Lisa was born to George and Jessica Trevor around the year 1953. Several years after her birth, Oswell E. Spencer hired George to design a special mansion complex for him high up in the secluded Arklay Mountains, which would also host a secret underground laboratory. Spencer, paranoid that George would someday leak the mansion's secrets to the public, began plotting a suitable fate for him and his family.
Inviting the Trevors to the mansion, George was expectantly forced to arrive several days after his wife and daughter's arrival. During this time, Lisa and Jessica were apprehended by Spencer's men and dragged to the Laboratory underground, where they were to be experimented on as human test subjects for the Progenitor virus.
When George finally arrived, he was informed by Spencer that the two had left earlier to attend an unwell relative. After finding the right opportunity, George was also apprehended, though managed to escape. He would never find his family, he'd soon realize that they were still in the estate somewhere.
On November 10, 1967; some time after George's death from starvation, Lisa was administered the "type-B" variation of the Progenitor virus, while her mother was administered with "type-A". Lisa's body didn't immediately begin to exhibit signs of mutation and absorb the virus. Over a period of time, under observation, both Lisa's mental and physical state were grotesquely altered.
Jessica made preparations to escape and sent a letter to Lisa informing her of it. The two were to pretend to be unconscious from the drugs while their water was changed. Jessica knew that this would be the right moment to run out of the door. However, the letter would never get to her in time.
Umbrella killed Jessica shortly after she was given the virus because she displayed no reaction to the treatment. In order to pacify Lisa, who had been separated from her mother during their imprisonment, Umbrella sent in staffers who had been disguised as Lisa's parents to provide her with a sense of security. However, Lisa was able to recognize them as impostors and violently killed them. Umbrella made repeated attempts to subdue Lisa, but all attempts failed when she ripped off their faces and attached them to her own body for safe-keeping. The increasingly mentally unstable and lonely Lisa grew obsessed with finding her true mother so that she could "give her back her face". Lisa was able to find the secret tomb of her mother, built under the Spencer Mansion. While she was able to recognize the scent of her mother, she was unable to open the stone coffin and "reunite" with her.
Even after her mother's death, Lisa continued to serve as a test subject for even more biological experiments. Unlike her fellow, more fortunate test subjects, Lisa was able to survive all of their tests, regardless of the potency of the implanted virus or parasite. This uncanny immunity earned the attention of Umbrella Corporation researchers, Albert Wesker and Dr. William Birkin, who injected their formidable guinea pig with a specimen of the NE-α Type. To their astonishment, Lisa not only overcame the specimen, but also managed to absorb it and adapt its powers into her system. Ultimately, this was a major breakthrough for the Umbrella Corporation, that would later go on to play a pivotal role in the engineering of the G-virus.
After the G-virus was extracted from Lisa, the Umbrella Corporation lost interest in her. As time passed, Lisa's mutations and loneliness lead her to become increasingly violent. On one occasion, she brutally assaulted and killed three lab researchers. As Lisa was now seen a vestigial threat, Umbrella Corporation officials called for Lisa's destruction. Sometime in 1995, Lisa was supposedly slain in an undisclosed area of Spencer's estate. However, little did the Umbrella Corporation realize, the myriad of experiments conducted on Lisa had left her impervious to almost all forms of physical battery, rendering her immune to all gunfire, to the extent an anti-tank missile had little to no effect on her aside from swatting her against a wall. Even with her death "confirmed" after three days of monitoring her vital signs, she was able to regain her life some time after being dumped in an unknown location. Lisa would go on lurking through the catacombs of Spencer's estate, secretly taking residency under a neglected, dilapidated cabin in the Courtyard.