Tobacco is the plant which contains nicotine. It is nicotine that is the reinforcing and addicting substance in the plant. The delivery system in smoking the cigarette, the cigar, or chewing the leaves is responsible for the severe health consequences. As noted by former Surgeon General Antonia Novello, "smoking represents the most extensively documented cause of disease ever investigated in the history of biomedical research." Cigarette smoking is a profound contributor to mortality. Each year more that 400,000 deaths, or 20% of the total deaths, in the U.S. are caused by smoking.