The Citizens of Genopolis are humans who have been genetically engineered to withstand the great extremes of flood and fire, but with the result that they cannot feel pain or emotion.

Although Genopolis is advanced in many ways, it is also primitive, because the Citizens are served by slaves and rely on barter instead of money; while the buildings and people are decaying because pain no longer acts as an early warning system against disease and injury, so it is very easy to die of a simple scratch.

Arlo, a ten-year-old orphan boy, lives in Genopolis, in a university called the Inn of Court, where he is looked after by his mentor, Doctor Ignatius.

Wandering through the sewers, the underworld of Genopolis, Usha falls in with a gang of abandoned children, who have been thrown out of society because of becoming disabled through accidents or illness.

After a botched robbery, Usha is kidnapped by smugglers and sold to the Circus, a semi-illegal underworld gladiatorial arena, where criminal Citizens, escaped Gemini and the occasional captured Natural fight against themselves, and against genetically-engineered monsters.

The laboratories of the pharms (which provide food, replacing the historical farms) have created hybrid animals along the lines of classical monsters using genetic fusion technology; the Minotaur, the Gorgon, the Cockatrice and the Sphinx.

Usha, Rem and Arlo, together with the friends they have met in the Circus and Ozzie's gang from the underworld, escape the island of Genopolis by boat, and find their way to the Natural outerlands.