Molecular Evidence For Tuberculosis From 9,000 Year Old Remains From Atlit-Yam, Israel

If you look at the time stamp of both Bora‘s and Greg Laden‘s posts, you’d notice that they just broke the embargo on a new study of a prehistoric case of tuberculosis that was supposed to go live at 5pm PST, 8pm EST. Now that the news is out, albeit slightly earlier than expected, I figure I should also cover it. The press release touts that the human remains from a site called Atlit-Yam in Israel have provided genetic evidence for the earliest known cases of tuberculosis, dated at 9,000 years old.

Atlit-Yam, Israel
Atlit-Yam, Israel

Atlit-Yam is a site currently submerged 8 to 12 meters below sea level in the North Bay of Atlit. The site is about 10 kilometers south of Haifa. Previous researchers have radiocarbon dated the site to be 9,250 to 8,160 years old. The site has yielded both floral and faunal remains along with tools. The floral remains and the faunal remains indicate that these people already made the transition from hunter gatherer subsistence to a fully Neolithic lifestyle.

Human remains were also recovered from the site, and some show characteristic bone lesions that are signs of tuberculosis, specifically the remains of a 25 year old woman buried with an infant. The age of the woman was estimated based on dental attrition, epiphyseal ring ankylosis and the symphysis of the pubis, which are all pretty solid markers. The bones were preserved in a muddy dark clay substance, an anaerobic condition which is very conducive for DNA preservation. Even though other elements have tuberculosis caused lesions, the researchers specifically analyzed the ribs and arm bones of the female adult and long bones of the infant.

Paleopathological lesions on Neolithic infant bones.
Paleopathological lesions on Neolithic infant bones.

Because of the excellent conditions for DNA preservation, the authors moved ahead with two molecular techniques to determine if tuberculosis was the causative agent of the lesions. First they deployed a PCR experiment, specifically designing a primer set to the fish out Mycobacterium tuberculosis sequences. Secondly, they utilized a reverse phase high performance liquid chromatography (HPLC) method that tried to isolate mycobacterial cell wall mycolic acids from the sample.

The PCR yielded positive results with the multi-copy IS6110 & IS1081 fragments, obtained from the rib of the woman and infant long bone. The fragments were confirmed to be valid by sequencing. These fragments are restriction fragment length polymorphisms and are commonly used as definitive signatures of Mycobacterium tuberculosis. The authors compared their PCR fragment sequences to Genbank and also reported that the sequences are identical to those in the NCBI database for M. tuberculosis.

The HPLC also provided evidence that there are mycobacterial cell wall molecules present in the samples. The woman had the highest amount per mg of bone, at 20.14 pg, while the infant had a smaller amount at 0.12 pg/mg. Nonetheless, both lines of evidence along with the visual lesions show that at least two of the people of Atlit-Yam had a tuberculosis problem.

As I mentioned, it seems that the press is going to love the ‘earliest evidence of TB’ sound bit. But it’s not particularly true because, John Kappelman announced the discovery of tuberculosis in a 500,000 year old Homo erectus cranial fragment last yet. I have my doubts about the H. erectus diagnosis though. The authors also did review other paleo-tuberculosis cases such as the 17,000 year old bison and the 4,000 year old Egyptian human bone and soft tissue sample. Either way, this is the earliest report of the disease in humans that has been confirmed by molecular means.

One last thing, Atlit-Yam is among the very few Pre-Pottery Neolithic sites where domesticated cattle have been found. Tuberculosis in humans was thought to have a zoonotic origin, perhaps transmitted to humans from domesticated cattle during the Neolithic revolution. But that theory has been on the rocks, and these individuals were clearly infected with Mycobacterium tuberculosis, not Mycobacterium bovi, which infects cattle. Could the cattle have caused the tuberculosis in these two individuals? What do you think?

    Israel Hershkovitz, Helen D. Donoghue, David E. Minnikin, Gurdyal S. Besra, Oona Y-C. Lee, Angela M. Gernaey, Ehud Galili, Vered Eshed, Charles L. Greenblatt, Eshetu Lemma, Gila Kahila Bar-Gal, Mark Spigelman, Niyaz Ahmed (2008). Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean PLoS ONE, 3 (10) DOI: 10.1371/journal.pone.0003426

4 thoughts on “Molecular Evidence For Tuberculosis From 9,000 Year Old Remains From Atlit-Yam, Israel

  1. Oh, the embargo time is provisional – once the paper is published and public, embargo is over – no way to enforce it any more. This sometimes happens a little early if the technical aspect of loading the papers goes without a glitch.

  2. Bora,

    In an email you wrote to me, dated on February 25th, 2008, you explicitly warned against us breaking an embargo. I quote,

    “What is really important is to make sure you never break an embargo… Please be sure never to break the embargo… Even if the post is up for just a few minutes, if someone notices you can get in trouble ( i.e., be removed from the Press list forever)…”

    What happened to that? Are you giving me the greenlight to basically publish whenever I see the link go live?


  3. The blog post has to occur AFTER the paper goes live, not a minute before. That is what that sentence means. As soon as the paper is published, it is public and thus fair game to blog about.

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