“No one is safe until everyone is,” the United Nations has cautioned about the covid-19 pandemic, a warning now amplified by coronavirus variations able to dodge vaccines that are, in any case, too few and too concentrated in wealthy parts of the world. That a global pandemic requires a global response is a lesson firmly rooted in medical history. It took over 200 years of international efforts to eradicate smallpox. The first attempt showed that a vaccine was necessary, but not sufficient. Ending the global transmission of a deadly disease also requires international travel that is safe and global relations based on terms of equality, two conditions that remain difficult to ensure.

History’s first global health initiative was Spain’s Royal Philanthropic Vaccine Expedition, which sailed around the world from 1803 to 1813 delivering smallpox vaccinations. The venture astonished people at the time. Such maritime circumnavigations were associated with death, not health, and doing anything good on a planetary scale was unprecedented.

Indeed, the effort was mostly driven by Spain’s imperial and economic concerns, not philanthropy or humanitarianism.

Beginning with the Canary Islands in the 1490s, Spanish overseas imperialism had blended military conquest, enslavement and commercial monopoly. Spain’s monarchs next used those tactics to blast into the Caribbean, then Central and South America. Spain also pioneered the biggest of land grabs — around the world — by sponsoring Ferdinand Magellan’s westward voyage that ended up making history’s first circumnavigation, 1519-1522, and inaugurating Spain’s colonization of the Philippines.

Imperialism brought Spain profits and prestige. It became the model for all European empires, even though the human cost of these invasions was appalling. Some American Indian populations may have diminished as much as 90 percent, in part from contagions new to them. The worst malady was smallpox, a 3,000-year old Eurasian disease that could kill up to 30 percent of the infected and disfigure and blind survivors. European invaders globalized this ancient horror, carrying it into West Africa, the Americas and the Pacific.

But in the early 1700s, Europeans and American colonists learned, from Ottoman Turks and West Africans, a miraculous remedy: inoculation, in which material from smallpox pustules was inserted into the uninfected, triggering a milder form of the disease — and lifetime immunity. In the 1790s, English physician Edward Jenner made inoculation even safer by using pus from sores caused by cowpox, a related though milder disease. Cowpox vaccine (“vacca” is Latin for “cow”) would be what the Spanish carried around the world, scant years after Jenner had reported his experiments in print.

The creation of a vaccine coincided with another historic first, the increasing safety of long-distance ship travel. Only by the 1800s could “around the world” signal life, not death. Magellan’s circumnavigation had barely succeeded: Only one of his five ships returned, carrying (at most) 18 of the 270 to 280 original crew members. Subsequent expeditions tried to recircle the planet, with similar fatalities. Not until the late-18th century would circumnavigators’ survival rates improve.