Sanctuary follows the exploits of Dr. Helen Magnus (Amanda Tapping) and her quest to protect various cryptids, legends, and abnormal animals/people with certain extraordinary powers and abilities - what most people would consider monsters. "The Sanctuary" serves as a safe haven for these "Abnormals". She is initially aided in her quest by her reluctant protege Will Zimmerman (Robin Dunne); her intrepid, if somewhat reckless, daughter Ashley (Emilie Ullerup); the talkative lycanthrope geek Henry Foss (Ryan Robbins), a computer and security expert; and her taciturn, Neanderthal-like assistant, played by Christopher Heyerdahl (unnamed, but listed as Bigfoot in the show's credits).
The history of Dr. Magnus is gradually revealed. In her youth she was trained by her father, a gifted Victorian-era scientist, to study the world and protect the unusual. Helen was a member of a group of experimental scientists known as "The Five", which included also Nikola Tesla (Jonathon Young), Nigel Griffin, Dr. James Watson (Peter Wingfield), and Magnus's lover John Druitt (Heyerdahl again), who wanted to push the boundaries of their understanding of the physical world through unconventional means. At some point during their partnership, Magnus acquired a vial of untainted vampire blood and used it in a serum that "The Five" injected into themselves. After the injection, they each developed Abnormal traits: Magnus experienced drastically slowed aging, and longevity with no clear limit; Nigel Griffin acquired the power to become invisible at will; Dr. James Watson's intellect was tremendously heightened; Nikola Tesla underwent transformation into a vampire, with the additional power of electrical manipulation; John Druitt developed longevity and the ability to teleport through time and space, but, already unstable and soon possessed by a malevolent energy creature, he was driven to give in to his dark impulses and became Jack the Ripper.
Episode Three introduces "The Cabal", a powerful shadow organization that captures, studies, and experiments on Abnormals, in the belief that the Abnormal population is a threat to the human species. During the first season finale, "Revelations", they test a small amount of a biological weapon named Lazarus that causes all types of Abnormals to become extremely violent, attacking anyone nearby and then dying painfully. This is part of The Cabal's overall plan to incite humanity against the Abnormals so that they can wipe out the entire Abnormal population and gain greater influence over humanity. They brainwash Ashley, and in season two, convert her into a vampiric supersoldier, using her as a template for a small army which attacks the Sanctuary network. Against all odds, Magnus and her teams stop them at the Old City Sanctuary, and Ashley, in a moment of clarity, apparently sacrifices herself. Her father, Druitt, hunts down and kills the heads of the Cabal, which seems to disband.
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