The fossil of Sue, the famous Tyrannosaurus rex, shows signs of gout, the same disease once called the disease of kings. This episode explains the mechanism: uric acid builds up in the blood and, in cooler joints like the big toe at night, precipitates into needle shaped monosodium urate crystals. When crystals escape their protein coating, immune cells trigger the NLRP3 inflammasome, caspase-1, and interleukin-1 beta, producing the swelling and pain. Most mammals break uric acid down with the enzyme uricase, but a mutation millions of years ago disabled that gene in the ancestors of humans and great apes.

Gout appears in Egyptian papyri from around 1550 BC. Hippocrates noted eunuchs and premenopausal women were spared, Celsus linked it to alcohol around 30 AD, and Antonie van Leeuwenhoek saw the crystals under a microscope in 1679. Global rates roughly doubled between 1990 and 2010, yet diet explains only about 12 percent of variation in uric acid levels. In about 90 percent of cases the kidneys underexcrete uric acid, shaped largely by genes such as SLC2A9 and SLC22A12.

• About half of cases strike the joint at the base of the big toe, a form called podagra
• Beer delivers both alcohol and a purine load from yeast, while fructose speeds uric acid production
• Studies from the early 2000s found purine rich vegetables like spinach and lentils do not trigger gout
• Under polarized light the crystals show negative birefringence, shifting between yellow and blue
• Pegloticase is an engineered form of the uricase enzyme humans lost