30 August 2011

Finding the bad guys

Nicholas Wade has an article in The New York Times about the bubonic plague:
Beneath the Royal Mint Court, diagonally across the street from the Tower of London, lie 1,800 mute witnesses to the foresight of the city fathers in the year 1348. Recognizing that the Black Death then scourging Europe would inevitably reach London, the authorities prepared a special cemetery in East Smithfield, outside the city walls, to receive the bodies of the stricken.
By autumn, the plague arrived. Within two years, a third or so of London’s citizens had died, a proportion similar to that elsewhere in Europe. The East Smithfield cemetery held 2,400 of the victims, whose bodies were stacked five deep.
The agent of the Black Death is assumed to be Yersinia pestis, the microbe that causes bubonic plague today. But the epidemiology was strikingly different from that of modern outbreaks. Modern plague is carried by fleas and spreads no faster than the rats that carry them can travel. The Black Death seems to have spread directly from one person to another.
Victims sometimes emitted a deathly stench, which is not true of plague victims today. And the Black Death felled at least thirty percent of those it inflicted, whereas a modern plague in India that struck Bombay in 1904, before the advent of antibiotics, killed only three percent of its victims.
These differences, as well as the fear that the Black Death might re-emerge, have prompted several attempts to retrieve DNA from Black Death cemeteries. The latest of these attempts is reported in the Proceedings of the National Academy of Sciences by a team led by Hendrik N. Poinar of McMaster University in Ontario, Canada and Johannes Krause of the University of Tübingen in Germany.
They looked for surviving fragments of DNA in bones and teeth that archaeologists had excavated from the East Smithfield site in the 1980s. The DNA matched that of the modern-day microbe, confirming, as have several other studies, that Yersinia pestis was indeed the agent of the Black Death. Sharon DeWitte, a member of Dr. Poinar’s team, was one of several skeptics who had doubted the microbe’s role. “I’m very happy to find out I was wrong,” said Dr. DeWitte, a paleodemographer at the University of South Carolina. “In science, if you’re open to alternative possibilities, you can change your mind.”
Dr. Poinar’s team also looked for the microbe’s DNA in another medieval London cemetery, that of St. Nicholas Shambles, which was closed before the Black Death struck. They found no sign of it there, indicating that Yersinia pestis was not already present in the English population before the Black Death, so it must have arrived from elsewhere.
If Yersinia pestis was indeed the cause of the Black Death, why were the microbe’s effects so different in medieval times? Its DNA sequence may hold the answer. Dr. Poinar’s team has managed to reconstruct a part of the microbe’s genetic endowment. Yersinia pestis has but a single chromosome, containing the bulk of its genes, and three small circles of DNA known as plasmids.
The team has determined the full DNA sequence of the plasmid known as pPCP1 from the East Smithfield cemetery. But, disappointingly, it turns out to be identical to the modern-day plasmid, so it explains none of the differences in the microbe’s effects.
“It was probably a naïve approach to assume we’d get the smoking gun on first attempt,” Dr. Poinar said.
Mark Achtman, an expert on plague who works at University College Cork in Ireland, said that the new study was “technologically interesting” but that a great deal more of the microbe’s DNA needed to be sequenced to obtain scientifically important results.
This is indeed Dr. Poinar’s plan. The challenge in reconstructing the microbe’s DNA from the East Smithfield cemetery is that it is highly fragmented. The Yersinia pestis chromosome is 4,653,728 units of DNA in length, but the bits of DNA from the cemetery are no more than fifty to sixty units long.
Determining the order of the chemical units in such fragments has become possible only in the last few years with the development of new DNA sequencing machines that work with short fragments.
Another technical challenge is to separate the plague DNA from that of the human and other microbial DNA in the ancient bones. One technique that Dr. Poinar’s team has used is to tether plasmid DNA from the modern plague microbe to plastic beads. DNA is quick to bind to strands of DNA of the complementary sequence, as in the DNA double helix. So the beads act as fishing rods to pull out the DNA of interest.
“It’s probably exceptionally important to find out what made this bug so deadly in the past,” Dr. Poinar said.
Rico says they're ignoring certain facts about medieval life: people had fleas, and were in poor health generally. Once you got sick, you were easily dead...

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