Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, and fruits, as well as shellfish, avocado, and beef (organs such as liver). Because copper is found in the earth's crust, most of the world's surface water and ground water used for drinking purposes contains small amounts of copper. Copper is involved in numerous biochemical reactions in human cells. Copper is a component of multiple enzymes, is involved with the regulation of gene expression, mitochondrial function/cellular metabolism, connective tissue formation, as well as the absorption, storage, and metabolism of iron. Copper levels are tightly regulated in the body. Copper toxicity is rare in the general population. Wilson's disease is a genetic disorder in which the body cannot rid itself of copper, resulting in deposition in organs and serious consequences such as liver failure and neurologic damage. Obstruction of bile flow, contamination of dialysis solution (in patients receiving hemodialysis for kidney failure), Indian childhood cirrhosis, and idiopathic copper toxicosis are other rare causes of potentially dangerous excess copper levels. Such individuals should be followed closely by a physician and nutritionist. Copper deficiency can occur in infants fed only cow-milk formulas (which are relatively low in copper content), premature/low-birth weight infants, infants with prolonged diarrhea or malnutrition, individuals with malabsorption syndromes (including celiac disease, sprue, or short bowel syndrome), cystic fibrosis, in the elderly, or those receiving intravenous total parenteral nutrition (TPN) or other restrictive diets. Medicinal use of copper compounds dates to Hippocrates in 400 B.C. Bacterial growth is inhibited on copper's surface, and hospitals historically installed copper-alloy doorknobs and push-panels as a measure to prevent transmission of infectious disease.