Looe Key is a coral reef located within the Florida Keys National Marine Sanctuary. It lies to the south of Big Pine Key. This reef is within a Sanctuary Preservation Area (SPA). Part of Looe Key is designated as "Research Only," an area which protects some of the patch reefs landward of the main reef. The reef is named after HMS Looe (1741), which ran aground on the reef and sank in 1744. In August 1994, RV Columbus Iselin, a research vessel owned by the University of Miami, ran aground on Looe Key and damaged approximately 164 m2 of living coral and a larger area of reef framework. In 1997, the University paid $3.76 million in natural resource damage claims to National Oceanic and Atmospheric Administration (NOAA). In 1999, a restoration project involving placement of limestone boulders, pouring of concrete, and reintroduction of benthic species was undertaken by NOAA and its subcontractors. The key was protected as Looe Key National Marine Sanctuary in 1981 until it was incorporated into Florida Keys National Marine Sanctuary in 1997.

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