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"Why the liver and not the pancreas?" asks Melton. The liver faces regular assault from the environment, in the form of alcohol and other blood toxins that the organ filters. Human skin also suffers damage, getting burned, scraped, and otherwise injured. Maybe, Melton speculates, these systems have evolved a way to endure frequent environmental insults by repairing themselves through regeneration.
Meanwhile, there may be good reason why the human body refuses to regenerate so many other tissues and organs, not to mention limbs. Unchecked regeneration resembles the runaway cell growth that characterizes cancer. In a study published May 18 in Science, Moon and collaborators reported evidence for concern.
Some proteins act as cellular brakes, regularly shutting down Wnt signaling and other cell-regeneration pathways. This "stop" mechanism keeps cell populations in check. For instance, scientists have documented that, in colorectal cancer and melanoma, mutations disrupt proteins that normally turn off Wnt.
Moon's team explained how this biochemistry might play out in Wilms' tumor, a form of pediatric kidney cancer. Through their investigations, the researchers discovered the potential involvement of WTX, a protein that normally acts as a tumor suppressor by degrading a protein network that activates the Wnt pathway. Working in zebrafish, frogs, and cultured cells, the team found that Wilms' tumor mutates the gene that encodes WTX, thus disabling the protein. Without WTX as a brake, the Wnt pathway is activated more than usual, triggering harmful cell growth that becomes a tumor.
Thus, although regenerative medicine has great potential, researchers looking for dramatic outcomes in humans might well proceed with caution, lest they re-create, in one way or another, Moon's surprise results long ago in tadpoles.
There may be a safer and more practical application of regeneration research—the familiar human condition of degeneration, which, according to Melton, is the flip side of regeneration. On that note, Moon and colleagues published an May study in the Proceedings of the National Academy of Sciences demonstrating that a single amino acid change in a protein that works with Wnt is associated with late-onset Alzheimer's disease. Moon concludes that Wnt biochemistry is all about balance. Too much—or too little—Wnt affects both regeneration and degeneration.
"We increasingly suffer from diseases of degeneration," Melton notes. "Diabetes, neurodegenerative disorders, cardiovascular disease. All have features in common: an unknown environmental stimulus, many genes, and a long time between cause and effect. If we're interested in slowing degeneration, we should be focusing on how the body maintains and repairs itself." 
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