In April 1782, a real, live giant appeared in London. Charles Byrne was said to be a majestic 8ft 4in (2.54 metres) in height and able to light his pipe on street lamps. Now, the macabre events that took place after his death have finally allowed modern genetics to deliver a new twist to the story of the Irish Giant – and could change the lives of patients today.
From double-headed cows to eight-legged pigs, the Georgians paid handsomely to gawp at all manner of wondrous creatures, and also people afflicted by rare conditions: bearded women, dwarves and giants. After death, many found their way to John Hunter , the anatomist and founder of modern surgery, who was an obsessive collector of anatomical curiosities. It is almost certain that he met Byrne – perhaps one of the tallest men ever to have lived – and decided that he had to have his skeleton.
But Byrne had other ideas. He not only refused Hunters requests for his body but asked to be buried at sea to make it an impossibility. Hunter was undeterred and, as Byrnes health deteriorated, had the young man followed. In 1783, aged just 22, Byrne died and, according to his wishes, his coffin was taken to the coast by friends. Hunters agents then sprung into action, getting the friends drunk before switching the body for stones. Hunter then boiled the corpse for 24 hours to procure the bones and hid the skeleton, not daring to show it for many years.
Today, we would recognise Byrnes gigantism as being caused by a tumour in the pituitary, the endocrine gland that secretes many essential hormones, including ones for growth. Depending on the patients age at the onset of the tumour, either gigantism or acromegaly (typically characterised by excessive growth of the jaw, hands and feet) develops but there are other problems, such as delayed puberty.
Márta Korbonits, a professor of endocrinology and metabolism at Barts and the London NHS Trust, has a special interest in an inherited form of pituitary tumour called familial isolated pituitary adenoma (Fipa), in particular a type caused by a variant in the AIP gene. She had already come across a family with several affected members in their recent history who hailed from County Tyrone, the same part of Ireland as Byrne. She began to wonder if they were linked – but to find out she needed some of his DNA.
In 2008, with the assistance of the Hunterian Museum at the Royal College of Surgeons in London, where Byrnes skeleton is displayed, she was able to send two of his teeth off to a German lab more used to extracting DNA from recovered sabre-toothed tigers. Korbonits wasnt initially very hopeful of an answer: The lab had never had a sample that had been cooked for 24 hours, she explains.
While she waited for the results, a man with a particular curiosity about Byrne, 58-year-old Irish businessman Brendan Holland, had got involved with TV documentary-maker Ronan McCloskey. Brendan, like other members of his family, had been affected by a pituitary tumour as a teenager. It was removed but left its mark. Holland is 2.06m (6ft 9in) tall, though still a foot shorter than Byrne, whose real height was 2.34m (7ft 8in). Both Holland and McCloskey came from Tyrone and were fascinated by the number of actual giants in the area, and by the way they figured in Irish folklore not as freaks, but as kings, seers and poets.
Holland was tested and found to have the AIP mutation. Then Korbonitss results came back – Byrne carried the same mutation. I always wondered, Why me? says Brendan. Ive wanted to know all my life. And the connection with Byrne was a bonus.
But was Byrne the first of his kind? Modelling work by Korbonitss team, just published in the New England Journal of Medicine, showed that both Byrne and todays patients inherited their genetic variant from the same common ancestor and that this mutation is some 1,500 years old. There really were giants in Ireland in far-off times.
The scientists calculations show that some 200 to 300 living people might be carrying this same mutation today, and their work makes it possible to trace carriers of this gene and treat patients before they grow to be a giant.
Holland feels nothing but sympathy for Byrne. He was a man born at the wrong time, he says. He knew he wasnt well and he was genuinely an object of fascination at a time when the average man was only 5ft 5in. Ive learned to live with it; Byrne never could. As for Hunter, in his haste to boil the body he never looked inside Byrnes skull, where the indentation of a pituitary tumour is plain to see. Had he done so, the cause of gigantism would have been another of his medical firsts.