Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple". The term "smallpox" was first used in Europe in the 15th century to distinguish variola from the "great pox" (syphilis). The last naturally occurring case of smallpox (Variola minor) was diagnosed on 26 October 1977.

Smallpox localizes in small blood vessels of the skin and in the mouth and throat. In the skin it results in a characteristic maculopapular rash and, later, raised fluid-filled blisters. V. major produces a more serious disease and has an overall mortality rate of 30–35%. V. minor causes a milder form of disease (also known as alastrim, cottonpox, milkpox, whitepox, and Cuban itch) which kills about 1% of its victims. Long-term complications of V. major infection include characteristic scars, commonly on the face, which occur in 65–85% of survivors.Blindness resulting from corneal ulceration and scarring, and limb deformities due to arthritis and osteomyelitis are less common complications, seen in about 2–5% of cases.

Edward Anthony Jenner (17 May 1749 – 26 January 1823) was an English physician and scientist from Berkeley, Gloucestershire, who was the pioneer of smallpox vaccine. He is often called "the father of immunology", and his work is said to have "saved more lives than the work of any other man".

Edward Jenner was born on 17 May 1749 (6 May Old Style) in Berkeley, as the eighth of nine children. His father was the vicar of Berkeley, so Jenner received a strong basic education. Jenner trained from the age of 13 for eight years in Chipping Sodbury, South Gloucestershire, as an apprentice to Daniel Ludlow, a surgeon . In 1770 Jenner became apprenticed in surgery and anatomy under surgeon John Hunter and others at St George's Hospital.

William Osler records that Hunter gave Jenner William Harvey's advice, very famous in medical circles (and characteristic of the Age of Enlightenment), "Don't think; try." Hunter remained in correspondence with Jenner over natural history and proposed him for the Royal Society. Returning to his native countryside by 1773, Jenner became a successful family doctor and surgeon, practicing on dedicated premises at Berkeley.