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

by David P. Clark

  Transmission of emerging viruses

  It is sometimes suggested that highly virulent diseases cannot spread very far unless they are carried by vectors such as fleas or mosquitoes. Granted, milder variants of a disease tend to spread further. Nonetheless, if Ebolavirus or Lassa fever had started out capable of infecting humans efficiently, the diseases could have spread much further. We know this from what happened when smallpox and measles first reached the American continent.

  So why have the outbreaks of Ebolavirus and Lassa fever burned out so rapidly? For a person-to-person disease, two factors affect transmission. First, how many other people does the infected victim contact? This depends on how long he survives and how far he can move. Clearly, this factor reduces the spread of more virulent diseases. Second, how well does the virus jump from one person to another upon contact? This is a property of the virus itself and varies greatly. As noted earlier, although both are highly virulent, neither Ebolavirus nor Lassa fever is especially infectious to humans.

  Moreover, for every person exposed to deadly viruses such as Ebola or Lassa, a thousand are exposed to other unknown viruses from rats, bats, monkeys, zebra, elephants, and other animals. Most of these unknown viruses will never make the headlines because the body’s immune system zaps them as soon as they set foot inside. In summary, humans could be highly susceptible to viruses they have never been exposed to, but most viruses that have not adapted to humans will be extremely susceptible to immune system destruction. Occasional strange viruses do escape the immune system and cause a great deal of damage. But because they are not adapted to humans, these chance invaders rarely have an effective way to move from person to person.

  Efficient transmission and genuine threats

  For a genuinely new human plague to emerge, the agent of disease must evolve (or already possess) some way to spread efficiently. Probably the best way is to spread through the air, directly from person to person, as with flu or measles. Despite killing only a tiny fraction of their victims, measles and flu both kill far more people than all the novel emerging viruses combined. This is because they infect vast numbers of victims.

  Influenza virus changes both by rapid mutation and by exchanging genes between flu strains from people, pigs, and poultry. Most new flu strains have only minor alterations, but now and then, major changes occur that produce variants with increased virulence. In the twentieth century, this occurred in 1918 and, less impressively, in 1933, 1957, 1968, and 1977. The virulent flu of 1918 had an overall mortality of only 2% to 3%, but because it infected most of the human population, the total death toll was huge: 30 million to 100 million, according to different estimates.

  In 1920, the world population was a little less than 1.5 billion, and in the year 2000, it was a trifle more than 6 billion. Thus, today’s population is about four times as dense as during the Spanish flu of 1918. As we know, the denser the host population, the more this favors the spread of virulent infections. Influenza and assorted respiratory infections, ranging in mildness down to the common cold, are caused by hundreds of different viruses that constantly mutate. These viruses are well adapted to transmission among humans. Sooner or later, one of these, not necessarily flu itself, will likely throw up a virulent variant. As Pasteur might have put it, chance favors the prepared microbe.

  The history and future of influenza

  The first definite flu epidemics were recorded in Europe in 1510, 1557, and 1580. The mortality rates of up to 20% were vastly more lethal than any recent epidemic except the 1918 Spanish flu. Over the centuries, either flu has been getting milder or humans have been getting more resistant. The flu epidemics of the 1500s killed a substantial proportion of the population and must have weeded out many sensitive members of the population.

  Flu is shared among people, pigs, and poultry. Most new variants of flu originate in China, where large numbers of ducks and pigs live close to humans. The Asian flu of 1957 and the Hong Kong flu of 1968 are typical examples. Direct chicken-to-human transfer of influenza is very rare. Generally, flu goes via ducks and pigs. However, in Hong Kong in 1997, a handful of people died from avian flu that was apparently transferred directly from chickens. Luckily, this flu virus did not transfer between humans. It’s unlikely that future outbreaks of flu will result from direct fowl-to-human transfer of a virus that is both lethal and capable of spreading from person to person, but this is still a nasty possibility.

  The great influenza epidemic of 1918–1919

  The outbreak started in the United States and spread to France in April 1918 with arriving American troops. From there, it spread to Spain, where it first caused public alarm (hence the name Spanish flu). It behaved strangely, in that half the victims killed were in the 20–40 age group. The greatest death toll, perhaps 20 million, occurred in India. In a few small communities where everyone fell ill simultaneously, leaving no one to attend the sick, nearly 50% died. Among people of European descent, about 5 per 1,000 died. The typical death toll among nonwhites was five to ten times higher. In South Africa, many baboons died alongside their human cousins; we cannot be sure, but they probably caught Spanish flu.

  It is often suggested that the Spanish flu was somehow caused by the crowded trenches and troopships and was spread by the troop movements of World War I. However, Europe was far more disrupted by World War II, in which both troop and refugee movements occurred on a larger scale than in the earlier war. The crowded air-raid shelters of World War II were ideal breeding grounds for a respiratory disease such as flu. Yet from the beginning of World War II, no major influenza outbreak happened until 1949. A related question is why no lethal flu virus has yet emerged from the massively overcrowded postwar cities of the Third World. These questions suggest that Spanish flu was just a chance mutation to a rare virulent form that coincided with the end of World War I. Troop movements probably spread it faster than normal, but if the world had been at peace, the new variant would surely have spread by trade and civilian travel.

  As I was writing this chapter, in April 2009, a novel version of swine flu has emerged from Mexico. Despite massive publicity, it has had little real effect, except on the Mexican tourist industry. Although it is aberrant in some ways, so far it is relatively mild. The World Health Organization has declared an official pandemic, based on the worldwide spread of the virus. However, most infected people have recovered without any need for medical care. Mutation to a more virulent form is always possible with flu, but as of now, it seems unlikely that this outbreak will bring about a major disaster.

  Disease and the changing climate

  The temperature of our planet has fluctuated considerably in the past. We have already mentioned the period of cooling in early medieval times that might have ultimately triggered the Black Death. Ice cores drilled in Greenland indicate that temperatures reached the most recent minimum (“mini Ice Age”) about a hundred years ago, when the Thames River that runs through London froze over in winter. Since then, the temperature has been slowly rising. Global warming will have a major impact on infectious disease—mostly for the worse, because disease tends to thrive in hotter moister climates.

  One major effect will be to extend the range of mosquitoes and the diseases they carry, especially malaria, yellow fever, and dengue fever. Temperate zones that have been largely malaria-free will likely suffer major intrusions. Deforestation and the creation of large areas of stagnant water by irrigation projects have added to the effects of global warming. Other insect pests and tropical diseases will follow suit.

  Global warming coupled with changing rainfall patterns also affects diseases spread by water, including cholera. Outbreaks of disease due to contaminated water in the United States mostly come when rainfall is unusually high. Cholera outbreaks are favored by warmer ocean temperatures and higher rainfall. Extra rainfall increases nutrient run-off from the land into the seas. This drives blooms of marine algae and plankton. This, in turn, allows the cholera bacteria that live inside plankton in coastal water
s to proliferate. Cholera in coastal waters is presently moving northward from Peru, where the last major outbreaks occurred.

  Floods, which are likely to increase in frequency due to a warmer, wetter climate, tend to aid the spread of disease, especially in poor countries, where hygiene is already dubious. Rodents driven from their homes during floods are apt to spread disease. One example is the outbreak of bubonic plague in Surat, India, in 1994. An earthquake followed by a flood left thousands homeless. Emergency supplies were provided for the human victims. However, hordes of rats were also flooded out and spread plague as they scavenged for food and shelter among the refugees.

  Technology-borne diseases

  Advances in technology both shut and open doorways for disease. Sewers remove human waste and decrease typhoid and dysentery. Sewers provide highways, or rather subways, for rats to scurry through carrying plague. Virtually every major change in technology has altered the risks of catching some infection. Today is no different. Irrigation projects can cause increased spread of malaria and bilharzia in Africa and Asia.

  Changes in food processing have increased food poisoning in the United States. Processing food in ever-larger batches is economically efficient but provides better opportunities for bacteria to spread. Hamburger contaminated with E. coli and peanut butter with Salmonella have become staple news items in the last few years. Although not novel themselves, many bacteria responsible for food poisoning do carry newly acquired virulence factors. Mad cow disease is one of the few truly new emerging diseases. Its spread was also triggered by changes in animal husbandry.

  In contrast, Legionnaire’s disease is not new, but its emergence from obscurity did rely on new technology. The bacteria can accumulate in water tanks or cooling towers and spread when humans breathe in the aerosols generated by showers, ventilators, and air-conditioners. Legionnaire’s disease was first identified following an outbreak at the American Legion convention in Philadelphia in 1976. Consequently, the bacterium causing it was named Legionella, in honor of the American Legion. Since then, sporadic outbreaks of Legionella have occurred at hotels and other institutions. Despite the journalistic hype that greeted its emergence on the world stage, Legionella is only a minor irritation in global terms. A few hundred cases a year, with a fatality rate of about 10%, occur in the industrial nations. This will probably continue for the foreseeable future.

  Emergence of antibiotic resistance

  In addition to the threat from truly novel infectious agents, well-established infections can gain new abilities. Since antibiotics were introduced in the 1930s, many bacteria have evolved resistance. Similar problems have been seen with antiviral drugs and with the insecticides used to control insects that carry disease. Before getting too panicky, we should remind ourselves that the great decline in infectious disease happened before antibiotics were discovered. Sanitation and vaccination eliminated most of the dangerous infections from industrial nations.

  Antibiotic resistance can appear as a result of a novel mutation or can be transferred from one bacterium to another. Even in the early days of antibiotic use, sporadic cases of resistance arose. Most of these were due to mutations in the bacteria that were being treated, and relatively few of these resistant strains spread. In the absence of the antibiotic, most resistance mutations are harmful to the bacteria. For example, spontaneous mutants of bacteria resistant to streptomycin have defects in protein synthesis. Mutants resistant to kanamycin or neomycin cannot respire properly. The situation is reminiscent of human mutations that give resistance to malaria but cause sickle-cell anemia or give resistance to typhoid but cause cystic fibrosis. In the absence of the threat (antibiotics for bacteria, malaria for people), the resistant mutants fade away.

  The bigger threat comes from transmissible antibiotic resistance. Plasmids are circular segments of extra genetic information that many bacteria carry. Some plasmids move from one bacterial strain to another and carry genes that are “optional extras”—handy under some conditions, but useless or a burden under others. Plasmids can confer the ability to grow on rare and unusual nutrients. They can also carry genes that protect bacteria against antibiotics or toxic metals, both due to human activity. The antibiotic resistance genes carried on plasmids rarely interfere with normal bacterial growth. Instead of risking alterations in vital bacterial genes, plasmids bring in extra genes from outside. These often destroy the antibiotic with no detrimental side effects on the bacteria. Consequently, even in the absence of antibiotics, the antibiotic-resistance plasmids are lost only very slowly. A single plasmid can carry resistance to several antibiotics. Alternatively, a single bacterium can contain several plasmids, each conferring resistance to a single antibiotic. Either way, the result is multiple-antibiotic resistance that can be passed from bacterium to bacterium.

  The emergence of antibiotic resistance was inevitable. When living creatures are killed in large numbers, a few resistant individuals usually survive to breed. Nonetheless, the rapid spread of antibiotic resistance has been helped by human greed and stupidity. Farmers often include antibiotics in animal feed. This keeps infection down and supposedly results in more meat per dollar. It also encourages the spread of resistance plasmids that can later transfer to bacteria that infect humans. Many European nations were smart enough to realize that the costs of extra hospital care vastly outweighed the few pennies saved by cheaper bacon and have greatly restricted this practice.

  Today agriculture consumes about two-thirds of antibiotics, and only about one-third is used medically. Third World nations are becoming major contributors to this problem, as the increasing demand for meat has led to widespread abuse of antibiotics. While the industrial nations start to clean up their act, many poorer nations are using more antibiotics to increase meat and chicken yields. The only factor in choosing which antibiotics to put in animal feed in poorer countries is the price. This undermines the growing tendency in advanced nations to reserve certain antibiotics for human use.

  Another problem is overprescription. Although antibiotics kill only bacteria, doctors often prescribe them for virus infections, such as colds and flu. This abuse is vastly more common in the United States. Partly, Americans want to get something to “cure” them. Explaining that antibiotics don’t cure viruses to people with the lowest education standard of any industrial nation is just too much effort. Doctors, in turn, are frightened that if they are honest, they might lose their patients to another, more obliging physician. (In reality, a recent survey by the CDC showed that few patients actually wander from doctor to doctor.) Doctors are also frightened of being sued for failing to provide “appropriate treatment.” In England, children with ear or throat infections are given antibiotics only in rare cases when the infection continues. In the United States, “Shoot first, ask questions later” is the motto not just of yesterday’s cowboy, but also of today’s yuppie parent.

  One way to combat resistance is to replace old antibiotics with newly invented ones. Soon after they were first discovered, there was a big rush to discover new antibiotics or modify old ones chemically, yielding new variants. When most known bacterial diseases had cures, complacency set in. Recently, drug resistance has hit the headlines and research has picked up again. Although some new antibiotics are now in the pipeline, it takes several years to get a new drug from laboratory to hospital. As new antibiotics are deployed, resistance will inevitably appear. We can look forward to a permanent cold war between bacteria and pharmaceutical companies.

  Where do the resistance genes on plasmids come from? They are gifts from Mother Nature, like most antibiotics. Long before humans isolated penicillin from the mold Penicillium, or streptomycin from the bacterium Streptomyces, these antibiotics were deployed to wage biological warfare in the soil. Bacteria and molds have been slugging it out for eons before humans joined in the fray. Not only did microorganisms develop antibiotics to kill each other, but they developed resistance mechanisms to counter each other’s attacks. Some bacterial cultures stor
ed before penicillin was discovered already had resistance genes. Thus, resistance to most antibiotics probably predates their use by humans. Increased use has led to the spread of these resistance genes.

  Disease and the food supply

  We have focused on human disease, but remember that livestock and crop plants suffer from infections, too. Modern farmers tend to rely heavily on a few main crops, with little crop rotation. Large areas of a single crop provide the same opportunities for plant diseases that overcrowded cities provide for human infections. The warmer, wetter weather that is becoming more prevalent favors fungal infections that attack plants. For example, wheat scab outbreaks in the United States and Canada caused massive losses in the 1990s.

  Decreased surpluses in the major grain exporters undermine the safety net for overpopulated third world nations. If major drought in tropical areas such as Africa or India coincides with major crop losses in the grain exporters, the result could be widespread famine. In 2006–2007, world grain reserves fell to 57 days of consumption, the lowest since 1972.