Since their earliest and most rudimentary introduction in the late 18th century, vaccines have fundamentally changed the way modern medicine is practiced and have eliminated or managed the incidence of some of the most devastating human diseases. Humankind has benefited from vaccines for more than two centuries, but the path to discovering effective vaccines was long and difficult. The work required a number of brave research pioneers and clinicians.

In this spirit of giving thanks this holiday season, we will explore the history of vaccines, beginning with Edward Jenner’s creation of the first modern vaccine in the 1790s.The history of vaccines begins with the story of smallpox. Smallpox was a disfiguring, often fatal infectious disease that plagued humanity for centuries.

The earliest evidence of skin lesions resembling those of smallpox is found on the faces of mummies from the 18th and 20th Egyptian Dynasties (1570-1085 BC) but it is believed smallpox first appeared around 10,000 BC at the time of the first agricultural settlements in northeastern Africa. Smallpox was introduced to Europe sometime between the fifth and sixth centuries and was later brought to the New World by Spanish and Portuguese conquistadors, where it decimated the native populations.

Smallpox spread by exposure to the Variola virus and infection typically began like a common cold. The victim would experience fever, lethargy, muscle pain, and headaches. After a few days, a rash would appear on the face and skin, with sores forming inside the mouth, throat, and nose. Fluid-filled pustules would develop and expand, covering large areas of skin. By the third week, if the victim survived, scabs formed and separated from the skin.Edward Jenner by James NorthcoteIn 18th century Europe, smallpox was widespread, claiming an estimated 400,000 lives each year, including five reigning monarchs. Researchers estimate that between 20% and 60% of all infected persons, and 80% of infected children, died from the disease. Survivors often had some degree of permanent scarring with a number of individuals losing their lips, nose, or ear tissue. Smallpox also caused corneal scarring and was responsible for one-third of all blindness.

Early scholars recognized that survivors of smallpox became immune to the disease. As early as 1000 CE, Chinese healers began inoculating patients by scratching matter from a smallpox sore and blowing the powdered material up the nose of a healthy patient.

Inoculation, the earliest form of vaccination and in this case referred to as variolation (to protect against the Variola virus), was introduced to Europe and North America in the 18th century. During this time, the procedure was commonly carried out by rubbing powdered smallpox scabs or fluid from pustules into superficial scratches made in a healthy individual’s skin. The patient would develop pustules identical to those caused by smallpox, but usually resulting in a less-severe disease. Variolation was not without risks however, as variolated persons could suffer from smallpox itself or become infected by another disease unintentionally transferred by the procedure such as syphilis.

In 1757, one of the thousands of children treated by variolation was eight-year-old Edward Jenner. As a boy, Jenner had a strong interest in the sciences and nature, which led him to the study of medicine, surgery, and even zoology. He eventually settled in rural England, outside of London, and began to practice medicine.

As part of his practice, Jenner performed variolation on his patients. In this rural setting he learned that dairymaids and other individuals who contracted cowpox, a minor infection marked by a few pustules, would not later contract smallpox.He also observed that he could not successfully inoculate such persons with smallpox. Noting this connection, Jenner concluded that cowpox not only protected against smallpox but could also be transmitted from one person to another as a deliberate mechanism of protection.

In May 1796, Jenner encountered a young dairymaid, Sarah Nelms, who had fresh cowpox lesions. Using material from her lesions, Jenner inoculated James Phipps. The child developed a mild fever and lost his appetite, but after ten days he was in good spirits. In July, Jenner inoculated the boy again, this time with fresh smallpox. No disease developed and Jenner concluded that protection was complete. Today we know that following infection by the cowpox virus, the infected person gained the ability to recognize the similar smallpox virus from its similarly shaped antigens and was able to defend against it more effectively.Jenner continued to inoculate children with cowpox with similar results. He named this procedure variolae vaccinae (“smallpox of the cow”) which has been Anglicized and shortened today to “vaccination.”

Although he did not know it at the time, Jenner had laid the groundwork for what would become live, attenuated vaccines. Today, some of the most common vaccines including measles, mumps, yellow fever, and others, use a similar approach. Viruses may be attenuated by passing the virus through a foreign host, including other live animals or embryonated eggs. The offspring of each virus gradually evolve and become less able to create a strong infection in humans. These weaker, less virulent viruses can be more easily fought off by the immune system, leading to long-term protection.British satirist James Gillray 1802 cartoon showing cowpox vaccine being administered to frightened young women.Edward Jenner was not the first to try to conquer smallpox and the problem certainly did not end with him, but his work represented the first scientific attempt to control an infectious disease by the deliberate use of vaccination. In coming years, the practice of smallpox vaccination spread across the globe and ultimately saved millions of lives. In 1980, the World Health Assembly announced that the world was free of smallpox. Jenner’s work captured the imagination of scientists and set the stage for future exploration, bringing the world into the age of modern vaccine research.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 is using its eVLP Platform technology to develop a next generation of safe and effective synthetic vaccines. Learn more >>