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. In epidemiology, this central character is known as Patient Zero—the case at the heart of an outbreak. This hour, Radiolab hunts for Patient Zeroes from all over the map.

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, and we re-imagine the moment the virus that caused the global pandemic sprang to life. After that, we're left wondering if you can trace the spread of an idea the way you can trace the spread of a disease. In the end, we find ourselves faced with a choice between competing claims about the origin of the high five. And we come to a perfectly sensible, thoroughly disturbing conclusion about the nature of the universe ... all by way of the cowboy hat.