Category Archives: smallpox

Evolutionary Clues in 17th-Century Smallpox Genome

By Michelle Ziegler

Smallpox is one of those diseases long believed to have an ancient pedigree, the suspected culprit of legendary epidemics. Yet, so far, smallpox hasn’t made a big impression in ancient DNA surveys. If it was truly endemic throughout the Old World before 1492, so much so that it pops up in the New World almost immediately after contact, it’s odd that it has not been more prominent in ancient DNA surveys. Be ready for a smallpox paradigm shift and reexamination of its reputed history.

In December, Ana Duggan, Maria Perdomo, and the McMaster Ancient DNA Centre team announced the first full ancient smallpox genome isolated from a mummified 17th-century child in Vilnius, Lithuania. Radiocarbon dates of the child place him or her in the mid 17th century (est. c. 1654) in the midst of dated smallpox epidemics from all over Europe.

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Fig 1 (Duggan et al, 2016): Left: Distribution of smallpox records in Europe. Right upper: Dominican Church of the Holy Spirit, Vilnius. Lithuania. Right lower: Crypt containing the child’s remains.

Their finding was unexpected. They were not looking for smallpox at all; the child had no observable lesions. They were hoping to find JC polyomavirus, of particular interest to one of the co-authors, and so they first enriched the specimen for this virus (McKenna 2016). After detecting variola virus (VARV), smallpox, instead they then enriched for VARV to confirm the initial signal.

duggan_cbsmallpox_finalMore than just confirming the signal, they were able to reconstruct the entire genome producing the entire sequence at an average depth of 18X. The surprising child had more revelations in his or her viral sequence. The sequence is ancestral to all existing reference strains. This is consistent with short stretches of aDNA amplified from 300-year-old frozen Siberian remains (Biagini et al, 2012). Unfortunately, the sequences from 2012 were not distinctive enough from the new Lithuanian sequence to give phylogicial resolution between them. Oddly, the frozen Siberian remains also lacked smallpox skin lesions with one showing signs of pulmonary hemorrhages.

Its ancestral position in the phylogeny suggests that a severe bottleneck occurred before c. 1654. As Duggan et al (2016) remark, vaccination would cause a very strong bottleneck, but this occurs after 1654 and there is new diversity among the descendent reference specimens producing two major clades. Yet to be determined is the evolutionary effect of extensive variolation practices in the early modern period. In contrast to vaccination, variolation is a form of intentional smallpox transmission that sometimes went horribly wrong.

Evolution continues unabated. The molecular clock is consistent among the 20th-century specimens and the latest aDNA from the Lithuanian child. The two clades of smallpox collected from 20th-century specimens diverged from each other sometime around the mid-17th century after vaccination began. Interestingly, the less virulent Variola minor strain is not predicted to have emerged from Variola major clade P-II until the mid-19th century.

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Evolutionary history of Variola (Duggan et al, 2016)

It’s not entirely surprising that smallpox, a highly transmissive human-only virus, has a relatively recent last common ancestor; other viruses like measles do as well. Measles last common ancestor is probably in the early 20th century (Furuse, Suzuki & Oshitani, 2010). The dominance of the 1918 influenza strain in recent influenza phylogeny is another example; incomplete because influenza swaps genes with influenza viruses that are circulating primarily in birds, but also in swine and earlier in equines (Taubenberger & Morens, 2005). Improved transmission strains are likely to out-compete strains with a lower transmission rate if they achieve a global spread. For some viruses, though not necessarily all, improved transmissibility and virulence go hand in hand. So, in the end, the relatively recent last common ancestor says more about its global transmissibility than anything else.

The antiquity of the virus needs two components to estimate. The molecular clock must be steady, and it is so far (though this could change with more ancient specimens), and a near relative ‘out group’, related strains outside the Variola clade (a branch of the larger genetic tree). One potential problem here is that as transmissibility improves the clock may speed up. The speed of the clock is determined by the reproduction rate. The relatively steady clock back to this 17th-century specimen suggests that the transmission rate was pretty steady — after the evolutionary/transmission leap that swept aside other Variola strains. The inactivation of several orthopoxvirus genes in smallpox that are functional in vaccinia (used in smallpox vaccines), camelpox, and taterapox  (the ‘out groups’ used) may suggest that one or more of these genes had been protective. When the genes were inactivated, smallpox probably became a much more dangerous virus to humans.

Historical epidemiology suggests that there was once more variation in the virulence of smallpox epidemics.  Securely identifying smallpox epidemics in the historical record is much harder than is generally assumed, and it is harder yet to make a claim for a significant demographic impact prior to the Renaissance (Carmichael & Silverman, 1987). This is the problem with theories that smallpox was the cause of the second-century Antonine plague and then failed to cause an epidemic with a major demographic effect for many centuries. I find this very hard to believe. Additionally, the infamous smallpox epidemics in the New World are now also be reevaluated in ways that diminish smallpox’s toll and add in a wide variety of contributing factors to produce a colonization syndemic. This has most recently been summarized in essays collected in Beyond Germs: Native Depopulation in North America (2015).

One other observation from these studies: All ancient smallpox DNA to date has been extracted from mummy tissue, not a tooth or bone. This may point toward one of the limitations of ancient DNA pathogen surveys that currently use primarily teeth. Since neither mummy had visible smallpox lesions, smallpox should be considered a possibility in any mummy.


References

Duggan, A. T., Perdomo, M. F., Piombino-Mascali, D., Marciniak, S., Poinar, D., Emery, M. V., et al. (2016). 17th Century Variola Virus Reveals the Recent History of Smallpox. Current Biology, 1–7. http://doi.org/10.1016/j.cub.2016.10.061

Biagini, P., Thèves, C., Balaresque, P., Géraut, A., Cannet, C., Keyser, C., et al. (2012). Variola virus in a 300-year-old Siberian mummy. The New England Journal of Medicine, 367(21), 2057–2059. http://doi.org/10.1056/NEJMc1208124

McKenna, Maryn (8 Dec 2016) Child Mummy Found with Oldest Known Smallpox Virus. National Geographic. (online)

Carmichael, A. G., & Silverstein, A. M. (1987). Smallpox in Europe before the seventeenth century: virulent killer or benign disease? Journal of the History of Medicine and Allied Sciences, 42(2), 147–168.

Furuse Y, Suzuki A, & Oshitani H (2010). Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries. Virology journal, 7 PMID: 20202190

Taubenberger, J. K., & Morens, D. M. (2005). 1918 Influenza: the mother of all pandemics. Emerging Infectious Diseases, 12(1), 15–22. http://doi.org/10.3201/eid1201.050979

Beyond Germs: Native Depopulation in North America. Edited by Catherine Cameron, Paul Kelton, and Alan Swedlund. University of Arizona Press, 2015.

Beyond Germs: Native Depopulation in North America

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Beyond Germs: Native Depopulation in North America. Edited by Catherine Cameron, Paul Kelton and Alan Swedlund. University of Arizona Press, 2015.


With the number of emerging infectious diseases climbing and new revelations about plague’s past, this book is a timely caution to the rhetoric surrounding so-called virgin soil epidemics. This book is the publication of an interdisciplinary conference held to discuss the causes of Native American depopulation hosted by the Amerind Foundation. Essays by David Jones, George Milner, Clark Spenser Larsen, Debra Martin, Gerardo Gutiérrez, Alan Swedlund, Catherine Cameron, Paul Kelton, Katheleen Hull, and James Brooks are included. Most of these essays are case studies in depopulation of specific areas.

David Jones opens the book with a discussion of the rhetoric surrounding so-called virgin soil epidemics that are credited with being the primary cause of native depopulation. Admitting the influence of his mentor evolutionary biologist Stephan J Gould, Jones favors social and contingent causes for depopulation over biological determinism. Perhaps the influential role that Gould played in my own formation as a biologist makes me sympathetic to Jones’ argument, but I can certainly live with that. Genetic determinism, in my opinion, is the easy way out to explain what can not be yet understood. His argument against the sweeping rhetoric of ‘virgin soil epidemics’ is, I think, very effective.

Milner’s chapter tackles the tricky problem of the pre-contact population collapse of the Mississippian culture centered at the mid-continent site of Cahokia, near St. Louis. This had been the largest and most (archaeologically) complex native culture in North America but it collapsed so entirely that the mid-continent was still sparsely populated when Europeans arrived a couple of centuries later. Medieval Cahokia had been more populous than  contemporary London. The example of Cahokia must give us pause for assuming that unrecorded demographic collapses that lack signs of massive destruction must be due to epidemics.

Larsen, Martin, Gutiérrez, and Hull cover the effect of the Spanish mission system in Florida, the Pueblo of the Southwest,  Mexico, and California respectively. Structural violence was seen throughout the Spanish mission system from hard, forced labor. Larsen discusses the changed how changed landscapes and lifestyles make natives more susceptible to infection. He sees a dramatic rise in cribra orbitalis/porotic hyperostosis as a sign of iron deficiency when it may actually be malaria. Wet Florida would have been susceptible to endemic malaria and a reservoir for it to spread through the southeast. Martin looks at the bioarchaeological evidence for a ‘creeping genocide’ in the peublos of the south west. Sporatic massacres of pueblo communities was used to enforce compliance by the wider culture. Cultural resilience was also stressed to the breaking point by a prolonged period of drought and environmental deterioration in the southwest that left them with marginal nutritional sufficiency. In this stressed environment, smallpox spread widely among the pueblo communities. Epidemics were part of a set of practices used to destroy or reorient native culture to make it acceptible, and more importantly controllable for the Spanish. Gutiérrez focuses on the methods and effects of identity erasure on demographics. The caste system that developed was very systematic “virtuous cycle”  with the goal of eliminating native identiy and indeed native (and African) ‘blood’ while maximizing Spanish identity and ‘blood’.

Chapters by Swedlund,  Cameron, and Kelton  examine tribes that dealt more closely with the English colonies and early American states. Swedlund looks at the great smallpox epidemic of 1633-34 beyond coastal New England up into the Connecticutt River valley. Cameron reviews the demographic effects of warfare and captive taking had on the Southeast, the northern Pays d’en Haunt (Great Lakes region), and the Southwest tribes. Colonial politics and trade caused more intertribal warfare than warfare directly with European colonists. Kelton writes about the disastrous experiences of the Cherokee with warfare, famine, and disease during the American Revolutionary War.

On of the overarching problems is the difficulty in determining population size before contact and then for the first couple centuries of the colonial period. Problematically, in the past abandoned villages have been assumed to be extinct due to disease rather than simply relocation or the movement of refugees to other tribes. The reality is that many areas that are fertile with Old World methods and domestic livestock were very difficult to make productive with native resources.

Over arching themes that I noticed which point toward other factors than just “germs” causing depopulation:

  1.  Use of starvation as an intentional weapon accomplished by burning fields and disrupting the agricultural cycle.
  2. Selective taking of women of reproductive age as captives/slaves causing a gender imbalance that prevented populations from rebounding.
  3. Selling captives to slavers rather than incorporating them into the tribe as pre-contact tribes often did to bolster their numbers and replace their dead. Sales were often to repay debts for European trade goods, especially weapons and ammunition.
  4.  Use of tribes as proxy militias by European powers to create intertribal warfare and recruitment of tribes by the British during the American revolution and war of 1812. Set up an adversarial relationship with the young American nation.
 In effect, I think the process they are all searching for is a syndemic that combined epidemics, nutritional deficiencies, systemic violence, slavery, and forced assimilation. Unfortunately they didn’t really consult the syndemic literature.

One of the things I took away from this collection is an appreciation for how long it takes to develop a fully agricultural culture. Many Native American groups were still in transition. Lacking domestic animals other than the dog, they were very vulnerable to climate and social disorder disrupting their agricultural cycle and yield. Some tribes adopted domestic animals from Europeans quickly. Colonists were greatly alarmed at how quickly the Cherokee adopted raising hogs and European crops, bringing them nutritional stability. Of course, horses are were adopted so well by natives that its hard for many of us today to even think of Native Americans without them.  The idea that domestic animals were worth the effort may have been what was missing most, rather than a lack of animals capable of being domesticated.

I highly recommend this book for anyone interested the dynamics of depopulation, “dark ages”, and most importantly for comparison to other “virgin soil” epidemic situations. I don’t think it’s a coincidence that other renowned virgin soil epidemics like the first and second plague pandemics occurred in times of ecological and social stress in addition to the epidemic in question. By opening the explanations for Native American depopulation up to other causes than disease,  it also opens up views into colonial life that even contemporaries tried to ignore. Wether their demise to disease was believed by contemporaries to be divine will or by modern historians as biological determinism, it has diverted attention away from the very human causes of depopulation and in some cases genocide.

Autumn Reading

Autumn 15

While autumn is not officially over yet, December always seems like winter to me so here is my reading review from autumn.
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This season I’m introducing a book review rating system. On my scale, an average book would get three scopes; a good book, four; and only the extraordinary book gets five scopes. I probably will not rate translations because I don’t feel qualified to evaluate them.

Books

Paul Kelton. Epidemics and Enslavement: Biological Catastrophes in the Native Southeast, 1492-1715. University of Arizona Press, 2007.   microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)

Catherine Cameron, Paul Kelton, and Alan Swedlund, eds. Beyond Germs: Native Depopulation in North America. U of Arizona Press, 2015. microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)

Pseudo-Dionysius of Tel-Mahre: Chronicle, Part III edited by Withold Witakowski, Liverpool University Press, 1997. (includes the largest section of John of Ephesus’ Church History/History of the Plague)

Zlata Blažina Tomic and Vesna Blažina  Expelling the Plague: The Health Office and the Implementation of Quarantine in Dubrovnik, 1377-1533. McGill-Queens University Press, 2015.microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)

Dorothy Crawford. Deadly Companions: How Microbes Shaped Our History. Oxford University Press, 2007. microscope23 (1)microscope23 (1)microscope23 (1)

Susan Mattern. The Prince of Medicine: Galen in the Roman Empire. Oxford University Press, 2013. microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)

Papers

Meier, D. (2004). Man and environment in the marsh area of Schleswig–Holstein from Roman until late Medieval times. Quaternary International, 112(1), 55–69. http://doi.org/10.1016/S1040-6182(03)00065-X

 

Stanley, J.-D., Bernasconi, M. P., & Jorstad, T. F. (2008). Pelusium, an Ancient Port Fortress on Egypt’s Nile Delta Coast: Its Evolving Environmental Setting from Foundation to Demise. Journal of Coastal Research, 242, 451–462. http://doi.org/10.2112/07A-0021.1

Schats, R. (2015). Malaise and mosquitos: osteoarchaeological evidence for malaria in the medieval Netherlands. Analecta Praehistoricaleidensia, 45, 133–140.

MacMaster, T. J. (2015). “Not With a Bang?” The Economics of Trade and the End of Byzantine North Africa. In M. Di Rodi, P. Frankopan, M. Lau, & C. Franchi (Eds.), Landscapes of Power: Selected Papers From the XV Oxford University Byzantine Society International Graduate Conference (pp. 73–91).

SHWARTZ, L. (2013). Gargano Comes to Rome: Castel Sant“Angelo”s Historical Origins. The Journal of Ecclesiastical History, 64(03), 453–475. http://doi.org/10.1017/S0022046912001704 (Blogged about here: St Michael, the Plague and Castel Sant’ Angelo,  in 2012 after his Kalamazoo talk. I just found in in print much as I remembered in the blog post.)

Rasmussen, S., Allentoft, M. E., Nielsen, K., Orlando, L., Sikora, M., Sjögren, K.-G., et al. (2015). Early Divergent Strains of Yersinia pestis in Eurasia 5,000 Years Ago. Cell, 163(3), 571–582. http://doi.org/10.1016/j.cell.2015.10.009 (See the previous post on this blog!)

Sun, Y.-C., Jarrett, C. O., Bosio, C. F., & Hinnebusch, B. J. (2014). Retracing the Evolutionary Path that Led to Flea-Borne Transmission of Yersinia pestis. Cell Host and Microbe, 15(5), 578–586. http://doi.org/10.1016/j.chom.2014.04.003

McCormick, M. (2015). Tracking mass death during the fall of Rome’s empire (I). Journal of Roman Archaeology, 28, 325–357.

Daniel Melleno. (2014) North Sea Networks: Trade and Communication from the Seventh to the Tenth Century. Comitatus. 45:65-90.

microscope23 (1)Icon made by Freepik from www.flaticon.com