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The History of Smallpox

Writer: FibonacciMD
FibonacciMD
3 days ago
10 min read

Updated: 12 hours ago

The Search for Prevention and the Resistance to Using It

By Stuart M. Caplen, MD 

The origins of smallpox are unknown, but it may have emerged thousands of years ago, as human populations grew and settled communities developed.  Although not definitive, evidence suggestive of smallpox has been identified in Egyptian mummies dating back approximately 3,000 years, including that of Pharaoh Ramesses V.  The disease was possibly described in ancient Sanskrit texts from India, and somewhat later in China.  Some historians have suggested that smallpox contributed to the decline of the Roman Empire.  The Antonine Plague (165–180 CE), which may have been caused by smallpox, is estimated to have killed as many as 7 million people, although the actual cause is uncertain.  The earliest unambiguous reports, of smallpox in Europe, were between the 5th and 7th centuries with epidemics being frequent in the Middle Ages.  The Crusades, which began in the 11th century, may have contributed to the further spread of the disease.  Spanish and Portuguese explorers brought the disease to the Americas, where it devastated Indigenous populations, including the Aztec and Inca civilizations.  In 1763, British officers at Fort Pitt reportedly gave Native Americans blankets and a handkerchief from a smallpox hospital in an attempt to spread the disease.  During the 18th century, an estimated 400,000 Europeans died of smallpox each year, and the disease was a major cause of blindness among survivors.  The fatality rate ranged from 20% to 60%, and was even higher in infants.  Due to its severe, scarring lesions, smallpox was widely referred to in England at the time as "the speckled monster”.


What is Smallpox? 

Smallpox is caused by the variola virus.  The term variola, first used by Bishop Marius of Avenches in 570 CE, was derived from the Latin words varius, meaning “stained,” or from varus, meaning “mark on the skin.” The suffix -ola means “little.”


Smallpox has two principal forms, variola major and variola minor. The more common variola major has an approximately 30% mortality rate in unvaccinated individuals, and the less common variola minor has a mortality rate of 1% or less.  The majority of variola major cases (about 90%) present as the ordinary form described below.  The two rarer forms of variola major, flat (malignant) smallpox, more commonly seen in children, and hemorrhagic smallpox, more commonly seen in pregnant women, are almost always fatal.  A milder form, known as modified smallpox, may occur in previously vaccinated individuals and is rarely fatal. 


In the ordinary form, the incubation period after infection is typically 7-19 days.  This is followed by a few days of high fever, headache, and body aches.  A rash first appears on the tongue and inside the mouth before spreading to the face and then to the arms and legs.   The skin lesions fill with thick, opaque fluid and often develop a characteristic central depression.  They then become firm, raised pustules.  After about five days, the pustules start to form scabs that eventually fall off, often leaving permanent pitted scars.  Individuals remain contagious until all scabs have separated, usually about four weeks after the rash first appears.


The virus spreads mainly through respiratory droplets produced during coughing or sneezing.  It can also, less commonly, be transmitted through direct contact with infected body fluids or contaminated bedding and clothing.

Smallpox lesions 
Smallpox lesions 

Immunity

As early as 430 BCE, during the Plague of Athens, whose cause remains unknown, the historian Thucydides observed that survivors were generally not reinfected and could care for the sick with less fear of contracting the disease again.  Before vaccination was developed, variolation (also called inoculation) was used to prevent smallpox.  The procedure involved introducing material from a pustule of an infected person and placing it into superficial cuts in the skin in a non-immune person’s arms or legs.  Variolation was probably practiced in Africa or Asia before being introduced into Europe in the 18th century.  According to some historical accounts, traders helped introduce variolation to the Ottoman Empire by the late 17th century.  Women from the Caucasus region were highly sought after for the Ottoman Sultan’s harem.  They had immunity to smallpox, having been inoculated as children, and may have helped spread the practice of variolation in the Ottoman Empire. 


Travelers to Istanbul in the 1700s described the practice.  However, British physicians were unconvinced.  The practice was introduced into England largely through the efforts of the English aristocrat Lady Mary Wortley Montagu.  She had lost a brother to smallpox and had also been left with facial scars from the disease.  When her husband was appointed ambassador in Istanbul, she learned about the procedure and had her five-year-old son variolated in 1718.  After returning to London, she had her three-year-old daughter inoculated in 1721, in the presence of physicians of the royal court.  After successful testing on prisoners and orphans, the two daughters of the Princess of Wales were inoculated, which increased acceptance of the procedure. 


Soon, physicians throughout Europe were performing variolation.  However, about 2% to 3% of those inoculated died from smallpox, though this was approximately one-tenth the death rate of a smallpox infection.  Additionally, blood-borne diseases, such as syphilis, could be transmitted by the procedure and inoculated people who got smallpox could start new outbreaks.  Many European royals underwent variolation and Frederick II of Prussia reportedly ordered the variolation of his army.


Variolation was first administered in the American Colonies in 1721.  Rev. Cotton Mather and Dr. Zabdiel Boylston were the two chief proponents.  During a Boston smallpox epidemic, Mather recommended variolation but only one physician, Boylston, began performing the procedure.  The practice was controversial and during this period a bomb was thrown into Mather’s house with the note “Cotton Mather, You Dog, Dam [sic] you, I’ll inoculate you with this, with a Pox to you.”  About half of Boston’s 12,000 citizens contracted smallpox, and Mather and Boylston reported a 14% fatality rate in the uninoculated and only 2% in those who underwent variolation.


Smallpox also influenced the American Revolution.  While the British troops had largely been variolated, few American soldiers had undergone the procedure and lacked immunity.  In 1775-76 the Americans failed in a bid to take over Quebec in part due to a smallpox epidemic which reduced the number of healthy troops.  Washington initially hesitated to variolate his troops because the procedure temporarily incapacitated them and also made them contagious while recovering.  He was afraid that widespread variolations would leave his troops vulnerable to British attack.  However, after concluding that smallpox posed a greater threat to his army than the British, Washington ordered the variolation of his troops in 1777.


Edward Jenner and the Smallpox Vaccine

Edward Jenner was a British physician born in 1749.  For years he had heard stories that milkmaids who had been infected with cowpox did not get smallpox.  Jenner tested this hypothesis in May 1796, when he found a milkmaid, Sarah Nelmes, who had fresh cowpox lesions on her hands and arms.  Using material from Nelmes’s cowpox sores, Jenner inoculated James Phipps, his gardener’s eight-year-old son.  Phipps developed a mild fever and discomfort in his armpits and felt unwell for several days.  In July of the same year, Jenner variolated the boy with material from a fresh smallpox lesion.  Phipps remained healthy, leading Jenner to conclude that he had developed protective immunity from the cowpox infection.  He submitted a paper reporting his findings to the Royal Society, which rejected it.  Undeterred, he successfully repeated the procedure in additional subjects before publishing his findings in 1798.  Jenner named the procedure “vaccination” derived from the Latin vacca, meaning cow, reflecting his use of cowpox to protect against smallpox.  His findings were met with mixed reactions in the medical community, but a number of physicians began using vaccination.  The practice spread throughout England and much of Europe, and the older procedure of variolation was banned in England in 1840. 


In the United States, Benjamin Waterhouse, a professor of medicine at Harvard University, received vaccine material from British physician John Haygarth, who had obtained it directly from Jenner.  Waterhouse performed the first U.S. vaccinations in 1800.  In 1813, Congress authorized a National Vaccine Agent, Dr. James Smith, to serve as a source of smallpox vaccine for citizens throughout the United States.


Initially, vaccination was performed using material derived from cowpox lesions.  By the 20th century, vaccinia virus, a related orthopoxvirus whose origin remains uncertain, had become the principal virus used in smallpox vaccines.


Anti-Smallpox Vaccine Movements

As smallpox vaccinations became more popular, anti-vaccine movements or leagues started to arise.  People opposed vaccination for several reasons.  Some worried that using material from cowpox sores could spread other infections.  Some religious critics considered the practice “unchristian” because it involved material from an animal.  Others distrusted physicians or objected to compulsory vaccination on grounds of personal liberty.  The Anti-Vaccination League arose after England passed the Vaccination Act of 1853, which ordered mandatory vaccination for infants within their first 3 months.  A later Vaccination Act of 1867 extended compulsory vaccination to children up to age 14 and strengthened penalties for vaccine refusal.  The act led to the formation of the Anti-Compulsory Vaccination League.  In one 1885 demonstration, an estimated 80,000-100,000 anti-vaccinators held a march in Leicester, England, with banners, a child’s coffin, and an effigy of Jenner.  In response to growing opposition, the Vaccination Act of 1898 introduced a conscientious-objector exemption, allowing parents who objected to vaccination to obtain an exemption certificate from a magistrate. (It also introduced the term “conscientious objector” into English law.) 


In the United States, smallpox outbreaks in the late 1800s led to both vaccine proponents and anti-vaccine societies such as The Anti-Vaccination Society of America (1879), The New England Anti-Compulsory Vaccination League (1882), and the Anti-Vaccination League of New York City (1885).  There were court battles to try to repeal vaccination laws in several states.  In 1902, the Board of Health of Cambridge, Massachusetts, mandated smallpox vaccination for all unvaccinated residents.  One citizen, Henning Jacobson, refused vaccination on the grounds that the law violated his right to care for his own body and the city then filed criminal charges against him.  The case (Jacobson v. Massachusetts, 1905) was eventually appealed to the United States Supreme Court, which ruled that states could enact mandatory laws to protect the public in the event of a communicable disease outbreak.  This ruling established the legal authority for instituting reasonable mandatory public health measures in the U.S.


Smallpox Eradicated 

In 1967, the World Health Organization (WHO) launched an intensified smallpox global eradication campaign, with widespread vaccination, surveillance, and disease containment.  The last naturally acquired case of smallpox was reported in Somalia in 1977.  In 1978, Janet Parker, a medical photographer at the University of Birmingham who worked directly above a smallpox research laboratory, contracted the virus and became the last known person in history to die from smallpox.  In 1980 the WHO declared smallpox eradicated worldwide.


Bioweaponization

There is concern that the variola virus could be used as a biological weapon, and for that reason, some countries keep stockpiles of vaccine ready for emergency use.  The only two WHO-authorized repositories holding live variola virus are located at the CDC in Atlanta, Georgia, and Russia's VECTOR Institute in Koltsovo.


Summary

Smallpox has afflicted humans for thousands of years.  Edward Jenner’s work helped establish vaccination as an effective way to prevent the disease.  After a coordinated global campaign, the World Health Organization declared smallpox eradicated in 1980, making it the first human disease to be eradicated worldwide.  Concerns exist that the virus may be used as a biological weapon in the future, which is the reason smallpox vaccines are still stockpiled today.


References

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