Meanwhile, elsewhere, the mysterious tentacled individual is finally revealed to be a new female Doctor Octopus. It is revealed that she is trying to break into Seward Trainer’s file system to get some information about research he conducted that would allow for simulations of organic matter within a virtual reality.

Ben and Seward discover an Octopus crest in the files, leading them to believe that whatever is going on may have been set in motion before the real Doctor Octopus was killed. Ben knows Peter has more knowledge and experience in the area but does not want to involve him, because he has too much to risk, so he decides to handle matters on his own. Before Ben leaves Seward’s lab, Peter and Mary Jane show up at the lab to ask Trainer to conduct an experiment on Peter to determine if there are more "time bombs" inside Peter.

After performing a few experiments, Seward detects no trace of any other anomalies. Happy and in the mood to celebrate, Peter and MJ head over to a restaurant to share a nice romantic dinner. While there, they tease each other about the sex of the baby and get to experience the child move for the first time.

Meanwhile, the female Doctor Octopus is testing her virtual reality bomb, causing people to think that dinosaurs are on the loose in the city. The prototype is successful so she prepares to build the real thing.

Seward Trainer is in his office, trying to break the encryptions when he finds the female Doctor Octopus in cyberspace. She is as surprised to find him there as he is but does not have a lot of time to dwell on it when the Scarlet Spider shows up to rescue him. That is easier said than done, because the female Doc Ock is revealed to be a lot stronger than expected. In the midst of the battle, Seward asks her why she is doing this, to which she replies that she was taught to revere scientific research above human life itself. When Scarlet realizes that Seward knows her and asks him about her, she reveals that she is his daughter.

In Spider-Man Volume 1 #63, Part Two of Three of the Greatest Responsibility storyline, the story opens up at the Parker apartment, where Peter Parker lies restless in bed. Ever since he felt his child move inside Mary Jane's belly, he cannot think straight. So, in order to burn off some energy, he heads out for a swing as Spider-Man.

The Scarlet Spider is taken aback by the revelation that the new female Doctor Octopus is Seward’s daughter Carolyn. Conversely, Carolyn is furious with her father because he seems to share a father-son bond with Ben (i.e. the Scarlet Spider), a bond she claims she never had with her father. Ben wants to keep Seward safe but Seward doesn't want to repeat the errors of his past and leave his daughter again. Ben makes an executive decision and decides to grab hold of Seward and take off, the female Doc Ock in tow. As they escape, Seward notices that Ben is using more wisecracks than usual when he speaks and he comments on it. Ben replies that he is just trying to pick up where he left off five years ago.

Miles away, Spider-Man is web-slinging across the city when his spider-sense suddenly kicks in, instinctively warning him that something wrong is happening to Ben. Following his spider-sense, he finds Ben on a rooftop under attack by the female Doc Ock. He manages to help Ben out but is knocked off the roof accidentally. As he falls, the female Doc Ock grabs hold of him and threatens to break his neck unless Ben surrenders Seward, her father. As this takes place, Spider-Man can only think of two people: Mary Jane and their unborn child. Ben comes to his rescue by using his impact webbing to break through a force field created by the female Doc Ock. The female Doc Ock taunts Ben and then proceeds to test his speed by letting Spidey fall from the sky. Within seconds, Ben throws himself off the building after Spidey and gains enough momentum to catch him. The female Doc Ock uses that opportune moment to get away. When Ben and Spidey join Seward back on the rooftop, Ben tells Seward that he'll bring his daughter back without harming her. Ben then turns to Spidey and asks if he is okay. Spidey replies that he is not and explains that, when Doc Ock had him at her mercy, all he could think of was that his offspring would be left without a father. He then tells Ben that he needs to talk to Mary Jane because he has to make a decision.

Meanwhile, Mary Jane is at a photo shoot for maternity wear where she is offered an extension to her modeling contract. She nicely declines the offer, citing that she intends to take some time off to spend with her baby, when she suddenly feels light-headed and subsequently passes out.

Peter and Ben return to Peter's place only to discover that Mary Jane has been hospitalized after fainting at her photo shoot.

Seconds later, Peter and Ben arrive at the hospital where they are informed by Mary Jane's doctor that microscopic traces of radioactivity were found in her bloodstream, which reacted with the normal hormonal changes caused by her pregnancy. Just then, Seward Trainer shows up and offers to assist the doctor in determining what can be done to help her. Peter welcomes the help with open arms. Seward informs Peter that both MJ and the baby are in grave danger and that the situation is even worse than he anticipated. However, he also informs Peter that he secretly prepared an antidote as he had a feeling that this would happen. He picks up his cell phone and makes a call to a messenger who has the antidote in his possession.

Unfortunately, the female Doctor Octopus intercepts the call and shares the information with an associate of sorts, whose identity is scrambled by a computer screen. The mysterious entity tells her that the information she intercepted may provide her with a bargaining chip, as long as her personal relationship with Seward Trainer does not cloud her judgment.

Minutes later, Seward's messenger is intercepted by goons working for the female Doctor Octopus and is stripped of the antidote he was carrying.

Back at the hospital, Peter is at MJ's bedside and is worried sick. All he wishes for is for her to get better because she is his life. Meanwhile, in the waiting area, Seward Trainer and Ben await the arrival of the messenger when Seward suddenly gets a phone call from his daughter Carolyn, the female Doc Ock, who tells him that she has gotten her hands on the antidote and that she'll give it to him in exchange for him. Seward notifies Peter and Ben and reluctantly agrees to her deal, knowing the Spider-Men will be close behind.

After telling MJ about what he must do, Peter dons his Spider-Man costume and he takes off into the night with Ben, as the Scarlet Spider, and Seward Trainer. Spidey and the Scarlet Spider drop Seward off on the docks and hide on a nearby rooftop where they can keep an eye on the situation. A short time later, Doc Ock's goons show up and, using some kind of electronic wand, manage to detect spider-tracers on Seward’s person. The goons destroy the spider-tracers and disappear inside a nearby van. Spidey and the Scarlet Spider come down from their rooftop and open the doors to the van, only to find it empty. Realizing where they must have gone, Spidey lifts the van off the ground, revealing a trap door leading to the water. Spidey and the Scarlet Spider fashion themselves some swimming gear made out of web and dive into the water to try and locate Seward and his captors.

In an underwater base, the female Doc Ock reveals to her father that she wants the access codes to a new technology he devised to project actual living matter into virtual reality. Having said that, she wraps one of her tentacles around his neck in an attempt to "persuade" him into revealing the codes. She starts to strangle him with the tentacle when she is alerted by the mysterious computerized entity that Spider-Man and the Scarlet Spider have breached their hideout and that he has sent a welcoming committee to take care of them. While Spidey and the Scarlet Spider face off against a few dozen of the female Doc Ock's goons, she (on the other hand) gets confirmation from the computerized entity that he has gained full access to her father's files, which detail the stable interface that allows organic matter to exist in cyberspace. Spidey and the Scarlet Spider manage to defeat their attackers and go out in search of the antidote and Seward respectively.

Back at the hospital, Mary Jane wonders when she and Peter will finally get their lives on track and start behaving like a real family. She complaints to herself that she has spent the majority of their married life worrying about him, wondering if he is dead or alive. She wonders how they can possibly provide a stable environment for their baby if he keeps putting himself in jeopardy, because it seems that every time he averts one tragedy, another one comes his way.

Spidey finds the antidote but as he’s about to grab hold of it, his spider-sense kicks in, warning him of danger, and the female Doc Ock appears and attacks him. A battle naturally ensues.

Meanwhile, in another part of the underground base, the Scarlet Spider finds Seward Trainer tied up to a table. When he attempts to free Seward, the Scarlet Spider comes under attack by traps set by the computerized entity, who informs him that he is more than just a machine.

While Spider-Man and the female Doc Ock battle it out, Spidey asks her why she hates her father so much. She replies that she does not hate him because she rarely thinks about him and hardly knows him. Spidey asks if he abandoned her and her mother to which she replies that he did not, although there were times she wished he had so she could get a new dad, one that would pay more attention to her. She goes on explaining that her father was and has always been obsessed with his work and that, consequently, her mother and her were barely rated second to him. Having finally managed to chip at her concentration with the conversation, Spidey shoots webbing at her face and, while she is distracted in her attempt to remove the webbing, Spidey grabs hold of one of her tentacles and throws her into a support wall, which ruptures on impact. This causes the ceiling to weaken and the base to start flooding. She screams at him that the emergency pressure system must be activated but a major undertow unexpectedly cuts her off in mid-rant and she is swept into the river. Spidey does not fare any better as the whole building starts to collapse around him, trapping him underneath tons of debris.

The Scarlet Spider is fending off more booby traps sprung by the computerized entity and is faring pretty well. Suddenly, there is a huge electrical surge in the room, which causes the computerized entity to initiate an immediate shut down or risk a network-wide crash. The Scarlet Spider proceeds to free Seward from his bond.

Trapped underneath a huge pile of rubble, Spidey's thoughts turn to his family. He thinks of Aunt May, who taught him that there is no greater responsibility than raising a family. He thinks of Mary Jane and regrets hitting her on that fateful day he learned he was the clone. He thinks of the baby and how he does not know what the sex of the baby will be and how he might never find out, unless he gets out of this predicament. He continues to struggle but time is running out and so is his air supply. Suddenly however, the Scarlet Spider appears and helps him out. They grab hold of the antidote, left there by the female Doc Ock, link up with Seward Trainer, fight their way to the nearest exit and return to the hospital.

Mary Jane is administered the antidote and Seward informs Peter and Ben that both she and the baby are responding well to it and that they are both going to be fine. Peter thanks them both and heads into MJ's room to check up on her.

MJ is out of bed already and she hugs Peter. Peter tells her that she has been very supportive and that he has come to a decision regarding being Spider-Man. He walks out the room.

Peter asks Ben to walk with him, as they have to talk. As they walk, Peter tells Ben that, even a man who has great responsibility can be humbled, when he sees even greater responsibilities on the horizon. As such, he has decided to hang up the webs forever and he hands his Spider-Man costume over to Ben, telling him that from now on, family comes first. Ben tells Peter that he is willing to accept the responsibility but he hasn't earned the costume yet. He gives the costume back to Peter and tells him to recycle it into a baby blanket or whatever he feels like. Ben then proceeds to wish him and Mary Jane the very best, and Peter walks away, thinking about what the future holds in store for him and Mary Jane. His thoughts then turn to Ben, as he wonders what Ben will do first with his new life.

The end...for now.