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Holding a PhD in botany from Gotham University, Pamela Isley was once employed by Chez Gerard, a cosmetics firm, as a research chemist in charge of developing new perfumes. She also offered a weekly lecture series at the university on rare and extinct plant species.

At some point, she met or introduced herself to District Attorney Harvey Dent, and they began dating. Unknown to him, she had marked him as a "murderer" for his part in arranging the excavation of land for the future site of Stonegate Penitentiary. The excavation had involved bulldozing a field of wildflowers, including a rare wild rose that would have gone extinct, had she not saved it first. Appropriately, she used extract from the rose to create a rare and deadly poison, which she administered to Dent through a deep kiss. Dent fell into a coma and was not expected to live.

A personal friend of Dent's, Bruce Wayne investigated the crime as Batman. Discovering the origin of the poison, Batman confronted Isley (who revealed her nom-de-crime, "Poison Ivy") at her greenhouse hideout. In the ensuing struggle, Batman captured the rose as a "hostage", forcing Ivy to surrender the antidote she had developed. He managed to save Harvey's life, and Ivy was imprisoned in Stonegate. She was later transferred to Arkham.

Months later, having escaped or been released, Ivy opened an all-natural resort spa outside Gotham, under the alias "Dr. Daphne Demeter". The "Eternal Youth Spa" was a bait through which Ivy attracted wealthy business men and women guilty of certain environmental crimes, and "treated" them with plant-derived toxins, which transformed the people into plants themselves.

By unfortunate coincidence, a greedy Wayne Enterprises executive had made a deal with a South American company to level a section of the Amazon rain forest, before Wayne aborted it. Ivy targeted Wayne for his perceived part in the deal, and Alfred Pennyworth attended in Wayne's place for a free spa getaway. When Alfred disappeared, Batman quickly deduced the doctor's true identity, and stopped Ivy's plan yet again.

She also developed a fierce feud with the Joker, at least one fight being over a channel to watch in Arkham Asylum's rec room.

After another escape, she was arrested at the Stacked Deck, over a poker game with Joker, Penguin, and Two-Face. Before the game, she exchanged a few amused reminiscences with her "old flame", Harvey Dent (the amusement was entirely one-sided).

Months passed, and for the first time, Ivy seemed to have returned to a normal life. Released from Arkham, Pamela Isley moved away from Gotham, married her psychiatrist, and embraced his two children as her own. Despite strange plant-related occurrences occurring, Batman and Robin were unable to link any connection to Isley. Unfortunately, Ivy had merely fooled the Dark Knight and Boy Wonder. Creating plant monsters to act as clones of her "family", Ivy had not only created a legitimate front for her activities, but also made a small drone factory. Though Batman and Robin once again foiled her plans, Ivy escaped.

After failing to meet the psychological requirements for rehabilitation, Ivy returned to Arkham and was present for the Trial of Batman. She acted as a juror and as a "witness", testifying towards Batman's involvement in her turning to crime.

A chance meeting during a heist at the Gotham Museum sparked one of Poison Ivy's most unique relationships. Harley Quinn, recently evicted from the Joker's gang, helped Ivy escape the clutches of the Gotham Police Department. Though the personalities of the two seemed completely opposite, their (somewhat) common goals bonded them into a formidable duo. Harley seemed to thrive on the experience of an honestly affectionate partner, while Ivy admired Harley's streak of fun and ingenuity, though she was exasperated by Harley's unshakeable devotion to "that psychotic creep", Joker.

Shortly after uniting, they took Gotham by storm with a crime spree. Dubbed "The New Queens of Crime", their actions went unstopped for a long time. Despite his best efforts, Batman was unable to capture the two damsels, and only after their home was destroyed by the Joker were they captured by Renee Montoya.

Still, the bond had been forged. Unlike most villain team-ups, Harley and Ivy seemed to have a genuine friendship, as each helped the other with problems, be they personal or other. Though each also pursued her own area of interest, it was not uncommon for the two to team up, share a hideout, or rendezvous for the holidays.

When Livewire was transferred to Gotham for further psychiatric treatment, a brief and unlikely trio formed. Though they initially subdued the two, the combined forces of Batgirl and Supergirl proved too much for the electric charged trio.

The two had many other capers, including various robberies, some holiday fun, and occasional turmoil amongst themselves. Throughout this time, however, their relationship nurtured, and it seemed the two fostered a general care for one another. At one point, the men of Gotham disappeared altogether. Ever the opportunists, Harley and Ivy raided the Gotham Police Department Special Crimes Dangerous Evidence Vault, stealing items from various villains including the Penguin, the Joker, and Mr. Freeze.

The two fled to the Gotham Monastery, Batgirl and Catwoman (who was the prime suspect in the men's disappearance) attempted to reason with the two, but Harley accidentally discovered the true cause of the male disappearance: a weapon designed by Mr. Freeze.

Renee Montoya and the GPD arrived to arrest the women. Harley and Ivy escaped, but were branded accomplices in Catwoman's supposed crime. Gotham went into a hard lock down, but eventually the four women united. Donning a Batgirl outfit, Poison Ivy broke into a warehouse in Gotham's West District. Unmasked, she managed to evade capture long enough for Batgirl to discover the true cause of the disappearances: Dora Smithy. After the mystery was resolved, Harley convinced Catwoman and Poison Ivy to turn themselves in, as they had promised to Batgirl. However, they made no assurances that they'd stay captured, and the three escaped.

Eventually, Harley and Ivy found themselves lacking in funds. Because of the "Big Bang" in Dakota, new metahumans had been created, several of whom were uncomfortable with their new-found powers and transformations. Through the internet, Harley and Ivy set up a mock therapy and treatment group, and began contacting the "Bang Babies". One of their victims, Nails, was a student at Dakota High. Thinking she was heading for help, she discovered she'd been lured into a life of crime. Though they convinced Nails to aid them in their plan (this time pilfering a shipment of gold from a cruiser), Static (who had followed Nails to Gotham) and Batman halted the scheme and captured Harley and Ivy once again.


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