During the outbreak, Greg formed a partnership with Peter Jenkins at Raccoon University with the offer of helping him create a vaccine for the t-Virus. T-Blood, blood from a creature infected with the t-Virus, was offered by Greg to be obtained to create the vaccine. Greg had it in mind to get the blood from Thanatos. However, Peter discovered that Greg was helping him create the vaccine purely due to a personal vendetta and that Greg actually sought to use the cure as leverage against Umbrella. As such, Peter refused to continue researching with him, and thus T-Blood from Thanatos was rendered useless. Thanatos, however, would not remain dormant.
Already aware of Umbrella's intent, Greg released his creation with the intention of wiping out the team.Sometime around the time of the mission's initiation, the UBCS team, comprised of five operatives including Karl, Dustin, and Nikolai Zinoviev, made contact with the creature in the back square. Keeping their distance, the team continued to open sub-machine gun fire in an attempt to take it down. The tactic failed to take it down, and the other component of the plan - Nikolai collecting the desired T-Blood from behind - led it on a homicidal rampage, killing the ground-side components of the team. Thanatos then carried off the body of one of the mercenaries to Greg for his researching purposes.[note 1] Nikolai then began preparations for another encounter, should it take place.
Thanatos then proceeded to pursue a rag-tag group of refugees throughout the university. It failed, and the survivors managed to escape it's grasp. In fact, the survivors temporarily managed to knock Thanatos out with an electric shock, taking the pod with T-Blood with them. After Greg's assassination by Nikolai, and the activation of the C-4 charges he spent the time in hiding setting up, Thanatos again tried, and failed, to kill the survivors while they fled. While they escaped to the temporary safety of the back square, the C-4 went off, destroying a section of the university building and bringing the ceiling down around Thanatos. Though this severely injured it and cost it an arm, it also caused it to mutate into its Super Tyrant form, known as "Thanatos R."
After its mutation, Thanatos resumed its chase for the survivors outside the university. As they made their way to evacuation, Thanatos cut them off. Though it could have easily overpowered and killed the group, their resilience proved an advantage. Still, Thanatos quickly resumed its chase at full strength. At the front square, Thanatos intercepted the survivors for the third and final time. By either using firearms or inserting a sample of the Daylight antigen - a vaccine to the t-Virus made with Thanatos' very blood - into an Ampule Shooter dropped by a dead soldier and shooting it into Thanatos, the survivors defeated it and escaped the city. However, Thanatos' body may have had the means to combat Daylight.