She defied convention most memorably with her pioneering of a smallpox inoculation, a course of action unparalleled in medical advance up to that point. Lady Mary's own brother had died of smallpox and her own famous beauty had been marred by a bout with the disease in 1715.
In 1717, she went to live in Turkey with her husband, the British ambassador to that country, and stayed for two years. In the Ottoman Empire, she visited the women in their segregated zenanas, learning Turkish, making friends and learning about Turkish customs. There she witnessed the practice of inoculation against smallpox—variolation—which she called engrafting, and wrote home about it. Variolation used live smallpox virus in the liquid taken from a smallpox blister in a mild case of the disease and carried in a nutshell. Lady Mary was eager to spare her children, and had her son inoculated while in Turkey. On her return to London, she enthusiastically promoted the procedure, but encountered a great deal of resistance from the medical establishment, because it was an "Oriental" process.
In later years, Edward Jenner, who was 13 years old when Lady Mary died, developed the much safer technique of vaccination using cowpox instead of smallpox. As vaccination gained acceptance, variolation gradually fell out of favour.