Brief history of vaccines: Smallpox

High on a slope above Farmington, Connecticut, far from settled places, there is a slab of granite angled so that its face is nearly vertical. Names have been chiseled into the rock. They are not the work of graffiti artists, but rather are carefully done, as if by stone masons with time on their hands in the 1790s. The site contained a smallpox hospital, probably only a cabin of which there remains no trace, where people who had vaccinated themselves with fluids from smallpox pustules stayed until the scabs fell off and they were no longer infectious. (I learned about these carvings after a talk I gave before the pandemic and in the five or six years since, sadly, I lost the names of the people who told me.)There were other hospitals in New York and New England, including the ruined smallpox hospital on Roosevelt Island in the East River of New York whose ruins remain.

Smallpox was ferociously contagious and deadly. It probably killed or disfigured more human beings over the centuries, perhaps more than any other disease. It came in waves, killing or scarring as much as 8% of the population at a time. The death rate once a person had smallpox was much higher. People knew it when they saw it because its symptoms, including frightening pustules, were unique. Wikipedia has an excellent summary, including images of patients and a U.S. Army training film from 1967. It is grim, but to understand the devastation of such viruses, far beyond Covid, and the painfully acquired knowledge that eradicated smallpox in 1977, read the text and watch the film.

The first preventative was variolation, a vaccine precursor used in China starting in about 1500 and introduced to Europe by Lady Mary Montagu, who is usually but inadequately described as the wife of a British diplomat posted to the Ottoman Empire. There was much more to her. She defied a tyrannical father who wanted her to live without books and to marry a wealthy man named Viscount Sir Clotworthy Skeffington (forgive me). The diplomat, Edward Wortley Montagu, took Mary to Constantinople and promptly found that she was intrepid and visited many places including the women’s baths which she described in letters and books. She was a gifted and curious traveler and writer. Mary Montagu had two children and when she returned to Great Britain, she had them ‘engrafted’ with smallpox, the first British children to be treated, against strong opposition from the British medical establishment who viewed the procedure as folk medicine.

What did the medical establishment know about infectious disease in 1800? The answer is practically nothing. They knew that once a person had a disease and survived, they were usually immune to it thereafter. They did not know about viruses or bacteria. Bacteria had seen under van Leuwenhoek’s microscope, but never associated with disease. Neither physicians nor scientists knew that living organisms were essential for making bread, wine, or vinegar. Viruses would not be described for a hundred years until 1894. They were called filterable agents and not seen until the 1940s when electron microscopes became available. The physicians and scientists of 1800 had no idea that there was something we now call the immune system, or that people and animals had defenses that could be mobilized.

The smallpox story turns to Gloucestershire and dairy farms where a disease, called cowpox is caused by a virus (we now know) that closely resembles smallpox in its DNA sequence. (Monkey pox is also part of this group.) Cowpox is relatively benign, causing only a few mild scabs on the arms of milkmaids and other dairy workers. Milkmaids who got cowpox, never got smallpox, and they noticed. It’s a little late, but credit to them.

Edward Jenner was a Gloucestershire physician who also noticed the peculiarities of cowpox and prepared many case studies, showing that prior infection with cowpox prevents infection by smallpox. Edward Jenner assembled his case studies with fine drawings and submitted them for publication to The Royal Society where he was rejected. Someone who did see virtue in Jenner’s work was Napoleon Bonaparte, then in power; he welcomed Jenner to France with honors and vaccinated his armies.

All of this might make you think that after 1800 there would be a deluge of new vaccines. But it took 80 years, or four generations, and much of the 19th century. To explain why, we will keep going, vaccine by vaccine: first anthrax, then animal cholera, and finally, the rabies vaccine, which arrived on a wing and a prayer in 1885.

Richard Kessin is Professor Emeritus of Pathology and Cell Biology at The Columbia University Medical Center and has been writing The Body Scientific column for 15 years.