Bugs and people: when epidemics change history

Salvatore Mangione
Philadelphia, Pennsylvania, United States (Winter 2018)


 The Four Horsemen of the Apocalypse, Albrecht Dürer, woodcut, c.1496-8 From left to right, Death (with a trident), Famine (with scales), War (with a sword) and Plague (with the arrows of pestilence) are crushing under their horses’ hooves all those unfortunate enough
to stand in their wake.

In a November 15, 2016 lecture at Oxford University Union, famed British astrophysicist Stephen Hawking predicted that mankind will not last more than a thousand years, and that the only way it can escape extinction is by finding another planet. In May 2017 he moved up the deadline to a mere 100 years. If his forecast is correct, our demise might not be the outcome of nuclear war, climate change, or even artificial intelligence run amok – but rather a mere chance encounter with a killer bug.  As Osler put it, “Humanity has but three great enemies: fever, famine, and war; of these by far the greatest, by far the most terrible, is fever.”1

Fever is a timely topic in 2018, since this year marks the 100th anniversary of the Spanish Flu epidemic, which cost more lives than the Great War and in fact may have even helped end World War I. It has also been argued that we are long overdue for another pandemic, since not only are we cramming people in cities like germs on a Petri dish, but we are putting them in closer contact with poultry and pigs — an ideal breeding ground for viral mutation. Meanwhile we are warming the planet, which promotes the spread of vectors, and shipping bugs to far-flung places thanks to modern international travel. These themes were all fictionally exploited by Steven Sodenbergh in his nightmarish movie Contagion, and may very well lead to the next real catastrophic pandemic.2 If so, they would be nothing new.

As humans fought one another throughout the centuries, they consistently shared a common foe: germs. Spurred by urban crowding, various epidemics swept continents, disrupted societies, ravaged civilizations, decimated armies, and took millions of lives. They also changed history. Hence, this essay will review three epidemics that over the span of a thousand years brought three mighty empires to their knees: 1) The Plague of Athens, that killed Pericles and ended the golden age of Athenian Democracy; 2) The Plague of Galen, that killed Marcus Aurelius and ended the golden age of Imperial Rome; and 3) The Plague of Justinian, that killed half of the population of Constantinople and left no soldiers to man the borders against the rising armies of Islam. For the last two “plagues” we have a fairly good inkling of the responsible organisms, though for the first one we are still unsure.


1.Plague of Athens (430-426 BC)

The Great Plague broke out at the onset of Athens’ twenty-seven-year conflict with Sparta that ultimately brought an end to Athenian cultural, political, and economic hegemony. The disease originated in Ethiopia, spread into Egypt, Libya, and the Near East, and eventually reached Athens’ harbor in May 430 BC. From there it moved rapidly into the city, with additional waves in the summer of 428 BC and winter of 427-426 BC. Over three years it infected most of the population and killed one third of the Athenians, including their charismatic leader, Pericles. It undoubtedly tilted the scales in favor of Sparta. The etiology remains unclear. This is in large part because our main historical source is Thucydides, who was not a physician but a general. Thucydides was a survivor of the disease, so he had direct knowledge of its presentation, but he often recounted it with confusing, non-medical terms. For instance, when describing the hallmark skin rash, he called it ὑπέρυθρος, Πελιδνός, φλύκταινα μικρός (reddish, livid, small blisters).3 Yet, φλύκταινα could also be interpreted as pustules or ulcers. Similarly, his term for “plague” (λοιμός) does not necessarily refer to bubonic plague, but rather to any severe pestilence. Still, what remains clear from Thucydides’ terse prose,4 is that the disease began with an abrupt involvement of the upper respiratory tract (“sneezing, red eyes, sore throat, hoarseness”); soon spread to the chest (“violent coughing”); and ultimately resulted in hiccupping and bilious vomiting. Then the rash appeared, and caused such an intense heat sensation that victims would jump into wells. If they survived, “the plague would descend to the bowels… causing an attack of uniformly fluid diarrhea which in most cases ended in death through exhaustion.” A few would slowly recover, but often with gangrenous fingers, toes, and genitalia. Some lost eyes and memory. In this way, over a period of ten days “the malady which first settled in the head passed through the whole body…”

Based on Thucydides’ description, seven suspects have been proposed: influenza, typhoid fever, bubonic plague, smallpox, epidemic typhus, Ebola, and measles.5 We can discard influenza because the rash would require a toxin-producing staphylococcal co-infection;6 typhoid because it would never kill 30% of the population; plague because Thucydides never mentions buboes; smallpox because there was no pox; and typhus because the rash was different.  So what killed those Athenians? Ebola is an attractive and recent hypothesis.7 It does indeed present with fever, headache, vomiting, diarrhea, plus many varieties of skin rashes. Hiccups are a hallmark too. Still, in the end it might have been lowly measles.5 Not the modern kind, though, since this only appeared after the millennium, 8,9 but perhaps a serotype that has long gone extinct. Like the Great Athens of Pericles.


2. Plague of Galen (165-180 AD)

In contrast to the Plague of Athens, the Plague of Galen has a convincing culprit: smallpox.10 This killed emperor Marcus Aurelius and then led to a “century of plague” that ultimately cost the lives of five million Romans. The outcome was a military, economic, and socio-political decline that might have contributed to the eventual collapse of the Western Empire.  In fact, the plague may have even had spiritual repercussions, since many Romans feeling powerless and anxious in the face of divine scourge, embraced Christianity.11

The disease was brought from the East by legionnaires campaigning in Persia, and quickly spread throughout the empire. Our main source is Galen, who not only treated plague victims but was also the medical authority of the time.12 Yet his observations are brief, scattered throughout his writings, and often incorrect. For instance, he calls the disease a “fever plague” and erroneously identifies it with the Plague of Athens. Still, he vividly describes the abrupt onset of fever, nausea, vomiting, and diarrhea (often melanotic); the subsequent productive cough; and ultimately the “total body exanthem” that appeared on the ninth day.  This was “ulcerated in most cases …eventually turning into black exanthem. If not ulcerated, the exanthem was rough and scabby and fell away like a husk. If ulcerated it fell away with a scar.” If patients survived, their recovery came by “crisis” so that “on the twelfth day they were usually able to rise from their bed.”13

Galen’s excellent description of the rash allows a firm identification of the disease as smallpox. In addition, the hemorrhagic characteristics of the exanthema and the associated intestinal bleeding suggest hemorrhagic smallpox, the most virulent form of the disease.10 The result was a devastating loss of life among civilians and soldiers, which in turn allowed Germanic tribes to settle in the most depopulated provinces of the empire and even to serve in the Roman army. Ultimately, a flood of Germanic refugees coupled with the loss of allegiance of a mercenary German army caused the collapse of the Roman West.14 Like the U.S. today, the Rome of the second century AD was a cultural, economic, political, and military superpower. Yet, all of this came to a screeching halt with the epidemic.


3. Plague of Justinian (541-543 AD)

This was the debut of bubonic plague in Europe, and it was probably triggered by unusual cold temperatures from a South-Pacific volcanic explosion.15 The result was rain and flooding in dry regions like Ethiopia that are also known plague reservoirs. Colder, wet weather caused a boom in the rat and flea population, and ultimately drove wild rodents into people’s dwellings, thus jump-starting the epidemic. From Ethiopia the disease spread to Egypt on ivory-carrying barges, and from there reached Constantinople with the grain ships. Emperor Justinian was stricken but survived. His empire did not. In the end, not only Byzantium was devastated, but also Persia and perhaps even China. As reported by Procopius, “the whole human race came near to being annihilated.” 16 Evidence in favor of bubonic and septicemic plague is solid, thanks to Procopius’ description of buboes and gangrenous toes, but also to the isolation of Yersinia pestis from victims’ remains.17 It was, in fact, the first of three plague pandemics, and raged on and off for almost two centuries. By the time it died out it had killed thirty million people. The consequences were dire, since the epidemic broke out when the Byzantines were trying to consolidate their recently liberated Western provinces. Instead, they found themselves without enough soldiers to protect their borders. Hence the empire was overrun, Persia simply disappeared, and the rest is history.18 In fact, the plague might have even contributed to the transition from the classical to the medieval period.19



These three examples illustrate how epidemics can bring down empires. Additional instances include the Black Death, a 1346-1353 pneumonic plague that killed one third of all Europeans and ended feudalism; and the Colombian Exchange, which devastated the newly discovered Americas by killing up to 90% of the native population. They should all serve as a reminder that diseases can change history, whether they afflict people or leaders.20 This remains an important issue for the twenty-first century. Still, if there is a silver lining to epidemics, is that they are the great equalizer: the multibillionaire in the penthouse and the homeless in the street are both utterly powerless against bugs. And that is a refreshing thought.



  1. Cushing H. The Life of Sir William Osler: Oxford, UK: Clarendon Press; Vol. I, ch. 14.
  2. Osterholm MTand Olshaker M. We’re Not Ready for a Flu Pandemic. The New York Times. Jan 8, 2018.  https://www.nytimes.com/2018/01/08/opinion/flu-pandemic-universal-vaccine.html/ Accessed Jan 8, 2018.
  3. The Peloponnesian War. New York/London: J. M. Dent/ E. P. Dutton Publishers; 1910. Book 2, Chapter 49 [with original Greek Text in the Perseus Digital Library, last consulted on 1/8/2017: http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.01.0199%3Abook%3D2%3Achapter%3D49
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  15. Keys D. Catastrophe: An Investigation into the Origins of the Modern World. New York, NY: Ballantine Books; 2000.
  16. History of the Wars. Trans. H. B. Dewing, Loeb Library of the Greek and Roman Classics. Cambridge, Mass.: Harvard University Press; 1914. Vol. I, pp. 451-473.
  17. Wagner DM et al . Yersiniapestis and the Plague of Justinian 541–543 AD: a genomic analysis. Lancet Infect Dis. 2014;14(4):319-26.
  18. Rosen W. Justinian’s Flea: The First Great Plague and the End of the Roman Empire. London, UK: Penguin Books; 2008.
  19. Little LK. Plague and the end of antiquity. Cambridge, UK: Cambridge University Press; 2006.
  20. Robins RS and Post J. When Illness Strikes the Leader: The Dilemma of the Captive King. New Have, CT: Yale University Press; 1993.



SALVATORE MANGIONE, MD, is a clinician-educator with a long interest in physical diagnosis, medical history, and community service. His innovative programs and engaging teaching style have been recognized by multiple awards for clinical teaching, and his work has been featured in the New York Times, the Los Angeles Times, the Wall Street Journal, the BBC, CNN, NPR, and Forbes. Dr. Mangione has been an invited speaker at many national and international meetings, especially in regard to using visual arts to teach bedside observation. He is the author of the book Secrets in Physical Diagnosis.


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