Smallpox was a terrible scourge on humanity, killing hundreds of millions of people over the centuries. But its origin remains obscure. Egyptian mummies from 3,000 to 4,000 years ago, including that of Pharaoh Ramses V, have pox-like skin lesions, but did they have smallpox? Recent genomic evidence puts that in doubt.
Whether or not ancient plagues were truly smallpox, by the 18th century the disease was endemic throughout the world. The widespread introduction of effective vaccination in the 19th century diminished – but did not eliminate – smallpox in the western world, and it persisted in many areas well into the 20th century.
I’m a microbiologist interested in how diseases jump from animals to humans and then evolve. Smallpox raged for centuries but was eradicated 40 years ago. While the idea of completely eradicating a disease has obvious appeal during the current pandemic, differences between the smallpox and SARS-CoV-2 viruses suggest that the path to ending COVID-19 pandemic will not be the same.
Wiping a Virus From the Face of the Earth
Smallpox is caused by a virus called variola. Although the primary route of infection is inhalation, the characteristic skin pustules are also filled with the virus. As long ago as the 10th century the Chinese knew that a person scratched with the pus from a pox sometimes gained immunity. It was, however, risky as some recipients developed smallpox and died.
This procedure, called variolation, was brought to Europe in the early 1700s. Later that century, English doctor Edward Jenner discovered that inoculation with a closely related virus, cowpox, also conferred immunity to smallpox but was much safer. Called vaccination, after “vacca,” the Latin word for cow, the process has remained essentially the same to the present.
The program’s intensified vaccination efforts employed a new technique called circle vaccination, which consists of surveillance and containment; when people in a community came down with the disease, health workers would try to vaccinate all their contacts to stop the spread of the virus.
However, variola’s evolutionary history with humans is far longer than that of SARS-CoV-2; exactly how long is the subject of ongoing research. To reconstruct the evolutionary history of smallpox, scientists need to compare the DNA from virus samples preserved at various times.
After eradication, scientists destroyed all known existing samples of variola except for 571 live samples that had been collected in the preceding 30 years. They’re kept at two secure facilities, one in the U.S. and one in Russia.
With viral DNA sequences in hand, scientists can construct genetic family trees by analyzing the small changes – mutations – that accumulated in the genes while the viruses were circulating in the human population.
These studies show that the variola strains that existed in the 20th-century cluster into two groups. One is made up of samples collected from West Africa and South America – an association probably due to the 18th-century slave trade – and the other consists of samples collected from the rest of the world.
The more rapid mutation rate predicts a few things. It means the available modern variola strains shared a common ancestor only 400 years ago; the two great clusters split only between 200 and 300 years ago; and strains within the two clusters began to diverge about 100 years ago.
Second, older strains of the virus may have disappeared, leaving no progeny to be collected in the 20th century. The rise of vaccination in the 19th century may have driven these other strains to extinction. That would leave only the one strain that gave rise to the two major groups that then diverged into the modern strains.
So, how did the original strain first make it into the human population?
At the level of their DNA, variola’s two closest relatives are camelpox, which infects only camels, and taterapox, whose only known host is an African gerbil. One interpretation of this family tree is that these three viruses emerged from a common ancestor, probably with a broad host range, about 3,000 years ago. The three viruses then independently narrowed their host range as they adapted to their new hosts, losing many of the genes that allow pox viruses to infect other host species.
Not all scientists who study the evolution of variola agree with this simplified scheme, arguing that the information gained from the available viral genomes cannot be extrapolated to the timing or the sequence of events that led to the original appearance of variola in people.
Few Similarities Between Smallpox and COVID-19
In addition to the differences between the viruses, the diseases that they cause are also very different, making the techniques used to eradicate smallpox less useful for the COVID-19 pandemic.
Surveillance and containment of cases, which was so successful for smallpox, also is less likely to work for COVID-19.
Our best hope is for an effective vaccine to stop the COVID-19 pandemic, just as it stopped smallpox.
ABOUT THE AUTHOR
Patricia L. Foster is a Professor Emerita of Biology at Indiana University. Patricia L. Foster has received funding from the US Army Research Office. She is a member of the Union of Concerned Scientists and Concerned Scientists at Indiana University. This article is published courtesy of The Conversation.