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Chapter 1: A General Introduction

Individual viruses have evolved interesting and unique lifestyles. One consequence is that battles have been won or lost when a particular virus infected one army but not its adversaries. Viruses have depleted the native populations of several continents. Entire countries have been changed geographically, economically, and religiously as a result of sweeping virus infections that were impervious to known cures.

Smallpox alone, in the twentieth century, has killed an estimated 300 million individuals, about threefold as many persons as all the wars of this century. In the sixteenth and seventeenth centuries, smallpox killed emperors of Japan and Burma, as well as kings and queens of Europe, thereby altering dynasties, control of countries, and alliances. Earlier, the successful conquest of Mexican Aztec and Peruvian Inca empires by a handful of Spanish conquistadors led by Hernando Cortes and Francisco Pizarro, respectively, resulted in large part from epidemics of smallpox and measles virus infection that decimated the native defenders. Most of the conquistadors had been exposed to these viruses in Europe, so were immune to (protected from) their effects, but those of the New World were completely vulnerable. In fact, neither the obvious technical superiority of the Spaniards and the superstitions that Quetzalcoatl or other gods would destroy the natives, nor the Spaniards' alliances with tribes subjugated by the Aztecs or Incas accounts for the Spanish victory. History asserts that the Aztecs, once incited to fight, savagely attacked and defeated the Spanish. However, on the very evening that the Aztecs drove the conquistadors out of what is now Mexico City, killing many while routing the rest, a smallpox epidemic began. As it raged in the city, not only did the susceptible Aztec forces die in droves, but the psychological aspect of seeing Spaniards, who fought under a Christian god, resist this new malady while warriors of the Aztec gods were dying of infection demoralized the natives even further. The Aztecs could not have known that smallpox was endemic in Europe at this time and that many in Spain exposed to smallpox earlier were resistant or immune to subsequent infection by this virus. The stricken Aztecs interpreted the death of their people while the Spaniards went untouched as a clear indication that the Christian god held dominance over native gods. Therefore, one direct consequence of mass smallpox infection was the subjugation and subsequent exploitation of native Americans and Mexicans by the Spaniards. A second and more lasting effect was destruction of the native culture; as the Spaniard culture assumed sovereignty, millions of Indians were converted to the Christian faith. During the time of the Spanish conquest in the New World it is estimated that more than one-third of the total native population had been killed by smallpox viruses.

In addition to propelling the establishment of Christianity in Mexico and Latin America, viruses played a role in enlarging the African slave trade throughout the Americas. African blacks are relatively resistant to yellow fever virus, whereas Caucasians and native Americans are much more susceptible. Because so many native Americans had died from yellow fever, too few workers remained to do chores in the fields and mines. The Spaniards then imported black slaves as labor replacements. The net result was expansion of black slave importation to the Americas; ironically, the yellow fever virus initially came from Africa aboard trading and slave ships.

In addition to Spain, other European countries staked out colonies in the Americas. The French colonized Haiti and, in keeping with their observation that the Africans resisted infection by yellow fever and therefore were stronger workers, used primarily black labor for their plantations. But viruses altered human history again when black slaves revolted in the early years of the nineteenth century. To put down that uprising, Napoleon sent over 27,000 crack troops to Haiti. Before long, the vast majority of these French men came in contact with the yellow fever virus transmitted by mosquitos and died from the infection. This huge loss influenced the decision not to risk the even larger numbers of troops necessary to protect other French territories in the New World and was one of the major considerations leading Napoleon to negotiate the sale of the Louisiana Territory to the United States.

England also colonized large parts of North America, including what was to become the early United States and Canada. During the Revolutionary War, the American colonial government sent an army to wrest Canada away from the English. Having captured Montreal, the colonial army, superior in numbers, marched on to engage in the conquest of Quebec City. But smallpox entered their ranks. The decimated American army, soon after burying their dead in mass graves, retreated in disorder from Quebec.

The bigger picture lies in the after-effects of smallpox, measles, and yellow fever viruses. Some historians link the Spaniards' New World riches with the initial dominance of Spain in Europe. Nevertheless, the later demise of Spain in European politics is attributed by some primarily to wealth acquired from the Americas, which fostered a leisure population that was slow to enter the industrial revolution. The situation may have been very different had the natives not been susceptible to the diseases the Spanish brought over. Viruses interfered so that Canada and the United States never united into a single country. Further, the virus-promoted Louisiana Purchase provided an opportunity for the United States to enhance its size by unprecedented western expansion, without precipitating a potential geo-political conflict with France. The aftermath of virus infection uprooted native cultures and peoples of south, central, and Latin America and replaced them with a European culture, where Christianity flourished. Enhanced transport and introduction of black African slaves in the New World filled a niche created by yellow fever viruses.

But at that time, who would have imagined that the ancient diseases of humankind, smallpox and measles, would eventually be controlled? Smallpox, after decimating the ancient Mexican population, still continued to kill, for example, until the early 1940s, being responsible for the deaths of over 10,000 Mexicans a year. Yet smallpox has now been eradicated not only from Mexico but also from the entire world as a result of vaccination programs. Eradication of measles virus is also a reasonable goal in view of its control in most industrialized countries. In 1970, measles viruses infected an estimated 130 million individuals and nearly killed eight million. Today in the underdeveloped countries of the Third World, measles virus infects about 40 million individuals per year with a death rate approaching one million.

Poliomyelitis virus is a relatively new virus. Polio epidemics were not recorded until the nineteenth century, followed by an increasing incidence in the twentieth century. At one time, poliomyelitis virus infection was responsible for one-fifth of the deaths from acute disease in Sweden (8). No one would have guessed then that poliomyelitis would now be under control or that its eradication from this planet would be a goal of the World Health Organization for the year 2000. Similarly, because of vaccination, yellow fever virus no longer spreads the havoc and fear it once did. These triumphs of medicine reflect the achievements that are possible when medical scientists and government agencies together devote their resources to solving health problems.

In contrast with these harnessed viruses, new plagues of fearful proportions have now appeared. Human immunodeficiency virus (HIV) is currently reported to infect nearly 100 million people. There is no satisfactory treatment to permanently arrest the disease. There is no vaccine to prevent it. There are no known spontaneous cures.

Other plagues are now also emerging. Hemorrhagic fevers made their formidable appearance in the second half of the twentieth century. Evident on all continents, exhibiting frightening death rates, they claim numerous victims. Ebola, Hanta, and Lassa viruses provoke the fear today that yellow fever, poliomyelitis, and smallpox did in previous times. One former plague, a type of influenza virus that killed over 20 million persons between 1918 and 1919 -- more victims than died in World War I -- may make a comeback.

Last in this list is the current scare that beef from cattle with mad cow disease is causing human dementia. However, both the probability of an epidemic and identification of the causative agent as a virus remain debatable.

To assist the reader in understanding how plagues of the past were first observed and then controlled, despite numerous difficulties, the next two chapters briefly review the principles of virus infection and its course. Chapter 2 defines what a virus is, how it replicates, and how it causes disease. The third chapter explores how the human immune system combats viruses, either aborting infections or becoming stimulated via vaccination to prevent viral diseases. For those interested in virology and immunology, Chapters 2 and 3 are recommended. Otherwise, the reader may skip directly to Chapter 4. Knowing how vaccines were envisioned and developed helps to explain why devising a vaccine for HIV is so difficult, and what steps are required in successfully attacking and combatting a virus infection. The balance of power between any virus and the host it infects reflects the strength, or virulence, of the virus and the resistance or susceptibility of the host.

Readers of this book will encounter the major personalities who became microbe hunters in the fight against smallpox, measles, yellow fever, poliomyelitis, Lassa fever, Ebola, Hantaviruses, HIV, influenza, and spongiform encephalopathies. The history of viruses and virology is also the history of men and women who have worked to combat these diseases. The conquest or control of any disease requires the efforts of many. However, several who became prominent by identifying, isolating, or curing viral infections have been singled out by history as heroes. This book also examines the research of medical investigators which eventually linked certain diseases with specific viruses and led to their ultimate control. Because these scientists -- virologists -- are human, inevitable conflicts arose among them, and some of these stories are also told.

The history of virology would be incomplete without describing the politics and the superstitions evoked by viruses and the diseases they cause. For example, armed private citizens and militias attempted to prevent frightened crowds from fleeing Memphis in 1878-79 during an epidemic of yellow fever, from leaving New York City in 1916 because of poliomyelitis, and from abandoning Zwitheba, Zaire (renamed Congo Republic in 1997), in 1995 to escape Ebola. Thus woven into the fabric of the history of viral plagues is the fear, superstition, and ignorance of man. Further, we can consider together how the people of a country like the United States could unite in a crusade to prevent poliomyelitis, yet succumb to controversy in alleviating the spread of and suffering from HIV. Believe it or not, a similar lack of support by industrialized countries of the world, including the United States, once halted the initial plans to eradicate smallpox.