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Spock gave his friend James T. Kirk an antique hardbound copy of the novel for the latter's 52nd birthday in 2285. Although Spock claimed that there was no implicit message in the gift, Kirk took special meaning from the final words of the book: "It is a far, far better thing that I do, than I have ever done; it is a far, far better rest that I go to than I have ever known." (Star Trek II: The Wrath of Khan)
A Tale of Two Cities was the favorite book of Miles O'Brien's mother. In 2375, Ezri Dax loaned Julian Bashir Jadzia's old copy of the novel. Bashir was only part-way through the novel when he was trapped in Luther Sloan's mind; he became aware of this fact when he went to read more of the book, and found the remaining content missing. (DS9: "Extreme Measures")