History of Porphyria
 King George III and Porphyria
Many of you have read that some historians
have speculated that King George III of England suffered from porphyria,
namely variegate prophyria. According to notes made by the physicians
attending him at that time, he suffered similar symptoms to those
seen in an acute attack of porphyria; abdominal pain, constipation,
rashes, confusion and severe weakness in his limbs. They also mentioned that
he had dark reddish urine during these sieges and that he was often "mad." The
royal physicians were not permitted to conduct extensive physical examinations,
so they had to greatly depend on what King George told them about his condition.
On one particular occasion when he was having one of the relapses
of the mental and physical symptoms, Parliament was debating his
ability to maintain his position as King. Interestingly, he spontaneously
recovered. Since George III ruled during the American Revolution,
he was thought to have had a significant impact on Britian's loss
to the revolutionaries. His mental and physical lapses were blamed
for much of the mishandling of the war. In 1811, George suffered
a severe relapse and subsequently was dethroned by the Prince of
Wales.
After researching the physician's reports, Drs. Ida Macalpine and
Richard Hunter proposed that King George might have had one of the
acute porphyries. They published their theory in the British Medical
Journal in 1966 and later wrote a book, George III and the Mad Business,
which presented more detailed accounts of King George's malady. It
is important to note that a number of porphyria specialists and other
physicians disagree with their theory. However, over the years it
has been widely publicized.
Porphyria in Turkey
In southeastern Turkey from 1956 to 1961, there were reports of
an epidemic of PCT. Apparently, in 1954 the Turkish government
distributed a supply of wheat seed that was treated with fungicides
containing 10% Hexachlorabenzine (HCB). It was originally intended
for planting, but the shipment arrived too late in the season
to plant. Because there was a limited food supply in the Turkish
provinces of Dijarbakir, Mardin, and Urfa, the seed was unintentionally
diverted for food production. It was difficult to quantify the
extent and duration of HCB exposure from existing surveys, because
the HCB-treated seed appeared no different from untreated supplies.
As many as 5000 individuals were reported to have been affected
by the HCB treated seeds. They exhibited PCT-like syndromes as early
as 1956. The government discontinued using the HCB-containing fungicide
in 1959, but it was not until around 1961 that the PCT outbreak waned.
Researchers from clinics near the areas began to trace the dietary
histories of the affected individuals and discovered that it appeared
as if the HCB had caused the acquired form of PCT.
Prior to this time, acquired porphyria associated with exposure
to environmental toxins was seen in experimental animal models but
only rarely in humans. Shortly after the reports from Turkey were
published, the association between the chronic administration of
HCB to induce excessive porphyrin accumulation was confirmed in animal
models as well
Although quantitative reports of HCB exposure from Turkey are incomplete,
some accounts estimate that the amount of HCB ingested by the individuals
who were affected ranged from 0.05 to 0.2 g/d over an unknown, but "relatively
long period," before changes in their skin became evident. Long-term
follow-up studies by Drs.Cripp and Peters and their colleagues at
the University of Wisconsin, indicated that the average lag time
between HCB ingestion and clinical manifestation of disease was about
6 months. Furthermore, their study indicated that the levels of excreted
porphyrins did not correlate with the individual's age at exposure,
sex, serum HCB levels, or severity of initial symptoms.
The circumstances may have occurred 40 years ago, but the lesson
is still very important today.
Rose Window
 Can you guess what this picture is? Most people say this photograph
looks like a Rose Window. These windows were characteristic features
of medieval architecture found in the cathedrals of that period.
Notre Dame Cathedral and the Cathedral of Reims contain especially
beautiful Rose Windows similar to the image above.
Although this photograph looks similar to a Rose Window, it is
not! Surprisingly, it is a photograph of the DNA in a single cell
taken under a x-ray crystallography. This particular photograph is
of the DNA double helix structure, which has been sliced through
the middle in cross section fashion, like the round slices of a cucumber.
If you would like to view other amazing photos taken with an electron
microscope, see the following site: http://micro.magnet.fsu.edu/dna/index.html
Long Ago and Far Away
Glasgow 1989
To mark a century of porphyria, a conference was held in April 1989
in the Western Infirmary, Glasgow. This syposium, dedicated to Professor
Sir Abraham Goldberg in the year of his retirement, reviewed the
porphyrias and all other aspects of tetrapyrrole chemistry and biology.
The meeting was hosted by The Tetrapyrrole Discussion Group and the
Porphyria Service, University Department of Medicine, Western Infirmary,
Glasgow, Scotland and coordinated by Dr. Michael Moore.
It was a great pleasure to welcome so many distinguished colleagues
in the field from all continents of the world. From its inception,
the welcoming ceilidh on Monday, March 3, 1989, in Dr. Michael Moore's
hometown of Kilsyth, to its close on Friday, July 4, 1989, the flow
of discussion and debate was continuous and stimulating.
As always on these occasions, old acquaintances were renewed and
new friendships made.
The photograph shows many of the delegates on The Lion & Unicorn
Staircase of the University of Glasgow, which dates back to its foundation
in 1451. In the center front are pioneers in porphyria metabolism,
Professor Charles Rimington and Professor Sir Abraham Goldberg.
First International Porphyria Patient Meeting
See what happened at the first
patient meeting of its kind.
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