The greatest mysteries have a shadowy figure at the center—someone who sets things in motion and holds the key to how the story unfolds—Patient Zero. This hour, Radiolab hunts for Patient Zeroes of all kinds and considers the course of an ongoing outbreak.

We start with the story of perhaps the most iconic Patient Zero of all time: Typhoid Mary. Then, we dive into a molecular detective story to pinpoint the beginning of the AIDS epidemic, and we re-imagine the moment the virus that caused the global pandemic sprang to life. After that, we update the show with a quick look at the very current Ebola outbreak in west Africa. In the end, we're left wondering if you can trace the spread of an idea the way you can trace the spread of a disease and find ourselves faced with competing claims about the origin of the high five.