Humans vs. Pathogens: The oldest parasites

The Plague Of Ashdod by Nicolas Poussin (1631).

One way Moses proved that he was a messenger of God was by turning his hand white with an affliction known as tzaraath and then reversing the procedure. Tzaraath is Hebrew for leprosy, an atrocious and debilitating disease that has been described and documented throughout human history. But for how long has it been infecting humans? New genetic studies of ancient human remains are helping to answer these and other questions about the oldest and most gruesome pathogens, including those that cause the bubonic plague and tuberculosis.

Digging up bones for DNA
Although researchers cannot directly study deadly bacteria that existed thousands of years ago, they can unearth and study the remains of victims of age-old bacterial outbreaks. The scientists who do this type of work (called paleopathologists) are able to sequence the bacterial genes preserved within human bones and teeth. Analyses of ancient microbial DNA are providing crucial information about the origins and evolution of lethal human bacteria, and are changing our view of some of most devastating pandemics in history, such as the Black Death.

How old is the plague?
In the past two thousand years there have been three well-documented outbreaks of the bubonic plague: the Plague of Justinian (6th century), the Black Death (14th century), and the so-called “third plague pandemic” (19th and 20th centuries). Yersinia pestis is the causative agent – the bacterial bad guy – in all three of these pandemics, but there’s been some debate as to whether or not the Justinian Plague and the Black Death came from the same strain of Y. pestis. In other words, are they different pests or the same pestis?

Researchers recently studied two 1,500-year old skeletons in Germany, from a cemetery that is home to victims of the Plague of Justinian. Y. pestis DNA was sequenced from the skeletons and the analysis showed that the strain of the bacterium present in the 6th century (during the Plague of Justinian) differs from the strain that caused the Black Death. The fact that different strains caused these two pandemics, suggests that new deadly strains could emerge in the future.

Despite a long and sordid history of killing large numbers of people, Y. pestis is neither the oldest nor the most deadly human pathogen; that award just might belong to Mycobacterium tuberculosis, which, as the name implies, causes tuberculosis.

Is tuberculosis our oldest enemy?
Tuberculosis, which is caused by M. tuberculosis, is a disease that primarily affects the lungs, although other parts of the body can also be infected. Despite the potential to be fatal, most infections are asymptomatic, resulting in a latent form of tuberculosis. Of these infections, about 10% will eventually progress into an active, and potentially deadly form of the disease.

In 2008, paleopathologists studied 9,000-year old skeletons exhumed from an abandoned village in Israel. The researchers were amazed to see signs of tuberculosis on the skeletons (lesions on the bones) and were ultimately able to identify tuberculosis DNA within the remains. This indicates that tuberculosis has been active for 9,000 years – and it continues to infect new individuals daily. But does that mean it is the oldest human-specific pathogen? Although nine millennia is a long run for any disease, the bacteria that cause leprosy (Mycobacterium leprae and Mycobacterium lepromatosis) may be even older.

What is leprosy?
Leprosy causes a loss of feeling on the surface of your skin, the severity of which varies depending on the number of M. leprae or M. lepromatosis bacteria in the body. Feeling no pain may not sound too bad, but it can lead to reoccurring accidental injuries – burning, cutting, bruising, etc. – eventually causing permanent disfigurement. Today, the majority of the world’s population is immune to leprosy, but the disease was highly prevalent in Europe up until the 16th century, when infection rates suddenly dropped. Although M. leprae and M. lepromatosis were not discovered until 1873 and 2008, respectively, there have been accounts of the disease over the millennia. Most historical documentation shows a stigmatization of leprosy, with lepers being ostracized and isolated from the general population.

The age of leprosy
The age of an organism is often difficult to determine, but new research managed to identify the DNA of skeletons and used genetic techniques to figure out additional information. By studying the genes of leprosy-causing bacteria trapped in human remains, scientists estimate that a leprosy-causing ancestor existed as far back as 20 million years ago, and the DNA hasn’t significantly changed in comparison to modern strains. Unlike tuberculosis, where evidence only dates back 9,000 years, leprosy was infecting the early ancestors of modern humans, making it the oldest infection discovered thus far. But why did the leprosy rates suddenly decline in the 16th century?

How we adapted to beat leprosy
Humans – their genome and immune system – change over time. In the present day population, 95% of people are immune to leprosy and numerous changes in our DNA have resulted in genes that contribute resistance to leprosy. The burden of this disease over the years has induced mutations on the human race, and it’s likely that this genetic selection is what accounts for the sudden drop in leprosy rates in Europe. With leprosy-resistant mutations on our side, most people in the world will never have to worry about getting hauled off to a leper colony anytime soon.

With the looming age of antibiotic-resistant bacteria and other infections, it’s easy to understand why we fear these ancient microbes. Many concerning reports have recently surfaced about the Ebola virus, MERS in the Middle East, and MRSA in our hospitals, but we don’t hear often enough about the victories on the microbiological battlefield. The World Health Organization is committed to increasing access to medication. Hygienic practices are being improved and regulated on a larger scale. It’s no longer common to see rodents infesting urban streets. Although there are many dangers out there, we have made so many advances that our oldest parasites – causing the plague, tuberculosis, and leprosy – might just have to find some other hosts.

Tirthankar Ray is a third-year undergraduate in Biology and Microbiology and Immunology at Western University. He attended the 2013/14 fall-semester biology seminar series as a science communications project with Dr. David Smith from the Biology Department. David Smith is an assistant professor in the Biology Department at Western University. You can find him online at www.arrogantgenome.com and @arrogantgenome.