The first words of Jeffrey Eugenides exuberant and capacious novel Middlesex take us right to the heart of its unique narrator: "I was born twice: first, as a baby girl, on a remarkably smogless Detroit day in January of 1960; and then again, as a teenage boy, in an emergency room near Petoskey, Michigan, in August of 1974."

Middlesex is the story of Cal or Calliope Stephanides, a comic epic of a family's American life, and the expansive history of a gene travelling down through time, starting with a rare genetic mutation. In 1922, Desdemona and Eleutherios ("Lefty") Stephanides, brother and sister, leave the war-ravaged village of Bithynios in Asia Minor. With their parents dead and their village almost empty, Desdemona and Lefty have gradually been drawn closer together and fallen in love. As the Turks invade and the Greeks abandon the port of Smyrna, Lefty and Desdemona -- Callie's grandparents -- escape to reinvent themselves as a married couple in America.

Jeffrey Eugenides recounts the Stephanides family's experiences over the next fifty years with gusto and delight. Upon their arrival in Detroit, Lefty goes to work at the Ford motor plant and the couple live with Desdemona's cousin Sourmelina -- a woman with her own secrets -- and her bootlegging husband Jimmy Zizmo. After Jimmy disappears and the Stephanides' son Milton is born, Lefty opens a speakeasy called the Zebra Room, and Desdemona goes to work tending silkworms for the Nation of Islam.

Milton serves in the Navy in World War II and returns to marry his cousin Tessie, Sourmelina's daughter, and the errant gene comes closer to expression. Milton takes over the family business and they have two children, Calliope and Chapter Eleven, but as their fortunes rise the city's fall, and Detroit is torn by riots with the intensity of warfare. The family moves into a new home called Middlesex in a tony suburb, and Calliope, who had been a beautiful little girl, is sent to private school.

So begins one of the strangest, most affecting adolescences in literature. As time passes Calliope gets taller and gawkier without developing into womanhood. Her classmates' bodies change and they grow interested in boys; Callie remains flat-chested and waits in vain for her first period. And she has a curiously intense friendship with a girl at her school, the beautiful and confident Obscure Object of Desire.

It is only when she has an accident at the Obscure Object's summer house and is examined by an emergency room doctor that Callie and her parents discover that she isn't like other girls. She is referred to an eminent New York doctor who, after extensive physical and psychological testing, pronounces her genetically male: 5-alpha-reductase deficiency syndrome caused her true genital characteristics to remain hidden until puberty. Callie is a hermaphrodite. Since she was raised as a girl, Dr. Luce recommends cosmetic surgery and hormone injections to make her seem more fully female.

But Callie refuses to be something she is not. She runs away, cuts her hair short and hitch-hikes across the country to California, calling himself Cal. And after some difficulties -- and performances in a strip club in San Francisco at the height of sexual liberation -- Cal learns to relish being both male and female. One more unexpected family tragedy, and some old revelations, await in Detroit.

This animated and moving story is narrated by Cal Stephanides, now an American diplomat living in Berlin. While telling us about his past, he fumbles towards a romantic relationship with an artist who might be able to accept him for the unique person he is.