A drug directed against malaria. The original antimalarial agent was quinine which took its name from the Peruvian Indian word "kina" meaning "bark of the tree." A large and complex molecule, quinine is the most important alkaloid found in cinchona bark. Until World War I, it was the only effective treatment for malaria. In fact, quinine was the first chemical compound to be successfully used to treat an infectious disease. Quinine was isolated in crystalline form in 1820 by J.B. Caventou and P.J. Pelletier. In one of the classical achievements of synthetic organic chemistry, R.B. Woodward and W. Doering first made synthetic quinine in 1944. Quinine acts by interfering with the growth and reproduction of the Plasmodium, the malarial parasite that lives within the victim's red blood cells. Quinine causes the parasites to disappear from the blood and the symptoms of the disease are thereby alleviated. However, when quinine treatment ends, many patients relapse. They suffer another attack of malaria due to the failure of quinine to kill the malarial parasites in cells of the body other than the red blood cells. These parasites persist and, after a time, they reinvade the red blood cells and precipitate the relapse. Since quinine does not permanently cure malaria, better drugs were sought. A number were discovered that replaced quinine during and after World War II. Some of these drugs (such as chloroquine and chloroguanide) are more effective than quinine in suppressing the growth of the blood forms of the malarial parasite. Others (such as primaquine and pyrimethamine) act upon both the blood and tissue phases of the parasite, producing a complete cure and preventing a relapse. Quinine was once used for the treatment of leg cramps, but it is no longer FDA approved for this use, due to serious side effects, including low platelet counts and death.