Pathogenesis: A History of the World in Eight Plagues

by Jonathan Kennedy

the more humans learn about the world, the more insignificant we realize we are—is

If we trace the Tree of Life to the base of its trunk, we find the Last Universal Common Ancestor (LUCA): a single-celled, bacterium-like organism that is the distant progenitor of all living things, humans included.

There are about 8.7 million species of animals, plants and fungi on earth,[6] compared to an estimated 1 trillion—1 million million—types of bacteria and archaea.[7] Less than 0.001 percent of all species on the planet are eukaryotes.

Such immense periods of time are hard for the human brain to conceptualize, but if we compressed 4.6 billion years into one calendar year then bacteria evolved in early spring. Humans don’t appear until about half an hour before midnight on 31 December.[11]

It’s no exaggeration to say that bacteria have made the planet habitable for complex life, including humans. It’s a bacterial world, and we’re just squatting here.

A retrovirus is a specific type of virus that reproduces by inserting a copy of its DNA into the genome of the host cell.

If one of our distant ancestors hadn’t been infected by a virus hundreds of millions of years ago, humans would reproduce by laying eggs.

infectious diseases have killed so many people throughout history that they are one of the strongest forces shaping human evolution.

It is therefore not the strongest or most intelligent members of our species who were most likely to survive long enough to pass on their DNA to the next generation; rather, it was humans who had the most effective immune system to cope with the onslaught of infectious diseases, or those who had mutations that made their cells unusable to microbes. Lots of these mutations not only conferred resistance to pathogens but also had a negative impact on cell function. This suggests that humans’ struggle for existence was a fight against microbes rather than alpha males and apex predators.

The evolutionary reason why bacteria produce chemicals that improve our moods may be that it makes us more likely to be gregarious and therefore provide them with opportunities to colonize other hosts.

In medicine, pathogenesis refers to the origins and development (genesis or γένεσις) of a disease (pathos or πάθος), with a particular focus on the way that pathogens infect our cells and the effect this has on our bodies. In the pages that follow, we will explore how viruses, bacteria and other microbes impact aggregations of bodies—that is, the body politic, body economic and body social. This is history from deep below. Rather than thousands or millions of “little” humans working together to change the world, we will explore the role that billions or trillions of microscopic viruses and bacteria have played in history.

A plethora of recent discoveries point to the fact that Homo sapiens weren’t, in fact, smarter than other species of human.

“While there are certainly biological differences between Neanderthals and H. sapiens, the behavioural gap has narrowed to a point where there seems to be little difference between the two.”[47]

Whereas hunter-gatherers had a child roughly every four years, women in early agricultural societies gave birth on average every two years.[22] A recent study of the Palanan Agta people in the Philippines demonstrates that, even in the twenty-first century, nomadic hunter-gatherer women have markedly fewer children than those who have adopted sedentary agriculture.[23] Farming allows women’s bodies to recover faster from the strain of childrearing because they get to eat calorie-rich cereals and dairy products rather than low-calorie game, seafood and plants, and expend much less energy on carrying their infants. The Neolithic diet also made it possible to wean children off breast milk faster.

The fact that dark-skinned hunter-gatherers were able to live in the British Isles indicates that they could get sufficient vitamin D from other sources: their diet was extremely rich in fish and meat. It was only after the Neolithic Revolution, when early farmers survived on a much less nutritious diet, that lighter skin conferred a survival advantage.[44]

Let’s consider the example of the 6,000- to 8,000-strong Cayapo tribe in South America, who accepted a single missionary in 1903. This contact precipitated the destruction of the tribe: by 1918 there were 500 survivors, by 1927 just twenty-five, and by 1950 only two or three people who could trace their descent to the Cayapo.[52]

People of European ancestry are a mixture of three genetically distinct population groups (plus, in some cases, trace amounts of other DNA).[79] First, Western Hunter-gatherers, such as Cheddar Man, who had dark skin and hair and light eyes.[80] Second, olive-skinned, dark-haired Neolithic European Farmers like Ötzi the Ice Man who migrated into Europe from Anatolia approximately 9,000 years ago, bringing farming with them, and arriving in Britain three millennia later. And third, the Steppe Herders: tall, fair-haired, light-skinned shepherds who migrated westward from the Eurasian Steppe about 5,000 years ago and adopted farming when they settled in Europe. The implications of this are momentous: contemporary Europeans are neither genetically “pure” nor are they the region’s indigenous people. Even white Europeans are mongrel immigrants.[81]

It is remarkable to think that the impact of the migration of a small number of shepherds out of the Western Eurasian Steppe 5,000 years ago, which was most likely made possible by a devastating plague pandemic, can literally still be seen and heard today across the world.

We can hazard an educated guess as to what language Europe’s first farmers spoke. As the Basque people have a high proportion of Neolithic Farmer ancestry and their language has no relation to any other, it is likely to be the last surviving descendant of the tongue spoken by Neolithic Farmers.

There is, however, something unsettling about a group of white, Oxford- and Cambridge-educated men extolling the virtues of colonialism, albeit for comedic effect. The implication—that Roman imperialism imposed a superior culture on the warring, uneducated and dirty people of the Middle East—echoes the common claim that the British Empire brought civilization (in the form of railways, the English language, capitalism, etc.) to the societies it conquered, and is also apparent in justifications for more recent neo-colonial interventions, such as the invasions of Iraq and Afghanistan.

But Ancient Rome experienced a much more notable jump in mortality among children and young adults in the hot summer months, a pattern we do not see today. The spike is almost definitely the result of gastrointestinal bugs that enter the body via water or food contaminated with feces. This happens more often in the summer because the bugs reproduce at a faster rate in warm weather. They disproportionately affected infants and new arrivals from the countryside who hadn’t yet developed immunity.

a series of pandemics caused immense damage and played a crucial role in weakening the Roman Empire, not just in absolute terms but also relative to the neighboring “Barbarians.” This is because, although the term “Barbarian” is problematic in that it lumps together an incredibly diverse set of communities into one indistinguishable and supposedly inferior mass, all these groups tended to have one thing in common: they lived in much less-populated and less-connected societies than the Romans. As a result, pandemics tended to cause far more devastation to the Romans than to Barbarian societies.

Instead, we have to rely on the surviving sermons of Cyprian, the Bishop of Carthage, who gave his name to the pandemic. On the basis of his description of high fever, vomiting, diarrhea and sometimes bleeding from the ears, eyes, nose and mouth, Harper believes the epidemic was most likely caused by a viral hemorrhagic fever similar to Ebola. Even today, if patients are treated in modern medical facilities with the latest drugs, Ebola still kills half the people who contract it. Assuming this was the case, the Plague of Cyprian would have been a particularly gory and deadly pandemic—even by the standards of this book.

It wasn’t a coincidence that the two high points of repression coincided with the Antonine and Cyprianic Plagues. Pagans believed that the presence of a new religion was displeasing the Roman gods or driving them away, and therefore Christianity was responsible for the widespread death and disruption.[44]

How do we explain the sudden transformation of Christianity from a marginal Jewish sect to a popular religion? The American sociologist Rodney Stark argues that infectious diseases are a crucial part of the story. The Christian faith skyrocketed because it provided a more appealing and assuring guide to life and death than paganism during the devastating pandemics that struck the Roman Empire in the second and third centuries CE. In fact, he goes as far as to say that if it wasn’t for the Antonine and Cyprianic Plagues, “Christianity might never have become so dominant a faith.”[47]

Christianity provided another more tangible benefit over paganism. Traditional Roman society was not uncharitable—in its heyday, the state doled out free wheat and later bread to 200,000 people in the imperial capital, for example—but their deities did not reward altruism. So when plagues were raging, people of means—including Galen—took flight, and those who remained tried to avoid contact with the sick. Observing the pagans, Bishop Dionysius of Alexandria noted: “their dearest they fled from, or cast them half dead into the road.” Christianity was different. Believers were expected to show their love for God through acts of kindness to each other. As a result, followers of Jesus tried to guarantee entry into heaven with good deeds in their earthly lives. Dionysius describes how Christians looked after the ill during the Plague of Cyprian: “Heedless of danger, they took charge of the sick, attending to their every need.” Christians would have been able to reduce mortality by up to two-thirds just with basic nursing, such as providing food and water.[48] The fact that so many more Christians survived, and that Christians managed to save pagans abandoned by their families, would have provided the best recruitment material any religion could ask for: miracles.

The renowned Belgian historian Henri Pirenne famously argued that without Muhammad, Charlemagne would be inconceivable.[73] The political vacuum in northwestern Europe ultimately led to the emergence of a new order that was dominated by a patchwork of small kingdoms, feudal lords and thriving city-states but was at the same time unified by its Christian identity, in opposition to its Muslim neighbors to the south and east.[74]

For Bergman, the outbreak of plague that hit Europe in the middle of the fourteenth century provided an obvious metaphor for the climate of existential angst and foreboding he was living through. Others made this link too. The American historian Barbara Tuchman not only describes the 1300s as a “violent, tormented, bewildered, suffering and disintegrating age” in which there was “no sense of an assured future,” she also argues that it was a “distant mirror” to our own troubled times.[1]

The Norwegian historian Ole Benedictow estimates that roughly 60 percent of the population of Europe—that is about 50 million out of 80 million people—died from the plague between 1346 and 1353.[18] Analysis of an ice core drilled in the Swiss Alps reveals that lead pollution disappeared from the air in these years.[19] No silver mining occurred during the Black Death. The economy appears to have simply ground to a halt.

The Erfurt massacre was far from an isolated incident. The orgy of violence began in northern Spain and southern France in the spring of 1348, ostensibly because the gentiles believed Jewish communities were the source of the Black Death. In the summer and autumn of 1348, several Jews in the French Alps confessed—albeit after being tortured on the rack—to causing the plague by poisoning wells.[22] Similar rumors spread across the German-speaking world faster than the disease itself—and so did the attacks against Jewish communities. These conspiracy theories appear to have been have widely accepted. The city council in Strasbourg wrote to nearby towns to ask whether the well-poisoning accusations were true. Of the nineteen responses that exist in Strasbourg’s municipal archives, just one professes skepticism.[23] This appears to have been taken as a sign to proceed. On Valentine’s Day 1349 the city’s 2,000 Jews were forcibly marched through the town as baying crowds ripped their clothes off, hoping to find gold sewn into the lining, and were then burned to death. Eyewitness accounts document a series of horrific attacks. The Jewish community in Mainz, perhaps the biggest and wealthiest in Europe, managed to repel the first attack and killed 200 assailants. But the next day the mob returned with reinforcements and annihilated all 3,000 of them. In Hansa towns in the north, Jews were walled up in their houses and left to starve. The Jewish community in Esslingen in the southw...

By the time the violence petered out in 1351, there had been about 350 attacks on Europe’s Jews.[27] Sixty large and 150 smaller communities were annihilated.[28] Many Jews who managed to survive the double blow of plague and persecution fled to eastern Europe, a region that until then had an insubstantial Jewish population.

The demographic scar left by wave after wave of plague was deep and abiding. The population did not return to its 1300 level until the sixteenth century in Italy and France, the eighteenth century in England, and the nineteenth century in Egypt, which was at the time part of the Ottoman Empire.[33]

As the Ottomans expanded they gave up the nomadic existence that had given them such an advantage and began to suffer the ill effects of the plague like the rest of the population; this may be why they never replaced the Balkan population in the way they did in Anatolia.[47] Some communities—most notably the Albanians and Bosnians—converted to Islam in large numbers, but the majority remained Christian. The consequences of this partial conversion of the region 500 years ago played out in the Yugoslavian Wars of the 1990s, when nationalist politicians attempted to carve the remnants of the relatively tolerant, diverse Ottoman Empire into religiously and/or ethnically homogenous states. The Orthodox Christian Bosnian Serb army committed acts of genocide against Muslim Bosnians, most notoriously when they murdered over 8,000 men and boys at Srebrenica. Another legacy is the Muslim-majority Albanian province of Kosovo’s ongoing struggle for independence from Serbia.

according to the American historian Alan Mikhail, the expansion of the Ottoman Empire disrupted trade routes with the Far East, and this compelled Spanish and Portuguese adventurers to seek out new ways to reach the Indies.[48] It isn’t a coincidence that two decades after the Genovese trading colony of Kaffa fell to the Ottomans, Christopher Columbus—himself a Genovese sailor—reached North America. What is more, according to Mikhail the colonization of the Americas was a response to the realization that the Holy Land was irretrievably lost.

The processions were an early and shockingly masochistic manifestation of a much broader, longer-lasting change in attitudes toward religion that occurred in the wake of the Black Death. Christianity had once replaced paganism because it provided a more appealing and assuring guide to life and death during the Antonine and Cyprianic Plagues. Now, as disease ravaged the population yet again, many people began to reject the teachings of the Catholic Church.

Even before the Black Death, the power and wealth of the Church attracted people to the priesthood who were motivated by personal advancement rather than spiritual concerns. So many clergy perished that the Church had no choice but to loosen the entry requirements in order to replace them, resulting in an influx of inexperienced and, in many cases, even more unsuitable people into the priesthood.[53] The portrayal of the clergy in the literature of the second half of the fourteenth century demonstrates how little they were respected. In Boccaccio’s Decameron, priests, monks, mendicant friars and even nuns are on the prowl for sex wherever they can find it. Chaucer’s Canterbury Tales satirizes English society, most of all the Church. It paints a picture of a lazy and greedy clergy, including a Monk who prefers to hunt on his fine horse rather than pray, and a Friar who has taken a vow of poverty but gleefully pockets money from destitute widows to fund his extravagant lifestyle.

Wycliffe criticized the Church for veering away from the word of the Bible. He argued that there was no justification in the scriptures for many of the ideas they promoted—such as attending Mass, repenting for one’s sins, praying to saints and buying indulgences. Wycliffe claimed that the clergy were not required to mediate laypeople’s relationship with God; rather, the Bible was the only reliable guide to how they should conduct themselves. People should study the Holy Book—in the vernacular if they didn’t speak Latin—and decide for themselves what God’s message was. Wycliffe played a prominent role in the first translation of the Bible from the Latin Vulgate into Middle English in 1382.

One factor was the newfound accessibility of heretical ideas. When Wycliffe was alive, scribes had to copy out manuscripts by hand in a laborious and expensive process, so reading was the preserve of a small, educated elite. Then, in the middle of the fifteenth century, Johannes Gutenberg invented the printing press. The increasing use of labor-saving devices was a direct response to the challenges created by the Black Death and subsequent outbreaks of the plague, because there were now so few workers that labor-intensive processes had become unviable.[57] Printed pamphlets provided a relatively quick and cheap way of communicating with previously unimaginable numbers of people, allowing an obscure friar from a small German town to spread his anti-Church message to vast audiences across Europe. Luther’s tracts were accompanied by crude, satirical woodcut images, so that in an age of low literacy his ideas reached as wide an audience as possible.[58] He was one of the bestselling authors of the sixteenth century. By 1521, 300,000 of his pamphlets and books had been printed and distributed;[59] after thirty years the figure was 3.1 million.[60] The impact of the printing press on the spread of Protestantism was so important that Luther is said to have referred to it as “God’s highest and most extreme act of grace.”[61]

In this sense, existential questioning triggered by the Black Death didn’t just lead to the rise of Protestantism but also paved the way for the emergence of secularism.

When Europeans started settling in the Caribbean, it was only a matter of time before the viruses and bacteria that had evolved in the Old World in the wake of the Neolithic Revolution made the jump across the Atlantic. The Taíno had never before been exposed to these pathogens and so hadn’t developed resistance. They were obliterated by wave after wave of virgin soil epidemics.[13] First came illnesses like common colds and stomach bugs that had relatively mild symptoms for Europeans but were devastating for the immunologically naive indigenous inhabitants of Hispaniola. Then smallpox hit in 1518, killing between a third and a half of the population. And then, over the next few years, came a plethora of other infectious diseases. These devastating epidemics made the conquest of the New World possible.

Just as Cortés was at his lowest ebb, his expeditionary force defeated and chased out of the capital, Old World pathogens gave him a shot at redemption. The reversal in fortune was so abrupt and profound that the Spanish assumed it was divine intervention. As Francisco de Aguilar, another follower, put it: “When the Christians were exhausted from war, God saw fit to send the Indians smallpox, and there was a great pestilence in the city.”[18]

Many of the indigenous people who weren’t killed by infectious diseases died from famine, as crops rotted in the fields because there was no one to harvest them. The malnourished survivors were susceptible to whatever pathogens would arrive next from Spain. The scale of the cumulative devastation is hard to imagine: the indigenous population of Mesoamerica was about 20 million when Cortés arrived but had fallen to 1.5 million a century later.[25]

Across the whole of the Americas, the introduction of infectious diseases from Europe resulted in a 90 percent fall in the population, from about 60.5 million in 1500 to 6 million a century later. The global population fell by 10 percent. The decline in slash-and-burn agriculture and the reforestation of tens of millions of hectares of cultivated land resulted in a reduction in carbon dioxide in the atmosphere that is visible in the ice cores drilled by scientists in the Antarctic. The demographic collapse cooled the global surface air temperature by 0.15 degrees Celsius, contributing to the Little Ice Age in the early 1600s.[28]

And yet there is evidence of only one infectious disease being transmitted from Native Americans to Europeans: syphilis.

The fact that diseases caused by Old World pathogens almost exclusively killed Native Americans was interpreted on both sides as an unequivocal sign that God or the gods supported the Spanish invaders. It added to the conquistadors’ belief in the righteousness of their gory, greedy mission. In contrast, the Mexica and Inca were left bewildered and despairing. Spanish chroniclers describe indigenous people dying by suicide, abandoning their newborn babies and murdering shamans “to see if by this means the distemper would cease.”[33] The Native Americans were ripe for conversion to what, based on the evidence they had available to them, appeared to be a far superior religion. They embraced Catholicism with a fervor that is still very much apparent: today, 40 percent of the world’s Catholics live in Latin America.[34] Spanish culture wasn’t adopted wholesale, however. Many of the conquistadors were young male fortune seekers who traveled alone. They settled down with women from the Mexica and Inca nobility—those who had survived the epidemics—and created a new hybrid, mestizo society that drew from both indigenous and European cultures.[35]

Stuck out in the north Atlantic, these communities were too small and remote to sustain infectious diseases in the same way as mainland Europe. Maladies like smallpox were endemic in late-medieval Spain. They constantly circulated among the vast population of Eurasia and Africa, so most children would be exposed and either die or develop immunity. But the same diseases were epidemic in the north Atlantic island colonies; they would periodically arrive on the ships that sailed from Denmark and Norway, infect anyone who wasn’t immune, then burn themselves out when there wasn’t anyone else to infect. Consequently, it is highly likely that the handful of Norsemen who tried to settle in Vinland were not carrying deadly infectious diseases.[48]

If modern-day Americans want to be historically accurate, then their gratitude at Thanksgiving should be directed to the Old World pathogens that made the settlement of Plymouth Colony possible.

The fact that European attempts to settle in the Americas foundered without the help of infectious diseases suggests that the Portuguese would have struggled to colonize West Africa even if malaria and yellow fever hadn’t intervened to help the indigenous population. But these mosquito-borne diseases created a defensive force field that made military conquest all but impossible. Writing in the sixteenth century, João de Barros, the historian who is referred to as the “Portuguese Livy,” lucidly captured the frustrations of the would-be colonists: But it seems that for our sins, or for some inscrutable judgment of God, in all the entrances of this great Ethiopia that we navigate along, He has placed a striking angel with a flaming sword of deadly fevers, who prevents us from penetrating into the interior to the springs of this garden, whence proceed these rivers of gold that flow to the sea in so many parts of our conquest.[74] In the late eighteenth and early nineteenth centuries, when Britain was on its way to becoming the dominant colonial force in the world, malaria and yellow fever—the flaming sword of deadly fevers—still made tropical Africa all but unconquerable.

Curtin’s data suggests that the average European would have survived for just four months in Mali—an annual mortality of 300 percent!

Alas, this was not an isolated incident. The Belgians cut off so many limbs that there was a rumor among the Congolese that dismembered body parts were used to make the canned corned beef that formed an important part of the European diet in the tropics.[95]