Ultimate Spider-Man (2000) #17
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Peter Parker's first true love, Gwen Stacy was killed during a rescue attempt by Spider-Man, the guilt from which Peter has never overcome.
Mary Jane Watson was the guiding light in Peter Parker's life, and their love had overcome countless obstacles.
Peter’s relatively normal life changed abruptly during a school trip to Osborn Industries, Inc, where the company had been working on a super soldier serum, the Oz Compound; a spider exposed to it escaped and bit Peter before it was destroyed.