French explorer Rene-Robert Cavalier, Sieur De La Salle., thought he had discovered the mouth of the Mississippi River, but in fact, he was 400 miles west at Matagorda Bay, Texas. After antagonizing the local Indians, the colonists crammed into a shelter near the bay. Brackish water led to an outbreak of dysentery. La Salle, still looking for the Mississippi, established an outpost on a smaller river called Fort St. Louis. Short of food and dying of myriad unlucky causes, the explorers turned on each other. After La Salle was murdered, the few survivors headed east and were rescued. Fort St. Louis was overrun by Indians. (Bettmann/Getty Images)