As the years passed, the First Civilization inevitably became extinct, though humankind continued to revere them as gods in their various Pagan religions. It was not until the rise of three monotheistic religions of Judaism, Christianity, and Islam, which soon spread across the globe, that humanity began to forget their "gods", though there were those who continued to worship them, and those who came to see the First Civilization for what they really were. Foremost among these groups were the Templars and the Assassins.
By the 12th century, both Orders firmly believed that the gods of old did not truly exist, and realized that many so-called "miracles" attributed to them had actually been the workings of the Pieces of Eden. However, upon the acquisition of one such Piece – an Apple of Eden – by the Assassin Altaïr Ibn-La'Ahad in 1191, humanity at last became aware of the true nature of the humanity's pagan gods.
Inside, Minerva warned Ezio of the catastrophe her species had suffered, and that it would happen to humanity once again. However, even this did not ensure humanity's knowledge of the true nature of the gods of old, and by the early 21st century, the Assassins once again knew very little of the true nature of the First Civilization.
However, this changed in 2012, when the Assassin Desmond Miles used the Animus, a device derived from the First Civilization technology, to relive the genetic memories of his ancestor Ezio Auditore, and witnessed the warning of the future cataclysmic event.
- “我们没有使他们变得明智。但现在他们是我们最后、有缺陷的希望。你代表他们。你有可能去理解 [...]几百年间我可说而你们仍然不知道我们。 你们只有五感，而我们有第六感。这便是我们与你们的区别。”
The human race was developed in the image of their creators, to serve as a docile workforce for the low numbered, but technologically advanced Isu. Artificially developed by drastically altering the pre-existing genetic make-up of native species, the creation of humanity left a sizable gap in terms of transitional species between archaic hominids and modern humans.
By 1997, the Templars, who were aware of the full and true nature of the First Civilization, had taken note of this, and arranged for fake skeletons to be planted in Ethiopia, so as to limit human exposure to the possibility of the existence of the First Civilization.
Early humans could not comprehend the true nature of their creators, choosing to see them as gods, and in order to ensure the obedience of their creations, the First Civilization bred a neurotransmitter into humanity, located deep within the brain. This neurotransmitter forced humanity to abide by the Pieces of Eden, which were technologically advanced pieces of equipment that granted a myriad of powers, including the ability to induce hallucinations in the minds of those bearing the transmitter, as well as telepathically control said humans.
However, there were humans born without the neurotransmitter, and as such were not susceptible to the mind-controlling powers of the Pieces of Eden. Over three centuries, their numbers grew, until they numbered enough to confront the First Civilization directly, resulting in the war which nearly destroyed both races.
Since some human individuals were born without a neurotransmitter, Clay Kaczmarek would later theorize that this was made possible by cross-breeding between humanity and their "gods", and that not only did this remove the neurotransmitter, or at least the neurotransmitters susceptibility to the Pieces of Eden, but also granted a number of genetically encoded abilities.
One such ability, known as Eagle Vision, was particularly prevalent in the bloodline of the Assassin Altaïr Ibn-La'Ahad, with many of his descendants also bearing the ability.
It was also prevalent in the bloodline of the Auditore family and Giovanni Borgia. Additionally, possession of the mixed bloodline granted the bearer increased control over the technologies of the First Civilization; Ezio Auditore was able to use the a Staff and Apple of Eden conjunction to open the Vatican Vault, whilst the pure-blooded human Rodrigo Borgia could not.