Scientists regenerated a functional, “almost complete” leg for a frog

The leg regrew after only 24 hours of treatment with a drug cocktail and a silicone ‘BioDome’.

Published: January 26, 2022 at 7:00 pm

From Doctor Who to Deadpool, there is no shortage of regenerative abilities in science fiction. Even some real-life animals can manage to regrow limbs, including starfish, salamanders, crabs and lizards. Unfortunately, medicine is a long way behind. However, in a study published in Science Advances, researchers have managed to regrow missing legs in African clawed frogs.

The legs, which were described as “almost complete”, were able to respond to touch stimuli and allowed the frogs to move and swim normally.

A team of scientists at Tufts University and Harvard University’s Wyss Institute created a cocktail of five drugs, applied via a silicone cap called a ‘BioDome’. After only 24 hours of treatment, the BioDome was removed and the regeneration process began.

Within the first few days, the researchers saw that molecular pathways normally used in a developing embryo had been activated. Over the course of the next 18 months, the frogs slowly regrew a leg which had a bone structure, internal tissue, including neurons, and 'toes', all of which were similar to the frogs’ original legs. However, there were some differences: for example, there were no bones in the toes.

Limbs are structurally complex, so regrowing them is no easy feat. Even humans do have some regenerative abilities, though: we can regrow tissue to close a wound, and we can lose up to 50 per cent of our livers and regrow them to full size. So, if we hope to be able to regrow human limbs one day, the way to go might be a method like this that harnesses the body’s own innate knowledge of how to build itself.

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“It’s exciting to see that the drugs we selected were helping to create an almost complete limb,” said Nirosha Murugan, research affiliate at TuftsUniversity and first author of the paper. “The fact that it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests that frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action.”

In previous research, the team had used the BioDome along with one drug – progesterone – to try to regrow frogs’ legs. Though the frogs did manage to regrow a “significant” amount of tissue, the limbs were spike-shaped and weren’t functional. This time, the team put together a cocktail of five drugs that aimed to reduce inflammation, encourage the growth of blood vessels, muscle and neurons, and inhibit the formation of scar tissue.

The team’s next step is to try to apply the technique to mammals. “Covering the open wound with a liquid environment under the BioDome, with the right drug cocktail, could provide the necessary first signals to set the regenerative process in motion,” said corresponding author Michael Levin, Vannevar Bush Professor of Biology at Tufts University.

“It’s a strategy focused on triggering dormant, inherent anatomical patterning programs, not micromanaging complex growth, since adult animals still have the information needed to make their body structures.”

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