The birthmark is another example of personification. Not only is it shaped like a human hand, it is also described as threatening Georgiana's life. In the first part of the story, Aylmer dreams about the birthmark's deadliness:
Its tiny grasp appeared to have caught hold of Georgiana’s heart.
Personification makes the birthmark an even more interesting object of attention. In this moment, the birthmark itself becomes the antagonist. The way in which the hand pursues the heart gives Aylmer an excuse to take extreme measures to remove it. He justifies his actions with the idea that the hand threatens Georgiana's life, when in reality the only threat to her life is his desperation to remove the birthmark.
In the final scene, the narrator describes
...the fatal hand [that] had grappled with the mystery of life, and was the bond by which an angelic spirit kept itself in union with a mortal frame.
The hand's personification becomes slightly more sympathetic at the end of the story. Though it once seemed "fatal," it is really a "bond" between Georgiana's body and soul. Readers come to realize that the fatal element of the story is not the birthmark itself but rather Aylmer's dangerous experiments to destroy it. Thus the narrator recognizes the mark as an essential, life-preserving link between the physical and spiritual realms. Appropriately personified, it represents how small imperfections in Georgiana's beauty preserve her humanity.
Throughout the story, Nature is personified as the enemy of human perfection. In this passage, the narrator describes Nature as a creative force that generates inevitably-flawed creatures:
It was the fatal flaw of humanity which Nature, in one shape or another, stamps ineffaceably on all her productions, either to imply that they are temporary and finite, or that their perfection must be wrought by toil and pain. The crimson hand expressed the ineludible gripe in which mortality clutches the highest and purest of earthly mould, degrading them into kindred with the lowest, and even with the very brutes, like whom their visible frames return to dust.
Nature and mortality are closely related. The hand humanizes the influence of Nature upon Georgiana; it seems as though Nature itself put its own handprint on a near-perfect creation to remind her of her mortality. Words like "ineffaceably" and "ineludible" give Nature great power in contrast to Aylmer's limited ability to create new worlds in his laboratory. In this case and many others, Nature is portrayed in a negative light as the enemy of scientific progress and perfection. However, the story shows that one must consider the consequences of defying natural laws. Despite Nature being personified as a tyrant, the true tyrant turns out to be Aylmer, who kills his wife in an attempt to create a being more perfect than nature would ever permit.