What killed King Tut?

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.

20 Comments

  1. Posted February 17, 2010 at 7:43 am | Permalink

    This is a nice discussion of the findings. In our blog on these kinds of subject, at ecodevoevo.blogspot.com, we took a somewhat less sanguine view of this article. Here’s our post: http://ecodevoevo.blogspot.com/2010/02/i-saw-mummy-kissing-mosquitos.html

    Readers of our post may not like our satirical treatment, but we felt that much of what was reported was not DNA-specific but could instead be seen with the naked eye (and/or the CT scan).

    We agree that the cause of death speculation was speculation, especially since malaria doesn’t kill all its victims. And finding the parasite with DNA methods is definitive if contamination can be ruled out. But since plasmodium’s been found in other mummies, this is less than a spectacular result.

    So we felt this was grandstanding rather than major new science.

  2. Posted February 17, 2010 at 8:46 am | Permalink

    Mr. Martin demonstrates the ramifications of genetic homozygosity:

  3. Occam
    Posted February 17, 2010 at 9:15 am | Permalink

    Lead author Zahi Hawass, Secretary General of the Egyptian Supreme Council of Antiquities, is a colorful and controversial figure… One wonders what he did to justify first authorship.

    Come on, the question contains the answer: Secretary General of the Egyptian Supreme Council of Antiquities. Everybody in the business knows Dr. Hawass and his Valley-of-the-Kings-sized ego. There’s no way anything significant with DNA in it from under his majestic guardianship could ever get published without him receiving the lion’s share of the media hullaballoo.

    As for the substantive merits of the paper, I am awaiting access to JAMA, but not yet holding my breath: hardly a year passes without newdefinitivescientificconclusionsthatwillendthedebateonceandforall as to who or what did Tut in. Be nice to be surprised.

  4. gillt
    Posted February 17, 2010 at 9:43 am | Permalink

    Coyne: “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.”

    Are you saying his great-grandparents were also his parents who were also siblings?

  5. Posted February 17, 2010 at 10:09 am | Permalink

    wow, very interesting and informative topic. I never thought he had so many complications that led to his death. Thanks to the technology nowadays like DNA which helps us dig up the history of great people.

  6. littlejohn
    Posted February 17, 2010 at 2:15 pm | Permalink

    Somebody needs to point this stuff out to the British royal family. Can “twit” be inherited through too much inbreeding?

    • Jonn Mero
      Posted February 18, 2010 at 7:48 am | Permalink

      Way too late, mate!

  7. Brian
    Posted February 17, 2010 at 2:32 pm | Permalink

    Jerry in the interests of ensuring that the fatheist squabble never dies:

    http://rationallyspeaking.blogspot.com/2010/02/podcast-teaser-great-atheist-debate.html

    • Sigmund
      Posted February 18, 2010 at 6:50 am | Permalink

      It’s become a sadly predictable that any attack the non-accomodationist position will have a badly stuffed strawman leading the charge.
      After mischaracterizing the anti-accomodationist position (sorry Massimo but the God that anti-accomodationsts feel confident in refuting is the interventionist God of theism rather than any type of possible pantheistic or non intervening deistic God) Pigliucci presents his prime argument – last thursdayism – the argument that God made everything in nature to appear as if he never existed (even though he does!). This type of oomphalistic argument is almost never used by theists these days. Both theistic evolutionists and creationists avoid it for the simple reason that they don’t like the two implications – that God is a devious trickster, and that the best way to figure out the workings of nature is to work along the lines that God doesn’t exist and that no possible evidence for him exists in nature (everything we discover in nature in future will make it appear less and less likely that he exists).
      At the moment there is only one ‘religion’ that uses the logic of last Thursdayism – Flying Spaghetti Monsterism. Is Massimo really arguing that this satirical belief makes more sense than standard theism (even allowing for the arguments of sophisticated theism)?

  8. Pink
    Posted February 17, 2010 at 3:30 pm | Permalink

    Tut tut, fear boys with bugs.

  9. Selena
    Posted February 17, 2010 at 9:34 pm | Permalink

    ” “Traumatic events to the face” ”

    I think we should call Dr William M Bass.

  10. whyevolutionistrue
    Posted February 18, 2010 at 6:38 am | Permalink

    Occam has asked me to post this comment as he/she has had trouble putting it up.

    Jerry kindly provided me with both a copy of the Hawass et al. (there! first author!) JAMA paper before my library would, and with an opportunity for making a fool of myself. Duly acknowledged.
    However, upon reading that Dr. Hawass is taking primo loco responsibility for the integrity of the data and the accuracy of the data analysis, I was heartened: after all, I could scarcely do worse.

    First impressions: The paper provokes more questions than it purports to answer, the most important ones being hidden in figures, footnotes, tables, and the online supplement.
    The cause of Tut˙s demise is not identified, just some likely tracks, despite a Medicare-sized bunch of pathologies. His forebears were not the healthiest either. But then, we must remember how miserable most people’s health was, way back when they were˛as God had intended them to be.
    The inbreeding is now genetically proven, but this was one aspect of pharaonic tradition exceedingly well documented; the contrary would have been news. The malaria: show me someone then and there who didn˙t have it. (Cf. L. Hviid, Naturally acquired immunity to Plasmodium falciparum malaria in Africa; doi:10.1016/j.actatropidoi:10.1016/j.actatropica.2005.06.012)

    The real bombshell, mentioned most offhandedly by Hawass et al., would be the identification of the KV55 mummy with Pharaoh Amenhotep IV alias Akhenaten. This is presented as likely beyond reasonable doubt: KV55 mummy = son of Amenhotep III and Tiye, father of Tut. Egyptology has been debating for over a century the identity of the mummy in tomb KV55. There are lots of problems with every identity proposed hitherto. Unfortunately, the devil is in the e-supplemented details (p. 5): The preliminary Y-chromosome data showed identical short tandem repeat constellations in Amenhotep III, KV55, and Tutankhamun. These paleogenetic findings do not in themselves prove any relationship between the 3 individuals but do increase the probabilities that they indeed share the same paternal lineage. […] Our recent anthropological analysis of the KV55 mummy showed that he was much older than previously assumed, which provided further evidence that this mummy could be the pharaoh Akhenaten. The proof that Amenhotep III and Queen Tiye are the parents of KV55, combined with this anthropological and archeological evidence, indicates that the mummy in KV55 is almost certainly Akhenaten.
    As Joschka Fischer, then Germany˙s foreign secretary, famously told Colin Powell during the WMD debate at the UN: I am not convinced. I˙d like to know exactly what the alternatives are, including the mysterious Semenkhkre. I˙d also like to know how the method handles missing data, i.e. siblings no included in the analysis. I˙d like the whole chain of reasoning and the statistics to go.

    A positive proof, or strong indication, that Akhenaten was actually not suffering from any condition (Marfan/Fröhlich/Klinefelter/Antley-Bixler syndromes) conducive to the feminine traits of his later Amarna iconography would cause serious uproar in Egyptian studies. Whatever the iconographic programme of the Amarna period (and the interpretations thereof are almost as varied as there are Egyptologists), there was a consensus about its initial realism, with an accentuation towards the grotesque. If KV55 was Akhenaten, and if the man didn˙t look at all like his depictions, a 900 ft. WTF neon sign hangs over this period in Egyptian history. Again, the evidence proposed is thin, the Egyptological correlates are thinner, and I am not yet convinced. (That the actual Tut didn˙t share these traits is not proof of anything: he was TutankhATEN before being re-Amuned, he would share Daddy˙s by-then official Amarna iconographic style. Wouldn˙t he?)

    I mean, this period is the world˙s first historically documented monotheistic craze, for Athena˙s sake! Whatever madness ensued in the region is, in some not quite elucidated ways, linked to Akhenaten and his cult of Aten. One would hope for a slightly less cavalier approach to such momentous conclusions.

    It comes as no surprise that the probable murder of the Younger Lady in KV35 (lethal injuries to her face, nose pushed through her sinuses) is featured as a mere footnote to Table 3.
    Comments on the plaster-botoxing over of Nefertiti˙s bust in Berlin, based on recent CT scans, are naive (cf. Illerhaus et al. for a robust assessment of the imaging results; freely available online: http://www.ndt.net/article/ndtnet/2009/illerhaus.pdf).

    If you have access to the online e-supplement, the Kinship analysis of microsatellite data is really neat: you can highlight specific alleles throughout the pedigree, or key in a mummy to follow the transmission of its alleles. Nice visualisation!

  11. Posted February 18, 2010 at 9:22 am | Permalink

    My oh my. No wonder our ancestors did not live very long. They say that King Tut was an inbreed. When you have children with siblings, cousins or parents you are mixing “like blood” so there is no way good genes can stamp out bad genes. This is because they are all the “same gene”. So if one parent had heart disease risks and the other parent had the same it will be 100% likely that there offspring will suffer the same fact.

  12. Posted February 18, 2010 at 9:24 am | Permalink

    The malaria: show me someone then and there who didn˙t have it.

    In the figure Jerry reproduced in the post, 16 samples, coming from at least 13 individuals (some, such as Tut himself, had multiple samples taken) are tested for the presence of plasmodial DNA. Four of the individuals have malaria. Discounting the two fetuses (no opportunity for infection before death), that’s seven individuals without malaria. These seven might be false negatives (e.g., the plasmodial DNA had degraded in these mummies, but not the other four), but here’s a prima facie case for the incidence of non-infection.

    • Occam
      Posted February 18, 2010 at 10:47 am | Permalink

      Sorry for mis-threading, my comment at #13 is actually in reply to your observation.

      • Posted February 19, 2010 at 8:59 am | Permalink

        I’d misthreaded too– my post was a reply to yours in #10.

  13. Occam
    Posted February 18, 2010 at 10:18 am | Permalink

    Good point. I plead guilty of gross rhetorical hyperbole. I also plead guilty of dabbling in epidemiology at 4 AM.

    What I meant was that we’ve been shown a highly biased sample of individuals from a malarial high-risk region and with a lifestyle entailing a high risk of exposure. Also, the sample shows the outcome of the cumulative lifetime risk of exposure of the individuals, not the incidence or prevalence at any given time for any given cross-section of the population. Under the circumstances, the cumulative lifetime risk must rate as relatively high (at least that’s how I would regard a ratio of 4/11). So, Tut’s malaria seems (to me) unexceptional, in the absence of convincing clinical indicators of its immediate fatality.

  14. Meret
    Posted February 24, 2010 at 10:45 pm | Permalink

    Zahi Hawass is a fool and I question everything that egomaniac says.


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