Smallpox, variolation and the first vaccination campaign
Smallpox killed and scarred people for millennia. Variolation made it milder at a cost, Jenner's cowpox vaccination prevented it without that cost, and Spain carried the vaccine across its empire in the first public health vaccination programme, passing it from orphan to orphan.
What smallpox did
Smallpox, a virus believed to have jumped from animals to humans, ravaged humankind from the time of the ancient Egyptians, killing 20% to 30% of an affected population with each outbreak. Survivors were left permanently scarred by pox marks, and permanent blindness was a common complication, but they were immune when the disease returned, as it repeatedly did. The name smallpox was coined in the 15th century to distinguish the disease from the Great Pox, now known as syphilis, and comes from the small permanent scars, called pocks, that its pustules left. The cause of neither disease was known, but both often proved fatal. Even in 18th-century Europe, after centuries of variolation, smallpox killed more than 400,000 people a year and left almost a third of survivors blind and nearly all permanently scarred. Four European monarchs died of it in that century, and so many heirs to the Habsburg throne died that the lineage changed four times.
Variolation, and what it cost
Because survivors were immune, early physicians in the East and the Middle East inoculated their patients with fluid from smallpox pustules. They observed that this variolation, inoculation with infectious material, could lessen the severity and complications of the illness, which made it preferable to natural infection. The practice can be traced to 1,000 BC in India and to 16th-century China. Historians credit Lady Mary Wortley Montagu, a severely scarred smallpox survivor married to an 18th-century British diplomat posted in Turkey, with introducing variolation to Great Britain, and she had her own children variolated in Constantinople so that they would be spared infection. Variolation was neither standardised nor regulated, and it gave syphilis to a significant number of healthy people. Syphilis was normally sexually transmitted, incurable, and considered the second biggest scourge of the day. Given the consequences of a smallpox outbreak, many people agreed to variolation willingly even knowing its consequences: it did not guarantee an ideal outcome, but it offered hope.
Variolation had prominent backers in Benjamin Franklin, who lost a child to smallpox, and Thomas Jefferson, who had his whole family variolated and then vaccinated once vaccination became available. In 1775 George Washington, as commander of the Continental Army, recognised the devastating effects disease could have on an army's readiness and ordered all Continental Army troops not previously diagnosed with smallpox to be variolated. The technique used on the troops is described as removing fresh pus from a smallpox pustule, adding it to water and soaking a thread and needle in it, then threading the needle and thread under the skin of the person being inoculated.
Jenner's cowpox
Dairymaids rarely caught smallpox, hence their smooth, unblemished skin, and Edward Jenner was not the first to notice it. In 17th-century England, a common compliment to a lady was that her skin was as smooth as a milkmaid's. Jenner was the first to be credited with discovering that acquiring the mildly irritating cowpox protected a person from contracting the more lethal smallpox. Building on observations John Fewster made in 1768, he demonstrated that inoculating a person with material from a cowpox pustule prevented smallpox. He named the process vaccination, from the Latin for cow, vacca, to distinguish it from variolation. The first practice of immunisation in western countries dates to 1796, when Jenner vaccinated a young boy against smallpox with cowpox, and the first smallpox vaccine followed in 1798. The use of vaccines and immunotherapies in medicine dates from this work at the end of the 18th century, and Jenner is called the father of immunology. His discovery is thought to have saved more lives than any other scientific discovery.
From the start, Jenner made his vaccine available free to all physicians and set up vaccination clinics in his community for those who could not afford it. Keeping the vaccine viable was a challenge from the start, because Jenner predated modern pharmaceutical practices and even the pharmaceutical industry. He devised a process of extracting material from a pustule, preserving it on a glass slide and sealing it with paraffin under vacuum, but it was less effective and efficient than passing the virus arm to arm, from a person infected with cowpox to an uninfected one.
Natural infection, variolation and vaccination compared
In the late 18th century there were three choices for dealing with smallpox.
| Choice | How the virus entered | Mortality | Course and after-effects | Contagiousness |
|---|---|---|---|---|
| Natural infection | Inhaled into the respiratory tract | 20% to 30% | A third of survivors left blind, and survivors often left severely scarred | Very contagious to others exposed to an active infection |
| Variolation | Fluid from a smallpox victim's pustule deliberately scraped into a naive person's skin | About 2% | Usually a somewhat milder infection, but with no guarantee and with significant scarring | An active infection, even a mild one, was contagious, and the infection passed on could be severe |
| Vaccination | Cowpox injected into a naive person's skin | 0% | Smallpox avoided entirely; the cowpox infection produced only a few small temporary pustules on the hands | The cowpox infection was not contagious to others |
Variolation seemed preferable to natural infection, although it carried risks to the person variolated and to others exposed to them while it ran its course, and it left permanent scarring. People who were vaccinated became immune to smallpox without even the mild case of smallpox expected with variolation, and they did not acquire syphilis.
The first public health vaccination programme
Spain turned Jenner's discovery into national policy. While Jenner was still experimenting, a severe smallpox outbreak in the Spanish court led King Charles IV to have the whole royal family variolated. In 1798 he decreed that every citizen of Spain be variolated, an order that was controversial because the risks of variolation were notorious. Presented with a copy of Jenner's work, he was so impressed that he switched the decree to vaccination, and by 1800 nearly all of Spain had been vaccinated.
Politics played a significant role in public health then, as it does now. Napoleon's armies invaded Spain, and the British under Lord Nelson defeated the Spanish and the French at Trafalgar. Spain depended on its New World colonies, and smallpox sweeping through them disrupted their productivity, so the treasury suffered and the monarchy had a financial problem as well as an image problem. To address both, Spain launched the Spanish Royal Expedition, popularly known as the Balmis-Salvany Expedition, as the world's first public health vaccination programme. It departed Spain in 1803, led by Francisco Javier de Balmis with Jose Salvany as his assistant. From 1804 to 1810 it traversed the Americas and the Pacific, vaccinating hundreds of thousands of people across the Spanish colonies. It set up vaccine boards, headed by government and Catholic Church officials, to keep vaccine production and programmes going in every Spanish domain it visited. Under the king's edict, the vaccine was supplied free of charge to all citizens and residents of the Spanish Empire.
The Spanish authorities agreed that arm-to-arm transmission worked better than preserved material, and it became the distribution method of choice. Prisoners and orphans had long been viewed as expendable. Prisoners were large, took up space, ate a lot and needed armed guards, while orphans were small, ate less and could be tended by a nun. So, with the Royal Medical Committee's agreement, the Church's blessing and the king's decree, but with no ethical regard, orphans became the world's first official biomedical transportation containers. Because the virus in a pustule was viable for only 4 to 10 days and the voyage took weeks, it had to be passed by serial inoculation throughout the Atlantic crossing. After calculations, 22 orphans boarded the ship to the colonies with the orphanage rector, the medical team and the crew. Opponents, religious leaders among them, raised many religious and even financial objections to the expedition, but no one raised an ethical objection to its use of orphans.
In Colombia, Balmis and Salvany split up to expedite the mission. Salvany led a team overland through South America toward Argentina, but he was ill almost from the start and died in Bolivia in 1810, and the expedition continued without him. Balmis sailed to Mexico, where he left the orphans who had sailed with him from Spain in the care of a bishop, then crossed the Pacific to the Spanish colonies in the Philippines, and in 1807 he sailed back to Spain via the Pacific. Both leaders acquired new orphans as needed, and an orphan who had fulfilled their purpose was left among the locals unless prior arrangements had been made for them to return home.
With the backing of royal and religious authorities, the expedition succeeded in completing its objectives in every Spanish domain it entered. By all accounts it was considered a success, for the public health of the colonies and for the political health of the king and his government.