The grapefruit originated as a hybrid of the sweet orange and pummelo in the Caribbean in the 18th century, and is still mainly grown in the Americas. The red types owe their color to lycopene, and first appeared as chance mutations in Florida and in Texas early in the 20th century (the more recent and popular Star Ruby and Rio Red varieties were created by intentionally inducing mutations with radiation). Unlike the anthocyanin coloration of blood oranges, grapefruit lycopene requires consistent high growing temperatures to develop well, appears evenly through all the juice vesicles, and is stable to heat. The characteristic moderate bitterness is caused by a phenolic substance called naringin, whose concentration declines as the fruit ripens. Like navel oranges, grapefruits also contain a precursor of limonin, and its juice becomes bitter on standing. Some grapefruit phenolic compounds turn out to interfere with our metabolism of certain drugs, cause the drugs to persist longer in the body, and thus cause the equivalent of an overdose, so medicine labels sometimes warn against consuming grapefruit or its juice along with the medicine. (These same phenolics are now being developed into activity-boosting drug ingredients.) Grapefruits have an especially complex aroma, which includes meaty and musky sulfur compounds.