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November 17, 2015

Evolution is a fascinating thing. Over time, the human race has evolved from cavemen to a bustling civilization fueled by technology, science, and economics. While we’ve gained many abilities that separate us from other mammals and our closest ancestors, the apes, we’ve also lost a number of skills along the way.

One of them is the ability to regenerate. Some animals such as lizards, fish, and frogs, have a robust capacity to regenerate entire limbs and organs while humans can only partially regenerate some tissues and organs on a much smaller scale. Why did we lose this advantageous trait?

A human gene that stops cancer also blocks regeneration

Scientists from UCSF have found a new piece to this evolutionary puzzle in a paper published today in eLife. They found that a gene responsible for preventing cells from growing uncontrollably into deadly cancers in humans is also able to block tissue regeneration in zebrafish.

Detailed in a UCSF news release, professor and senior author on the study, Jason Pomerantz, was always intrigued by why humans can’t regenerate limbs like salamanders. To answer these questions, he turned to model organisms like fish and amphibians:

Jason Pomerantz, UCSF

In the last 10 to 15 years, as regenerative organisms like zebrafish have become genetically tractable to study in the lab, I became convinced that these animals might be able to teach us what is possible for human regeneration. Why can these vertebrates regenerate highly complex structures, while we can’t?


Like other scientists, Pomerantz was curious to know if humans “grew out of” their regenerative abilities in order to acquire systems that block cancer growth. Humans and other mammals have genes called tumor-suppressors that are important for regulating tissue differentiation during development and for preventing excessive cell growth and tumor formation after birth and beyond. Many of these tumor suppressor genes are conserved across a wide range of species, but Pomerantz knew of one that wasn’t shared between humans and regenerative animals, a gene called ARF.

Pomerantz and his team decided to see what happened when they added the human Arf gene into the genome of a highly regenerative animal, the zebrafish. While the addition of ARF did not affect zebrafish development, it did almost fully block their ability to regrow their tail fins after the tips were removed.

Normal zebrafish can regrow their tail fins after they are clipped, but fish that have the ARF gene cannot. (eLife)

Pomerantz explained ARF’s anti-regenerative role in the fish:

“It’s like the gene is mistaking the regenerating fin cells for aspiring cancer cells. And so it [ARF] springs into action to block it.”

Is Wolverine our future?

Wolverine. (Courtesy of

Knowing that ARF suppresses tissue regeneration in fish, the obvious question that arises from this study is whether blocking the Arf gene in humans would promote tissue regeneration. Would doing this mean we could all be regenerative super heroes like Wolverine one day?

Pomerantz explained further in the UCSF new release that boosting regeneration in humans that need new organs or limbs could be possible but would require a careful balance to avoid setting off rampant tumor growth:

Future efforts to promote regeneration in humans will likely require carefully balanced suppression of this anti-tumor system. The same pathway in humans theoretically could be blocked to enhance researchers’ ability to grow model organs from stem cells in a laboratory dish, to enhance patients’ recovery from injury. Since tumor suppressors are thought to play a role in aging by limiting the rejuvenating potential of stem cells, blocking this pathway could even be a part of future anti-aging therapies.

Scientists will likely have to weigh the risks and benefits for human tissue regeneration on a case by case basis. Pomerantz concluded with this admission:

The ratio of risk and benefit has to be appropriate. For instance, there are certain congenital diseases that cause craniofacial deformities so severe that the risks of such a treatment might be clinically reasonable.


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