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The fifth-year residents return for the first day of a year that will make or break their careers: Meredith faces the consequences of tampering with Derek's clinical trial and is terminated at the hospital; April tries to step up to the plate as Chief Resident in the wake of a giant sinkhole in the middle of Seattle; and Cristina and Owen are still at odds over their drastically different feelings for their unborn child.
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News of Meredith and Derek's unsteady relationship raises a red flag for Zola's adoption counselor; Alex quickly realizes that he has become the outcast of the group after ratting out Meredith; and Cristina makes a tough decision regarding her unexpected pregnancy. Also, Chief Webber brings Henry in for a last minute surgery, alarming Teddy.
This is an historic episode that finally crosses a long-standing barrier.
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The Chief makes a career-changing decision that shocks Seattle Grace Hospital; Cristina and Owen try to find normalcy in their relationship; April continues to struggle in her new role; and the 5th year residents are given their first solo surgeries, only to find out that even the most routine procedures aren't always easy.
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The doctors of Seattle Grace are called upon to man up when a stampede at a comic book convention causes an influx of colorful characters in the OR - blurring the lines of fantasy and reality; Mark shows his softer side with baby Sofia when Arizona and Callie go out of town, but at work he continues to give Jackson a hard time; Ben returns to the OR, only to find that Nurse Eli has moved in on Bailey; and the male doctors bond over their frustrations with women.
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The residents try their hardest to impress surgical great Catherine Avery-who also happens to be Jackson's mother-when she arrives at Seattle Grace to perform a groundbreaking transplant surgery; Arizona and Alex find their hands tied with a confidentiality issue when a familiar patient comes into the ER; meanwhile, a love-struck Teddy throws a dinner party for the couples, and Bailey makes a decision regarding her love life.
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After being blackballed by most of the surgeons, Meredith uses Lexie to spark Derek's interest in her patient's rare brain tumor case and, in secret, gives guidance to April with Bailey's clinical trial; Callie's wish for Arizona and Mark to form a friendship comes to fruition and she realizes it's more irritating than helpful; Alex and Teddy research alternative surgeries for a very superficial patient; and Callie and Cristina struggle with a very difficult spinal surgery.
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While Chief Hunt attempts to build team-working skills amongst the doctors of Seattle Grace Mercy West in preparation for their big game against Seattle Presbyterian, Alex investigates into the legal proceedings around Zola's adoption. Derek prepares for a surgery never before preformed and Teddy has a seemingly unusual plan for Cristina's future in surgery.
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The doctors become nostalgic when George O'Malley's mother, Louise, returns to Seattle Grace for medical help after a botched surgery at a neighboring hospital; the residents are inspired by a medical miracle when they witness a harvested heart that continues to beat outside the body; a new pediatric fellow excites Arizona and makes Alex feel threatened; Jackson lets his suspicions about Mark and Lexie interfere with his work; and Henry and Teddy have their first marital fight when he expresses interest in pursuing medical school.
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Teddy puts her husband's life in the hands of her peers when Henry is sent to the OR for surgery and she's called away on another case; Meredith and Derek receive the long-awaited news about Zola; Callie and Jackson come under fire when their patient experiences post-surgery complications; and Meredith and Alex are involved in a life-threatening situation when they travel to a neighboring hospital to tend to a sick newborn.
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A severe car crash involving an entire family results in an all-hands-on situation in the ER, as the eldest daughter is left to make the toughest decision of her life. Meanwhile Teddy, still in the dark about Henry's death, calls upon Cristina to help with her patient in the O.R., and Lexie finds herself working alongside Mark's new girlfriend, Julia, during an eye surgery.
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The doctors split into teams for a risky surgery involving conjoined twins; Bailey recruits Meredith to be a buffer between her and Ben when he puts pressure on moving their relationship to a more serious level; Richard teaches Alex a tough lesson in the OR; meanwhile Teddy questions Cristina about what exactly happened to Henry during his surgery.
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While Derek prepares to operate on a tumor deemed entirely inoperable, Hunt pressures Meredith to declare a specialty. As Cristina and Teddy try to steal a prized cardio surgery, the doctors celebrate Richard's 10,000th surgery.
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What if Meredith had had a happy childhood? What if Ellis Grey had never gotten sick? What if Derek and Addison had stayed together? Then what would have happened? We see the very different lives of the doctors of Seattle Grace in an alternative world and wonder who controls our destiny? Are certain things meant to be?
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On Valentine's Day, Lexie volunteers to watch Zola for Meredith and Derek; Callie plans an evening for Arizona; and Ben shows Bailey how much he cares. Meanwhile, Christina and Owen drift farther apart, despite the fact that he saves her when a car crashes into the hospital. Meredith and Bailey treat a woman who has headaches and seizures. Webber and Lexi treat a man who was hit by a car during a fight with his girlfriend. And Alex treats a 10-year-old girl who has a severe reaction to peanuts when her boyfriend gives her a Valentine's Day gift.
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In a final attempt to save Erica's life, Amelia arrives at Seattle Grace to beg Derek for help with the gliosarcoma case; Cristina and Owen engage in heated arguments during marriage counseling; Alex realizes that in order to be a good doctor, he'll need to improve his people skills; and Meredith is given a chance to shine when a man enters the ER after getting his hand stuck in meat grinder. Meanwhile, the residents continue to study for their upcoming oral boards.
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As Adele's condition continues to deteriorate, Richard considers altering their living situation; an explosion at a local coffee shop results in a busy day in the ER for the doctors; Callie takes Meredith under her wing by helping her study for her boards; Lexie joins Arizona and Alex in peds, as they continue to care for intern Morgan's premature son; and when Jackson snaps at a patient, Mark encourages him to find ways to relieve his stress. Meanwhile, Cristina lets her suspicions get the best of her.
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Derek encourages a hesitant Meredith to work with him again in neurology; Jackson's mother, Catherine Avery, returns to Seattle Grace with a urology fellow and develops an interest in Richard; and Cristina becomes increasingly suspicious of Owen's every move. Meanwhile, Alex tries to deny the fact that Morgan may be falling for him.
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A pet lion on the loose gives the hospital some fierce injuries to deal with. Meanwhile, Cristina continues to ignore Owen, Lexie reconsiders her feelings for Mark, Callie has to face Arizona's romantic past with other hospital staff, and Alex starts to feel uncomfortable about his relationship with Morgan.
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Grey, Bailey, and Webber work on a multi-organ transplant but run into some barriers when Dr. Sloan, the temporary Chief, orders them to cancel the surgery. Meanwhile, Cristina and Owen spend the day at home, working through their marital problems.
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While the hospital becomes the center of attention as the victim of a famous kidnapping case is brought to the hospital, the fifth years take their placement interviews. Meanwhile, Adele Webber's memory continues to deteriorate, forcing Richard to reconsider their relationship.
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As the fifth years head off to San Francisco to take the most important exam of their lives, with some surprises along the way; Owen and Teddy continue to fight back at the hospital, Mark and Lexie reconnect, and Tommy's condition worsens even more.
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Six hours after their oral boards, the fifth years relive their answers and worry about their chances. Back at the hospital, Bailey has to woo potential candidates for the hospital and Mark is startled when Julia makes a proposal about their future.
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Before the Seattle Grace doctors head to Boise to take part in an operation on conjoined twins, the Attendings pressure the 5th years for final decisions on their posts next year. Meanwhile, Arizona must face the reality of her friend's condition and Ben tries to get Bailey to go on a special lunch date.
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As Meredith, Cristina, Derek, Mark, Lexie, and Arizona face the aftermath of their accident, the doctors back at the hospital face the future that seems to be taking them all in different directions.