Cholera Specimen Reveals Its Genetic Secrets
The building is abuzz today after the online publication in the New England Journal of Medicine of a paper (full text available) analyzing a Mütter Museum specimen.
Encased in a glass jar, floating in an alcohol solution, is an 8-inch-long segment of small intestine taken from a victim of the 1849 Philadelphia cholera epidemic. Scientists, including the Museum curator Anna Dhody, were able to extract and analyze cholera DNA from the intestine.
The study aim was to describe the type of cholera that was responsible for the 1849 epidemic, which was part of the second cholera pandemic. It has been assumed that the classical biotype of Vibrio cholerae caused the 19th century pandemics, and that a newer type, known as the El Tor strain, did not emerge until the 20th century. This hasn’t however, been thoroughly studied.
The Museum’s specimen, then, was a unique chance to examine the genetic makeup of an early cholera strain, if, in fact, cholera DNA in the human tissue could be successfully extracted and studied.
A team from McMaster University's Ancient DNA Center and a number of other institutions determined that the cholera DNA from the intestine, though degraded, was usable. DNA from the human was also examined.
The donor was likely a man of African descent (his mitochondrial DNA was of a type today identified with people from sub-Saharan western Africa). The cholera strain that led to his death turns out to be very genetically similar to the classical strain. However, its DNA contains several regions not found in the classical strain. The authors note that some of these regions might be responsible for making the strain more deadly. In particular, these regions relate to cholera toxin phage, a virulence factor for cholera that results in increased water loss from gastrointestinal cells. Factors leading to increased water loss would be likely to cause more severe disease and faster death.
If the observed genetic differences have to do with severity of symptoms, then this could explain why more recent cholera epidemics have been less deadly, even before the emergence of the El Tor strain. The classical strain may have shed these observed virulence factors as a result of selective pressures over the years.
Dhody looks forward to mining the Museum collections for more research opportunities like this one. She says, "This result is exciting because it opens the door for collaborations to delve into our historical anatomical collections with new resources to help unlock countless secrets of human health. " As techniques for extracting and examining DNA improve, our extensive collections of wet and osteological specimens may reveal many more findings in the years ahead.
The New York Times covers the findings today. You can read more about the history of cholera and the development of cholera vaccines on our timeline.