The novel starts with a narration by its protagonist, Cal (his masculine identity), also known as Calliope (feminine): He recounts how 5-alpha-reductase deficiency, a recessive condition, caused him to be born with female characteristics. The book continues with accounts of his family's history, starting with his paternal grandparents in their home village and ending with his father's funeral. These accounts cover the conception of Cal, his teenage years, and the discovery of his intersex condition. Throughout the book, Cal weaves his opinion of the events in hindsight and of his life after his father's funeral. Eugenides sets Middlesex in the 20th century and interjects historical elements, such as the Balkan Wars, the Nation of Islam, the 1967 Detroit riot, and the Watergate scandal in the story.A city burns in flames in the foreground, a large battleship sits in the water. A smaller vessel is berthed next to her. Another small ship sails away from the city on the left.Cal's grandparents flee from Smyrna, boarding a passenger ship, as the city burns in flames.The accounts of Cal's family history start in 1922. His grandfather, Eleutherios Lefty Stephanides, lives in Bithynios, a village in Asia Minor. Eugenides places the village high on the slope of Mount Olympos, above the city of Bursa, and describes incestuous marriages between cousins as a quietly accepted custom among the villagers. Lefty makes a living selling silkworm cocoons harvested by his sister, Desdemona. The siblings are orphans their parents are victims of the ongoing Greco-Turkish War. As the war progresses, Lefty and Desdemona develop a romantic relationship. Fleeing the chaos brought by the war, they board a ship amid the Great Fire of Smyrna and set sail for the United States. Their histories unknown to the other passengers, they marry each other on board the vessel.After arriving in New York, they locate their cousin, Sourmelina Lina Zizmo, in Detroit, Michigan, and go to stay with her. Lina is a closeted lesbian and the only person there to know of the siblings' incestuous relationship. Starting a new life, Lefty takes on a job at Ford Motor Company, but is later retrenched. He unknowingly joins Lina's husband, Jimmy, in bootlegging. Desdemona gives birth to a son, Milton, and later a daughter, Zoe. Lina gives birth to a daughter, Theodora or Tessie....Pulitzer Prize in 2003.