The First is a relic featured in The Darkness II. It is a knife wielded by Cain as he murdered Abel.
As Cain committed the first murder, he was vulnerable to the Darkness. However, God would not let the Darkness take over Cain, so God made him unkillable. As the Darkness deals in death, having Cain unable to die would make him immune to the Darkness's influences.
After making Cain unkillable, God sent Cain on a path to atonement, commanding him to rid the world of darkness. Unfortunately for Cain, unkillable did not mean immortal.