Many of the earliest isolated pure compounds with biological activity were alkaloids. This was due to the ease of isolation. The nitrogen generally makes the compound basic and the compound exists in the plant as a salt. Thus, alkaloids are often extracted with water or mild acid and then recovered as crystalline material by treatment with base.

Prior to approximately 300 years ago, malaria was the scourge of Europe, likely having been introduced through the Middle East. Malaria is caused by protozoa of the genus Plasmodium, contained as spores in the gut of the Anopheles mosquitos, which then spreads the spores to humans when it bites. As the Spanish and Portugese explorers began to colonize South America, they discovered a cure for malaria known to the native Indians. This was the bark of the Cinchona trees. The use of Cinchona bark to treat malaria was first reported in Europe in 1633, and the first bark reached Rome about 12 years later. Teas made from the bark cured people suffering from malaria, one of the major scourges in Europe at the time, and the bark became known as Jesuit's bark. Because of the philosophical differences between Protestants and Catholics, many Protestants refused to be treated with the bark. One of the most prominent Protestants of the time, Oliver Cromwell, reportedly died of malaria because of this stubbornness.