Misty was mentally scarred by the randomization that occurred in FireRed and became a Poison-type gym leader in an attempt to poison the city's water supply. She was taken into therapy and returned years later and resumed her role as gym leader.
During the initial runthrough, some viewers who had recently joined the chat and saw that Red was in Cerulean City were unaware that Misty had already been defeated and started saying "We need to beat Misty!" This subsequently became a meme, and later mutated into various other sayings, such as "We need to milk Whitney!" or "We need to beat [gym leader of current city]!"