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Germs, Genes, and Civilizations: Our Debt to Disease

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In this introduction to his book, David Clark explains how, over the long term, a positive side to disease emerges.
This chapter is from the book

Early in the fifth century A.D., the Huns, led by Attila, emerged from the Asian steppes and swept across Europe. They faced no serious resistance. What was left of the greatest civilization the world had seen, the Roman Empire, was a tottering wreck. One more good shove and the remains of Roman civilization would have taken a final nose-dive. But strangely, on the verge of storming Rome itself, Attila withdrew. Why?

For many centuries the official answer was that God had intervened in some mysterious way to protect his chosen city, Rome, seat of the papacy. In more recent times, such supernatural explanations have fallen out of favor and the question has arisen anew. Some have suggested that Attila was overawed by the sanctity of Rome. But why would a pagan warlord like Attila stand in awe of a Christian center? Attila was by no means an ignorant barbarian: For example, he invited Roman and Greek engineers into Hun territory to install bathing facilities. However, his respect for Roman civilization was clearly of a pragmatic rather than a religious nature. Another theory is that Attila was worried about leaving unattended his newly acquired homeland, in what is now Hungary. But then why did he venture out almost as far as Rome and hang around indecisively for so long before returning? All these explanations founder on the same point. It seems clear that Attila did indeed set out with every intention of taking Rome, but his expedition came to a premature halt.

Mounting modern evidence suggests that Attila was stopped by a virulent epidemic of dysentery, or some similar disease. Most of his men were too ill to stay on their horses, and a significant number died. In short, bacteria saved Rome. The ancient world had no knowledge of bacteria. Instead, most ancient cultures believed that epidemics were one of the main ways the gods expressed their displeasure. In the Bible, pestilence is often a punishment for wickedness, both for disobedience by the Israelites themselves and for intrusions by outsiders. For example, an epidemic saved the holy city of Jerusalem from the Assyrian invaders, providing a precedent for the failure of Attila to take Rome. So, in a curious way, the earlier explanation of God preserving Rome has reemerged in a modern scientific guise.

But before we rush to enroll the bacteria as honorary Roman citizens, we must consider another aspect of the issue. A major reason Rome itself was in such disarray when Attila approached was that it, too, had fallen victim to pestilence. Several catastrophic epidemics had swept through Rome in the period before the Huns surged into Europe. So whose side were the microbes really on?

Nowadays, floods, earthquakes, and volcanic eruptions are regarded as "acts of God," at least by insurance companies. The implication is that neither the victims nor anyone else is responsible. This is not entirely true. People who persistently rebuild their homes on a flood plain or along a fault line are at least partly to blame. Similarly, epidemics do not just happen to anyone at anytime anywhere without good reason. Neither the epidemics that struck Rome nor the disaster that overcame Attila's Huns were just random outbreaks of disease. What's more, their origins were interrelated.

Before Attila, Rome had several narrow escapes from other hordes of barbarians. Several times it looked as if the end was near and that the Romans would be overwhelmed. Yet somehow the Romans scraped by. Part of the credit must go to the Romans, who were an unusually determined people, not prone to giving up easily. Yet much of the credit also belongs to the unseen and unsung legions of microbes. It is relatively easy for us today to understand why an overcrowded, unhygienic ancient city suffered from persistent outbreaks of pestilence. Why disease so often intervened to protect the same city from successive waves of barbarians is more difficult to understand.

Imagine an ancient society that is moving along the path to urbanization. Large numbers of people are crowding into a growing city, such as Babylon, Athens, or Rome, which is much larger than neighboring communities. Infections normally spread more efficiently through crowded cities than through sparsely populated villages and rural areas. Sooner or later, some pestilence or plague will strike the emerging city. Its population will be decimated, and for a while it will be vulnerable. But if it recovers, its population will consist largely of those who are resistant to the plague of the day. In other words, denser populations are the first to build up resistance to the current infectious diseases in their region of the world. Next time a major conflict arises, the movements of armies or of refugees will spread infection around the war zone. People from rural communities or smaller towns will have built up less resistance than the population of the city-state, so pestilence will fight on the side of the biggest city.

Once a major population center gains a significant lead over its competitors, the pestilence factor will make it extremely difficult to overthrow. This indeed is what happened to ancient Rome. A series of epidemics whose identities remain unknown devastated the Romans early in their history. Later, barbarians who ventured too close to Rome routinely succumbed to massive epidemics that had only mild effects on the Romans. As long as the Huns retained their nomadic lifestyle, they would have been little affected by epidemics. Even if an occasional marauder caught some infection from more settled and crowded regions, it was difficult for pestilence to spread among small, scattered groups of nomads. Once the Huns aggregated into a horde, under centralized leadership, the situation changed radically. On the one hand, they had little previous exposure to pestilence, so they lacked resistance. On the other hand they now formed a large, dense population, ripe for the spread of invading microorganisms. In a way, Attila's tragedy was the result of this vulnerable intermediate situation between nomadism and urbanization.

The general principle that pestilence favors societies that have become resistant because of prior infection has had a vast effect on human history. It has not only directed the growth and survival of the empires of the Old World, but it also was the major factor in European invaders' takeover of the American continent.

Epidemics select genetic alterations

Another result of ancient epidemics that experts have only recently come to understand is the accumulation of alterations in the human genome. Through the millennia, a never-ending stream of hostile microbes has attacked and decimated human populations. Each time a human population is devastated by infectious disease, genetic selection takes place. People carrying genetic alterations that confer resistance, even if only partially, have a greater chance of survival. Consequently, their descendents will make up a greater proportion of the surviving population.

The result of constant epidemics is that, over the ages, distinct acquired genetic changes now protect us against many individual infections. We still carry these modifications in our DNA sequences, and recent investigations are revealing a steady stream of such genetic alterations, many surprisingly recent. Thus, in many ways, we are what disease has made us.

Yet another convoluted twist of fate appears here. Several well-known hereditary defects turn out to be side effects of resistance to disease. For example, sickle cell anemia is the result of hereditary resistance to malaria, and cystic fibrosis is associated with resistance to intestinal diseases that cause diarrhea and dehydration. A single copy of the cystic fibrosis mutation reduces water loss, thus protecting against a range of diseases whose most dangerous effect is dehydration. Two copies of the cystic fibrosis mutation slow water movements in the lung too much. So one copy of the mutation protects against disease, and two copies of the same mutation cause a hereditary defect.

The case of cystic fibrosis is especially revealing. The cystic fibrosis mutation is unusually common in those of northwest European ancestry. Calculations based on mutation rates and population genetics suggest that these mutations arose shortly after the collapse of the Roman Empire. This collapse led to a massive loss of general hygiene, especially in the water supply. Doubtless waterborne intestinal diseases spread like wildfire, and eventually, mutations providing resistance accumulated.

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