No discussion of vaccines can be considered complete without a discussion of smallpox and Edward Jenner, a country doctor in England who is credited with performing the world’s first vaccination in 1796.[5] The eradication of smallpox is probably the world’s greatest success story. For thousands of years, epidemics swept across continents, decimating populations and at times changing the course or history.

The Crusaders brought smallpox back with them from the Holy Land. The Conquistadors carried it to the New World. This disease destroyed the Incan and Aztec empires. In the American colonies, smallpox helped decimate the indigenous peoples, including Pocahontas who died of smallpox in 1617 after visiting London. Rich and poor, famous and unknown, smallpox did not discriminate. Queen Mary II of England, Emperor Joseph I of Austria, King Luis I of Spain, Tsar Peter II of Russia, and King Louis XV of France are a few of the heads of state who died from smallpox.

The disease, for which no effective treatment was ever developed, killed as many as 30 percent of those infected. Between 65 percent and 80 percent of survivors were marked with deep-pitted scars (pockmarks), most prominent on the face. George Washington, for example, survived a bout with smallpox but was severely scarred.

Long before the causes of this disease were known and understood, many tried to protect the population from this disfiguring and deadly disease. The Chinese may have begun intentionally infecting themselves with smallpox virus as early as the 10th century, trying to prevent the disease by exposing uninfected individuals to the pus and fluid from a smallpox lesion. The thinking was that the dried pus would confer protection to the individual. This practice, called variolation, was also used hundreds of years later in other parts of the world. Specifically, in the early 18th century, Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, who as a young girl contracted smallpox and whose brother died of the disease, popularized variolation upon her return to England. Because of Lady Montagu’s efforts, the Princess of Wales in 1722 was persuaded to have her two children inoculated against smallpox.

Although the physiological effects of variolation varied, ranging from a mild illness to death, its effectiveness was evident. Smallpox mortality and morbidity rates were lower in populations that used variolation than in those that did not.[6]

Across the Atlantic Ocean, smallpox was threatening Boston. Clergyman Cotton Mather and Dr. Zabdiel Boylston in Massachusetts practiced variolation in an attempt to inoculate residents of this city. Although inoculations were illegal in the American colonies, their efforts helped prevent a wide-scale smallpox epidemic.

They documented that the smallpox case fatality rate was much lower among those inoculated than those not inoculated.[6]

Although Jenner was not the first to experiment with inoculation against smallpox, his efforts, which most certainly would be considered to be unethical by 21st-century standards, are acknowledged to mark the beginning of widespread vaccination. Jenner observed that milkmaids who had cowpox (a mild disease) rarely developed smallpox (a serious and potentially fatal disease).  This observation prompted him to experiment and ultimately devise the first vaccine to protect individuals from this dreaded disease. Jenner’s experiment on eight-year-old James Phipps spared the boy from developing smallpox, but still Jenner’s peers did not readily accept his findings. Rebuffed by the Royal Society of London, Jenner was undeterred and completed more experiments and self-published his findings in 1798. His results were so compelling that thousands of people elected to protect themselves by infecting themselves with cowpox.[7] Though it took several years until Jenner’s theories about vaccination were accepted by the professional societies, by 1800, more than 100,000 people had been vaccinated against smallpox worldwide. Vaccination was made compulsory in Bavaria, Denmark, Sweden, and,  by the mid-19th century, in Great Britain. Massachusetts was the first U.S. state to make vaccination compulsory in 1809.[8]

By the mid-20th century, 150 years after the introduction of vaccination, an estimated 50 million cases of smallpox occurred in the world each year, a figure that dropped to around 10 to 15 million per year by 1967 because of successful vaccination efforts. In 1967, when the World Health Organization (WHO) launched an intensified plan to eradicate smallpox from the earth, the “ancient scourge” threatened 60 percent of the world’s population, killed every fourth victim, scarred or blinded most survivors, and eluded any form of treatment.[9] A massive, worldwide outbreak search and vaccination program was initiated. Through the success of this global eradication campaign, smallpox was finally limited to the Horn of Africa and then to a single last natural case, which occurred in Somalia in 1977, although one fatal laboratory-acquired case occurred in the United Kingdom in 1978. The global eradication of smallpox was certified by a commission of eminent scientists in December 1979, based on intense verification activities in countries, and subsequently was endorsed by the WHO in 1980. Three known repositories of the virus were left: one in Birmingham, England, which was later destroyed after an accidental escape from containment caused many deaths, and two still remaining for possible antibioweaponry (stored under extremely strict conditions at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and at the State Research Center of Virology and Biotechnology in Koltsovo, Russia).

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Tony Rosen, MPH, MD
Tony Rosen, Division of Geriatric Medicine and Gerontology, Weill Cornell Medical College, Cornell University, New York, New York;

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REFERENCES

1. Barquest N, Domingo P. Smallpox: the triumph over the most terrible of the ministers of death. Ann Internal Med. 1997;127:627.
2. US Centers for Disease Control and Prevention. Ten great public health achievements in the twentieth century, 1900-1999.
3.   Parker AA. Implications of a 2005 measles outbreak in Indiana for sustained elimination of measles in the United States. New Engl J Med. 2006;355:1184.
4. Okonek BAM, Peters PM. Vaccines: how and why
5. Baxby D. Vaccination: Jenner’s Legacy. Berkeley, UK: Jenner Educational Trust; 1994. 6. Parish HJ. A History of Immunization. Edinburgh, UK: Livingstone; 1965.
6. Gross CP, Sepkowitz K. The myth of the medical breakthrough: smallpox, vaccination, and Jenner reconsidered. Int J Infect Dis. 1998;3:54-60.
7. Salmon DA,  et al.  Compulsory vaccination and conscientious or philosophical exemptions: past, present, and future. Lancet. 2006;367(9508):436-442.

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