The Plague Cycle

by Charles Kenny

  That’s the irony of our progress against death from infection over the past two centuries. It has helped create the perfect environment for the emergence of a new disease outbreak and the perfect environment for that outbreak to have catastrophic social and economic impact. The world’s population (human and livestock alike) has never been as large, nor commerce so global, nor peace so widespread. Covid-19 is only the latest in a succession of new infections that have emerged and spread in our closer and connected world. Before the current novel coronavirus were previous coronaviruses—as well as AIDS, Ebola, and bird flu.

  At the same time, we’re abusing our most effective tools against disease—misusing antibiotics by feeding them to farm animals in bulk; leaving our children unvaccinated; funding research on new bioweapons while underfunding new vaccines, treatments, and cures; and letting weak medical systems fester in the world’s poorest countries. And our reaction to disease too often echoes that of our distant forebears; at a time when global human interaction is central to our wealth and welfare, we call for flight bans and trade restrictions. Globally, we respond to new infectious threats too late. We don’t prepare and we don’t coordinate.

  We have to do better for next time, because there will be a next time. Phenomena ranging from evolution to climate to demographics mean that many infectious diseases tend to follow cycles: flu seasons move back and forth between hemispheres in a regular yearly pattern. Epidemics of diseases like measles and smallpox would strike every few years or decades as the number of new potential victims in a community climbed. The plague of the Black Death spread mass mortality in the sixth, the fourteenth, and the late nineteenth century at times of instability combined with closer global connections. And some epidemiologists argue that we’re in the midst of a new stage of an even longer cycle. After a first transition toward greater disease threats sparked by the rise of farming, followed by a second transition toward reduced threat thanks to interventions including sanitation, vaccines, and antibiotics, we’re now in a third epidemiological transition back toward greater infectious risk as a result of emerging new diseases spread worldwide by globalization.

  This last idea likely underestimates humanity’s ability to respond to disease threats. We are flattening the plague cycle. But through sufficient neglect or miscalculation, we could allow communicable diseases to fight back and reclaim their place as death’s most popular weapon. History suggests such a reversal would shape the coming century more than almost any other conceivable event—more than climate change, far closer to limited thermonuclear war. And even if that full threat doesn’t materialize, we could allow poor response to new diseases like Covid-19 to stifle global progress.

  But at least recent history suggests humanity’s response to the new threat can be rapid and effective if we so choose. And that reassures us that humanity in the twenty-first century is in a considerably better position in the fight against infection than earlier generations. Because for most of humanity’s time on the planet, effective responses never came.

  CHAPTER TWO Civilization and the Rise of Infection

  Being subject therefore to so few causes of sickness, man, in the state of nature, can have no need of remedies.

  —Rousseau

  Hippocrates, the “father of medicine” who’d treated victims in the plague of Athens, refuses gifts from the Persian king Artaxerxes, who is seeking the same help in dealing with a plague in his country. (Source: Hippocrates Refusing the Gifts of Artaxerxes. A. L. Girodet-Trioson, 1792. Wikimedia Commons)

  “Mitochondrial Eve,” as she was called, was a creation of scientific theory based on genetic analysis of her offspring—namely, us. In 1987, a team of population geneticists analyzed mitochondrial DNA from 147 people around the world. This segment of genetic code at the heart of every one of our cells is passed down from mothers—and only mothers—to sons and daughters. Using estimates of how long it takes DNA to mutate, the researchers calculated the time needed for all of the existing mitochondrial material around in humans today to have evolved from a single ancestral source. That single source they labeled Mitochondrial Eve. In theory, everyone on the planet today is her direct descendant, and she’s the most recent human of which that can be said.

  According to the DNA evidence, our common ancestor was alive more than one hundred thousand years ago.1 Mitochondrial Eve would have lived with a small tribe of people. Hunting and gathering takes a lot of land per person for food, so large communities simply aren’t practical.2 She lived far before the dawn of civilization and the rise of agriculture and cities. And she lived before the time when many of the world’s greatest infectious killers had evolved and spread—diseases including smallpox, measles, and the flu.

  Even so, there were many prehistoric parasites afflicting mankind. One example may have been the guinea worm, now near the edge of eradication. Larvae of the worm float in pools of water until a lucky few are swallowed by the cyclops—a small water flea. Once inside they grow, feast on the flea’s ovaries or testes, and wait for their host to get swallowed in turn—by a human drinking the water. This isn’t pleasant for the flea—or for us. As the cyclops dissolves in human digestive juices, the more robust guinea worm larva burrows through the human’s intestine and settles briefly in the abdominal wall. If the female larva finds a male to impregnate her, she eventually makes her way to the leg, where she hooks on, feeds, and grows over the course of a year—up to a yard in length. Most of that distance is made up by a hugely distended uterus packed with half a million embryos.

  The human host suffers from an irritating blister at the end of the worm. When it bursts, the wound reveals the uterus. To relieve the burning and itching, the victim often stumbles to the nearest water hole to douse the blister. As he or she does, the worm ejects embryos, releasing the next generation of guinea worms back into the pool.3 Clinical parasitologist Rosemary Drisdelle argues that the worm might be the origin of the fiery serpent that wraps around the rod of Asclepius as the symbol of medicine—because the traditional way of removing the guinea worm is to wrap its end around a stick and slowly, over the course of a month, wind the body around it until the whole worm is pulled out.

  Confronting, hunting, and eating wild animals could also have exposed early woman and her mate to tularemia (related to bubonic plague), toxoplasmosis, hemorrhagic fevers, and anthrax, alongside gangrene, botulism, and tetanus. And that’s to say nothing of the ticks and fleas growing on those animals (potentially carrying plague or sleeping sickness), or the mosquitoes that fed off primates ill with yellow fever, before snacking on human blood.4

  But while infectious diseases had a dramatic impact on human biology and instincts, and undoubtedly played a role in keeping the original human population in Africa in check, they may not have been the dominant factor. Many diseases were geographically concentrated. And the contagious diseases that were specific to humans couldn’t kill too effectively—there were too few humans, too spread out, to allow most deadly conditions to thrive without a reservoir of animal victims to fall back on.5 Again, hunting and gathering takes a lot more land per person than farming, and early humans would have been constantly on the move. That would have taken them away from areas with parasite-laden feces or mosquitoes gorged on the blood of fellow humans—in turn, reducing the risk of subsequent infection. Any condition that was too deadly would wipe out its hosts before meeting new victims to infect.6 That suggests it may have been a time of comparatively long natural life expectancy.7

  Something kept the number of humans planet-wide low. One factor may have been low birth rates among hunter-gatherers. Women who are part of San tribes (the bushmen of Southern Africa) historically gave birth between four and five times, a rate that is similar to Australian aboriginal women.8 Evidence from other hunter-gatherer communities in Africa—the Kung and the Efe—suggest a woman who lived through her reproductive years would give birth between 2.6 and 4.7 times.9 That compares to a total fertility rate for Sub-Saharan Africa as a who
le that was closer to 7 as recently as 1980. The lower numbers for the Stone Age groups probably reflect a combination of factors that includes a late age of sexual maturity, extended breastfeeding, and considerable movement.10

  Violence also had a large role in keeping populations in check—perhaps even larger than it did in later ages. In his history of violence, The Better Angels of Our Nature, Steven Pinker argues that average pre-civilization rates of violence were higher than anything we’ve seen since except in modern hunter-gatherer societies. Scientists examining prehistoric hunter-gatherer remains in Southern California found that one in five male skeletons showed signs of injury from a projectile like a spear or arrow. At one extreme, Azar Gat of Tel Aviv University concludes his review of hunter-gatherer warfare by suggesting violence accounted for as much as 15 percent of all deaths.11 Others argue for lower rates of violent deaths overall, and estimates vary considerably across different periods and locations.12 But the combined result of low birth rates, violence, and the prehistoric infections that did exist was that global populations could be counted in the millions—a tiny fraction of their size today.

  * * *

  The original parasites that preferred Homo sapiens had no other option but to live in the tropics—their victim of choice has resided in Africa and nowhere else for most of its time on the planet. Until the rise of civilization sparked the creation of a whole new set of infections, the bacteria, viruses, worms, and other organisms that called humanity home were evolved to complete their life cycle in Africa.

  Even today, pathogen diversity (the number of different kinds of microbes in an area that infect humans) remains far higher in the tropics than elsewhere.13 But because these microbes tend to maim and kill primarily in the developing world, where most people are poor and new drugs to treat the conditions won’t make money, they don’t attract much in the way of medical research. There’s a certain irony that some of humanity’s oldest parasitic foes are now grouped together under the moniker “neglected tropical diseases,” but that’s why.

  The control of fire and the invention of clothing allowed for mankind to survive cold winters, and gave us access to the world’s temperate zones. By moving to Europe, Asia, and the Americas, we outran some of those parasites. While globalization eventually spread many of the original tropical diseases of Africa to tropical parts of those newly inhabited regions, the long evolution and concentration of human infections in tropical climates is one reason why humans living in temperate zones to the north or south of the tropics remain healthier to this day.14

  Sometimes when an organism finds itself away from its usual predators and prey, the result is a population explosion, like the Japanese vine kudzu planted in the US, or rabbits in Australia. Humans outside the tropics benefited from this “ecological release.” The early years of new occupation in temperate zones like southern Europe and Asia north of the monsoon zone were a period of low infection and rich hunting.15 That may account for the global spread of humanity in a very brief period. Over about thirty thousand years starting in 40,000 BCE, humans reached every continent but Antarctica.16

  The expanding human populations that resulted may have played some role in wiping out a number of different large-bodied game animals. South America was home to horses and camels prior to its original human settlement, but they were gone soon after.17 Even if not, more humans meant more human creativity, which would have been a factor behind the technological innovations that created agriculture.

  * * *

  While plagues don’t get a mention in the early chapters of the Bible, once that text reaches Egyptian civilization, it’s flooded with stories of pestilence—not only frogs, but boils, lice, flies, and other unknown horrors.18 That may reflect an underlying historical truth: agriculture and civilization set off a global firestorm of disease.

  Even the most inefficient early agriculture was associated with populations per square mile that were ten or twenty times higher than among nomadic groups. And the landscaping and irrigation alongside granaries that accompanied larger-scale farming meant more people had to stay in place—early civilizations enslaved nearby herders to farm their fields.19 While less movement equals less exposure to new disease pools, the combination of population density and settlement was vital to the growth of infection.

  At first, staying in one place for a long time would have been a boost to the traditional afflictions of pre-civilization humans—mosquitoes, for example, would find more people to feed on, and more irrigated and cleared land to live in. And the malaria that used mosquitoes as a vector would spread more rapidly when the chance of the same insect biting, in succession, an infected victim followed by an uninfected one increased by orders of magnitude.20 A 3000 BCE Egyptian papyrus on medicine contains a reference to “the pest of the year” that may have been malaria, and mummies from the period show evidence of malarial infection.21

  Bolstering this same point that the more humans are loitering about, the greater the chance of illness: worms excreted onto a village path or into a field or nearby pond were far more likely to wriggle their way into another human than if they’d been defecated in the forest. Microbes that can only survive a small time outside their host, including the bacteria that cause leprosy, typically spread with greater ease in close-packed towns.22 Finally, the piles of garbage that are the hallmark of any permanent human habitation attract flies, wild dogs, and rats—each with their own disease-spreading potential.

  Because civilization involves lots of people and domesticated animals living in close proximity, it also provided the perfect environment for species-hopping infectious killers to spread. Take pigs: they’ve long had an important role as refuse collectors, demonstrated in Egypt in 2009 when the government took the fateful decision to cull all three hundred thousand of the country’s pig population, ostensibly as a measure to prevent the spread of swine flu. Less than a year later, Egypt’s parliament was holding a stormy session decrying the policy, which had led to mounting garbage piles across the country. Hamdy el-Sayed, legislator and chairman of the Doctors’ Association, called it a “national scandal.”23 But precisely because they eat almost anything, pigs can be a major source of infection themselves. That’s likely why both the Jewish and Islamic faiths suggest you shouldn’t eat pork. Deuteronomy warns that “the pig, because it has a split hoof, but does not chew the cud; it is unclean for you. You shall neither eat of their flesh nor touch their carcass.”

  Trichinosis is caused by the pork worm—three millimeters long at their tallest. Thousands of the parasites invade the body of humans unwise enough to eat an infected and undercooked sausage or pork chop. Besides triggering vomiting, diarrhea, and fever, the larvae, as they occupy muscle cells, weaken the victim’s heart and diaphragm. Respiratory, heart, or kidney failure related to the parasite can all prove fatal. Pigs themselves pick up the worms by eating garbage containing bits of raw meat or animal remains—or cannibalizing their former farm-mates, or eating a rat that happens to be attracted to the same garbage.24

  And while sausage lovers may have heard enough already, pigs and humans also share the pork tapeworm. Infected humans can develop cysticercosis, where the worm’s larval cysts spread to the brain. The condition can cause seizures, stroke, or death. As many as fifty thousand people still die each year from cysticercosis.25 While humans were infected by tapeworms long before pig domestication, closer proximity may have increased infection rates.26

  Over time, and largely within the last few thousand years, a more insidious effect of civilization and domestication emerged: the evolution of new infections. Some diseases of civilization may have evolved from livestock illnesses. Proximity to a dense population of inter-bred domesticated animals presented considerable opportunities for infections to develop and jump species: we’ve seen that influenza is similar to diseases in pigs and ducks, for example, while diphtheria and rotavirus may have spread from domesticated cattle and sheep (tuberculosis may have jumped the other way, from humans to
cows).27

  Human population density really matters for a number of the most harmful single-species diseases that emerged thanks to civilization. That’s because the minimum population required to sustain an infection depends on how rapidly a disease spreads, how deadly it is, and whether infection gives lifelong immunity to survivors.

  Microbes that tend to survive in small host populations are those that spread easily, can live outside hosts for a long time, and then live inside their hosts for a long time as well—meaning they kill infrequently and promote no immunity. These were the diseases unique to humans that could best survive the low population densities of pre-civilization. Consider the type of herpes virus that causes cold sores: it has been infecting humans since before they evolved from our ancestor Homo erectus. You’re quite likely to be living with the virus: about two-thirds of people do. But most of the time cold sores are all it ever causes, and it lives relatively peacefully in your nerve cells until you die.28

  Compare the torpor of herpes to the relentless-as-Voldemort measles, one of history’s biggest murderers. At some point the virus jumped species from cattle to humans. Its first symptoms are a cough and sneezing, which is how it spreads. Only later does the characteristic rash develop. Hosts can die from complications related to a swollen brain caused by encephalitis, diarrhea and dehydration, or pneumonia.

  The first time that a disease like measles or smallpox arrives, it rips through the entire population, infecting widely and killing off those particularly susceptible—because of factors like age, malnutrition, or genetic variation. But the survivors become immune, often for life. And if most of the population has been exposed, that creates “herd immunity”: the number of potential victims has shrunk, and so the chance that a coughed-out measles virus reaches a non-immune host drops. If that chance falls far enough so that the average person with measles infects less than one new victim, the epidemic eventually dies out.