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Frank Detomello is a slovenly zookeeper, and simple father to the only young and bright girl named Shane, who catches a cold right after when he swallowed a germ-ridden egg! The inside of his body is known as the "City of Frank". An unlikely hero of a policeman white blood cell, by the name of Osmosis Jones works as a member of Immunity, for Frank's immune system, as a white blood cell. But with that germ-ridden egg comes a mortal danger Osmosis discovers Frank has really contracted a villainous and black-hearted deadly virus known as Thrax who arrives and plotting to ultimately overheat Frank's body, killing him from the inside out! Thrax is motivated by trying to become the nastiest new virus, attempting to kill each new victim faster than the previous. His grandiose plan for Frank is death in 48 hours, breaking previous medical records! Meanwhile the pill that Frank took, Drix arrives in the body and covers Frank's throat with ice to cover the irritation. Osmosis Jones becomes his newest partner. Now it's all up to only Osmosis and Drix to put an end of Thrax's plans before Frank gets sick forever and Shane will become an orphan!