Looking back on the autumn

fall-2016

This fall was quite the chaotic jumble — not all bad. One project successfully completed. A door closed but I think another better one may be opening. Somehow in the midst of all this I managed to do a little reading, so here is what that stood out for the fall (and early winter).

My publications

Ziegler, M. (2016) Landscapes of DiseaseLandscapes, 17.2. 99-107. An introduction to the concept of ‘landscapes of disease’ and the articles in the issue. (Open access)

Ziegler, M. (2016) Malarial Landscapes in Late Antique Rome and the Tiber Valley  Landscapes, 17.2: 139-155.

Books

  • Yong, Ed. (2016) I Contain Multitudes: The Microbes Within Us and a Grander View of Life. Ecco.  microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)
  • Holland, John. (2014) Complexity: A Short Introduction. OUP microscope23 (1)microscope23 (1)microscope23 (1)
  • Bronton, Jerry (2004) The Renaissance: A Short Introduction. OUP. microscope23 (1)microscope23 (1)microscope23 (1)
  • Tim Clarkson (2016) Scotland’s Merlin: A Medieval Legend and It’s Dark Age Origins. John Donald/Birlinn.      microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)
  • Hamerow, Helena. (2012) Rural Settlements and Society in Anglo-Saxon England. OUP. microscope23 (1)microscope23 (1)microscope23 (1)microscope23 (1)

Articles

  • Arnold, E. F. (2017). Rivers of Risk and Redemption in Gregory of Tours’ Writings. Speculum, 92(1), 117–143. http://doi.org/10.1086/689460
  • Arnold, E. F. (2014). Fluid Identities: Poetry and the Navigation of Mixed Ethnicities in Late Antique Gaul. Ecozon@, 1–19.
  • Bahl, J., Pham, T. T., Hill, N. J., Hussein, I. T. M., Ma, E. J., Easterday, B. C., et al. (2016). Ecosystem Interactions Underlie the Spread of Avian Influenza A Viruses with Pandemic Potential. PLoS Pathogens, 12(5), e1005620–20. http://doi.org/10.1371/journal.ppat.1005620
  • 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.

  • 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
  • Fauci, A. S., & Morens, D. M. (2016). Zika virus in the Americas—yet another arbovirus threat. New England Journal of Medicine, 374(7), 601–604.

  • Jones, L. (2016). The Diseased Landscape: Medieval and Early Modern Plaguescapes. Landscapes, 17(2), 108–123. http://doi.org/10.1080/14662035.2016.1251102
  • Marciniak, S., Prowse, T. L., Herring, D. A., Klunk, J., Kuch, M., Duggan, A. T., et al. (2016). Plasmodium falciparum malaria in 1st–2nd century CE southern Italy. Current Biology, 26(23), R1220–R1222. http://doi.org/10.1016/j.cub.2016.10.016
  • Slavin, P. (2016). Epizootic Landscapes: Sheep Scab and Regional Environment in England in 1279–1280. Landscapes, 17(2), 156–170. http://doi.org/10.1080/14662035.2016.1251040
  • Valtuena, A. A., Mittnik, A., Massy, K., Allmae, R., Daubaras, M., Jankauskas, R., et al. (2016). The Stone Age Plague: 1000 years of Persistence in Eurasia. BioRxiv Preprint, 28. http://doi.org/10.1101/094243
  • Walsh, M. G., Amstislavski, P., Greene, A., & Haseeb, M. A. (2016). The Landscape Epidemiology of Seasonal Clustering of Highly Pathogenic Avian Influenza (H5N1) in Domestic Poultry in Africa, Europe and Asia. Transboundary and Emerging Diseases, 1–14. http://doi.org/10.1111/tbed.12537
  • Whittemore, K., Tate, A., Illescas, A., & Saffa, A. (2017). Zika Virus Knowledge among Pregnant Women Who Were in Areas with Active Transmission. Emerging Infectious …. http://doi.org/10.3201/eid2106.150270

  • Yue, R. P. H., Lee, H. F., & Wu, C. Y. H. (2016). Navigable rivers facilitated the spread and recurrence of plague in pre-industrial Europe. Scientific Reports, 1–8. http://doi.org/10.1038/srep34867

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 teterapox  (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.

The Pathogen Buzz of 2016

by Michelle Ziegler

Altmetrics recently released the Top 100 scholarly articles list for the year (captured on 15 Nov 2016). Their ranking captures the public discussion on academic articles judged by shares of the online edition, news articles, blog posts and tweets that include the digital object identifier code (doi). (So if you want to improve the Altmetrics number of your papers make sure that all blog posts/tweets/news articles have the doi somewhere.) Note that generating discussion is not the same as being the best papers produced. At least one one this list, on ‘Patient 0’ HIV-1,  seemed to generate a fair amount of complaints.

Overall, the list was dominated by medical and health science (49) and biological science (14), altogether being 63% of the top 100 articles. Some of the other categories are a little vague, such as physical science (6) vs. earth and environmental science (6) vs. material science (1). History and archaeology combined to produce only six of the top 100 and one of them, on the ‘Tully monster’, really should be paleontology (or biology?). We also have to keep in mind that Altmetrics misses most of the humanities journals. The Altmetric scores in the top hundred have also approximately doubled between 2014 and 2016. The lowest score in 2016 is 1605 and the lowest score in 2014 was only 746.

One highlight this year is that 47% of the top 100 were either freely available or open access. I noticed about midway through this past year that papers expected to get a lot of attention were often freely available or open access. The difference between freely available vs open access may be whether or not the authors had to pay for the open availability (?). I wonder if the freely available remain free forever, or only until the news dies down?

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Zika vector Aedes aegypti (Courtesy of CDC/Public Health Image Library #9261)

When it comes to pathogens, this year’s list comes with the distinctive buzz of a mosquito, Aedes aegypti, carrying this year’s emerging infectious disease, the Zika virus. Of the twelve papers directly related to infection, six are on Zika. Looking at the 2015 list, it’s clear that Zika put pathogens in the news this year. There are hardly no pathogen related papers in the 2015 list and in 2014, there were only five  – four on ebola and one on ancient Yersinia pestis. So clearly Zika has made a far bigger splash than even the much more lethal ebola.

Pathogens in the 2016 Top 100:

6. Rasmussen, S. A., Jamieson, D. J., Honein, M. A., & Petersen, L. R. (2016). Zika virus and birth defects—reviewing the evidence for causality. New England Journal of Medicine, 374(20), 1981-1987. DOI: 10.1056/nejmsr1604338

17. Zipperer, A., Konnerth, M. C., Laux, C., Berscheid, A., Janek, D., Weidenmaier, C., … & Willmann, M. (2016). Human commensals producing a novel antibiotic impair pathogen colonization. Nature, 535(7613), 511-516. DOI: 10.1001/jama.2016.0287

19. Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., … & Hotchkiss, R. S. (2016). The third international consensus definitions for sepsis and septic shock (sepsis-3). Jama, 315(8), 801-810.17. DOI: 10.1001/jama.2016.0287

20. Mlakar, J., Korva, M., Tul, N., Popović, M., Poljšak-Prijatelj, M., Mraz, J., … & Vizjak, A. (2016). Zika virus associated with microcephaly. New England Journal of Medicine, 374(10), 951-958. DOI: doi/10.1056/NEJMoa1600651

 
25. Miranda, R. C., & Schaffner, D. W. (2016). Longer contact times increase cross-contamination of Enterobacter aerogenes from surfaces to food. Applied and Environmental Microbiology, 82(21), 6490-6496. DOI:10.1128/aem.01838-1620.

31. McGann, P., Snesrud, E., Maybank, R., Corey, B., Ong, A. C., Clifford, R., … & Schaecher, K. E. (2016). Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First report of mcr-1 in the USA. Antimicrobial agents and chemotherapy. DOI: 10.1128/aac.01103-16

 
37. Cao-Lormeau, V. M., Blake, A., Mons, S., Lastère, S., Roche, C., Vanhomwegen, J., … & Vial, A. L. (2016). Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. The Lancet, 387(10027), 1531-1539. DOI: 10.1016/s0140-6736(16)00562-6

46. Worobey, M., Watts, T. D., McKay, R. A., Suchard, M. A., Granade, T., Teuwen, D. E., … & Jaffe, H. W. (2016). 1970s and ‘Patient 0’HIV-1 genomes illuminate early HIV/AIDS history in North America. Nature, 539(7627), 98-101. DOI: 10.1038/nature19827

49. Fauci, A. S., & Morens, D. M. (2016). Zika virus in the Americas—yet another arbovirus threat. New England Journal of Medicine, 374(7), 601-604. DOI: 10.1056/nejmp1600297

54. Tang, H., Hammack, C., Ogden, S. C., Wen, Z., Qian, X., Li, Y., … & Christian, K. M. (2016). Zika virus infects human cortical neural progenitors and attenuates their growth. Cell stem cell, 18(5), 587-590. DOI: 10.1016/j.stem.2016.02.016

86. Liu, Y. Y., Wang, Y., Walsh, T. R., Yi, L. X., Zhang, R., Spencer, J., … & Yu, L. F. (2016). Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. The Lancet Infectious Diseases, 16(2), 161-168.54. DOI: 10.1016/S1473-3099(15)00424-7

92. Brasil, P., Pereira, Jr, J. P., Raja Gabaglia, C., Damasceno, L., Wakimoto, M., Ribeiro Nogueira, R. M., … & Calvet, G. A. (2016). Zika virus infection in pregnant women in Rio de Janeiro—preliminary report. New England Journal of Medicine. DOI: 10.1056/NEJMoa1602412

Before we leave the buzz of 2016, we have to mention this year also saw the passing of Dr. Donald Henderson (1928-2016) who led the effort to eradicate smallpox. Henderson died in August; his obituary from the New York Times can be found here.

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Henderson administering a smallpox vaccine in about 1972 (WHO).