THERE HAS BEEN a lot of imperfect thinking about disease the past two years. As the world has collectively experienced a throwback to an era without the protections of effective medical interventions, more broadly conceived histories — true pandemic histories — are hard to find. Many of the bigger questions have gone unanswered, and sometimes unasked. Where do infectious diseases come from? When and how do they disappear? Have there been times or circumstances when disease burdens were heavier or lighter? Where do we, in our present COVID-19 moment, sit within that history?
Billed as “a monumental history of humans and their germs,” Plagues Upon the Earth: Disease and the Course of Human History by Roman economic historian Kyle Harper offers an opportunity to consider what “good thinking” in disease history might look like. Harper’s background as a Classicist, as well as his demonstrated interest in the new ways climatology and genetics enable reinvestigation of Roman history, would, one might expect, situate him as a welcome new interpreter of humans’ encounters with disease. Plagues Upon the Earth is a book meant to impress. The notes run to nearly 60 of its 700 pages, the list of references to nearly 90. In all, over 2,100 references are cited. Surely this is the global history the world has needed. Presumably, we will find a story that differs significantly from the half-century-old accounts of Alfred Crosby and William McNeill, who wrote in the pre-AIDS 1970s about infectious diseases as history-altering forces. Given the extraordinary strides in global historical thinking in the same half-century, one would especially hope to see framings beyond a European focus. These hopes are only partially fulfilled.
Harper’s thesis is simple: “Our germs are a product of our history.” By that, he means that different infectious diseases have arisen at different inflection points in humans’ collective journey on the planet, often due to human behaviors themselves. The oldest diseases, such as gastrointestinal parasites, date from our time as hunter-gatherers. Sedentism and domestication of animals brought other types of pathogens, as did the new respiratory environments of increasingly crowded urban communities in the Bronze and Iron Ages. The interconnected world of medieval trade intensified disease spread in Eurasia and Africa, while the unification of the world’s tropical zones during the age of European colonialism allowed additional diseases to spread intercontinentally. Finally, new sources of energy and new transportation technologies of the 19th and 20th centuries allowed the speed of spread to increase nearly a hundredfold, even as urban communities (the ultimate microbial playgrounds) grew ever larger.
The history of infectious diseases is one of the more difficult fields within the history of medicine. The documentary record on which it is grounded has inherent limitations. In, say, the Hippocratic Corpus or Ayurvedic traditions (composed in a pre-laboratory age when observation of microorganisms was impossible), the disease conceptions differ so much from germ theory conceptions that, in the absence of very precise symptom descriptions, it is impossible to translate past categories into modern terms. This is known as the problem of retrospective diagnosis.
For the material history of disease, paleopathologists (a sister subspecialty within physical anthropology) can look at lesions created on bones or teeth by chronic health conditions, such as malaria or sustained malnutrition. But microorganisms are impossible to discern even with a microscope, since they (like most soft tissues) are destroyed as postmortem decay sets in. A quick-killing disease like plague could never be assessed from ocular examination of the bones alone.
Riding the crest of a decade-old shift in infectious disease research, Harper exploits a new generation of scholarship that engages openly with data yielded by genetics. Why genetics? Harper cutely describes the twin contributions of this field as “tree thinking” and “time travel.” Nicknames notwithstanding, this is high-tech science of the first order.
“Tree thinking” is phylogenetics, which analyzes either whole genomes or partial genomic sequences to find common variants in different lineages of pathogens. Simply put, it studies the evolution of microorganisms. Tuberculosis (TB), for example, has nine known lineages, each with many localized strains. Analyzed one against another, these variants allow construction of phylogenetic trees — family trees showing, for example, how closely related a strain of tuberculosis in India might be to a strain in the Philippines or Ethiopia. (It’s a pity that a book with more than two dozen images, figures, maps, and tables couldn’t have offered a single figure showing how visually-oriented “tree thinking” analysis works.)
Understanding phylogenetics is crucial to exploiting the second contribution of genetics: “time travel,” or palaeogenetics, where the coin of the realm is aDNA — ancient DNA. Palaeogenetics circumvents both the semantic deficits of historical disease descriptions and the ocular limits of paleopathology by retrieving fragments of microorganism genomes. Sometimes these come out of tooth pulp, sometimes out of the bones themselves. The retrieved fragments are pieced together and compared with the genomes of modern descendant organisms to show how they’ve changed.
Even a single retrieved genome from a well-dated archaeological site allows researchers to put a “pin” in their phylogenetic trees, with a fixed location (the site of archaeological excavation) and a more or less fixed time (the result or carbon-dating or archaeological contextualization). The more “pins” in a tree, the more historically precise the reconstruction becomes. Whereas with phylogenetic analysis of modern genomes, researchers could only roughly guess when evolutionary splits and divergences occurred, with palaeogenetic data they can approach real chronological precision.
Here, then, is genetics’s superpower: it permits us to write the history of disease from the perspective of the pathogen, not simply from the necessarily blinkered perspective of human (macroscopic) observation. Diseases thought to have afflicted humankind “since time immemorial” have turned out to be younger — in some cases, much younger — than previously believed. That pushes their history closer to eras like the Iron Age, Classical Antiquity, and the Middle Ages, where we have considerable archaeological and documentary records to contextualize disease emergence and proliferation.
The ability to more closely interrogate the circumstances of disease emergence makes apparent genetics’s other superpower, one only obliquely discussed by Harper: tracking. Precisely because it is built on the foundation of hundreds or even many thousands of modern genome sequences gathered from around the world, palaeogenetics allows tracking of diseases across space and time. Genetics converts pathogen history into a universal language of science, equipped with GPS.
Harper revels in the idea that he is writing global history. The word “global” appears several hundred times. Yet there are gaps and omissions that signal a more partial view. Harper proposes six distinct periods of globalization, a list that omits the migration of First Peoples into the Americas and Oceania. These migrations completed humans’ distribution into every longitude at least 300 years before Columbus and Magellan. From his opening lines, Harper makes clear that the “we” of his narrative is wealthy and Western: “Our whole way of life depends on the control of infectious disease.” That may be a universal truth, but these words launch a vignette about a household with running water, an indoor toilet, electricity for appliances, and a refrigerator to ensure that food remains fresh.
The current COVID-19 pandemic has made abundantly clear that the “we” of global health is every human on the planet. This is the first time in history that a single pathogen has touched every continent, and virtually all populations, within perhaps three to four months of its origin. Our worldwide communications networks, and a common language of genetic science and epidemiology, have allowed us to see, in real time, what “global” really means. And what we see is a vast sea of inequality.
A historical perspective shows that that inequality lies in more than unequal access to newly developed vaccines. Unequal burdens of disease themselves have histories. Most “global” historiographies exacerbate those inequalities by ignoring them. Any act of storytelling entails elisions and exclusions, of course, but in privileging a Western “we,” in making the story of Europe’s or the United States’s experience of disease central, Harper is compounding several centuries of Eurocentrism in the history of medicine that have occluded not only the experiences of populations beyond Europe but also, importantly, information about how infectious disease processes actually work.
New efforts to track disease across historical landscapes have thus far been most successful with plague, a rather ironic result since plague (which arose about 7,000 years ago in the context of the Eurasian steppe) was, and remains, a disease of rodents rather than people. As palaeogenetics becomes more sophisticated in its techniques, the evolutionary histories of human-adapted diseases can also come more clearly into view.
A plague-like disease that most people have never heard of is paratyphoid fever. Caused by the bacterium Salmonella enterica serovar Paratyphi C, paratyphoid fever has almost disappeared from the world. Enough of it still exists, however, to enable the recent reconstruction of its evolutionary history. S. Paratyphi C is one among about 2,500 serovars of Salmonella, the genus of bacteria often implicated in food poisoning. Harper lists the typhoid and paratyphoid diseases as “quiet, persistent killers” that “for millennia” have haunted human communities. That it true enough for the general class of S. enterica, but Harper flits over S. Paratyphi C’s particular story in a couple of paragraphs, even though in a footnote he calls it “[probably] [t]he most important paleogenomic discovery of a pathogen so far.” S. Paratyphi C, he suggests, emerged as a specialist human pathogen in Europe around the time of pig domestication — in other words, as much as 10,000 years ago. In fact, that’s not at all the story that the genetic record tells us.
Current “tree thinking” indicates that this particularly virulent strain of Salmonella only decisively diverged from strains circulating in pigs sometime around the late ninth century. The stunning discovery Harper alluded to was the retrieval in 2018 of this Eurasian-origin disease in a mass mortality burial in 16th-century central Mexico. This was followed in 2020 with evidence from mass burial sites in Lübeck, which were thought to be due to plague but instead yielded multiple samples of S. Paratyphi C. Further retrievals in Europe have since been made.
Why is the story of this obscure disease significant? In part, because its discovery in medieval Norway, Belgium, and Germany, as well as 16th-century Mexico and 17th-century Spain, tells us that the disease had the potential to cause as much damage to European communities as to Indigenous populations in the Americas. Moreover, even its modern distribution has it moving between Europe and Asia, on the one hand, and Europe and Africa on the other. This is a global disease par excellence. How it arose within Europe is an important question. But how it then came to afflict populations outside of Europe is equally important.
In moving from Europe to Mexico, paratyphoid fever falls within the stew of diseases involved in what has been called, since Alfred Crosby coined the term in 1972, the “Columbian Exchange” across the Atlantic, which Harper identifies as the fourth of his six periods of globalization. Harper places the history of tuberculosis, another disease of Old World origin, within his second and third eras of globalization: the Iron Age and “Peak Old-World globalization,” about 1,000 years ago, when “Europe, Asia, and Africa were linked by vibrant overland networks of exchange as well as by Indian Ocean commercial circuits.”
Whereas paratyphoid fever seems to be passing into extinction, TB is, even today, still found in one-quarter of the world’s population, a century and a half after its laboratory identification by Robert Koch and 80 years after effective antibiotic treatments became available. Like recent work on the Pacific migrations of Polynesians, TB has disrupted narratives about the timing of globalization, having passed into the Americas and apparently even the Pacific before regularized European transoceanic crossings.
In 2014, genetic sequencing from Peruvian mummies confirmed that pre-Contact Indigenous peoples in the Americas suffered from TB at least as early as ca. 1000 CE. This finding, in itself, was not surprising since paleopathological work had established decades earlier that these and other pre-Contact remains in North and South America bore telltale marks of TB infection. More remarkably, the 2014 study also established that the disease strain most closely resembled not a human form of the disease, but one hitherto found only in pinnipeds — seals and sea lions.
Harper includes this story in his book, but he sensationalizes the zoonotic involvement of pinnipeds while failing to ask what effects TB had in the Americas in the 700 years before European strains arrived. The pre-Contact lineages of TB are extinct; how they became so is unclear. What is clear is that the major epidemics of TB in Indigenous populations in the modern period were caused by the younger, more lethal European strains. Similarly, the dominance of equally virulent Beijing strains in East and Southern Africa are the result of introductions in the colonial period, and not a function of ancient endemicity. Harper has more to say about TB, but it is mostly about Europe’s experiences “conquering” the disease in the late 19th and 20th centuries. Although we know better now than to frame TB’s history within “from time immemorial” vagueness, Harper’s historical framework cannot explain why over two billion people still live with TB in the third decade of the 21st century.
COVID-19 has been both a great equalizer and a great revealer of truths too many wished to ignore. It has educated richer nations in the humbling failures of modern medicine. Vaccine inequity is playing out in real time, even as the United States — developer of three of the most successful vaccines — squanders its technological wealth. But it is only the most recent among many inequities, one of which is historiographical.
Harper’s Plagues Upon the Earth is Western Civ with a veneer of science. Too much of the world is missing. The COVID-inflected world is ready to see what “global health” means in all its permutations, past and present. The first step is to see the earth whole.
Monica H. Green is an expert in the history of medicine in premodern Europe and global infectious diseases.