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Yet... The Mangekyou Sharingan we've seen on-screen actually were achieved by killing their closest friends (I'm fairly sure the manga stated that Itachi assisted in Shisui's suicide) (although those acts themselves weren't shown onscreen).
I'm not saying it is the only way. But there aren't many things that are such a powerful contradiction. I mean, if you're truly willing to kill someone to obtain more power, you can't really call them your closest friend.
On the other hand, if circumstance forces you to kill them, that's a different matter.
...
Well, maybe Shisui's eyes were awakened differently, I'm not sure. Anyway, the assumption that killing your best friend = Mangekyou isn't exactly wrong. It can't be just any old loss though. Guilt probabably is a factor, but not any old guilt.
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