William Watson’s use of controlled clinical experiments in 1767

Sir William Watson (1717–1787) began his scientific career as an apothecary and gained distinction as a botanist. He was elected to the Royal Society in 1741 and appointed a founding trustee of the British Museum. From about 1744, Watson experimented with electricity, becoming a collaborator and ally of Benjamin Franklin. In 1757, he resigned from the Apothecaries Society to pursue a career in medicine. In 1762, Watson was appointed physician to the Hospital for the Maintenance and Education of Exposed and Deserted Children, universally known as the Foundling Hospital. This had been established in 1739 to provide a home for some of London’s abandoned children, and Watson’s practice was devoted entirely to the care and treatment of children accepted into this charitable establishment. At the time, the leading cause of death among children in London was smallpox. The infection was endemic and killed about one in four children born in the city. When the Foundling Hospital was opened, the board of governors recognised that because large numbers of children were housed in dormitory rooms, they were at high risk for contracting the disease. To protect their charges, the governors ordered that all children who were not already immune to smallpox be inoculated. Introduced in 1721, 75 years before Jenner’s studies of vaccination – inoculation was the practice of infecting a patient with a tiny amount of fluid from a smallpox pustule placed in a small incision or puncture wound, usually on the upper arm. Quantitative studies reported by James Jurin and by Zabdiel Boylston had established that mortality among inoculated persons was about one in 50, whereas mortality among patients with naturally acquired smallpox was about one in six. By 1765, refinements in the technique of injecting the virus and complicated formulas for the pretreatment of recipients had been associated with a reduction in mortality to less than one in 500. Although inoculation was widely used and relatively safe, there were a number of controversies about specific aspects of the practice. Watson had already satisfied himself that when the eruption appeared, allowing the inoculated children to play freely on the hospital grounds was preferable to keeping them in bed. Now he decided to study two other questions: What was the best source of the inoculum? Was mercury, then a popular component of the pretreatment regimen, beneficial? Most doctors preparing patients for inoculation used a combination of a meatless diet and purgatives to expel matter from the stomach and bowels. Many also prescribed antimony and mercury, a mixture first suggested by Hermann Boerhaave as an antidote to the ‘variolous poison’ that was thought to cause smallpox. Watson doubted that the poisonous mercury was beneficial, but since most fashionable physicians used it, he needed to have convincing evidence of its lack of efficacy before he rejected the substance. There was also no consensus on the best source of the inoculum. Some physicians used a very early lesion, some a mature pock, and others a late, almost resolved lesion as the source of the inoculum.