In Angel of Death professor of medicine Gareth Williams covers all of this, in a clear, informative and lively account with a good balance of broad picture and local detail. It has a British focus, but does cover events worldwide. And it is illustrated with halftones and eight pages of colour plates.
Williams starts with the basic virology. There are two forms of smallpox and the lethal Variola major may be relatively recent — perhaps 400 to 1600 years old, probably originating in Asia — which would explain why smallpox, presumably Variola minor, was considered a minor disease in antiquity. The closest relative of the two variola viruses is a virus isolated from gerbils, while the vaccinia virus used in vaccines is not, despite its name, closely related to cowpox and may be derived from a now-extinct horsepox. Williams also describes the effects of the smallpox virus on the human body, often leading to disfigurement when it didn't kill.
The early history of smallpox is touched on briefly. Smallpox had a significant effect on human demographics, most notably wreaking a terrible swathe on entirely unexposed populations in the New World. Medical treatments ranged from the useless but harmless, such as immersion in the colour red, to bleeding, purging and even starvation. "On balance, doctors were a liability whose treatments helped smallpox to kill its victims."
The Welsh village of Marloes had used a form of inoculation, a custom called "burying the smallpox", since at least the early 17th century. And different forms of variolation were also widespread in China and the Islamic world. Despite repeated reports, however, including several published by the Royal Society, the British medical establishment was slow to take notice.
One spur was Lady Mary Wortley Montagu, who encountered smallpox inoculation, or variolation, on a visit to Turkey and helped introduce it to Britain through a "top-down" approach which involved members of the royal family. In Boston, in contrast, the introduction of inoculation set off a prolonged and vitriolic conflict, pitting preachers and doctors against one another.
Variolation was rapidly appropriated by the medical profession, with many doctors combining it with traditional treatments such as purging and bleeding: "The preparation of the patient became an elaborate ritual that would have baffled the old women of Constantinople."
But variolation had serious limitations: the infectiousness of variolated patients, which made it good for the subject but not so good for others, and its failure to provide life-long immunity. It also remained a protracted and painful procedure.
Turning to vaccination, Williams looks at precursors to Jenner and the later debates over precedence, before presenting a biography of Jenner. He was influenced by John Hunter and did work on cuckoos, but as a scientist he was dilatory and slapdash. And his personality helped polarise supporters and opponents.
Vaccination spread rapidly around the world, initially using arm-to-arm vaccination chains. Williams describes the Spanish Royal Philanthropic Expedition which brought vaccination to Latin America, the forgery of an ancient Sanskrit text to get religious sanction in India, the use of calves to produce vaccine and glycerine to improve storage, and so forth.
"In its best year, 1805, the Royal Jennerian Society carried out almost 7,000 vaccinations; during this same period, over 20 times as many (146,000) were performed in Madras. ... In many other countries, vaccination was so obviously better than variolation that the old procedure was declared redundant or even illegal."
Three chapters cover the anti-vaccination movement and the intense and often vitriolic debates over vaccination, especially in Britain, where heavy-handed legal compulsion brought virulent opposition. Williams' chapter titles here give a feel for the emotive language involved: "an affront to the rights of man" and "more fatal than smallpox". This was "the first big public debate in which statistics served as ammunition" — and was misused and abused by both sides. The kooky strands in the anti-vaccination movement are still around.
The results included smallpox outbreaks in Gloucester and other towns that were strongholds of anti-vaccination sentiment. But there were also positive effects: the conflict brought — eventually — the acceptance that revaccination was necessary and that arm-to-arm vaccination carried risks. The 1840 Vaccination Act had made vaccination compulsory in the UK, but an 1898 Act allowed "conscientious objection" (the origin of the term), and a 1907 Act allowed exemption by simple statutory declaration.
Smallpox was driven into retreat by vaccination and the spread of the less lethal Variola minor, but it still killed over 300 million people in the 20th century. Williams describes four episodes: the 1897 outbreak in Middlesbrough, which killed several hundred people and crippled the area economically, a case in India in 1945, an outbreak of haemorrhagic smallpox in Bradford in 1962, with six deaths and more avoided only by the prompt vaccination of nearly 300,000, and a single case in Copenhagen in 1970, which "paralysed much of Copenhagen's health system for six weeks".
The WHO campaign to eradicate smallpox ran on a shoestring and faced challenges from within, in the form of hostile bureaucrats, as well as from wars and inhospitable terrain and the other challenges of the field. D.A. Henderson was the leader, but the campaign involved heroic work by tens of thousands. Methods were steadily improved: the bifurcated vaccination needle was introduced, recognition cards were deployed to help detect outbreaks, and surveillance-containment was used as well as mass vaccination.
Williams ends on a less triumphant note, with an account of the Birmingham laboratory accident, the debate over whether samples should be kept at all, and the threat of a smallpox bioweapon. There is little preparation for an outbreak and there is still no real treatment, with some candidate drugs largely untested.
There are other books which tackle specific elements of the smallpox story, focusing on Jenner or other prominent individuals, on the eradication program, or on bioterror risks. An earlier work with a similar breadth is The Life and Death of Smallpox by Ian and Jenifer Glynn. This is shorter, with slightly more on the early history and the eradication campaign but much less on the conflicts over vaccination and not so clear a treatment of the basic biology.
Angel of Death is highly recommended to anyone curious about smallpox and the complex and contested history of human responses to it.