Despite the diversity, some consensus can be gleaned from the essays, and the epidemiological overview presented here is an attempt to highlight some new findings and old answers as well as the many perennial questions that remain unanswered.

Hunter-gatherers and early agriculturalists of the Old World, although hardly disease free, are gener ally held to have been free of epidemic diseases as well as of many other illnesses now regarded as "diseases of civilization." In fact, there is some agreement that the cradle of many epidemic viral ailments, such as smallpox, was ancient South Asia, which was among the first regions to develop civilizations large enough to support these ailments. From there the diseases traveled east to China and then accompanied Buddhist missionaries to Korea and Japan.

Much evidence suggests that the West was relatively free of eruptive fevers such as smallpox, measles, and rubella until the first millennium A.D., when they finally settled in. These fevers are not mentioned in Greek texts, and as Stephen Ell points out in his study of the disease ecologies of Europe, the military fortunes of the Romans and their enemies do not seem to have been influenced by the kinds of diseases that decimated later European armies - or at least this influence was not felt until very late in the Empire's decline. But at that time, the eruptive ailments had apparently taken root, as is indicated by a change in Roman strategy and by the fate of wave after wave of invaders who enjoyed initial success only to go finally into sharp decline.

It is now clear that leprosy was a serious health problem for Europeans during much of the Middle Ages. Excavations of leper cemeteries leave no doubt that those interred were suffering from that disease and not something else such as yaws, as earlier writers have argued. The reason or reasons for the disappearance of leprosy remain subject to dispute. Some researchers believe that it had to do with the rise of tuberculosis - a disease that provides some immunity to leprosy; others argue that the plague killed so many lepers that the disease itself died out.

As for the plague, a great number of the questions regarding its course in Europe remain unanswered. It is generally accepted that it originated in the Himalayan borderlands between India and China and that the plague of Justinian (542-3), which reached Europe by 547, was in fact bubonic plague. But why it disappeared from Europe for some 800 years remains a mystery. Plague certainly seems to have been active in China during this period. The circumstances of its reappearance are also obscure. Our authors note that it may have reached the West from the Middle East. But the most likely explanation is that a plague epidemic began in China in 1331, found its way to the Crimea by 1346, and then diffused over Europe. Yet how this disease could linger on for centuries, very possibly without a sylvatic focus and with little evidence of widespread rat mortality, has not been explained. Nor have the circumstances of the eventual disappearance of plague from western Europe in the late seventeenth and early eighteenth centuries been determined. Explanations ranging from a mutation of the bacillus to the rise of strong governments able to regulate trade (and, often by accident, disease) continue to be advanced.

Among scholars of diseases in the Americas, there is a noticeable tendency to accept the notion that much larger Indian populations developed in isolation from the rest of the world than has previously been believed. Indeed, even the now nearly empty Amazon basin was teeming with them. Like the Old World hunter-gatherers, these people were not disease free. Intestinal parasites, a form of tuberculosis that may have become extinct, encephalitis, and hepatitis tormented them along with some kind or kinds of treponemal infection, and in certain locales, such uniquely American ailments as Carrion's disease and Chagas' disease were present. But despite the fact that some populations were dense enough to host them, neither the Old World epidemic diseases, nor malaria or yellow fever, infected the native Americans. If the Indians lacked pathogens to kill them, they seem to have made up for it by violence, because burial sites often reveal that trauma was an important cause of death.

European diseases changed this state of affairs -abruptly in the case of Caribbean Indians, somewhat more slowly in the Inca and Aztec empires, and substantially more slowly among other groups in Brazil and North America. But it is generally conceded that, despite locale, about 90 percent of the population eventually died out before demographic recovery began. Ann Ramenofsky has pinned down at least 13 diseases that arrived in the Americas with the Europeans and Africans during the first two centuries after the discovery of the American continent: viral diseases including influenza, measles, mumps, rubella, smallpox, and yellow fever; bacterial ailments embracing pneumonia, scarlet fever, pertussis, anthrax, and bubonic plague; typhus, whose causative microorganism stands midway between a virus and bacteria; and one protozoal infection — malaria. There is general agreement that, outside of Brazil, smallpox was the most devastating disease, though there is puzzlement as to how a relatively benign disease suddenly became deadly in Europe as well as the Americas in the sixteenth century. But all authors concerned with the matter point out the devastating impact of disease after disease sweeping over a people and the social disloca tion caused by the death of adults who normally provided food and care for the young and the old. Malaria is blamed for having depopulated much of the interior of Brazil, which brings us to still other Old World ailments, and to Africa.

If it is generally conceded that Asia was the cradle of many of the illnesses so far discussed (i.e., diseases that probably reached humankind via domesticated animals), there is no doubt that Africa was the cradle of another group of illnesses - those of wild animals and thus diseases that in many instances antedated the human species. These African diseases include some malarial types and other protozoal infections, such as African trypanosomiasis, which first infected our primate predecessors, as well as viral infections such as yellow fever and dengue.

Malaria, of course, has plagued India and China for millennia. But Africans and those of African descent living elsewhere around the globe are almost completely refractive to vivax malaria. This suggests that they have had the longest experience with what is generally believed to be the most ancient of the malarial types to affect humans. Indeed, because black Africans are so refractory to vivax malaria, the disease has disappeared from almost all of sub-Sahara Africa. By contrast, falciparum malaria, which is the most deadly of the malarial types, is also the newest; it too seems to have an African origin (or at least to have plagued Africans the longest), because Africans have by far the greatest variety and highest frequencies of genetic defenses against it.

Nonetheless, falciparum malaria spread out across the Sahara desert to take up residence around the Mediterranean and to become a serious threat in classical times, whereas vivax malaria had diffused much earlier over much of the globe. Vivax malaria doubtless reached the New World in the blood of early Spanish conquistadors, and falciparum malaria in the blood of the first slaves to be imported, if not before. Yellow fever, by contrast, was confined to Africa until the slave trade brought it to the Americas in the mid-seventeenth century. It seems to have begun tormenting European cities only in the eighteenth century, and never became established in Asia despite a plethora of suitable vectors, as well as monkey and human hosts. One possible explanation for the latter is that Asia supports so many other group B arborviruses that there has been no room for another.

In any event, such was not the case in the Americas. Both malaria and yellow fever joined in the slaughter of Indians; in the Caribbean this African wave of disease, coming hard on the heels of the European wave, almost obliterated them. But African diseases also killed whites, while sparing blacks, who seemed immune to both. These differences in susceptibility suggested to the Europeans that neither Indians nor whites could survive hard labor in warmer regions of the hemisphere. This brought about an accelerated slave trade and, of course, an accelerated flow of African pathogens to the New World. Indeed, much of tropical and subtropical America became more an extension of the African disease environment than of the European, until late in the nineteenth century. Even smallpox arrived from African, as opposed to European, reservoirs.

Whether the Indians gave syphilis to the rest of the world is a question taken up by a number of authors in this work. The biological anthropologists report that the treponemal lesions found in the bones of pre-Columbian Indians are probably not those of syphilis (as previously thought), or at least not of syphilis as we know it today. Moreover, the ability of Indians to resist the disease, which has been taken by some as proof of its pre-Columbian presence in the Americas, can be explained to some extent by the prevalence of pinta and perhaps nonvenereal syphilis - both milder forms of treponemal disease that nonetheless would have provided some cross-immunity. Also, our authors take into account the opinion of European physicians who claimed that the syphilis they saw at the beginning of the sixteenth century was simply a more virulent form of an old disease they had always treated. In view of these circumstances it is tempting to speculate that two treponemal infections, one from the Old World and the other from the New World, somehow fused to become the disease that ravaged Europe for more than a century before becoming more benign.

Somewhere around the beginning of the eighteenth century, Europe's population began to increase and, despite fits and starts, has continued to do so. How much of this growth can be credited to improved nutrition, the abatement of disease, increasing fertility and decreasing infant and child mortality, medical intervention, the growth of nation-states and improved public health, and changes in human attitudes and behavior has long been a subject of considerable debate. Stephen Kunitz believes that all are important factors and that no single one provides a full explanation. Nonetheless, he, along with other authors considering the problem in Asia, does stress the importance of the growth of cities in which diseases could become endemic and thus transformed into childhood ailments.

Meanwhile, from the 1770s onward, the natives of Australia and Oceania were subjected with increasing ferocity to the same trial by disease that had begun almost two centuries earlier in the Americas. And according to David Stannard, the results were similar, at least in Hawaii, where he places the population decline at 90 percent and blames smallpox, as well as other epidemic illnesses and venereal disease, for both increased mortality and reduced fertility. Elsewhere the process was often more gradual and is unfortunately still ongoing in some places, such as Brazil and Colombia.

As the world's cities grew in importance, so did tuberculosis, in both Asia and the West. Our authors leave no doubt about the relationship between urbanization and tuberculosis. Yet the disease began receding while urbanization was still accelerating and long before medicine had acquired its therapeutic "magic bullet." This leaves still another unresolved medical mystery, although it would seem that the explanation lies somewhere within the parameters of improving nutrition and the development of resistance to the illness.

Crowded nineteenth-century cities with poor sanitation and impure water supplies were natural targets for another of the plagues from India - Asiatic cholera. In his essay, Reinhold Speck demonstrates the role of the British army in unwittingly unleashing the disease. He traces each of the pandemics, straightens out the problem of dating one of them, and shows how cholera did much to emphasize the importance of public health and sanitation programs.

The end of the 1800s brought an understanding of the role of vectors in a number of diseases, including malaria and yellow fever, and this along with an increase in the production of quinine permitted the Europeans finally to venture beyond the coasts into the interior of Africa. Tropical medicine became an integral part of colonizing efforts, although as both Maryinez Lyons and K. David Patterson make clear, the initial aim was not so much to help those colonized as it was to preserve the health of the colonizers. Moreover, in modifying environments to suit themselves, the latter inadvertently facilitated the spread of such illnesses as African trypanosomiasis, onchocerciasis, schistosomiasis, and leishmaniasis.

The twentieth century dawned with the principles of germ theory still being digested by the world's medical community. As our authors on Asia and Africa indicate, Western medicine has (perhaps fortunately) not always supplanted local medicine but rather has often coexisted with it. Nonetheless, the effectiveness of Western medicine in combating trauma and illnesses such as rabies, cholera, typhoid, gangrene, puerperal fever, and yaws was quickly recognized.

Yet Western medicine was completely overwhelmed as influenza became the next great plague to sweep the earth just as World War I was winding down. As Alfred Crosby emphasizes, although the case mortality rate for the disease is low, the disease killed upward of 30 million across the globe, making it perhaps the "greatest single demographic shock that the human species has ever received." Nor did the dying cease after the pandemic was over: As R. T. Ravenholt reveals in his essay on encephalitis lethar-gica, this illness was a peculiar sequela to the so-called Spanish flu.

After the influenza epidemic, the developed world enjoyed perhaps its first extended respite from epidemic disease since classical times. Medical science made great strides in understanding and controlling infectious illnesses. Because of the emphasis on germ theory, however, the etiologies of nutritional ailments remained elusive for a time, but eventually those of beriberi, pellagra, rickets, and scurvy were unraveled and the role of vitamins discovered. In the tropical and subtropical worlds, Rockefeller programs were launched to rid these regions of long-standing illnesses, and if hookworm disease and yellow fever were not eradicated as had been confidently expected, at least much was learned about their control.

Rickettsial diseases have always been troublesome for armies. Typhus has been credited with defeating Napoleon in Russia, and during World War I the disease killed some 2 million to 3 million soldiers and civilians. But in World War II and its aftermath, important advances were made in combating rickettsial diseases. In addition, new drugs were developed against malaria.

As the authors writing on the ailments of infants and children make evident, the young have historically suffered most from epidemic and endemic diseases. But in the past several decades this has been changed by the development of antibiotics and by accelerated worldwide programs of vaccination. In fact, as Alfred Crosby points out, in his essay on smallpox, one of these programs led by the World Health Organization appears to have ended the career of that disease, which killed so many for so long. Poliomyelitis, which briefly loomed as another of the world's great plagues, was also brought under control by similar programs, although as H. V. Wyatt reminds us, such efforts are not without some risk and the disease lingers in many parts of the world.

Unfortunately, other diseases of the young continue to be prevalent, especially in the developing world, where protein-energy malnutrition, respiratory infections, dysenteries, and helminthic and protozoal parasites, separately and working in concert, kill or retard the development of millions each year. As our specialists make clear, much headway must be made in that world against other potentially crippling ailments such as yaws, leprosy, and ophthalmia. Some malarial strains have become drug resistant, and continued dengue epidemics, carried by the same vectors that spread yellow fever, raise the very real possibility of yellow fever making a comeback in the Western Hemisphere, as it seems to be doing in parts of Africa.

In the developed world, chronic diseases such as cancer, heart-related illnesses, and Alzheimer's disease have supplanted infectious diseases as the important killers, and increasingly the role of genes in the production of these diseases has come under scrutiny. In addition, medicine has concentrated on understanding the genetic basis for such diseases as cystic fibrosis, Down syndrome, epilepsy, favism, hemophilia, Huntington's disease, leukemia, multiple sclerosis, muscular dystrophy, Parkinson's disease, sickle cell anemia, and Tay-Sachs disease. Some of these, such as sickle-cell anemia, favism, and possibly Tay-Sachs disease, are an unfortunate result of the body's evolutionary attempt to protect itself against other diseases.

As this research has gone forward, it has become clear that many other disease conditions, such as lactose intolerance and diabetes, are strongly influenced by heredity. Leslie Sue Lieberman argues that in the latter instance a "thrifty gene" left over from the feast and famine days of our hunter-gatherer ancestors may be at work. Genes also play a vital role in selecting cancer and heart disease victims or even gout patients, although in these cases genetic predisposition can often be modified by behavioral changes - and to that extent these illnesses can be viewed as human made. No wonder, then, that there has been a recent upsurge of concern about the air we breathe and the food and other substances we take into our bodies.

It may well be that environmental factors are bringing us back face to face with epidemic illnesses. For example, as more and more individuals are entering our shrinking rain forests, new and deadly viruses are being released into the rest of the world. In fact, AIDS, which almost certainly originated in non-human primates, has become a plague of such proportions that it may eventually be ranked along with the Black Death, smallpox, cholera, and influenza as among the most disastrous epidemic scourges of humankind. In addition, as Wilbur Downs shows, other extraordinarily lethal viruses such as Ebola, Marburg, and Lassa also lurk in these rain forests and pose a serious threat to us all.

When Hirsch wrote in the preceding century, few understood and appreciated the extent to which hu mans have created their own disease ecologies and their own diseases by the ways they live and the ways they manipulate their environments. As we approach the twenty-first century, we have finally begun to acquire that understanding. Whether at the same time we have acquired a sufficient appreciation of what we have done is another matter.

Kenneth F. Kiple


Medicine and Disease: An Overview

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