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Tutankhamen 'killed by sickle-cell disease'

King Tutankhamen, Egypt's boy king, was killed by the inherited blood disorder sickle-cell disease – not malaria. So says a German team in what appears to be the best shot yet at solving the mystery of the pharaoh's early demise.
From falling off a chariot to murder by poison, the cause of Tutankhamen's death has been a source of avid speculation since his mummified youthful remains were discovered in 1922. He was 19 when he died around 1324 BC after ruling for just nine years.
The first extensive scientific investigation of the mummy was reported by Egypt's chief archaeologist Zahi Hawass and colleagues earlier this year (JAMA, vol 303, p 638). After running a battery of tests, including X-rays and genetic analysis, they concluded that an inherited bone disorder weakened the king, before an attack of malaria finished him off.
Key pieces of evidence were severe necrosis in the bones of Tutankhamen's left foot, and the detection of genes from Plasmodium falciparum, the parasite that causes malaria.

But in a letter to JAMA this week, Christian Timmann and Christian Meyer of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, suggest that Hawass's observations can be explained much more elegantly by a diagnosis of sickle cell disease (SCD).

Early death

People with SCD carry a mutation in the gene for haemoglobin which causes their red blood cells to become rigid and sickle-shaped. A single copy of the sickle-cell gene confers increased immunity to malaria, so it tends to be common in areas where the infection is endemic – such as ancient Egypt. People with two copies of the gene suffer severe anaemia and often die young.
Timmann and Meyer point out that SCD is the most common cause of bone damage like Tutankhamen's. The deformed blood cells block capillaries, preventing oxygen from reaching bone tissue. Tutankhamen's parents are thought to be related, boosting the chance that they both carried the sickle-cell gene.
People with SCD can still carry the malaria parasite in their blood, despite their increased immunity. In King Tut's case, such an infection could have triggered a fatal "sickle cell crisis" in which his essential organs were starved of oxygen, Timmann says.
Members of Hawass's team describe the suggestion as "interesting and plausible" and say that they are "currently investigating". That would presumably require testing Tutankhamen's mummy for the presence of the sickle-cell gene.
Timmann's lab has developed a test: given access to the DNA, "we could do it in an hour", he says. But if that is the line the Egyptians are taking, they are going it alone. Timmann says he contacted them, offering to collaborate, but has received no reply.
Other researchers would also like to receive information from the Egyptian team. In a second letter in JAMA this week, a pair of US researchers suggests that King Tut and his relatives might have had a hormonal disorder which causes, among other things, deformed skulls and small male genitals. They need detailed photographs of the skull of Tut's father to confirm their theory, but the Egyptian team has exclusive access to the mummies and has not yet released the relevant pictures.

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