What the humble planarian teaches us about the building blocks of life
At first glance, planarians aren’t exactly awe-inspiring. These brownish flatworms, each less than half an inch long, have few defining features: At one end, a tail comes to a rounded point; at the other, a head is punctuated by a pair of large, cartoonish eyes.
As unremarkable as the worms may seem, however, they have an ability we could only dream of. Cut off a planarian’s head, and it’ll sprout a new one. Lop off its tail, and it’ll soon be replaced. Even rending its body into tiny pieces is no big deal. Each chunk, regrowing from its wounded edges, replaces nerves, muscle, and other tissue until it becomes a separate, fully formed, individual worm in just a couple weeks.
“One of the big questions we want to answer is how it does this on a genetic level,” says Bo Wang, assistant professor of bioengineering at Stanford. “What’s in the worm’s DNA that lets it choose which body parts to grow, how much they’re going to grow, where to stop, and when to stop?”
Wang studies planarians’ alien-like regeneration. Part of what drives this astonishing ability, he says, is the fact that the worms’ bodies are filled with pluripotent stem cells, a type of “universal” cell that can grow into any type of tissue. When a worm is sliced in half, biochemical signals radiate outward from the damaged site, kicking those stem cells into action. Gradually, the cells differentiate into muscle, nerves, and other structures, forming a new head or tail over several days.
Although this sort of research is his primary focus today, Wang says he never expected to wind up in the field. Originally trained as a physicist, he spent much of his early career studying Brownian motion, the random movement of tiny particles suspended in a liquid or gas. Then, by chance, he saw a video of the worm C. elegans developing from a fertilized egg.
“As a physicist, I thought that when you’re dealing with things at the microscopic scale, all movement should be random, propelled by thermal energy and probability—but cells in these worm embryos could divide and move synchronously in a programmed manner even though they were just a few microns in size,” he says. “That blew me away. I think it’s what really converted me from working on physics to working on biology.”
Today, Wang is digging into some of the most fundamental building blocks of life: the various types of cells that make up an organism. His lab is sequencing the DNA and messenger RNA, the linear molecules that guide protein synthesis, within individual cells of several animals, including planarians, and is developing computational methods to compare them with cell types in other animals ranging from sponge to human in order to find commonalities and differences.
In the process, they’re learning how each of these organisms has developed unique and powerful ways to use conserved cell types for building new structures and has invented new cell types to survive in its environment.
Wang doesn’t want to stop at just cataloging those cell types, however. He’s got his sights set on bigger goals. With a deeper understanding of how cell types make tissues and how DNA in a cell nucleus controls the fate and identity of that cell, he says, it may one day be possible to harness the power of biology for our own purposes.
“As a bioengineer, I’m constantly thinking about that. Once we know the novel functions of a piece of DNA, we can transfer them to other cells—it’s really a matter of shifting the knowledge we get from one system to another,” he says. “I think we could eventually use them to program ‘living machines’ that do a specific job.”
It’s not so far-fetched. New technologies developed in the past decade make it easier than ever to manipulate DNA and insert it into a living cell. Biologists do it every day with microbes and human cell lines, reprogramming them into tiny “factories” that spit out drugs or other products. In theory, constructing entirely new cells, or even new organisms, in the lab could be right around the corner. Wang thinks it’s just a matter of imagination.
“We really don’t know the possibilities ahead of us yet,” he says. “But that’s the most exciting aspect of being a scientist. We’re constantly searching for new things, new surprises. That’s what gets me up each day.”