[1] Set in the mid-18th century, the novel follows the picaresque adventures of James Dyer, an Englishman born without the ability to feel pain or pleasure.

[6] The novel opens in 1771 with the autopsy of James Dye by two gentleman surgeons keen on understanding the deceased's famed inability to feel physical pain.

Against all expectations the baby lives, growing up to be a mute boy with an inordinately precocious countenance that disconcerts everyone, foremost of all his schoolteacher, a crippled spinster who prides herself on being an expert on children.

Once James has perfected his screams, they set out to tour the country fair circuit in England, peddling a quack nostrum touted as capable of warding off pain.

At night he wanders the seemingly endless corridors of Canning's manor house, encountering a librarian, a painter, and a pair of Siamese twins.

Thanks to the librarian he is given access to a near-inexhaustible supply of anatomy books, from the painter the ability to finetune drawing (a skill he had picked up in his earlier childhood), and from the twins his first experience of sexual intercourse.

Meanwhile, the Siamese twins die as a result of an awry attempt to surgically separate them; James is the only one unmoved by the blood-splattered carnage that accompanies the event.

Any hopes of a return to the days of Gummer's successful quackery are put to an immediate end, however, when James allows for the two of them to be pressganged into the royal navy.

With his practice snubbed and his clinic periodically falling prey to vandalism by the city's outraged denizens, James opts to participate in a race among other English doctors to inoculate Empress Catherine of Russia.

[8] It was again reviewed by The Independent a year later by Lilian Pizzichini who opined that Miller's "understanding of contemporary mores is thorough, the period detail precisely evoked, and his characters come alive with flashes of humour and compassion.

He also praises the pacing of the novel; and draws comparison to John Fowles's novel The French Lieutenant's Woman; Graham Swift's Waterland; and Peter Ackroyd's "early flamboyant historical pastiches.