A Royal Malady
Charles C. Smith, Jr., M.D.
Presented in October, 1971
II George III and Porphyria
A. Historical Setting
B. Clinical Systems
F. Effect on handling of mental disease
III Porphyria Itself
For decades now the above title has suggested bleeding royalty, the adjective having a hematologic rather than a cockney connotation. Tonight I would like to bring together two favorite subjects of mine, both of which deserved more personal study.
As a third year medical student I worked at the General Hospital during a polio epidemic in which two patients were discovered more accurately to have acute intermittent porphyria with ascending paralysis. Later in the year, while on the surgical ward, a young negro male was admitted to the service with his third attack of abdominal pain and psychosis having had previously two negative laporotomies. Another third year student and myself collaborated to come forth with a positive porphobilinogen. As an intern on the VA service in Birmingham, a young pilot was transferred in with peripheral neuropathy whose urine, when left sitting in the sunlight turned dark brown in color. And finally, an elderly patient during residency days at LGH with proven AIP developed acute abdominal pain on the day of discharge. When we finally looked under the cover he had an incarcerated inguinal hernia!
The British Royalty have impinged themselves into our daily lives via the “tube” recently in several series, most notably “The Wives of Henry VIII” as well as several recent plays e.g.: “A Man for All Seasons”; “A Lion In Winter”; “Cromwell”; and “Elizabeth Regina”. To tie this all together, a small book appeared in 1970 entitled “The Pathology of Leadership” (1) which reviewed the effect of the health of world leaders on 20th century events from Sir Edward Grey, whose advancing blindness made it difficult to follow dispatches which may have contributed to the outbreak of World War I, to Ike, Jack and LBJ.
So becoming aware of a book entitled “George III and the Mad Business” (2) led to a review of the Revelation in 1966 in the B.M.J. that this king may have had Porphyria.
George III reigned from 1760 to 1820. These years saw the consolidation of the conquest of Canada, the discovery of Australia and New Zealand, the annexation of the West Indies, the final triumph in India or, from a few islands hardly visible on the globe, an extent of territory unequaled in the history of nations.
It also saw the loss of the American colonies and the threat of Napoleon. But in English rule a profound change occurred which saw the Parliamentary system rise to ascendancy over monarchy. So as Churchill states “The problems of his reign may in the longer run of events, have been fortunate for the ultimate liberty of England”. (3)
The tenor in the country was not dissimilar to that today in this country. During the war on the Colonies powerful English politicians denounced not only the military but the intervention at all. Rejoicing and gloating occurred over every setback and disaster to the British cause. Slogans “Seek out and Destroy” (search and destroy) “Concentrate your force” (Enclave theory) “Maintain your objective” (Bomb the north) sound suspiciously similar to today’s.
George III has even returned to haunt a contemporary Supreme Court justice who wrote an article in a magazine. (Show pictures from Evergreen) (4)
Now to the clinical side of my talk. “On June 11, 1788, the King was seized with bilious fever attended with violent spasm in the stomach and bowels”. (2) The next day in a note to William Pitt, the King writes “a pretty smart bilious attack prevents my coming this day to town. Sir George Baker approves of what I have done and trust his advice will remove the remains of this complaint.” Sir George Baker, President of the Royal College of Physicians of London, Fellow of the Royal Society, was renowned for his classical learning and address to the University of Cambridge in 1755, “on the affection of the mind and disorders that sprange from them” and had shown by elegant reasoning and experiment that contamination of cider by lead was the cause of endemic colic of Devonshire.
Subsequent to this the King continued over the next three months to have some symptoms but on October 17, 1788, Sir George was called to find the King sitting up in bed his body bent forward with acute pain in the stomach. The pulse was noted to be 60 but rose to 90. He was purged and Tr. Laudanum prescribed. Over the next 5 days the abdominal pains continued and delirium appeared laced with anger. Incessant loquaciousness continued and he could not keep the point in conversation.
Gout was diagnosed but the King doubted this since he could kick his feet together without pain.
On November 3, Dr. William Heberden, Sr. then 78 and retired, was called in. He left no notes. On the third day the king wrote his last letter to the Prime Minister for almost four months in which he reported difficulty in reading his dispatches.
Agitation and cramping pain increased and the pulse rose to 120, after bleeding it fell to 100 (Dr. Benjamin Rush later gave some advice regarding treatment.)
In the meantime, Dr. Richard Warren arrived, the most sought-after society doctor of his time. After his consultation he visited the Prince of Wales and this began the rumblings of the first regency crisis.
At this point we need background knowledge of 18th century medical practice. There was yet no science of physical signs. The concept of motor and sensory nerves was not known. There were no stethoscopes, percussion hammers, or clinical thermometers. Protocol was carried out and if the king did not speak he was not spoken to. As a result, whole visits were spent in fruitless silence.
With the continuation of symptoms in early December “persons who make this branch of medicine their particular study” as psychiatrists were delicately referred to in Parliament installed themselves in the palace and took charge of the sickroom. A Rev. Dr. Francis Willis, clergyman and keeper of a madhouse in London was sent for. On being introduced to the king, his majesty said “Sir, your dress and appearance bespeaks you of the church, do you belong to it?” Dr. Willis replied, “I did formerly, but lately I have attended chiefly to physick. “I am sorry for” replied the king, “ you have quitted a profession I have always loved and you have embraced one I most heartily detest.” Willis replied “Sir, our Savior himself went about healing the sick.” “Yes, yes” replied the king testily, “but he had not 70 Quid per year for it. “ (2)
Next began a battle for ascendancy between Willis, his son Dr. John, and his three physical assistants and the physicians. Willis’ method was to “break in” patients and the king was soon in a strait waistcoat and from that time recourse was frequently bad to it. For every non-compliance - refusing food, return of colic, resisting going to bed, throwing off bedclothes – he was clapped into the waistcoat.
It was Willis’ contention that the king suffered from Consequential Madness as opposed to “Original Madness” and that he would eventually recover. Dr. Warren, however, felt that the king was insane and incurable. As a result, debates raged in the House of Commons over immediate and absolute Regency for the Prince of Wales, versus a limited regency for the emergency. William Pitt, on the other hand, maintained that it belonged to the other branches of the legislature to provide according to their direction temporary exercise of the Royal authority.
Meanwhile, back at the palace, the physicians quarreled about the daily bulletins, wording, order of names appended to the bulletin.
However, by February 1789, as a regency bill had passed commons and was in progress through Lords, the king was recovering and resumed authority of March 10.
The physicians were remunerated as follows: Dr. John Willis, the son, 650 lbs. a year for life, the London physicians, ten guineas a visit, Sir George Baker, 1380 lbs., The Rev. Dr. Francis Willis, a 1000 lb. pension for 21 years. However, his fame having spread, he was soon called to the Queen of Portugal “who had a conviction she was doomed to everlasting perdition.” Although, not totally successful with this patient, he received 20,000 lbs.
A recurrence of the illness did not occur until February 1801, with recovery by mid-March. Another attack occurred in 1804, short-lived in duration, and finally in 1810, in October, the king began to show increasing agitation, incessant talking, and sleeplessness. Again, nausea, colic, and constipation returned and the pulse rose to 120. Symptoms continued and a regency was established in February 1811.
Long periods of “being silent and weak on his legs” followed by periods of contentment and tranquility playing the flute or harpsichord interrupted by the old painful paroxysms. The king expired in January 1820 at age 82.
So the king’s illness characterized by colic and constipation, pain and weakness in the extremities, tachycardia and sweating, and encephalopathy, make a good cause for acute intermittent porphyria. Not many observations were available on the urine since the day of the piss prophets (the first clinical pathologists) was over but we do have four references to discolored urine.
Now since AJP is a Mendelian dominant one would expect other members of the family to be affected so a search was made to diagnose porphyria in descendents of George III. By 1938, every ruling sovereign of Europe with the exception of the King of Albania traced descent from Elizabeth of Bohemia, daughter of James I and great-grandmother of George III. (Slide 1) Since a systematic investigation of this magnitude was impossible, living descendents were searched for who could be tested. A diagnosis was able to be made in four living family members. Examination suggested that the diagnosis was variegate porphyria. (5) Acute attacks similar to AJP occur but some light sensitivity also occurs. Increases in urinary porphobilinogen and delta aminolevilinic acid occurs during the acute phases and high faecal porphyrin even in remission. These people are especially sensitive to barbiturates. The defect is thought to be abnormal induction of aminolevilinic acid synthetase.
Now the question as to from whence it came. For this we look north of the border to Scotland. James VI of Scotland and of England (1566-1625) and of the House of Stuart was attended by a remarkable physician, Sir Theodore Turguet de Mayerne whom he had invited from France to become his physician and who first definitely established in England the clinical study of medicine. Dr. Mayerne describes in detail repeated attacks of abdominal colic, fast and irregular pulse, weakness, and spasm of James’ limbs which left him with a foot drop and fits of unconsciousness accompanied by bloody urine the color of port wine. Autopsy showed no stones.
Furthermore, James I told his physician that he had inherited his disorder from his mother.
Mary, Queen of Scots, is one of history’s great invalids. From her late teens she had attacks of excruciating pain and vomiting, painful lameness, fits, and mental disturbance.