Professor Proton, Sheldon's favorite childhood show, is being rebooted. After unsuccessfully auditioning for the part, he goes to Wil Wheaton for acting tips for his second audition. However, Sheldon is later dismayed when Wil is offered the role instead. Talking it over with Arthur in his dreams, he is still upset to see his idol replaced and considers Wil an enemy again. Meanwhile, Howard gets a vasectomy while Bernadette is on bed rest. Penny offers to take care of Halley for them, but they insult her by expecting her to be irresponsible. Halley ends up saying her first word by calling Penny "Mama."
Penny and Bernadette attend a pharmaceuticals conference, where Bernadette's business rival Danny tries to recruit Penny. Bernadette is offended that Penny is considering the offer. At the meeting with Danny, Bernadette steps in to say Penny is the best saleswoman she knows and Penny agrees to keep working for Bernadette. Meanwhile, the rest of the gang does simple behavioral experiments on the Wolowitz children using a book Sheldon found. Leonard is shocked that his childhood was filled with these experiments; although his mother remembers that time with him fondly, she admits the experiment with him is not over. Raj figures Amy planted the book to get Sheldon to like babies, though Sheldon later states he would be open to having kids.
In March 2017, CBS renewed the series for two additional seasons, bringing its total to twelve, and running through the 2018–19 television season. On August 22, 2018, CBS and Warner Bros. Television officially announced that the twelfth season would be the series' last. This stems from Jim Parsons' decision to leave the series at the end of the season if the show were to have been renewed for a thirteenth season. The series concluded with an hour-long finale consisting of two back-to-back episodes on May 16, 2019. A retrospective, hosted by Johnny Galecki and Kaley Cuoco, aired at 9:30 P.M. ET/PT, the night of the finale, following the season two finale of Young Sheldon.
Although the original pilot was not picked up, its creators were given an opportunity to retool it and produce a second pilot. They brought in the remaining cast and retooled the show to its final format. Katie was replaced by Penny (Kaley Cuoco). The original unaired pilot has never been officially released, but it has circulated on the Internet. On the evolution of the show, Chuck Lorre said, "We did the 'Big Bang Pilot' about two and a half years ago, and it sucked ... but there were two remarkable things that worked perfectly, and that was Johnny and Jim. We rewrote the thing entirely and then we were blessed with Kaley and Simon and Kunal." As to whether the world will ever see the original pilot on a future DVD release, Lorre said, "Wow, that would be something. We will see. Show your failures..."
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The sixth season boasts some of the highest-rated episodes for the show so far, with a then-new series high set with "The Bakersfield Expedition", with 20 million viewers, a first for the series, which along with NCIS, made CBS the first network to have two scripted series reach that large an audience in the same week since 2007. In the sixth season, the show became the highest rated and viewed scripted show in the 18–49 demographic, trailing only the live regular NBC Sunday Night Football coverage, and was third in total viewers, trailing NCIS and Sunday Night Football. Season seven of the series opened strong, continuing the success gained in season six, with the second episode of the premiere, "The Deception Verification", setting the new series high in viewers with 20.44 million.
By season seven, Galecki, Parsons, and Cuoco were also receiving 0.25% of the series' back-end money. Before production began on the eighth season, the three plus Helberg and Nayyar, looked to renegotiate new contracts, with Galecki, Parsons, and Cuoco seeking around $1 million per episode, as well as more back-end money. Contracts were signed in the beginning of August 2014, giving the three principal actors an estimated $1 million per episode for three years, with the possibility to extend for a fourth year. The deals also include larger pieces of the show, signing bonuses, production deals, and advances towards the back-end. Helberg and Nayyar were also able to renegotiate their contracts, giving them a per-episode pay in the "mid-six-figure range", up from around $100,000 per episode they each received in years prior. The duo, who were looking to have salary parity with Parsons, Galecki, and Cuoco, signed their contracts after the studio and producers threatened to write the characters out of the series if a deal could not be reached before the start of production on season eight. By season 10, Helberg and Nayyar reached the $1 million per episode parity with Parsons, Galecki, and Cuoco, due to a clause in their deals signed in 2014.
Cosmologist Stephen Hawking made a short guest appearance in the fifth-season episode; in the eighth season, Hawking video conferences with Sheldon and Leonard, and makes another appearance in the 200th episode. In the fifth and sixth seasons, NASA astronaut Michael J. Massimino played himself multiple times in the role of Howard's fellow astronaut. Bill Nye appeared in the seventh and twelfth seasons.
When Raj misses out on a job at the planetarium, his father says he has no confidence because Howard always makes fun of him. Raj distances himself from Howard and later gets the job. Howard is hurt by this (even after apologizing to him) and tries to make amends with Raj after his first performance at the planetarium but, when he sees him get a date, he leaves without speaking to him, thinking that the latter's life is better without him. Meanwhile, Sheldon and Amy try randomly dividing up wedding tasks, but they keep arguing. The only thing they can agree on is to get married, so they decide to just get married at City Hall. However, Sheldon decides that he wants a first dance with his new wife and they go home to plan their wedding.