Despite these hurdles, we know the basic steps that a regenerating limb must go through. After an amputation, cells from the outermost layer of skin climb over to seal the wound. At this point, humans would lay down lots of scar tissue, and that would be that. But in salamanders, the new cells transform into a structure called the wound epidermis, which sends chemical instructions to those below it. In response, nerves in the stump to start to grow again, while mature cells such as muscles and connective tissues revert to an immature mass called a blastema. This is what restores the limb. Regeneration is about taking a few steps back to take many steps forward.

“Somehow, the cells know their positions, and they’ll only regenerate what’s missing,” says Enrique Amaya, developmental biologist at the University of Manchester. If the limb is amputated at the shoulder or hip, the blastema creates the full leg. If it’s amputated at the wrist, the blastema makes just a hand and digits. As they grow and divide, the cells take up specific positions, so they know up from down, or left from right. They fashion a miniature version of the full limb, which eventually grows to full size.

The basic outline is there, but the details have been hard to fill. Why does the wound epidermis form, and what does it do to the cells beneath it? The limb won’t regenerate if the nerves inside don’t start growing, but what exactly do the nerves do? When cells in the stump rewind their fates to become a blastema, how far back to they go?