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Hojo is a scientist with a God complex, undertaking radical experiments without any regard for ethics or the potential consequences of his research on his test subjects. Hojo regards the subjects of his experiments as mere "specimens," though most are human or otherwise sentient. It was because of these actions that Hojo played a key role as the one who orchestrated the many horrible events that almost destroyed the Planet.
Hojo's notoriety begins approximately thirty years prior to the start of the game in Nibelheim, where he was sent by Shinra to assist Professor Gast and Lucrecia with the Jenova Project, a project headed up by Gast and intended to produce modern day humans with the abilities of the Cetra, which Jenova was mistakenly believed to be a member of. It was believed that this goal may be realized by testing the effects of Jenova cells on an unborn child. Thus, the three Shinra scientists — with Lucrecia and Hojo's complete cooperation — injected some of Jenova's cells into the womb of Lucrecia, who was pregnant with Hojo's child at the time. The child that would come of this experiment was Sephiroth and Vincent, the only man who was against the experiment, was shot and underwent physical alterations by Hojo himself. At some undisclosed point in time, Gast abandoned his research due to a guilty conscience and Hojo continued his increasingly immoral experiments such as implanting Felcia/Elfé with the Ziroconade materia and obtaining Nanaki for his experiments. After Sephiroth "died", Hojo began a new series of Jenova related experiments, first at Nibelheim and, later, the Shinra building, using such unwilling test subjects as Cloud, Zack and uncounted others of Nibelhiem who barely survived. Much of this later research involved the effects of Jenova's cells, leading to the development of the Sephiroth "Clones" Project (not to be confused with genetic duplicates; the term merely indicates that experiments similar to those conducted on Sephiroth were conducted on ordinary humans). Ultimately, Hojo's true ambitions were tied to Omega Weapon, after learning of it and its other siblings from the research of both Grimore Valentine and Gast, intend on using Jenova to force Omega's advent. Once Meteor began to decend toward the planet, tired of experimenting on others and injected himself with Jenova cells to prepare himself for Omega WEAPON as a super-being. However, Hojo succumbed to Jenova and mutated into a monster as he willingly attempted to give Sephiroth the power of the Planet so that he could witness his most esteemed experiment reach its ultimate stage of development. While attempting to carry out this process, he was mortally wounded by AVALANCHE and was left for dead.
As the Maiden who Travels the Planet novella revealed, Hojo's soul was now unable to properly diffuse through the Lifestream as in accordance with the natural order due to the experiments he had conducted on himself, and he allowed his spiritual energy to be assimilated into Sephiroth's body.
In Dirge of Cerberus: Final Fantasy VII, it is revealed that Hojo managed to barely return into his body for a brief moment to upload his mind into the World Network as a backup before it was destroyed during Meteorfall. However, due to Meteor, his conscious mind was fragmented. It would be three years before Hojo's mind was able to have its "reunion" upon the World Network's restoration. Deciding to finish what he started, Hojo took over the body of the 'in-stasis' Deep Ground SOLDIER commander Weiss. During the events of Dirge of Cerberus, Hojo had the Deep Ground abduct those not under the effects of Geostigma to serve as incubators of enough pure Spirit Energy to enable Weiss' body to absorb Omega, which would activate due to fooling it to awaken. However, upon Weiss' defeat, Nero appeared and merged into Weiss's body, "defiling" Hojo's host and forcing Hojo to leave Weiss' body as all traces of himself were eliminated.