The episode opens with a short montage of clips from the series' twelve seasons, then segues to Sheldon and Amy, who are up late waiting for a call from the Nobel Committee. Following a prank call from Kripke, they are told they've won the Nobel Prize in Physics for their super-asymmetry work. The attention from the media and the university bothers Sheldon. Amy is saddened by an unflattering picture of her in a news report, so Raj convinces her to get a makeover. She loves her new look but Sheldon demands she change it back. Leonard calls him out for being rude, but Sheldon flees when he sees Penny emerge from the newly repaired elevator. Sheldon and Penny go to the Cheesecake Factory and Penny tells Sheldon that change is the only constant thing in life. On a TV, they see Bernadette and Howard take credit as Sheldon and Amy's best friends. Raj and Leonard defend Amy, with Leonard accidentally breaking Sheldon's DNA molecule model in Apartment 4A. Penny convinces Sheldon to ride in the elevator.
The scene is all business – at least as much as you can expect from a bunch of cut-ups making a sitcom – and no one seems distracted by two significant events: The episode will mark the show’s 276th, moving it past “Cheers” to set a record for a sitcom filmed in front of a studio audience, and only three more remain to be shot for "Big Bang," co-created by Chuck Lorre and Bill Prady.
Sheldon and Amy recruit Leonard to research and write citations for their paper on super asymmetry. While working in the campus library, Leonard and Raj discover a Russian paper that asserts that super asymmetry has no merit. Reluctantly, Leonard shares the news with Sheldon and Amy, who fall into a depressive state and do not leave their apartment. Meanwhile, Bernadette asks Denise to teach her how to play Fortnite: Battle Royale so that she can beat Howard. Despite losing to Howard in a rematch after all of her training, Bernadette revels in beating a disinterested Penny.
After learning Sheldon went behind their backs to work with the military again, Leonard and Howard say Sheldon is like Thomas Edison, taking credit for others' ideas, while they are more like Nikola Tesla. Leonard and Howard bring in Barry Kripke to help create a better idea than Sheldon's, but Kripke goes to the military himself, cutting all three of them out. Meanwhile, Bernadette fears Ruchi is trying to steal her projects at work while she is on maternity leave and enlists Raj to spy on her. Though he finds proof that Ruchi may be stealing from Bernadette, Raj tries to defend Ruchi like a boyfriend would, pointing out Bernadette's hypocrisy as she would most likely have stolen from other people's projects as well. Ruchi is not happy about this and promptly dumps Raj.
The show's pilot episode premiered on September 24, 2007. This was the second pilot produced for the show. A different pilot was produced for the 2006–07 television season but never aired. The structure of the original unaired pilot was substantially different from the series' current form. The only main characters retained in both pilots were Leonard (Johnny Galecki) and Sheldon (Jim Parsons), who are named after Sheldon Leonard, a longtime figure in episodic television as producer, director and actor. A minor character, Althea (Vernee Watson), appeared in the first scene of both pilots that was retained generally as-is. The first pilot included two female lead characters - Katie, "a street-hardened, tough-as-nails woman with a vulnerable interior" (played by Canadian actress Amanda Walsh) and Gilda, a scientist colleague and friend of the male characters (played by Iris Bahr). Sheldon and Leonard meet Katie after she breaks up with a boyfriend and they invite her to share their apartment. Gilda is threatened by Katie's presence. Test audiences reacted negatively to Katie, but they liked Sheldon and Leonard. The original pilot used Thomas Dolby's hit "She Blinded Me with Science" as its theme song.