How does one study an ancient disease? How do you study something that is no longer around? What kind of information do we want and how do we get it? As a geneticist I always want to look at DNA because DNA is an excellent source of information. It can tell us things like was it a virus or a bacteria? Is it closely related to bacteria that are around today? What made it become an epidemic? The real question though, is how do you get your hands on DNA of an ancient disease? Well, you rob graves of course.
The Bubonic plague is probably one of the most famous epidemics of all time. It was also called the Black Death and killed ~25 million people which was around 30 – 50% of Europe’s population in the 1350s. The disease has many symptoms but two of the most famous were the swelling of lymph nodes (ew) and where the tissue in the extremities (like fingertips, arms and nose) would get gangrene and this rotting tissue would turn black (double ew). This symptom is what gave the disease its lovely name the Black Death. Apparently these symptoms would occur within just a few days of getting the disease and people would die a very painful death soon thereafter.
The disease is thought to have been caused by a bacteria called Yersinia pestis. Although there have been reports of the plague occurring more recently it has been debated whether it is actually the same strain of bacteria as what caused the major epidemic ~600 years ago. One of the things we could do with the ancient DNA is to find out if the plague is still around, of course to find this out we need to get our hands on some of its DNA.
Bos and colleagues took a really interesting tactic to getting this DNA. They wanted to know how its DNA changed to make it go from a regular old bacteria to one that is capable of killing millions of people. To figure this out they had to get DNA from the actual bacteria that was killing people in the 1350s to see what it looked like. So where to find it? Well, one of the big problems they had during the epidemic in the 1300 hundreds was what to do with all of the bodies, and one of the things they did was to create mass graves just for victims of the Black Death (awesome). Bos and colleagues took advantage of that and went to one of these old gravesites and actually dug up bodies and took teeth from five individuals and got DNA of the bacteria from those teeth (I wonder what they said they wanted to be when they grew up?).
What does the ancient DNA tell us, well to understand this we need to know a little bit about bacteria genomes. Bacteria have really cool genomes, they have one circular chromosome (different from our 23 pairs of chromosomes) and they have other little pieces of DNA called plasmids. Plasmids are little circles of DNA that can be easily passed from one bacteria to the next. These plasmids have been really important in the evolution of bacteria. For example, if a gene that makes a bacteria resistant to an antibiotic is on a plasmid and that plasmid gets transmitted to new bacteria then the new bacteria is instantly resistant to antibiotics. This is thought to be one of the reasons we have so many problems with antibiotic resistance.
The genome of Yersinia pestis has one large bacterial chromosome and two plasmids. Boss and colleagues found that the DNA from the ancient strain of bacteria is different from the strains of Yersinia pestis that are around today, but that it is likely that all of the strains that are around today are descendants of the ancient bacteria. What is even more interesting is that they did not find any single spot on the chromosome or on the two plasmids that could explain why the bacteria became so infectious. Instead they suggest that there were a lot of other things going on during that time period that added to the problem of this disease, like maybe people were more susceptible to getting sick, and the conditions were just right for spreading the disease.
It is fascinating to think about the issues around diseases and that many times other factors must fall into place for a disease to be really successful (and not necessarily just a genetic change), things like sterility, medical applications and knowledge, human health, and how the disease is transmitted. It may be that some bacteria or virus could be completely capable of causing a huge epidemic but we have other things in place that prevent those things from happening. The recent Cholera epidemic in Haiti is a good example of this. We have known what Cholera is and how it is spread since the days of John Snow, but we still were unable to prevent this problem in Haiti because the conditions were right for the disease to be spread.
Paper Referenced: Bos et al. 2011. A draft genome of Yersinia pestis from victims of the black death. Nature 478: 506-510.