It was in Star Trek that Nichols gained popular recognition by being one of the first black women featured in a major television series not portraying a servant; her prominent supporting role as a bridge officer was unprecedented. During the first year of the series, Nichols was tempted to leave the show, as she wanted to pursue a Broadway career; however, a conversation with Dr. Martin Luther King, Jr., changed her mind. She has said that King personally encouraged her to stay on the show, telling her that he was a big fan of the series. He said she "could not give up" because she was playing a vital role model for black children and young women across the country, as well as for other children who would see African Americans appearing as equals. It is also often reported that Dr. King added that "Once that door is opened by someone, no one else can close it again."
Former NASA astronaut Mae Jemison has cited Nichols's role of Lieutenant Uhura as her inspiration for wanting to become an astronaut and Whoopi Goldberg has also spoken of Nichols's influence. Goldberg asked for a role on Star Trek: The Next Generation, and the character of Guinan was specially created, while Jemison appeared in an episode of the series.
In her role as Lieutenant Uhura, Nichols famously kissed white actor William Shatner as Captain James T. Kirk in the November 22, 1968, Star Trek episode "Plato's Stepchildren". The episode is popularly cited as the first example of an inter-racial kiss on United States television.
The Shatner-Nichols kiss was seen as groundbreaking, even though the kiss was portrayed as having been forced by alien telekinesis. There was some praise and some protest. In her 1994 autobiography, Beyond Uhura, Star Trek and Other Memories, on page 197 Nichols cites a letter from one white Southerner who wrote: "I am totally opposed to the mixing of the races. However, any time a red-blooded American boy like Captain Kirk gets a beautiful dame in his arms that looks like Uhura, he ain't gonna fight it." During the Comedy Central roast of Shatner on August 20, 2006, Nichols jokingly referred to the groundbreaking moment and said, "Let's make TV history again ... and you can kiss my black ass!"
Despite the cancellation of the series in 1969, Star Trek lived on in other ways, and continued to play a part in Nichols's life. She again provided the voice of Uhura in Star Trek: The Animated Series; in one episode, "The Lorelei Signal", Uhura assumes command of the Enterprise. Nichols noted in her autobiography her frustration over this never occurring in the original series. Also, Nichols has co-starred in six Star Trek motion pictures, the last one being Star Trek VI: The Undiscovered Country.
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