Did Tutankhamum have sickle cell disease?

In 2010 two doctors, Professor Meyer and Dr Christian Timmann, at the Bernard Knocht Institute for Tropical Medicine, in Hamburg, made the novel suggestion that the Pharaoh Tutankhamum had sickle cell disease, and that he had died from complications of this, perhaps provoked by an attack of malaria. Their suggestion was made in response to a detailed paper in the Journal of the American Medical Association, earlier that same year, which described the work of Dr Zahi Hawass, head of The Supreme Council of Antiquities in Cairo, and his colleagues, who had undertaken extensive investigations of Tutankhamum’s mummy together with others preserved from the same period.


Dr Hawass and his colleagues spent several years examining the mummies of Tutankhamum and 11 of his relatives using modern CT scanning and DNA analysis techniques.

Many people have speculated about the cause of the young Pharaoh’s death. What is the evidence for and against sickle cell disease and why does this matter?

Tutankhamum became Pharaoh of Egypt in 1332 BC, over 3000 years ago. He was only 9 years old at the time and was to reign for a brief 10 years, dying aged 19. He married his sister Ankhesenamum, and they had two daughters, neither of whom survived childhood; his older, full brother, Smenkhkare also died young, aged 25 years. With the death of Tutankhamum the Thutmoside dynasty, which had seen one of the most glorious periods in the history of ancient Egypt, came to an abrupt end. The short reign of the boy-Pharaoh is, in itself, an insignificant blip in the 3,000 year history of ancient Egypt; there were no wars, famous battles or great events whilst he was Pharaoh, however, his reign was important politically in one respect. His father Akhenaten, whose wife was the famous Nefertiti, had revolutionised the religion of ancient Egypt, doing away with the old Gods and replacing them with the worship of the Sun God, Aten, a far from popular change. Tutankhamum’s name was originally Tutankhaten (“the living image of the Aten”) to reflect the new God, but it was changed when he became Pharaoh, in honour of Amum, one of the old Gods. During his reign the religious reforms of his father were swept away and Egypt returned to the old ways of worship. But that would only have been of interest to scholars of ancient Egypt, and the reign of Tutankhamum would have disappeared into obscurity, where it not for an event on the 26th November 1922, when Howard Carter, an archaeologist, and three companions, broke into Tutankhamum’s  tomb in the Valley of the Kings, a tomb which had remained virtually untouched since the boy’s death. The treasures they discovered there that day would make Tutankhamum the most famous Pharaoh of all time.

Howard Carter, English archaeologist and Egyptologist (1874-1939)

Howard Carter, English archaeologist and Egyptologist (1874-1939)

About that famous moment, Carter later wrote: “With trembling hands, I made a tiny breach in the upper left hand corner. Widening the hole a little, I inserted the candle and peered in. At first I could see nothing, the hot air escaping from the chamber causing the candle to flicker. Presently, details of the room emerged slowly from the mist, strange animals, statues, and gold – everywhere the glint of gold.”

The first room of the tomb as seen by Howard Carter.

The first room of the tomb photographed at the time of the discovery.

The four chambers of the tomb were packed with treasures of unimaginable opulence, together with the intact royal coffin and mummy, in the inner shrine.

The opening to the inner shrine with guardian ?

The opening to the inner shrine flanked by the guardians – “two strange, ebony-black effigies of a King, gold sandalled, bearing staff and mace”.

The coffin was eventually opened 3 years later to reveal the magnificent, solid gold death mask which, more than anything else, has come to symbolise the young King.

The solid gold death mask of Tutankhamum

The gold death mask of Tutankhamum

It was the Curse of the Pharaohs, which added further spice to the story of the tomb’s discovery. By some accounts, Carter found an engraved plaque at the entrance to the tomb spelling out the warning “Death will come on swift wings to him who disturbs the sleep of the King”. He wisely hid the plaque to avoid alarming his workmen! Lord Carnarvon, who sponsored the dig and was present at the opening of the tomb, died six weeks later from blood poisoning, probably due to a mosquito bite on his cheek. It was Sir Arthur Conan Doyle, the author of the Sherlock Holmes stories, who first suggested that Carnarvon’s death may have been related to “elementals” placed in the tomb by Egyptian priests to guard the King’s body. Other deaths followed, Lord Carnarvon’s two half brothers, Aubrey Herbert MP and Mervyn Herbert, died in 1923 and 1929, of blood poisoning and malaria respectively and Captain Richard Bethell, Howard Carter’s personal secretary, was found, smothered in his bed, in an exclusive Mayfair club, in 1929. Bethell’s father later committed suicide. All this added fuel to the flames of the Pharaoh’s Curse and served to add to the glamour and mystery of the tomb’s excavation. Howard Carter himself had no time for such nonsense, he died many years afterwards in 1939, aged 65 years of natural causes, and a subsequent analysis of over 58 deaths, in people connected with the opening of the tomb, found no statistical evidence of premature mortality. So much for the Pharaoh’s Curse, what of the boy-Pharaoh himself?

Tutankhamum is thought to have been a weak and sickly boy; tall at 5 feet 11 inches (1.80 meters) but only slightly built. He appears to have had a left club foot (talipes equinovarus), an abnormality he would have been born with and, as a consequence, must have had a limp during life. He is often depicted in tomb paintings walking with a cane for support or sitting on ceremonial occasions when, conventionally, he would be expected to be standing.

Tutankhamum, supported by a cane, and his wife ?

Tutankhamum, supported by a cane, with his wife and sister Ankhesenamum. Over 130 walking sticks and canes were found in the tomb, for the use of Tutankhamum in the afterlife. Many of them showed signs of wear implying they were well used during his life and not just there as symbols of power and kingship.


Tutankhamum was frequently portrayed seated at ceremonial events – is this an indication of his disability?

In addition, the tomb was a veritable pharmacy, with stocks of many plants, herbs and seeds, used as medicines in ancient Egypt, including thyme, garlic cloves, coriander and sesame seeds, cumin, almonds and cuttings from willow and persea trees, the latter belonging to the Laurel family. There were also alabaster unguent jars containing cyprus seeds in olive oil, sometimes used as an antiseptic, and calcite jars with the resin of fir trees which, when mixed with “salt and the dregs of sweet beer”, was used as a bandage for “stiff limbs”. Although these items may all just have been “grave goods” and not necessarily there as medical treatments, the ancient Egyptians were skilled in medicine, practising minor surgery and the setting of broken bones and were familiar with a wide range of natural remedies for treating common ailments.

Many have speculated about the cause of Tutankhamum’s early death. Murder, by a blow to the head, was an early theory, suggested by a fragment of bone within the cranium, implying a skull fracture. This was disproved, when the fragment was demonstrated to have probably arrived inside the skull when Howard Carter removed the famous, gold death mask, rather than at the time of death.

However, the Pharaoh is known to have sustained a complex fracture to his lower left femur (thigh bone), which resulted in loosening of the patella (kneecap). In CT pictures the radio-opaque embalming material spills around the edges of the fracture implying that the break occurred close to the time of death and that the wound was open at the time. In other words, this was a compound fracture and would almost certainly have become infected. In the absence of antibiotics such an infection, or osteomyelitis, would be very likely to prove fatal.

CT scan of the left knee showing CT images of the left knee showing a peculiar fracture of the lower part of the thigh bone with the dense embalming material covering its edges (shown with arrow) suggesting its occurrence shortly before death. There was no evidence of violent premortum trauma to the skull," says Ashraf Selim, from the Cairo University in Egypt. "But there is a possible femoral fracture that may have led to his death. Although the break itself was not life-threatening, it would have left an open wound which could have become lethally infected.

CT images of the left knee showing a peculiar fracture of the lower part of the thigh bone with the dense embalming material (pink arrow) covering its edges  suggesting the fracture was open to the air and occurred shortly before death.

The fracture may have resulted from a fall, or possibly from involvement in a chariot crash. Six chariots were found in the tomb and there has been speculation that this implies a particular interest in chariot driving on the part of Tutankhamum. Analysis of the mummy has led some to conclude that the overall damage to the body was indeed consistent with a chariot crash, however, it seems more probable that this gross damage occurred predominately after death, during mummification or subsequently.

Recently, a new possibility has been raised. Egyptian scientists, led by Dr Hawass, using DNA extracted from Tutankhamum’s bone marrow, demonstrated the presence of several strains of the severe form of malaria (Plasmodium falciparum), indicating that the Pharaoh had been infected with malaria on one or more occasions.

Severe infection with Plasmodium falciparum; the ring shaped parasites live inside the red cells of the blood.

A severe infection with Plasmodium falciparum; the ring shaped parasites live inside the red cells of the blood and cause severe anaemia and fatal “sludging” of the blood in the circulation of the brain (cerebral malaria)

Although a possibility, it cannot be said with any certainty however that the malaria infection was fatal. In areas where malaria is common most of the mortality is in young children, those surviving to adult life have a degree of naturally acquired immunity, which usually protects them against the fatal effects of malaria.

There is therefore good evidence for at least two, plausible causes of death, osteomyelitis and malaria, why suggest that sickle cell was involved? Well firstly, Tutankhamum came from an area of the world where malaria was and remains a public health issue. That severe forms of malaria existed in ancient Egypt was unambiguously demonstrated in 2008 by analysing DNA extracted from the tissues of several mummies and, as noted above, it was detected in Tutankhamum as well. Malaria remained prevalent in Egypt for centuries, but indigenous transmission was eventually eliminated in 1998, only to return earlier this year with an outbreak of Plasmodium vivax infection in Aswan province.

Being a carrier for sickle cell offers some protection against the complications of malaria in childhood and therefore the sickle cell mutation tends to occur, and to increase in frequency, in populations regularly exposed to this infection, such as in ancient Egypt. In contrast, malaria infection in someone with sickle cell disease, the homozygous state,  often provokes a severe crisis and is frequently fatal.

The sickle cell mutation is uncommon in Egypt generally (<2%) but occurs at higher frequencies (9-22%) in the oases of the western desert. There is a "hot spot" in southern Sudan, ancient Nubia.

The sickle cell mutation is uncommon in modern Egypt generally (<2%) but occurs at higher frequencies (9-22%) in the oases of the western desert. There is also a “hot spot” in Sudan, ancient Nubia or Kush.

When and how did sickle cell arrive in Egypt? We know that the sickle cell mutation itself probably first appeared, on several separate occasions, in West Africa at least 10,000 years ago. Plenty of time for it to spread to Egypt along the Sahel trade routes by the time of Tutankhamum. Analysis of DNA from several mummies from about 3200 BC by an Italian team in 1999, did indeed reveal direct evidence of the sickle cell mutation in 3 of the 6 analysed, so it seems likely that sickle cell was present in ancient Egyptian populations. Confirmation that the sickle cell found in Egypt originated in West Africa comes from haplotype analysis, which indicates that all of the modern Egyptian sickle cell mutations analysed to date are of the Benin type, originating in the area of what is now modern Nigeria.

Map of Africa showing the distribution of the different haplotypes of the sickle cell mutation. All the sickle cell chromosomes in Egypt are of the Benin haplotype.

Map of Africa showing the distribution of the different haplotypes of the sickle cell mutation. All the sickle cell chromosomes analysed from Egypt are of the Benin haplotype. Haplotypes are defined by the pattern of DNA on a particular stretch of a chromosome. There are 5 different sickle cell haplotypes, implying that the mutation arose on at least 5 separate occasions on different chromosomal backgrounds.

Other DNA studies also support the flow of genetic information from sub-Saharan Africa into the populations of ancient Egypt; Rameses III and his son, who came after Tutankhamum, both had a type of Y-chromosome (E1b1a) that is characteristic of black Africans. We can conclude therefore, that there is tentative evidence for the sickle cell mutation in ancient Egyptian populations and that this would have been derived by gene flow from West Africa. Under the selective pressure of malaria, which was prevalent in ancient Egypt, the mutation would have spread widely throughout the population.

Incestuous marriages were common among the Pharaohs, Tutankhamum’s mother and father were brother and sister and he himself also married his sister. If a family carries a recessive genetic mutation like sickle cell, then marriages between family members are much more likely to result in children with the disease state, where the abnormal gene has been inherited from both parents. If sickle cell was present in Tutankhamum’s family, then the fact that he was the child of sibling parents would greatly increase his risk of having the disease. It is known that his parents lived into their 50’s, a fact compatible with them being carriers for sickle cell.

On the other hand Tutankhamum lived to 19 years of age and some have argued that this would be very unlikely, for someone with sickle cell disease, under conditions where no effective medical treatments were available. Most individuals under these circumstances would be expected to die from severe infections or other complications of the disorder in early childhood. Whilst this is undoubtedly true, it is possible to survive into the teenage years with sickle cell, particularly if the disease is one of the milder variants or associated with persistently high levels of foetal haemoglobin. So his age at death does not completely preclude the possibility that Tutankhamum did indeed have sickle cell disease.

Is there any evidence from his tomb or examination of his mummy which support the notion? We have already mentioned the numerous walking sticks and medicinal compounds in the tomb, but other evidence comes from the skeleton. Evaluating the pathology of ancient remains is notoriously difficult due to the effects of time, the embalming process itself in the case of mummies, and damage or contamination caused by post-discovery handling. Nevertheless, the following findings might be relevant.

Examination of Tutankhamum’s skeleton revealed a shortened second toe on his right foot (hypophalangism) due to absence of the middle phalanx (middle bone of the toe).  Short fingers or toes can occur in sickle cell disease, as a late complication of dactylitis. This is a painful crisis affecting the fingers or toes in childhood, usually between the ages of 6 months and two years; the crisis disturbs bone growth and leads to a shortened digit. However, in sickle cell disease, X-rays do not normally show total loss of a phalanx, which is the appearance in the images of Tutanhamum’s foot.

In addition to these changes, osteonecrosis, or areas of bone death, were noted in some other bones of the feet, particularly the heads of the 2nd and 3rd metatarsals of the left foot. It is possible that these changes may have been introduced by the embalming or bandaging process after death, and caution is therefore necessary about their interpretation.


X-rays of Tutankhamum’s feet. Box A (top left) shows the actual right foot with normal anatomy. Box B (top right) shows the actual left foot; the yellow and blue arrows indicate the heads of the 2nd & 3rd metatarsals which are deformed by osteonecrosis. This is also seen on the lateral view – box C (bottom left) indicated by the yellow arrow. Box D (bottom right) is a reconstruction of the feet showing the shortened 2nd left toe (black arrow) with a missing middle phalanx.

However, these appearances led the investigators in Egypt to suggest that Tutankhamum had a condition called Freiberg-Kohler syndrome. This is a rare condition of childhood where the blood supply to the developing bones of the foot is disrupted causing pain and disability. It was also this pathological finding, in particular, which led the German investigators to make the alternative suggestion of sickle cell disease, which they considered a more likely explanation of the findings than Freiberg-Kohler.

Sickle cell very commonly leads to osteonecrosis or, as it is more commonly called, avascular necrosis, however, this is almost always seen in the hip and shoulder joints and spinal vertebrae, and only very rarely does it cause these changes in other bones, such as those of the feet. Whatever the cause of the osteonecrosis this, together with the left club foot, would have caused significant chronic pain and disability and makes the need for walking sticks and canes and a multitude of natural medicines understandable.

On balance, the claim that Tutankhamum had sickle cell disease must remain speculative at this time. There is, on the other hand, good evidence for two, potentially life threatening conditions, namely falciparum malaria and an infected, compound fracture of the left femur. The issue could be resolved quickly and easily by looking at extracts of Tutankhamum’s DNA for evidence of the sickle cell mutation, although results for this have not been reported to date.

The famous gold death mask with the reconstructed facial appearance of Tutankhamum. The facial features are "europeanised", proving the existence of sickle cell disease would require a re-evaluation to reflect gene flow from sub-saharan Africa.

The famous gold death mask with the reconstructed facial appearance of Tutankhamum. The facial features are “europeanised”.

Proving the presence of sickle cell disease in Tutankhamum would require us to re-evaluate how we see the young Pharaoh, to properly reflect the gene flow into ancient Egypt from sub-Saharan Africa.

Ancestry and pathology in Tutankhamum’s family. Hawass Z, Gad YZ, Ismail S et al. Journal of the American Medical Association (2010), volume 303, pages 638-47.

King Tutankhamum’s family and demise. Timmann C & Meyer CG. Journal of the American Medical Association (2010), volume 303, page 2473

Malaria, mummies, mutations: Tutankhamum’s archaeological autopsy. Timmann C & Meyer CG. Tropical Medicine and International Health (2010), volume 15, pages 1278-80.

King Tut’s death explained? Butler D. Nature News (2010) available at: http://www.nature.com.news/2010/100216/full/news.2010.75.htlm 

Plasmodium falciparum in ancient Egypt. Nerlich AG, Schraut B, Dittrich S et al. Emerging Infectious Diseases (2008) doi:10.3201/eid1408.080235

Use of the amplification refractory mutation system (ARMS) in the study of Hb S in pre-dynastic Egyptian remains. Marin A, Cerutti N & Massa E. Bollettino della Societa Italiana di Biologia Sperimentale (1999), volume 75, pages 27-30


About rogerjamos

I am a consultant haematologist who has worked in Hackney, London, UK with patients who have sickle cell disease for many years. Knowledge is power; the hope is that this blog will empower patients by putting them in touch with contemporary research into sickle cell disease and facilitating informed discussion on the issues raised. Dr Roger Amos MA, MD, FRCPath
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