In the Resident Evil series, Alice was created by the Umbrella Corporation as a clone of Alicia Marcus, the daughter of co-founder James Marcus. Alice's purpose was to protect the Mirror House, and she remained unaware of her true identity as a clone, believing herself to be the original—since all Umbrella clones were made to think this way. Publicly, she was married to Spence; however, their marriage was a sham intended to safeguard the mansion. They became romantically involved at a later point.

In 2002, Alice started communicating with an Umbrella researcher named Lisa Addison, who was secretly working for former FBI agent Matt Addison. Instead of arresting her, Alice offered to help Lisa expose Umbrella's bioweapons research by devising a plan to disable the Red Queen security system and facilitate the theft of a T-virus sample. Alice was likely influenced by Alicia's inherent sense of compassion. Unbeknownst to them, Spence discovered their plan. Believing that bringing down Umbrella in such a manner was worthless, he instead formulated his own scheme to steal a virus sample using his own security clearance, sell it on the black market, and escape with the proceeds, taking Alice with him.