Radiolab's episode explores the concept of "Patient Zero," the initial case driving an outbreak. The program revisits a 2011 episode focusing on iconic Patient Zeroes. It begins with the story of Typhoid Mary, a famous historical example. The episode then delves into a molecular investigation to identify the origin of AIDS. It also reconstructs the emergence of the virus responsible for the global pandemic. The show questions whether ideas can be traced like diseases. Finally, it examines conflicting accounts regarding the origin of the high five. Listeners can engage further through newsletters and by supporting Radiolab. The show also encourages interaction via social media and email.