Real-time tracking of recent pathogen evolution
Making use of biological specimens preserved in natural history and pathology collections to understand recent pathogen evolution is not a new idea. Some labs have already obtained stunning successes with this respect, e.g. Jeff Taubenberger working on 1918 influenza or Mike Worobey on early HIV-1 cases. Yet, this amazing resource is still very rarely used.
We are disease ecologists and evolutionary biologists working at the Robert Koch Institute (RKI) in the Leendertz Lab and we are interested in zoonotic emergence. To study this phenomenon, we usually collect information on infectious agents in contemporary wild animals, particularly at human/wildlife interfaces in sub-Saharan Africa. These comparative approaches are powerful but we felt more than once that our projects would have benefited greatly from adding information gleaned from historical specimens.
A couple of years back, our dream came true and we were able to set up an ancient DNA lab, here at RKI. Since then, we have started a number of projects and collaborations that explicitly build on the use of ancient samples. This little webpage will tell you more about this aspect of our work.
A non-exhaustive list of what happens at the moment in the ancient pathogen lab
Check our blog post above!
Vaccination against measles started in the 1960s. We are very interested in characterizing how this massive intervention influenced the original genomic make-up of measles viruses. We have already been lucky enough to identify more ancient measles cases, and we will soon start working on those.
Rinderpest virus (RPV) is the closest relative of measles virus. Any information about its past genomic diversity may bring new insight regarding the divergence of the two viral lineages. With smallpox virus, RPV is also one of the only two pathogens (and viruses) ever eradicated by mankind. Now that sequence-and-destroy initiatives are close to an end, the only sources of information about RPV are in the closets of veterinary pathology collections, of which a number have already accepted to grant us access to interesting specimens.
Canine distemper virus
We do not aim at only working on measles virus relatives (morbilliviruses), but this one was just too interesting for our vets not to investigate the question at all. Canine distemper virus may have emerged as recently as in the 18th century - so historical collections may cover the full period of its circulation in dogs. And one of the envisioned emergence scenarii involves vampire bats feeding on blood from dogs! We already generated two complete CDV genomes which we hope will help us clarify this virus origins.
1918/9 influenza virus
We are caught in the middle of a major pandemic of respiratory disease and of course this rekindles our interest in similar events from the past. The 1918 flu, which killed 50-100 million, is probably the first example that comes to mind. Many questions regarding its causative agent, a H1N1 influenza A virus, remain open. We have been working hard on identifying and working specimens from pathology collections and we will soon make public a first batch of three nearly complete genomes. We intend to push this topic much further, in a collaborative effort involving many other labs.
Our institute was founded by Robert Koch himself, and we still preserve some biological material that was used by our predecessors when Koch was active. The three bottles on the picture are an excellent example and represent remnant of experiments Koch performed in the late 19th century to set up a cure against tuberculosis (whose causative agent he had discovered). His cure, which he called tuberculin, ended up in a fiasco - part of which resulting from Koch's bad record of tuberculin preparation. We have already analyzed the genetic material contained in these bottles (of which unfortunately none was a bona fide tuberculin bottle) both to cast a new light on the tuberculin controversy and to open a molecular window on Koch's lab.
Pathogen museomics comes as the ultimate cherry on the cake for all the folks below, who also happen to belong to a larger, extremely cool research structure: the Leendertz Lab!
Those we (co-)spearheaded
Those we helped friends with
Measles virus and rinderpest virus diverged in the 6th century BCE
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Pathogen museomics and Research sections of the site: Navena Widulin/Berlin Museum of Medical History at the Charité
Measles virus in Projects section: Otis Historical Archives of “National Museum of Health & Medicine” (OTIS Archive / CC BY (https://creativecommons.org/licenses/by/2.0)
Rinderpest virus in Projects section: Jan Smit (II) - Rijksstudio: http://hdl.handle.net/10934/RM0001.COLLECT.479868 , Objectnr. RP-P-OB-83.842, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2891054
Canine distemper virus in Projects section: https://wellcomeimages.org/indexplus/obf_images/33/6e/be645f33873c32157d34dd37c74d.jpgGallery: https://wellcomeimages.org/indexplus/image/L0022418.htmlWellcome Collection gallery (2018-04-02): https://wellcomecollection.org/works/hw96nt5y CC-BY-4.0, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=35997551
1918 flu in Projects section: Otis Historical Archives, National Museum of Health and Medicine / Public domain
Tuberculin in Projects section: Robert Koch Institute
Copyright © 2020 Sébastien Calvignac-Spencer. All rights reserved.