European immigrants brought the age-old concept of four square gardens to America, where dense prairie sod and clay-filled soil limited plant growing. The design used four squares with intersecting paths, sized according to the gardener and available land, with each square as a raised bed formed by wooden borders to improve drainage, aeration, and warming of the soil. Settlers grew vegetables such as peas, beans, lettuce, radishes, and carrots for food, herbs such as dill, rosemary, and parsley for seasonings, and plants such as stinging nettle and sage for medicinal purposes, usually within a fenced garden to keep out animals. Early settlers also brought horseradish to North America and began cultivating it in the colonies, and commercial cultivation in America began in the mid-1850s when immigrants started horseradish farms in the Midwest. Herbal medicine, the oldest form of healthcare known to humans, has been used by all cultures through the ages, with much plant-based medical use developed through observation of wild animals and trial and error. About 25% of prescription drugs in the United States contain at least one active ingredient derived from plant material, whether from plant extracts or synthesized to mimic natural compounds. The history of herbology is intertwined with modern medicine: salicylic acid, a precursor of aspirin, was originally derived from white willow, and cinchona is the source of quinine used to fight malaria. Pharmaceuticals became popular during the 19th century as improved chemical analysis allowed scientists to isolate and extract beneficial plant compounds, while traditional medicinal plant use relied on whole roots or leaves rather than single extracted components. Pharmaceuticals undergo extensive testing before public use, but scientists report more side effects with pharmaceuticals than with medicinal plants, and although less scientific evidence exists for medicinal plants' effectiveness, research interest and investment are increasing.