We're talking about direct explicit low level self modification. ie, uploading, then using that more convenient form to directly study one's own internal workings until one decides to go "hrm... I think I'll reroute these neural connections to... that, add a few more of this other kind of neuron over here and..."
Yes, but that would be the stupidest possible way of doing it, when there are already systems in place to do structured modification at a higher level of abstraction. Doing it at an individual neuron level would be like trying to... well, I would've said "write a property management program in Z-80 assembly," except I know a guy who actually did that. So, let's say, something about 1000 times harder. ;-)
What I find extremely irritating is when people talk about brain modification as if it's some sort of 1) terribly dangerous thing that 2) only happens post-uploading and 3) can only be done by direct hardware (or simulated hardware) modification. The correct answer is, "none of the above".
Well, we're talking about the kind of modifications that ordinary, non-invasive, high-level methods, acting through the usual sensory channels, don't allow. For example, no amount of ordinary self-help could make someone unable to feel physical pain, or can let you multiply large numbers extremely quickly in the manner of a savant. Changing someone's sexual orientation is also, at best, extremely difficult and at worst impossible. We can't seem to get rid of confirmation bias, or cure schizophrenia, or change an autistic brain into a neurotypical brain (or...
..fragments of a book that would never be written...
* * *
Captain Selena, late of the pirate ship Nemesis, quietly extended the very tip of her blade around the corner, staring at the tiny reflection on the metal. At once, but still silently, she pulled back the sword; and with her other hand made a complex gesture.
The translation spell told Hirou that the handsigns meant: "Orcs. Seven."
Dolf looked at Hirou. "My Prince," the wizard signed, "do not waste yourself against mundane opponents. Do not draw the Sword of Good as yet. Leave these to Selena."
Hirou's mouth was very dry. He didn't know if the translation spell could understand the difference between wanting to talk and wanting to make gestures; and so Hirou simply nodded.
Not for the first time, the thought occurred to Hirou that if he'd actually known he was going to be transported into a magical universe, informed he was the long-lost heir to the Throne of Bronze, handed the legendary Sword of Good, and told to fight evil, he would have spent less time reading fantasy novels. Joined the army, maybe. Taken fencing lessons, at least. If there was one thing that didn't prepare you for fantasy real life, it was sitting at home reading fantasy fiction.
Dolf and Selena were looking at Hirou, as if waiting for something more.
Oh. That's right. I'm the prince.
Hirou raised a finger and pointed it around the corner, trying to indicate that they should go ahead -
With a sudden burst of motion Selena plunged around the corner, Dolf following hard on her heels, and Hirou, startled and hardly thinking, moving after.
(This story ended up too long for a single LW post, so I put it on yudkowsky.net.
Do read the rest of the story there, before continuing to the Acknowledgments below.)
Acknowledgments:
I had the idea for this story during a conversation with Nick Bostrom and Robin Hanson about an awful little facet of human nature I call "suspension of moral disbelief". The archetypal case in my mind will always be the Passover Seder, watching my parents and family and sometimes friends reciting the Ten Plagues that God is supposed to have visited on Egypt. You take drops from the wine glass - or grape juice in my case - and drip them onto the plate, to symbolize your sadness at God slaughtering the first-born male children of the Egyptians. So the Seder actually points out the awfulness, and yet no one says: "This is wrong; God should not have done that to innocent families in retaliation for the actions of an unelected Pharaoh." I forget when I first realized how horrible that was - the real horror being not the Plagues, of course, since they never happened; the real horror is watching your family not notice that they're swearing allegiance to an evil God in a happy wholesome family Cthulhu-worshiping ceremony. Arbitrarily hideous evils can be wholly concealed by a social atmosphere in which no one is expected to point them out and it would seem awkward and out-of-place to do so.
In writing it's even simpler - the author gets to create the whole social universe, and the readers are immersed in the hero's own internal perspective. And so anything the heroes do, which no character notices as wrong, won't be noticed by the readers as unheroic. Genocide, mind-rape, eternal torture, anything.
Explicit inspiration was taken from this XKCD (warning: spoilers for The Princess Bride), this Boat Crime, and this Monty Python, not to mention that essay by David Brin and the entire Goblins webcomic. This Looking For Group helped inspire the story's title, and everything else flowed downhill from there.