The First Global Immunization Campaign

Francisco Xavier de Balmis and his twenty-two orphans’ vaccine expedition

Image: Francisco Pérez, Public domain, via Wikimedia Commons
Image: Francisco Pérez, Public domain, via Wikimedia Commons

It is said that King Carlos IV of Spain may have made the decision to send Francisco Javier de Balmis on the Royal Philanthropic Vaccine Expedition of 1803 with his broken heart. Carlos’ beloved daughter Maria Teresa had died of smallpox, and the expedition was the first global immunization campaign waged by humanity.

Smallpox’ mortality rate of one-in-three among those infected made it a severely lethal ailment in Europe, but the pandemic was devastating in the Americas. The conquistadors had subjugated the natives with guns, steel, and germs to which, in their isolation, had not developed genetic resistance. It cannot have escaped the calculations of his Majesty’s Royal Tax Collectors that among His Majesty’s subjects native to the Americas, the death rate exceeded fifty percent. When the Spaniards arrived in the Inca Empire, they found between 10 and 12 million inhabitants. When it gained its independence, the Viceroyalty of Peru, which roughly covered the same territory, had only 1.3 million inhabitants, and that is after counting all European transplants.

Those who survived suffered pus filled skin eruptions or pocks, which left them deeply scared for life. Now, English milkmaids were famed for their clear, smooth skins. Edward Jenner, an English physician, realized that their exposure to cowpox, which was similar to smallpox but milder in humans, and did not leave scars, later conferred immunity to the much more lethal smallpox.

To test his hypothesis, Jenner inoculated James Phipps, the eight-year-old son of his gardener with pus scraped from the cowpox blisters on the hands of milkmaid Sarah Nelmes. When Jenner later exposed Phipps to smallpox, the boy showed no sign of infection. He was immune.

The warm chain

Inspired by Jenner’s discovery, the Spanish Crown tasked de Balmis with organizing the most ambitious public health mission the world had seen, to vaccinate the populations living in Spanish territories in the Americas and the Far East. It is around this time that vaccines got their name, from vaca, the Spanish word for cow.

The First order of business was to ensure the viability of the vaccine as it crossed the Atlantic from Spain to México. Nowadays, we would rely on cold chain, the uninterrupted logistics of low temperature storage and distribution systems that are the key components of contemporary vaccine distribution.

Lacking our modern refrigeration technologies, de Balmis had to rely on warm human bodies to transport the vaccine and maintain its potency. To this end, with the promise of a better life in the Americas, he enlisted the help of orphanage rector Isabel Zendala y Gómez, and her 22 orphans, aged three to ten.

De Balmis and his crew set sail on the corvette Maria Pita from La Coruña on November 30, 1803. To keep the cowpox alive, he chain-vaccinated the children during the crossing by serial arm-to-arm inoculation. A brief stopover in the Canary Islands served as a successful trial run. Then, after a stormy ocean voyage, the expedition arrived in first in Puerto Rico in February 1804, then Caracas, Venezuela in March, where they immunized more than 12,000 people in less than a month.

Reinforced with new local boys, the expedition split. Second in command, José Salvany went south through Peru, Chile, and Argentina. De Balmis headed north, to Cuba and Mexico. They would never meet again.

In vitro versus in vivo

In many places, de Balmis and Salvany found that enterprising locals were already starting to offer immunization. Oftentimes, some random pus was harvested from the local cows. Other times, the vaccines were transported by soaking cloths in the pus, or in glass vials, but the vaccines quickly lost their potency after having been harvested from their hosts. Unfortunately, aside from the profiteering behavior that irked de Balmis, the benefits were predictably haphazard.

This was the second great contribution of the expedition: Training local physicians, and establishing the local vaccination boards responsible for distributing, administering and maintaining the efficacy of the vaccine.

The fate of the orphans

In Mexico, the expedition immunized at least 100,000 people. The Spanish orphans that had crossed the Atlantic, now named Meritorious Sons of the Motherland, were left under the care of the local Royal Orphan Asylum and put into adoption. Their caretaker during the odyssey, Isabel Zendala y Gómez, adopted one of the orphans, Benito Vélez.

Their feat was dramatized in the 2016 Spanish film, 22 Ángeles.

Having secured the welfare of his original orphans, de Balmis and twenty-six new Mexican boys set sail for the Philippines aboard the Magallanes. He would go on to establish vaccination centers in Manila, Macao, and Canton, in China.


I don’t imagine the annals of history furnish an example of philanthropy so noble, so extensive as this, wrote Edward Jenner on de Balmis’ achievement. But great deeds court controversy, especially when seen through modern eyes.

That the vaccine saved countless lives is incontestable. The speed and intensity of the demand for the vaccine did not give de Balmis time to pause to contemplate the safety of the inoculation method. A serious risk of the arm-to-arm method was the transmission of other infectious diseases, for example. Nevertheless, it was considerably safer than previous immunization methods, such as variolation, which had a mortality rate of one fifth or a percent.

Using children as the vessels for the vaccine exposed them to the risks of infection and perilous voyages. Although they seem to have been well taken care of, and the prize of a better life in the colonies was real, a government’s decision to use people as a tool may be problematic for our modern sensitivities. This may be justified, as experimentation with goat pox on foundlings in Madrid was in serious consideration. This initiative was, luckily, stopped by the orphanage’s Ladies’ Board of Directors. Or as was the case of forced inoculations in which twenty Indian women dragged by the authorities, and compelled to vaccinate their children. After, these women then ran to the apothecary clamoring for an antidote for the poison that had been introduced into their children’s arms.

Once vaccines are out of the laboratory, they become part of the public discourse. The methods adopted in the research and distribution of vaccines affect public confidence, and therefore, immunization rates.

Many disagreements punctuated de Balmis’ relationships with the local authorities during his voyages. These were sometimes attributed to de Balmis’ arrogance. From the perspective of modern practitioners, though, these were the result of the start of the professionalization of the practice of public health. De Balmis was claiming the preeminence of the opinion of the public health expert over that of the local authorities and their political calculations.

These tensions survive to this date, with the politics of the current COVID-19 pandemic serving as the latest reminder.

Read the original story in Medium.

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