Wednesday, September 10, 2014

A Modern Solution to an Ancient Problem

Eight centuries before the Black Death, a plague swept through the Byzantine Empire and then Europe with devastating consequences. More than 100 million people were killed from the 6th to 8th centuries in a pandemic known as the Plague of Justinian, or the first pandemic. Until last year, the cause of the disease was disputed, with arguments ranging from influenza to smallpox. Dave Wagner, an associate professor at Northern Arizona University, worked with scientists from around the world to confidently identify the bacterium Yersinia pestis as the cause of the pandemic.

Their work began in an ancient cemetery in Aschheim, Germany, a village near Munich. German archaeologists extracted DNA from the teeth of two skeletons believed to be victims of the Plague of Justinian. Using radiocarbon dating methods, they were able to date the graves to around 540 A.D. Despite issues with DNA fragmentation and contamination -- 1500-year-old DNA is not in the same condition as our modern DNA -- Wagner and his colleagues isolated crucial pathogen DNA.

“We pulled DNA out and were able to develop a whole genome sequence, which allowed us to then place that strain from the first pandemic in the family tree,” Wagner said.

This pathogenic family tree has some very interesting members. Y. pestis is now implicated as the cause of the first pandemic (Plague of Justinian, 6th-8th centuries), the second pandemic (14th-17th centuries, including the Black Death), and the third pandemic (modern plague, 19th century to present). Yersinia pestis certainly has a dramatic place in history, but what is the interest or use in studying ancient diseases? The answer lies in the collections used.

“DNA collections, strain collections, and even animal collections,” Wagner said, “are important to the research that we do.”

Large DNA collections allow Wagner and his team to have a kind of library within which they can place their research. His lab “fingerprints” Y. pestis DNA by analyzing the specific DNA sequence that differ among strains. By understanding the evolution, history, and genetic relation to other Y. pestis strains, Wagner was able to identify the Justinian strain as completely unique. This evolutionary history of a family tree, or phylogeny, is a powerful tool that can track a pathogen in both time and space.

Both live-strain and museum collections allow Wagner to track from where and when a particular disease came. All three pandemics, he believes, originated in China or surrounding regions and spread via the help of humans. Their methods used to study plague both in ancient populations and in modern day prairie dogs allows them to prepare for a human outbreak.

“When we start observing plague die-offs in prairie dogs, there’s plague activity on the landscape,” Wagner said.

He is also aware of how Y. pestis might be used in a bioterrorism event. The work his lab does is “for developing tools for biodefense application.” Fortunately, antibiotics are very effective against the plague, so access to good health care during outbreaks can quickly halt its progress.

Safeguarding against bioterrorism is certainly important, but Wagner’s work is also pertinent on a basic level of disease research. Plague has appeared from natural reservoir populations multiple times, each with a slightly different genetic signature. If we can track the travel patterns of an ancient disease through fossils, museum collections, and DNA samples, we might be able to predict the pattern of a future outbreak.

References:

David Wagner et al. Yersinia pestis and the Plague of Justinian 541-543 AD: a genomic analysis. The Lancet, 2014; http://dx.doi.org/10.1016/S1473-3099(13)70323-2.

Plague History. (n.d.). In Centers for Disease Control and Prevention online. Retrieved from http://www.cdc.gov/plague/history/index.html.




Glossary

pandemic
An outbreak of a disease over a wide geographic range (over a country or the world) and affecting a high proportion of the population.
phylogeny
The history of how a species or group has evolved over time.
natural reservoir
The long-term host of a disease pathogen. Natural reservoirs of the plague are wild rodents, such as prairie dogs and black rats that carry Y. pestis infected fleas.

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