Many of us may have had our first introduction to medieval history
thought this great Monty Python movie. And as is their nature, this bit from “The
Holy Grail” is pretty accurate. The Black Death, the epidemic of plague that
ripped through medieval England and Europe, killed thousands of people and led
to creation of the middle class (people were finally in demand once 30-60% of
them died). But I digress. The reason I’m writing about the Black Death is
because a paper came out last week in the journal Nature describing a new genomic analysis of bacterial DNA samples
collected from infected people buried in a cemetery outside of London. There was a great summary paper published in the same issue that
described what the current paper found and some of the controversies that exist
between scientists in this field. I highly recommend reading this, I think it
is very widely accessible. Below I discuss some of the things I learned from
the papers and why I think it’s interesting. (Note: unless you have access through a university you may not be able to see the primary source paper. Hopefully everyone can get to the summary paper, though)
First, a little background. Bubonic plague is caused by a
flea-vectored bacteria, Yersinia pestis.
Human cases of the plague are rare but still occur (are easily treatable with antibiotics)
but plague epidemics are a big problem in some wildlife populations, such as
prairie dogs in the American west. The Black Death describes the plague epidemic
that occurred in Europe between 1347-1351. Since the sanitation conditions in a
big city like London was probably more abysmal that we can imagine today, you
can expect there to be fleas everywhere. So, the main questions people studying
these old strains of the bacteria are trying to answer are, Why did the Black
Death kill so many people?, and Why are cases today much less severe than
symptoms described during this ancient period?
Two hypotheses that tried to explain these observed
differences between the 14th century plague and cases today are that
the Black Death wasn’t actually caused by Yersinia
and that a more virulent strain of the bacteria was the culprit for the deaths
during medieval times. The first of these hypotheses was rejected when Y. pestis bacteria was recovered from
the teeth of two individuals known to have died of the plague during the 14th
century. However, some researchers weren’t convinced of this conclusion because
it was very difficult to repeat these methods, i.e. it is really had to get
usable DNA from human remains that are 600 + years old and make sure the
results aren’t contaminated. Subsequently, if it is hard to recover samples
that are in good enough condition to be analyzed, it is almost impossible, with
the tools available in the early 2000s, to construct a genome with a good
amount of confidence, so scientists were not able to test that second
hypothesis.
Enter this new paper and new fancy technology! Researchers
from Canada, Germany, and the United States began collaborating to unearth new
information from bodies buried in the East Smithfield cemetery (or “plague pit”
as some called it) that was used during the Black Death. Samples that had been
collected and stored over many years were re-analyzed using what is called
next-generation pyroseqencing. This is a really amazing method that amplifies
DNA from a sample thousands of times with extreme precision. This means that
even if there is a very small amount of bacterial DNA in a tissue sample, it
will be amplified to the point of detection. Older methods, like PCR
(polymerase chain reaction), which is still the workhorse of a lot of
microbiology, were not sensitive enough to extract detailed DNA sequence
information from these medieval tissue samples. So, this new analysis was able
to compile this new sequence data into a genome of Yersinia pestis and compare it to modern samples of this bacteria
and see how they are related.
What they found was that the ancient and modern strains of
the bacteria are very similar, showing not a whole lot of evolutionary changes between
the 14th century and now. It also showed that the Black Death strain
of Yersinia is probably the ancestor
to modern strains, meaning that the Black Death strain of the bacteria is the
source of most modern cases (see the paper for a picture of the phylogeny if
you’re interested). This means that the “strain with increased virulence”
hypothesis that was proposed is not supported by this data. What this suggested
to researchers was that there was some kind of environmental interaction with
the Yersinia infection that caused
people to be much more susceptible or have more severe symptoms. This could be
due to wars that were happing around this time, wearing down the men that came
back from fighting. Also, there are other flea hosts besides the rats living in
the city, which may change the probably transmission of the bacteria to humans
if the fleas were infected from this alternate reservoir.
These findings are interesting for a lot of reasons, but
some are very close to my research. First, I am planning on using the
sequencing method used by the authors to analyze the bacterial communities in my
ticks and rodent blood samples. Analyzing “meta-communities” is one of the main
applications of next-generation sequencing because it gives you so much data on
the composition, in terms of number and quantity, of microbial communities that
wouldn’t be possible with previously used methods. Second, the finding that the
ancient and modern strains of the bacteria are very closely related highlights
how complex the pathogen-host interaction is. How a host will respond to an
infection depends on a whole suite of characteristics, of both host and pathogen.
Scaling up from the individual, how a population will respond to an epidemic
will depend greatly on population composition, taking into account age
structure, host quality or health, contact rates, and immuneocompetence. Some
of these aspects may be very difficult to measure when your population lived
over 600 years ago, but I bet the researchers in this field have methods they
can use to figure them out. It is quite amazing what we are able to do now to investigate
questions that have been unanswered for so long. And since this is a hot topic,
I am sure there will be competing genomes and other analyses published in the
near future.
I haven’t watched “Monty Pyton and the Holy Grail” for a
long time, but I have the feeling I’ll be bringing this paper up next time.
Sorry in advance to any family or friends that will have to bear with my
extreme nerdyness!
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