After losing his arm in an explosion, Dr. Curtis Connors devoted his life to creating a serum to regenerate lost limbs. Using DNA from reptiles, who naturally regrew lost limbs, Connors created a serum he was sure would work.
Using himself as the first test subject, Connors injected himself with a dose of the formula, and was ecstatic when his arm began to regenerate. However, the reptilian DNA his serum was based on mixed with, and altered, his own DNA, and turned him into a vicious creature known as The Lizard.
While Connors was eventually "cured" by Spider-Man and returned to his human appearance, in times of anger, stress or sadness, Connors body often reverts back into his reptilian form.
More recently, his Lizard alter-ego took over his body, also "evolving," not being able to turn into a human any more.