But I don't think there's any one event that would affect his drive to establish OH and ZL more than the parasite infection. After that, he's more determined than ever to wall off and protect his men.
It was just so poorly executed.
Back when we learned about MGS3, who would have thought that the legendary big boss actually learned everything he knew from a badass female WW2 vet?
That revelation was literally out of the blue and one that nobody could have seen coming - the repercussions of him having to kill her is perhaps the key moment in the entire franchise.
Considering we never knew about that story beat prior to MGS3 and it's so important shows that there's no reason there couldn't have been an equally incredible moment we didn't know about that caused him to become the shitheel Big Boss we all know about.
I mean, hell I could try to come up with something right now - pretend venom is the real big boss for a moment, have it so he was forced to kill quiet to prevent the English strain from wiping out most people on earth. Imagine that at the end of the game the big reveal is that every single person on motherbase. this army you built and have become attached to, your brothers in arms - they have been infected with a sleeper english strain parasite and BB must choose to either kill them all to save the world, or continue on despite knowing they're they are all deadly bioweapons just waiting to be used by zero/skullface to cause a holocaust, and this is to get BB to finally rejoin the patriots.
BB chooses not to kill them and instead fight back against Zero and all the worlds governments he has under his thumb and create outer heaven. This leads to MG1 where the secret reason solid snake must take down that entire facility was to actually make sure the parasite never got out, as BB called zero's bluff.
I mean shit, it even parallels his son's choice at the end of MGS4 to kill himself to stop Foxdie from causing a holocaust, but unlike his shitty dad solid is the ultimate good guy who sacrificed himself (till BB showed up an...you know the rest)