It started in the Village hidden in the Leaves during the First great Shinobi war.
The peace brought by the God of Shinobi, Hashirama Senju did not last as ambition assailed the villages, greed for Ressources, Glory and Power.
The conflict's escalation for the first war began on the fateful day of Hashirama's death.
Thus, the second Hokage, Tobirama Senju rose to Power. But he lacked the power and respect his elder brother had commanded and soon found himself assailed on all fronts.
Slowly, the pressure chipped away at Morals and wishes, giving way to Pragmatism and necessity. More and more Jutsu were developed, all in hope to strengthen the leaf. More and more lines were crossed, all in hopes of protecting his older brothers legacy.
Until, even that line was crossed. And the right arm of the Legendary Hashirama Senju was cut off away from his corpse and molded into a human.
But as the experiment failed, the Hokage finally took notice of the depravity hanging around him, leading to him locking away forbidden Jutsu and disposing of Experimentation.
Until years later, during the rise of the third Hokage and the tension between villages rising during the Second Great Shinobi War, the experiment was discovered, reassembled and begun anew.
And this time, it did not fail as the vitality of Hashirama's chakra was balanced with the hateful red eye of the Uchiha.
Thus, a curse awakened, the very spirit of the first Hokage and the forest, howling in protest at the depravity of the Shinobi world.