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Spanish Island is an island in the Black Brake Swamp on the Louisiana/Mississippi border. It is near the towns of Malfourche, Mississippi and Sunflower, Louisiana. It is the center of old rumors and ghost stories involving the swamp. Spanish Island is surrounded by a maze of vegetation-choked waterways and is very difficult to reach without an experienced local guide.

Spanish Island was home to a hunting camp owned by Carlton and June Brodie, the secretary to deceased former Longitude Pharmaceuticals CEO Charles Slade. A week after Slade apparently died in a fire, Brodie disappeared, apparently throwing herself off a bridge in grief.

In reality, Slade and the Brodies retreated to Spanish Island. They converted the hunting lodge into an isolated refuge and laboratory where Slade, who suffered from a neurological disease that caused him to be extremely sensitive to sensory input, could live in solitude. Fourteen years later, Special Agent Pendergast and Captain Laura Hayward tracked them there. Pendergast confronted Slade with an overload of uncomfortable stimuli and Slade killed himself. After Slade's death, the Brodies burned the laboratory and left Spanish island.

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