Discouraged by the inability to make a difference in the world, the woman who would become Itsy Bitsy resorted to drugs in order to cope with her vision of reality. However, her life changed when she met Patient Zero, a man hellbent on getting revenge on Deadpool and Spider-Man as part of a deal with Mephisto. She became Patient Zero's willing test subject, and was injected with genetic samples of Deadpool and Spider-Man in order to mutate her body. Following the procedure, she was given the name of Susan Mary.
She was first let loose in Wall Street during a fight between Spider-Man, Deadpool and the Hateful Hexad. Susan Mary interrupted the battle and killed the Hateful Hexad's members Bearboarguy, Gibbon, and Ox while singing the nursery rhyme Itsy Bitsy Spider, and left the scene after teasing the two heroes. The song she sang prompted Spider-Man to nickname her "Itsy Bitsy."
