In 1911, G. Elliott Smith, an anatomist and Egyptologist, was investigating the process of mummification at the Cairo Museum of Antiquities when he came upon an odd looking vesicular lesion all over the body of one of the mummies.  He brought a sample of the mummy with this rash to two physicians,  Ruffer and Ferguson,  who identified the outbreak over the mummy’s skin as smallpox. They published their study in the Journal of Pathology; this being one of the earliest physical findings of the disease.  The mummy, identified as the Pharaoh Rameses V,  ruled the Egyptian Kingdom from 1149-1145 BC.

Smallpox boy
A young boy with a severe hemorrhagic form of smallpox.

Smallpox has been one of the deadliest diseases of civilization, and historians believe humanity had been suffering from this virus since 10,000 BC from ancient writings describing a disease resembling it.

When infected, smallpox killed three out every ten people often in a gruesome death. Mostly by sending the body into shock with multi-organ failure or by a coagulopathy causing bleeding from the nose, mouth, and eyes. 

No other virus has tallied up this striking of a body count quite like smallpox.  In 1519, after the Spanish conquistador Hernan Cortes and his army landed in Mexico, a soldier infected with smallpox started an epidemic in the Aztec empire killing millions of the natives and reducing the Aztec population by 25%.  In the 20th century, an estimated 300-500 million people died as a result of smallpox.  Some of those who survived are left with terrible disfiguring scars for the remainder of their lives.

Screen Shot 2018-02-17 at 4.15.02 PM
Edward Jenner (1749-1823). His experimentation of cowpox inoculation on smallpox immunity became the basis for vaccinations.

But then in the late 18th century, like many other breakthroughs in scientific discovery, serendipity happened.  Edward Jenner, an English physician, noticed that milkmaids who contracted cowpox were not affected by smallpox outbreaks. Cowpox is a closely related virus to smallpox but not nearly as contagious and typically results in a milder non-deadly rash.

Since smallpox was one of the greatest killers in England, especially in children, Jenner decided to carry out his first inoculation experiment with his gardener’s 9-year-old son, Pipp (Clearly, this is before there were such a thing as IRB).  In Jenner’s inoculation technique, he took material from cowpox sores and rubbed it into Pipp’s arm. 

Exposure after exposure to smallpox, Pipp never contracted this disease. More experiments followed, and, in 1801, Jenner published his manuscript “On the Origin of the Vaccine Inoculation,” and his work became the basis for vaccination.  In fact, Jenner coined the term vaccine from the Latin word “Vacca” which means cow.  

He was so hopeful that his vaccination technique would eradicate smallpox that in his manuscript he said: “the annihilation of smallpox, the most dreadful scourge of the human species, must be the final result of this practice.”

In the beginning, Jenner found heavy skepticism and public ridicule. His critics, especially the clergy, found this practice of vaccination as abhorrent and “ungodly.” 

Cow head cowpox
 Here is a satirical cartoon of 1802 showing people who had been vaccinated sprouting cow’s heads.  At first, Jenner had many critics and opposition to his vaccination idea.

However, as his vaccination technique became more broadly used, his critics became silenced as the apparent advantage of vaccination helped many survive smallpox outbreaks

So how exactly did the cowpox inoculation work?  Since cowpox and smallpox are nearly related viruses, they share antigens on the virus’ surface. Antigens are antibody recognition sites for our immune cells in our body (Think of a key and lock interaction where the antigen is the “key” and our immune cells are the “lock”). When exposed to the cowpox antigen, our immune system generates antibodies to neutralize the virus. These antibodies are still present if the patient is later exposed to smallpox.  They bind to the smallpox antigen, tagging it so other parts of the immune system can destroy the virus.

Jenner’s technique was soon replaced with other safer vaccination techniques.  Also, the cowpox virus was replaced with the much less harmful vaccinia virus.   

By 1959, the World Health Organization (WHO) initiated a plan to rid the world of smallpox. Unfortunately, this global eradication campaign suffered many setbacks. Although vaccinations eradicated smallpox from North America and Europe in the 1950s;  a lack of funds, personnel, commitment from countries, and shortages of vaccine donations all contributed to continued outbreaks in Africa, Asia, and South America.

But then in 1966, another turning point occurred in Nigeria.  William Foege, a 30-year-old physician towering at 6 foot 7 inches, came to Africa from the state of Washington as a medical missionary to help stop the suffering of Smallpox.  One day, getting word that several villages in Nigeria were reported to have people infected with smallpox, he and his team found themselves in a dire situation with only a limited supply of vaccines. Their next shipment of vaccines would not arrive in a few months.

Foege came up with a plan: Since Smallpox virus is not contagious during the incubation period (Smallpox has a 14 day incubation period before the first symptoms arise), he proposed they should use the vaccines only on the infected people’s close contacts.  This meant finding their family members and other close contacts. The contacts would be easy to find because transmission of smallpox usually required prolonged face-to-face contact. They also made sure to isolate all infected individuals to contain the spread.  So they went to the villages using this strategy. 

Will Foege
Photograph of  William Foege in the center (with pipe) in Nigeria 1968. (CDC)

Anxiously awaiting to see if their strategy worked, the secondary location of infections started occurring, but many of the people in those locations were protected from the vaccine and did not become infected.  By four weeks, using their minimal supply, all the smallpox infections in the villages had been eradicated.

Typically, health authorities required mass vaccinations needing 80-100% vaccination rates to achieve this type of results.  However, Foege’s “surveillance/containment” strategy did it with 50% vaccination rates.  This made their approach much more efficient requiring less need of vaccine resources and costs.

Foege returned to America shortly after due to a Nigerian civil war, and started work at the CDC.  He pitched his idea of “surveillance/containment” to the CDC director, and he agreed to try it in certain parts of Africa.  Although at first, there was concerning skepticism, low and behold it worked. And it worked again and again.

This strategy then became part of the WHO’s worldwide vaccination campaign to eradicate smallpox, and it accelerated the program’s success.  

Almost two centuries after Edward Jenner published with the hopes that vaccination could annihilate smallpox, on May 8, 1980, the WHO’s 33rd World Health Assembly officially declared the world free of this disease. 

Foege would go on to become director of CDC from 1977-1983. After leaving the CDC, he became the founder of The Task Force for Global Health, a nonprofit organization that works to improve the health of people in need, primarily in developing countries.  

In 2012, for his humanitarian achievements, Foege was awarded the United State’s highest civilian award–the Presidential Medal of Freedom–by President Obama. It is estimated due to this ingenious idea of a “surveillance/containment” strategy in the global smallpox vaccination campaign, 131 million lives were saved.  Today, the eradication of smallpox by vaccination is one of the greatest achievements in medicine and global health.

Additional Readings:

I am a gynecologic oncologist, a husband, and a father. My blog is mostly about our healthcare system and well-being, but occasionally I get inspired to write about other "stuff" too.

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