During a session in the Animus at Abstergo's facility in Rome, Italy, Clay awoke, started tearing his clothes and skin before drawing images on the floor with his blood. After around ten minutes, security intervened and he was sedated and treated. Though precautions had been taken, he was found the next day freed from the straps, in a pool of his own blood and surrounded by blood symbols on his walls. He was interned at St. Erembert Psychiatric Hospital.
Some months later, Clay escaped from the hospital, after killing a man and assaulting an orderly, saying that although he was called "Subject 16", no one would call him that again. Some time later, he showed up at an Assassin safehouse and demanded to be put into an Animus, threatening Tom, Desmond Miles and Lucy Stillman. Lucy knocked him out and asked Tom to move Clay to somewhere where he wouldn't harm himself or their project, though he escaped as soon as he awoke.