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He looked in her eyes, and she looked in his, and River knew that he had absolutely no idea who she was. According to her journal, the Doctor would first recognize her in a few years with her mom and the weeping angels. Her mom. All she wanted was to cry out for her mommy, but she had to be brave for the Doctor. She turned on the self-destruct.
River was, truthfully, nobody special to the Doctor. Not yet, at least. She told him he would know who she was eventually, and it was nothing new. He had already met a few people with jumbled timelines who knew him before he did. He couldn’t tell why she in particular felt so different.
Maybe it wasn’t her death that affected him; it was how she looked at him before she died. It was the way she knew things about his future, and she just looked at him with pure, unadulterated pity on her face.
“You and me, time and space, watch us run,” she had said, crying as she sacrificed herself for him. The Doctor couldn’t do anything but watch, and he felt himself grieve for a woman he didn’t know.