Pathogenesis: A History of the World in Eight Plagues

by Jonathan Kennedy

Less than 0.001 percent of all species on the planet are eukaryotes.

They live miles below ground and miles above it, where they influence the formation of clouds and possibly even lightning.

They are so numerous that, despite their tiny size, the total mass of all bacteria on the planet is thirty-five times that of all the animals and 1,000 times the weight of all humans.

All plants and animals produce energy through aerobic respiration, which is twenty times more efficient than anaerobic respiration—and therefore much better suited to supporting large, multicellular organisms.

In total, phytoplankton—photosynthesizing microorganisms in the sea—account for at least half of the oxygen produced by living organisms.

Viruses are tiny, even by the standards of microbes. They can be hundreds of times smaller than the average bacterium. Viruses are so minuscule that they haven’t left a mark on the fossil record.

The total number on the planet is estimated at about 1031—that is, one followed by thirty-one zeros.[19] But only about 220 types of virus are known to be capable of infecting humans.

An astonishing 8 percent of the human genome is made up of such genes.

One remarkable example is a gene inherited from a retrovirus infection about 400 million years ago that plays a crucial role in memory formation. The gene does this by coding for tiny protein bubbles that help to move information between neurons, in a manner similar to the way that viruses spread their genetic information from one cell to another.

Another mind-blowing example of a function that human ancestors acquired from retroviruses is the ability to give birth.

When geneticists looked at the gene responsible for creating it, they realized that it was almost identical to those used by retroviruses to produce the proteins that attach to cells they are infecting without triggering an immune response.

it has been estimated that viruses account for 30 percent of all genetic mutations since our species’ divergence from chimpanzees.

Since the adoption of settled agriculture in sub-Saharan Africa between 5,000 and 4,000 years ago, malaria has killed so many people that it is the “strongest known force for evolutionary selection in the recent history of the human genome.”

This suggests that humans’ struggle for existence was a fight against microbes rather than alpha males and apex predators.

Each of us hosts an estimated 40 trillion bacteria—meaning they slightly outnumber human cells.[28] Viruses? At least ten times that figure. In total, the human microbiome—all the microbes living in our body—weighs around the same as our brain, between one and two kilos.

While our cells carry between 20,000 and 25,000 genes, the microbiome contains around 500 times more than that.

Of over 500 strains of bacteria they tested, more than 90 percent were able to produce neurotransmitters like dopamine and serotonin that play a key role in regulating human moods.

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.

The researchers then compared the microbiomes of volunteers who had been diagnosed with depression with those who had not, finding two types of bacteria—Coprococcus and Dialister—that were common in the guts of healthy participants but absent in those who suffered depression. Both of these bacteria produce substances known to have antidepressive properties.

But if bacteria and viruses are such a fundamental part of who we are on an individual level, what role do they play on a collective level? Or, put another way, how have microbes impacted the evolution of human societies and politics? How have they influenced history?

The main alternative to the Great Men theory of history is what Lucien Febvre, the French historian, referred to in the early 1930s as “histoire vue d’en bas et non d’en haut,” or “history from below and not from above.”[35] This approach focuses on the masses of ordinary men and women, often fighting against exploitation and oppression. In this view, it is the cumulative impact of all their struggles that drives progressive social, political and economic transformations. E. P. Thompson’s The Making of the English Working Class (1963) and Howard Zinn’s A People’s History of the United States (1980) are classic examples of this genre. The idea of history from below is much more inclusive than the worship of a few heroic individuals, but still it focuses on humans as the driving force of history.

In this way, pathogens have been the protagonists in many of the most important social, political and economic transformations in history: the transition from a planet inhabited by multiple species of human to one in which Homo sapiens reigned supreme; the replacement of nomadic hunter-gatherer society with sedentary agriculture; the demise of the great empires of antiquity; the transformations of Christianity and Islam from small sects in Palestine and the Hijaz to world religions; the shift from feudalism to capitalism; the devastation wrought by European colonialism; the Agricultural and Industrial Revolutions; and the creation of the modern welfare state.

Denisovans would have looked similar to Neanderthals although they appear to have had much bigger teeth, and they carried a number of gene mutations, including one that affected red blood cells and allowed them to live comfortably at high altitudes.

According to this argument, we came out on top because we were more intelligent. It isn’t difficult to understand why many people find this idea appealing. It allowed humanity to regain the privileged position that it lost when Darwin’s theory of evolution by natural selection made it clear that we were just another species of animals. We might be apes, but at least we are exceptionally brainy apes.

The assumption that we are uniquely clever is apparent in the name we have given our species—Homo sapiens, of course, literally means wise man. Symbolic behavior is seen as so vital to the essence of modern humans that several influential academics have referred to us as the “symbolic species” or “Homo symbolicus.”[22]

The idea of the cognitive revolution is conveniently Eurocentric. It locates modern-day France and Germany as the site of the metamorphosis of human behavior and identifies the first Homo sapiens capable of symbolic thought as those who left Africa and then turned left when they reached the Levant.

When the first complete skeleton of a Neanderthal was discovered by three Catholic priests in 1908 in La Chapelle-aux-Saints in southern France—about 300 kilometers west of Chauvet—the Church made sure it ended up in the hands of someone who shared their worldview, Marcellin Boule, director of the Laboratory of Paleontology at Muséum d’Histoire Naturelle in Paris, reconstructed the specimen so that it looked much more simian than human, with its forward-jutting head, slouching shoulders, hunched spine, bent knees and even opposable toes. Boule’s work was flawed, but it had a profound impact on scientific understanding of Neanderthals for the next half-century and it still informs the popular stereotype of the ape-like cave man.

One recent academic article argues that it is the result of a “modern human superiority complex,” while an anonymous archeologist quoted in the New York Times refers to “modern human supremacists.”

The remarkable artistic accomplishments that seemingly emerged from nowhere between 40,000 and 30,000 years ago in western Europe may have occurred when Neanderthals and Homo sapiens began to mix and exchange ideas after being separated for several hundred thousand years.[49] While the hypothesis that Neanderthals inspired Homo sapiens’ creative explosion is speculative, it is certainly plausible. The American geneticist David Reich cites evidence that Neanderthals borrowed tool-making technology from Homo sapiens.

anyone alive today whose ancestors are Europeans, Asians or Native Americans has inherited about 2 percent of their genes from Neanderthals.[52] While this might not sound like much, we don’t all have the same bits of Neanderthal DNA and when we pool all these gene variants they account for about 40 percent of the Neanderthal genome

When scientists looked at the calcified plaque of a 48,000-year-old Neanderthal’s teeth, they found the DNA of a strain of archaea called Methanobrevibacter oralis that is present in the mouths of humans today and is associated with gum disease.[56] After comparing the Neanderthal sample with a modern strain, it became clear that the microbes’ last common ancestor lived about 120,000 years ago. As that is several hundred thousand years after Neanderthals and Homo sapiens diverged, the germ must have been transmitted between the two species. The most likely way this happened was through kissing or perhaps sharing food.

But Homo sapiens took a much quicker route to immunity—by interbreeding. Reproducing with another closely related species is an unintentional kind of biohacking: it immediately endows a species with gene variants that are already adapted to the new environment. Introgressed Neanderthal DNA was crucial in helping Homo sapiens to adapt to the new pathogens that they encountered as they migrated out of Africa. This process has been called the “poison-antidote model” of adaptive introgression: Neanderthals gave Homo sapiens a “poison” by exposing them to a novel pathogen, but also the “antidote” in the form of introgressed gene variants that confer resistance to the pathogen.

Neanderthal gene variants most likely to be retained by Europeans today are those which code for proteins that interact with RNA viruses, particularly HIV and flu, and were first acquired about 50,000 years ago.

Tibetans carry a Denisovan gene mutation that affects red blood cells, making it possible to live comfortably on a 13,000-feet- or 4,000-meter-high plateau where the air contains 40 percent less oxygen than at sea level.[67] Another gene variant that increases the size of the spleen is carried by the Sama-Bajau, nomadic people who live on flotillas of houseboats in the seas off the Philippines, Malaysia and Indonesia.[68] The spleen stores oxygen-carrying red blood cells, and when humans hold their breath it expels these cells to boost oxygen levels; this helps to explain how Sama-Bajau are able to dive to depths of over 230 feet or 70 meters with nothing more than a set of weights and a pair of wooden goggles. The Inuit of northern Canada and parts of Greenland and Alaska have retained Denisovan genes that influence the storage of fats, which helps them to thrive in an exceptionally cold climate.

Estimates for their population size vary from 5,000 to 70,000—tiny when one considers that they were spread across a region that stretched from the Atlantic Ocean to Siberia.[71] It shouldn’t come as a surprise that there is evidence of long-term inbreeding. DNA analysis of a female Neanderthal who was alive over 50,000 years ago in the Altai Mountains demonstrates that her parents were half-siblings and that mating between close relatives had been common among her recent ancestors.

There were between 120,000 and 325,000 modern humans when they began to venture out of Africa,[73] and their genome had four times greater diversity.[74] Homo sapiens would therefore have been more resilient to infectious diseases carried by Neanderthals.

The vast majority of pathogens that are capable of infecting humans are zoonotic—that is, they originate in animals and then jump the species barrier to infect us. So the greater variety of life in tropical regions means that there are many more deadly pathogens there than in temperate zones. Homo sapiens, whose ancestors had lived in Africa for millions of years, carried a far greater disease load than Neanderthals, who had inhabited Europe for hundreds of thousands of years. As a result, Homo sapiens would have developed resistance to Neanderthal viruses and bacteria before Neanderthals became tolerant to Homo sapiens’ pathogens.

To understand the potential impact of contact between Homo sapiens and Neanderthals, consider that Native Americans and Europeans had been separated for about 17,000 years before renewed contact literally decimated the indigenous population of the Americas in the sixteenth century. Modern humans and Neanderthals were separated for at least thirty times longer.

A study based on observations of foraging communities over the last fifty years or so estimated the average lifespan of hunter-gatherers to be around seventy-two years.[10] Remarkably, this figure is only one year less than the global life expectancy today according to World Bank data.

A recent study demonstrated that our planet is capable of supporting no more than 10 million hunter-gatherers.[18] By 1800 CE, the world’s population had grown to about 900 million with only very basic technology, so this estimate is pretty much spot on.

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 American anthropologist Marshall Sahlins sardonically refers to the adoption of agriculture as the “Neolithic Great Leap Forward”—an allusion to the Chinese Communist Party’s Second Five Year Plan (1958–1962), which contributed to the greatest famine in history and tens of millions of deaths.

Many of the infectious diseases that afflict contemporary humans are caused by Neolithic pathogens.

The Aedes aegypti mosquito that spreads yellow fever also benefited greatly from recent human activity because it likes to reproduce in containers full of stagnant water. This had led the American historian John McNeill to suggest that they are, in fact, a domesticated insect.

A recent study analyzed the evolution of the more than 1,500 genes that play a role in humans’ innate immune system, revealing that most adaptations—where a favorable new gene mutation quickly spreads throughout the population—occurred in the last 6,000 to 13,000 years, which roughly corresponds to the period when humans took up settled agriculture.

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.

Yersinia pestis did not evolve into a flea-borne bubonic plague until the beginning of the first millennium BCE.[70] Prior to that it would have been transmitted by sneezing and coughing and infected the lungs. According to the World Health Organization (WHO), pneumonic plague kills almost all infected people if it is left untreated, compared to between 30 and 60 percent for bubonic plague.

The Steppe Herders that swept across Europe after the Neolithic Black Death are also the most likely source of all Indo-European languages, which are now spoken by just under half of the world’s population.

All Indo-European languages share similar vocabulary for words related to wagons, including axle pole, harness and wheel. This is very strong evidence that the population responsible for Proto-Indo-European must have migrated into Europe after wheeled vehicles started appearing in the archeological record between 6,000 and 5,000 years ago.

Followers of these new religions were convinced that it was the righteousness of their beliefs that explains their rapid growth. But, as we shall see, infectious diseases played a vital role in both the demise of the Greco-Roman gods and the rise of two new religions: Christianity and Islam.