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Edward Jenner and the History of Smallpox and

Vaccination

Stefan Riedel

To cite this article: Stefan Riedel (2005) Edward Jenner and the History of Smallpox
and Vaccination, Baylor University Medical Center Proceedings, 18:1, 21-25, DOI:
10.1080/08998280.2005.11928028

To link to this article: https://doi.org/10.1080/08998280.2005.11928028

Published online: 11 Dec 2017.

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 Edward Jenner and the history of smallpox
and vaccination
STEFAN RIEDEL, MD, PHD

In science credit goes to the man who convinces the world, not the man the Middle Ages. The disease greatly affected the development of
to whom the idea first occurs. —FRANCIS GALTON 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
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F
or many centuries, smallpox devastated mankind. In people (6). The Arab expansion, the Crusades, and the discovery
modern times we do not have to worry about it thanks of the West Indies all contributed to the spread of the disease.
to the remarkable work of Edward Jenner and later de- Unknown in the New World, smallpox was introduced by the
velopments from his endeavors. With the rapid pace of vaccine Spanish and Portuguese conquistadors. The disease decimated the
development in recent decades, the historic local population and was instrumental in
origins of immunization are often forgot- the fall of the empires of the Aztecs and the
ten. Unfortunately, since the attack on Incas. Similarly, on the eastern coast of
the World Trade Center on September 11, North America, the disease was introduced
2001, the threat of biological warfare and by the early settlers and led to a decline
bioterrorism has reemerged. Smallpox has in the native population. The devastating
been identified as a possible agent of bioter- effects of smallpox also gave rise to one of
rorism (1). It seems prudent to review the the first examples of biological warfare (1,
history of a disease known to few people in 7). During the French-Indian War (1754–
the 21st century. 1767), Sir Jeffrey Amherst, the commander
Edward Jenner (Figure 1) is well known of the British forces in North America,
around the world for his innovative contri- suggested the deliberate use of smallpox to
bution to immunization and the ultimate diminish the American Indian population
eradication of smallpox (2). Jenner’s work hostile to the British. Another factor con-
is widely regarded as the foundation of im- tributing to smallpox in the Americas was
munology—despite the fact that he was the slave trade because many slaves came
neither the first to suggest that infection from regions in Africa where smallpox was
with cowpox conferred specific immunity endemic.
to smallpox nor the first to attempt cowpox Smallpox affected all levels of society. In
inoculation for this purpose. the 18th century in Europe, 400,000 people
Figure 1. Edward Jenner (1749–1823). Photo cour- died annually of smallpox, and one third of
SMALLPOX: THE ORIGIN OF A DISEASE tesy of the National Library of Medicine. the survivors went blind (4). The symptoms
The origin of smallpox as a natural dis- of smallpox, or the “speckled monster” as
ease is lost in prehistory. It is believed to have appeared around it was known in 18th-century England, appeared suddenly and
10,000 BC, at the time of the first agricultural settlements in the sequelae were devastating. The case-fatality rate varied from
northeastern Africa (3, 4). It seems plausible that it spread from 20% to 60% and left most survivors with disfiguring scars. The
there to India by means of ancient Egyptian merchants. The case-fatality rate in infants was even higher, approaching 80% in
earliest evidence of skin lesions resembling those of smallpox is London and 98% in Berlin during the late 1800s.
found on faces of mummies from the time of the 18th and 20th The word variola was commonly used for smallpox and had
Egyptian Dynasties (1570–1085 BC). The mummified head of the been introduced by Bishop Marius of Avenches (near Lausanne,
Egyptian pharaoh Ramses V (died 1156 BC) bears evidence of
the disease (5). At the same time, smallpox has been reported in
From the Department of Pathology, Baylor University Medical Center, Dallas,
ancient Asian cultures: smallpox was described as early as 1122 BC Texas.
in China and is mentioned in ancient Sanskrit texts of India. Corresponding author: Stefan Riedel, MD, PhD, Department of Pathology, Baylor
Smallpox was introduced to Europe sometime between the University Medical Center, 3500 Gaston Avenue, Dallas, Texas 75246 (e-mail:
fifth and seventh centuries and was frequently epidemic during docriedel@aol.com).

BUMC PROCEEDINGS 2005;18:21–25 21

 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 Eng-
land 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 medi-
eval 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 be-
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fore 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 Figure 2. Lady Mary Wortley Montague (1689–1762). Photo
nonimmune individuals. The inoculator usually used a lancet wet courtesy of the National Library of Medicine.
with fresh matter taken from a ripe pustule of some person who
suffered from smallpox. The material was then subcutaneously Sublime Porte. A few weeks after their arrival in Istanbul, Lady
introduced on the arms or legs of the nonimmune person. The Montague wrote to her friend about the method of variolation
terms inoculation and variolation were often used interchangeably. used at the Ottoman court. Lady Montague was so determined
The practice of inoculation seems to have arisen independently to prevent the ravages of smallpox that she ordered the embassy
when people in several countries were faced with the threat of surgeon, Charles Maitland, to inoculate her 5-year-old son. The
an epidemic. However, inoculation was not without its atten- inoculation procedure was performed in March 1718. Upon their
dant risks. There were concerns that recipients might develop return to London in April 1721, Lady Montague had Charles
disseminated smallpox and spread it to others. Transmission of Maitland inoculate her 4-year-old daughter in the presence of
other diseases, such as syphilis, via the bloodborne route was physicians of the royal court.
also of concern. After these first professional variolation procedures, word of
Inoculation, hereafter referred to as variolation, was likely the practice spread to several members of the royal family (11).
practiced in Africa, India, and China long before the 18th Charles Maitland was then granted the royal license to perform a
century, when it was introduced to Europe (9). In 1670, Circas- trial of variolation on six prisoners in Newgate on August 9, 1721.
sian traders introduced variolation to the Turkish “Ottoman” The prisoners were granted the king’s favor if they submitted to
Empire. Women from the Caucasus, who were in great demand this experiment. Several court physicians, members of the Royal
in the Turkish sultan’s harem in Istanbul because of their legend- Society, and members of the College of Physicians observed the
ary beauty, were inoculated as children in parts of their bodies trial. All prisoners survived the experiment, and those exposed to
where scars would not be seen. These women must also have smallpox later proved to be immune. In the months following this
brought the practice of variolation to the court of the Sublime very first trial, Maitland repeated the experiment on orphaned
Porte (4, 10). children, again with success. Finally, on April 17, 1722, Maitland
Variolation came to Europe at the beginning of the 18th successfully treated the two daughters of the Princess of Wales.
century with the arrival of travelers from Istanbul. In 1714, the Not surprisingly, the procedure gained general acceptance after
Royal Society of London received a letter from Emanuel Timoni this last success.
describing the technique of variolation, which he had witnessed
in Istanbul. A similar letter was sent by Giacomo Pilarino in 1716. THE SPREAD OF VARIOLATION
These reports described the practice of subcutaneous inocula- In Europe, where the medical profession was relatively or-
tion; however, they did not change the ways of the conservative ganized, the new methods of variolation became known quickly
English physicians. among physicians. Since there was also a demand for protection
It was the continued advocacy of the English aristocrat Lady against smallpox, physicians soon began the variolation procedure
Mary Wortley Montague (Figure 2) that was responsible for on a massive scale. Although 2% to 3% of variolated persons
the introduction of variolation in England (10). In 1715, Lady died from the disease, became the source of another epidemic, or
Montague suffered from an episode of smallpox, which severely suffered from diseases (e.g., tuberculosis and syphilis) transmit-
disfigured her beautiful face. Her 20-year-old brother died of ted by the procedure itself, variolation rapidly gained popularity
the illness 18 months later. In 1717, Lady Montague’s husband, among both aristocratic and common people in Europe. The case-
Edward Wortley Montague, was appointed ambassador to the fatality rate associated with variolation was 10 times lower than

22 BAYLOR UNIVERSITY MEDICAL CENTER PROCEEDINGS VOLUME 18, NUMBER 1

 that associated with naturally occurring smallpox. In the 1750s older brother. During his early school years, Edward developed a
more European princes died of smallpox, giving further impetus strong interest in science and nature that continued throughout
for the use of variolation (3). Among those variolated were Em- his life. At age 13 he was apprenticed to a country surgeon and
press Marie-Therese of Austria and her children and grandchil- apothecary in Sodbury, near Bristol (16). The record shows that
dren, Frederick II of Prussia, King Louis XVI of France and his it was there that Jenner heard a dairymaid say, “I shall never
children, and Catherine II of Russia and her son. King Frederick have smallpox for I have had cowpox. I shall never have an ugly
II of Prussia also inoculated all his soldiers. In fact, variolation pockmarked face.” It fact, it was a common belief that dairymaids
was widely practiced in Europe until Jenner’s discovery. were in some way protected from smallpox.
The regular practice of variolation reached the New World In 1764, Jenner began his apprenticeship with George Har-
in 1721 (9). Under the guidance of the Rev. Cotton Mather wicke. During these years, he acquired a sound knowledge of
(1663–1728) and Dr. Zabdiel Boylston (1679–1766), variola- surgical and medical practice (10). Upon completion of this ap-
tion became quite popular in the colonies. Mather, a graduate of prenticeship at the age of 21, Jenner went to London and became
Harvard College, was always very interested in science and medi- a student of John Hunter, who was on the staff of St. George’s
cine. When a ship from the West Indies carried persons sick with Hospital in London. Hunter was not only one of the most famous
smallpox into Boston in 1721, an epidemic broke out in Boston surgeons in England, but he was also a well-respected biologist,
and other parts of Massachusetts. Mather wrote a cautious letter anatomist, and experimental scientist. The firm friendship that
recommending immediate variolation. However, he persuaded grew between Hunter and Jenner lasted until Hunter’s death in
only Dr. Boylston. With Mather’s support, Boylston immediately 1793. Although Jenner already had a great interest in natural
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started a variolation program and continued to inoculate many science, the experience during the 2 years with Hunter only
volunteers, despite many adversaries in both the public and the increased his activities and curiosity. Jenner was so interested in
medical community in Boston. As the disease spread, so did the natural science that he helped classify many species that Cap-
controversy around Mather and Boylston (12). At the height of tain Cook brought back from his first voyage. In 1772, however,
the epidemic, a bomb was thrown into Mather’s house. Jenner declined Cook’s invitation to take part in the second
To make their point, Mather and Boylston used a statisti- voyage (4).
cal approach to compare the mortality rate of natural smallpox Jenner occupied himself with many matters. He studied geol-
infection with that contracted by variolation. During the great ogy and carried out experiments on human blood (17). In 1784,
epidemic of 1721, approximately half of Boston’s 12,000 citizens after public demonstrations of hot air and hydrogen balloons by
contracted smallpox. The fatality rate for the naturally contracted Joseph M. Montgolfier in France during the preceding year, Jen-
disease was 14%, whereas Boylston and Mather reported a mortal- ner built and twice launched his own hydrogen balloon. It flew
ity rate of only 2% among variolated individuals (12). This may 12 miles. Following Hunter’s suggestions, Jenner conducted a
have been the first time that comparative analysis was used to particular study of the cuckoo. The final version of Jenner’s paper
evaluate a medical procedure. was published in 1788 and included the original observation that
During the decades following the 1721 epidemic in Boston, it is the cuckoo hatchling that evicts the eggs and chicks of the
variolation became more widespread in the colonies of New Eng- foster parents from the nest (17, 18). For this remarkable work,
land. In 1766, American soldiers under George Washington were Jenner was elected a fellow of the Royal Society. However, many
unable to take Quebec from the British troops, apparently because naturalists in England dismissed his work as pure nonsense. For
of a smallpox epidemic that significantly reduced the number of more than a century, antivaccinationists used the supposed defects
healthy troops (13). The British soldiers were all variolated. By of the cuckoo study to cast doubt on Jenner’s other work. Jen-
1777, Washington had learned his lesson: all his soldiers were ner was finally vindicated in 1921 when photography confirmed
variolated before beginning new military operations (14, 15). The his observation (19). At any rate, it is apparent that Jenner had
success of variolation in the New World was not without effect a lifelong interest in natural sciences. His last work, published
on Europe. In fact, the rapid adoption of variolation in Europe posthumously, was on the migration of birds.
can be directly traced to the efforts of Cotton Mather during In addition to his training and experience in biology, Jenner
the Boston smallpox epidemic in 1721. Although many British made great progress in clinical surgery while studying with John
physicians remained skeptical even after Mather’s success, the Hunter in London. Jenner devised an improved method for pre-
data he had published were eventually influential. Variolation paring a medicine known as tartar emetic (potassium antimony
was subsequently adopted in England and spread from there tartrate). In 1773, at the end of 2 years with John Hunter, Jenner
throughout Western Europe. returned to Berkeley to practice medicine. There he enjoyed
In 1757, an 8-year-old boy was inoculated with smallpox in substantial success, for he was capable, skillful, and popular. In
Gloucester (4); he was one of thousands of children inoculated addition to the practice of medicine, he joined two local medical
that year in England. The procedure was effective, as the boy groups for the promotion of medical knowledge and continued to
developed a mild case of smallpox and was subsequently immune write occasional medical papers (4, 18). He also played the violin
to the disease. His name was Edward Jenner. in a musical club and wrote light verse and poetry. As a natural
scientist, he continued to make many observations on birds and
EDWARD JENNER the hibernation of hedgehogs and collected many specimens for
Edward Jenner was born on May 17, 1749, in Berkeley, John Hunter in London.
Gloucestershire, the son of the Rev. Stephen Jenner, vicar of While Jenner’s interest in the protective effects of cowpox
Berkeley. Edward was orphaned at age 5 and went to live with his began during his apprenticeship with George Harwicke, it was

JANUARY 2005 EDWARD JENNER AND THE HISTORY OF SMALLPOX AND VACCINATION 23
 1796 before he made the first step in
the long process whereby smallpox,
the scourge of mankind, would be
totally eradicated. For many years,
he had heard the tales that dairy-
maids were protected from small-
pox naturally after having suffered
from cowpox. Pondering this, Jen-
ner concluded that cowpox not only
protected against smallpox but also
could be transmitted from one person
to another as a deliberate mechanism
of protection. In May 1796, Edward
Jenner found a young dairymaid,
Sarah Nelms, who had fresh cowpox
lesions on her hands and arms (Figure Figure 4. The Temple of Vaccinia. Photo courtesy of the Jenner Museum, Berkeley,
3). On May 14, 1796, using matter Gloucestershire, England.
from Nelms’ lesions, he inoculated an
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8-year-old boy, James Phipps. Subse- Although sometimes embarrassed by a lack of supply, Jenner
Figure 3. The hand of Sarah
quently, the boy developed mild fever sent vaccine to his medical acquaintances and to anyone else
Nelms. Photo courtesy of the and discomfort in the axillae. Nine who requested it. After introducing cowpox inoculation in their
National Library of Medicine. days after the procedure he felt cold own districts, many recipients passed the vaccine on to others.
and had lost his appetite, but on the Dr. John Haygarth (of Bath, Somerset) received the vaccine
next day he was much better. In July 1796, Jenner inoculated the from Edward Jenner in 1800 and sent some of the material to
boy again, this time with matter from a fresh smallpox lesion. Benjamin Waterhouse, professor of physics at Harvard University.
No disease developed, and Jenner concluded that protection Waterhouse introduced vaccination in New England and then
was complete (10). persuaded Thomas Jefferson to try it in Virginia. Waterhouse
In 1797, Jenner sent a short communication to the Royal received great support from Jefferson, who appointed him vac-
Society describing his experiment and observations. However, cine agent in the National Vaccine Institute, an organization set
the paper was rejected. Then in 1798, having added a few more up to implement a national vaccination program in the United
cases to his initial experiment, Jenner privately published a small States (20).
booklet entitled An Inquiry into the Causes and Effects of the Vario- Although he received worldwide recognition and many
lae Vaccinae, a disease discovered in some of the western counties of honors, Jenner made no attempt to enrich himself through his
England, particularly Gloucestershire and Known by the Name of discovery. He actually devoted so much time to the cause of vac-
Cow Pox (18, 10). The Latin word for cow is vacca, and cowpox cination that his private practice and his personal affairs suffered
is vaccinia; Jenner decided to call this new procedure vaccination. severely. The extraordinary value of vaccination was publicly
The 1798 publication had three parts. In the first part Jenner acknowledged in England, when in 1802 the British Parliament
presented his view regarding the origin of cowpox as a disease of granted Edward Jenner the sum of £10,000. Five years later the
horses transmitted to cows. The theory was discredited during Parliament awarded him £20,000 more. However, he not only
Jenner’s lifetime. He then presented the hypothesis that infection received honors but also found himself subjected to attacks and
with cowpox protects against subsequent infection with smallpox. ridicule. Despite all this, he continued his activities on behalf of
The second part contained the critical observations relevant to the vaccination program. Gradually, vaccination replaced vari-
testing the hypothesis. The third part was a lengthy discussion, olation, which became prohibited in England in 1840.
in part polemical, of the findings and a variety of issues related to Jenner married in 1788 and fathered four children. The family
smallpox. The publication of the Inquiry was met with a mixed lived in the Chantry House, which became the Jenner Museum
reaction in the medical community. in 1985. Jenner built a one-room hut in the garden, which he
Jenner went to London in search of volunteers for vaccina- called the “Temple of Vaccinia” (Figure 4), where he vaccinated
tion. However, after 3 months he had found none. In London, the poor for free (10, 17). After a decade of being honored and
vaccination became popular through the activities of others, reviled in more or less equal measure, he gradually withdrew from
particularly the surgeon Henry Cline, to whom Jenner had public life and returned to the practice of country medicine in
given some of the inoculant (4). Later in 1799, Drs. George Berkeley. In 1810, his oldest son, Edward, died of tuberculosis. His
Pearson and William Woodville began to support vaccination sister Mary died the same year and his sister Anne 2 years later.
among their patients. Jenner conducted a nationwide survey in In 1815, his wife, Catherine, died of tuberculosis (17). Sorrows
search of proof of resistance to smallpox or to variolation among crowded in on him, and he withdrew even further from public
persons who had cowpox. The results of this survey confirmed his life. In 1820, Jenner had a stroke from which he recovered. On
theory. Despite errors, many controversies, and chicanery, the use January 23, 1823, he visited his last patient, a dying friend. The
of vaccination spread rapidly in England, and by the year 1800, next morning Jenner failed to appear for breakfast; later that day
it had also reached most European countries (10). he was found in his study. He had had a massive stroke. Edward

24 BAYLOR UNIVERSITY MEDICAL CENTER PROCEEDINGS VOLUME 18, NUMBER 1

 guardianship of the World Health Organization and finally suc-
ceeded in the eradication of smallpox in 1977. On May 8, 1980,
the World Health Assembly announced that the world was free of
smallpox and recommended that all countries cease vaccination:
“The world and all its people have won freedom from smallpox,
which was the most devastating disease sweeping in epidemic
form through many countries since earliest times, leaving death,
blindness and disfigurement in its wake” (22).
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 eradi-
cation of smallpox: this is Edward Jenner’s ultimate vindication
and memorial.

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JANUARY 2005 EDWARD JENNER AND THE HISTORY OF SMALLPOX AND VACCINATION 25