Smallpox (Variola) is a member of the orthopox virus family, which also includes cowpox, buffalopox, camelpox, monkeypox, rabbitpox, and raccoonpox. (Chicken pox, however, is not related.) It is theorized to have evolved from a virus present in rodents in Africa several thousand years ago, but to have caused much more severe effects when the virus jumped to humans. Until settlements of around 200,000 people arose, it was probably a rare disease, but these large groups of people are enough to keep the disease constantly going to new hosts before previous hosts die or recover.

Smallpox should be as well-known to people as the bubonic plague for its effect on human history. The disease is mentioned in ancient Egyptian writings, circa 3700 B.C., and the mummified body of Ramses V shows the pustules on his skin. A smallpox epidemic in Athens weakened the city shortly before the Peloponnesian War, contributing to Athens' defeat. Smallpox attacked the soldiers of Alexander the Great in India, contributing to his decision to turn back his conquering army. Emperor Marcus Aurelius' death from smallpox probably accelerated the decline of the Roman Empire.

But even greater results from smallpox epidemics was found during the European colonization of the Americas. Europeans were generally more resistant to the disease because of its constant presence in Europe; Native Americans had no resistance at all. In the Caribbean Islands, up to half the Indians died from smallpox brought over by Europeans; this led to the first importations of African slaves, who were more resistant. Hernando Cortes might have been expelled from Mexico by the Aztecs if it were not for the smallpox epidemic that gripped the Aztec capital of Tenochtitlan after the Spaniards' first visit. The disease spread from Mexico down into South America through native traders, and afflicted the Inca civilization, killing Emperor Huayna Capac and his designated heir. The remaining claimants to the throne got into the civil war which allowed Francisco Pizarro the chance to overthrow the entire government.

Enough trading went on in North America that smallpox affected those Indians also. Almost nine-tenths of the native population in the Massachusetts Bay area died of smallpox in the four years before the Pilgrims landed in 1620; Pilgrim leader John Winthrop wrote that "the natives, they are all near dead of the smallpox, so as the Lord hath cleared our title to what we possess." The disease kept spreading into populations that had not been exposed to it; Elizabeth Fenn estimates that in the years 1775-1781, smallpox reached the Comanches, Mandans, Hidatsas, Arikaras, Apaches, Crows, Sioux, Ojibwas, and many other tribes of the North Plains and Northwest Coasts of the U.S. and Canada. Records show that more than 61,500 Native Americans died of smallpox during those seven years in what is now the U.S. and Canada (possibly many more, since that total is based only on surviving records). During the same years, the region that is now Mexico recorded at least 46,000 deaths from the disease (this includes anyone who had been baptized Christian, whatever their racial background).

Colonists of European descent were nearly as vulnerable as Indians after a generation or so in the New World, where smallpox tended to sweep through the population every twenty years or so rather than being as endemic as it was in much of the Old World. During the American Revolution, the British were accused by the colonists of intentionally spreading the disease in the besieged city of Boston right before the British abandoned the area in March 1776. Smallpox-weakened forces were definitely one cause of the failure of the U.S. attack on Quebec around the same time.

The contagious nature of smallpox was well-known in any area that had experienced it. Smallpox cannot be transmitted through animals, but the virus is present in an infected person's saliva, mucus, urine, pus, and blood. So it can be spread through sneezing, coughing, or talking, but also even coming in contact with dried pus or scabs from pustules could pass along the disease (laundry workers handling bed linens from smallpox wards were at great risk of coming down with the disease). Quarantine was the favored solution, though it often left the sick unable to help themselves without enough health workers who had already had the disease.

Variolation (sometimes called inoculation) was practiced in some areas. This was the practice of deliberately infecting people with the disease through a scratch in the skin; acquiring it this way seemed to lead to milder cases of the disease than catching it naturally by breathing it in (the fatality rate dropped from 30% to 1%). This idea seems to have been invented in India, spread both east and west from there, and was brought to Europe by Lady Mary Wortley Montagu, wife of the British ambassador to Constantinople, in 1718. Anyone who has actually had smallpox, either naturally or through variolation, is immune for life, and this was a powerful incentive for many to undergo variolation. Others, though, refused to go and catch a possibly deadly disease on purpose. Another problem with variolation was that the mild cases might lead people to return to their normal activities while they were still infectious; the people who caught it from them would not have a mild case.

In 1796, Dr. Edward Jenner was doing research on cowpox, a mild disease humans can catch from cows, and its relation to smallpox; milkmaids who had had cowpox never seemed to catch smallpox. He inoculated an eight-year-old boy with cowpox, and one month later with smallpox. The child proved immune to smallpox, and two years later after more research Jenner published his results. This started the era of vaccination, though for the next century it proved difficult to keep cowpox samples available with which to give vaccinations. It also turned out that smallpox vaccination did not offer lifelong immunity, but only about a decade's worth. (This is still the case with modern smallpox vaccine.) Some people, especially those with compromised immune systems, also have serious reactions to the vaccine.

Smallpox was still causing an estimated two million deaths per year in the 1960s. Freeze-dried vaccines supplied by developed countries and a special needle used for vaccinations made it easier to vaccinate in rural areas of developing countries, and the World Health Organization went on a campaign to eradicate the disease, which finally became a reality in 1980. But this only made it more dangerous in many ways, as supplies of vaccine have dropped and medical personnel now assume smallpox could not be a possible diagnosis. Officially, all samples of the smallpox viruses have been either destroyed or sent to one of the two remaining stashes in the United States and Russia. The Soviet Union was revealed in 1992 to have been working with the smallpox and related viruses as agents of biological warfare; this was revealed by Kanatjan Alibekov, a former researcher who was helped by the CIA to move to the United States. It is also possible that other countries or organizations have samples of the virus, either stolen or just not destroyed when they were supposed to be. (North Korea and Iraq are suspected to have these stockpiles.) Because of its extreme contagiousness, smallpox is considered a likely choice for bioterrorists if they were to have access to it. On the other hand, the technical difficulty of working with the virus and growing enough of it to use for large-scale operations without killing off those on their own side does reduce the likelihood of a bioterrorist attack with smallpox.

Whether the last two known archives of the virus should be destroyed has been argued for over a decade. Some feel that since the DNA sequence of the smallpox virus has been recorded and the vaccine is actually made from a related virus, not smallpox itself, that there's no reason to keep samples, and destroying the American and Russian repositories would reduce risk of the virus escaping in any way from them. Others feel that future research may need the actual virus (particularly for drugs to treat the disease), or that intentionally making an organism extinct is wrong even if it's a virulent disease.

Due to fears of bioterrorism, in 1997 the U.S. Department of Defense started to order a large amount of smallpox vaccine; two years later the Department of Health and Human Services followed suit. There are no plans to vaccinate most people in the U.S. because of the occasional serious reaction to the vaccination; however, in July 2002 U.S. plans to vaccinate health care and emergency workers were expanded from 15,000 to 500,000 people. The CDC is handling the logistics of this plan and the contingency plans for mass vaccinations in case of smallpox attacks. Vaccination within three or four days of being exposed to the virus usually prevents the disease from taking hold in a person. Not every virologist agrees that the "ring approach," used by WHO in their eradication of the natural disease and in the current U.S. plans, will work in modern society. The ring approach involves vaccinating all known contacts of every known smallpox case, preventing them from getting the disease and spreading farther; some argue that this worked in rural villages but will not in large cities with a mobile population. Hopefully it will never have to be tested.

Sources:
Broad, William J. "U.S. Plans Mass Smallpox Shots," The Tampa Tribune 7 July 2002.
Fenn, Elizabeth A. Pox Americana: The Great Smallpox Epidemic of 1775-1882. New York: Hill and Wang, 2001.
Tucker, Jonathan B. Scourge: The Once and Future Threat of Smallpox. New York: Atlantic Monthly Press, 2001.