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The study and treatment of disease is a neverending pursuit due to human evolution and our ability to adapt to and resist diseases over time. Research shows that disease increased as foraging stopped and humans began settling together in one place. Only in the twentieth century did epidemiologists recognize that hosts and germs adjust to one another, so symptoms (and medical diagnoses) change.
Disease refers to many kinds of bodily malfunction: some lethal, some chronic, and some merely temporary. Some diseases, like cancer and Alzheimer’s disease, increase with age and result from disordered processes within our bodies; others arise from infection by invading germs and afflict children more frequently than adults because we develop immunities after early exposure to them. Symptoms of infectious diseases vary with time and place, owing to changes in human resistance and to evolutionary changes in the germs themselves. Consequently, written descriptions of ancient infections, even when quite detailed, often fail to match up with what modern doctors see. Hence, even when records exist, determining exactly when a particular infection first afflicted people in a given place is often unknowable. And no one can doubt that major disease encounters also took place among peoples who left no records for historians to examine. Nonetheless, and despite all such difficulties, some landmarks in the history of the human experience of disease are discernible from the deeper past, while in recent times the changing impact of diseases and medical efforts to control them are fairly well known.
Diseases among Foragers and Early Farmers
It is safe to assume that our remote foraging ancestors encountered many sorts of parasites, some of which, like the organism that causes malaria, were seriously debilitating. Sleeping sickness, spread by tsetse flies, was so lethal for human hunters that parts of east Africa remained uninhabited until recently, thus preserving vast herds of game animals that tourists now come to see. All the same, it is probable that our early ancestors were tolerably healthy and vigorous most of the time. That, at any rate, is the case among surviving African foragers as observed by modern anthropologists. Probably infectious organisms and their human hosts were fairly well adjusted to one another, having evolved together in tropical Africa; diseases of aging scarcely mattered since their lives were far shorter than ours.
Since many of Africa’s tropical parasites could not survive freezing temperatures, infections probably diminished sharply when human bands expanded their range, penetrating cooler climates and spreading rapidly around the entire globe. Leaving African infections behind presumably increased human numbers and helped to sustain their extraordinary geographic expansion.
But infections began to increase again when, in different parts of the Earth, a few human groups began to cultivate the soil and settled down in the same place all year round. That was partly because food production allowed more people to crowd together and exchange infections, and more especially because supplies of water were liable to become contaminated by bacteria from human wastes. This increased exposure to infections of the digestive tract. Moreover, wherever farmers resorted to irrigation, wading in shallow water exposed them to a debilitating infection called schistosomiasis (or bilharzia), which they shared with snails. And whenever cultivators came to depend on a single crop for nearly all their food, dietary deficiencies were liable to set in. A diet of maize, for example, lacks some of the amino acids humans need and provokes a chronic disease called pellagra. Finally, the domestication of animals, though their meat and milk improved farmers’ diets, intensified disease transfers back and forth between humans and their flocks and herds. A large array of bacteria and viruses traveled this path.
Yet intensified exposure to such diseases did not halt the increase in farming populations. Instead more people cultivated more ground, producing more food to feed more children. Farming villages therefore multiplied and spread from the regions where they had initially established themselves, and human beings soon ceased to be rare in the balance of nature, as their foraging ancestors and other top predators, such as lions and tigers, had always been.
All the same, farmers had to labor longer and at more monotonous tasks than foragers did, and they faced famine whenever bad weather or an outbreak of plant disease provoked crop failure. Seizure of stores of food by human raiders was another serious risk that increased wherever grain farmers became dense enough to occupy nearly all suitable farmland. And when raiders became rulers by learning to take only part of the harvest as rent and taxes, farmers faced another drain on their resources and had to work still harder to feed themselves and their new overlords. Life remained short by our standards, so diseases of old age remained exceptional.
Then, beginning about 3500 BCE, rulers and their various hangers-on began to create cities in a few densely inhabited farming regions of Earth, and disease patterns changed again, manifesting diverse and unstable local equilibria. These may be described as regional agrarian disease regimes; they were succeeded after about 1550 CE by an equally unstable global disease regime within which we still find ourselves. The balance of this research paper will explore these successive disease environments.
Regional Agrarian Disease Regimes
When large numbers of persons began to cluster close together in cities, the problem of waste disposal multiplied as never before. Exposure to new infections multiplied as well, since long-distance comings and goings by soldiers, merchants, seamen, and caravan personnel often crossed disease boundaries and spread infections far and wide. Moreover, when urban populations exceeded a critical threshold, a new class of herd diseases began to afflict humans for the first time. These diseases existed initially among large populations of wild flocks and herds, or dense populations of burrowing rodents and other small animals. A distinguishing characteristic of these diseases was that when they were not fatal, they provoked antibodies in their animal or human hosts, so survivors became immune from a second infection. This meant that the germ could only persist when it found enough newborns to feed upon for a few weeks before death or recovery created another crisis of survival for the infection in question.
Just how large the total host population had to be to permit a chain of infection to continue indefinitely depended on birth rates and how closely in contact potential hosts might be. To move from host to host, many infections depended on airborne droplets, set adrift by breathing, coughing, and sneezing, and therefore they needed close encounters for successful transmission. In the modern era (from about 1750), for example, measles—a viral disease dependent on droplet propagation—required at least 7,000 susceptible individuals within a community of something like 300,000 persons to keep going. Obviously, infections like measles could only persist in urban settings and among villagers in contact with large urban centers.
Some of these, like smallpox and measles, were highly lethal; others like mumps and influenza were milder. No one knows when or where they made good their transfer from animal herds to human hosts, but it is certain that it took place somewhere in Asia, perhaps at several different times and places. It is equally sure that they could do so only in and around cities, thus becoming distinctive new “civilized” diseases.
Their arrival had paradoxical effects. By killing off urban dwellers, they soon made most cities so unhealthful that they needed a stream of migrants from surrounding villages to sustain their numbers. Yet these same diseases also created a new and very powerful advantage for disease-experienced populations in contact with previously unexposed populations. That was because among peoples who lacked acquired immunities, herd infections spread like wildfire, killing adults as well as children. In the modern era, initial exposure to measles or smallpox commonly killed off something like a third of the entire population in a few weeks, leaving survivors dazed and distraught and quite unable to resist further encroachment by the disease-bearing newcomers. The effect was multiplied when successive civilized diseases followed one another in rapid succession. Smallpox, measles, influenza, and even the common cold could all be, and often were, lethal.
Before that drastic pattern could establish itself generally, different centers of civilization had to survive the arrival of these infections from wherever they first started. Everything about the initial spread of herd diseases within Eurasia and Africa remains unknown, but disease disasters that ravaged the Roman Empire between 165 CE and 180 CE, and a second time between 251 CE and 266 CE, probably register the arrival of smallpox and measles in Mediterranean lands, brought back by soldiers returning from Mesopotamia. Written records also show that China suffered unusually lethal epidemics in 161–162 CE and again in 310–312 CE.
It looks, therefore, as though extended contacts within Eurasia, arising from the establishment of the so-called Silk Roads that connected China with Syria, allowed highly lethal outbreaks to occur at both extremes of Eurasia at nearly the same time, inflicting severe damage both on the Roman and Chinese empires. But surviving records say little or nothing about lands in between, and guesswork is useless. By contrast, we know that the Americas were exempt from these herd diseases until the Spaniards arrived, and the same was true of other isolated populations around the globe. Consequently, in the sixteenth century, when European seamen began to encounter people lacking immunities to these diseases, massive die-offs regularly ensued.
By then the agrarian peoples of Eurasia had another twelve hundred years of disease exchange and exposure behind them. One well-known episode came between 534 CE and 750 CE, when sporadic outbreaks of bubonic plague ravaged Mediterranean coastlands, only to disappear for the next six centuries. The historian Procopius wrote an exact description of the initial onset of that plague, explaining that it came by ship and originated in central Africa. Other factors were in play; modern studies show that bubonic plague is spread normally by bites of rat fleas, which transfer to humans only after their normal hosts die of the disease. The domestic rats in question were probably native to India, and in 534 CE they were relatively recent arrivals in Mediterranean coastlands.
The infection itself was at home in underground burrows of various species of rodents in central Africa and northern India, where it behaved like a childhood disease among rats and became a lethal epidemic only when it invaded inexperienced populations of domestic rats and, of course, humans. But under those circumstances it was indeed highly lethal.
Procopius says that when the disease first struck in 534 CE, ten thousand persons died daily in Constantinople for forty days. Loss of population and wealth were certainly severe and prevented the Byzantine emperor Justinian (reigned 527–565 CE) from reconquering the richest provinces of the western empire, which he had started to do.
Germanic and northern Europe escaped this bout with plague, probably because rats had not yet established themselves there. But in the so-called Dark Ages other serious epidemics—including smallpox, measles, and influenza—did break out in the north from time to time, and as ships began to travel the northern seas more frequently, all of Europe became more and more tightly tied into the disease pool centered upon the network of Mediterranean cities. Leprosy, tuberculosis, and diphtheria were among the infections that spread more widely during these centuries. But their spread cannot be traced since they did not provoke sudden, massive die-offs as smallpox, measles, and the plague did.
Nothing equally detailed is known about how other centers of civilization in Eurasia and Africa encountered new infections in ancient and medieval times. But two Chinese texts describe an outbreak of bubonic plague along the southern coast in 610 CE, so it looks again as though China’s disease history matched that of Europe quite closely. This is not really surprising, since the ships and caravans that moved back and forth among all the Eurasian civilized lands carried infections with them, and invading armies occasionally exposed thousands of inexperienced soldiers to a new infection all at once.
North and East Africa shared in this homogenizing process, while the African interior, Southeast Asia, and northern Eurasia took more sporadic parts and so lagged somewhat behind. But overall, as disease exposures intensified across the entire Old World, resistance to infections increased, and local populations got used to living with heavier disease burdens. The assortment of prevalent diseases always differed from place to place, since climate set limits to many infections. In general, warmer and wetter conditions favored disease organisms; infections that depended on mosquitoes, fleas, or other insects to move from host to host also fared best under those conditions. Winter frost set limits to the spread of many kinds of parasites, and so did desert heat and dryness. In addition, local customs sometimes minimized disease exposures. In southwestern China, for example, where bubonic plague germs were endemic among burrowing rodents, European doctors in the nineteenth century scoffed at superstitious villagers who fled to higher ground whenever they found dead rats in their houses, yet half a century later, after Europeans had learned how the plague was transmitted, they realized that such behavior was an effective precaution against catching the disease. Some customs, on the other hand, intensified infections. Religious pilgrimage is a prime example, as was ritual footwashing in Muslim mosques, where the water in the fountains sometimes contained the organisms that cause bilharzia.
Most disease disasters were soon forgotten, which is why so little is knowable about the spread of infections. But the Black Death was an exception. The heavy die-off provoked when bubonic plague returned to Europe in 1346 continued to haunt folk memory and still colors our common speech. About a third of the population of Europe died of the plague between 1346 and 1350, but what kept the memory of the Black Death alive was the fact that plague continued to break out from time to time in Europe and North Africa down to the present, even after effective antibiotic cures were discovered in the 1940s. We know something about how this came to pass.
First of all, the vast Mongol Empire, extending from China to Russia, permitted rapid, long-range movement throughout Eurasia on a far greater scale than ever before. Plague was only one of several infections that took advantage of this fact to expand their domain. More particularly, a Mongol army invaded the borderland between China and India in 1252, penetrating a region where plague infection was chronic, and seems to have carried the infection back to its homeland in the steppes. At any rate, Pasteurella pestis (Yersinia pestis), as the bacterium that causes plague is called, somehow found a new home and spread among burrowing rodents of the northern grasslands, where it was discovered by Russian scientists only in the 1890s. This was the reservoir from which the plague of 1346 broke upon Europe and the Muslim world.
Ships spread it swiftly from Feodosiya (or Kaffa) in the Crimea, where it first broke out, to other Mediterranean and north European ports. Then the infection moved inland. Wherever the plague arrived, death came quickly and unpredictably to young and old. More than half of those infected died. In Muslim lands, the disease took a similar toll; China, too, lost about half its population from a combination of plague and warfare by the time the Mongol Empire collapsed and the Ming dynasty took power in 1368.
Plague continued to visit all these lands at irregular intervals thereafter. The population in Europe continued to decline until about 1480, when the accumulated resistances among survivors at last permitted population growth to resume. It accelerated once the plague disappeared from England and northern Europe after a final visit to London in 1665, partly because efforts at quarantining ships coming from plague-infected ports reduced exposure and partly because slate roofs, introduced as protection against fire, created greater distance between humans and hungry rat fleas than when rats nested overhead in the thatch. In Eastern Europe and Asia, plague continued to break out until the twentieth century, but little by little local adaptations reduced its impact everywhere.
Overall, the most enduring change came to the steppes—the Mongol homelands—where nomadic herdsmen found themselves permanently exposed to a very lethal infection. Losses were so heavy that nomads even withdrew from the fertile grasslands of the Ukraine, leaving them vacant for agricultural pioneers to encroach upon, beginning about 1550. This reversed a human tide that had favored nomad expansion ever since the first millennium BCE, carrying first Indo-European and then Turkish languages across Europe and much of Asia.
Other changes in disease patterns accompanied or soon followed the sudden expansion of bubonic plague. The most conspicuous was the retreat of leprosy, emptying thousands of leprosaria that Europeans had built to isolate lepers in accordance with biblical injunctions. Many lepers died of plague during the first onset; but something else must have been at work to overcome the various skin infections that medieval Europeans lumped together and called leprosy. One possibility is Europe’s reduced population had a proportionally larger supply of wool with which to clothe themselves, and by wearing long, warm nightclothes and thereby reducing skin-to-skin contact between people, they may have cut down on the transmission of skin diseases. No one knows for sure.
Ironically, another skin disease, yaws, caused by a bacterium indistinguishable from the one that causes syphilis, may also have been nearly banished from European populations. The epidemic of syphilis that broke out after 1494 may have been the result of the bacterium finding a new path of propagation via the mucous membranes of the sex organs. Again, no one can be sure.
Yet all the mingling and transformations of diseases across Eurasia and Africa before 1500 never erased local differences. Above all, large parts of the Earth remained unaffected by the rising tide of infection among Old World peoples, and they found themselves correspondingly vulnerable when crossing the oceans became routine and a new global disease regime began to emerge.
Global Disease Regimes
The first and most overwhelming effect of oceanic navigation was to spread a large array of lethal infections among inexperienced human populations. This process continues in remote Amazon jungles and Arctic shores even today, but by now almost every human population has been at least partially exposed, and the initial shattering effect is past. But when it was new, whole peoples disappeared, and vast landscapes in the Americas and Australia were severely depopulated. Immigrants from Europe and Africa—and subsequently also from Asia—were therefore able to supplant the older inhabitants, creating the mixture of peoples we know today.
Native Americans were the largest population exposed to destruction by the new disease regime. The native population of Hispaniola, where Columbus set up his headquarters, disappeared entirely within a few decades, and within the first fifty years of their exposure to new infections, the much larger populations of Mexico and Peru diminished to about a tenth of what they had been in 1500. Millions died of smallpox and innumerable other infections until immunities accumulating in survivors’ bloodstreams checked the die-off. In Mexico and Peru the worst was over by 1650. Gradually population growth began again, though in more isolated parts of the Americas local die-offs continued. Warfare and less organized forms of human violence played a part in destroying Native Americans, but Afro-Eurasian diseases always had the principal role.
Caribbean islands and tropical coastlands of the Americas also proved hospitable to malaria and yellow fever from Africa once the species of mosquito that carried them came across the Atlantic on board slave ships. No exact time horizon for the arrival of malaria in the New World can be discerned, but in 1648 a lethal epidemic of yellow fever in Havana announced the arrival of that disease unambiguously. When it subsequently became endemic, survivors acquired a very potent protection against invading armies, since soldiers from Europe regularly fell ill and died of it within about six weeks of their arrival. This allowed the Spanish to overcome British efforts to conquer the sugar islands in the eighteenth century, doomed Napoleon’s attempt to reconquer Haiti in 1801, and persuaded him to sell the Louisiana territory to Thomas Jefferson in 1803. Quite a political career for a virus from tropical Africa!
Elsewhere, inhabitants of Australia, New Zealand, and other isolated communities experienced approximately the same fate as Native Americans did when disease-experienced Europeans arrived among them. Always the newcomers also brought a rich array of other organisms with them: crops and weeds, together with domesticated animals and pests like lice, rats, and mice. The Earth is still reverberating from the ecological upheavals initiated when humans and innumerable other organisms began to cross the oceans, making the biosphere into a single interacting whole as never before.
Disease exchanges ran almost entirely one way, spreading from Afro-Eurasia to other lands. Reverse transmissions are hard to find, though some experts believe that syphilis came to Europe from the Americas. Europeans discovered that disease when it broke out in a French army besieging Naples in 1494, so its connection with Columbus’s return in 1493 is indeed possible. But there is no clear evidence of the prior existence of syphilis in the New World, so no one can be sure.
Another disease, typhus, also invaded Europe in 1490; but it came with soldiers from Cyprus and may not have been new, but only newly recognized by doctors of the day. More recently, other infections have also invaded disease-experienced populations of the Earth. AIDS is the most serious and widespread, and it may have been transferred recently from monkeys somewhere in the African interior, or perhaps, like typhus, AIDS is much older and remained unrecognized until increasing sexual promiscuity turned it into an epidemic.
Three other new disease exposures affecting industrialized populations in modem times are also worth mentioning. Tuberculosis (TB), a very ancient infection, gained fresh impetus after about 1780 when new factories, powered by coal and steam, began to crowd people together in industrial towns under unsanitary conditions. Its ravages crested in Europe about 1850, shortly before a German professor, Robert Koch, discovered the bacillus that caused it in 1882, thereby inaugurating a new age for preventive medicine. Yet despite modern medical skills, TB remains the most widespread and persistent human infection worldwide, sustained by the extraordinary growth of cities that had carried more than half of humankind into crowded urban settings by 1950 or so.
Cholera, too, was an ancient disease at home in India, where it flourished among Hindu pilgrims who came to bathe in the Ganges. The cholera bacillus can survive independently in freshwater for considerable periods of time, but it multiplies very rapidly in the human alimentary tract and causes diarrhea, vomiting, fever, and often death within a few hours of its onset. Bodily shrinkage from dehydration and skin discolored by bursting capillaries make the symptoms of cholera especially horrible. So when the disease broke through long-standing boundaries in 1819, spreading to Southeast Asia, China, Japan, East Africa, and western Asia, it aroused intense fear and panic even though mortality rates remained rather modest—a mere 13 percent of the total population of Cairo, for instance. Between 1831 and 1833 a fresh outbreak carried cholera across Russia to the Baltic and thence to England, Ireland, Canada, the United States, and Mexico. Even more important, cholera established itself in Mecca in 1831, where it infected Muslim pilgrims. They in turn carried it home with them, periodically spreading cholera all the way from Mindanao to Morocco until 1912. Then cholera disappeared from Mecca, and Muslim pilgrims ceased to spread it far and wide; but it lived on in India, where Hindu pilgrims continued to be its principal carriers.
European and American responses to this dread infection were strenuous indeed. Reformers in England set out to reengineer the water supply and sewer systems of London and other cities to assure germ-free drinking water. It took years to build new water systems, but as they spread from city to city, many other sorts of infections diminished sharply. Helped by vaccination against smallpox, dating back to the eighteenth century, cities became far more healthful than before. This sanitary effort involved new laws and medical boards of health with mandatory power to enforce preventive measures. It was the first great medical breakthrough of modem times. Bit by bit, vaccination and sanitation spread around much of the globe, changing human experience of infectious disease so fundamentally that we have difficulty imagining times when infant death was a matter of course and adults died of infections more often than from degenerative diseases of old age.
Yet some diseases were little affected by these preventive measures. The viruses that cause influenza, for example, vary from year to year, and regularly find receptive human hosts whose immunities from previous years are ineffective against the new variants. In 1918–1919 a new strain of the virus proved particularly lethal, killing about 20 million persons as it spread around the world, which made it far more deadly than World War I. Yet, as so often before, survivors soon almost forgot about their encounter with such a lethal epidemic.
That was partly because a second medical breakthrough, comparable to the sanitary successes of the nineteenth century, came after World War II. Suddenly, use of DDT to poison mosquito larvae almost eliminated malaria from many regions of the Earth, while penicillin and other antibiotics became generally available to kill other infections. All at once, instant cures for ancient diseases became a matter of course. On the prevention side, the World Health Organization carried out a successful campaign that eliminated (with the exception of laboratory specimens) smallpox in 1976. Yet these triumphs did not last very long. While effective against mosquitoes, DDT also poisoned so many forms of life that its use was soon abandoned. More generally, infectious agents began to develop resistances to the new antibiotics. As a result, malaria reclaimed some of its old importance, and other ancient infections did likewise.
Then when AIDS was recognized in 1981 and successfully resisted chemical cures, doctors, once so confident of victory over infections, had to admit that their new skills had unexpected limitations. Infections were coming back, and diseases of old age were increasing. All too obviously, and despite all the recent medical marvels, human bodies remain subject to infection and degenerate with age.
Diseases change, and have always done so. Human behavior changes too, affecting how diseases afflict us. Since 1750 or thereabouts, medical knowledge and practice drastically altered the global disease regime and lengthened human life for billions of persons. But all our skills do not change the fact that we remain part of the web of life on Earth, eating and being eaten, everywhere and always.
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