Malaria.
Or inbreeding.
Or both. That’s the tentative conclusion of a new paper in the Journal of the American Medical Association. (Lead author Zahi Hawass, Secretary General of the Egyptian Supreme Council of Antiquities, is a colorful and controversial figure who was profiled in The New Yorker last November; subscription required to see full article. One wonders what he did to justify first authorship.)
The paper with its 17 authors is a laborious genetic, phenotypic, and archaeological study of 16 mummies from ancient Egypt, with particular emphasis on the boy-king Tutankhamun, who died, aged 19, around 1324 B.C. DNA was extracted from bones and analyzed to construct pedigrees; the mummies were X-rayed to look for aberrant morphology; and samples were PCRed to look for DNA of microorganisms that could have caused fatal infections. Hawass is no stranger to publicity, and it’s clear that finding out what killed King Tut, probably the most famous of all ancient Egyptian kings, would garner considerable attention. It has. But the study is still a good one, a felicitous combination of forensic archaeology, pathology, and genetics.
Here’s what it found:
1. Analysis of both Y-chromosomal and nuclear DNA produced a five-generation pedigree for Tut, his ancestors, and perhaps two of his children (some of the relationships had previously been inferred from archaeological data). His great-grand parents were identified as Yuya and Thuya, and his parents, Akhentan and a mummy known as KV35YL, were classified as brother and sister based on genetic data. If these data are right, Tut was pretty inbred.
2. Ancient Egyptian art depicts Tut, and some of his male relatives, as having a feminized appearance, sometimes with enlarged breasts. This has led to speculation that royals of that era had various genetic conditions that could produce feminized appearance, including Marfan syndrome (once supposed to have afflicted Abe Lincoln) and gynecomastia (abnormally enlarged breasts in males). None of these diagnoses were supported by the morphological studies, so the peculiar depiction of the rulers in ancient Egyptian art is taken as a stylistic device.
3. Nevertheless, Tut and his relatives were really screwed up. Table 3 gives a list of pathologies found in the royalty, and hardly one of them is free from something bad, including rotting teeth, heart disease, cancer, arteriosclerosis, “traumatic events to the face”, and so on. Here’s what was wrong with Tut himself:
cleft palate
clubfoot
mild curvature of the spine
foot abnormalities (missing bones)
bone disease, leading to bone bone loss in the foot
Now some of these (particularly the abnormalities in Tut’s relatives) were likely due to the absence of medical care, but I suspect (as do the authors) that this preponderance of abnormalities reflects the well-known tendency of Egyptian royalty to intermarry, leading to inbreeding and all the attendant problems that come with genetic homozygosity. Based on the bone problems, it’s likely that Tut limped, a diagnosis supported by the presence of 130 canes in his tomb (some of which showed wear) and the depiction in Egyptian art of Tut sitting during ceremonies when other Egyptian kings would have been standing.
4. Oh, and there was one more thing wrong with Tut: he had malaria. Not just malaria, but the deadliest form of the disease, falciparum malaria. Now there’s no independent evidence that malaria existed in ancient Egypt, but its presence there seems likely, given its present distribution and the swampy areas around the Nile. But the DNA tells the tale. PCR amplification of genes in the malaria parasite (a sporozoan), clearly shows that Tut had it, and so did both of his great-grandparents:
Fig. 1 (Fig. 6A in the paper): Evidence for malarial infection of Tut and relative. From the paper: A. Polymerase chain reaction amplification of a 196–base pair (bp) apical membrane antigen 1 (AMA1) fragment of Plasmodium falciparum in Egyptian mummies. DNA marker indicates molecular size marker phiX/ 174 HaeIII. Successful amplification is indicated by “ .” [JAC note: Thuya and Yuya were Tut’s great-grandparents].
We’ll never really know what did young Tut in, but the authors speculate that it was the combination of malaria and inbreeding:
He might be envisioned as a young but frail king who needed canes to walk because of the bone-necrotic and sometimes painful Köhler disease II, plus oligodactyly (hypophalangism) in the right foot and clubfoot on the left. A sudden leg fracture23 possibly introduced by a fall might have resulted in a life-threatening condition when a malaria infection occurred. Seeds, fruits, and leaves found in the tomb, and possibly used as medical treatment, support this diagnosis (eAppendix, eFigures 3D and 3E).24-25,53-57
This seems reasonable, although Hawass, with his usual penchant for publicity, is going around telling reporters, with no reservations, that malaria definitely killed the young king. Well, maybe, but falciparum malaria isn’t always fatal. Two of of Tut’s great-grandparents had it, and, as the authors note, they died in their 50s, and the infection might have been chronic, or suppressed by their immune systems.
________________
Z. Hawass et al. 2010. Ancestry and pathology in King Tutankhamun’s family. JAMA 303:638-647.