Germs, Genes, & Civilization: How Epidemics Shaped Who We Are Today

by David P. Clark

  These diseases are still a major problem in tropical regions. According to the World Health Organization (WHO), some 500 million clinically observed cases of malaria cause a little over a million deaths each year, the majority in Africa. Of these deaths, about half are of children younger than five years old. Recently, AIDS overtook malaria and tuberculosis to become the leading cause of death among the infectious diseases, with around three million deaths. (Diarrheal disease and respiratory infections still head the mortality tables, but these are each due to several different infectious agents.) Tuberculosis kills around 1.5 million victims per year, slightly more than malaria. However, these deaths result from about 10 million cases, far fewer than the 500 million cases of malaria. Relatively few malaria victims die outright. Instead, they suffer life-long debilitation, which not only lowers their productivity, but also makes them vulnerable to other infections.

  How important was malaria?

  Malaria is sometimes quoted as having killed more people than all the wars and all the plagues in recorded human history. But although infectious disease as a whole has undoubtedly killed far more people than warfare, little compelling evidence indicates that malaria has outperformed all other infectious diseases. Although malaria has taken a steady death toll in Africa and other tropical zones, it was absent on the American continent until European colonization. Furthermore, although malaria nibbled at the heels of Europe until recently by infesting marshlands, the dense urban populations of temperate Europe and Asia were fairly unaffected. Moreover, until the recent population explosion, the population density of Africa and other tropical regions where malaria is endemic was relatively sparse.

  Even in Africa, the evolutionary homeland of both man and his earliest diseases, was malaria really the number one killer before the last few centuries? Today Plasmodium falciparum causes most lethal attacks of malaria, whereas the other three species of malaria cause relatively milder disease and are rarely lethal. Although P. falciparum is presently spreading from Africa around the tropical world, the sickle cell mutation that provides resistance is found only in Africans indigenous to regions harboring P. falciparum malaria. The fact that the sickle cell trait is so harmful by itself suggests that it is a recent, emergency, evolutionary adaptation. Over longer periods, we would expect the build-up of resistance with less deleterious side effects, as is the case for many other diseases, including the milder variants of malaria. This suggests that the malignant, falciparum form of malaria is of relatively recent origin and that, even in Africa, malaria was present in its milder forms for much of early human history.

  Moreover, in precolonial Africa, many other diseases that have since been largely eradicated due to Western technology were still active. Relative to malaria, yellow fever may be trivial today, but in the early colonial period, sailors to tropical parts feared it at least as much. Again, among many West African tribes, smallpox, which has now been completely eradicated, was historically feared the most. Although malaria has survived the onslaught of modern technology better, this does not necessarily mean it was the major killer before other diseases were brought under control.

  Our fellow travelers

  Malaria is the best known example of a disease that has accompanied our species from its earliest beginnings and remains a major health problem. However, it is by no means the only disease to have accompanied us since our origin. Tuberculosis, herpes, and typhoid are other well-known examples. This raises the issue of how an infectious disease avoids getting left behind when its human victims consist only of small, scattered bands.

  Consider first a “recent” disease such as measles. This humans-only disease is highly contagious and is spread from human to human without relying on any insects or other carriers. After recovery, humans gain immunity from measles. Consequently, measles faces the problem of constantly finding fresh victims. When measles has finished infecting all members of a small isolated tribe, it has nowhere to go. Thus, diseases such as measles cannot persist unless civilization provides a densely packed crowd of victims. Clearly, measles is not one of our original diseases; we consider its origins later.

  One way for a disease to avoid the predicament of measles is to be shared among multiple animals. Malaria and sleeping sickness are examples of this approach. Another approach is to remain dormant inside a host until fresh victims are available. Herpes, caused by a virus, and typhoid and tuberculosis, caused by bacteria, have all taken this route. Viruses of the herpes family may lie quiescent in nerve cells for years until provoked by stress to emerge. They may then spread to new victims. Typhoid can hide in the gall bladder of human hosts who show no symptoms but are a constant source of infection to others. Tuberculosis, caused by Mycobacterium tuberculosis, hibernates in the lungs.

  Human remains showing signs characteristic of tuberculosis (TB) have been found dating as early as the Neolithic period, when settled agricultural communities first appeared (9,000 B.C. onward). X-rays of Peruvian mummies dating to before the European conquest show signs of tuberculosis, implying that the American Indians brought TB with them when they crossed the Bering Straits some 10,000–15,000 years ago. Extraction of DNA characteristic of Mycobacterium tuberculosis from some of these mummies has confirmed that it really was tuberculosis. The signs of TB in the skull of a half-million-year-old Homo erectus from Turkey are vastly more ancient.

  It was once thought that tuberculosis might have moved into the human population from cattle, which suffer from a closely related form of the disease. However, recent DNA analysis suggests the reverse—that we humans transmitted tuberculosis to cows after domestication.

  Many human diseases originated in animals

  Despite the new DNA evidence that exonerates the cow from spreading tuberculosis, most of our present infections probably did originate from other animals. It seems likely that prehistoric hunter-gatherers were relatively free of infectious diseases, compared with historical and present-day man. The unusual susceptibility of American Indians to most diseases brought across the Atlantic from the Old World argues that the indigenous people of the American continent had never been exposed to these diseases. This implies that these diseases emerged after the ancestral American Indians split off from their Asian relatives approximately 15,000 years ago. Because the migrating tribes evidently did not import them into America, it seems that smallpox, measles, and so forth must have been human diseases for less than 15,000 years—perhaps less, even, than that.

  Before rushing forward, a word of caution is in order. We are fairly sure that malaria is an ancient disease. However, malaria was not present among American Indians before contact with the Old World was reestablished. The reason is that malaria is carried by mosquitoes, which failed to survive when humans migrated from the tropics into the colder regions of Asia. The Asian ancestors of the American Indians had therefore left malaria behind before they entered the American continent. When invoking New World susceptibility for the age of a disease, we must keep this factor in mind. Other tropical diseases that cannot persist in colder climates may also be ancient despite not being carried to the Americas.

  Note also that, apart from the domestic dog, the American Indians lacked the domestic animals characteristic of the Old World. When the Bering Strait was crossed, cattle, sheep, horses, and pigs had not yet been domesticated by the tribes who made the crossing. Many human diseases have come from these animals. Because the first humans to colonize the Americas did not take these animals along, they could not have caught their diseases after migrating.

  As humans expanded around the globe and populations grew ever denser, our species became a living paradise for infectious disease. No other large animal in the known history of our planet has provided such crowds of individuals, packed closely together, just waiting for some pestilence to move in and multiply. Over the ages, infectious diseases have migrated from their original hosts whenever they made contact with the human species. Animals that have the closest relationships with humans have b
een the source of most diseases. This includes not just the deliberately domesticated animals, but also the rats and mice that have taken up residence in and around human settlements. Even today, most human towns and cities are home to more rodents than humans.

  Dense herds of domestic animals and fields of closely planted crops have provided similar opportunities for colonization by diseases from related wild animals and plants. Some of these, in turn, have moved on to humans. Today, as the remaining jungles and rain forests are being explored and exploited, they have yielded more novel diseases. Lassa fever, Hantavirus, and Ebolavirus have all made the jump to man, the ubiquitous host. Although mankind has done a good job of exterminating other larger animals, we have kept many of their diseases.

  Recent diseases from animals

  When Hippocrates compiled his treatise in the fifth century B.C., the ancient Greeks did not know of smallpox, measles, bubonic plague (an Asian disease), syphilis (an American import), yellow fever (from Africa), or leprosy. They were aware of herpes, typhoid and/or typhus, tetanus, amebic dysentery, rheumatic fever, chlamydia (both venereal and trachoma), and gonorrhea (or something very similar).

  Zhouhou Beijifang, written by Ge Hong in fourth-century-A.D. China, lists malaria, erysipelas, typhoid, dysentery, and cholera. In contrast to the ancient Greeks, leprosy and smallpox were now known, implying that these appeared roughly 2,000 years ago. These records, together with a variety of other ancient accounts, suggest that many diseases we are familiar with today were absent in early historical times and have appeared only within the last thousand years or so.

  Viral diseases, which colonized humans only after civilization provided sufficiently crowded victims, include mumps, measles, German measles, smallpox, polio, influenza, and even the common cold. At least our hunter-gatherer forefathers didn’t have to worry about scaring away the game with violent sneezing! These viral diseases all have close relatives in various animals. After making the jump to humans, they adapted over the centuries to their new hosts and, in many cases, lost the ability to infect their original hosts. For several of these diseases, evidence suggests that they were originally more virulent and have become milder over the years.

  For all these diseases, victims who recover become immune. Consequently, these viruses must all keep moving through a constant supply of new hosts. Flu and colds do return year after year and reinfect the same people, but each successive epidemic comes from a newly evolved strain of virus. Although you may be reinfected with such new strains, you remain permanently immune to variants of flu or cold viruses from previous years.

  Smallpox is a good candidate for a very recent addition to humanity’s panorama of parasites. It was still quite virulent in the twentieth century, even among Old World populations. Smallpox was once thought to be derived from cowpox. However, recent genetic analysis has shown that camelpox is its nearest relative, so transfer from camels to humans in the Middle East seems plausible.

  Probably the earliest recorded smallpox epidemic is mentioned in the Koran, which is consistent with a Middle Eastern origin. The siege of Mecca by the Ethiopians in 569/570 A.D. was routed by this epidemic. A.D. 570 was the year Mohammed was born, and Islam had not yet been founded. Nevertheless, Mecca was already the holy city of the Arabs, and the Ethiopian Christians were hoping to destroy Allah’s sacred shrine, the Ka’aba. The Koran credits Allah with slaughtering the Ethiopians.

  The Islamic expansion of the seventh and eighth centuries spread smallpox throughout the Mediterranean area—or perhaps we might better say that smallpox cleared the way for Islam to expand, much as it later cleared the way for the Spanish conquest of Central America. The Islamic Empire crossed the Straits of Gibraltar from North Africa to conquer Spain in 710. The Arabs were still in Spain when the Black Death pandemic of the mid-1300s occurred. This seems to have helped tip the situation in favor of the native Spanish kingdoms, and the Arabs were gradually expelled over the next couple centuries. Smallpox moved quickly. In the year 737 A.D., a great smallpox epidemic in Japan caused major depopulation.

  Which diseases from which animals?

  Although apes and monkeys are more closely related to humans, they have provided few diseases. Herded livestock and rodent pests are more frequent sources of human infections. This is not really surprising: The greater the population density of the animals a disease infects, the more opportunity that disease has to grow more virulent, to evolve new variants, and to spread. In addition to population density, another critical factor is intimacy. Cattle, sheep, and goats are grazing animals and live in fields separate from their human owners. In contrast, pigs and chickens are found in farmyards and have had much closer contact with humans. Dogs live closest of all, often sharing the house with humans and the uninvited mice and rats found in and around all human habitations. As a result, dogs, pigs, chickens, and mice have tended to pass on more infections than sheep, goats, and cattle.

  Nonetheless, our cousins the apes and monkeys have provided us with a few infections. Amebic dysentery probably came from the Rhesus monkey, which lives in the forests of Asia. AIDS, from the Human Immunodeficiency Virus (HIV), comes from African monkeys via the chimpanzee. Some 30%–50% of green monkeys found in Africa today carry Simian Immunodeficiency Virus (SIV), a close relative of HIV. In contrast, green monkeys living in the Caribbean show no traces of infection. These monkeys were brought from Africa during the seventeenth and eighteenth centuries, indicating that the modern group of SIV/HIV viruses has emerged since then.

  Not all human diseases come from other mammals. Birds are almost certainly responsible for influenza, which still circulates among pigs, people, chickens, and ducks. Even today, birds live in large flocks, and in earlier times, colossal swarms of waterfowl inhabited the wetlands of Europe and North America. As the herds and flocks of domestic animals grew in size, they picked up diseases from birds and eventually passed them on.

  Who owns which disease?

  Despite our self-centered outlook, very few diseases are restricted to humans alone. If no reservoir of infection exists among animals, curing, immunizing, or quarantining all human victims should drive such a disease to extinction. This has been done for smallpox. The WHO began the eradication program in 1966 and completed it in the 1970s. So far, smallpox is the only human disease to be totally eradicated in the wild, although ongoing attempts have targeted polio and the parasitic Guinea worm.

  Total eradication is rarely possible because most diseases, even those that primarily infect humans, also infect other animals. Malaria, yellow fever, and many tropical diseases also infect monkeys and apes; bubonic plague and rabies can infect cats and dogs. Are malaria and rabies really human diseases, or are they animal diseases that humans sometimes have the misfortune to catch? Although the dividing line is somewhat arbitrary, we can distinguish diseases that circulate mostly among humans, animal diseases that are occasionally caught by humans, and shared diseases that routinely infect several host species.

  Some animal infections are occasionally transmitted to humans by accident and are rarely, if ever, passed from person to person. Rabies is certainly infectious but is almost never acquired from being bitten by another person. Glanders is a disease of horses that is occasionally transmitted to humans, such as stable hands who come in close contact with infected animals. Anthrax is primarily a disease of cattle but may cause epidemics with high mortality among humans. Under natural conditions—that is, before civilization—these diseases were probably unknown among humans. Only after the domestication of cattle, horses, and dogs did their diseases come into close enough contact to jump the species boundary. Some of these animal diseases adapted to their human hosts and have become genuine human diseases. Others have remained primarily animal diseases and only sporadically infect humans.

  Different diseases evolve at different rates. Generally, the fewer genes are involved, the more rapidly the diseases evolve. Thus, viruses evolve faster than bacteria, which, in turn, evolve faster than prot
ozoa. Consequently, many virus diseases have evolved so quickly that distinct human diseases have appeared. Often these have diverged so far from their ancestors that they no longer infect even other animals. Good examples are smallpox, probably derived from camelpox, and measles, which is related to distemper, a disease of dogs and related carnivores. In contrast, bacteria evolve more slowly than viruses, and we still share most of our bacterial diseases with other animals, although there are often specialized, human-adapted variants. For example, “epidemic” typhus is a human-specific version of “murine” typhus, which infects both rodents and humans. Protozoa evolve more slowly than bacteria, and we still share our best-known protozoan disease, malaria, with other apes and monkeys.

  Are new diseases virulent to start with?

  We often get the impression that whenever a novel disease jumps the species boundary and infects humans for the first time, it is incredibly virulent, as with Lassa fever or Ebolavirus. This is an artifact of journalism. If half a dozen people in some out-of-the-way place contracted a novel but mild illness, it would probably not even be investigated, let alone hit the headlines. Microbes are constantly invading the human body. Few make it past the human defense system. If a novel infectious agent does survive, whether it causes a mild or lethal illness is largely a matter of chance.

  Lassa and Ebola illustrate this well. Recent investigations have revealed that milder strains of Lassa fever and Ebolaviruses have been infecting humans many years before the official “discoveries.” People who are infected with a virus are immune to further infection, and their blood contains circulating antibodies that are specific to the virus in question. Analysis of blood samples from inhabitants close to the Lassa River in Nigeria revealed frequent cases of people with antibodies to Lassa fever virus. Many had no recollection of any illness recognizable as Lassa fever; others remembered attacks of moderate to severe fever, often attributed to malaria. Earlier outbreaks of Lassa fever in Nigeria thus ranged in virulence from scarcely noticeable to moderate, with the latter usually diagnosed as “aberrant” cases of malaria. Lassa was recognized as a new disease only when a highly virulent version hit the headlines in 1969. Ebolavirus has behaved in much the same way, emerging officially in Zaire in 1976.