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Salisbury was born in Scott, New York, in 1823. He earned a Bachelor of Natural Sciences degree from the Rensselaer Polytechnic Institute in 1844. He joined the New York Geological Survey as an assistant chemist, was promoted in 1849 to principal chemist, and remained in this position until 1852. He earned his medical degree from Albany Medical College in 1850, and a Master's degree from Schenectady College in 1852. He was elected a member of the American Antiquarian Society in 1862.
Salisbury was one of the earliest health food faddists and taught that diet was the main determinant of health. He believed vegetables and starchy foods produced poisonous substances in the digestive system which were responsible for heart disease, tumors, mental illness and tuberculosis. He believed that human dentition demonstrated that humans were meant to eat meat, and sought to limit vegetables, fruit, starches, and fats to one-third of the diet.
The Salisbury steak, his means of achieving this goal, is ground beef flavored with onion and seasoning and then deep-fried or boiled, and was introduced in 1888. Salisbury believed that beef was excellent defense against many different physical problems. He suggested that Salisbury steak should be eaten three times a day, with lots of water to cleanse the digestive system. He was an early American proponent of a low-carbohydrate diet for weight loss, and he promoted his diet for that purpose.
Salisbury steak — essentially a hamburger — might have faded from the collective memory if World War I had not inspired a drive in English-speaking nations to rename German-sounding things. Salisbury steak became a popular substitute for the (bunless) hamburger.