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Study Unveils New Insight To The Madness Of King George III

Researchers from Dana-Farber Cancer Institute had discovered a new molecular explanation for the episodic attacks of irrational and demented behavior in the disease called porphyria, the disease that was probably behind the // madness of king George III.

The Dana-Farber scientists say in a report featured on the cover of the August 26 issue of the journal Cell that the nutritional component of porphyria involves a key master metabolic molecule, PGC-1 alpha, in cells of the liver. The gene that makes PGC-1 alpha was isolated some time back.

King George III suffered from five prolonged, severe episodes of madness during his rule from 1760 to 1820. The symptoms recorded at the time sound to modern diagnosticians as typical of porphyria, though the King’s attacks were unusual in their severity and that they didn’t appear until he was 50.

Earlier this year, The Lancet had published a report saying that a test of strands of George III’s hair contained arsenic, which can provoke porphyria attacks.

PGC-1 alpha is a “transcriptional co activator” that acts as an on-off switch for a number of genes involved in manufacture of glucose in the liver and in the “heating system” of brown fat cells that help prevent damage from cold in certain animals.

The researchers had found that PGC-1 alpha is an important factor controlling the expression of ALAS-1 in the fasted and fed liver. Moreover, they had showed that hepatic PCG-1 alpha is a major determinant of the severity of acute porphyric attacks in mouse models of chemical porphyria.

The findings suggest that patients with porphyria should avoid any drugs or foods that turn on PGC-1 alpha activity in the liver, the researchers say. There could be implications for treatment as well: high-carbohydrate diets aren’t a satisfactory therapy for affected patients as it make them gain, and fasting in order to lose the weight risks provoking attacks. Hopefully, the research
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