The Pathography of King George III

In 1788 King George III, in the middle of a sixty year reign, was suddenly acting crazy. The ‘mad doctors’ were called in and parliament considered the need for his son to assume power as ‘regent’. Then he got better. Eventually his power was transferred to his son, but not until 1811. Until then, the King’s episodic ill health, mental and physical, continued to distress and perplex the court and his doctors. What was wrong with the King? Can pathography solve the puzzle?

Selected reading...

Crazy Behavior

By ‘acting crazy’ we mean that in October of 1788 the King couldn’t sleep, spoke incessantly and was shaking hands with a tree (he thought it was the King of Prussia). By the April following he was back to normal. Services were held for prayers of thanksgiving and all was well—for a while. Major relapses occurred on three occasions: 1801, 1804 and 1810.

There was a reluctance to declare the King insane. Dr. Willis testified to parliament on the differences between delirium and insanity, favoring the former. While there was no formal science of neurology, this was a scientifically curious era and Dr. William Battie had, fifty years previoiusly, distinguished in his Treatise on Madness between Original and Consequential Madness, or in today’s parlance, primary functional psychosis and secondary acquired organic disease.

George III. (r. 1760-1820)

George III. (r. 1760-1820)

Crazy Idea?

Pathography is “The study of the life of an individual or the history of a community with regard to the influence of a particular disease…” The pathography of King George was for 150 years essentially the story of a King with relapsing mental illness and what that meant politically.

The most famous of doctors at the time hedged their bets on a diagnosis, the presentation being peculiar—now crazy, now not, no febrile dementia. Amidst the professional discourse, sometimes aligned by political bent—Whig or Tory—there was much less discussion of the physical signs and symptoms, such as chronic abdominal pain and discolored urine. These clues today are not missed by house officers on popular TV medical dramas.

Notions of a biological basis for the King’s behavior lay largely dormant for 150 years, until 1966 when a now famous paper was published in the British Medical Journal by a mother-son collaboration of two psychiatrists, Macalpine and Hunter. They promulgated a specific organic cause, and their thesis caught fire—with doctors, historians and filmmakers (The Madness of King George). And it became the foil for contrary theories, such as manic-depression and arsenic poisoning.

The Evidence

The authors cite four sources of primary material that they scoured for clues that the King suffered from acute intermittent porphyria (AIP): the 47 volume Willis Manuscripts, 10 boxes of Queen’s Council Papers, Sir Henry Halford’s daily record of the illness in 1811, and Sir George Baker’s diary. They identity a nine episodes of major and minor “attacks”, from 1765 to 1810.

The evidence for AIP is best presented in their own words:

“The commonest misdiagnoses today were also considered in the king's case: biliary colic for abdominal pain; rheumatism for neuropathy; psychosis for encephalopathy.

…the physicians' daily record makes the diagnosis of manic-depressive psychosis untenable … his excitement lacked the cardinal feature of exaltation … and his physical sufferings were an integral part of the illness.

“Lead poisoning, which also causes colic, palsy, and encephalopathy, can be excluded by … distinct attacks over many years without other members of the household being affected. [Lead poisoning was a known entity at the time].

Their conclusion:

“the triad alone of abdominal symptoms, polyneuritis, and mental disturbance the condition is at once recognizable as acute intermittent porphyria … the symptomatology and course of the royal malady reads like the description of a text-bookcase: colic and constipation; painful paresis of arm and legs; vocal paresis, visual disturbances and other signs of bulbar involvement; radicular pain; autonomic disturbances with marked tachycardia and sweating attacks; and encephalopathy ranging from insomnia to excitement, raging delirium, stupor, and fits.

In keeping with acute intermittent porphyria are also: age of onset; attacks precipitated by mild infections; rapid fluctuations; protracted convalescence; … patients appear demanding, irascible, and difficult to manage.

Purple urine in Porphyria (right)

Purple urine in Porphyria (right)

Color Me Convinced

Porphyria is a disease of inborn metabolism, first elucidated by Hoppe-Seyler in 1871. There are many variants, all having to do with a build up of porphyrin molecules that are intended to be part of hemoglobin. In the ‘acute’ type, the porphyrin build up is toxic to the nervous system. Byproducts spill over into the urine, causing a blue or purple discoloration during attacks. Porphyra is Greek for ‘purple’.

Malcalpine and Hunter scoured their primary sources for reports of urine anomalies by the King’s physicians. They found four: “bilious”, “pale blue”, “bluish” and “bloody”. Furthermore “All these observations were made during paroxysms when the excretion of porphyrins … is known to be greatest.”

Acute intermittent porphyria (AIP) is an inherited disease. The authors mention the case of King George’s sister, Caroline Matilida, Queen of Denmark and Norway. She died at age 24 with neurologic signs that could possibly be due to AIP.

Au Contraire?

There have been detractors. Among them is Timothy Peters, an archeologist. His screed is worth a look, but I find his alarmist, and largely unsupported, counter-arguments unpersuasive, despite an appeal to Bayesian analysis.

There have been alternative theories of organic etiology as well, specifically arsenic poisoning. A paper in The Lancet in 2005 reported on posthumous analysis of the King’s hair. Their sample contained high levels, which could have caused his symptoms of aggravated those from porphyria.

While arsenic may have played a role, or the role, in the case of King George III, any evidence of hereditary porphyria would argue for that as the principle diagnosis. This brings us to Macalpine and Hunter’s exhaustive, and exhausting, follow-up paper: Porphyria in the Royal Houses of Stuart, Hanover and Prussia.

Pathography deals with nebulous and often inaccessible information—but who can resist the temptation to indulge?

Selected reading...

A Royal Experiment: Love and Duty, Madness and Betrayal―the Private Lives of King George III and Queen Charlotte. Janice Hadlow.

The stunning debut of an important new history writer

In this magnificent biography of a marriage-between Great Britain's King George III and Queen Charlotte...

The Madness of George III. Alan Bennett.

Alan Bennett's play explores the court of a mad king, and the fearful treatments he was forced to undergo. It is about the nature of kingship itself...

The Madness of King George. Nigel Hawthorne, Helen Mirren.

The movie version. Look for a used copy or rent on Amazon Prime. 4/5 stars.