Issac is reason why Natani thinks she's a male because Issac used a forbidden spell that destroyed part of Natani's soul, which Zen repaired by combining his soul with Natani's. (Natani is "he" because of this) After Natani was "alive" again, they heard that Issac died at casting the forbidden spell, and their mission was considered completed. Zen and Natani later fed the rumors about them being so good that Issac killed himself out of fear when he saw them at first. This is why Zen and Natani are called "Magi Brothers" too.
Issac tended to travel alone wielding a staff between villages and was considered old for a keidran. Natani and Zen attacked him from the trees and threw two throwing knives with grey handles at him, which he stopped by holding his staff in their path. When natani attacked with a sword, Issac cast the forbidden magic spell on her. He then died, which lead to Natani and Zen's mission being considered a success.
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