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According to his own account, Nick was born in the (fictional) town of Caslin, Nebraska to a poor and indebted farming couple. Several months before Nick was born, while en route to a routine doctor visit, his parents were in an automobile accident, the shock of which gave Nick's father a fatal heart-attack.
It is implied (though not stated) that the same accident caused fetal injuries to Nick that resulted in his deafness and muteness. The latter is so thorough Nick can only laugh or weep in complete silence, incapable of even uttering an involuntary scream of pain.
Nick lived with his mother until the age of nine, when she was killed walking across an intersection. Sent to an orphanage, unable to communicate and bullied by the other children, Nick retreated within himself, until a fellow deaf-mute named Rudy Sparkman forced him out of his shell and taught him to read and write. When the orphanage went bankrupt a teenaged Nick ran away, struggling to earn GED credits and taking odd manual jobs to get by.
Nick is a twenty-two year old drifter at the time of the superflu outbreak, travelling through Shoyo, Arkansas. There, several of the town's bullies beat him up, steal his week's wages and leave him in the road for dead, where he is nearly run over by Dr. Soames.
Sherriff John Baker initially jails him on suspicion of vagrancy. But Nick quickly wins his sympathies and together they hunt down and imprison most of the men who attacked him. Unfortunately the group's ringleader — Baker's own brother-in-law Ray Booth — manages to evade capture.
Baker deputizes Nick in order to look after the prisoners, as both they and he are beginning to show signs of the superflu. When it becomes apparent that the plague is wiping out the town's population (including the sheriff, his wife, the doctor, and one of the inmates) Nick lets his attackers go so they have a chance of survival.
However, a dying and enraged Booth finally comes out of hiding, stalks Nick, and attempts to strangle him. In the resulting struggle Nick suffers a gouged eye, and a bullet wound when his unholstered gun accidentally fires; but he manages to shoot and kill Booth.
After recovering from his injuries (including a near-fatal infection from the gunshot-wound) Nick leaves Shoyo and ends up in May, Oklahoma. There he meets Tom Cullen, and invites him to come along with him to Hemingford Home, Nebraska.
On the way they pause in Pratt, Kansas and encounter Julie Lawry. Immature, flirtatious and self-absorbed, Julie initially manages to seduce Nick; however he quickly realizes she is emotionally and mentally unstable. When she maliciously upsets Tom by telling him the Pepto-Bismol Nick is offering him is really poison, Nick becomes fed up. He slaps her, and orders her away at gunpoint. She retaliates by disabling their bicycles, scattering their supplies, and attempting to snipe them with her own firearm until they flee town.
Picked up by Ralph Brentner, Nick and Tom are in the first group to reach Mother Abagail in Nebraska, and the first to reach the Boulder Free Zone, where Nick becomes a key member of the Boulder Free Zone Committee.
Later, Harold Lauder constructs a dynamite bomb, which Nadine Cross plants in Nick's closet so it can be detonated during a Committee meeting. Spurred by a premonition, Nick is at ground zero hunting for the bomb, and literally holding the device in his hands when it explodes; afterwards, what is left of his physical remains can only be identified by means of "certain scars".
After his death Nick continues to appear to Tom Cullen in his dreams, guiding and giving him advice. In Tom's dreams, Nick Andros can both speak and hear.