Correspondence
Yersinia pestis and the three plague pandemics The recent Article by David Wagner and colleagues1 reports the sequencing of a draft genome of Yersinia pestis extracted from two bodies interred at Aschheim, Bavaria, in the late 6th century CE.2 However, this study goes beyond the genetic analysis of these remains to make claims about the three known plague pandemics: the Justinianic (541–750), the Black Death, which began in the 1340s, and the third pandemic, usually dated from the start of its spread around the globe from Hong Kong in 1894. Three of these claims are unproven and problematic: that the pathogen travelled overland from China towards Europe in the 6th century; that the strain associated with the second pandemic travelled from Europe or north Africa to central Africa via trade routes along the Nile river; and that it “spread back to China from Europe (or northern Africa)”, eventually giving rise to the strains that caused the third pandemic. These contentions are also argued visually in a map (figure 4 in the Article1). The investigators assert that “Historical records are consistent with this scenario…”, and yet only one historical work is cited: a 1951 study by WHO3 that, in our opinion, does not support any of these claims. The first claim, of overland spread from the Qinghai plateau to Europe and north Africa during the first pandemic, although plausible, has not yet been proven. Meanwhile, Wagner and colleagues ignore substantial written evidence that the pathogen first arrived in the Mediterranean basin in the eastern Nile delta via the Red Sea, and spread from there throughout the Near East, the Byzantine empire, and the former western provinces of the Roman empire.4 As for the route by which the 1.ANT strain reached central Africa, to our knowledge, this has never been debated in the historical 918
literature and no evidence to support the theory that it came directly from the Mediterranean basin is offered here. We contend that such a route seems implausible on the grounds that the Nile was not a navigable route from the Mediterranean Sea to central Africa in historical times.5,6 The third claim—transmission of strains on branch 1 of the phylogenetic tree from Europe back to territories now considered part of China—is supported by neither molecular data nor any written records known to us. All the modern specimens of 1.IN that were used in Yujun Cui and colleagues’ 2013 study7 came from Qinghai province, Xinjiang (Uyghur Autonomous Region), Tibet, Gansu, and Yunnan, and—aside from the human cases and one case in a dog—were sampled from animals native to those territories. In view of the present state of the evidence, we find no reason to think that Y pestis ever disappeared, even temporarily, from the regions of its origin. We declare no competing interests.
*Monica H Green, Lori Jones, Lester K Little, Uli Schamiloglu, George D Sussman [email protected] School of Historical, Philosophical, and Religious Studies, Arizona State University, Tempe, AZ, USA (MHG); School of Historical Studies, The Institute for Advanced Study, Princeton, NJ 08540, USA (MHG); Department of History, University of Ottawa, Ottawa, ON, Canada (LJ); Department of History, Smith College, Northampton, MA, USA (LKL); Department of Languages and Cultures of Asia, University of Wisconsin–Madison, Madison, WI, USA (US); and Department of Social Science, LaGuardia Community College, The City University of New York, Long Island City, NY, USA (GDS) 1
2
3
4
Wagner DM, Klunk J, Harbeck M, et al. Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis 2014; 14: 319–26. Wiechmann I, Grupe G. Detection of Yersinia pestis DNA in two early medieval skeletal finds from Ashheim (Upper Bavaria, 6th century AD). Am J Phys Anthropol 2005; 126: 48–55. Pollitzer R. Plague studies. 1. A summary of the history and survey of the present distribution of the disease. Bull World Health Org 1951; 4: 475–533. Little LK, ed. Plague and the end of antiquity: the pandemic of 541–750. Cambridge: Cambridge University Press, 2007: 7–15, 59–64, 101–03.
5
6
7
Jeal T. Explorers of the Nile: the triumph and tragedy of a great Victorian adventure. New Haven: Yale University Press, 2011. Chrétien JP. The Great Lakes of Africa: two thousand years of history, trans. S Straus. New York: Zone Books, 2003. Cui Y, Yu C, Yan Y, et al. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proc Natl Acad Sci USA 2013; 110: 577–82.
David Wagner and colleagues1 have reported their results of a genomic analysis of Yersinia pestis obtained from two individuals who died in the Justinian Plague, providing further supportive evidence that Y pestis did cause this plague epidemic. This clinically obvious fact was confirmed more than a decade ago by different molecular techniques. 2 We were interested to note that the technique used by Wagner and colleagues to extract DNA is the one that we described first in 1998,2 which uses dental pulp to establish the cause of illnesses detected in ancient corpses (work that was not cited in Wagner and colleagues’ study1). In 2004, Thomas Gilbert—who has written a Comment3 discussing Wagner and colleagues’ study—challenged the usefulness of our technique to identify Y pestis in teeth after he and his colleagues were unable to amplify Y pestis DNA from DNA extracted from teeth of potential plague victims,4 so we were grateful to see that he is now reaching the conclusion that no DNA was present in his plague victims’ samples. However, annoyingly, neither Wagner and colleagues nor Gilbert recognise that they started a debate that they are now closing themselves. We even asked colleagues to make a blind exchange of samples to resolve the debate of whether or not the Black Death was caused by Y pestis,5 which could have been resolved a long time ago, but Gilbert and collaborators have never accepted this offer. Scientific mistakes are common, but to acknowledge a study that confirmed our results without recognising our work2 is unusual, especially after having raised a debate of such a dimension, and having encouraged the idea that our results were false in the scientific literature. www.thelancet.com/infection Vol 14 October 2014
Correspondence
We declare no competing interests.
Michel Drancourt, *Didier Raoult [email protected] Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Émergentes (URMITE), UMR63 CNRS 7278, IRD 198, INSERM 1095, 13005 Marseille, France 1
2
3
4
5
Wagner DM, Klunk J, Harbeck M, et al. Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis 2014; 14: 319–26. Drancourt M, Aboudharam G, Signoli M, et al. Detection of 400-year-old Yersinia pestis DNA in human dental pulp: an approach to the diagnosis of ancient septicemia. Proc Natl Acad Sci USA 1998; 95: 12637–40. Gilbert MTP. Yersinia pestis: one pandemic, two pandemics, three pandemics, more? Lancet Infect Dis 2014; 14: 264–65. Gilbert MT, Cuccui J, White W, et al. Absence of Yersinia pestis-specific DNA in human teeth from five European excavations of putative plague victims. Microbiology 2004; 150: 341–54. Raoult D. Was the Black Death yersinial plague? Lancet Infect Dis 2003; 3: 328.
Authors’ reply Monica Green and colleagues take issue with three claims made in our Article1 because they say they are unproven. We suggested that Yersinia pestis might have travelled overland from China to Europe to cause the first plague pandemic, spread from Europe or north Africa to central Africa during the second plague pandemic leading to the establishment of the 1.ANT group, and spread back to Asia from Europe or north Africa giving rise to the 1.IN populations in China. We described these ideas as a viable explanation for the phylogeographic patterns that we noted and a “hypothetical scenario for the geographic spread of Yersinia pestis”. Green and colleagues might have had issue with our statement that “Historical records are consistent with this scenario…” possibly because they took this statement out of context or misunderstood our intent. Our intent was to point out that historical information, as recorded by Robert Pollitzer,2 describes the spread of plague from Yunnan province, China, starting around 1855. This spread of plague is widely considered to be the start of the third plague pandemic, which involved the eventual worldwide spread of the www.thelancet.com/infection Vol 14 October 2014
1.ORI group.3–5 We pointed out that the 1.IN3 group is also currently found in Yunnan province,4 where the third pandemic is thought to have originated. In addition to the co-occurrence of these groups in Yunnan province, we noted,1 as have others,4,5 that the most closely related group to the 1.ORI group is the 1.IN3 group (which is again the group associated with the third pandemic). Finally, we stated that Yujun Cui and colleagues4 reported that some 1.IN3 strains from Yunnan province possess the Orientalis phenotype, which is conserved in all known 1.ORI strains, but not identified in any other groups within Y pestis except these few 1.IN3 strains from Yunnan province. In view of all of these patterns, we suggested that the 1.IN populations could have given rise to the 1.ORI group. Science leads to advances by putting forth hypotheses that can be tested by subsequent studies. We never suggested that our ideas that are disputed by Green and colleagues were proven; rather, they are hypotheses that can be tested with additional sampling of ancient and contemporary Y pestis samples. Indeed, we are actively pursuing Y pestis samples that can be used to rigorously test these hypotheses and we encourage other researchers to do the same. We are confused by the comments made by Michel Drancourt and Didier Raoult who claim to have shown the microbial cause of the Justinianic plague in their 1998 paper, because that paper reports the potential presence of Y pestis in samples from 16th century France, which are 1000 years more recent than those described by us1 and from an entirely different pandemic. In a later study6 they claimed that the contemporary Orientalis biovar of Y pestis was found in teeth dating back to the Justinianic plague, which is at odds with our discovery of a unique lineage that is clearly distinct from lineages currently circulating in human and animal populations, as well as finding by others4,5 that the Orientalis biovar probably arose within the past
200–210 years and, therefore, is much too recent to have been associated with the Justinianic plague. The methods they used in this later study have also been questioned.7 Finally, despite claims to the contrary, the work of Drancourt and Raoult is not the first use of DNA from dental pulp.8 We declare no competing interests.
David M Wagner, Paul S Keim, Holger C Scholz, Edward C Holmes, *Hendrik Poinar [email protected] Department of Biological Sciences and Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA (DMW, PSK); Bundeswehr Institute for Microbiology, Munich, Germany (HCS); Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia (ECH); and McMaster Ancient DNA Centre, Department of Anthropology, McMaster University, Hamilton, ON L8S 4L8, Canada (HP) 1
2
3
4
5
6
7 8
Wagner DM, Klunk J, Harbeck M, et al. Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis 2014; 14: 319–26. Pollitzer R. Plague studies. 1. A summary of the history and survey of the present distribution of the disease. Bull World Health Organ 1951; 4: 475–533. Achtman M, Morelli G, Zhu P, et al. Microevolution and history of the plague bacillus, Yersinia pestis. Proc Natl Acad Sci USA 2004; 101: 17837–42. Cui Y, Yu C, Yan Y, et al. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proc Natl Acad Sci USA 2013; 110: 577–82. Morelli G, Song Y, Mazzoni CJ, et al. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat Genet 2010; 42: 1140–43. Drancourt M, Roux V, Dang LV, et al. Genotyping, Orientalis-like Yersinia pestis, and plague pandemics. Emerg Infect Dis 2004; 10: 1585–92. Vergnaud G. Yersinia pestis genotyping. Emerg Infect Dis 2005; 11: 1317–18. Potsch L, Meyer U, Rotschild S, Schneider P, Rittner CH. Application of DNA techniques for identification using human dental pulp as a source of DNA. Intl J Leg Med 1992; 105: 139–43.
Antibiotics for acute sore throat We read Paul Little and colleagues’ report 1 of their cohort study of antibiotic prescription strategies for acute sore throat with great interest. The authors conclude that in most patients, antibiotics are not needed, but that a delayed prescription 919
Yersinia pestis and the three plague pandemics The recent Article by David Wagner and colleagues1 reports the sequencing of a draft genome of Yersinia pestis extracted from two bodies interred at Aschheim, Bavaria, in the late 6th century CE.2 However, this study goes beyond the genetic analysis of these remains to make claims about the three known plague pandemics: the Justinianic (541–750), the Black Death, which began in the 1340s, and the third pandemic, usually dated from the start of its spread around the globe from Hong Kong in 1894. Three of these claims are unproven and problematic: that the pathogen travelled overland from China towards Europe in the 6th century; that the strain associated with the second pandemic travelled from Europe or north Africa to central Africa via trade routes along the Nile river; and that it “spread back to China from Europe (or northern Africa)”, eventually giving rise to the strains that caused the third pandemic. These contentions are also argued visually in a map (figure 4 in the Article1). The investigators assert that “Historical records are consistent with this scenario…”, and yet only one historical work is cited: a 1951 study by WHO3 that, in our opinion, does not support any of these claims. The first claim, of overland spread from the Qinghai plateau to Europe and north Africa during the first pandemic, although plausible, has not yet been proven. Meanwhile, Wagner and colleagues ignore substantial written evidence that the pathogen first arrived in the Mediterranean basin in the eastern Nile delta via the Red Sea, and spread from there throughout the Near East, the Byzantine empire, and the former western provinces of the Roman empire.4 As for the route by which the 1.ANT strain reached central Africa, to our knowledge, this has never been debated in the historical 918
literature and no evidence to support the theory that it came directly from the Mediterranean basin is offered here. We contend that such a route seems implausible on the grounds that the Nile was not a navigable route from the Mediterranean Sea to central Africa in historical times.5,6 The third claim—transmission of strains on branch 1 of the phylogenetic tree from Europe back to territories now considered part of China—is supported by neither molecular data nor any written records known to us. All the modern specimens of 1.IN that were used in Yujun Cui and colleagues’ 2013 study7 came from Qinghai province, Xinjiang (Uyghur Autonomous Region), Tibet, Gansu, and Yunnan, and—aside from the human cases and one case in a dog—were sampled from animals native to those territories. In view of the present state of the evidence, we find no reason to think that Y pestis ever disappeared, even temporarily, from the regions of its origin. We declare no competing interests.
*Monica H Green, Lori Jones, Lester K Little, Uli Schamiloglu, George D Sussman [email protected] School of Historical, Philosophical, and Religious Studies, Arizona State University, Tempe, AZ, USA (MHG); School of Historical Studies, The Institute for Advanced Study, Princeton, NJ 08540, USA (MHG); Department of History, University of Ottawa, Ottawa, ON, Canada (LJ); Department of History, Smith College, Northampton, MA, USA (LKL); Department of Languages and Cultures of Asia, University of Wisconsin–Madison, Madison, WI, USA (US); and Department of Social Science, LaGuardia Community College, The City University of New York, Long Island City, NY, USA (GDS) 1
2
3
4
Wagner DM, Klunk J, Harbeck M, et al. Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis 2014; 14: 319–26. Wiechmann I, Grupe G. Detection of Yersinia pestis DNA in two early medieval skeletal finds from Ashheim (Upper Bavaria, 6th century AD). Am J Phys Anthropol 2005; 126: 48–55. Pollitzer R. Plague studies. 1. A summary of the history and survey of the present distribution of the disease. Bull World Health Org 1951; 4: 475–533. Little LK, ed. Plague and the end of antiquity: the pandemic of 541–750. Cambridge: Cambridge University Press, 2007: 7–15, 59–64, 101–03.
5
6
7
Jeal T. Explorers of the Nile: the triumph and tragedy of a great Victorian adventure. New Haven: Yale University Press, 2011. Chrétien JP. The Great Lakes of Africa: two thousand years of history, trans. S Straus. New York: Zone Books, 2003. Cui Y, Yu C, Yan Y, et al. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proc Natl Acad Sci USA 2013; 110: 577–82.
David Wagner and colleagues1 have reported their results of a genomic analysis of Yersinia pestis obtained from two individuals who died in the Justinian Plague, providing further supportive evidence that Y pestis did cause this plague epidemic. This clinically obvious fact was confirmed more than a decade ago by different molecular techniques. 2 We were interested to note that the technique used by Wagner and colleagues to extract DNA is the one that we described first in 1998,2 which uses dental pulp to establish the cause of illnesses detected in ancient corpses (work that was not cited in Wagner and colleagues’ study1). In 2004, Thomas Gilbert—who has written a Comment3 discussing Wagner and colleagues’ study—challenged the usefulness of our technique to identify Y pestis in teeth after he and his colleagues were unable to amplify Y pestis DNA from DNA extracted from teeth of potential plague victims,4 so we were grateful to see that he is now reaching the conclusion that no DNA was present in his plague victims’ samples. However, annoyingly, neither Wagner and colleagues nor Gilbert recognise that they started a debate that they are now closing themselves. We even asked colleagues to make a blind exchange of samples to resolve the debate of whether or not the Black Death was caused by Y pestis,5 which could have been resolved a long time ago, but Gilbert and collaborators have never accepted this offer. Scientific mistakes are common, but to acknowledge a study that confirmed our results without recognising our work2 is unusual, especially after having raised a debate of such a dimension, and having encouraged the idea that our results were false in the scientific literature. www.thelancet.com/infection Vol 14 October 2014
Correspondence
We declare no competing interests.
Michel Drancourt, *Didier Raoult [email protected] Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Émergentes (URMITE), UMR63 CNRS 7278, IRD 198, INSERM 1095, 13005 Marseille, France 1
2
3
4
5
Wagner DM, Klunk J, Harbeck M, et al. Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis 2014; 14: 319–26. Drancourt M, Aboudharam G, Signoli M, et al. Detection of 400-year-old Yersinia pestis DNA in human dental pulp: an approach to the diagnosis of ancient septicemia. Proc Natl Acad Sci USA 1998; 95: 12637–40. Gilbert MTP. Yersinia pestis: one pandemic, two pandemics, three pandemics, more? Lancet Infect Dis 2014; 14: 264–65. Gilbert MT, Cuccui J, White W, et al. Absence of Yersinia pestis-specific DNA in human teeth from five European excavations of putative plague victims. Microbiology 2004; 150: 341–54. Raoult D. Was the Black Death yersinial plague? Lancet Infect Dis 2003; 3: 328.
Authors’ reply Monica Green and colleagues take issue with three claims made in our Article1 because they say they are unproven. We suggested that Yersinia pestis might have travelled overland from China to Europe to cause the first plague pandemic, spread from Europe or north Africa to central Africa during the second plague pandemic leading to the establishment of the 1.ANT group, and spread back to Asia from Europe or north Africa giving rise to the 1.IN populations in China. We described these ideas as a viable explanation for the phylogeographic patterns that we noted and a “hypothetical scenario for the geographic spread of Yersinia pestis”. Green and colleagues might have had issue with our statement that “Historical records are consistent with this scenario…” possibly because they took this statement out of context or misunderstood our intent. Our intent was to point out that historical information, as recorded by Robert Pollitzer,2 describes the spread of plague from Yunnan province, China, starting around 1855. This spread of plague is widely considered to be the start of the third plague pandemic, which involved the eventual worldwide spread of the www.thelancet.com/infection Vol 14 October 2014
1.ORI group.3–5 We pointed out that the 1.IN3 group is also currently found in Yunnan province,4 where the third pandemic is thought to have originated. In addition to the co-occurrence of these groups in Yunnan province, we noted,1 as have others,4,5 that the most closely related group to the 1.ORI group is the 1.IN3 group (which is again the group associated with the third pandemic). Finally, we stated that Yujun Cui and colleagues4 reported that some 1.IN3 strains from Yunnan province possess the Orientalis phenotype, which is conserved in all known 1.ORI strains, but not identified in any other groups within Y pestis except these few 1.IN3 strains from Yunnan province. In view of all of these patterns, we suggested that the 1.IN populations could have given rise to the 1.ORI group. Science leads to advances by putting forth hypotheses that can be tested by subsequent studies. We never suggested that our ideas that are disputed by Green and colleagues were proven; rather, they are hypotheses that can be tested with additional sampling of ancient and contemporary Y pestis samples. Indeed, we are actively pursuing Y pestis samples that can be used to rigorously test these hypotheses and we encourage other researchers to do the same. We are confused by the comments made by Michel Drancourt and Didier Raoult who claim to have shown the microbial cause of the Justinianic plague in their 1998 paper, because that paper reports the potential presence of Y pestis in samples from 16th century France, which are 1000 years more recent than those described by us1 and from an entirely different pandemic. In a later study6 they claimed that the contemporary Orientalis biovar of Y pestis was found in teeth dating back to the Justinianic plague, which is at odds with our discovery of a unique lineage that is clearly distinct from lineages currently circulating in human and animal populations, as well as finding by others4,5 that the Orientalis biovar probably arose within the past
200–210 years and, therefore, is much too recent to have been associated with the Justinianic plague. The methods they used in this later study have also been questioned.7 Finally, despite claims to the contrary, the work of Drancourt and Raoult is not the first use of DNA from dental pulp.8 We declare no competing interests.
David M Wagner, Paul S Keim, Holger C Scholz, Edward C Holmes, *Hendrik Poinar [email protected] Department of Biological Sciences and Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA (DMW, PSK); Bundeswehr Institute for Microbiology, Munich, Germany (HCS); Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia (ECH); and McMaster Ancient DNA Centre, Department of Anthropology, McMaster University, Hamilton, ON L8S 4L8, Canada (HP) 1
2
3
4
5
6
7 8
Wagner DM, Klunk J, Harbeck M, et al. Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis 2014; 14: 319–26. Pollitzer R. Plague studies. 1. A summary of the history and survey of the present distribution of the disease. Bull World Health Organ 1951; 4: 475–533. Achtman M, Morelli G, Zhu P, et al. Microevolution and history of the plague bacillus, Yersinia pestis. Proc Natl Acad Sci USA 2004; 101: 17837–42. Cui Y, Yu C, Yan Y, et al. Historical variations in mutation rate in an epidemic pathogen, Yersinia pestis. Proc Natl Acad Sci USA 2013; 110: 577–82. Morelli G, Song Y, Mazzoni CJ, et al. Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat Genet 2010; 42: 1140–43. Drancourt M, Roux V, Dang LV, et al. Genotyping, Orientalis-like Yersinia pestis, and plague pandemics. Emerg Infect Dis 2004; 10: 1585–92. Vergnaud G. Yersinia pestis genotyping. Emerg Infect Dis 2005; 11: 1317–18. Potsch L, Meyer U, Rotschild S, Schneider P, Rittner CH. Application of DNA techniques for identification using human dental pulp as a source of DNA. Intl J Leg Med 1992; 105: 139–43.
Antibiotics for acute sore throat We read Paul Little and colleagues’ report 1 of their cohort study of antibiotic prescription strategies for acute sore throat with great interest. The authors conclude that in most patients, antibiotics are not needed, but that a delayed prescription 919
