King James medical mystery unraveled

— -- England's King James I gave us Jamestown and the King James Bible. But historians have long suspected he also gave his descendant King George III an inherited case of madness.

Best known from the 1994 movie, The Madness of King George, the bouts of insanity afflicting George III, the bad guy in the American Revolution, have long been blamed on his predecessor, James. James was a bit odd, and porphyria, an inherited affliction of the nervous system and skin linked to unusual behavior in some cases, has long been suspected as the culprit.

But historians and porphyria experts who have looked through the medical letters surrounding King James have run the monarch's symptoms through diagnostic software and suggest another syndrome better explains the oddness of King James I.

"He certainly was an unusual chap," says archaeologist-physician Timothy Peters of the United Kingdom's University of Birmingham. He's the lead author on the History of Psychiatry journal report that takes a closer look at the "recurrent disputes" surrounding the afflictions, possibly inherited, of an "interesting but enigmatic king."

James I ascended the Scottish throne in 1567 and the English one in 1603, the age of Shakespeare, Galileo and Sir Walter Raleigh. Interesting times, and King James survived the execution of his mother, Mary, Queen of Scots, the murder or execution of at least three of the aristocrats appointed to raise him as a child, and a thwarted plot to blow him up along with Parliament, still celebrated with fireworks in England. He inveighed against tobacco (" this vile custom"), wrote poetry and in 1606 chartered England's first permanent North American colony, Jamestown.

What finally ended his reign was a stroke in 1625. "It is generally agreed that the last five years of his life were accompanied by intellectual deterioration," says the History of Psychiatry study. Born prematurely, James rarely impressed his contemporaries as a physical specimen, who saw him as feeble, "clumsy in riding and hunting," according to one historian, suffering from itchy skin, gout and abdominal pain. English psychiatrist Ida Macalpine, concluded in 1968 that all those symptoms added up to a mild case of porphyria — a rare family of inherited afflictions that affects about 200,000 people in the U.S. today caused by a buildup of compounds called "porphyrins" in the bloodstream.

Macalpine's diagnosis of James I, and a similar one she made for Mary, Queen of Scots, along with her determination of a severe case affecting King George III, inspired the 1994 movie. She also swayed popular thinking about "Porphyria — A Royal Malady," as she titled one of her books.

The only problem is that royal diagnosis seems a bit odd itself. "To our surprise, the more we look the less we see any signs of porphyria," says Peters, who regularly treated porphyria patients in his career as a physician. Looking at James I, the "very outstanding medical notes" of the royal physician written in 1623 detail a series of kidney problems, and his autopsy ("they suspected he was poisoned," Peters says) reports kidney stones in his shriveled left kidney, the site of recurrent abdominal pain that had been key to the porphyria diagnosis.