The eradication of smallpox is perhaps one of humanity’s most impressive achievements. Conquering one of history’s great killers, however, was not an easily won battle. In a bid to understand how human interventions, seasonality, and social shifts changed the path of this disease, researchers have analyzed thousands of weekly records documenting the deaths of smallpox victims in London, England for almost three centuries.

By closely studying the many outbreaks of smallpox, they hope to reveal new insights into how to tame, control, and potentially eradicate other diseases, not least COVID-19. The findings are fiddly and complex, but one factor sticks out: the discovery of a vaccine was a monumental step in the control and eventual eradication of the disease. 

As reported in the journal PLOS Biology, The researchers pored through over 13,000 weekly smallpox mortality records from London that span from 1664 to 1930. In the city alone, they identified more than 320,000 people who died of the disease within this 266-year period. 

Within this mass of data, they found some clear patterns. Economic changes brought about big shifts in how the disease spread. For example, malnutrition associated with changes in wheat prices was often seen with a rise in smallpox mortality rates. Weather and seasonality were equally important. Humidity and temperature also appear to have influenced the severity of smallpox outbreaks. 

Wars and the Industrial Revolution also brought major shifts in demographics, which can be seen in how smallpox spread across London. The Industrial Revolution brought about rapid urbanization, with London’s population more than doubling from about 730,000 in 1765 to 1.9 million in 1831. With this increase in population density came an increasing number of opportunities for disease transmission. 

Above all, however, medical breakthroughs and well-executed health policy guided the path and control of the disease. 

“It is clear that the introduction of smallpox control measures— variolation and later vaccination— made eradication possible. Our analysis also suggests that greater use of control measures and changes in public health policies were correlated with changes in the frequency of the epidemics,”  Olga Krylova, study author and a former PhD student in the Department of Mathematics & Statistics at McMaster University in Ontario, said in a statement.

Variolation was an early method of inoculation that involved infecting a healthy individual with the smallpox virus taken from a pustule or dried scab of a person suffering from the disease. Although this method did work, it was highly risky and began to decline as the more refined smallpox vaccine was developed and became available. 

As this study shows, the introduction of vaccination was slow and subtle, but the researchers argue it can clearly be seen in the data. For example, a “strikingly large smallpox epidemic” broken out in London from 1837 to 1838 and quickly exploded into mainland Europe. To fight the outbreak, authorities in England introduced the first Vaccination Act of 1840, providing vaccination free of charge and banning variolation. This was followed by other laws, such as the Vaccination Act of 1867, which introduced penalties for not complying with compulsory vaccination.

Although these actions were not clear-cut events that stamped out the outbreaks overnight, their effects snowballed and the disease was eventually defeated. 

“After 1840, epidemics became more regular with a longer interepidemic period of 3 to 4 years," the study authors write. "After the exceptionally large epidemic of 1871 subsequent smallpox outbreaks were much smaller and irregular. The last substantial outbreak was in 1902, after which there were very few smallpox deaths reported.”