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He recalled meeting Paul Newman there, and that the older actor encouraged him to work in the theatre in 1993 when filming a British TV production of the Tennessee Williams play Suddenly, Last Summer with (the now) Dame Maggie Smith and Natasha Richardson.and two Golden Globe Award nominations for Best Actor in a Drama Series.In 2011, Lowe appeared on The Oprah Winfrey Show and stated that he left the show because he did not feel he was being respected, when the other lead characters received a raise and he did not. In 2005, he starred as Lieutenant Daniel Kaffee in a London West End production of Sorkin's play A Few Good Men, the first time the two had worked together since The West Wing.After leaving the show, Lowe was the star and executive producer of a failed NBC drama, The Lyon's Den (2003). Although Lowe had expressed unhappiness about his decreased role on that show at the time of his departure, he has now repeatedly said that any animosity between them is over and that he was pleased to be working once more with Sorkin, whose talents as a writer Lowe highly regards. Derek Shepherd of Grey's Anatomy, which eventually went to Patrick Dempsey.Despite his two cancelled TV series and flops like View From the Top and the made-for-TV movie Perfect Strangers during his post–West Wing run, Lowe found success in the TV miniseries genre.The year 2004 marked his return to this genre; he had appeared in 1994's The Stand, based on Stephen King's book of the same name.
Lowe and series creator Aaron Sorkin soon found themselves at odds over the network's meddling with the show, most notably the network demanding changes in the Sam Seaborn character.
In June 2006, he was the guest host for an episode in the third series of The Friday Night Project for the United Kingdom's Channel 4.
Lowe has also appeared in a televised advertisement for 'Visit California', along with other celebrities including Governor Arnold Schwarzenegger.
Eventually, Lowe left the series, not long before Sorkin and director/executive producer Thomas Schlamme unceremoniously quit over a dispute with NBC.
During the final season of The West Wing, Lowe returned to his role of Sam Seaborn, appearing in two of the final four episodes.
Lowe was drawn to the role because of his personal love of politics, and his longstanding personal relationship with Martin Sheen, who was cast as President Bartlet.