Centuries after spreading smallpox, the Spanish led a global campaign to fight it

Colonizers brought Old World diseases to the Americas, devastating indigenous populations. Nearly 300 years later the Spanish king ordered an ambitious mission involving orphans, warships, and the first vaccine to fight one of the deadliest of all.

By Riley D. Champine and Oscar A. Santamariña


The spread of smallpox in the Old World

Smallpox likely originated in Egypt more than 3,000 years ago and spread across Asia, Africa, and later into western Europe. Invading Moors carried smallpox into Spain in a.d. 711. (Read about how devestating pandemics change us.)

Circa 1492

Precontact Americas

An estimated 60.5 million people lived in North and South America prior to the arrival of Europeans. The Aztec and Inca Empires were the most densely populated, with more people in the cultivated areas.
Area controlled by an empire
Known agricultural area

Slavery and Contagion

The Spanish and Portuguese initially forced indigenous Americans to work in mines and on plantations; many died from disease and harsh labor. People from West Africa, some carrying smallpox, were enslaved to replace them. The first known case of smallpox arrived in the Americas on a slave ship.

Two Empires Destroyed

Unleashed in the wake of Spanish conquistadores, smallpox quickly killed about half the Aztec population. The outbreak then raced south, killing the Inca emperor and sparking a civil war—further clearing the way for the Spanish invaders.

A deadly century

The native population of the Americas declined by an estimated 90 percent in the first century after Europeans arrived. Smallpox was a leading cause of death.
After three centuries of smallpox outbreaks in the Americas, a vaccine is developed.

Edward Jenner showed in 1796 that injection with less virulent cowpox could protect people against deadly smallpox. Other physicians in England and elsewhere soon joined the cause. But Spain’s King Carlos IV went much further, ordering an audacious maritime expedition to disseminate vaccination throughout the Spanish Empire.

Area controlled by Spain in 1800
The Royal Philanthropic Vaccine Expedition would become the first global public health initiative.

The goal was to establish regional boards throughout the empire to maintain a supply of vaccine and oversee its use, train vaccinators, and administer the vaccine at no cost. A Guatemalan physician residing in Spain, José Flores, who had years of experience inoculating people to prevent smallpox, helped plan the expedition. He advocated using indigenous languages, working with trusted community leaders, and treating patients humanely.


Orphans and science

The expedition, under the command of physician Francisco Xavier de Balmis, carried 22 boys, ages three to nine, from orphanages. The orphans ensured a live supply of vaccine. Each time the medical team vaccinated a pair of the boys, they later used matter from their pustules to inject another pair, and so on in succession during their 10-week voyage.

Transatlantic Crossing

The expedition sailed in the corvette María Pita. The boys were cared for by the lone woman on the voyage, orphanage rectoress Isabel Zendala y Gómez.

The Expedition Splits

After a warm welcome in Caracas, the main expedition led by Balmis sailed on to introduce the vaccine to Cuba. The expedition’s surgeon, José Salvany, headed south on another leg of the humanitarian mission, entailing years of discomfort and danger in the campaign against smallpox.


The Salvany contingent carried the vaccine overland on a 2,500-mile route down the Pacific coast from present-day Colombia to Ecuador, Peru, and Bolivia. Salvany and his teams vaccinated more than 200,000 people in South America. He died in Bolivia in 1810, at just 36, of an apparent heart condition.

The Vaccine Reaches Chile

Another subgroup, led by Manuel Grajales and Basilio Bolaños, split from the expedition in Lima, Peru, to sail to the southernmost reaches of the Spanish Empire. They delivered the vaccine to areas that are now part of modern-day Chile.

Balmis in Mexico

Meanwhile, the Balmis group reached many towns in Mexico, traveling as far north as Durango. Then they went to the port city of Acapulco to prepare for the next phase of their journey: bringing the vaccine across the Pacific.

Crossing the Pacific

The Spanish foundlings were adopted by Mexican families, and 26 Mexican boys replaced them for the Pacific crossing—with the promise that they'd be returned to their families. The main expedition sailed to the Philippines, where smallpox was endemic before colonization.

Circling the Globe

After delivering the vaccine to Macau and Canton (Guangzhou, China), Balmis circled the globe with a stop in the British possession of St. Helena. He was received by the Spanish king in September 1806. Balmis remained devoted to the cause, working to spread vaccination overseas until 1813.

(Read about how devastating pandemics change us.)

Richard Conniff. Eve Conant and Taryn Salinas, NGM staff; Scott C. Elder

Sources: Catherine Mark and José G. Rigau-Pérez, The World's First Immunization Campaign: The Spanish Smallpox Vaccine Expedition, 1803-1813; Frank Fenner and others, Smallpox and its eradication; Colin McEvedy and Richard Jones, Atlas of World Population History; Alexander Koch and others, Earth system impacts of the European arrival and Great Dying in the Americas after 1492