The expression "When you hear hoof-beats behind you, think horses not zebras," which Cox tells J.D., is a well-known real-life axiom in medicine. It was coined in the 1940s by Dr. Theodore Woodward at the University of Maryland School of Medicine in Baltimore, Maryland, and the original phrasing is, "Don't look for zebras on Greene Street," referring to the street on which the University of Maryland Medical Center is located.
J.D. brings up kuru as a possible diagnosis for a patient. The disease only exists in New Guinea and is transmitted by eating the brains of a family member, a rare form of funeral rite practiced by the Fore people.
Dr. Cox quotes "the zebra rule" ("If you hear hoof beats, assume horses, not zebras") from the book House of God by Samuel Shem.