Over the last decade a substantial amount of molecular evidence confirming the etiology of the plague over virtually the entire medieval period has been produced. In this rapidly evolving field, evidence for the Black Death of the 14th century has been produced by each new method in turn.
Given the conditions of remains sampled to date, the methods fall into two main categories: genomics and immunology. There are pros and cons to each. Genomics has well-recognized specificity and the ability to compare with living and ancient strains, but non-nucleic acid methods are both specific and far more sensitive. Non-nucleic acid methods (using immunology) will give a better indication of the true incidence within a population, especially important when testing moves beyond mass graves. Immunologic methods have been the primary means of diagnosing clinical infectious disease for at least 30 years. The Rapid Diagnostic Test (RDT) now used to diagnose ancient and modern plague uses technology that has existed for over 25 years with a good track record. The downside of immunology is that it doesn't give strain specific information. On the other hand, detection of degraded DNA much less getting good enough sequence for strain matching is difficult and inefficient.
This map charts all of the medieval plague molecular data that I have seen (view Plague Map in a larger map). The red balloons mark 6th-9th century, Plague of Justinian, sites. All three early medieval sites are beyond the Alps proving that the plague of Justinian penetrated well beyond the Mediterranean basin. The yellow balloons represent 14th century data, with the starred balloon specifically dated to the first wave of the Black Death pandemic. The blue balloons represent post-14 century data (14th-17th century). Click the balloons for references.
Even a cursory look at the map makes it apparent that both pandemics reached beyond the Alps into the European plain. Further, the distribution represents the areas of activity of 3-4 research groups rather than as an indication of plague incidence across Europe. Every region so far examined and published has found some evidence of plague. There is both DNA and immunological evidence for the 14th century. Unfortunately, DNA data has been produced by three different groups who have not yet produced a consensus sequence or analyzed their differences. Despite the differences between their sequences, there is plenty of homology between their data and modern reference sequences to ensure that they all identified Yersinia pestis. Their differences are most likely to be primarily related to interpretations of degradative changes in the ancient DNA, though it is possible that more than one strain was active in 14th century Europe.
The map also makes it apparent that we only have molecular evidence from a very small sliver of the territory covered by the medieval pandemics. There are too few sites so far to make any predictions about the routes the plague traveled based on molecular evidence. It never travels from point A to point B as the crow flies! Plague spreads more like a spiderweb than a wave. So, long distance transmission may well exist before lateral spread fills in the countryside. It is absolutely necessary to take in consideration medieval trade and communication routes.
This is an exciting time to be working on the plague. So far, only the tip of the iceberg has been exposed. To date, the molecular evidence has been the most useful for confirming the etiology of the plague of Justinian, the Black Death pandemic, and plague's endurance in western Europe. We have the technology now to map the geographic extent of Yersinia pestis for the first and second pandemic. It will take at least a generation of work from archaeologists, geneticists, and paleomicrobiologists to gather enough sites and resolve the fine-detail sequencing issues to begin to do strain mapping.
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