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New study reveals smallpox’s origins dating back 3,800 years

[Apr. 10, 2023: Staff Writer, The Brighter Side of News]

Smallpox was once one of humanity’s most devastating diseases, but its origin is shrouded in mystery. (CREDIT: Creative Commons)

Smallpox has been one of the deadliest diseases in human history, responsible for killing at least 300 million people in the 20th century alone. While the disease has been eradicated worldwide, it is still shrouded in mystery, with the exact origins of the smallpox virus being debated by scientists and historians alike.

Now, a new study published in the journal Microbial Genomics has provided fresh insight into the origins of the disease, revealing that smallpox is far older than previously believed, dating back 3,800 years.


The study, conducted by researchers at the Scientific Institute Eugenio Medea and University of Milan in Italy, used genetic analysis to trace the evolution of the smallpox virus through time.

By comparing the genomes of modern and historic strains of variola virus, the researchers were able to establish that smallpox all descended from a single common ancestor, with a small fraction of genetic components found in Viking-age genomes persisting until the 18th century.


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However, what is truly significant about the study is the confirmation that smallpox has been plaguing human societies for thousands of years, which has been a subject of debate for decades.

Historians have long suspected that smallpox was present in ancient societies, but without scientific evidence to support this theory, it has remained a subject of debate among scientists. The new study offers confirmation that the disease has been around for at least 3,800 years.


The study's lead author, Dr Diego Forni, explained the significance of the findings, saying, “Variola virus may be much, much older than we thought. This is important because it confirms the historical hypothesis that smallpox existed in ancient societies. It is 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.”

Smallpox was a major cause of death until relatively recently, causing devastating epidemics throughout human history. The disease is caused by the variola virus, and it was not until the 20th century that a vaccine was developed, leading to the eradication of the disease worldwide. While smallpox is no longer a threat, the new study's findings provide an important insight into the history of one of humanity's deadliest diseases.


The study's findings were based on something called the “time-dependent rate phenomenon,” which means that the speed of evolution depends on the length of time over which it is being measured, so viruses appear to change more quickly over a short timeframe and more slowly over a longer timeframe.

Smallpox virus. (CREDIT: iStock/Peddalanka Ramesh Babu)

The phenomenon has been well-documented in DNA viruses like variola, and using a mathematical equation, scientists were able to account for this phenomenon to give more accurate dates for evolutionary events, such as the appearance of a new virus.


The new estimate for the first emergence of smallpox is based on the time-dependent rate phenomenon and accounts for the virus's evolution over thousands of years. Until relatively recently, the earliest genetic evidence for smallpox was only from the 1600s. However, in 2020, a study that sampled skeletal and dental remains of Viking-age skeletons recovered multiple strains of variola, confirming the virus's existence at least another 1,000 years earlier.

While the new study confirms that smallpox has been around for thousands of years, it is still unclear how the virus first emerged. The study's findings suggest that the virus could have originated in Africa or Asia, but the exact location remains a mystery.

The study's co-author, Professor Edward Holmes of the University of Sydney, noted that the findings had important implications for our understanding of how infectious diseases emerge and spread, saying, "Understanding the origin and evolution of smallpox is critical for understanding the emergence and evolution of many other human pathogens. The emergence of smallpox likely involved a zoonotic transmission event, where the virus jumped from an animal host to humans."

Indeed, the smallpox virus is thought to have originated in a species of rodent, possibly a type of ground squirrel, in central Africa. From there, it may have spread to other animal hosts, such as monkeys, and eventually to humans.


The study's findings also shed light on the history of smallpox vaccination. The first successful smallpox vaccine was developed by English physician Edward Jenner in the late 18th century, based on the observation that milkmaids who had contracted the milder cowpox virus did not contract smallpox. By deliberately infecting patients with cowpox, Jenner was able to confer immunity to smallpox.

The success of the smallpox vaccine led to widespread vaccination campaigns around the world, which eventually led to the eradication of the disease in 1980. However, the vaccine itself was not without risks, and could cause serious side effects, including death. In the 1970s, the World Health Organization launched a global smallpox vaccination campaign, which resulted in the vaccine being administered to hundreds of millions of people in more than 30 countries.

Today, smallpox is the only human disease to have been eradicated by vaccination. However, the threat of smallpox as a bioweapon remains, and stockpiles of the virus are kept in laboratories in the United States and Russia for research purposes. The possibility of accidental or intentional release of the virus is a concern for public health officials.

The study's lead author, Dr. Diego Forni, emphasized the importance of continued research into the origins and evolution of smallpox, saying, "While smallpox has been eradicated, there is still much to learn about this deadly disease. Our findings provide important insights into the history of smallpox, and highlight the need for ongoing research to better understand the emergence and spread of infectious diseases."

The researchers hope that their findings will help settle a long-standing controversy over the origins of smallpox, and provide new insights into the history of one of humanity's deadliest diseases.


Symptoms of Smallpox

According to the Mayo Clinic, the first symptoms of smallpox usually appear 12 to 14 days after you're exposed to the smallpox virus. However, the virus can be in your body from 7 to 19 days before you look or feel sick. This time is called the incubation period.

After the incubation period, sudden flu-like symptoms occur. These include:

  • Fever

  • Muscle aches

  • Headache

  • Severe fatigue

  • Severe back pain

  • Vomiting, sometimes

A few days later, flat, red spots appear on the body. They may start in the mouth and on the tongue and then spread to the skin. The face, arms and legs are often affected first, followed by the torso, hands and feet.

Within a day or two, many of the spots turn into small blisters filled with clear fluid. Later, the blisters fill with pus. These sores are called pustules. Scabs form 8 to 9 days later and eventually fall off, leaving deep, pitted scars.


Smallpox can be spread from person to person when the rash appears and until the scabs fall off.

Causes of Smallpox

Smallpox is caused by the variola virus. The virus can spread:

  • Directly from person to person. You can catch the smallpox virus by being around someone who has it. An infected person can spread the virus when they cough, sneeze or talk. Coming in contact with skin sores also can cause you to get smallpox.

  • Indirectly from an infected person. Rarely, smallpox can spread through the air inside buildings, infecting people in other rooms or on other floors.

  • Through contaminated items. Smallpox can also spread through contact with contaminated clothing and bedding. But getting smallpox this way is less likely.

  • As a terrorist weapon, potentially. Using smallpox as a weapon is an unlikely threat. But because releasing the virus could spread the disease quickly, governments are preparing for this possibility.


Complications from Smallpox

Most people who get smallpox survive. However, some rare types of smallpox are almost always deadly. These more-severe forms are most common in pregnant women and children.

People who recover from smallpox usually have severe scars, especially on the face, arms and legs. Sometimes, smallpox causes vision loss (blindness).

For more science and technology stories check out our New Discoveries section at The Brighter Side of News.


Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.


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