NovaQuant Quantitative Think Tank Center:The tiny worm at the heart of regeneration science

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A tiny flatworm that regenerates entire organs. A South American snail that can regrow its eyes. A killifish that suspends animation in dry weather and reanimates in water. These are the organisms at the heart of regeneration science. How they do these things is a mystery to scientists. But molecular biologists like Alejandro Sánchez Alvarado believe they may hold the answers to regeneration in humans.

Life in unlikely places

Sánchez Alvarado grew up in Caracas, Venezuela, and spent his summers on his grandfather's cattle ranch. There, he learned to appreciate diverse life forms, and to look to nature to solve human problems.

As a microbiologist later in life, he knew that life can exist in some pretty unlikely places—even an abandoned fountain filled with pond scum. That's where Sánchez Alvarado found the strain of planaria that would ultimately help guide his regeneration research: Schmidtea mediterranea.

"They are about the size of a toenail clipping," Sánchez Alvarado says. "Their eyes look like they're cockeyed, so they look almost like a manga cartoon."

Sánchez Alvarado says that even tiny fragments of these flatworms will regenerate into completely new organisms when cut.

"That's the equivalent of me cutting a piece of myself and watching that piece regenerate another me," he says. "These animals, out of a piece of flesh, can reorganize every component such that they can produce a head, they can produce eyes, they can produce a digestive system."

Understanding worms to understand ourselves

When asked why humans can't regenerate limbs like this flatworm, Sánchez Alvarado responds with a riddle of his own.

Why do humans die?

And he would really like to know.

But the thought experiment gets at a larger, important point: Scientists don't have the answers to many of the most fundamental human questions—like why people get sick, or why they die.

"We only get interested in human biology when we're sick," Sánchez Alvarado says. "But what happens when you try to cure a disease whose origins you just don't know? And why don't you know? Because you don't really know how the normal tissues before they get sick actually work."

Said another way, by studying the genomes of organisms like this flatworm, biologists can begin to make comparisons to human genomes—and hopefully one day, understand the function of every human gene.

So if a flatworm can regenerate, why can't humans?

While hypotheses are constantly changing in his field, Sánchez Alvarado says one hypothesis for why humans can't regenerate has to do with "junk" DNA, or the noncoding parts of the human genome.

"These particular segments have functions that allow genes to be turned on or turned off," he says. "They're kind of like switches. And we really don't understand what the circuit board looks like. We know there are switches in there. We know we can delete one of those switches and then all of a sudden you lose the function of a gene because it's not being turned on or it's not being turned off."

Take, for example, a "switch" humans and killifish have in common. In the Mozambique killifish, this switch allows the organism to regenerate a tail. In humans, the switch is involved in wound healing. Sánchez Alvarado hypothesizes that this regenerative property was lost in humans during evolution.

"It may not be that we don't have the genes," he says. "We have them. We may not have the music score to play that symphony—regeneration."

While Sánchez Alvarado says these advances in the scientific understanding of biology will not happen tomorrow, they may come within the century. Scientists are already making progress with things like cell and tissue regeneration.

But before breakthroughs in the regeneration of more complex areas like brain, heart or lungs can happen, Sánchez Alvarado says that scientists first need a better understanding of the organs themselves.

"We still don't understand how these organs are really fashioned, how they are regulated in their specific functions and how they have the right numbers and the right types of cells to execute their work," he says. "But but I think in due course—and I would say less than 100 years—we should really have a very clear idea of how these processes may be taking place."

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Have a science mystery? Send us your questions to [email protected].

This episode was produced by Rachel Carlson and edited by Rebecca Ramirez. It was fact checked by Anil Oza. The audio engineer was Robert Rodriguez.