the ferric state, cannot carry oxygen, and makes the rest of the molecule cling to its oxygen, so blood turns chocolate brown and skin looks blue. The acquired form is more common, triggered by some antibiotics, local anesthetics like benzocaine, and nitrate-laced well water given to infants. It travels to Lurgan in Northern Ireland, where two blue brothers were treated in 1942, and ends with the counterintuitive modern antidote. Above 70 percent methemoglobin the condition is almost universally fatal, while 10 to 20 percent brings blue skin and mild symptoms The EPA limits nitrate nitrogen in public drinking water to 10 parts per million to protect infants from blue baby syndrome Standard pulse oximeters can read around 85 percent even as patients are starved of oxygen, so doctors turn to CO-oximetry Dr. James Deeny cleared the Lurgan brothers' blue color with vitamin C and sodium bicarbonate, one in 12 days, the other in about a month Intravenous methylene blue rapidly restores the iron, but can cause serotonin toxicity alongside SSRIs

Chemist John Dalton believed blue fluid in his eyes filtered out red and green, and asked that his eyes be preserved after his death. In 1995, scientists analyzed DNA from the eye, kept since 1844, and found a genetic variation instead. This episode explains color vision deficiency, which affects about 8 percent of men and 0.5 percent of women with red-green types. True grayscale vision, monochromacy, is very rare. Most cases involve the L, M and S cones, either with one missing, called dichromacy, or with one shifted so its signal overlaps another, called anomalous trichromacy, the most common form. The red and green opsin genes sit on the X chromosome, which explains why men are far more affected, while the rare blue-yellow type comes from chromosome 7. Cataracts, sildenafil and industrial solvents can change color vision too. The episode covers daily friction from ripe bananas to traffic lights, then flips the story: people with deuteranomaly can tell apart shades of khaki others cannot, and reports say colorblind spotters were sought in World War II to see through camouflage. It ends with railway bans, glasses and a cyborg antenna. The upside-down Tipperary Hill traffic light in Syracuse, New York, with green above red Why a grayscale check is not enough for accessible design, and why shapes, icons and labels work Deuteranomalous subjects picked out 15 shades of khaki that looked identical to typical viewers After the 1875 Lagerlunda train crash in Sweden, Frithiof Holmgren's wool matching test led to bans on colorblind rail workers Artist Neil Harbisson's Eyeborg antenna turns color, including infrared and ultraviolet, into sound

In February 2015 Cecilia Bleasdale photographed a lace dress at the Cheshire Oaks Designer Outlet in England and sent it to her daughter Grace, who was getting married on the Scottish island of Colonsay. Grace saw white and gold. Cecilia, who had just seen the dress in person, saw blue and black, which it was. After the wedding, singer Caitlin McNeill posted the photo on Tumblr, a BuzzFeed poll took off, and the page hit 14,000 views a second and a record 673,000 concurrent visitors, with 4.4 million tweets in a day and Taylor Swift admitting she felt confused and scared. The science centers on color constancy. The brain must separate an object's color from the color of its light, and the cropped, overexposed photo gave it no clues. Bevil Conway tied the split to daylight shifting from warm to blue, and Pascal Wallisch found that early risers, with more lifetime exposure to natural daylight, leaned toward white and gold while night owls saw blue and black. Brain scans and philosopher Barry C. Smith's comparison with the rabbit-duck drawing explain why almost no one could switch. A Current Biology study of 1,400 people found 57 percent saw blue and black, 30 percent white and gold, and 11 percent blue and brown Women and older people disproportionately saw white and gold White and gold viewers showed more frontal and parietal activity, a sign of top-down processing Roman Originals sold out in 30 minutes, and Ellen DeGeneres gave the family a honeymoon trip and $10,000 The Salvation Army in South Africa used the image for a domestic violence campaign asking why it is so hard to see black and blue