To avoid confusion, the narrator and main character in Middlesex is referred to here as "Cal" and by the pronoun "she." The novel opens noting two birthdates, the first when Cal was born as a baby girl in Detroit in 1960 and the second when she was born again as a teenage boy in a hospital in Michigan in 1974. She notes that she was written up in a gender study in 1975 and discussed in a medical journal, and she gives a brief history of her life, listing her various jobs and experiences. The novel's title refers to the name of the street where she lives in Grosse Point, a suburb of Detroit, and it is also an allusion to her sexual location between the polarities of male and female and incorporating some traits of each.
Cal, who is now forty-one, says that she feels "another birth coming on." As a result, she has determined to write down the history of "the recessive mutation on [her] fifth chromosome" that "polluted" her family's genetic pool and eventually caused her to be born a hermaphrodite.
Cal notes that three months before she was born, her grandmother, Desdemona, tried to divine her gender by dangling a spoon over her mother's pregnant belly. She predicted a boy, which turns out was only half right. On the night Cal was born, her grandfather, Lefty, had the first of his thirteen strokes and lost the ability to speak.
Cal's narrative turns to the story of her grandparents' union, which begins in 1922 in Bithynios, a village on Mount Olympus in Asia Minor, later part of Greece. Twenty-one-year-old Desdemona lived there with her brother, Lefty. The two had always been close, but lately, he had been going into town looking for women. Desdemona tries to find a mate for him, but Lefty rejects them all. One night, in their village where "everyone was somehow related," the siblings admit and consummate their love for each other.
Cal shifts the narrative to the present when she lives in Berlin, working for the Foreign Service. She notes that she has "all the secondary sex characteristics of a normal man" except for her immunity to baldness. While she has lived as a man for half of her life, at times her feminine side emerges. She explains that she needs to go back to her grandparents' story to explain her own.
As the Turkish army advances, Lefty and Desdemona decide to immigrate to the United States, where their cousin Sourmelina lives. They set off for Smyrna where they hope to find a ship to carry them across the Atlantic. Desperate to get out before the Turkish troops arrive, they wait one week amid the chaos of the city's evacuation. A physician, Dr. Nishan Philobosian, treats a wound on Lefty's hand and gives him bread. As the Turks advance, they set fire to the city, forcing all of the residents to the wharf where Lefty convinces Desdemona to marry him. Posing as French citizens, they eventually gain entry on a ship bound for the United States. After Dr. Philobosian's family is brutally murdered by Turkish soldiers, Lefty claims he is his cousin and gains him passage as well.
Desdemona and Lefty pretend to meet and fall in love on the ship where they are soon married. Cal claims that they both carried a single mutated gene that they subsequently passed on to her. Lefty assures Desdemona that Sourmelina, called Lina, will keep quiet about their true identities because she has a secret as well: her lesbianism.
Desdemona and Lefty move in with Lina and her husband, Jimmy Zizmo, in Detroit, and Lefty takes a job with the Ford Motor Company. When the management discovers Jimmy's criminal record, Lefty is fired.
Desdemona and Lina become pregnant with Cal's parents, and Lefty starts to work with Jimmy smuggling alcohol from Canada. Desdemona is convinced that the intermarriage will cause their child to be deformed. One night as they cross the lake into Canada, Jimmy accuses Lefty of having an affair with Lina. In a jealous rage, Jimmy races the car across the lake and cracks through the ice just after Lefty jumps clear....
(The entire section is 2,665 words.)