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Microbial Mysteries

By Emily Mynar

When you hear the word “plague”, you probably think of the Black Death that ravaged Europe in the 14th century. However, countless epidemics and pandemics have occurred throughout human history, from the Justinian plague in the first century CE to the Spanish flu in the early 1900s. As the fields of microbiology and epidemiology have evolved in recent years, scientists have been exploring the causes of these plagues and how they spread. In the article The Plague of Athens: Epidemiology and Paleopathology, Robert J. Littman of the University of Hawaii explores what is known about the Plague of Athens and investigates what pathogen may have been responsible for it.

The Plague of Athens presents an interesting case for scientific study because so little is known about it. The plague struck Athens in the 5th century BCE while the city was under siege during the Peloponnesian War, killing an estimated 25% of the city’s population. Despite its significant impact—the plague is considered the primary reason Athens lost the war—little record of it was kept. The one account of the plague that does exist was written by the Athenian historian Thucydides and is considered one of the great passages of Greek literature. Thucydides described the disease as including a rash, high fever, diarrhea, and violent cough. It was highly contagious, he wrote, and usually resulted in death. In recording the symptoms and impact of the disease, the historian hoped that future generations would be able to identify the disease if it were to appear again.

Despite Thucydides’ intentions, the symptoms he described were vague enough that scientists are still not sure what disease actually caused the plague. As modern scientists began to search for the pathogen behind the plague, the most common diagnosis has been smallpox, which is characterized by symptoms similar to those Thucydides recorded. However, other scientists believe the plague to have been caused by typhus. Beyond these common explanations, other possible causes include measles, typhoid fever, bubonic plague, and scarlet fever.

To further investigate what disease caused the Plague of Athens, Littman used mathematical modeling to examine theoretical infection and mortality rates of the various disease candidates. Diseases like measles were more easily ruled out because the population of the city was too small to sustain an epidemic for the several years that the plague lasted, narrowing the possibilities down to typhus, typhoid fever, and smallpox. To further narrow down those remaining diseases, Littman modeled theoretical patterns of occurrence for each disease over a specified period for the population and density of Athens at the time of the plague. In theory, whichever disease best fit the model created based on Thucydides’ description would likely be the cause of the plague.

Littman’s analysis indicates that the disease spread through either an animal reservoir or respiratory transmission. Smallpox, a respiratory disease, and typhus, a reservoir disease, both match the mathematical modeling. Smallpox appears to be the better candidate because it more closely fits Thucydides’ description, but it remains unclear. Because the two diseases appear to both be reasonable candidates, Littman and other scientists had to seek a different way of identifying which disease actually caused the plague.

Since the late 20th century, as new technologies and a better understanding of DNA have been developed, scientists have used the analysis of ancient DNA to investigate previously unanswerable questions like what caused the Plague of Athens. Extracting the DNA from ancient microbes can allow us to identify them and track changes in their genetic history. In 2001, a mass grave was found in Athens that dates to the plague period. The Greek archaeologist Effie Baziotopoulou-Valvani was able to extract ancient S. enterica serotype Typhi bacterial DNA, which causes typhoid, from the skeletons.

Though this newer finding appears to show that the plague was caused by typhoid fever, we cannot be certain. Hippocrates’ writings indicate that typhoid was likely endemic (regularly found) in ancient Greece, meaning it may have infected people without necessarily being the cause of death. As a result, scientists are still divided on whether the plague was caused by typhus, typhoid fever, or smallpox. Regardless, this DNA analysis is an interesting new way of investigating ancient plagues for which we only have written descriptions. It is likely that future technology will enable us to look more closely at these historical epidemics and give us a better understanding of microbial evolution that can be used to help us combat diseases that are affecting us today.


Littman, R. J. (2009). The plague of athens: Epidemiology and paleopathology. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, 76(5), 456–467.

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