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Big Brain is an apparent leader of the Jupiter's Clan as he is shown issuing commands to others Mutants on multiple occasions through a walkie-talkie. Big Brain apparently suffers from an extreme case of hydrocephalus and goitres, explaining his large and distended head and bloated throat. Due to his physical condition, Big Brain is incapable of walking and is confined to an old-fashioned wheelchair. Located in an electronics filled house in the mutants' nuclear test village home, Big Brain is found by protagonist and friend of the Carters, Doug Bukowski. Attempting to interrogate Big Brain, Doug learns about the origin of the mutants; when he threatens Big Brain with his baseball bat, Big Brain summons an axe-wielding Pluto.
Doug eventually succeeds in killing Pluto but, concerned for his baby, cannot spare the time to kill Big Brain. The mutant is later attacked, and presumably mauled to death by Doug's dog, Beast.
During his first appearance he is seen ironically singing "The Star Spangled Banner". This is most likely a homage to the cause of the Hill People's deformities, a nuclear bomb, because he was stopped just after he said "the bombs bursting in air".
"Your people asked our families to leave the towns, and you destroyed our homes. We went into the mines, you set off your bombs, and turned everything to ashes. You made us what we've become. Boom! Boom! Boom!"