The Science Movie Day allows Ms. Hoover to fall asleep as her class watches a film that Lisa feels doesn't fit in the lesson plan. Lisa even goes as far as creating her own lesson plan that would have covered what the students should have been learning. What appears to be an earthquake disrupts Lisa's agenda. It turns out that the shaking is caused by students stampeding in the hallways because it's Taco Tuesday. Homer and his co-workers sneak into the school to take advantage of this day. Lisa observes Bart eating his sixth taco and the lunch lady retaining the salad for another meal. After Lisa questions whether the vegetables will rot or not, the lunch lady tells her that the veggies are genetically modified, so they should last. While Lisa reads about the effects of eating genetically modified foods in the car, Marge rushes to get to the church before the volunteer sign-up position she wants are gone. Too late, as Marge gets suckered by Ned into giving the sex talk to kids. It's no use, though, when both teenagers at the meeting just go at it in front of Marge. Afterwards, Lisa presents her argument at the parent teacher meeting at school. After watching a confusing video Lisa runs off to do 'actual research' and discovers genetically modified foods can actually be a good thing much to the surprise of her audience.
When a corporation takes interest in Lisa's initiative to drive genetically modified foods home, little does Lisa and her family know that Sideshow Bob is the chief scientist behind it all. Once Bob recounts how he became a test subject so that monkeys would not be injured too much, he tries to rekindle his relationship with the Simpsons. Lisa, especially, connects with Bob through their mutual love of Walt Whitman, and Bob notes that Lisa was always the best family member out of the Simpson clan. Meanwhile, Marge returns to giving her sex talk to teenagers, but this time she prepares with finger puppets. While the teenagers snicker, Marge fails miserably to get her point across about sex. Elsewhere, Lisa enjoys Bob's company despite Homer's usage of the Bunsen burner to toast the rest of the marshmallows since he already ate all the chocolates. At home, Homer tries to squeeze in some alone time with Marge, yet an angry Marge decides to use Homer as an example for her sex education class. Marge brings Homer to church to tell her class that she has abstained from sex with her partner for two days. The mere image of Homer and Marge touching each other gives the teenagers enough reason to pledge to wait until marriage for sex.
Lisa, on the other hand, is having a blast with Bob at the museum. Despite having to carry his concrete ankle block from prison, Bob enjoys his time with Lisa. When Lisa passes through an exhibit, a heavy display model comes close in squashing Lisa, but Bob saves the day. But Lisa wants to know, how Bob had the strength to prevent the sheet metal from crushing her. That's when Bob reveals to Lisa that with the success of genetically modified foods, he has been able to change his own DNA. Bob also tells Lisa that the real reason behind their trip to the museum is because of his plans on using the DNA of the geniuses in the exhibit to become the smartest of them all. 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 "grasshopper 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. He obliges, but Marge, Homer and the teen-abstinence group come to stop him. When Lisa talks about Walt Whitman, Bob realises he has become a monster and attempts suicide by drowning, but then remembers he has gills.
In an epilogue (done as a tribute to Marcia Wallace), Ned recalls how much he loved Edna, and is sad about her death.