Generally, a protagonist is someone the reader recognizes as the hero of the story, the one we cheer for on the sidelines. But, no such heroes exist in Cat's Cradle. Instead, we get John. John is the protagonist because he's the straight man, the character the audience relates best to, especially considering all the insanity and crazy characters filling this novel.
Here's a small example. San Lorenzo's rum is made with a special ingredient: acetone, a.k.a. model-airplane cement. This repulsive ingredient seems to go unnoticed by H. Lowe Crosby, who downs the rotgut. But like the reader, John finds the idea of drinking acetone a little hard to shallow (ba-dum-tish!). We'll talk more about John being in on the joke in our "Character" section.