The Ancient Origins of a Deadly Foe

Smallpox, caused by the variola virus, ranks among history’s most devastating diseases. While its exact origins remain uncertain, scientists believe it evolved from an animal-borne virus—likely a harmless relative affecting livestock—that mutated to infect humans during early agricultural societies. The earliest physical evidence comes from Egyptian Pharaoh Ramses V (died 1156 BCE), whose mummy bears telltale skin lesions.

By the 6th century BCE, Indian medical texts documented smallpox outbreaks. The disease followed trade routes and military campaigns, eventually establishing itself as a global pandemic. Unlike bubonic plague (the “Black Death”), which ravaged Europe in concentrated waves, smallpox maintained a relentless presence across civilizations for millennia.

The Devastating Toll Across Continents

Smallpox operated as an equal-opportunity killer. Mortality rates reached 30%, with malignant cases causing fatal hemorrhaging within weeks. Survivors often bore lifelong scars—the origin of terms like “pockmarked” in English and “mázi” (麻子) in Chinese.

Europe suffered profoundly:
– 18th century: 100 million deaths
– Royal victims included Queen Mary II of England, Tsar Peter II of Russia, and King Louis XV of France

But the most catastrophic demographic impact occurred in the Americas. When European colonizers arrived in the late 15th century, their inadvertent biological warfare—including distributing smallpox-contaminated blankets—reduced Native American populations from ~30 million to under 1 million within a century.

China’s Pioneering Defense: Variolation

While smallpox reached China during the Han Dynasty (206 BCE–220 CE), Chinese physicians developed the first effective countermeasure: variolation. Documented by 4th-century alchemist Ge Hong and refined over centuries, this technique involved:
1. Collecting pus from mild smallpox cases
2. Inoculating healthy individuals via nasal insertion or powdered scabs
3. Inducing mild infections that conferred immunity

By the Qing Dynasty (1644–1912), variolation became systematized:
– Emperor Kangxi promoted it after surviving smallpox himself
– The 1742 Imperial Medical Compendium detailed four inoculation methods
– Knowledge spread globally via medical diplomacy to Russia (1688), Japan (1744), and Korea (1790)

Though revolutionary, variolation carried a 2–3% mortality risk—a dangerous gamble that demanded improvement.

Edward Jenner’s Cowpox Breakthrough

The paradigm shift came from British physician Edward Jenner (1749–1823). His 1796 experiment—inoculating 8-year-old James Phipps with cowpox pus, then exposing him to smallpox—proved cross-immunity. Despite initial ridicule (satirical cartoons depicted vaccine recipients growing bovine features), the safer “vaccination” (from vacca, Latin for cow) gained acceptance.

Key milestones in vaccination history:
– 1805: Introduced to China via Macau
– 19th century: European/American vaccination mandates
– 1950: China’s nationwide immunization campaign
– 1960: China’s last indigenous case

The Final Campaign and Legacy

The World Health Organization launched its eradication program in 1967, employing:
– Mass vaccination campaigns
– Surveillance-containment strategies
– International cooperation

On October 25, 1979—declared “Smallpox Eradication Day”—WHO confirmed the virus’s extinction in nature. The last known case occurred in 1978 through a laboratory accident.

Smallpox’s defeat transformed global health, proving that:
– International collaboration can overcome pandemics
– Vaccination remains medicine’s most powerful tool
– Eradication requires both scientific innovation and political will

Today, smallpox exists only in two high-security labs, while its legacy informs battles against polio, malaria, and emerging viruses. The story of its conquest stands as humanity’s greatest public health triumph—a testament to perseverance across cultures and centuries.