Leonard gives an interview on public radio where he admits physics research might be at a dead end. The university is furious and, while trying to think of reasons to put in a retraction, he depresses Sheldon into thinking he might be right. Howard and Raj come over and end up just as depressed. Getting drunk with Penny, the men go to the grave of Richard Feynman and realize there is hope for physics as long as they believe in it. Leonard accidentally sends a drunken email to Human Resources. Meanwhile, Amy and Bernadette agree with each other to keep quiet about the success in their careers so as not to upset Sheldon and Howard. While bragging to each other, they end up arguing which of their fields is better.
Sheldon and Amy are surprised to find that Wil Wheaton's new Professor Proton show is actually very entertaining and that Wil had Howard on as a guest. On Howard's suggestion, Sheldon apologizes to Wil, mending their friendship, and tells him he wants to be on the show; but Wil asks for Amy. Sheldon tells her to do it, but she says she often doesn't do things to avoid upsetting him. Sheldon is horrified when he realises how selfish he has been, especially when he finds out that the men do the same for him. Sheldon encourages Amy to go on the show to inspire girls to pursue science while trying to control his obvious jealousy for her. Meanwhile, Leonard writes a book about a physicist that solves a murder, the protagonist Logan Dean is based on himself. Bernadette points out Logan's mean boss Illsa is similar to Penny, who thinks it is based on Bernadette, though Leonard does not correct her. However, Bernadette tells Penny the truth, upsetting her and making her mad at Leonard. After calling his mother for advice, Leonard learns that Illsa is actually like her; but abandons the book when he realizes he wrote romantic tension into the relationship between the characters.
Sheldon's mother Mary refuses to attend his wedding unless he invites his older brother George, with whom he is no longer speaking. Sheldon and Leonard fly to Texas to talk to George, who now owns a chain of tire stores. He refuses to attend and later explains to Leonard and Sheldon that the family sacrificed a lot to fund Sheldon's education, and he was stuck caring for their mother and sister Missy after their father died while Sheldon was in college. Sheldon never thanked him for this. Leonard takes George back to the hotel room where Sheldon apologizes for what he did and the brothers reconcile. George agrees to attend the wedding. Meanwhile, Howard and Bernadette's children contract pinkeye, infecting everyone except Penny, much to Amy's fury.
Mayim Bialik as Amy Farrah Fowler (guest star season 3, starring seasons 4–12): A woman selected by an online dating site as Sheldon's perfect mate. Amy is from Glendale, CA. While she and Sheldon initially share social cluelessness, after befriending Penny and Bernadette she eventually becomes more interested in social and romantic interaction. Her relationship with Sheldon slowly progresses to the point at which Sheldon considers her his girlfriend, eventually they get married. Amy believes she and Penny are best friends, a sentiment that Penny does not initially share. Amy has a Ph.D. in neurobiology.
Johnny Galecki as Leonard Hofstadter: An experimental physicist with an IQ of 173, who received his PhD when he was 24 years old. Leonard is a nerd who loves video games, comic books, and Dungeons & Dragons. Leonard is the straight man of the series, in which he shares an apartment in Pasadena, CA, with Sheldon. Leonard is smitten with his new neighbor Penny when they first meet, and they eventually marry.
Two nerdy physicists share an apartment and an unlikely friendship with their beautiful neighbor with whom one of them is infatuated. Like the universe after the big bang, the show's popularity expanded, thanks to breakout star Jim Parsons, along with the chemistry among the friends and the developing romance between Leonard and Penny. The addition of Melissa Rauch and Mayim Bialik in later seasons also enhanced the stories and relationships of the leads.
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.
While opening their wedding gifts, Sheldon and Amy cannot figure out the purpose of the glass shard Leonard and Penny gave them. They decide it must be a clue to a scavenger hunt to the real gift. They eventually end up in the coffee shop where they first met and find a locket in the lost and found that they think must be the real gift. The glass shard was actually a crystal chakra wand that Raj gave as a gift to Howard and Bernadette, who then re-gifted it to Leonard and Penny, who finally passed it on as a joke. Leonard and Penny find it less funny when they are given a coded thank-you note they have to use to unlock their WiFi. After making out with his employee Denise at Sheldon and Amy's wedding reception, Stuart finally asks Denise out on a date; while preparing for the date, he has a spray-tan accident, but she just finds it funny and still goes out with him. Raj is depressed everyone else has a relationship and asks his father to arrange a marriage.
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