Genetic engineers Clive Nicoli (Adrien Brody) and Elsa Kast (Sarah Polley) achieve fame by successfully splicing together the DNA of different animals to create incredible new hybrid animals. Now they want to use human DNA in a hybrid that could revolutionize science and medicine. But the pharmaceutical company that funds their research, N.E.R.D. (Nucleic Exchange Research & Development), forbids it, instead mandating that their department be reorganized to focus on finding & extracting certain proteins from the creatures they have already created. Not wishing to spend all their time engaged in what they consider mundane research for the next 5-10 years, Clive and Elsa secretly conduct their own experiments, blending human DNA with that of other animals.
Though they disagree about actually bringing the hybrid to term, Elsa pushes the issue and she persuades Clive to go along with it, in continued secrecy. They name their creature Dren (nerd backwards), who exceeds their wildest dreams; she begins to grow and learn at an accelerated rate. As their lab becomes exceedingly crowded, and the risk of Dren being discovered increases, they move Dren to Elsa's late mother's farm.
One of the original hybrid animals that they had created, which was originally female, had changed sex, unbeknownst to the preoccupied Clive & Elsa. This led to a disastrous presentation during a company shareholders' meeting, when the two original hybrids, previously one male and one female very much in love with each other, became both male, saw each other as rivals and bloodily killed each other in front of a shocked audience of shareholders and potential investors. Following this meeting, N.E.R.D., found itself in danger of going out of business unless they could find a profitable discovery.
Their work at the company suffers as their attention is focused on Dren. Meanwhile, Dren has become amphibious and omnivorous with a toxic sting and retractable wings coming out of parts of her arm and back. Elsa, who had formed a maternal bond with Dren, changes her mind after Dren shows violent behavior, killing her own pet cat out of spite and assaulting her. She cuts off Dren's stinger and uses organic tissue from it to finally isolate and synthesize a protein they had been searching for.
Soon after, Clive is seduced by Dren and has sex with her, much to Elsa's disgust; during her sexual encounter with Clive, Dren reveals that she has regenerated her stinger. Elsa and Clive have a heated argument about Clive having cheated, during which he confronts her with his discovery that she used samples of her own DNA in the creation of Dren. Deciding to deal with Dren, they go back to the farm, only to discover her body in the water tank, apparently dead.
They bury Dren near the farmhouse but before they leave, their boss from pharmaceutical company arrives, having figured out that there was some sort of human hybrid because of the DNA present in the protein they had finally synthesized. Elsa tells her boss he can dig up Dren's body if he really wants to see it. Suddenly, they are attacked by Dren, who was not dead, but apparently in some sort of coma as her body underwent changes that turned her into a male. After killing her boss and Clive's brother, Dren drags Clive into a freezing pond. Elsa pulls him out, but he is unconscious and Elsa flees. Dren finds her and rapes her. As Dren is raping Elsa, Clive comes to the rescue, impaling Dren with a large sharp branch. Dren kills Clive with a toxic sting, but is dealt a fatal blow by Elsa when she smashes its head with a rock.
Later on, Elsa is seen in the office of the pharmaceutical company's head and is given a massive amount of money in exchange for her silence and taking the experiment to the "next stage". The head of the company then thanks Elsa for the personal risk that she is undergoing. Elsa stands up and is revealed to be pregnant with Dren's baby.