King George III.

What illness did King George III have?

King George III has been portrayed as the ailing yet dashing monarch on Netflix’s Bridgerton spinoff “Queen Charlotte,” a comic fop in the Broadway hit “Hamilton” and dramatized in Alan Bennett’s 1991 play and 1995 film “The Madness of King George.” Though he had a long reign of almost 60 years, he is remembered now for being the monarch who lost America, and for suffering periodic bouts of serious illness and erratic behavior, leaving him unable to rule for his last decade.

Some modern diagnosticians retrospectively concluded that George III had a physical, genetic, liver-based disease. But that well-publicized theory has also been cast into doubt.

The notion that the king had acute porphyria, which interferes with the body’s ability to make hemoglobin, was put forth most famously in the mid-1960s by Drs. Ida Macalpine and Richard Hunter, a mother-and-son team of psychiatrists. They made this claim after studying more than 100 volumes of George III’s medical records — which are based on very different concepts of illness and disease than our present day. They later wrote several papers in prominent medical journals and a book, “George III and the Mad-Business,” advancing their work.

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Anxiety, hallucinations, severe pain, nausea and vomiting, palpitations, high blood pressure, numbness, muscle weakness, red or brown urine and blindness count among the many symptoms of acute porphyria.

To name just a few of his ailments, King George suffered from abdominal pain and sometimes had seizures, during which his attendants would need to restrain him by sitting on him. His urine was blue (though not brown or red), which was likely caused by a medication he took called gentian violet. In his last decade, he became blind from cataracts and possibly deaf.

Soon after Macalpine and Hunter published their work, several other experts in biochemistry and metabolic disorders heartily disagreed with this diagnosis. Nonetheless, the “fact” that the king suffered from porphyria caught on like a wildfire in the medical and historical literature and, later, the popular vernacular. In 1982, while taking genetics as a first-year medical student in Ann Arbor, I well recall my professor supporting this diagnosis.

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Much more recently, a team of researchers at St George’s, University of London, countered that George III’s madness was not caused by porphyria but was simply a version of severe mental illness.

Queen Charlotte.

King George III is portrayed as the ailing yet dashing monarch on Netflix’s Bridgerton spinoff “Queen Charlotte.” Portrait of the queen via Sepia Times/ Universal Images Group via Getty Images)

Researchers Peter Garrard and Vassiliki Rentoumi went to the archives to review the king’s handwritten letters and focused on his use of language. What is intriguing about this retrospective study is that George’s sentences were much longer during his episodes of illness than when he was well. For example, when stricken with symptoms, he composed creative, if not outlandish, 400-word long sentences.

Psychiatrists see this same form of nonstop speech and writing during the manic phase of bipolar disorder. Once the euphoria and hyperactivity of the illness resolves, the person often falls into an abyss of depression.

The idea that George may have gone through manic periods also matches late 18th century descriptions of his illness by actual witnesses. He could talk incessantly – even, as one court observer wrote, until “he was exhausted, and, the moment he could recover his breath, [begin] again, while the foam ran out of his mouth.”

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Meanwhile, a 2005 hair analysis found high amounts of arsenic, which can lead to poor mental health and neurologic problems. This toxin was a common medicine at the time and he might have actually been prescribed it for his attacks – though arguably it would have made them worse.

When British porphyria expert Dr. Timothy Peters reviewed Macalpine and Hunter’s archival work, he found that they were quite selective in their reporting and interpretation of George’s signs. His conclusion was that the diagnosis of the acute porphyria could no longer be supported and needed to be revised. Perhaps, Peters claimed, diagnosing a king with metabolic rather than a mental health condition was easier to swallow, especially in an era when mental health was not widely discussed in public.

Kew Palace, Richmond upon Thames, London.

George III would spend his days recuperating at Kew Palace. The Print Collector/ Getty Images

George’s recurring illness caused him to withdraw from daily business to recuperate out of the public eye at the secluded Kew Palace. But each time he retreated from London, a constitutional crisis arose. Who would make the decisions ruling England? After a national debate over whether to make his son, the Prince of Wales, defacto leader in 1788, the king’s failing health led Parliament in 1811 to name George IV officially as Prince Regent.

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It should be noted that George III was considered a fair and decent monarch during his healthy periods. He had a great appetite for knowledge and books, and was the first king to study science, even if popular opinion and fictional accounts have made him out to be a debilitated fop.

So what caused the erratic behavior of mad King George III? I honestly cannot say. But the porphyria-bipolar arguments demonstrate one of the greatest problems when diagnosing those who died 200 years ago and without the physical evidence to back up such claims.

A poor diagnosis is especially difficult to disprove, especially when it becomes part of popular “historical” accounts. With respect for my colleagues on both sides of the George III madness versus porphyria debate, even a plausible retrospective diagnosis on a patient the doctor has never seen let alone examined can be difficult, for many, to accept, let alone prove with any certainty.