Special Agent Pendergast's late wife Helen Esterhazy Pendergast, became interested in a strain of avian flu which transformed the brains of those it infected. The flu caused sufferers to become acutely aware of external stimuli and could trigger heightened perception and enhanced creativity. Unfortunately, over time the inability to turn off the enhanced sensitivity would drive the afflicted insane.

Helen became aware of the disease after studying the history of the painter John James Audubon. She noticed that his early works were crude and lacked the fine detail of his later paintings. She found that his technique greatly improved after a stay in a sanatorium to recover from an unknown illness. Helen found, through his diary entries, that immediately before falling ill he had been dissecting specimens of the Carolina parakeet. She tracked the preserved specimens to Oakley Plantation in Lousiana and managed to extract a strain of avian flu.

Helen took her findings to her old Doctors with Wings supervisor Morris Blackletter, now consulting for Longitude Pharmaceuticals of Itta Bena, Mississippi. Blackletter convinced Longitude's CEO, Charles Slade, to hire her and they began to research the avian flu in hopes of mitigating the negative side effects and developing a drug to enhance human creativity (Project Aves).

A parrot infected with the flu escaped the lab and flew across the Black Brake Swamp to Sunflower, Louisiana, where it was found by the Doane family. The parrot infected the Doanes, who for a brief time became shining pillars of the community before the disease drove them insane. The son, William Doane, murdered two people with an ax. The father was shot by police in a standoff at his home, and the mother committed suicide. After these incidents, Project Aves was cancelled and the lab was burned. Slade, who was himself infected with the avian flu, retreated to a secret laboratory on Spanish Island to continue his research.

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