The Pandemic of the Millennium

Smallpox, the pandemic that lasted for millennia, is believed to have existed as far back as the 3rd century BCE during the reign of the Egyptian Empire, as upon examination, traces of smallpox rashes were found on 3,000 yr old mummies. It wasn’t until the late 20th century that this pandemic truly came to an end,
but why did it take so long to rid the world of this virus?

Smallpox Timeline, from the beginning to the end.

Smallpox was an acute, highly contagious disease caused by a virus from the orthopoxivirus family, the Variola virus, which is related to the Vaccinia virus, more commonly known as cowpox. Smallpox was so contagious it rapidly infected all corners of the world; during the 18th century it was believed to have killed 60 million people, including 5 reigning monarchs in Europe alone.

As for the 20th century, it only got worse.  Here it was estimated that it infected over 300 million people globally, with 3 out of every 10 people dying from the disease, and for those that survived were left with devastating scars covering their body, particularly their faces; and the unfortunate few were traumatised with blindness.

The last naturally occurring case of Smallpox was in 1977 in Ethiopia, and following the 1959 global vaccination programme lead by WHO, it was declared eradicated in 1980.

What made this virus so deadly?

Smallpox was very easily transmitted between humans, which contributed highly to the spread of the virus. It liked to ‘hang on’ to mucous droplets that would then directly pass on to others whenever we coughed or sneezed, rather similar to the common cold, and we all know how quickly that spreads…

The virus caused scabs and lesions to form on the skin and these contained puss, and the puss contained the smallpox virus. This means that infected individuals could then contaminate all materials they touched such as bedding, towels or clothing. There is no evidence that smallpox was a zoonotic infection, this means transmission only occurred between humans, and not animal to human.

Upon infection, the first symptoms start with a sore throat which becomes rapidly worse, the virus then travels to the lymph nodes which is where it starts replicating. This is called the incubation phase, the virus will replicate continuously for approximately 10-14 days before it enters the blood stream. It then circulates the body, infecting other lymph nodes around the body as well as the bone marrow.

Both the lymph nodes and bone marrow are power houses for the immune response, producing key white blood cells called B and T cells, and with their impairment by the virus, means that its virulence prevails.

Related image
This cycle shows how viruses, like smallpox, work to invade our cells and then spread throughout our body

A rash of red puss filled spots will then proceed to form, starting from the top of the forehead, and work its way down the body, this rash usually correlated with the fatality rate of the patient, the more severe, the more likely they would die from the infection.

The Variola virus is able to evade an immune response by producing proteins that mimic proteins that we produce to inactivate our immune response to foreign invaders . It is thought that the virus inhibits the immune response by manipulating the complement pathway – this is the pathway which directly attacks pathogens, i.e. viruses and virus infected cells in the body. The Variola virus produces a complement regulatory protein which interferes with this pathway and stops it from carrying out its antiviral effects.

How was Smallpox wiped out?

In history, it was noted that those who became infected with smallpox could not become infected with small pox ever again. In 10th century China, it was discovered by accident that those who became infected with the virus via a skin lesion rather than a natural contraction of infection have a much less severe reaction to the virus. This lead to the practice of purposely infecting individuals with smallpox scabs from infected patients to prevent a more fatal reaction to the disease, this is called variolation.


In 1796, Edward Jenner, a pro-found biologist for his time was eager to find out why dairymaids who had been infected with cowpox, would not become ill with smallpox. He knew a dairymaid, who was infected with cowpox, and decided to inoculate an 8-year-old child with scabs from her cowpox lesions.  The child developed symptoms, but recovered fairly quickly. He then inoculated the child with a fresh smallpox lesion; no infection occurred and assumed complete long lasting protection.

The vaccine was then made mandatory in the UK in 1853, many were vaccinated against the virus.

From this he created the vaccine for smallpox, and this vaccine proved to be the beginning to the long-standing fight for eradicating the Variola virus, of which the world was finally relieved of in 1980. The only chance of smallpox ever returning is via the means of bio-terrorism, which in the foreseeable future, looks unlikely.


“I hope that someday the practice of producing cowpox in human beings will spread over the world – when that day comes, there will be no more smallpox”
Edward Jenner 



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