George Prufrock was doing what he always did, trying to earn his father's love and respect. He was hired by A.I.M to steal the Programma Virus from Programma labs in upstate New York. During his attempt he was discovered by the compounds security and tried to flee. However, as he made his escape, he was accidentally infected with the virus he was so desperately trying to steal. The infection was instantaneous. Within seconds George started to transform into what would become Lifeform. Unbeknownst to George, Frank Castle, Punisher, was staking out Programma labs for a case he was investigating concerning the production of biological weapons. By the time Punisher ran into George (Lifeform) his transformation was well under way, although he still resembled a human at that point. Punisher instinctively opened fire but soon realized his bullets were of no use against the 'lifeform'. He made a safe retreat and decided to follow his other leads in the case. His information led him to the home of Jethro Prufrock, father of George Prufrock, and was surprised to learn that the Lifeform had followed. During their scuffle, Lifeform murdered his father and set his eyes upon his sister and Punisher. Luckily, Punisher was led to the estates armory, where he found an anti-tank weapon, and used it on Lifeform. the force of the blast threw Lifeform into the river. Believing nothing could survive such a blast, Punisher takes his leave.

Lifeform pulled himself out of the water and eventually crossed paths with Daredevil. By this time his transformation had worsened. The change brought about a dual personality and the presence of constant pain. George's ability to speak had been slowly deteriorating and he quickly realized the only way to subdue the pain was to consume human flesh. He wandered the alleys consuming all those unfortunate enough to cross his path until, upon hearing their screams, Daredevil came to investigate. At first, Lifeform was scared of Daredevil, believing him to be a demon. This belief caused uncontrollable fear in Lifeform, and he ran trying to escape. As he fled, he came across Typhoid Mary, whose beauty mesmerized him and prevented him from eating her. Mary was able to talk Lifeform into leaving her behind and going to find other sources of food to quench his hunger. As he left Mary, Daredevil caught up with him once more. During their second battle the police had arrived and filled him full of tranquilizers which, apparently, caused him to melt away. Thinking the menace of Lifeform was over, Daredevil headed into the night.

Further transformed and having survived his encounter with Daredevil, Lifeform ran into Mercy, who usually helped those who suffered by offering death. Sensing his dueling personalities confused her at first but reminded her of her encounters with the Hulk. She transported Lifeform to Hulk's location in the Midwest to face him. Mercy merged with the Hulk making a duplicate of Bruce Banner so that he and the Hulk could speak with Lifeform. All four personalities debated for awhile. Banner wanted to save the Lifeform, the Hulk wanted to destroy the Lifeform, Prufrock begged for death and the malevolent Lifeform persona wanted to destroy and eat everyone. Lifeform apparently killed Banner which caused the Hulk to become enraged and throw Lifeform into a fire. The fallen Banner was actually Mercy, who revived herself unharmed. As Lifeform renewed himself he was transported back to New York by Mercy. He begged for death but she refused and instead restored his humanity. It did not last though, slowly he mutated back into Lifeform.

Now in the hospital under observation, by the doctors and SHIELD, George started to feel the change again. Unable to maintain his human form, George reverted back to Lifeform. He started devouring everyone he ran into at the hospital. When S.H.I.E.L.D. lost contact with the hospital Nick Fury contacted Reed Richards (Mr. Fantastic) to investigate. Reed acquired the help of the Silver Surfer, who had ventured to Earth to inform them of the apparent death of Thanos. Together they tracked the Lifeform to the East River where it was feasting on the marine life. By now it had grown to enormous proportions. Reed was quickly knocked out of commission leaving the Silver Surfer to battle the Lifeform alone. The Silver Surfer analyzed the situation and concluded the amount of power needed to destroy the Lifeform would cause countless casualties. The Surfer devised a plan to take the threat away from Earth. He decided he would allow the Lifeform to consume him and he then fly it deep into space until he arrived at a planet Galactus had already devoured. Prufrock's mind re-surfaced as the Silver Surfer mustered the energy needed to destroy him. He begged for his destruction stating that the Lifeform could not die. Hearing these pleas the Surfer decided he could not harm an innocent. After concluding he could not separate the two entities he left the Lifeform on the uninhabited planet. Doing so caused the Silver Surfer to question if he too was a monster for leaving George Prufrock to his eternal fate.