After being revealed at the close of Assassin's Creed II, The Isu (or, "The Ones Who Came Before") - a race of Gods who helped bestow the mythical Pieces of Eden with fancy mind-control powers - take hold of Desmond's mind.
Commanding him to kill Lucy as she was masquerading as a Templar, we were all suitably shocked that our hero could be effectively weaponised so easily.
The whole point of the Assassin Order was that these were the free-spirited humans who could break free from the Isu's mind-controlling spells way back in the days of Adam and Eve.
Where legions of humans were forced into servitude, the Assassins forged their own path - hence the entire role of the assassins being the manifestation of their mantra, "nothing is true, everything is permitted". It means to rebel, break free; understand the "shackles" of your surroundings and learn to reach past them.
Desmond is of course descended from thousands of years of assassin blood - he's played up to be the free thinking, peace-bringing messiah in AC III, after all - and should never have succumbed to Isu mind control.