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Curtis Connors is a scientist working for Empire State University. Connors lost his arm as a result of an Oscorp Industries weapons testing accident (Wide Area Explosive Fragmentation Round aka WAFER). This version of Dr. Connors is more serious and colder than other versions. When he transforms into the Lizard, he becomes aggressive and feral but maintains his ability to talk, at least when his serum is lowered. He goes after Harry Osborn as revenge for the loss of his arm. During the battle between him and Spider-Man, his arm is again cut off. At one point, Spider-Man dangles the Lizard from a web while attached to a helicopter. Spider-Man tries to reason with him, but the Lizard strikes out, cutting the web and causing the reptilian menace to fall to his apparent death, but he survived and became Connors again.

Connors is a Columbia University physics professor concerned for Peter Parker's well-being and academic performance in his quantum mechanics course. Peter is seen studying with several textbooks for this course, two of which can be made out as quantum mechanics and photonics books. Curt's friend, Doctor Otto Octavius, recalls Peter's name and tells Peter that Connors considers him "brilliant, but lazy." Otto chuckles about his friend's assumption regarding Peter's laziness once he finds out Peter is also Spider-Man. Peter later turns to Connors to analyze the substance of the Venom symbiote and Connors informs him that it makes one more aggressive and that it has a particular liking for him.

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