King George III (1738-1820) held the throne of the British monarchy during the American Revolution and the defeat of Napoleon, and he was rather crazy.
His long reign was punctuated by severe bouts of mental derangement.
A new hair analysis suggests that the king's doctors may have exacerbated his illness by inadvertent arsenic poisoning.
In 1969, it was proposed that George III suffered from hereditary porphyria -- a genetic condition that affects the synthesis of heme, an important component in blood. This posthumous diagnosis was based on historical medical records and the presence of the disease in other members of the royal line.
An attack of porphyria can cause a variety of symptoms including abdominal pain, a racing pulse, constipation, and red or discolored urine, as well as mental disturbances such as hallucinations, depression and paranoia.
Although this genetic defect can explain the king's physical suffering and mental incapacity, the persistence, severity and late onset of his episodes are unusual.
It's possible that environmental factors contributed.
Scientists have previously studied a lock of the king's hair, which was collected at the time of his death and is now owned by a museum, but attempts to glean genetic information have failed.
Martin Warren of the University of Kent, UK, and his colleagues have now analyzed the heavy metal content of the hair and detected a high level of arsenic.
Arsenic interferes with the same heme-synthesis, so its presence could have induced and perhaps worsened the king's acute attacks of porphyria, the researchers say.
'Disturbing' clinical notes
The source of this arsenic may have been the king's own doctors. During his illness outbreaks, they prescribed him emetic tartar -- an antimony-based medicine used to induce vomiting.
"The Royal physicians' clinical notes make for disturbing reading, since the medication was clearly administered by force or deception," write the researchers in their July 23 article for Lancet.
Antimony is a metallic element, frequently found in nature with arsenic. For this reason, antimony-based compounds, which were popular with doctors for centuries, were often contaminated with arsenic.
If this were the case in the king's medications, he could have been receiving several milligrams of arsenic a day (a lethal dose, in comparison, is between 60 and 80 milligrams). The body can expel arsenic, but over time a chronic toxicity develops.
The concentration found in the king's hair was 17 times what is believed to be the threshold for arsenic poisoning.
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