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You would start to run into the whack-a-mole problem. Basically, whenever you make a hard "don't ever do X" rule, you will absolutely wind up having to make dozens of exceptions each time the AI works around said rule.
Ex: Make a medical research AI and program it to Not harm Living Creatures
AI halts, since any action it takes will cause harm to at least one single-celled organism
You make an exception for anything under a few hundred cells
AI creates a new medication that has a side effect of killing gut flora/fauna—anyone who takes it dies of malnutrition
You make an exception to the exception for things living inside humans
AI halts trying to make a de-worming drug because it cannot harm things living in humans