User blog comment:Willbachbakal/Singleplayer Plasmids/@comment-175.139.62.248-20130909035314/@comment-75.36.143.17-20130910091957

The Big Sisters in BS2 werent murderously insane. Murderous yes, but they seemed to take orders to collect ADAM or to protect LS  or attack you like they did just outside the isolation room.

Just them turning into teenageres should be enough of an explanation for the original  'conditioning' not to work any more (Lamb could use her psychological tricks on them by that point)