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There were originally four core interns, but producers felt that another male intern should be added. Enter Alex, who had to be both digitally added to the pilot and required new scenes to be filmed. Considering Alex is one of the most beloved characters on the show, it is an example of this trope turning out well.
Budget cuts for Season 9 were partly to blame for the loss of three regular characters.
Fake American: Jo Wilson is played by an English actress, while Kevin McKidd is Scottish.
Reality Subtext: Early in the show, George is constantly asked whether he's gay. He's not, but his actor T.R. Knight is.
What Could Have Been: Ellen Pompeo revealed that the producers wanted to couple Meredith with Burke, and that Isaiah Washington's disappointment after this idea was scrapped contributed to off-screen tension (that eventually ended up getting him fired).
Word of God: All of the female characters are versions of or parts of Shonda Rhimes' personality, according to her.
What Could Have Been: Sandra Oh (Cristina) had played Brooke Smith (Erica)'s lesbian lover in an unrelated production, and the two mentioned that they would be comfortable with their characters hooking up.