The disease, now eradicated, was once one of the world's deadliest.

Smallpox ranks among the most devastating illnesses ever suffered by humankind. It dramatically altered the course of human history, even contributing to the decline of civilizations. Officially the deadly virus no longer exists. After a final outbreak in the United States in 1949, the virus was declared eradicated in 1980 following a successful vaccination program regarded as one of the greatest triumphs of modern medicine.

Smallpox is an acute contagious disease caused by the variola virus. It gets its name from the Latin word for "spotted," referring to the raised, pustular bumps that break out over the face and body of those affected. Historically the virus killed around 30 percent of people who caught it. Those who survived were often left blind, sterile, and with deep pitted scars, or pockmarks, on the skin.

Spread through direct contact with infected people, body fluids, or contaminated objects such as bedding, the disease had two main types. Variola major was the most common form–and most lethal. Variola minor produced a milder disease, which was fatal in less than one percent of cases. Two other, rarer forms also existed: hemorrhagic and malignant. Both invariably resulted in death.

Early Victims

Smallpox is thought to have originated in India or Egypt at least 3,000 years ago. The earliest evidence for the disease comes from the Egyptian Pharaoh Ramses V, who died in 1157 B.C. His mummified remains show telltale pockmarks on his skin.

The disease later spread along trade routes in Asia, Africa, and Europe, eventually reaching the Americas in the 1500s. Indigenous peoples there had no natural immunity. An estimated 90 percent of indigenous casualties during European colonization were caused by disease rather than military conquest.

Smallpox Mystery

Join researchers as they probe the mysteries of history. Why, when Europeans came to America, did their diseases devastate native populations—but not the other way around?

Smallpox contributed to the decline of the Aztec Empire, in what is now Mexico, following the virus's arrival with Spanish conquerors in 1519. More than three million Aztec succumbed to the disease. Severely weakened, the Aztec were easily defeated. Likewise, smallpox claimed the life of an Inca emperor and wiped out much of the Inca population in western South America.

In Europe, smallpox is estimated to have claimed 60 million lives in the 18th century alone. In the 20th century, it killed some 300 million people globally.

Vaccination Victory

The human fight against smallpox dates back some 2,000 years. In Asia, a technique known as variolation involved deliberately infecting a person by blowing dried smallpox scabs up their nose. Those who received this treatment contracted a mild form of the disease, developing a lifelong immunity.

A key breakthrough came in 1796 when an experiment by English doctor Edward Jenner showed that inoculation using closely related cowpox could protect against smallpox. Jenner's discovery paved the way for later vaccination programs—especially crucial since there is no effective treatment for smallpox.

In 1967, a year when some 10 million to 15 million people contracted smallpox, the World Health Organization launched a worldwide eradication campaign based on vaccination. Gradually, the disease was pushed back to the Horn of Africa, and the last known natural case occurred in Somalia in 1977.

Despite being consigned to the history books, there's still a chance of smallpox coming back to haunt us—as a biological weapon. Such fears escalated dramatically in the United States following the September 11, 2001, terrorist attacks. While the risk of such a bioterror attack is considered very low, the U.S. has since stockpiled enough of the vaccine to inoculate every citizen.