Harry Osborn was a childhood friend of Peter Parker who was sent off to a boarding school at a young age by his father, Norman. When he graduated, he moved to California and lived the life of a womanizing, spoiled rich boy.
Ten years later, Harry returned to New York to see his terminally ill father. Norman explained to him that his illness is hereditary, and that Harry is now at an age where it first develops. He gave Harry a small device which he claimed contained his life's work. The next morning, Norman had died, and Harry is named CEO of OsCorp. Eventually, the first symptoms of Harry's illness began to show, but he used the device his father gave him to figure out that Spider-Man's blood could potentially save him. Harry asked Peter, who he knew was sending pictures of Spider-Man to the Daily Bugle, to get into contact with Spider-Man and give him a transfusion, but Peter refused, unsure of what effects the transfusion would have on him. Harry then attempts to ask Spider-Man for a blood sample, correctly deducing that Spider-Man's powers come from the genetically-engineered spiders that Oscorp created and have since been destroyed, but Spider-Man refuses, feeling that the risk that the transfusion could mutate Harry is too great.
The circumstances surrounding Harry only got worse when the Oscorp board framed him for covering up Max Dillon's accident (as well as subsequent creation of Electro) and voted to remove him from his position as CEO. However, Harry's assistant Felicia Hardy informed him of technology within Oscorp which could help him. Becoming increasingly desperate, Harry breaks into Ravencroft, releases Electro and forms an alliance with him. With Electro's help, Harry breaks into Oscorp’s Special Projects lab to recover the remaining venom samples taken from the spiders prior to their destruction. He then injects a spider venom serum directly into his bloodstream, causing his illness to worsen. The venom hideously mutates his physiology, requiring him to don a prototype battlesuit with automatic healing abilities to cope with the trauma his body is experiencing. He also boards a hi-tech glider that came with the suit, and flies off to use them to confront Spider-Man.
After seeing Gwen Stacy alongside him, Harry deduces that Spider-Man is actually Peter. As revenge for Spider-Man denying him the blood transfusion, Harry kidnaps Gwen and throws her from a great height into a clock tower. Peter manages to save her, leaving her dangling by a web while him and Harry continue their fight. Peter subdues Harry, but the web securing Gwen breaks and she falls to her death. Harry is later held in Ravencroft Institute and recovering from the transformation.
Five months later, a mysterious man visits Harry, making plans to use the rest of the equipment in special projects for their own ends, with Harry planning to create a small team in order to enforce his rule on the city. At Harry's suggestion, their first recruit is the recently imprisoned Aleksei Sytsevich.
