On a research trip, Lisa is shocked to discover that Sideshow Bob is now the chief scientist at a massive chemical engineering company, but they bond over their appreciation for high-culture. Meanwhile, Marge attempts to preach healthy sexual practices to a teen church group, which goes awry.
The episode starts off with a Taco Tuesday in Springfield Elementary. Students rush out of everywhere to get to the tacos. After Lisa finds out that the vegetables in the cafeteria are Genetically Modified Organisms, she organizes a meeting with the town to alert them of this. However, after research she finds out that GMOs are actually good for the world. Meanwhile, Marge tries to talk to a teen-abstinence group with finger puppets and the teens aren't taking it seriously. When a representative of the Monsarno research campus meets Lisa at a fair, she asks her to come to the campus. There, they find that the company's chief scientist is none other than Sideshow Bob.
He assures the Simpsons that he is done with being evil and convinces Lisa that they could talk about fine art together. She plans to visit him and they have a nice talk. At Marge's abstinence courses with the teenagers, she finally makes progress with them, however bottling their urges causes them to become stressed out and destructive. Bob and Lisa visit a museum and after Bob saves Lisa from falling objects, she asks why he's so strong. He admits that he's been changing his DNA and the real reason they are at the museum is so he can steal DNA of the most intelligent people that ever lived. When Bart comes to save Lisa, Bob warns he can be tempted into a murderous rage very easily.
After a couple bothers him for a minute, he does have a rage and goes after Bart and Lisa. He runs after them with his new "grass-hopper thighs" and "sonar of a killer-whale". He chases them to a body of water and they beg him to sing before he kills them. So he does but Marge, Homer and the teen-abstinence group come to stop him. When Lisa talks about Walt Whitman, Bob realizes he's become a monster and attempts suicide by drowning, but then remembers he has gills.
In an epilogue, Ned Flanders recalls how much he loved Edna by reminiscing them doing the tango together, and is sad about her passing (as he is shown wearing a black armband). Then Nelson comes by to say "Ha-ha" until he offered his sympathy to Ned about how he also misses her.