Plagues upon the Earth

Disease and the Course of Human History

Kyle Harper

• Publisher: Princeton University Press
• Year: 2021
• ISBN:
  9780691224725
• Topic: Historia
• Subtopic: Historia social

A sweeping germ's-eye view of history from human origins to global pandemics Plagues upon the Earth is a monumental history of humans and their germs. Weaving together a grand narrative of global history with insights from cutting-edge genetics, Kyle Harper explains why humanity's uniquely dangerous disease pool is rooted deep in our evolutionary past, and why its growth is accelerated by technological progress. He shows that the story of disease is entangled with the history of slavery, colonialism, and capitalism, and reveals the enduring effects of historical plagues in patterns of wealth, health, power, and inequality. He also tells the story of humanity's escape from infectious disease—a triumph that makes life as we know it possible, yet destabilizes the environment and fosters new diseases.Panoramic in scope, Plagues upon the Earth traces the role of disease in the transition to farming, the spread of cities, the advance of transportation, and the stupendous increase in human population. Harper offers a new interpretation of humanity's path to control over infectious disease—one where rising evolutionary threats constantly push back against human progress, and where the devastating effects of modernization contribute to the great divergence between societies. The book reminds us that human health is globally interdependent—and inseparable from the well-being of the planet itself.Putting the COVID-19 pandemic in perspective, Plagues upon the Earth tells the story of how we got here as a species, and it may help us decide where we want to go.

PART I

Fire

1

Mammals in a Microbe’s World

The Mightiest Living Beings

In 1877, a colleague sent Charles Darwin an academic journal with an unusual series of photographs. Taken by the German scientist Robert Koch, they were the first photographs of bacteria ever published. Darwin’s correspondent realized the importance of what he was seeing. They were “the least but also perhaps the mightiest living beings.” Darwin recognized it too. “I well remember saying to myself between twenty and thirty years ago, that if ever the origin of any infectious disease could be proved, it would be the greatest triumph to Science; and now I rejoice to have seen the triumph.”¹

In 1882, just weeks after Darwin died, Koch made public his sensational discovery of the bacterium that causes tuberculosis. The idea that microscopic, particle-like forms of life might exist and cause disease had long floated around the margins of respectable science. Over the course of the nineteenth century, the tide turned. Scientists—some of their names hallowed, like Koch and Louis Pasteur, and others little remembered, like Agostino Bassi and Casimir Davaine—built an irresistible case for what we retrospectively call germ theory. As the evidence continued to accumulate, the old consensus, the idea that disease was caused by filth or by deadly vapors in the atmosphere known as miasma, crumbled. Koch’s discovery of Mycobacterium tuberculosis was an especially poignant moment, laying bare the counterintuitive truth that such a tiny life-form could cause such vast human misery. The notion that infectious diseases have microscopic agents with their own motives was ascendant only in Darwin’s dying days. But his theory of evolution, the great unifying explanation of all life, is the foundation for understanding the pathogens that cause human disease.²

In Darwin’s lifetime, increasingly powerful microscopes helped to facilitate the mental revolution that germ theory required. We are now living through an equally radical sea change, in which the ability to observe the genomes of microbes thanks to new sequencing technologies helps us to perceive how utterly pervasive and diverse they are. They have been here far longer than we have—from the beginning of life on earth—and, odds are, they will be here long after we are gone. It is thrilling if also humbling to learn that our story inserts itself as a minuscule chapter in a much vaster and much older struggle between hosts and parasites.³

It’s a microbe’s world. We’re just living in it.

Defining Basic Terms

We experience disease as a medical phenomenon: naturally, we think of germs as things that make us sick. From nature’s perspective, though, we are hosts, not patients, and they are parasites. They are rewarded and punished according to how well they succeed in sending their genes into future generations. Our parasites have evolved wildly different strategies and abilities to do so. Some use poison, some use disguise. Some are aggressive, some are ingeniously subtle. Yet every one of them is the product of natural selection. In the well-known words of the biologist Theodosius Dobzhansky, “nothing in biology makes sense except in the light of evolution.” Ultimately, the driving logic in the history of infectious disease is ferocious and unforgiving Darwinian selection.⁴

Darwin’s theory provides the framework to answer questions about the patterns of human disease in both the past and the present. Why are some diseases, and many of our oldest ones, adapted only to the tropics? Why do humans have such an array of diarrheal diseases? Why did smallpox and measles emerge along with large-scale empires, and why did those same viruses fail to establish in small-scale societies like those on remote islands? What made bubonic plague so deadly? How does the influenza virus so often outsmart our vaccines? Why is HIV so insidious? No answers make sense except in the light of evolution.

Our germs have no intentions or consciousness. We can anthropomorphize them for the sake of simplicity—we speak of them “trying” to do things like evade our immune system or adapt to new circumstances. That is fine, so long as it is understood that evolution is a blind, physical process that rewards those individuals whose traits are most effective at transmitting genes to succeeding generations. The pathogens that seem exquisitely designed to exploit our body and its defenses are simply the winners of past contests. And as with a stock portfolio, the past is no guarantee of future success.

Let us begin by acquainting ourselves with humanity’s enemies. Evolution furnishes the logic of taxonomy, or the biological classification of organisms. Over the last generation, the tools of taxonomy have changed radically, especially for microbes. Consider that, before genomic data became widely available, the family trees of microbes had to be pieced together by observing their characteristics. For obvious reasons, it is hard to observe microbial organisms directly. In consequence, a whole array of criteria and chemical tests were devised as aids to classification. Gram-staining is maybe the most familiar; this technique involves a dye that will soak into the cell walls of some bacteria and turn them a violet color. Gram-staining captures something fundamental about bacterial physiology (whether or not a certain kind of sugar is used in the cell wall—a matter of great interest to your immune system as well). But compared to genome sequencing, such tests are limited and slow, what the abacus is to the supercomputer.⁵

Genome sequencing has revolutionized microbial taxonomy. It has also underlined the fact that the preponderance of the world’s biodiversity is microbial. It is now possible to see more clearly the place of our disease-causing microbes in the tree of life and to view them against the backdrop of a much bigger invisible world. Most of the planet’s microbial inhabitants are indifferent to us, and many of them are even helpful, playing an essential role in ecosystems and in our bodies. Microbes are everywhere—around, on, and inside us. We are far more porous and permeable than we had ever thought, but only a tiny sliver of the earth’s microbes would or could do us harm. Recognizing this diversity can help to sharpen some fundamental questions, like “What is a pathogen?” and “What is a parasite?”⁶

The word pathogen is a modern English coinage derived from two Greek roots meaning “to cause to be” and “disease.” Simply stated, a pathogen is an organism that causes disease. The term is a handy and helpful way of describing certain phenomena in nature. Pathogens form a category much like “creatures that fly,” which encompasses birds, bees, bats, butterflies, and a rare fish or two. These organisms are defined by what they do rather than genetic relatedness. But unlike winged creatures, what pathogens do, by definition, is affect other organisms in a particular way. Moreover, flying creatures dependably fly. Many pathogens, by contrast, are rank opportunists, only causing disease under certain circumstances. It would be better to say, then, that a pathogen is an organism capable of causing disease in another organism.⁷

The word parasite derives from an ancient Greek term referring to a person who eats at the table of someone else. A parasite is an organism that lives at the expense of another, taking energy from its host and causing at least some level of harm. Often, the word parasite in vernacular English is reserved to denote macroscopic parasites such as worms. But the bacteria and protozoa that exploit us meet the textbook definition of parasite, even if English usage has never caught up. What about viruses? The idea that viruses are parasites grates against the etymology of the term, because viruses do not “eat” (i.e., perform metabolism). Even though viruses are more like hijackers than thieves, in most other senses, viruses fit the definition of a parasite. Sometimes the word microparasite is used to distinguish microbial parasites from worms. There is not perfect consistency in English usage, in part because the concepts behind the words are slippery. We will use pathogen to mean any organism that can cause disease, and parasite to mean any organism, macroscopic or microscopic, that exploits a host.⁸

Pathogen is a medical term. Parasite is an ecological one, which is to say that it describes something fundamental about the place of organisms within the flow of energy through the environment. In nature, organisms either produce their own food or take it from others. Producers are autotrophs, organisms like plants and some bacteria that use energy from the sun or chemical compounds to make their own food. The rest of us are heterotrophs who acquire energy from producers—or from other consumers who have taken it first. Parasitism is functionally similar to predation; the host is a kind of prey. As E. O. Wilson put it, “Parasites, in a phrase, are predators that eat prey in units of less than one.” In simple terms, parasitism is a strategy for taking the essentials of life from another organism. Parasites are simply heterotrophs like us, in search of energy and materials to do the work of reproducing their genes. By looking at it this way, you can see yourself a little more clearly from their perspective. You are an organized bundle of refined energy, essential elements, and machinery for making proteins: an irresistible target.⁹

Parasitism is a strategy that has arisen countless times through different evolutionary pathways in the 3.5 billion years during which life has existed on earth. Precisely because the strategy has evolved repeatedly, our parasites form an unruly and biologically diverse cast of characters. Collectively, our parasites are more like what ecologists call a guild, a group of unrelated species that share an ecological resource or territory. The human parasite guild has numerous species as members, but there is not even remote agreement about how many organisms cause human disease. One standard and often cited catalog of human pathogens includes 1,415 species. A more recent and systematic survey identified 1,611. Oddly enough, there is only about 60 percent overlap between these lists, so the number of unique pathogens identified between them is 2,107. Yet the Global Infectious Diseases and Epidemiology Online Network (GIDEON), a standard database of infectious diseases created for clinicians, lists 1,988 bacteria alone that have been found to infect humans. More than one thousand of these are not in either of the other lists, meaning the total surpasses three thousand, and this tally surely understates the number of organisms that could infect humans.¹⁰

Why is there so much uncertainty about how many organisms cause disease in humans? The simple reason is that most of the species in the tallies cited above are fundamentally unimportant as pathogens of humans. Most organisms capable of causing disease in humans do so rarely. They only infect humans incidentally and transiently, but as human populations have grown, and genome sequencing has become more common, these rare and ephemeral infections get caught, cataloged, and counted. Consider an example drawn from the genus Mycobacterium. One study counted sixty-four different species in this genus as pathogens of humans. Another study found twenty-eight. If you asked a global health expert concerned with human well-being, she would probably say that there are five medically important species of Mycobacterium (including the bacteria that cause tuberculosis, leprosy, and Buruli ulcer). The other species can infect humans and cause disease, so, strictly speaking, they can be human pathogens. But it is relatively meaningless to include the other species in any count of human pathogens.¹¹

What we would truly like to know is how many major identified species of human pathogens there are. Of course, every one of these terms is complicated; there is even debate over what constitutes a species, let alone what makes a pathogen a human pathogen. And where should we draw the line regarding what constitutes a major human pathogen? There is a lot of ground between a species that infects only a handful of humans each year and one like the bacterium that causes tuberculosis, which is responsible for about ten million new cases annually. Although drawing a line to determine what counts a...