It was first mentioned by Hitomi in chapter 33 when he told Sakura about it, but died before he could say any more. It was then mentioned variously throughout the story, until one of the Four Founders of Eden, Masaomi Heike, began to explain it in chapter 144. He explained that when the blood of a Rare Kind and a Power User come in contact with each other, it causes a phenomenon called Negation. On December 32, Ogami and Sakura, for an unknown reason, tried to kill each other, resulting in a negation, which killed many Power Users and Ogami.
In chapters 179 and 180, Heike reveals that he lied and told them what really happened. At the time, nobody knew about Negation; however, in some unknown circumstance, they discovered it. Code:Emperor, in an attempt to prevent Negation from ever happening, tried to separate all Rare Kinds and Power Users from ever having any contact. But a number of Rare Kinds, two of which were Shibuya and Sakura Sakurakouji, didn't want to be seperated from their families. One day, after failing several persuasion attempts, Code:Emperor began killing any Rare Kind who didn't do as he said. "Fussy Lunch", who, along with Ogami and Sakura, witnessed this, used his Rare Kind-powers to kill Ogami and the Power Users present. By doing so, however, he would cause a mass Negation that would destroy the world. At this point, Sakura somehow sealed the phenomenon, and into a golden box that would later be called Pandora's Box. After it's creation the box also absorbed people and objects, but, as result of their strong wills stopping them from being absorbed, Ogami, Sakura, "Fussy Lunch" and Mishiru/Kagerou trancended time and space, making them stay young, till about ten years before the story.