The Madness of King George

King George the III presided over an important time in British history — 1760 to 1820. He kept the UK secure during the Napoleonic Wars. He lost the American colonies. And, on five occasions throughout his reign, he lost his mind.
Scholars have attributed the madness of King George to a hereditary disorder of heme synthesis, called porphyria. Heme is the important iron-carrying component of the hemoglobin protein, and its oxygenation gives blood its red color.
In fact, the complicated heme synthetic pathway can go wrong at a number of steps, and thus, there are at least seven kinds of porphyria. Each is a little different, but some of George’s family seems to be afflicted with variegate porphyria, due to a faulty protoporphyrin oxidase gene. During intermittent attacks, symptoms often included extreme skin sensitivity to sunlight, excessive hair growth, GI symptoms, seizures, and hallucinations.
(About twenty years ago, a fantastic notion was advanced: what if the vampires of European lore were porphyria victims? In addition to the sunlight-sensitivity thing, they had paleness, and a thirst for blood. This was taught to some of us in biochemistry class, but we weren’t given the straight dope.)
No one’s saying that George was a vampire (though the Colonials did ascribe to him some monstrous tendencies in the Declaration of Independence). But the severity and duration of his attacks seems excessive for porphyria.
Recently, researchers writing in the Lancet offered an explanation:

We report the analysis of hair obtained from George III. Although no genomic DNA could be obtained, metal analysis revealed high concentrations of arsenic. Since arsenic interferes with haem metabolism, it might have contributed to the King’s unusually severe and prolonged bouts of illness. We have identified sources of arsenic in the context of the medication George III received from physicians.

The sources of arsenic were described in the paper, and in the news:

…there is little information available to account for the unusual persistence, severity, and late onset of attacks. One possible explanation is exposure to heavy metals, including lead and mercury.
Martin Warren (University of Kent, UK) and colleagues … found that the principal compound administered to the King during his illness was emetic tartar. Emetic tartar contains a substance called antimony, which can be contaminated with arsenic.
The authors believe that the King’s medication was the source of the arsenic found in the hair sample.
Professor Warren states: “The presence of arsenic in a sample of the King’s hair provides a plausible explanation for the length and severity of his attacks of illness; and contamination of his antimonial medications is the probable source of the arsenic. We propose that exposure to arsenic would exacerbate attacks of porphyria in a genetically predisposed individual.”

So, the doctors’ therapy worsened the King’s condition. Of course, there are other instances of leaders brought down by health authorities in history.
In 1994, a movie about King George’s bouts with madness was released. In the UK, it was called “The Madness of George III”. There’s a persistent rumor that the US title was changed to “The Madness of King George”, in part because Americans might mistake the “III” as referring to a sequel or nonexistent trilogy.
We think that’s exactly the kind of hubris that led to the Revolution. Will the British ever stop underestimating us? It’s obvious that this movie occurs in the middle of a series, and the prequels haven’t been made yet.
That’s all for this week. Enjoy the weekend and see you Monday!