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The origin is unknown. Smallpox if believed to date back to the Egyptian Empire around the 3rd century BCE, according to smallpox rashes examined on mummies.

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Origin of Smallpox

The origin of smallpox is unknown. The finding of smallpox-like rashes on Egyptian mummies suggests that smallpox has existed for at least 3,000 years. The earliest written description of a disease like smallpox appeared in China in the 4 th century CE (Common Era). Early written descriptions also appeared in India in the 7 th century and in Asia Minor in the 10 th century.

Spread of Smallpox

Historians trace the global spread of smallpox to the growth of civilizations and exploration. Expanding trade routes over the centuries also led to the spread of the disease.

Highlights from History:

6th Century-Increased trade with China and Korea brings smallpox to Japan.

7th Century-Arab expansion spreads smallpox into northern Africa, Spain, and Portugal.

11th Century-Crusades further spread smallpox in Europe.

15th Century-Portugal occupies part of western Africa, bringing smallpox.

16th Century-European settlers and the African slave trade import smallpox into:

The Caribbean

Central and South America

17th Century-European settlers bring smallpox to North America.

18th Century-Explorers from Great Britain bring smallpox to Australia.

Early Control Efforts

Smallpox was a terrible disease. On average, 3 out of every 10 people who got it died. People who survived usually had scars, which were sometimes severe.

One of the first methods for controlling smallpox was variolation, a process named after the virus that causes smallpox (variola virus). During variolation, people who had never had smallpox were exposed to material from smallpox sores (pustules) by scratching the material into their arm or inhaling it through the nose. After variolation, people usually developed the symptoms associated with smallpox, such as fever and a rash. However, fewer people died from variolation than if they had acquired smallpox naturally.

The basis for vaccination began in 1796 when the English doctor Edward Jenner noticed that milkmaids who had gotten cowpox were protected from smallpox. Jenner also knew about variolation and guessed that exposure to cowpox could be used to protect against smallpox. To test his theory, Dr. Jenner took material from a cowpox sore on milkmaid Sarah Nelmes' hand and inoculated it into the arm of James Phipps, the 9-year-old son of Jenner's gardener. Months later, Jenner exposed Phipps several times to variola virus, but Phipps never developed smallpox. More experiments followed, and, in 1801, Jenner published his treatise "On the Origin of the Vaccine Inoculation." In this work, he summarized his discoveries and expressed hope that "the annihilation of the smallpox, the most dreadful scourge of the human species, must be the final result of this practice."

Vaccination became widely accepted and gradually replaced the practice of variolation. At some point in the 1800s, the virus used to make the smallpox vaccine changed from cowpox to vaccinia virus.

Global Smallpox Eradication Program

In 1959, the World Health Organization (WHO) started a plan to rid the world of smallpox. Unfortunately, this global eradication campaign suffered from a lack of funds, personnel, and commitment from countries, and a shortage of vaccine donations. Despite their best efforts, smallpox was still widespread in 1966, causing regular outbreaks across South America, Africa, and Asia.

The Intensified Eradication Program began in 1967 with a promise of renewed efforts. Laboratories in many countries where smallpox occurred regularly were able to produce more, higher-quality freeze-dried vaccine. Other factors that played an important role in the success of the intensified efforts included the development of the bifurcated needle, the establishment of a case surveillance system, and mass vaccination campaigns.

By the time the Intensified Eradication Program began in 1967, smallpox was already eliminated in North America (1952) and Europe (1953). Cases were still occurring in South America, Asia, and Africa (smallpox was never widespread in Australia). The Program made steady progress toward ridding the world of this disease, and by 1971 smallpox was eradicated from South America, followed by Asia (1975), and finally Africa (1977).

Last Cases of Smallpox

In late 1975, three-year-old Rahima Banu from Bangladesh was the last person in the world to have naturally acquired variola major. She was also the last person in Asia to have active smallpox. She was isolated at home with house guards posted 24 hours a day until she was no longer infectious. A house-to-house vaccination campaign within a 1.5-mile radius of her home began immediately. A member of the Smallpox Eradication Program team visited every house, public meeting area, school, and healer within 5 miles to ensure the illness did not spread. They also offered a reward to anyone who reported a smallpox case.

Ali Maow Maalin was the last person to have naturally acquired smallpox caused by variola minor. Maalin was a hospital cook in Merca, Somalia. On October 12, 1977, he rode with two smallpox patients in a vehicle from the hospital to the local smallpox office. On October 22, he developed a fever. At first healthcare workers diagnosed him with malaria, and then chickenpox. The smallpox eradication staff then correctly diagnosed him with smallpox on October 30. Maalin was isolated and made a full recovery. Maalin died of malaria on July 22, 2013, while working in the polio eradication campaign.

Janet Parker was the last person to die of smallpox. In 1978, Parker was a medical photographer at England's Birmingham University Medical School. She worked one floor above the Medical Microbiology Department where staff and students conducted smallpox research. She became ill on August 11 and developed a rash on August 15 but was not diagnosed with smallpox until 9 days later. She died on September 11, 1978. Her mother, who was providing care for her, developed smallpox on September 7, despite having been vaccinated two weeks earlier. An investigation suggested that Janet Parker had been infected either via an airborne route through the medical school building's duct system or by direct contact while visiting the microbiology corridor.

World Free of Smallpox

Almost two centuries after Jenner hoped that vaccination could annihilate smallpox, the 33 rd World Health Assembly declared the world free of this disease on May 8, 1980. Many people consider smallpox eradication to be the biggest achievement in international public health.

Stocks of Variola Virus

Following the eradication of smallpox, scientists and public health officials determined there was still a need to perform research using the variola virus. They agreed to reduce the number of laboratories holding stocks of variola virus to only four locations. In 1981, the four countries that either served as a WHO collaborating center or were actively working with variola virus were the United States, England, Russia, and South Africa. By 1984, England and South Africa had either destroyed their stocks or transferred them to other approved labs. There are now only two locations that officially store and handle variola virus under WHO supervision: the Centers for Disease Control and Prevention in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology (VECTOR Institute) in Koltsovo, Russia.

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smallpox (variola major and variola minor)

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It is believed the first use of variolation began in Asia. Dried smallpox scabs were blown into the nose who then contracted a milder form of the disease

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In 1717, Lady Mary Wortley Montagu, the wife of the British ambassador, learned about variolation in Constantinople. In 1721, at the urging of Montagu and the Princess of Wales, several prisoners and abandoned children were inoculated by having smallpox inserted under the skin. Several months later, the children and prisoners were deliberately exposed to smallpox.

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Due to Japan trading with China and Korea, they were introduced to Smallpox. It was believed that red light would cure those that were sick of smallpox.

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Smallpox began causing illness and death more than a thousand years ago. Follow its spread and eventual eradication in the timeline below.

Entrance into Europe

Crusades further contribute to the spread of smallpox in Europe with the European Christians moving to and from the Middle East during the next two centuries.

Smallpox moves north

Population expansion and more frequent travel renders smallpox endemic in previously unaffected Central and North Europe, with severe epidemics occurring as far as Iceland.

European colonization and the African slave trade import smallpox into the Caribbean and Central and South America.

Illustration by the Franciscan missionary Bernardino de Sahagun who wrote detailed accounts of the Aztec history during his life there from 1545 until his death in 1590 into 12 books entitled "General History of the Things of New Spain." Introduction of smallpox into Mexico by the Spanish around 1520 was one of the factors that led to the demise of Aztec Empire. Scanned from (2009) Viruses, Plagues, and History: Past, Present and Future, Oxford University Press, USA, p. 60. Public Domain.

Variolation-a process of grinding up dried smallpox scabs from a smallpox patient and inhaling them or scratching them into an arm of an uninfected person-is being used in China (inhalation technique) and India (cutaneous technique) to control smallpox.

A container from Ethiopia used to store the powdery variolation material, which was produced by grinding up dried smallpox scabs taken from a smallpox patient. Source: CDC, photo credit Brian Holloway.

Increased use of variolation

Variolation (cutaneous technique) is a widespread method for preventing smallpox in the Ottoman Empire (former Asia Minor, present-day Turkey) and North Africa.

Smallpox spreads into North America

European colonization imports smallpox into North America.

Variolation is introduced into England by Lady Mary Wortley Montagu, the wife of the British ambassador to Turkey.

Lady Mary Wortley Montagu, the wife of the British ambassador, learned about variolation during their appointment in Turkey. A survivor of smallpox herself, she had both of her children variolated and was the foremost person responsible for the introduction of the technique to England.

In 1796, Edward Jenner, an English doctor, shows the effectiveness of previous cowpox infection in protecting people from smallpox, forming the basis for vaccination.

Edward Jenner (1749-1823). Photo courtesy of the National Library of Medicine.

Smallpox is widespread in Africa, Asia, and South America in the early 1900s, while Europe and North America have smallpox largely under control through the use of mass vaccination.

The map shows the worldwide distribution of smallpox and the countries in which it was endemic in 1945. Source: CDC, photo credit Dr. Michael Schwartz.

After a global eradication campaign that lasted more than 20 years, the 33rd World Health Assembly declares the world free of smallpox in 1980.

WHO poster commemorating the eradication of smallpox in October 1979, which was later officially endorsed by the 33rd World Health Assembly on May 8, 1980. Courtesy of WHO.

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Smallpox began causing illness and death more than a thousand years ago. Follow its spread and eventual eradication in the timeline below. Entrance into Europe Crusades further contribute to the spread of smallpox in Europe with the European Christians moving to and from the Middle East during the next two centuries.

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Primary sources from Fray Bernardino describes the Aztec people falling ill to diseases such as Smallpox during the 1500s. This led to the deaths of millions of Natives and empires.

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From Fray Bernardino de Sahagún, Florentine Codex, Book 12, Chapter 29 (Mexica)

Here it is told how, at the time the Spaniards left Mexico, there came an illness of pustules of which many Mexicas died; it was called "the great rash" [smallpox].

[Even] before the Spaniards appeared to us, an illness broke out, a sickness of pustules. It began in Tepeilhuitl, and it spread over the people as a great destruction. Large bumps spread on people; some were entirely covered--on the face, the head, the chest, etc. [The disease] brought great desolation; a great many [people] died from it.

[People] with the illness could not walk, they could only lay in their dwellings and sleeping places. They could not move; they could not stir; they could not change position, nor lie on one side, nor face down, nor on their backs. And when they stirred, they screamed. The pustules that covered people caused great desolation; a great many people died of them, and many just died of hunger; [for] no one took care of others any longer.

On some people, the pustules were widely separated, and they did not suffer greatly, nor did many of them die of it. But many people's faces were marred by it; their faces or noses were pitted. Some lost their eyes; some were blinded.

At this time, the pestilence lasted sixty days, sixty fateful days. It began in Cuatlan, where it became so well established that nothing could stop it, and it spread in the direction of Chalco. And many were disabled or paralyzed by it, but they were not disabled forever. It broke out in Teotleco, and it abated in Panquetzaliztli. The Mexicas were greatly weakened by it.

And after this, the Spaniards came; they marched from Tezcoco. They appeared from the direction of Quauhtitlan and stopped at Tlacopan. There, they gave out assignments and divided themselves. Pedro de Alvarado was made responsible for the road coming to Tlatelolco, and the Marquis [Cortés] went to Coyoacan. Here, he took charge of the Acachinanco [road], which led to Tenochtitlan. The Marquis considered that those of Tenochtitlan were valiant warriors.

And at Nextlatilco, or Iliacac, the war first began. The [the Spaniards] quickly reached Nonoalco, with the [Mexica] warriors pursuing them. None of the Mexicas died; then the Spaniards turned back. The warriors fought in boats; the warboatmen threw darts at [the Spaniards]. Then [the Mexicas] entered [Nonoalco]. Subsequently, the Marquis sent [his soldiers] toward Tenochtitlan, following the Acachinanco [road]. Many times they fought, and the Mexicas confronted him.

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From Fray Bernardino de Sahagún, Florentine Codex , Book 12, Chapter 29 (Mexica) Here it is told how, at the time the Spaniards left Mexico, there came an illness of pustules of which many Mexicas died; it was called "the great rash" [smallpox].

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In 1492, Christopher Columbus and the crew arrived on San Salvador Island and met the Taino. The Taino population drop to less than 500 people in the 1548 because of smallpox, influenza, and etc.

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American Association for the Advancement of Science

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How Europeans brought sickness to the New World

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Isolated tribes who emerge today face echoes of the epidemics that began in 1492 and were repeated for centuries

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In 1796, Edward Jenner inoculated an 8-year-old boy by the name of James Phipps with fresh cowpox lesions. The boy became immune to smallpox and Jenner created the term "vaccination" for this method.

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In science credit goes to the man who convinces the world, not the man to whom the idea first occurs.

-Francis Galton

For many centuries, smallpox devastated mankind. In modern times we do not have to worry about it thanks to the remarkable work of Edward Jenner and later developments from his endeavors. With the rapid pace of vaccine development in recent decades, the historic origins of immunization are often forgotten. Unfortunately, since the attack on the World Trade Center on September 11, 2001, the threat of biological warfare and bioterrorism has reemerged. Smallpox has been identified as a possible agent of bioterrorism ( 1). It seems prudent to review the history of a disease known to few people in the 21st century.

SMALLPOX: THE ORIGIN OF A DISEASE

The origin of smallpox as a natural disease is lost in prehistory. It is believed to have appeared around 10,000 BC, at the time of the first agricultural settlements in northeastern Africa ( 3, 4). It seems plausible that it spread from there to India by means of ancient Egyptian merchants. The earliest evidence of skin lesions resembling those of smallpox is found on faces of mummies from the time of the 18th and 20th Egyptian Dynasties (1570-1085 BC). The mummified head of the Egyptian pharaoh Ramses V (died 1156 BC) bears evidence of the disease ( 5). At the same time, smallpox has been reported in ancient Asian cultures: smallpox was described as early as 1122 BC in China and is mentioned in ancient Sanskrit texts of India.

Smallpox was introduced to Europe sometime between the fifth and seventh centuries and was frequently epidemic during the Middle Ages. The disease greatly affected the development of Western civilization. The first stages of the decline of the Roman Empire (AD 108) coincided with a large-scale epidemic: the plague of Antonine, which accounted for the deaths of almost 7 million people ( 6). The Arab expansion, the Crusades, and the discovery of the West Indies all contributed to the spread of the disease.

Unknown in the New World, smallpox was introduced by the Spanish and Portuguese conquistadors. The disease decimated the local population and was instrumental in the fall of the empires of the Aztecs and the Incas. Similarly, on the eastern coast of North America, the disease was introduced by the early settlers and led to a decline in the native population. The devastating effects of smallpox also gave rise to one of the first examples of biological warfare ( 1, 7). During the French-Indian War (1754-1767), Sir Jeffrey Amherst, the commander of the British forces in North America, suggested the deliberate use of smallpox to diminish the American Indian population hostile to the British. Another factor contributing to smallpox in the Americas was the slave trade because many slaves came from regions in Africa where smallpox was endemic.

Smallpox affected all levels of society. In the 18th century in Europe, 400,000 people died annually of smallpox, and one third of the survivors went blind ( 4). The symptoms of smallpox, or the "speckled monster" as it was known in 18th-century England, appeared suddenly and the sequelae were devastating. The case-fatality rate varied from 20% to 60% and left most survivors with disfiguring scars. The case-fatality rate in infants was even higher, approaching 80% in London and 98% in Berlin during the late 1800s.

The word variola was commonly used for smallpox and had been introduced by Bishop Marius of Avenches (near Lausanne, Switzerland) in AD 570. It is derived from the Latin word varius, meaning "stained," or from varus, meaning "mark on the skin." The term small pockes ( pocke meaning sac) was first used in England at the end of the 15th century to distinguish the disease from syphilis, which was then known as the great pockes ( 8).

VARIOLATION AND EARLY ATTEMPTS OF TREATMENT

It was common knowledge that survivors of smallpox became immune to the disease. As early as 430 BC, survivors of smallpox were called upon to nurse the afflicted ( 9). Man had long been trying to find a cure for the "speckled monster." During medieval times, many herbal remedies, as well as cold treatment and special cloths, were used to either prevent or treat smallpox. Dr. Sydenham (1624-1689) treated his patients by allowing no fire in the room, leaving the windows permanently open, drawing the bedclothes no higher than the patient's waist, and administering "twelve bottles of small beer every twenty-four hours" ( 10).

However, the most successful way of combating smallpox before the discovery of vaccination was inoculation. The word is derived from the Latin inoculare, meaning "to graft." Inoculation referred to the subcutaneous instillation of smallpox virus into nonimmune individuals. The inoculator usually used a lancet wet with fresh matter taken from a ripe pustule of some person who suffered from smallpox. The material was then subcutaneously introduced on the arms or legs of the nonimmune person. The terms inoculation and variolation were often used interchangeably. The practice of inoculation seems to have arisen independently when people in several countries were faced with the threat of an epidemic. However, inoculation was not without its attendant risks. There were concerns that recipients might develop disseminated smallpox and spread it to others. Transmission of other diseases, such as syphilis, via the bloodborne route was also of concern.

Inoculation, hereafter referred to as variolation, was likely practiced in Africa, India, and China long before the 18th century, when it was introduced to Europe ( 9). In 1670, Circassian traders introduced variolation to the Turkish "Ottoman" Empire. Women from the Caucasus, who were in great demand in the Turkish sultan's harem in Istanbul because of their legendary beauty, were inoculated as children in parts of their bodies where scars would not be seen. These women must also have brought the practice of variolation to the court of the Sublime Porte ( 4, 10).

Variolation came to Europe at the beginning of the 18th century with the arrival of travelers from Istanbul. In 1714, the Royal Society of London received a letter from Emanuel Timoni describing the technique of variolation, which he had witnessed in Istanbul. A similar letter was sent by Giacomo Pilarino in 1716. These reports described the practice of subcutaneous inoculation; however, they did not change the ways of the conservative English physicians.

After these first professional variolation procedures, word of the practice spread to several members of the royal family ( 11). Charles Maitland was then granted the royal license to perform a trial of variolation on six prisoners in Newgate on August 9, 1721. The prisoners were granted the king's favor if they submitted to this experiment. Several court physicians, members of the Royal Society, and members of the College of Physicians observed the trial. All prisoners survived the experiment, and those exposed to smallpox later proved to be immune. In the months following this very first trial, Maitland repeated the experiment on orphaned children, again with success. Finally, on April 17, 1722, Maitland successfully treated the two daughters of the Princess of Wales. Not surprisingly, the procedure gained general acceptance after this last success.

THE SPREAD OF VARIOLATION

In Europe, where the medical profession was relatively organized, the new methods of variolation became known quickly among physicians. Since there was also a demand for protection against smallpox, physicians soon began the variolation procedure on a massive scale. Although 2% to 3% of variolated persons died from the disease, became the source of another epidemic, or suffered from diseases (e.g., tuberculosis and syphilis) transmitted by the procedure itself, variolation rapidly gained popularity among both aristocratic and common people in Europe. The case-fatality rate associated with variolation was 10 times lower than that associated with naturally occurring smallpox. In the 1750s more European princes died of smallpox, giving further impetus for the use of variolation ( 3). Among those variolated were Empress Marie-Therese of Austria and her children and grandchildren, Frederick II of Prussia, King Louis XVI of France and his children, and Catherine II of Russia and her son. King Frederick II of Prussia also inoculated all his soldiers. In fact, variolation was widely practiced in Europe until Jenner's discovery.

The regular practice of variolation reached the New World in 1721 ( 9). Under the guidance of the Rev. Cotton Mather (1663-1728) and Dr. Zabdiel Boylston (1679-1766), variolation became quite popular in the colonies. Mather, a graduate of Harvard College, was always very interested in science and medicine. When a ship from the West Indies carried persons sick with smallpox into Boston in 1721, an epidemic broke out in Boston and other parts of Massachusetts. Mather wrote a cautious letter recommending immediate variolation. However, he persuaded only Dr. Boylston. With Mather's support, Boylston immediately started a variolation program and continued to inoculate many volunteers, despite many adversaries in both the public and the medical community in Boston. As the disease spread, so did the controversy around Mather and Boylston ( 12). At the height of the epidemic, a bomb was thrown into Mather's house.

To make their point, Mather and Boylston used a statistical approach to compare the mortality rate of natural smallpox infection with that contracted by variolation. During the great epidemic of 1721, approximately half of Boston's 12,000 citizens contracted smallpox. The fatality rate for the naturally contracted disease was 14%, whereas Boylston and Mather reported a mortality rate of only 2% among variolated individuals ( 12). This may have been the first time that comparative analysis was used to evaluate a medical procedure.

During the decades following the 1721 epidemic in Boston, variolation became more widespread in the colonies of New England. In 1766, American soldiers under George Washington were unable to take Quebec from the British troops, apparently because of a smallpox epidemic that significantly reduced the number of healthy troops ( 13). The British soldiers were all variolated. By 1777, Washington had learned his lesson: all his soldiers were variolated before beginning new military operations ( 14, 15). The success of variolation in the New World was not without effect on Europe. In fact, the rapid adoption of variolation in Europe can be directly traced to the efforts of Cotton Mather during the Boston smallpox epidemic in 1721. Although many British physicians remained skeptical even after Mather's success, the data he had published were eventually influential. Variolation was subsequently adopted in England and spread from there throughout Western Europe.

In 1757, an 8-year-old boy was inoculated with smallpox in Gloucester ( 4); he was one of thousands of children inoculated that year in England. The procedure was effective, as the boy developed a mild case of smallpox and was subsequently immune to the disease. His name was Edward Jenner.

EDWARD JENNER

Edward Jenner was born on May 17, 1749, in Berkeley, Gloucestershire, the son of the Rev. Stephen Jenner, vicar of Berkeley. Edward was orphaned at age 5 and went to live with his older brother. During his early school years, Edward developed a strong interest in science and nature that continued throughout his life. At age 13 he was apprenticed to a country surgeon and apothecary in Sodbury, near Bristol ( 16). The record shows that it was there that Jenner heard a dairymaid say, "I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face." It fact, it was a common belief that dairymaids were in some way protected from smallpox.

In 1764, Jenner began his apprenticeship with George Harwicke. During these years, he acquired a sound knowledge of surgical and medical practice ( 10). Upon completion of this apprenticeship at the age of 21, Jenner went to London and became a student of John Hunter, who was on the staff of St. George's Hospital in London. Hunter was not only one of the most famous surgeons in England, but he was also a well-respected biologist, anatomist, and experimental scientist. The firm friendship that grew between Hunter and Jenner lasted until Hunter's death in 1793. Although Jenner already had a great interest in natural science, the experience during the 2 years with Hunter only increased his activities and curiosity. Jenner was so interested in natural science that he helped classify many species that Captain Cook brought back from his first voyage. In 1772, however, Jenner declined Cook's invitation to take part in the second voyage ( 4).

Jenner occupied himself with many matters. He studied geology and carried out experiments on human blood ( 17). In 1784, after public demonstrations of hot air and hydrogen balloons by Joseph M. Montgolfier in France during the preceding year, Jenner built and twice launched his own hydrogen balloon. It flew 12 miles. Following Hunter's suggestions, Jenner conducted a particular study of the cuckoo. The final version of Jenner's paper was published in 1788 and included the original observation that it is the cuckoo hatchling that evicts the eggs and chicks of the foster parents from the nest ( 17, 18). For this remarkable work, Jenner was elected a fellow of the Royal Society. However, many naturalists in England dismissed his work as pure nonsense. For more than a century, antivaccinationists used the supposed defects of the cuckoo study to cast doubt on Jenner's other work. Jenner was finally vindicated in 1921 when photography confirmed his observation ( 19). At any rate, it is apparent that Jenner had a lifelong interest in natural sciences. His last work, published posthumously, was on the migration of birds.

In addition to his training and experience in biology, Jenner made great progress in clinical surgery while studying with John Hunter in London. Jenner devised an improved method for preparing a medicine known as tartar emetic (potassium antimony tartrate). In 1773, at the end of 2 years with John Hunter, Jenner returned to Berkeley to practice medicine. There he enjoyed substantial success, for he was capable, skillful, and popular. In addition to the practice of medicine, he joined two local medical groups for the promotion of medical knowledge and continued to write occasional medical papers ( 4, 18). He also played the violin in a musical club and wrote light verse and poetry. As a natural scientist, he continued to make many observations on birds and the hibernation of hedgehogs and collected many specimens for John Hunter in London.

In 1797, Jenner sent a short communication to the Royal Society describing his experiment and observations. However, the paper was rejected. Then in 1798, having added a few more cases to his initial experiment, Jenner privately published a small booklet entitled An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and Known by the Name of Cow Pox ( 18, 10). The Latin word for cow is vacca, and cowpox is vaccinia; Jenner decided to call this new procedure vaccination. The 1798 publication had three parts. In the first part Jenner presented his view regarding the origin of cowpox as a disease of horses transmitted to cows. The theory was discredited during Jenner's lifetime. He then presented the hypothesis that infection with cowpox protects against subsequent infection with smallpox. The second part contained the critical observations relevant to testing the hypothesis. The third part was a lengthy discussion, in part polemical, of the findings and a variety of issues related to smallpox. The publication of the Inquiry was met with a mixed reaction in the medical community.

Jenner went to London in search of volunteers for vaccination. However, after 3 months he had found none. In London, vaccination became popular through the activities of others, particularly the surgeon Henry Cline, to whom Jenner had given some of the inoculant ( 4). Later in 1799, Drs. George Pearson and William Woodville began to support vaccination among their patients. Jenner conducted a nationwide survey in search of proof of resistance to smallpox or to variolation among persons who had cowpox. The results of this survey confirmed his theory. Despite errors, many controversies, and chicanery, the use of vaccination spread rapidly in England, and by the year 1800, it had also reached most European countries ( 10).

Although sometimes embarrassed by a lack of supply, Jenner sent vaccine to his medical acquaintances and to anyone else who requested it. After introducing cowpox inoculation in their own districts, many recipients passed the vaccine on to others. Dr. John Haygarth (of Bath, Somerset) received the vaccine from Edward Jenner in 1800 and sent some of the material to Benjamin Waterhouse, professor of physics at Harvard University. Waterhouse introduced vaccination in New England and then persuaded Thomas Jefferson to try it in Virginia. Waterhouse received great support from Jefferson, who appointed him vaccine agent in the National Vaccine Institute, an organization set up to implement a national vaccination program in the United States ( 20).

Although he received worldwide recognition and many honors, Jenner made no attempt to enrich himself through his discovery. He actually devoted so much time to the cause of vaccination that his private practice and his personal affairs suffered severely. The extraordinary value of vaccination was publicly acknowledged in England, when in 1802 the British Parliament granted Edward Jenner the sum of £10,000. Five years later the Parliament awarded him £20,000 more. However, he not only received honors but also found himself subjected to attacks and ridicule. Despite all this, he continued his activities on behalf of the vaccination program. Gradually, vaccination replaced variolation, which became prohibited in England in 1840.

Jenner married in 1788 and fathered four children. The family lived in the Chantry House, which became the Jenner Museum in 1985. Jenner built a one-room hut in the garden, which he called the "Temple of Vaccinia" (Figure ​(Figure4 4 ), where he vaccinated the poor for free ( 10, 17). After a decade of being honored and reviled in more or less equal measure, he gradually withdrew from public life and returned to the practice of country medicine in Berkeley. In 1810, his oldest son, Edward, died of tuberculosis. His sister Mary died the same year and his sister Anne 2 years later. In 1815, his wife, Catherine, died of tuberculosis ( 17). Sorrows crowded in on him, and he withdrew even further from public life. In 1820, Jenner had a stroke from which he recovered. On January 23, 1823, he visited his last patient, a dying friend. The next morning Jenner failed to appear for breakfast; later that day he was found in his study. He had had a massive stroke. Edward Jenner died during the early morning hours of Sunday, January 26, 1823. He was laid to rest with his parents, his wife, and his son near the altar of the Berkeley church.

CONCLUSION

Jenner's work represented the first scientific attempt to control an infectious disease by the deliberate use of vaccination. Strictly speaking, he did not discover vaccination but was the first person to confer scientific status on the procedure and to pursue its scientific investigation. During the past years, there has been a growing recognition of Benjamin Jesty (1737-1816) as the first to vaccinate against smallpox ( 21). When smallpox was present in Jesty's locality in 1774, he was determined to protect the life of his family. Jesty used material from udders of cattle that he knew had cowpox and transferred the material with a small lancet to the arms of his wife and two boys. The trio of vaccinees remained free of smallpox, although they were exposed on numerous occasions in later life. Benjamin Jesty was neither the first nor the last to experiment with vaccination. In fact, the use of smallpox and cowpox was widely known among the country physicians in the dairy counties of 18th-century England. However, the recognition of these facts should not diminish our view of Jenner's accomplishments. It was his relentless promotion and devoted research of vaccination that changed the way medicine was practiced.

Scientific advances during the two centuries since Edward Jenner performed his first vaccination on James Phipps have proved him to be more right than wrong. The germ theory of disease, the discovery and study of viruses, and the understanding of modern immunology tended to support his main conclusions. The discovery and promotion of vaccination enabled the eradication of smallpox: this is Edward Jenner's ultimate vindication and memorial.

References

3. Hopkins DR. Chicago: University of Chicago Press; 1983. Princes and Peasants: Smallpox in History. [ Google Scholar]

5. Lyons AS, Petrucelli RJ., II . New York: Abradale Press, Harry N Abrams Inc; 1987. Medicine-An Illustrated History. [ Google Scholar]

8. Moore JC. The History of the Smallpox. London: Longman; 1815. [ Google Scholar]

12. Beall OT, Shryock RH. Cotton Mather: First Significant Figure in American Medicine. Baltimore: Johns Hopkins University Press; 1954. [ Google Scholar]

13. Bardell D. Smallpox during the American war of independence. ASM News. 1976;42:526-530. [ Google Scholar]

16. Parish HJ. Victory with Vaccines: The Story of Immunization. Edinburgh: E & S Livingstone; 1968. [ Google Scholar]

19. Scott EL. Edward Jenner FRS and the cuckoo. Notes and Records of the Royal Society. 1974;28(2):235-240. [ Google Scholar]

20. Underwood EA. Edward Jenner, Benjamin Waterhouse and the introduction of vaccination into the United States. Nature. 1949;163:823-828. [ Google Scholar]

22. World Health Organization. The Global Eradication of Smallpox: Final Report of the Global Commission for the Certification of Smallpox Eradication. Geneva: World Health Organization; 1980. Global Commission for Certification of Smallpox Eradication. [ Google Scholar]

Articles from Proceedings (Baylor University. Medical Center) are provided here courtesy of Baylor University Medical Center

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Edward Jenner and the history of smallpox and vaccination

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In science credit goes to the man who convinces the world, not the man to whom the idea first occurs. -Francis Galton For many centuries, smallpox devastated mankind. In modern times we do not have to worry about it thanks to the remarkable work of Edward Jenner and later developments from his endeavors.

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In 1721, Lady Mary Wortley Montagu used the practice of inoculation on her children and found that they did not develop Smallpox. The British Royal Family promoted the practice of inoculation, or variolation.

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Vaccination is taking a different disease that are milder than the target disease and has similar immunity. Then injecting that into  a person. Variolation is taking a mild version of the disease such as pus from earlier stages of Small Pox and then injecting it into a person.

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by Dr. Talya Housman, Threadable Books

In the winter of 1764, smallpox descended on Boston and John Adams went to get inoculated against it. You might have heard that Edward Jenner pioneered the smallpox vaccine in 1796 - so how did Adams get inoculated in 1764?

Adams used an earlier method of inoculation called "variolation," rather than Jenner's "vaccination." Inoculation is the process of introducing a small amount of viral matter into the body in order to teach the body's immune system to fight off the virus, thus making the patient immune to future infection. Variolation used viral matter from smallpox patients, usually pus from a light case of smallpox. Jenner's vaccination, meanwhile, used matter from the milder cowpox virus. As a milder disease carrying the same immunities, cowpox matter was much safer.

Zabdiel Boylston, the uncle of John Adams's mother, Susanna Boylston Adams, is often credited for introducing variolation to the Americas in 1721. In fact, Onesimus, one of Cotton Mather's slaves, told Mather of the practice and Mather convinced his friend Boylston to try inoculation.[1] Around the same time, Lady Mary Wortley Montagu had her daughter inoculated in England after learning about variolation during her husband's diplomatic posting at the Ottoman court in Istanbul. Variolation was used in not only Africa and the Ottoman Empire but also China and India long before the Western world ever discovered this secret.

The impetus for Boylston and Mather's efforts in 1721 was the arrival in Boston of the sixth large outbreak of smallpox.[2] Boylston began inoculating hundreds but controversy erupted over his efforts.[3] Many worried about the intentional spread of disease. Others felt that if anyone died from inoculation, Boylston was guilty of murder. Fierce debate raged in Boston between supporters and opponents of the practice of variolation. The debate did not remain on the page - Boylston was physically assaulted on the street. However, Boylston and Mather collected information on infections and were able to show that inoculation dropped the smallpox mortality rate to 1 or 2% from approximately 15%.[4] By 1749, William Douglass, the fiercest opponent of inoculation, published an essay admitting inoculation's benefits and encouraging society to inoculate.[5]

Though variolation was well accepted by the time of Adams's 1764 inoculation, there remained about "500 Persons, who continue to stand it out, in spight of Experience, [and] the Expostulations of the Clergy." These individuals caused Adams to wonder if man was truly "a rational creature" since he would have seen himself as "a deliberate self Murderer" if he had refused to inoculate himself.[6] In addition, inoculation in 1764 was not an entirely uniform process. Adams wrote that in his recovery from the inoculation, "Each [doctor] has a few Particulars in Point of Diet, in which he differs from the others, and Each has Pills and Powders, different from the others to administer."[7]

As we all wait for scientists to develop a vaccine for the coronavirus, it's important to remember the controversy that followed the 1721 Boston inoculations as well as the gradual normalization of the variolation process that preceded Jenner's discovery. The development, adoption, and improvement of infectious disease response are messy processes - not a single "eureka" event. It is common to have initial disagreements among experts on treatments and often the first workable treatment is later replaced with an improved option.

It's easy to see dates like 1796 as the shining beacons in the lines of smallpox history - but to John Adams and much of Boston in 1764, they were thankful to live after 1721. Adams celebrated "Inoculation for the Small Pox" as evidence of America's "Glory of the Invention."[8] He praised Boylston's 1721 "discovery" and "practice" of smallpox inoculation "which has since proved of such inestimable benefit to Mankind."[9]
Dr. Housman's first book project uses digital tools to explore sexual crime in seventeenth century England. She has written on numerous historical topics including slavery, suffrage, religious freedom, industrialization, charitable giving, and pandemics for various public history organizations.
[1] Stefan Riedel, "Edward Jenner and the History of Smallpox and Vaccination," Baylor University Medical Center Proceedings, 18:1, (2005), 22.

[2] Shawn Buhr, "To Inoculate or Not to Inoculate?: The Debate and the Smallpox Epidemic of Boston in 1721," Constructing the Past, 1:1, (2000), 63.

[3] For more on this controversy, see Christianna Elrene Thomas Hurford, " In His Arm the Scar": Medicine, Race, and the Social Implications of the 1721 Inoculation Controversy on Boston, unpublished doctoral dissertation, (Ohio State University, 2012); Amalie M. Kass, "Boston's Historic Smallpox Epidemic," Massachusetts Historical Review, 14 (2012), 1-51.

[4] Buhr, "To Inoculate or Not to Inoculate," 66.

[5] William Douglass, A Summary, Historical and Political, of the first Planting Progressive Improvements, and present State of the British Settlements in North America, (Boston: Rogers and Fowle, 1749).

[6] John Adams to Abigail Smith, 17 April 1764 in Adams Family Correspondence, Vol. 1. [ link]

[7] John Adams to Abigail Smith, 14 April 1764 in Adams Family Correspondence, Vol. 1. [ link]

[8] John Adams to the President of Congress No. 9, 25 February 1780 in Papers of John Adams, Vol. 8. [ link]

[9] Obituary of Susanna Boylston Adams Hall, 29 April 1797 in Adams Family Correspondence, Vol. 12. [ link]

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Variolation vs. Vaccination: 18th Century Developments in Smallpox Inoculation

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by Dr. Talya Housman, Threadable Books In the winter of 1764, smallpox descended on Boston and John Adams went to get inoculated against it. You might have heard that Edward Jenner pioneered the smallpox vaccine in 1796 - so how did Adams get inoculated in 1764?

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By 1800, vaccinations has reached most of Europe and 100,000 people worldwide was vaccinated for smallpox

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Smallpox- The Triumph over the most Terrible of the Ministers of Death.pdf

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By 1959, WHO passed a resolution to eradicate smallpox around the world, but it wasn't until 1966 that the WHO provided funding to the ‘Intensified Smallpox Eradication Program.’ This increased the efforts for smallpox eradication.

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Smallpox is the only human disease that has been successfully eradicated.¹

Smallpox, an infectious disease caused by the variola virus was a major cause of mortality in the past, with historic records of outbreaks across the world. Its historic death tolls were so large that it is often likened to the Black Plague.

The eradication of smallpox is therefore a major success story for global health for several reasons: it was a disease that was endemic (and caused high mortality rates) across all continents; but was also crucial to advances in the field of immunology. The smallpox vaccine was the first successful vaccine to be developed.

In this entry we cover:

the historical and epidemiological context of smallpox disease [jump to section]

a global overview of the long-run data on smallpox cases and mortality rates [jump to section]

the global decline of smallpox and its eradication in 1977 [jump to section]

the journey through varioliation to vaccination that led to its eradication [jump to section]

the impact of smallpox vaccination on life expectancy [jump to section]

the estimated costs of and lives saved from smallpox eradication [jump to section].

All our charts on Smallpox

What is smallpox?

Smallpox is a disease that is caused by the variola virus. It is an infectious (also known as 'communicable') disease meaning it can spread from one person or animal to another, either directly or indirectly. The variola virus, however, infects only humans (meaning animals are unable to catch smallpox).

There are two types of variola viruses - variola major and variola minor - with the former type being a much more severe form.

Humans are infected with the variola virus by coming in touch with droplets of a smallpox-infected patient. A healthy person can become infected if they inhale fluid droplets from another infected individual (e.g. through coughing or sneezing).²

Symptoms

Smallpox is most known for a rash of pustules covering a patient's entire body. After being infected with the variola virus, patients usually had no symptoms for 10-14 days (an incubation period) and symptoms of a common cold for 2-3 days (unspecific symptoms).³

On average, it then took the rash 24 hours to cover the body and an additional three weeks for pustules to grow in size, form crusts and eventually fall off. A surviving patient would be marked for life with depigmented skin and scars in places where pustules had formed.

While an infection of the variola minor virus would lead to death with a probability of less than one percent, the case fatality rate of the variola major virus has been estimated to be around 30 percent.⁴

The specific way a smallpox infection would lead to a patient's death remains unclear.⁵

The Oxford Textbook of Medicine notes symptoms of prostration (total exhaustion), toxaemia (usually poisoned by bacterial toxins) and hypotension (low blood pressure) but the exact biological mechanism causing such symptoms are unknown.⁶

Death usually occurred 10 to 16 days after the onset of symptoms.⁷

If a patient successfully fought off the infection and survived, (s)he would never catch smallpox again. A side effect of the body's fight against the variola virus was that memory cells were produced that were able to quickly detect and activate killer cells for any variola viruses that a survivor encountered in the future.

There was never a treatment for smallpox. Once a person was infected it was impossible to treat them; one could only helplessly let the disease run its course. It might be possible that modern antiviral drugs would now allow a treatment of the disease if the disease still existed: The Centers for Disease Control and Prevention (CDC)⁸ now lists three antiviral drugs as potential treatment options, but since they have never been tested on infected humans, their effectiveness remains unknown.

Origins of smallpox

The origin of the variola virus and the time since when it infected humans are uncertain. The WHO⁹ considers two theories for its origin: either, humans were infected by a variola-like virus from rodents "16,000 or 68,000 years before present"¹⁰ or by a proto-variola mutated into the disease we now know as smallpox.

The fact that the variola virus has remained distinct from the other members of its orthopoxvirus family for 3,000 years makes the former hypothesis more likely than the latter.¹¹

Epidemiologists hypothesized the virus's origin by making use of the fact that it exclusively infected humans and therefore depended on a sufficiently large human population which could continuously provide new human hosts for it to survive (infected humans either die or recover and become immune for life). Egypt hosted one of the earliest concentrations of human civilization along the River Nile about 3,000 years ago, making it a likely candidate for the origin of the continued existence of various infectious diseases, including smallpox and polio.

This hypothesized origin was supported by archeologists finding "dome-shaped vesicles [...] similar to those found in smallpox"¹²on three mummies whose skin, bones and muscles were preserved thanks to the Egyptian mummification practice. One of these was Pharaoh Ramses V who died in 1157 BCE. The photograph of his skull below clearly shows small pustules, especially on his cheeks. At the time of the mummy's discovery, electron microscopy was unfortunately not yet available. This analysis would have allowed for a definite diagnosis; authorities have not allowed investigators to extract tissue samples from the mummies since then.¹³

Ramses V is believed to be the first known victim of smallpox after examining the pustules found on his cheeks.¹⁴

How many died of smallpox?

In his review paper 'The eradication of smallpox - An overview of the past, present, and future' Donald Henderson reports that during the 20th century alone "an estimated 300 million people died of the disease."¹⁵

In his book Anderson suggests that in the last hundred years of its existence smallpox killed "at least half a billion people."¹⁶ 500 million deaths over a century means 5 million annual deaths on average.

Long-run smallpox deaths in Europe

The graph shows the deaths per 1000 citizens from over the long-run, dating from 1774 to 1900 in European countries for which data was available. Two phenomena are illustrated here. First, Swedish data which pre-dates an effective means against smallpox (in 1796) shows the large disease burden and endemicity of smallpox in the 18th century. In peak years, up to 7 out of 1000 Swedes died of smallpox and the volatile nature of outbreaks is a symptom of a disease being endemic (explained in our section on epidemiological definitions further below).

Second, it can be seen that among selected countries, those that had adopted vaccination legislation earlier saw their smallpox death rates decrease more substantially and suffered fewer casualties during the Franco-Prussian War of 1870/71. Austria and Belgium, both of which never made smallpox vaccination mandatory, still recorded large numbers of smallpox deaths from 1875 onwards whereas other European countries displayed had already driven down smallpox fatalities significantly by then.

Nevertheless, smallpox was still endemic in every European country at the end of the 19th century.

Number of smallpox cases

The chart depicts the number of smallpox cases by country, for most countries dating 1920 until 1977. Here we see that by the time the World Health Organization (WHO) launched its Intensified Smallpox Eradication Program in 1966, most countries in Western Europe and North America had almost eliminated smallpox whilst the countries across South America, Africa and Asia, especially India, still recorded very large numbers (note the large differences in color brackets below).

Global data on the number of smallpox cases is shown in the chart. Shown here is the number of reported smallpox cases worldwide from 1920 until the last case in 1977. Just the reported number of smallpox cases between 1920 and 1978 already amounted to 11.6 million cases; and that number was certainly smaller than the actual number of cases, although we do not know by how much. Even though smallpox had a high visibility and should therefore be relatively easy to document, the lack of an international organization dedicated to global health means the number of reported cases is probably substantially lower than the true number of cases. Crosby (1993) estimates that in 1967 10-15 million people were still being infected with smallpox every year while the chart on the reported cases below indicates only 132,000 for that same year.¹⁷

The reasons and extent of discrepancies between reported and estimated cases are discussed in our section on Data Quality.

The chart shows global case numbers (as shown in the section above) disaggregated by world region, extending to 1977, the year of the last case globally.

Even though absolute numbers are almost certainly far too low (as explained above and in our section on Data Quality), it can be seen that in relative terms, South Asia had by far the highest number of smallpox cases. This was primarily driven by incidence in India: in 1973, for instance, in a state that had reported approximately 500 cases a week, the WHO search team found 10,000 cases.¹⁸

Eradication of smallpox

The last variola major infection was recorded in Bangladesh in October 1975, and the last variola minor infection occurred two years later in Merka, Somalia, on October 26th, 1977. During the following two years, WHO teams searched the African continent for further smallpox cases among those rash-like symptoms (which is a symptom of numerous other diseases). They found no further cases.

In 1978, a laboratory accident in the United Kingdom occurred where a variola virus sample was spread through the university laboratory's ventilation system, infecting two people and killing one.¹⁹

The world map shows the year in which each country recorded the last endemic case of smallpox. Europe, North America and Australia managed to eliminate smallpox relatively early, most by the 1940s (predating the WHO's Intensified Smallpox Eradication Program, which was launched in 1966). Countries across Sub-Saharan Africa, Latin America and Asia eliminated smallpox several decades later in the 1960s and 70s.

In May 1980, the World Health Assembly, the governing body of the World Health Organization, officially certified the global elimination of smallpox, the first ever eradication of a disease in human history. It further "recommended that all countries cease vaccination, all laboratories should destroy their remaining stocks or transfer them to" two certified high security laboratories in Moscow (State Research Center of Virology and Biotechnology) or the Centers for Disease Control and Prevention (CDC) in Atlanta.²⁰

These are the only two known places that still hold samples of the variola viruses for research purposes.

Variolation

Variolation (sometimes also inoculation), refers to the deliberate transmission of viral matter.

Before the year 1000, Indians and the Chinese had already observed that contraction of smallpox protected children against any future outbreaks of the disease. As a consequence they developed a procedure that involved the nasal inhalation of dried smallpox scabs by three-year-olds.²¹

Another commonly practiced technique (whose geographic and temporal origin are unknown) encompassed the injection of the liquid found inside the pustules of a smallpox patient underneath the skin of a healthy person. This would usually result in a milder infection of smallpox after which the person was immune against the disease. Both practices became known as variolation (inoculation) techniques.

The disadvantage of variolation, however, was that during the course of the mild infection the person became a carrier of the disease and could infect other people. Additionally, it was difficult to control the severeness of the infection which sometimes developed into a full-blown smallpox case that could lead to the person's death.²²

This meant that the practice usually reduced the severeness of an infection and the likelihood of deaths but that it would never lead to eliminating the virus. If anything, it helped to spread the virus in a population even further and thereby encouraged its survival.

A British ambassador's wife, Lady Mary Wortley Montague (1869-1762) was the force that pushed for government-mandated variolation in England. She herself had suffered a smallpox infection and lost her younger brother to the disease at the age of 26. She first learned about variolation when she arrived in Istanbul in 1717, where variolation was commonly practiced. She later had the embassy inoculate her two children.

News spread among the royal family and after following trials Maitland successfully inoculated the two daughters of the Princess of Wales in 1722. Thereafter, variolation became a common practice in Great Britain and became known in other European countries. It became an even more established practice when the French King Louis XV died of smallpox in May of 1776 and his successor and grandson Louis XVI was inoculated with the variola virus one month later.

Vaccine against smallpox

At the end of the 18th century British surgeon and physician Edward Jenner (1749-1823) pioneered the first ever vaccination against an infectious disease. He himself had been inoculated with smallpox at the age of 8 and later as a surgeon, variolation was part of his work.²³ He observed that people who had suffered from cowpox would subsequently have a very mild, if at all visible reaction to the smallpox variolation. At the time unknowingly, he had discovered that the cowpox and variola viruses were members of the same orthopoxvirus family.

He hypothesized that variolation using the cowpox virus would protect children against smallpox as well. Since cowpox infections were much milder and never fatal, this would eliminate the problem of variolated children being carriers of smallpox and sometimes dying of the virus developing into a full-blown infection. On top of protection against the symptoms, it could reduce the stock of humans that the variola virus needed for survival and brought elimination and eventually eradication of smallpox into the realm of possibility.

In May 1796, Jenner inoculated a boy with cowpox, and then a few months later with the smallpox virus. When the boy did not develop any smallpox symptoms in response to being variolated, his hypothesis of the cowpox offering protection from smallpox was confirmed motivating his further research trials.

Initially, Jenner faced major barriers to spreading the word about his discovery. When he submitted a paper outlining his findings to the journal Philosophical Transactions edited by the Royal Society, it was rejected. They even advised him not to pursue his ideas any further, pointing to the detrimental impact on his career and reputation. Undeterred, he published his work with an increased number of trials at his own expense two years later (in 1798). He also went on to convince colleagues and supply them with vaccines in other British cities of his new procedure that became known as vaccination (derived from the Latin word for cow, vacca).

By 1802, the British Parliament did acknowledge his important contribution and awarded him £30,000. Meanwhile, vaccination had spread to most of Europe and New England.²⁴

His 1798 publication Inquiry into the Variolae vaccinae known as the Cow Pox had been translated into German, French, Spanish, Dutch, Italian, and Latin within three years. US President Thomas Jefferson figured importantly in the widespread application of vaccination throughout the United States and in 1806, he thanked Edward Jenner in a letter for his discovery and famously predicted "Future generations will know by history only that the loathsome smallpox existed and by you has been extirpated."²⁵

The dramatic decline in smallpox fatalities in response to Jenner's vaccine can be traced in the chart, which shows the number of deaths due to smallpox as a share of all deaths in London from 1629 to 1902. Before the introduction of a smallpox vaccine in 1796, on average 7.6% (1-in-13) of all deaths were caused by smallpox. Following introduction of the vaccine, we see a clear decline in smallpox deaths.

Smallpox Eradication Program

It was only with the establishment of the World Health Organization (WHO) in the aftermath of World War II that international quality standards for the production of smallpox vaccines were introduced. This shifted the fight against smallpox from a national to international agenda. It was also the first time that global data collection on the prevalence of smallpox was undertaken.

By 1959, the World Health Assembly, the governing body of the World Health Organization (WHO) had passed a resolution to eradicate smallpox globally. It was not until 1966, however, that the WHO provided the 'Intensified Smallpox Eradication Program' with funding to increase efforts for smallpox eradication.

By 1966, the number of infections of smallpox had already substantially been reduced by national governments' efforts. Nonetheless, skepticism about the feasibility of eradication prevailed and the WHO lacked experience in administering projects that required both technical and material support, as well as coordination across countries. Furthermore, the funding provided to the Intensified Smallpox Eradication Programme was insufficient to meet global needs, resulting mostly in vaccine shortages.²⁶

Further still, continued globalization and growth of international air travel resulted in the continual re-introduction of the disease into countries that had previously managed to eliminate smallpox.

Overcoming the last mile problem: ring vaccination

Smallpox's eradication was greatly spurred by making use of the fact that smallpox transmission occurs via air droplets. Initially, the WHO had pursued a strategy of mass vaccination which attempted to vaccinate as many people as possible, hoping that herd immunity (explained in our vaccine entry) would protect the whole population. Soon, however, vaccination efforts were targeted locally around smallpox cases as smallpox was transmitted by sick patients' air droplets. This is known as the ring vaccination principle.

People who had been in direct contact with a smallpox patient over the last two weeks were quarantined and vaccinated. The downside of such an approach was that the virus could spread easily if it was re-introduced from overseas. This was the case in Bangladesh, for example, which had previously eliminated smallpox until 1972 when it was brought back from across its border with India.²⁷

Despite the risk of re-introductions, ring vaccination greatly reduced the cost of the eradication campaign. The number of administered vaccines dropped and smallpox was increasingly brought under control. Regional elimination came within reach.²⁸

One of the last strongholds of the variola virus was India. While 57.7 percent of global reported smallpox cases were reported in India in 1973, this increased to 86.1 percent in 1974.²⁹ One major push in vaccination campaigns, however, successfully drove down the number of infections to zero in India in 1976.

Impact on life expectancy

Did smallpox variolation and vaccination against smallpox have a notable impact on life expectancy?

Many have made the claim that inoculation against smallpox was one of the first measures that had a positive effect on life expectancy. Angus Deaton (2013) makes this claim based on a book by Razzell (1977), which reviews existing birth, baptism and burial records in various counties of 18th century Britain.³⁰ ³¹ Whilst some anecdotal evidence suggests smallpox deaths declined over the course of the 18th century, we cannot be sure that the spread of inoculation practices were the cause of that decline. Furthermore, the local communities for which records were available may not have been representative of Great Britain as a whole. Such evidence therefore seems insufficient to show a causation relationship between inoculation and increases in life expectancy.

It is hard to prove such claims because of the lack of and low quality of data on both life expectancy and smallpox cases/deaths prior to the invention of Jenner's vaccine in 1796. Whilst we have presented data on smallpox deaths in London dating back to 1629, we only know the aggregate life expectancy of Great Britain (rather than London specifically) over this period. It's unlikely that London's smallpox deaths are nationally representative which means that the direct comparison is not possible.

When comparing these charts on London smallpox deaths and British life expectancy we see that neither smallpox deaths or life expectancy dramatically deviated from their averages following the wider adoption of variolation in 1722.

But can we say something about the impact of Jenner's vaccination on life expectancy? The high case fatality rate of approximately 30 percent (for the variola major virus strand) meant that smallpox shortened the lives of many. Since the virus predominantly affected children during endemic periods, smallpox deaths are likely to have had a disproportionate impact on average life expectancy.

The chart visualizes Sweden's life expectancy (in red) and deaths from smallpox (in blue) from 1774 to 1900. Large-scale smallpox outbreaks were documented for the years 1779, 1784, 1789, 1795 and 1800. These years exactly coincide with sharp declines in life expectancy, implying that smallpox endemicity did have a substantial effect on life expectancy. Furthermore, while the available data did not show a clear decline in smallpox deaths after the introduction of inoculation in Britain, they do show dramatic declines in mortality in London as well as in Sweden (below) from 1800 onwards. Once smallpox mortality fell at the turn of the eighteenth to nineteenth century, life expectancy in Sweden for the first time was put on an upwards trending trajectory.

Overall, the impact of inoculation on life expectancy remains uncertain. Jenner's vaccine appears to have had a notable impact on increased life expectancy but this, to our knowledge, has not been studied in significant detail.³²

Costs of smallpox and its eradication

By the time the World Health Organization launched the Intensified Smallpox Eradication Program in 1967 many countries, most of them high income countries, had already eliminated smallpox. Therefore, the true cost of eradicating smallpox will never be known as individual country programs reach back to before records of public health expenditure existed. Nonetheless, the Intensified Smallpox Eradication Program has been estimated to have cost $300 million in total from 1967 to 1977³³ with one-third of the funding provided by international donors and the remaining two-thirds financed by endemic country governments.³⁴

Beyond direct program costs, smallpox incurred much higher indirect costs in the form of foregone economic performance. It has been estimated that smallpox cost low-to-middle income countries more than $1 billion per year at the beginning of the Intensified Smallpox Eradication Program in 1967, with more than $20 million dedicated to the care of infected patients.³⁵

Industrialized countries incurred much lower costs: $350 million in 1968 which included vaccination programs and absence from work costs.³⁶

Overall, the Center for Global Development³⁷ estimated that direct and indirect costs of smallpox cost the world approximately $1.35 billion in the late 1960s.

Following its eradication, countries now do not have to spend money on vaccine development and administration. Estimates on the savings from forgone costs thanks to the eradication of smallpox exist, but we are not aware of estimates that we would consider reliable.³⁸

Lives saved from smallpox eradication

To date the eradication of smallpox saved millions of lives. It is impossible to know very exactly how many people would have died of smallpox since 1980 if scientists had not developed the vaccine, but reasonable estimates are in the range of around 5 million lives per year, which implies that between 1980 and 2018 around 150 to 200 million lives have been saved.³⁹

Epidemiological definitions/context

The origin of the naming of smallpox and the variola virus
The name of smallpox originates from a common confusion with syphilis in 15th century France. The diseases shared similar symptoms (rashes) even though syphilis was caused by spirochaete bacteria and smallpox by the variola virus. Syphilis had already been known as variola, so smallpox became known as la petite vérole. Petite is French for small so the disease became known as smallpox in English.

The name of the variola virus, in turn, can be derived from the Latin words varus (pimple) or varius (changing color) which derive from smallpox's symptoms described above.⁴⁰

The variola virus family tree
The variola virus is a member of the so-called orthopoxvirus family, whose other members are the vaccinia, cowpox and monkeypox viruses.⁴¹

This is important as Jenner's vaccine used the cowpox virus, a much milder and not lethal disease, to protect humans against smallpox. The variola virus is the family's only virus that exclusively infects humans.

The variola virus consists of two strands, known as the variola major and variola minor viruses. Infections of the variola major strand led to a patient's death in approximately 30% of cases, whereas the variola minor virus proved lethal in only less 1% of infections.⁴²

Eradication is the "permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts".⁴³

Elimination refers to the "reduction to zero of the incidence of infection caused by a specific agent in a defined geographic area as a result of deliberate efforts." A disease can be eliminated from a specific region without being eradicated.⁴⁴

Infectious Diseases are "disease[s] caused by the entrance into the body of organisms (as bacteria, protozoans, fungi, or viruses) which grow and multiply there".⁴⁵

Variolation refers to the deliberate transmission of viral matter, for example by inserting material from an infected person's skin underneath a healthy person's skin.⁴⁶

Endemic refers to the constant presence [...] of a disease in a population within a geographic area.⁴⁷

Endemic vs. non-endemic populations
The severity and most common age group for smallpox infections was dependent on whether the virus was endemic in a population. If a population had never been exposed to smallpox before, all age groups were vulnerable to infection, meaning outbreaks led to high case and death rates across the population. McMillan (2016)⁴⁸

terms this a 'virgin soil epidemic', i.e. when a disease touches "soil" it has never touched before. The most prominent example of smallpox attacking an unprotected and never-exposed population in history is the introduction of the variola virus in North America by British colonialists. Data on the deaths of Native American tribes suffered were unfortunately not collected at the time but available sources agree that tribes were substantially decimated.⁴⁹

Regularity and severity
In an endemic population, on the other hand, smallpox outbreaks with large numbers of cases and deaths usually occurred only every two to four years. In the periods between large outbreaks, the disease would persist at lower levels of incidence (with lower numbers of cases and deaths).

Such a pattern is common among viral diseases in an endemic population: by the time the virus had infected a population, an outbreak either engendered immunity or death, so a renewed outbreak in a subsequent year would infect fewer people.⁵⁰

These cyclical outbreaks can be observed in the volatile pattern of the smallpox share in London deaths and also the smallpox death rates across Europe.

Age profile of patients
Smallpox could infect people of any age. However, when the virus was endemic in a society (uninterrupted transmission without depending on re-introduction from elsewhere), it mainly infected children. Adults in an endemic population would have been infected with the virus at an earlier stage in their lives already and since the only two possible outcomes of an infection were death or survival and life-long immunity, the virus could only infect and be transmitted by individuals that had never been exposed before: children.

In 17th century Britain, this led to children not being considered full members of the family until they had survived their smallpox infection. At the time, the British had not yet come up with a protection against smallpox so children were almost guaranteed to fall prey to an infection and families could do nothing but watch the infection run its course and hope the child would survive.⁵¹

Why are there differences between reported and estimated cases?

Three main reasons are responsible for the huge differences between reported and the estimated (thought to be closer to the truth) number of cases and deaths due to smallpox. First, many infections and deaths were not recorded simply because the monitoring public health system was dysfunctional and that was predominantly the case in developing countries where the disease burden was highest. Fenner et al. (1988) write: "It is clear that the reporting of cases of smallpox was the most efficient in countries in which the health services were well developed, which was usually where the disease was least common. It was very inefficient elsewhere."⁵²

Second, classifying deaths posed another challenge. For instance if smallpox patients had already been suffering from pneumonia or even just a flu when becoming infected with smallpox and then died, it is unclear whether smallpox or pneumonia or the flu were the cause of death. Had a patient survived the smallpox infection if (s)he had not already been weakened by another disease, this creates a major challenge in classifying the cause of deaths which is likely to have further diminished the number of smallpox cases and deaths actually reported and recorded.

Third, some anecdotes suggest that some smallpox outbreaks were deliberately kept secret.⁵³

Razzell (1977) writes in his book about British market towns: "Many tradesmen in market towns may have suppressed information about smallpox in their families and certainly the townspeople as a whole were very anxious to avoid advertising the presence of smallpox in their own town so as to avoid frightening country people from the surrounding area - there are many examples of markets being ruined for more than a year because of the presence of smallpox."⁵⁴

Extent of reporting discrepancy

The World Health Assembly was aware of the underreporting and therefore attempted to correct the number of reported smallpox cases upward for the years 1959 to 1966, just before the Intensified Smallpox Eradication Program was launched. The chart illustrates that the corrections were highest for 1965, where the originally reported smallpox cases only amounted to 64,000 cases which was corrected to almost double its value, 112,000 cases.

Many sources suggest, however, that even these corrections were small in comparison to what the actual extent of smallpox's disease burden was. Fenner et al. (1988) write "it is not unreasonable to regard the official figures reported to WHO as representing only 1-2 percent of the true incidence - probably nearer 1 percent for the years before the initiation of the global eradication programme. In the early 1950s, 150 years after the introduction of vaccination, there were probably some 50 million cases of smallpox in the world each year, a figure which had fallen to perhaps 10-15 million by 1967."⁵⁵

These figures are also mentioned in the final report by the WHO that confirmed smallpox's eradication, along with the disease still causing approximately 2 million deaths in 1967.⁵⁶

Henderson (1976) adds that the global cases numbers reported to the WHO in 1967 probably were the number of infections taking place in northern Nigeria alone.⁵⁷

In 1973, the World Health Organization conducted a thorough search for smallpox cases in line with its ring vaccination strategy in India: in a state that had reported approximately 500 cases a week the search team found 10,000 cases.⁵⁸

Data: Global number of smallpox cases

Geographical coverage: Global (total)

Time span: 1920-2016

Available at: Link under the data tab at the right on the Earth Policy Institute's website here.

Data: The year of the last recorded smallpox case and the reported number of smallpox cases

Geographical coverage: Global (by country)

Time span: Year of the last recorded smallpox case: 1910-1977
Reported number of smallpox cases: 1886-1966

Available at: Chapter 8 of Fenner, F., Henderson, D., Arita, I., Jezek, Z., & Ladnyi, I. (1988). Smallpox and its eradication. Geneva: World Health Organization. Fully available for download here.

Data: The reported number of smallpox cases

Geographical coverage: Global (by country)

Time span: 1967-1977

Available at: Archived Weekly Epidemiological Records available on the WHO website but the links to the relevant decades at the bottom of the list are unfortunately dysfunctional. Therefore, the search function at the top right was used and search times such as "Weekly Epidemiological Record 1970" were used. Direct links to the individual volumes used for graphs on this entry can be found under the "Sources" tab of the graph The number of reported smallpox cases.

Data: The number of deaths caused by smallpox as a share of all deaths

Geographical coverage: London

Time span: 1629-1902

Available at: The Guy (1882) paper is available on JSTOR here. For detailed information on which data sources we used in addition to Guy (1882), click on the Sources tab at the bottom of our graph for individual years' references.

Data: The number of smallpox deaths per 1,000 (living) population

Geographical coverage: Austria, Belgium, England, Netherlands, Prussia, Scotland, Sweden

Time span: 1774-1900

Available at: Edwardes (1902) A concise history of small-pox and vaccination in Europe. H.K. Lewis. Available online here.

Further reading recommendations

S.L. Kotar and J.E. Kessler's novel Smallpox: A history

Christian W. McMillen's Pandemics: A very short introduction

Jonathan B. Tucker's Scourge: The Once and Future Threat of Smallpox

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Smallpox is the only human disease that has been successfully eradicated.1 Smallpox, an infectious disease caused by the variola virus was a major cause of mortality in the past, with historic records of outbreaks across the world. Its historic death tolls were so large that it is often likened to the Black Plague.

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In 1975, there was a little girl in Bangladesh that had variola major. In 1977, Ali Maow Maalin was the last person to have variola minor since he had two patients with Smallpox.

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Origin of Smallpox

The origin of smallpox is unknown. The finding of smallpox-like rashes on Egyptian mummies suggests that smallpox has existed for at least 3,000 years. The earliest written description of a disease like smallpox appeared in China in the 4 th century CE (Common Era). Early written descriptions also appeared in India in the 7 th century and in Asia Minor in the 10 th century.

Spread of Smallpox

Historians trace the global spread of smallpox to the growth of civilizations and exploration. Expanding trade routes over the centuries also led to the spread of the disease.

Highlights from History:

6th Century-Increased trade with China and Korea brings smallpox to Japan.

7th Century-Arab expansion spreads smallpox into northern Africa, Spain, and Portugal.

11th Century-Crusades further spread smallpox in Europe.

15th Century-Portugal occupies part of western Africa, bringing smallpox.

16th Century-European settlers and the African slave trade import smallpox into:

The Caribbean

Central and South America

17th Century-European settlers bring smallpox to North America.

18th Century-Explorers from Great Britain bring smallpox to Australia.

Early Control Efforts

Smallpox was a terrible disease. On average, 3 out of every 10 people who got it died. People who survived usually had scars, which were sometimes severe.

One of the first methods for controlling smallpox was variolation, a process named after the virus that causes smallpox (variola virus). During variolation, people who had never had smallpox were exposed to material from smallpox sores (pustules) by scratching the material into their arm or inhaling it through the nose. After variolation, people usually developed the symptoms associated with smallpox, such as fever and a rash. However, fewer people died from variolation than if they had acquired smallpox naturally.

The basis for vaccination began in 1796 when the English doctor Edward Jenner noticed that milkmaids who had gotten cowpox were protected from smallpox. Jenner also knew about variolation and guessed that exposure to cowpox could be used to protect against smallpox. To test his theory, Dr. Jenner took material from a cowpox sore on milkmaid Sarah Nelmes' hand and inoculated it into the arm of James Phipps, the 9-year-old son of Jenner's gardener. Months later, Jenner exposed Phipps several times to variola virus, but Phipps never developed smallpox. More experiments followed, and, in 1801, Jenner published his treatise "On the Origin of the Vaccine Inoculation." In this work, he summarized his discoveries and expressed hope that "the annihilation of the smallpox, the most dreadful scourge of the human species, must be the final result of this practice."

Vaccination became widely accepted and gradually replaced the practice of variolation. At some point in the 1800s, the virus used to make the smallpox vaccine changed from cowpox to vaccinia virus.

Global Smallpox Eradication Program

In 1959, the World Health Organization (WHO) started a plan to rid the world of smallpox. Unfortunately, this global eradication campaign suffered from a lack of funds, personnel, and commitment from countries, and a shortage of vaccine donations. Despite their best efforts, smallpox was still widespread in 1966, causing regular outbreaks across South America, Africa, and Asia.

The Intensified Eradication Program began in 1967 with a promise of renewed efforts. Laboratories in many countries where smallpox occurred regularly were able to produce more, higher-quality freeze-dried vaccine. Other factors that played an important role in the success of the intensified efforts included the development of the bifurcated needle, the establishment of a case surveillance system, and mass vaccination campaigns.

By the time the Intensified Eradication Program began in 1967, smallpox was already eliminated in North America (1952) and Europe (1953). Cases were still occurring in South America, Asia, and Africa (smallpox was never widespread in Australia). The Program made steady progress toward ridding the world of this disease, and by 1971 smallpox was eradicated from South America, followed by Asia (1975), and finally Africa (1977).

Last Cases of Smallpox

In late 1975, three-year-old Rahima Banu from Bangladesh was the last person in the world to have naturally acquired variola major. She was also the last person in Asia to have active smallpox. She was isolated at home with house guards posted 24 hours a day until she was no longer infectious. A house-to-house vaccination campaign within a 1.5-mile radius of her home began immediately. A member of the Smallpox Eradication Program team visited every house, public meeting area, school, and healer within 5 miles to ensure the illness did not spread. They also offered a reward to anyone who reported a smallpox case.

Ali Maow Maalin was the last person to have naturally acquired smallpox caused by variola minor. Maalin was a hospital cook in Merca, Somalia. On October 12, 1977, he rode with two smallpox patients in a vehicle from the hospital to the local smallpox office. On October 22, he developed a fever. At first healthcare workers diagnosed him with malaria, and then chickenpox. The smallpox eradication staff then correctly diagnosed him with smallpox on October 30. Maalin was isolated and made a full recovery. Maalin died of malaria on July 22, 2013, while working in the polio eradication campaign.

Janet Parker was the last person to die of smallpox. In 1978, Parker was a medical photographer at England's Birmingham University Medical School. She worked one floor above the Medical Microbiology Department where staff and students conducted smallpox research. She became ill on August 11 and developed a rash on August 15 but was not diagnosed with smallpox until 9 days later. She died on September 11, 1978. Her mother, who was providing care for her, developed smallpox on September 7, despite having been vaccinated two weeks earlier. An investigation suggested that Janet Parker had been infected either via an airborne route through the medical school building's duct system or by direct contact while visiting the microbiology corridor.

World Free of Smallpox

Almost two centuries after Jenner hoped that vaccination could annihilate smallpox, the 33 rd World Health Assembly declared the world free of this disease on May 8, 1980. Many people consider smallpox eradication to be the biggest achievement in international public health.

Stocks of Variola Virus

Following the eradication of smallpox, scientists and public health officials determined there was still a need to perform research using the variola virus. They agreed to reduce the number of laboratories holding stocks of variola virus to only four locations. In 1981, the four countries that either served as a WHO collaborating center or were actively working with variola virus were the United States, England, Russia, and South Africa. By 1984, England and South Africa had either destroyed their stocks or transferred them to other approved labs. There are now only two locations that officially store and handle variola virus under WHO supervision: the Centers for Disease Control and Prevention in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology (VECTOR Institute) in Koltsovo, Russia.

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smallpox (variola major and variola minor)

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In May 8, 1980, the WHO had declared that Smallpox had been eradicated. There didn't seem to be anymore traces of Smallpox in the three years fom Ali Maow Maalin

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Smallpox is believed to have first infected humans around the time of the earliest agricultural settlements some 12,000 years ago. No surviving evidence of it, however, predates the so-called New Kingdom of Egypt, which lasted from about 1570 B.C. to 1085 B.C.

A few mummies from that era contain familiar-looking skin lesions. Ramses V, for example, who ruled for roughly four years in the 12th century B.C., looks to have had the raised bumps on his face and body for which smallpox is named (it's derived from the Latin word for "spotted").

Moreover, an ancient Egyptian papyrus scroll briefly describes what could be smallpox, as do Hittite clay tablets. The Hittites, who lived in the Middle East, even accused the Egyptians of infecting them during a war between the two empires.

Many historians speculate that smallpox likewise brought about the devastating Plague of Athens in 430 B.C. and the Antonine Plague of A.D. 165 to 180, the later of which killed an estimated 3.5 million to 7 million people, including Emperor Marcus Aurelius, and hastened the decline of the Roman Empire.

At any rate, it reached Europe no later than the 6th century, when a bishop in France unmistakably described its symptoms-a violent fever followed by the appearance of pustules, which, if the patient survived, eventually scabbed over and broke off. By that time, the contagious disease, caused by the variola virus, had spread all across Africa and Asia as well, prompting some cultures to worship special smallpox deities.

In the Old World, the most common form of smallpox killed perhaps 30 percent of its victims while blinding and disfiguring many others. But the effects were even worse in the Americas, which had no exposure to the virus prior to the arrival of Spanish and Portuguese conquistadors.

Tearing through the Incas before Francisco Pizarro even got there, it made the empire unstable and ripe for conquest. It also devastated the Aztecs, killing, among others, the second-to-last of their rulers. In fact, historians believe that smallpox and other European diseases reduced the indigenous population of North and South America by up to 90 percent, a blow far greater than any defeat in battle.

Recognizing its potency as a biological weapon, Lord Jeffrey Amherst, the commander-in-chief of British forces in North America during the French and Indian War, even advocated handing out smallpox-infected blankets to his Native American foes in 1763.

Knowing that no one can contract smallpox twice, survivors of the disease were often called upon to try and nurse victims back to health. Throughout much of the last millennium, this involved herbal remedies, bloodletting and exposing them to red objects.

One prominent 17th-century English doctor realized that those who could afford care actually seemed to be dying at a higher rate than those who couldn't. Yet that didn't stop him from telling a smallpox-infected pupil to leave the windows open, to draw the bed sheets no higher than his waist and to drink profuse quantities of beer.

Far more effective was inoculation, also called variolation, which involved taking pus or powdered scabs from patients with a mild case of the disease and inserting them into the skin or nose of susceptible, healthy people. Ideally, the healthy people would suffer only a slight infection this way and, in so doing, would develop immunity to future outbreaks.

Some people did die, but at a much lower rate than those who contracted smallpox naturally. Practiced first in Asia and Africa, variolation spread to the Ottoman Empire around 1670 and then to the rest of Europe within a few decades. Its first proponent in the present-day United States was Cotton Mather, a Puritan minister best known for vigorously supporting the Salem witch trials. Benjamin Franklin, who lost a son to smallpox, was another early American supporter.

Variolation notwithstanding, smallpox continued wreaking havoc on princes and paupers alike. In the 17th and 18th centuries, it killed several reigning European monarchs, including Habsburg Emperor Joseph I, Queen Mary II of England, Czar Peter II of Russia and King Louis XV of France, as well as an Ethiopian king, a Chinese emperor and two Japanese emperors.

Queen Elizabeth I of England and U.S. President Abraham Lincoln also apparently contracted smallpox during their time in office, though they fortuitously lived to tell the tale. Meanwhile, in Europe alone, an estimated 400,000 commoners were succumbing to smallpox annually.

Finally, in 1796, English doctor Edward Jenner performed an experiment that would, in good time, cause the virus' downfall. By inserting pus from a milkmaid with cowpox, a disease closely related to smallpox, into the arms of a healthy 8-year-old boy and then variolating him to no effect, Jenner was able to conclude that a person could be protected from smallpox without having to be directly exposed to it. This was the world's first successful vaccine, a term that Jenner himself coined. He tried to get his results published by the prestigious Royal Society, only to be told not to "promulgate such a wild idea if he valued his reputation."

Persisting anyway, his vaccine gradually started catching on. The advantages over variolation were many. Unlike a variolated person, a vaccinated person could not spread smallpox to others. Moreover, the vaccine seldom left a rash and proved fatal in only the rarest of circumstances.

"Future generations will know by history only that the loathsome smallpox existed and by you has been extirpated," U.S. President Thomas Jefferson wrote to Jenner in 1806. The following year, Bavaria declared vaccination mandatory, and Denmark did the same in 1810.

Because the vaccine originally had to be transferred from arm to arm, its use spread slowly. It was also much less effective in tropical countries, where the heat caused it to quickly deteriorate. Nonetheless, one country after another managed to rid itself of the disease. The last reported U.S. case came in 1949.

Spurred by two new technological advances-a heat-stable, freeze-dried vaccine and the bifurcated needle-the World Health Organization then launched a global immunization campaign in 1967 with the goal of wiping out smallpox once and for all. That year, there were 10 million to 15 million cases of smallpox and 2 million deaths, according to WHO estimates. Yet just a decade later, the number was down to zero. No one has naturally contracted the virus since a Somali hospital worker in 1977 (though a laboratory accident in England did kill someone in 1978).

After searching far and wide for any remaining trace of smallpox, the WHO's member states passed a resolution on May 8, 1980, declaring it eradicated. "The world and all its peoples have won freedom from smallpox," the resolution stated, adding that this "unprecedented achievement in the history of public health ... demonstrated how nations working together in a common cause may further human progress."

Today, guarded laboratories in Atlanta and Moscow hold the only known stores of the virus. Some experts say these should be destroyed, whereas others believe they should be kept around for research purposes just in case smallpox somehow remerges.

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Take a look back at the history of the pernicious disease.

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After the eradication of smallpox, scientist and public health official wanted to conduct more research on the variola virus. There was four countries that where able to work on the virus in 1981. In 1984, only two countries officially store it, which are the US in Atlanta, Georgia, and in Koltsovo, Russia.

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Origin of Smallpox

The origin of smallpox is unknown. The finding of smallpox-like rashes on Egyptian mummies suggests that smallpox has existed for at least 3,000 years. The earliest written description of a disease like smallpox appeared in China in the 4 th century CE (Common Era). Early written descriptions also appeared in India in the 7 th century and in Asia Minor in the 10 th century.

Spread of Smallpox

Historians trace the global spread of smallpox to the growth of civilizations and exploration. Expanding trade routes over the centuries also led to the spread of the disease.

Highlights from History:

6th Century-Increased trade with China and Korea brings smallpox to Japan.

7th Century-Arab expansion spreads smallpox into northern Africa, Spain, and Portugal.

11th Century-Crusades further spread smallpox in Europe.

15th Century-Portugal occupies part of western Africa, bringing smallpox.

16th Century-European settlers and the African slave trade import smallpox into:

The Caribbean

Central and South America

17th Century-European settlers bring smallpox to North America.

18th Century-Explorers from Great Britain bring smallpox to Australia.

Early Control Efforts

Smallpox was a terrible disease. On average, 3 out of every 10 people who got it died. People who survived usually had scars, which were sometimes severe.

One of the first methods for controlling smallpox was variolation, a process named after the virus that causes smallpox (variola virus). During variolation, people who had never had smallpox were exposed to material from smallpox sores (pustules) by scratching the material into their arm or inhaling it through the nose. After variolation, people usually developed the symptoms associated with smallpox, such as fever and a rash. However, fewer people died from variolation than if they had acquired smallpox naturally.

The basis for vaccination began in 1796 when the English doctor Edward Jenner noticed that milkmaids who had gotten cowpox were protected from smallpox. Jenner also knew about variolation and guessed that exposure to cowpox could be used to protect against smallpox. To test his theory, Dr. Jenner took material from a cowpox sore on milkmaid Sarah Nelmes' hand and inoculated it into the arm of James Phipps, the 9-year-old son of Jenner's gardener. Months later, Jenner exposed Phipps several times to variola virus, but Phipps never developed smallpox. More experiments followed, and, in 1801, Jenner published his treatise "On the Origin of the Vaccine Inoculation." In this work, he summarized his discoveries and expressed hope that "the annihilation of the smallpox, the most dreadful scourge of the human species, must be the final result of this practice."

Vaccination became widely accepted and gradually replaced the practice of variolation. At some point in the 1800s, the virus used to make the smallpox vaccine changed from cowpox to vaccinia virus.

Global Smallpox Eradication Program

In 1959, the World Health Organization (WHO) started a plan to rid the world of smallpox. Unfortunately, this global eradication campaign suffered from a lack of funds, personnel, and commitment from countries, and a shortage of vaccine donations. Despite their best efforts, smallpox was still widespread in 1966, causing regular outbreaks across South America, Africa, and Asia.

The Intensified Eradication Program began in 1967 with a promise of renewed efforts. Laboratories in many countries where smallpox occurred regularly were able to produce more, higher-quality freeze-dried vaccine. Other factors that played an important role in the success of the intensified efforts included the development of the bifurcated needle, the establishment of a case surveillance system, and mass vaccination campaigns.

By the time the Intensified Eradication Program began in 1967, smallpox was already eliminated in North America (1952) and Europe (1953). Cases were still occurring in South America, Asia, and Africa (smallpox was never widespread in Australia). The Program made steady progress toward ridding the world of this disease, and by 1971 smallpox was eradicated from South America, followed by Asia (1975), and finally Africa (1977).

Last Cases of Smallpox

In late 1975, three-year-old Rahima Banu from Bangladesh was the last person in the world to have naturally acquired variola major. She was also the last person in Asia to have active smallpox. She was isolated at home with house guards posted 24 hours a day until she was no longer infectious. A house-to-house vaccination campaign within a 1.5-mile radius of her home began immediately. A member of the Smallpox Eradication Program team visited every house, public meeting area, school, and healer within 5 miles to ensure the illness did not spread. They also offered a reward to anyone who reported a smallpox case.

Ali Maow Maalin was the last person to have naturally acquired smallpox caused by variola minor. Maalin was a hospital cook in Merca, Somalia. On October 12, 1977, he rode with two smallpox patients in a vehicle from the hospital to the local smallpox office. On October 22, he developed a fever. At first healthcare workers diagnosed him with malaria, and then chickenpox. The smallpox eradication staff then correctly diagnosed him with smallpox on October 30. Maalin was isolated and made a full recovery. Maalin died of malaria on July 22, 2013, while working in the polio eradication campaign.

Janet Parker was the last person to die of smallpox. In 1978, Parker was a medical photographer at England's Birmingham University Medical School. She worked one floor above the Medical Microbiology Department where staff and students conducted smallpox research. She became ill on August 11 and developed a rash on August 15 but was not diagnosed with smallpox until 9 days later. She died on September 11, 1978. Her mother, who was providing care for her, developed smallpox on September 7, despite having been vaccinated two weeks earlier. An investigation suggested that Janet Parker had been infected either via an airborne route through the medical school building's duct system or by direct contact while visiting the microbiology corridor.

World Free of Smallpox

Almost two centuries after Jenner hoped that vaccination could annihilate smallpox, the 33 rd World Health Assembly declared the world free of this disease on May 8, 1980. Many people consider smallpox eradication to be the biggest achievement in international public health.

Stocks of Variola Virus

Following the eradication of smallpox, scientists and public health officials determined there was still a need to perform research using the variola virus. They agreed to reduce the number of laboratories holding stocks of variola virus to only four locations. In 1981, the four countries that either served as a WHO collaborating center or were actively working with variola virus were the United States, England, Russia, and South Africa. By 1984, England and South Africa had either destroyed their stocks or transferred them to other approved labs. There are now only two locations that officially store and handle variola virus under WHO supervision: the Centers for Disease Control and Prevention in Atlanta, Georgia, and the State Research Center of Virology and Biotechnology (VECTOR Institute) in Koltsovo, Russia.

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smallpox (variola major and variola minor)

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From the beginning of variolation to present day vaccines, vaccinations has always had opposition groups advocating for the nonpractice of vaccines.

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Monitoring Editor: Alexander Muacevic and John R Adler

Abstract

There have been recent trends of parents in Western countries refusing to vaccinate their children due to numerous reasons and perceived fears. While opposition to vaccines is as old as the vaccines themselves, there has been a recent surge in the opposition to vaccines in general, specifically against the MMR (measles, mumps, and rubella) vaccine, most notably since the rise in prominence of the notorious British ex-physician, Andrew Wakefield, and his works. This has caused multiple measles outbreaks in Western countries where the measles virus was previously considered eliminated. This paper evaluates and reviews the origins of the anti-vaccination movement, the reasons behind the recent strengthening of the movement, role of the internet in the spread of anti-vaccination ideas, and the repercussions in terms of public health and safety.

Keywords: vaccination, mmr vaccine, measles outbreak, virus, anti-vaccine movement

Introduction and background

Vaccines are one of the most important measures of preventative medicine to protect the population from diseases and infections. They have contributed to decreasing rates of common childhood diseases and, in some cases, have even wiped out some diseases that were common in years past, such as smallpox, rinderpest, and have nearly eradicated malaria and polio [ 1]. In fact, according to the World Health Organization's Polio Global Eradication Initiative, the inactivated polio vaccine (IPV) will be used as a backbone for eradicating poliovirus in the next decade. However, there has been a recent rise in anti-vaccination sentiments surrounding beliefs that vaccines cause more harm than benefits to the health of the children who receive them. The premise of the anti-vaccination movement can also be contributed to the demonization of vaccinations by news and entertainment outlets. Voices such as Jenny McCarthy's have proven to be influential, sweeping fear and distrust into parents' minds by parading as "autism experts". Social media and television talk show hosts, such as Oprah Winfrey, played a big role in this miseducation by giving credence to the campaign. This has caused vaccination rates to sustain a surprising drop in some Western countries [ 2]. The decrease in vaccinations has led to recent outbreaks of diseases that were thought to be "eliminated", such as measles. Still, other reasons for the anti-vaccination movement can be due to personal reasons, such as religious or secular views. A drop in immunizations poses a threat to the herd immunity the medical world has worked hard to achieve. Global communities are now more connected than ever, which translates to a higher probability of the transmission of pathogens. The only thing that can protect populations against a rapidly spreading disease is the disease's resistance created by herd immunity when the majority are immune after vaccinations. Given the highly contagious nature of diseases like measles, vaccination rates of 96% to 99% are necessary to preserve herd immunity and prevent future outbreaks [ 3].

Review

Origins of the anti-vaccination movement

Fear of vaccines and myths against them are not a new phenomenon. Opposition to vaccines goes as far back as the 18th century when, for example, Reverend Edmund Massey in England called the vaccines "diabolical operations" in his 1772 sermon, "The Dangerous and Sinful Practice of Inoculation" [ 4]. He decried these vaccines as an attempt to oppose God's punishments upon man for his sins [ 5]. Similar religious opposition was seen in the "New World" even earlier, such as in the writings of Reverend John Williams in Massachusetts, who also cited similar reasons for his opposition to vaccines claiming that they were the devil's work [ 6]. However, opposition against vaccines was not only manifested in theological arguments; many also objected to them for political and legal reasons. After the passage of laws in Britain in the mid-19th century making it mandatory for parents to vaccinate their children, anti-vaccine activists formed the Anti-Vaccination League in London. The league emphasized that its mission was to protect the liberties of the people which were being "invaded" by Parliament and its compulsory vaccination laws [ 7]. Eventually, the pressure exerted by the league and its supporters compelled the British Parliament to pass an act in 1898, which removed penalties for not abiding by vaccination laws and allowed parents who did not believe vaccination was beneficial or safe to not have their children vaccinated [ 8]. Since the rise and spread of the use of vaccines, opposition to vaccines has never completely gone away, vocalized intermittently in different parts of the world due to arguments based in theology, skepticism, and legal obstacles [ 9].

Anti-vaccination propaganda

While pushback against the measles vaccine due to fears of its connection to autism is the most recent example that comes to mind, there have been other instances of outbreaks of previously "extinct" diseases in modern times. One example is the refusal of some British parents to vaccinate their children in the 1970s and 1980s against pertussis in response to the publication of a report in 1974 that credited 36 negative neurological reactions to the whole-cell pertussis vaccine [ 10]. This caused a decrease in the pertussis vaccine uptake in the United Kingdom (UK) from 81% in 1974 to 31% in 1980, eventually resulting in a pertussis outbreak in the UK, putting severe strain and pressure on the National Health System [ 11- 12]. Vaccine uptake levels were elevated to normal levels after the publication of a national reassessment of vaccine efficacy that reaffirmed the vaccine's benefits, as well as financial incentives for general practitioners who achieved the target of vaccine coverage [ 13]. Disease incidence declined dramatically as a result.

The anti-vaccination movement was most strongly rejuvenated in recent years by the publication of a paper in The Lancet by a former British doctor and researcher, Andrew Wakefield, which suggested credence to the debunked-claim of a connection between the measles, mumps, and rubella (MMR) vaccine and development of autism in young children [ 14]. Several studies published later disproved a causal association between the MMR vaccine and autism [ 15- 18]. Wakefield drew severe criticism for his flawed and unethical research methods, which he used to draw his data and conclusions [ 19]. A journalistic investigation also revealed that there was a conflict of interest with regard to Wakefield's publication because he had received funding from litigants against vaccine manufacturers, which he obviously did not disclose to either his co-workers nor medical authorities [ 20]. For all of the aforementioned reasons, The Lancet retracted the study, and its editor declared it "utterly false" [ 21]. As a result, three months later, he was also struck off the UK Medical Registry, barring him from practicing medicine in the UK. The verdict declared that he had "abused his position of trust" and "brought the medical profession into disrepute" in the studies he carried out [ 22].

Repercussions of declining vaccination rates

The damage, however, was already done and the myth was spread to many different parts of the world, especially Western Europe and North America. In the UK, for example, the MMR vaccination rate dropped from 92% in 1996 to 84% in 2002. In 2003, the rate was as low as 61% in some parts of London, far below the rate needed to avoid an epidemic of measles [ 23]. In Ireland, in 1999-2000, the national immunization level had fallen below 80%, and in part of North Dublin, the level was around 60% [ 24]. In the US, the controversy following the publication of the study led to a decline of about 2% in terms of parents obtaining the MMR vaccine for their children in 1999 and 2000. Even after later studies explicitly and thoroughly debunked the alleged MMR-autism link, the drop in vaccination rates persisted [ 25].

As a result, multiple breakouts of measles have occurred throughout different parts of the Western world, infecting dozens of patients and even causing deaths. In the UK in 1998, 56 people contracted measles; in 2006, this number increased to 449 in the first five months of the year, with the first death since 1992 [ 26]. In 2008, measles was declared endemic in the UK for the first time in 14 years [ 27]. In Ireland, an outbreak occurred in 2000 and 1,500 cases and three deaths were reported. The outbreak was reported to have occurred as a direct result of a drop in vaccination rates following the MMR controversy [ 28]. In France, more than 22,000 cases of measles were reported from 2008 - 2011 [ 29]. The United States has not been an exception, with outbreaks occurring most recently in 2008, 2011, and 2013 [ 30- 32].

Perhaps the most infamous example of a measles outbreak in the United States occurred in 2014-2015. The outbreak was believed to originate from the Disneyland Resort in Anaheim, California and resulted in an estimated 125 people contracting the disease [ 33]. It was estimated that MMR vaccination rates among the exposed population in which secondary cases have occurred might be as low as 50% and likely no higher than 86% [ 34]. Physicians in the region were criticized for deviating from the CDC's (Center for Disease Control and Prevention) recommended vaccination schedule and/or discouraging vaccination. As a result, California passed Senate Bill 277, a mandatory vaccination law in June 2015, banning personal and religious exemptions to abstain from vaccinations [ 35].

Technology and its effects on anti-vaccination movement

Access to medical information online has dramatically changed the dynamics of the healthcare industry and patient-physician interactions. Medical knowledge that was previously bound to textbooks and journals, or held primarily by medical professionals, is now accessible to the layman, which has shifted the power from doctors as exclusive managers of a patient's care to the patients themselves [ 36]. This has led to the recent establishment of shared decision-making between patients and healthcare physicians [ 37]. While this is beneficial in some ways, the dissemination of false and misleading information found on the internet can also lead to negative consequences, such as parents not giving consent to having their children vaccinated. When it comes to vaccines, the false information is plentiful and easy to find. An analysis of YouTube videos about immunization found that 32% opposed vaccination and that these had higher ratings and more views than pro-vaccine videos [ 38]. An analysis of MySpace blogs about HPV immunization found that 43% portrayed the immunization in a negative light; these blogs referenced vaccine-critical organizations and cited inaccurate data [ 39]. A similar study of Canadian internet users tracked the sharing of influenza vaccine information on social media networks, such as Facebook, Twitter, YouTube, and Digg. Of the top search results during the study period, 60% promoted anti-vaccination sentiments [ 40]. A study that examined the content of the first 100 anti-vaccination sites found after searching for "vaccination" and "immunization" on Google concluded that 43% of websites were anti-vaccination (including all of the first 10) [ 41].

Online anti-vaccination authors use numerous tactics to further their agendas. These tactics include, but are not limited to, skewing science, shifting hypotheses, censoring opposition, attacking critics, claiming to be "pro-safe vaccines", and not "anti-vaccine", claiming that vaccines are toxic or unnatural, and more [ 42]. Not only are these tactics deceitful and dishonest, they are also effective on many parents. A study that evaluated how effectively users assessed the accuracy of medical information about vaccines online concluded that 59% of student participants thought retrieved sites were entirely accurate; however, out of the 40 sites they were given, only 18 were actually accurate, while 22 were inaccurate. These sites were not evidence-based and argued vaccines were inherently dangerous without any merit-based argument. More than half of participants (53%) left the exercise with significant misconceptions about vaccines [ 43]. Research has also shown that viewing an anti-vaccine website for merely 5 - 10 minutes increased perceptions of vaccination risks and decreased perceptions of the risks of vaccine omission, compared to visiting a control site [ 44]. The study also found that the anti-vaccine sentiments obtained from viewing the websites still persisted five months later, causing the children of these parents to obtain fewer vaccinations than recommended [ 45]. The role of the online access to false anti-vaccination information just cannot be understated in examining the rise and spread of the anti-vaccination movement.

Ethical and legal issues regarding vaccination

Opposition to the MMR vaccine among parents leads to an ethical dilemma that can be analyzed using both medical ethics and moral principles. Medical ethics call for health professionals to abide by a code of bioethics upholding autonomy, non-maleficence, beneficence, and justice. The most relevant in mandating vaccinations are autonomy and non-maleficence [ 46]. Patients are entitled to the right to refuse vaccination using "our children, our choice" based on their autonomy, while health care providers are morally obligated to treat everyone with non-maleficence and avoiding harm to society at all costs.

At the individual level, religion is a common reason to refuse vaccination. The MMR vaccine specifically has been the cause of instigating debate among the Hindu, Protestant, Orthodox Jewish, and Jehovah's Witness communities. Specific religious views on vaccines in general, however, are not normally the cause for debate but instead the components of the MMR vaccine [ 47]. The MMR vaccine, combined with the rubella vaccine, was originally derived from the cells of aborted fetal tissue. Hindu, Protestant, Muslim, and Jewish communities are generally opposed to abortion for moral reasons based on religious teachings; thus, individuals from these beliefs may cite religious reasons for filing vaccine exemptions. Further, the MMR vaccine contains porcine gelatin as a stabilizer, a means for ensuring effective storage. The porcine ingredients are unlike gelatins used for oral consumption and purified down to small peptides, commonly used in medicine capsules as well [ 48]. As there is a wide range of practice preferences in every religion, some individuals belonging to religions, such as Judaism, Islam, and Hinduism (to name a few), may be opposed to injecting a porcine product into their body along with the vaccine [ 47]. Further, other religious views, such as the ones held by Dutch-Protestant Christian congregations, consider vaccinations "inappropriate meddling in the work of God". These groups, therefore, believe that we should not change the predestined fate of someone who becomes ill [ 49].

While exercising autonomy and refusing vaccination is valid for sensitive personal issues, it will cause more harm than good if a certain percentage of the population does not get vaccines causing the immunization rate to fall below the herd immunity threshold. This threshold varies in every disease. The development of vaccines is considered one of the greatest strides made in medicine due to the enormous benefits to an entire population. From an ethics perspective, achieving herd immunity and minimizing the amount of "freeloaders" is in the best interest of society as a whole [ 48- 49].

Further, studies liken the decision to object to vaccinations to military service drafts. For the conscientious objectors, military duty and receiving a vaccine hold the same costs: liberty, personal risk, and utility in terms of time [ 41]. Naturally, the costs of military duty are more taxing and demand more from an individual than receiving a vaccine. In terms of herd immunity and depending on the severity of impending diseases, these costs are ones that they should incur for the benefit of themselves as well as society.

At the forefront of the legal complications lies the state-regulated vaccinations for all children attending school. Anti-vaccination proponents argue that this is an infringement upon autonomy; however, public health policymakers justify their actions using rule utilitarianism. Rule utilitarianism is the ideology that a rule for society should be established that has the best outcome for the greatest amount of people in the society. In addition to this, John Stuart Mill's essay, "On Liberty", explains the Harm Principle that is often used to justify mandated infectious disease control methods, including vaccines [ 50]. The Harm Principle justifies interfering with autonomy and individual liberties, against their will, if it is done so as to prevent harm to others. An example of this was seen in California in 2014-2015 after an outbreak of measles led to the passing of Senate Bill 277 calling for state-mandated vaccinations for everyone - no personal exemptions. The root of the problem, however, was most likely to be contributed to Wakefield's fraudulent findings striking the fear of a vaccination-autism link in parents, which led to an all-time low rate of people receiving the MMR vaccine. The hoax has been called the most damaging medical hoax in 100 years after bringing about outbreaks of diseases otherwise eradicated [ 8- 9, 11].

In the times that we have achieved herd immunity, there remain two questions then. Can legal exemptions still be justified? And should these exemptions be limited to religious reasons or should they include secular reasoning as well [ 21, 25]? Most scientists and medical experts suggest that exemptions should only even be considered if society is well within the limits for herd immunity. As for the religious versus secular debate, it is difficult to ignore secular objections as most of them are rooted in spiritual or holistic personal views [ 6, 47]. Since herd immunity is cumulative, the ability to waive immunizations is concluded to be difficult but not impossible. If the waivers are given to a small number of individuals who sincerely need them rather than ones who are inconvenienced by them, waivers may be ethically and legally sound.

Conclusions

The rise of anti-vaccination movements in parts of the Western world poses a dire threat to people's health and the collective herd immunity. People of all ages have fallen victim to recent outbreaks of measles, one of the most notable "eliminated" diseases that made a comeback as a direct consequence of not reaching the immunization threshold for MMR vaccines. These outbreaks not only put a strain on national healthcare systems but also cause fatal casualties. Therefore, it is of the utmost importance that all stakeholders in the medical world - physicians, researchers, educators, and governments - unite to curb the influence of the anti-vaccination movement targeting parents. Research has shown that even parents favorable to vaccination can be confused by the ongoing debate, leading them to question their choices. Many parents lack basic knowledge of how vaccines work, as well as access to accurate information explaining the importance of the process. Furthermore, those with the greatest need for knowledge about vaccination seem most vulnerable to this information. Further, we must effectively combat the wrongful demonization of vaccinations through social media and news media platforms. A qualitative study that explored how parents respond to competing media messages about vaccine safety concluded that personal experiences, value systems, and level of trust in health professionals are essential to parental decision making about immunization. Therefore, to combat the anti-vaccination movement, there must be a strong emphasis on helping parents develop trust in health professionals and relevant authorities, educating them on the facts and figures, debunking the myths peddled by the anti-vaccination movements, and even introducing legislation that promotes vaccination, if not mandating it.

Acknowledgments

We would like to thank Dr. Alice Anne Brunn, Ph.D., Associate Professor of Psychiatry and Ethics, and Chairman of Behavioral Sciences and Ethics Department, as well as Dr. Xenia Sotiriou, Ph.D., Assistant Professor of Behavior Science and Ethics at St. Matthew's University School of Medicine.

Notes

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

Footnotes

The authors have declared that no competing interests exist.

References

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The Anti-vaccination Movement: A Regression in Modern Medicine

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There have been recent trends of parents in Western countries refusing to vaccinate their children due to numerous reasons and perceived fears. While opposition to vaccines is as old as the vaccines themselves, there has been a recent surge in the opposition ...