Last year a remarkable exhibit came to light. Hidden in the vaults of a London museum was a scrap of paper containing a few strands of hair.
King George's wigs were laden with arsenic
The paper was crudely fashioned into an envelope but the words on it immediately caused a stir: "Hair of His Late Majesty, King George 3rd."
For Professor Martin Warren, it was the clue that would help him finally solve the mystery of King George's illness. His investigation is featured in a BBC documentary, Medical Mysteries.
"King George is largely remembered for those periods when he lost his mind. But it's been difficult to explain these attacks, so I was keen to analyse this hair sample," said Professor Warren.
When the hair was tested by the Harwell International Business Centre for Science & Technology in Didcot, Oxfordshire, the results were surprising.
The king's hair was laden with arsenic. It contained over 300 times the toxic level.
"This level is way above anything we were expecting - it's taken us completely by surprise."
More detective work
Far from being an answer, this remarkable finding was just the start of Warren's detective work.
In King George's time, his bizarre behaviour and wild outbursts were treated as insanity.
He was bound in a straitjacket and chained to a chair to control his ravings. King George was officially mad.
It wasn't until the 1970s that a new and controversial diagnosis was made.
Two psychiatrists - Ida MacAlpine and her son Richard Hunter - revisited the king's medical records and noticed a key symptom; dark red urine - a classic and unmistakable sign of a rare blood disorder called porphyria.
Porphyria can be a devastating disease. In the acute form, it can cause severe abdominal pain, cramps, and even seizure-like epileptic fits.
It is frequently misdiagnosed, and even in modern times, some sufferers have been thought to be mentally ill.
Pauline Bradshaw was 40 when she was finally diagnosed with acute porphyria.
"I was very confused and frightened, because I didn't know why I was feeling so bad," she said.
"Every day was this battle, you know, feeling sick and dizzy not knowing what was wrong or what was causing it."
For years her GP put her symptoms down to depression and prescribed anti-depressants, but when a relative wrote to say she had been diagnosed with acute porphyria, Pauline's symptoms fell into place.
Since then, with support from the British Porphyria Association, she has learnt how to live with this incurable condition.
One of the great mysteries of King George's porphyria was the severity of his attacks.
It is rare for men to suffer this acute form at all - normally males show no symptoms.
And - a final puzzle - King George didn't have any attacks before his 50s.
Arsenic to blame?
Professor Warren knew that porphyria attacks can be triggered by a wide range of substances - alcohol, common medication, even monthly hormones. Perhaps arsenic could also be a trigger.
Analysis produced surprising results
He contacted Professor Tim Cox, an expert on extreme cases of porphyria at Addenbrookes Hospital in Cambridge.
Professor Cox confirmed his guess - arsenic was listed as a trigger. And the massive levels found in King George's hair suggested that the arsenic had been liberally ingested over a long period of time.
The two professors began poring over the King's medical records preserved in the Royal archive at Windsor.
There was passing reference to arsenic used as a skin cream, and as wig powder, but nothing that could explain the staggering levels of arsenic showing up in the king's hair.
The most common medication he was given was James' powders, a routine medicine he was being given several times a day - made of a substance called antimony.
Tracking down James' powders at the Royal Pharmaceutical Society, Warren found the final piece of the puzzle in a 19th century almanac.
Antimony, even when purified, contains significant traces of arsenic.
The arsenic from the very medication he was being given to control his "madness" was triggering more attacks.
His porphyric attacks had been brought on after a lifetime's arsenic accumulated in his body, and then were made much more prolonged and more severe by the medicine to treat him.
For professor it is the end of a long trail.
"It is a very convincing explanation of the king's attacks, and could account for why he had them at such a late stage in life and why they were so severe.
"So in that sense, yes, it's very satisfying."
For more details about porphyria contact the British Porphyria Association on 01474 369 231. Email: firstname.lastname@example.org
Medical Mysteries: George III - Mad or Misunderstood? is broadcast on BBC One on Wednesday 14 July at 2235 BST.