The first cities big enough to keep diseases like measles continuously supplied with new people to infect appeared in the Middle East, and somewhat later in Greece, in the period 1000–500 B.C. Nonetheless, before this, there were densely settled human populations in the valleys of the Nile in Egypt and of the Tigris and Euphrates in the Middle East. To what extent epidemic disease spread before 1000 B.C. depended on the amount of contact between the individual communities strung along the river banks.
Somewhat later than the Middle East, dense populations arose in India and China, and provided similar opportunities for animal diseases to migrate into humans. Eventually, the three major centers of Old World civilization made good enough contact for infectious diseases to move from one to the other. Between around 500 B.C. and roughly 500 A.D., the disease pools of the Old World merged. The latter centuries of this period saw great political turmoil throughout the Eurasian continent. In the West, the Roman Empire fell, and in the East, China fragmented into multiple states, many under foreign domination. A thousand years later, over a period of less than a century, the combined infectious burden of the Old World was carried to the American continent, where it caused colossal devastation.
Disease and manpower
The massive casualty rates due to infant mortality plus periodic epidemics meant that many ancient societies were limited in their economic growth or military expansion by shortage of manpower. This is nicely illustrated by the values the Franks placed on different members of society. As the Roman Empire faded, these Germanic tribesmen took over Gaul, whose modern name, France, commemorates them. Shortly after 500 A.D., the Frankish law code (the Pactus Legis Salicae) set the wergild, the fine paid for wrongful death, for various people. A freeborn Frank was valued at 200 solidi. (A solidus was worth roughly one cow.) A woman who had survived to childbearing age was worth 600 solidi, as much as a member of the king’s retinue. However, girls too young to bear and women past childbearing were worth only the standard 200 solidi.
Throughout history, the bulk of the human population was poorly fed and lived short, squalid, thoroughly unhygienic lives. In better-than-usual periods of history, those who survived infancy might hope to make it to 40 years, on average. In truly miserable periods of history, such as the early Middle Ages, blighted by war, famine, and pestilence, the overall life expectancy may have sunk as low as 20 years. As emphasized by Richard Dawkins in his book The Selfish Gene, evolution is a mechanism for spreading genes. The purpose of life is not to provide idle luxury for our bodies, or even challenging problems for our minds, but merely to pass on our genetic information to future generations. The chicken is just a fancy machine for laying eggs. The massive toll of premature death throughout human history has selected the fitter and stronger. In particular, it has selected for those who carry genes conferring resistance to the infectious diseases that have been our biggest killers. From a Darwinian perspective, civilization spreads successful genes, especially those that combat infectious disease, not cultural achievements.
How do microorganisms become dangerous?
Now let’s pick up the story from the microbial viewpoint. Infectious agents vary greatly in their ability to cause harm. Before discussing the “professional” diseases, we must not forget the opportunists. When a person is weakened by injury, exposure, or starvation, or if the immune system is malfunctioning, microbes that are otherwise harmless may cause disease. Such opportunistic diseases have received a lot of attention in connection with AIDS. Victims of AIDS suffer damage to their immune systems, hence the name acquired immunodeficiency syndrome. Death results not from AIDS itself, but from the opportunistic diseases that can invade only humans lacking immune defense. These may be normal inhabitants of our skin or guts that invade tissues where they cannot normally survive. Others are microorganisms that do not normally infect humans.
The existence of such opportunistic invaders tells us that many microbes are poised on the edge of invasion. They can degrade and live on human tissues. If they could survive counterattack by the immune system, they would be able to invade us. Such microorganisms can become dangerous to healthy humans in two ways. The first is by gradual accumulating mutations that allow them to survive in human tissues. The second is by acquiring a preassembled set of virulence factors.
Cells carry their genetic information written in genetic code along the famous DNA molecule. Every now and then, DNA molecules are damaged by various causes and the information they contain is altered—or, as biologists say, mutated. Radiation of various kinds, including ultraviolet rays from the sun, can cause mutations. So can certain chemicals, such as those in soot, tar, and cigarette smoke. However, about half the mutations occurring in nature are spontaneous mistakes. Every time a living cell divides into two, it must duplicate its DNA so that its descendants get a copy of its genes. This process is not perfect, and occasional errors creep in. About one gene in a million suffers a mutation every generation. Many mutations have little effect; others are lethal. Despite this, a steady stream of mutations accumulates in living creatures.
Viruses mutate much faster than bacteria. Higher organisms, including protozoa such as malaria, change slowest of all. This is not because of a scarcity of mutations, but on how well the mutations are tolerated. This, in turn, depends on the relative genetic complexity. Random mutations are less likely to totally cripple a simpler organism, so the fewer the number of genes, the more rapidly an organism can change yet remain functional. Higher organisms have approximately 10,000–50,000 genes, bacteria have 500–5,000 genes, and viruses have 3–1,000 genes. Consider two machines, one with just a few components and the other with many. The more parts that interact with each other, the less flexibility we have to alter any individual component. If we randomly change the shape of one part of a complex machine, this will probably clash with the operation of another component. If we randomly change one part of a simpler machine, this is less likely to cause conflict. For example, we could double the length of the handle or the blade of a bread knife and still be able to slice bread. But if we doubled the size of a randomly chosen component inside an automobile engine, it would probably immobilize the car. Thus, the fewer genes, the more likely mutations will be tolerated and the faster evolution may occur.
Diseases from worms, fungi, or protozoa have changed relatively little during the course of human history. It is no accident that ancient descriptions of malaria are the earliest records of an infectious disease whose symptoms are clearly recognizable today. Conversely, viral diseases change so rapidly that they tend to become unrecognizable over the ages. Bacteria are intermediate in their rate of change. Around 400 B.C., the ancient Greeks described many infectious diseases still identifiable today. Most of these are bacterial, but the only recognizable viral infection is herpes. Many ancient epidemics cannot be identified today, even when their symptoms were carefully recorded. These were probably viral infections that have changed beyond recognition.
Genes are normally made of DNA. For day-to-day operations, cells make working copies of their genes in the form of RNA, a molecule related to DNA. The original DNA copy is stored safely until the cell divides. RNA is less stable than DNA and is copied less accurately. Therefore, it is much more likely to mutate. Nonetheless, some viruses contain genes made of RNA. These viruses suffer a massive mutation rate that no living cell could survive. Even among viruses, only those with few genes (no more than a dozen or so) can tolerate being RNA based. Even so, many of the individual virus particles produced are defective. Despite these drawbacks, many successful and widespread viruses use RNA. The benefit to the virus is that constant alterations camouflage it from the immune system. For example, influenza and AIDS are both RNA viruses. Influenza mutates so fast that this year’s flu vaccine will be useless against next year’s flu. AIDS mutates even faster. The AIDS viruses inside a single patient vary significantly from one another. This makes treatment with drugs extremely difficult, as resistant virus mutants arise inside a sin
gle patient.
Packages of virulence genes are often mobile
Although bacteria evolve slower than viruses, every now and then, some previously harmless bacterium becomes a full-fledged killer overnight. This results from the transfer of blocks of genes between different bacteria. One bacterium may spend a thousand years gradually mutating a few genes to better invade the tissues of its host animal. Then suddenly, the whole package may be transferred to a different bacterium, perhaps a harmless inhabitant of a different animal, and a novel disease emerges almost instantaneously.
Bacterial cells carry their genes, typically 3,000 or so, on a single giant circular molecule of DNA, the bacterial chromosome. Mobile clusters of extra genes are often carried on smaller DNA circles, known as plasmids. These divide in two when bacteria divide, so the genes they carry are inherited just like the genes on the main chromosome. About half of all bacteria found in nature contain one or more plasmids. Many plasmids can move between bacteria. Although most move only between closely related bacteria, a few promiscuous plasmids can move across family boundaries.
The enteric family is a related group of bacteria that mostly live inside animals, in their digestive tracts. They are widespread, and most are harmless. However, virtually all may become dangerous if they get a plasmid carrying virulence genes. Thus, bubonic plague is caused by Yersinia pestis. Its relative Yersinia enterocolitica sometimes causes mild diarrhea. Yersinia pestis itself has three virulence plasmids, while its less impressive relative has just one.
Although these blocks of virulence genes move from cell to cell on plasmids, they may occasionally be inserted into the bacterial chromosome. From being an optional extra, the virulence genes have become permanent fixtures. Among the enteric bacteria, the best-known cases are found in Salmonella. The typhoid bacterium, Salmonella typhi, has at least three integrated blocks of virulence genes, and its less dangerous relatives, which cause food poisoning or mild fevers, have one or two. In addition, some Salmonella also carry virulence plasmids.
Viruses, plasmids, and virulence
Plasmids are clusters of extra genes, and viruses are packages of genes that infect cells. Is there a relationship? Sometimes, undoubtedly. Some viruses that infect bacteria have two alternative lifestyles. They may act like a typical virus and destroy the bacteria. Alternatively, instead of killing the host cell, the viruses may take up residence as circles of DNA. In other words, they become plasmids and replicate in step with the host cell. Other bacterial viruses may take up residence by inserting their DNA into the bacterial chromosome.
The best-known enteric bacterium, Escherichia coli, is a normally harmless gut inhabitant that has become famous because of its star role in genetic engineering. However, it can harbor assorted plasmids and viruses carrying virulence genes. As a result, some truly nasty strains of E. coli have emerged. E. coli O157:H7 debuted on the world stage in January 1993. It appeared simultaneously in Seattle, Nevada, Idaho, and California in contaminated hamburgers shipped from a central supplier to outlets of a single fast-food chain. Bloody diarrhea was followed by kidney failure that was sometimes fatal in children. In addition to virulence factors on plasmids, E. coli O157:H7 has a resident virus that carries the gene for shigatoxin. This toxin damages the kidneys and makes E. coli O157:H7 life-threatening instead of merely obnoxious. Shigatoxin is named after Shigella, which causes bacterial dysentery. At some point, this virus presumably infected Shigella and picked up the shigatoxin gene before moving on to E. coli.
Thus, plasmids or viruses can carry virulence genes. Transfer between closely related bacteria is obviously easier, but given time, a cluster of genes can move one step at a time between unrelated bacteria. Detailed molecular analysis has shown that the clusters of virulence genes found in enteric bacteria did not originate in members of this family. Presumably, these virulence clusters evolved long ago in bacteria of some other family and have subsequently moved. Where they first arose is still unknown.
4. Water, sewers, and empires
Introduction: the importance of biology
It is a major contention of this book that infectious disease has greatly influenced historical events. In this chapter, we consider the effect of disease, especially waterborne infections, on three major civilizations: the ancient Egyptians, the Indus Valley civilization, and the Roman Empire. Orthodox history emphasizes the actions of leaders, the strategies of generals, the policies of governments, and so forth. Sometimes the subsurface layer of economics is put forward as an underlying cause. But economics depends on the availability of raw materials and natural resources. However competent your rulers are and enlightened your fiscal policy is, creating a thriving society in a desert is difficult—unless, of course, you strike oil! This brings us to the realm of biology. Oil and coal are largely biological in origin: the decayed remains of vegetation that died many millions of years before man walked on Earth.
Behind politics lies economics, and behind economics lies biology. So then, I argue, to fully understand both history and current events, we need to include the biological perspective. Although this book focuses on the effects of disease, other biological effects are also important—these include environmental degradation, climate change, overpopulation, and pollution. In addition, these factors can help promote the spread of disease.
Irrigation helps agriculture but spreads germs
The first cities grew up alongside rivers: the Tigris and Euphrates, the Nile, and the Yellow River. Irrigation led to increased crop yields, which led to higher population density. These ancient river-based cultures then came to dominate the surrounding areas.
Ancient Egypt is remarkable for the long periods its regimes survived. The imperial Chinese dynasties that originated in the valley of the Yellow River were similarly long-lived. Settled agricultural societies based on irrigation are noted historically both for long-term stability and for the subservience of their common people. Irrigation requires large-scale public works, which, in turn, requires organized mass labor, which requires an autocratic state to control the lower classes. This political explanation ignores the fact that needs are not fulfilled by magic. Infection supplies the missing mechanism. Irrigation is extremely effective in spreading infections among agricultural workers. Waterborne diseases included a wide range of bacteria, viruses, and parasitic worms.
The class system, water, and infection
Throughout history, human societies have tended to divide into classes or castes of varying rigidity. Even in the same nation, even if they share the same religion and speak the same language, individuals of higher status avoid mixing with those of lower status. Early societies, primitive tribes, and social apes such as baboons all have a hierarchy, although they lack rigid divisions. Class systems are not based on merely social forces. Although those forces might contribute to class segregation, deeper biological reasons exist.
Infectious disease has always hit the poor and lowly far worse than the prosperous and powerful. Avoiding members of lower and more disease-ridden groups was not merely a matter of status. In the eighteenth and nineteenth centuries, for an upper-class Englishman to associate too closely with the working classes would have doubled his risk of tuberculosis. Respectable people did not associate with their social inferiors or visit houses of ill repute. Both sexual and social respectability reinforce avoiding infection. Today the threat of infectious disease has greatly diminished in the industrial nations. And yes, now that it’s safe, every political leader who wants to pick up some cheap popularity arranges to “mix with the people.”
Infection might also help keep the lower orders in their proper place. Even nowadays, some 50% of the Egyptian population is infected with assorted parasitic worms. Their feeble performance in the Arab–Israeli wars has been attributed in part to the debilitation of Egyptian soldiers by disease. In ancient Egypt, the peasants who waded barefoot in the flooded fields would almost all have been infected by parasitic worms carried by water snails (schistosomiasis).
The military aristocracy would have been far healthier, stronger, and more vigorous. In contrast, unsettled peoples, such as the Huns, Mongols, Vandals, and Arabs, tend to be difficult to rule and their empires short-lived. Here, the lower classes are not subject to debilitating disease as an inevitable result of their economic role.
The origin of diarrheal diseases
The human gut provides a home for colossal numbers of bacteria. In the small intestine, mixed in with the material being digested are several million bacteria per gram (1 oz = 28.4 g). In the large intestine, the numbers per gram can rise to 100,000 million, or more than 20 times the world’s human population. The vast majority of these bacteria are harmless, and some are beneficial by aiding digestion, making vitamins, or defending their habitats against other, more dangerous intruding microorganisms.
As we have already seen, from time to time, one of our harmless microbial inhabitants goes bad and causes disease. In addition, harmful newcomers might originate from other animals. Most of these newcomers probably arrived only after denser city populations provided more opportunities. In primeval times, outbreaks of a novel infection would have been confined to one or a few bands of nomadic hunters, and the disease would not have survived for long. As human populations got denser, they provided more scope for rogue microorganisms to circulate further and live longer.
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