Scientists want to regrow human limbs. Salamanders could lead the way.

Could humans be capable of growing new limbs? Scientists are trying to figure that out with the aid of an unexpected resource: salamanders. Research shows that the amphibians' regeneration abilities come from mechanisms that humans could also potentially access. This would open the door to a new understanding of human genes and their capabilities.

Going up in arms

Salamanders famously have the ability to regrow their limbs, but "one of the outstanding questions that has really plagued the field is how a salamander knows what to grow," said James Monaghan, a Northeastern University biologist, to The Washington Post. At long last, researchers have gotten some answers thanks to a study led by Monaghan and published in the journal Nature Communications.

The study examined the aquatic salamander, or axolotl. "This species is special," said Monaghan to the Post. They have "really become the champion of some extreme abilities that animals have." The axolotl is considered a "comeback king" because it is "able to regrow not only lost limbs but also tissue in the heart, lungs and even the brain," said the Post. The key to these abilities lies in retinoic acid. Found in retinol acne and anti-aging treatments, the substance is "responsible for signaling what body parts an axolotl's injured cells should regenerate — and how," said CNN.

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But that was only half of the story. "For years we've known that retinoic acid, a derivative of vitamin A, is a crucial molecule that screams to cells 'build a shoulder!'" Monaghan said to Wired. "But the puzzle was how the cells in the regenerating limb-stump controlled their levels so precisely to know exactly where they were on the axis from shoulder to hand." As it turns out, the answer was in the exact concentration of retinoic acid in the body.

"Higher concentrations of retinoic acid tell an axolotl's body to keep growing leg length, while lower concentrations signal it's time to sprout a foot," said Popular Science. "Too much retinoic acid, and a limb can grow back deformed and extra-long, with segments and joints not present in a well-formed leg, hampering an axolotl's ability to easily move." One enzyme in particular, CYP26b1, is responsible for setting the correct concentration of the acid.

Getting a leg up

Retinoic acid is "important in the development of human embryos too, telling the cells where to grow a head, heads and feet," CNN said. However, "for an unknown reason, most of our cells lose the ability to 'listen' to the molecule's regenerative cues while in utero." For that reason, people can grow limbs while in utero, but not out of it. The question remains as to whether humans could actually find a way to access those same genetic mechanisms after birth.

"We might not need to turn on thousands of genes or turn off thousands of genes or knock out genes," Monaghan said. "It might just be triggering the reprogramming of a cell into the proper state where it thinks it's an embryo." This may potentially be done using CRISPR, a technology that can modify the DNA of living organisms. "While we are still far from regenerating human limbs, this study is a step in that direction," said Prayag Murawala, an assistant professor at MDI Biological Laboratory in Maine, to the Post. "Better understanding of gene regulatory circuit is essential if we have to re-create this in humans."