Humans are a species of bipedal primates that originated on Earth and are, currently, the dominant form of life on the planet. An evolutionary development brought about by the Isu in order to create a numerous, hardy, and docile workforce humans were the result of forced evolution.
Genetically engineered from a pre-existing primate species, humans were moulded to suit the specific requirements of their Isu masters; some, such as Homo neanderthalensis, were built to serve as a military force, whilst Homo sapiens were destined to serve as laborers.
Following a prolonged period forced subservience, humanity eventually rebelled against the "gods" and a decade-long war broke out. This conflict only came to an end due to the Great Catastrophe, which saw both species brought to the edge of extinction. Whilst humanity's numbers ensured the species could survive the catastrophe, the Isu did not fare so well.
Within 100 years of the catastrophe, humanity's creators became extinct, leaving only ruins and scattered artifacts as testament to their existence. Now orphaned of their creators, Homo sapiens assimilated some of their fellow genus and rose to become the dominant form of life on the planet.
Humanity, including many species of the Homo genus, such as Homo sapiens or Homo neanderthalensis, was artificially created by the Isu at some point between 1923 and 2296 Isu Era (c.75,383 - 75,010 BCE) to serve as docile servants, workers, or soldiers, for their Isu creators, whom humanity came to look upon as gods. However, as time progressed, humanity eventually came to resent the rule of their "gods", and the period of peace that had existed between master and servant gave way to times of war.
Preceded by the theft of an Apple of Eden by the hybrids Adam and Eve, the war blinded both humanity and the Isu to the goings-on beyond their planet, and as such neither race foresaw the pending Great Catastrophe, a solar flare, that would nearly destroy both races, until it was too late.
Brought to the brink of extinction, humanity and their "gods" came together to rebuild. Together, both species built at least three Vaults beneath what would later become the city of Rome, to serve as a warning to humanity's descendants; unlike their "gods", whose small population was approaching complete extinction, humanity's sheer weight of numbers ensured their survival.
As the years passed, the Isu inevitably became extinct, though humankind continued to revere them as gods in their various religions. It was not until the rise of monotheistic religions such as Judaism, Christianity and Islam began to spread across the globe that humanity forget their pagan "gods", though there were those who continued to worship them, and those who came to see the Isu for what they really were. Foremost among these groups were the Assassins and Templars.
By the 12th century, both Assassins and Templars 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 started to become aware of the true nature of the old pagan gods.
Inside, Minerva warned Ezio of the catastrophe her species had suffered, and that it would happen to humanity once again. However, poor documentation and continued strife with the Templars made it difficult for knowledge of the Isu to be retained for long periods at a time. By the early 21st century, the Assassins once again knew very little of the true nature of the Isu.
This changed in 2012, when the Assassin Desmond Miles used the Animus, a device derived from the Isu technology, to relive the genetic memories of his ancestor Ezio Auditore, and witnessed the warning of the future cataclysmic event.
- "We did not build them to be wise. And now they are our final, faulted hope. You are they. You possess the potential for understanding [...] A hundred years I might speak and still you would not know us. You with five senses. Us with six. The one we kept from you."
- ―Juno on humanity.[src]
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 Isu, had taken note of this, and arranged for fake skeletons to be planted in Ethiopia, so as to limit the general populous' exposure to the possibility of the existence of the Isu.
Early humans could not comprehend the true nature of their creators, instead choosing to see them as gods. In order to ensure the obedience of their creations, the Isu developed a neurotransmitter that was inserted into the neural network of their workforce. This neurotransmitter responded to the commands of certain Pieces of Eden and ensured humanity's obediance by controlling their thoughts, emotions, and behaviors. Over time, however, interbreeding between Isu and humans led to the development of a hybrid species that were 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 Isu directly, resulting in the war which nearly destroyed both races.
Following the birth of the hybrids, and their eventual interbreeding with pure-blooded humans, humanity's bloodlines became mixed with that of the Isu. After millennia of dilution, a typical human in the 21st century possessed roughly 0.0002% to 0.0005% Isu DNA in their genome, though certain bloodlines more directly related to the original hybrids possessed significantly higher amounts. Even then, however, these bloodlines paled in comparison to the Sages, who typically possessed upwards of 5% to 6% Isu DNA in their genome.
The individuals descended from the hybrids also benefited from a variety of genetically encoded abilities, presumably inherited from their Isu ancestors. Such abilities included increased strength and dexterity, an affinity in using and resisting the Pieces of Eden and other Precursor relics and a natural, albeit limited, access to the Isu's Sixth Sense: Eagle Vision. Such individuals did not lose their sanity upon exposure to the Pieces of Eden. Ezio Auditore, for example, was able to use a Staff and an Apple of Eden in conjunction to open the Vatican Vault, whilst the pure-blooded human Rodrigo Borgia could not.
During the 5th century BCE, some such individuals were recognised by the greater human population and believed to be directed descendants of the gods. Because of this, individuals like Kassandra and Alexios were often referred to as a "Demigod." Others, such as the Order of the Ancients, who despised these traits and considered those who possessed them as "less than human" referred to such individuals as Tainted Ones, however.
Clay Kaczmarek correctly theorized that this was the result of cross-breeding between humanity and their "gods", and that not only did this allow these bloodlines to make use of the Pieces of Eden, but also removed, or at least rendered non-functional, the neurotransmitter.