Middlesex, by Jeffrey Eugenides

Gender confusion and Greek tragedy have bred an American epic, reports Julie Wheelwright

Like Tristram Shandy, the narrator of Jeffrey Eugenides' epic novel is a witness to his own conception. Mother Tessie is longing for a daughter, and times her lovemaking with husband Milton to produce the right result. In January 1960, a daughter is born to this second-generation Greek-American couple. Normality appears to reign in their Detroit household. But the narrator, who has already provided a panoramic portrait of his grandparents' union in Turkey, deliciously strings out a series of revelations.

Unlike Shandy, the narrator Cal is born twice, and views history through the perspective of both genders. Tessie's child is born a hermaphrodite, raised as a daughter named Calliope and then, following an accident at 14, undergoes this second birth to become Cal. The grandparents' own shameful secret compounds the chances that result in Cal inheriting a disorder in which a genetic male is born with what appear to be female genitals.

Cal's grandparents, who fled Smyrna during the Turkish invasion of 1922, were also brother and sister. Tessie and Milton are second cousins. Such a crowded gene pool dramatically increases the possibility of this disorder sailing down generations.

But, of course, a genetic disorder among Greeks can be the seed for unfolding a series of dramas. Eugenides, author of The Virgin Suicides, brilliantly weaves together strands of genetic heritage, mistaken identity and transformation, over three generations.

Desdemona and Lefty Stephanides, orphaned after their parents' death, hide the truth about their life in Smyrna. In America, they present themselves as husband and wife. They head for Detroit to live with cousin Sourmelina, who guards the couple's secret because she has one of her own. Married to Jimmy Zizmo, a rum runner, she keeps her lesbian affairs under wraps. The two couples live together in Zizmo's house, occupying separate worlds. "Two spheres with separate concerns, duties," Cal comments, "even – the evolutionary biologists would say – thought patterns."

There are other transformations. At a YMCA camp for immigrants, Desdemona's braids are cut off and she is given a cloche cap to get rid of her peasant look. She carries the braids until she dies. Social workers at the Ford plant where Lefty briefly works inspect Zizmo's home to ensure that unhygienic Mediterranean practices (such as using garlic) are eschewed. Ford's inspectors, upholders of a new morality, have Lefty dismissed when they inform his boss that Zizmo runs a bootleg operation. Lefty takes up where his life in Smyrna ended, running a speakeasy café called the Zebra Room.

Milton is conceived on the same night as Tessie – another allusion to the incestuous twinning between Lefty and Desdemona. Although the Stephanides' son (and later a daughter) appear unaffected by their parents' genetic legacy, Desdemona does not want to tempt the gods and undergoes a tubal ligation. One night, Lefty lies next to her and wonders that "the sleeping form next to him is less and less his sister ... and more and more his wife. The statute of limitations ticks itself out, day by day, all memory of the crime being washed away. (But what humans forget, cells remember. The body, that elephant ... )".

Biology is an inescapable tragedy waiting to happen. Only in the next generation, when Callie is born and raised as a girl, does the past catch up with them.

Eugenides sets up an intriguing parallel between the relationship of Lefty and Desdemona, and Callie's double identity. The Stephanides are reborn after the fire of Smyrna, the tragedy that wipes away their past and demands they transform themselves. Their violation of a powerful taboo means that someone must pay the price. Callie's genetic disorder represents a very Greek form of hubris.

Eugenides is good on period detail, providing brooding, bold sketches of the family barricaded in their home during the Detroit race riots of 1967, the decline of Nixon, the reverberations of the Turkish invasion of northern Cyprus. All these events have their symbolic meaning in Cal's story. Milton, now a restaurateur himself, heads into the turmoil of the riots to protect the Zebra Room from looters. "The following morning as the smoke cleared, the city's flag could once again be seen ... A phoenix rising from its ashes." Milton emerges from this second fire wealthy enough, from his over-insured building, to open up a hot-dog franchise.

Daughter Callie is sent off to a posh girls' school. She plays field hockey, studies Greek, and falls in love. But while the crush might be explained as adolescent exploration, Callie becomes increasingly worried that she shows no signs of starting her period or growing breasts. When her feelings for her girlfriend confusingly stir the "bulb" between her legs into something like an erection, she becomes convinced that she is different.

Callie's parents are forced to seek the opinion of the famous Dr Luce: a thinly disguised version of a famous 1970s sexologist. Luce tells Callie's frightened parents that gender-identity development is determined by sex assignment and rearing, not by the gonads. Although Callie is genetically a male, she must grow up into a woman. The price she must pay for this is, effectively, a castration.

The real sexologist, Dr John Money, argued at the time against assigning children with this particular deficiency to the male sex. A new criterion for clinical practice suggested that, in cases of ambiguous sexual genitalia, the sex of assignment up to the age of two and a half was the best predictor of healthy gender development. Switching genders after this age was considered an extremely risky proposition. Ironically, the real Dr Money and fictional Dr Luce seem to side with the 1970s feminist view that gender identity is determined by socialisation, not biology.

When Callie appears in Luce's office, aged 14, she is beyond saving. A few shots of progesterone, a snip and a tuck, and Callie would be rendered as female as she possibly could: "I was a living experiment dressed in white corduroys and a Fair Isle sweater."

Yet, when Callie realises that Luce's treatment will denude her of her "bulb" and all erotic feeling, she decides to become the midwife of her own second birth. To become Cal, Callie undertakes a brutal journey across America, in which she is forced to unlearn everything she has learnt in the female sphere.

Eugenides portrays Cal as a deeply sympathetic character: a man of vision and wit, who manages to overcome his own Greek tragedy. Middlesex reminds us that those who fit awkwardly outside science's categories of sex, desire and gender have much to teach.

Julie Wheelwright is the author of 'Amazons and Military Maids'