The Body Scientific
November 22, 2024
A Brief History of Vaccines
SMALLPOX
Richard H. Kessin
On a slope above Framingham CT, far from settled places, there is a slab of natural stone on which names have been chiseled. They are not graffiti, but rather are carefully done, as if by stone masons with time on their hands. They are dated to the 1790s. The site contained a smallpox hospital, probably a cabin, of which no trace remains, where people who had vaccinated themselves with fluids from smallpox pustules stayed until the scabs fell off and they were no longer infectious. There were other such hospitals in New York and New England, including the 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 than any other disease. It came in waves, killing and scarring as much as 8% of the population at a time. The death rate once a person had smallpox was high. 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 US Army training film from 1967. It is grim beyond description, but to understand the devastation of a smallpox virus, 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 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. She was a gifted writer and curious traveler. She saw variolation and its organized widespread use. Mary Montagu’s two children were ‘engrafted’ with smallpox when she returned to Great Britain, 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? Practically nothing. They knew that once a person had an infectious disease and survived, they were usually immune. They did not know about viruses or bacteria. Bacteria had been seen under Antoine van Leuwenhoek’s microscope in the late 17th century but not associated with disease. Physicians and scientists did not know that living organisms were essential for making bread, wine, and vinegar. It took a major a battle, led by Louis Pasteur in the 1850s and 1860s, to prove that microorganisms in their multitudes converted sugar to alcohol, acetic acid, or carbon dioxide to make wine and bread. 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 in England and dairy farms where a disease, called cowpox was caused by a virus (we now know) that closely resembles smallpox in its DNA sequence. Cowpox is benign, causing a few mild scabs on the arms of milkmaids and other dairy workers. Milkmaids who got cowpox never got smallpox, and they noticed, which is not trivial. It’s a little late, but credit to them. Their observation was critical to the germ theory of fermentation, disease, and putrefaction in the hands of Louis Pasteur. It was a fertile theory and gave rise to much of modern medicine.
Edward Jenner was a Gloucestershire physician who also noticed the peculiarities of cowpox and proved that prior infection with cowpox prevents infection by smallpox. Jenner submitted his case studies to The Royal Society for publication, where he was rejected. He published them privately. Napoleon, then in power welcomed Jenner to France with honors and vaccinated his armies.
This description might make us think that after 1800 there would be a deluge of new vaccines. But it took 80 years and much of the 19th century. New vaccines appeared in the late 1870s, first anthrax, then animal cholera, and finally, the rabies vaccine, which arrived on a wing and a prayer in 1885. Why did it take so long?
Richard Kessin is Professor Emeritus of Pathology and Cell Biology at The Columbia Irving University Medical Center and has been writing The Body Scientific column for 15 years.