Smallpox has plagued humans since ancient Egyptian times, 2,000 years earlier than previously thought, according to new research.
The disease was once one of humanity’s most devastating - but its origin has been shrouded in mystery.
Thought to have originated with the Vikings 1,400 years ago, now a study has dated it back 2,000 years further than previously believed - to the Land of the Pharaohs.
Smallpox, known medically as variola virus, is the only human infectious disease to have been eradicated following a global immunization campaign.
Investigating its origins could help fight future pandemics, which are expected to become more frequent.
First author Dr. Diego Forni, of Eugenio Medea Scientific Institute, said: "Variola virus may be much, much older than we thought."
The Italian team compared genomes of modern and historical strains. A mathematical equation then found it began appearing more than 3,800 years ago.
It confirms past accounts of smallpox - with cases being found in the analysis of Egyptian mummies.
It was a major cause of death until the 1980s - killing at least 300 million people in the 20th century. This is roughly the equivalent of the population of the United States.
Relatively recently, the earliest evidence of smallpox was only from the 1600s. Then in 2020, multiple strains were identified in skeletal and dental remains of Viking skeletons.
Suspicious scarring on the Pharoah Ramses V, who died in 1157 BC, led some to believe the virus stretches back at least 3,000 years.
The study in the journal Microbial Genomics fills in the "missing piece of the jigsaw," say the researchers.
Various strains descended from a single common ancestor. A small fraction of the genetic components found in Viking-age genomes persisted until the 18th century.
Dr. Forni and colleagues accounted for something called the 'time-dependent rate phenomenon.'
Surprisingly, the speed of evolution depends on the length of time over which it is being measured.
So viruses appear to change more quickly or slowly over a shorter and longer time frame, respectively. It has been well-documented in DNA viruses like smallpox.
It's hoped the findings will settle a longstanding controversy and provide new insight into the history of one of humanity's biggest killers.
Dr. Forni said: "This is important because it confirms the historical hypothesis that smallpox existed in ancient societies.
"It's also important to consider that there are some aspects in the evolution of viruses that should be accounted for when doing this type of work.”
The smallpox vaccine has been hailed as the most significant milestone in global public health. It led to universal childhood immunization programs.
Over thousands of years, smallpox killed hundreds of millions of people - the rich, the poor, the young, and the old.
It was a disease that didn't discriminate, claiming the lives of at least one-in-three people infected - often more in the most severe forms.
The symptoms were gruesome. They included high fever, vomiting and mouth sores followed by fluid-filled lesions on the whole body.
Death would come quickly - often within two weeks. Survivors could be left with permanent harm such as blindness and infertility.
Famous smallpox survivors included Queen Elizabeth I, Mary Shelley, Mozart, Beethoven, George Washington and Abraham Lincoln.
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