Spark of Life
If a newt can regrow a limb, why can't you? Tufts biologist Michael Levin is in search of the switches that control how body parts form, heal, and regenerate.
You are slicing onions. You miss. Your skin splits and bleeds, you run it under water, you bandage it, you wait. After the pain subsides, you probably give little thought to the miracle going on under the Band-Aid. Your cut finger knits neatly back together, replacing skin and blood vessels in a matter of days. Eventually, the wound disappears completely, and you forget it was ever there.
Regeneration is one of biology's great mysteries. Why is it that humans can repair their skin after a cut, but can't regrow a severed finger? Why is it that starfish and salamanders can regrow their limbs but a rabbit can't? How can some worms regrow their entire bodies from microscopic pieces of tissue, wriggling around afterward with the same knowledge they had before they were sliced?
"People have this idea that regeneration is for primitive organisms," says Michael Levin, A92, director of the Tufts Center for Regenerative and Developmental Biology. "The fact is, it is sprinkled very capriciously throughout the tree of life. You can have a worm that regenerates everything, then you can have a very close relative that regenerates nothing. A deer can regrow meters of bone, velvet, and vasculature every single year, producing a new set of antlers in the same pattern." Even humans have more ability to regenerate than is commonly recognized. Children under the age of eleven have regrown fingertips, for example, and adults can regenerate their livers from a small piece.
The riddle of regeneration has tantalized Levin since before he was an undergraduate at Tufts two decades ago. Now, as a brand-new member of Tufts' biology department, he is in pursuit of the cellular switches that could allow us to regrow any part of our bodies. "You did it as an embryo," he insists. "Forty years ago, my cells knew how to grow every structure in my body. That information has not gone anywhere. It's still there."
The quest for the magic switch has led developmental biologists to hunt for clues in gene expression and chemicals within cells. Virtually alone, Levin's lab has been searching for the key in an altogether different area: electricity. The idea is not completely new. Scientists have known for more than a century that tiny electric charges, on the scale of millivolts, are emitted from skin and bone when those tissues regenerate after a wound such as that cut you got slicing onions. Along the way, however, most scientists lost interest in the charges, focusing instead on the biochemical pathways uncovered through traditional molecular genetics. Levin has pioneered research on the molecular level to show that not only are these electrical flows significant—they might also be the signals that control how and why regeneration occurs.
To understand the mechanism is to put some of that control in human hands. "By learning about the way these bioelectrical signals are naturally used to determine biological shape," Levin says, "we can capitalize on this to alter structure rationally." Already, his lab has used tiny electrical jolts to alter regeneration in worms, frogs, and chickens. Applied to humans, he says, the same techniques could one day repair structures damaged by birth defects, regrow amputated limbs, or even reverse the growth of cancerous tumors.
Levin talks with the easy confidence of a scientist who is used to doing the impossible. His casual dress and laid-back demeanor—he is wearing a hoodie when I meet him, and has a Simpsons blanket draped on the back of his chair—make him seem younger than his forty years. His piercing green eyes, however, match the intensity with which he pursues his research. "Probably without exception, everything of significance that we have done pretty much everyone had told me wasn't going to work," he says with a smile. "Everybody's first reaction is ‘This is never going to work.' Sometimes they are right, but if you push hard enough and pay attention, I think you can make it work."
Prodigy may not be too strong a word to describe Levin's early career as a scientist. He lived in Russia until he was nine years old, and even at an early age, he was fascinated to learn how complicated structures were put together. "When I was four or five, we had this gigantic black-and-white TV, and my father would take the back off so I could see what was in there. I distinctly remember thinking that all that stuff didn't end up there by accident. Somebody knew how to put it together so that it worked. Whoever did that clearly had something special going on." As a student at Swampscott High School on Boston's North Shore, Levin got deep into computers. He learned difficult programming languages and made money as a designer of software for data visualization and robotic control.
Continuing in computers as an undergraduate at Tufts, he turned his mind to modeling complex systems. Yet the more he learned about computer science, the more he saw how much the field had to learn from the complexity of nature. "It's clear that the biological world is leaps and bounds beyond anything we can duplicate in engineering," Levin says.
With virtually no biology behind him, he approached the developmental biologist Susan Ernst to do an independent study in her lab. "The first day he came in to talk with me about the possibility of doing a project together, he had a notebook filled with reference after reference," Ernst recalls. "It was very easy for me to see that Michael was special. He had been thinking about living systems in a different way than most people were at the time." Coming out of physics and engineering, he was more interested in knowing what information cell groups exchanged during an embryo's self-assembly than in studying how specific genes influenced development, the vogue in developmental biology at the time.
He took magnetic coils—borrowed from the physics department—and wrapped them around sea urchin embryos to observe how electromagnetic waves affected their growth. The results showed those kicks of magnetism could change the animals' rate of cell division and early development. Before Levin, no student in Ernst's lab had been the lead author on a research paper; Levin was the lead author on two of them.
After graduating from Tufts, Levin carried on his exploration of cell communication as a Ph.D. student in the genetics department of Harvard Medical School, in the lab of the developmental biologist Cliff Tabin. At the time, Tabin's lab was doing research on genes that control the development of the nervous system and limbs of chick embryos. One of the molecules involved in the process enabled Levin and collaborators to identify how a chick embryo knows its right from left in early development—for example, how it knows to put the heart on one side and the liver on the other. That might seem like a simple distinction, but it's a thorny problem for a developing embryo. While "top" and "bottom" can be determined by gravity, there is no external force that can says which side is which. (continued)
MICHAEL BLANDING is an award-winning magazine writer whose work has appeared in The Nation, The New Republic, Boston Magazine, and The Boston Globe Magazine. This is his second cover story for Tufts Magazine.
Top photo by John Soares. Additional photos by Alonso Nichols, University Photography
This story originally appeared in the Spring 2009 edition of Tufts Magazine. It ran online on July 20, 2009.