Was the Black Death yersinial plague?

Didier Raoult and Michel Drancourt argue that their recovery of DNAsequences specific to Yersinia pestis from skeletons believed to date from the mid-14th-century Black Death should put a stop to further “speculation” regarding the cause of the epidemic “unless our work is proved to be wrong.” There are several reasons to question the ancient DNA results reported for the Black Death pathogen by Raoult et al. First, the dating of their samples is uncertain. Based on archaeological evidence, the skeletons that were examined could only be dated to within an interval of more than 100 years that broadly bracketed the first European outbreak of the Black Death (1347–51). The investigators nonetheless argue that the skeletons must be from the Black Death because they were found in a “common catastrophe grave”. This burial contained only three individuals, which distinguishes it from the genuine mass burials of several hundred skeletons found in cemeteries such as East Smithfield in London, UK, and Heiligen Geist in Lübeck, Germany. Later the same authors write, “The Black Death killed up to 90% of the Medieval population of the Montpellier area [where their samples were found] within 30 years [referring to an unpublished source]. The human remains we obtained in a catastrophe grave were dated to be from the 14th century. Therefore, any remnant of this period has a 90% probability of being related to the Black Death. And the fact that the three skeletons we studied were lying in a common catastrophe grave enhances this probability”. This assertion is based on dubious assumptions. If the first several outbreaks of the Black Death in Montpellier did indeed kill 90% of the local population, this figure would greatly exceed estimates from other regions based on sources such as manorial court records and bishops’ registers of institutions to vacated benefices, estimates that generally fall below 50%. And even in the event that 90% of the standing population died during each of the various outbreaks of the Black Death during the 14th century, that is not equivalent to saying that 90% of all deaths over the course of the 14th century can be attributed to the Black Death. Therefore the claim that any skeletons from 14th-century Montpellier have a 90% probability of being related to the Black Death is a statistical non sequitur. If we further question the claim that the sampled skeletons come from a common catastrophe grave (rather than a slightly unusual non-catastrophe grave), and if we allow for a realistic degree of uncertainty in the dating of the grave, the association between their samples and the Black Death seems less certain. Another cause for concern is the possibility of laboratory contamination with modern yersinial DNA. Ancient DNA analysis is based on PCR, which renders it exquisitely sensitive to contamination by DNA from sources other than the intended samples. Raoult and Drancourt’s new method of “suicide PCR” is an important contribution because it eliminates re-amplification of past ancient DNA amplicons studied in the same laboratory, but it does not prevent accidental amplification of intact modern DNA. This fact would not be an issue if modern Y pestis DNA had never been present in Raoult and Drancourt’s lab. Raoult et al were careful to ensure that no modern Y pestis sequences were used (eg, as positive controls) in their study of the Montpellier skeletons, but an earlier paper reveals that DNA from Y pestis strain 6/69 M biotype orientalis had been used as a positive control in previous research in their laboratory. The PCR products reportedly obtained from the medieval skeletons were identical to the homologous sequences in that same modern strain—or at most differed from them at a single base pair. This fact in itself is not proof of contamination since all known modern strains of Y pestis share the same sequence for this portion of the pla gene. But it still leaves open the possibility of contamination by modern Y pestis DNA. A recent ancient DNA analysis of skeletons from East Smithfield, the only well-documented mid-14thcentury Black Death cemetery ever excavated, failed to recover any sequences specific to Y pestis. It is, of course, difficult to interpret negative results, especially in ancient DNA analysis, but it is perhaps relevant that this particular research group had never used modern yersinial sequences as positive controls in their laboratory (M B Prentice, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London, UK, personal communication). We suggest, therefore, that the ancient DNA work of Raoult, Drancourt, and their colleagues stands in need of replication and should not forestall further research on the cause of the Black Death. We agree with Graham Twigg that recent epidemiological studies of the Black Death point to a pathogen very different from modern Y pestis. In view of the intervening 650-year period of microbial evolution, we suggest that the Black Death pathogen is unlikely to exist in anything like its original form.