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The Innovator
When Erin Lavik got a chemistry set at age seven, the first thing she did was mix the chemicals she wasn’t supposed to mix. In high school she built a catapult that cracked her parents' windshield. As a biomedical engineer, she created the next best thing to a miracle.
January/February 2005
by Cathy Shufro
Cathy Shufro, a freelance writer based in New Haven, writes frequently about medical issues.
If you want to understand the essence of Erin Lavik’s groundbreaking work on spinal-cord injury, you have a choice: you can read a dense six-page paper in the Proceedings of the National Academy of Sciences, or you can watch a 60-second video. That video contains what are surely the most emotionally affecting images of two white rats ever made. Both rats' spinal cords had been severed on one side a few months earlier. One received an experimental spinal implant; the other was given general care for recovery from a wound. In the video, the one who received standard care drags herself forward on two legs. Her body is twisted, and one hind foot trails behind. Then the second rat skitters across the floor, both hind legs working well. Watching them, one thinks: could we heal a human being like this?
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“I am interested in doing something that will make a difference in my lifetime.” |
Lavik, who designed the spinal implants as a graduate student in biomedical engineering at MIT, believes we can. The experiment launched her career; she is now an assistant professor at Yale, which is investing in its biomedical engineering faculty and facilities in a calculated effort to build a strong department. And in 2003, two years out of graduate school, Lavik was chosen as one of the “TR100,” Technology Review’s juried list of 100 leading young investigators. Today, she is working to improve the spinal implants. They are far from ready for human spinal cords, and, as she points out, treatments that work well in rats don’t always work as well when scaled up for people. She’s hopeful, though: not that she herself will create the solution—that would be arrogance, she says—but that she may be able to contribute. “I am interested in doing something that will make a difference in my lifetime,” she says. “If we get lucky, it will.”
Lavik, a playful woman of 32 with memorable red hair, is an accomplished baker, a playwright, and a mentor to New Haven science students. On a Friday afternoon in November, she’s talking to a group of seventh- and eighth-graders who are planning to enter the annual science fair. They propose to find out whether rock music makes bean plants grow faster, but Lavik is not impressed.
“Do you see any benefit to society from this information?” she asks them. They admit that playing U2 to bean seedlings may not lead to real-world applications. Lavik suggests an alternative: growing beans in very sandy soil. “The Sahara desert is encroaching on the arable land in Africa at an alarming rate,” she tells them. “It’s one of the problems in Sudan.”
Later, Lavik jokes: “This is what I do in my spare time: I thwart eighth-graders’ attempts to do simple science projects. Probably next week they’ll say, ‘We’re using classical music. Now are you happy?’”
The question of societal benefit almost derailed Lavik’s own career. She earned a bachelor’s in materials science and engineering from MIT in 1995 and stayed on for graduate school, starting out by researching the properties of ceramic surfaces. “The work we were doing was really cool,” she says. “But it wasn’t going to have a major impact in any tangible way on people’s lives.” She decided that she should leave.
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Lavik specializes in tissue engineering. |
Lavik was trying to choose between becoming a veterinarian and teaching high school chemistry when her mother happened to take a seat on a plane next to Martha Gray, a biomedical engineering professor at MIT. Listening to Gray talk about solving problems in medicine and biology, Lavik’s mother realized that this was a field her daughter might find meaningful. When Lavik herself talked with Gray, she felt she had found an intellectual home.
Lavik specializes in tissue engineering, a field that originated in the late 1980s to investigate repairing the body by combining synthetic and natural materials with living cells. Some tissue engineers hope to fashion usable organs such as livers and kidneys; Lavik concentrates on the spinal cord. Spinal-cord injuries affect 11,000 people in the United States each year, 247,000 Americans in all. When spinal vertebrae are fractured—usually in car crashes, falls, or gunshot wounds—they press on or tear the spinal cord within, disrupting the ability to feel, to move, and to maintain bowel, bladder, and sexual function. Very few of those injured recover significantly.
Although Lavik is among an estimated 500 scientists worldwide studying ways to repair the spinal cord, physical therapy remains the only standard treatment. It can restore some sensation and function, but it is arduous, and the gains may be minimal. Actor Christopher Reeve pursued an ambitious and expensive course of physical therapy after breaking his neck in a riding accident. He did regain some sensation and movement in his hands, and he was able to push off with his legs in a pool, but he was never able to use his body for daily tasks.
lavik was seven when she got her first chemistry set, and right away she noticed that the instructions warned against mixing certain chemicals. “I immediately mixed them,” she says. “It seemed to me that if there was a warning, it must do something really interesting.” She already knew that a childhood friend of her father’s once engineered a schoolyard explosion that shattered windows: “He was my hero.”
Her father, a lawyer, and her mother, an accountant, were indifferent to the allure of science. Lavik would inform them that she was working on a particular project, and they would reply: “Science… We’re both really bad at that. Good luck!”
As a student at the National Cathedral School in Washington, D.C., Lavik had to push for permission to take upper-level science courses at the affiliated boys' school, St. Albans. “It made me really angry. This was 1990; it wasn’t pre-women’s rights. They constantly told us ‘Women can do anything.’” Unlike the physics classes at Cathedral, the St. Albans class included hands-on projects, like designing a catapult to lob golf balls. (Only when they read this magazine will her parents learn how their windshield developed a crack in Lavik’s senior year.)
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Only when they read this magazine will her parents learn how their windshield cracked. |
Lavik loved MIT. Her circle of friends ate together in the dining hall every night, always crowding another person in around the table no matter how many arrived. They still maintain a thriving e-mail list, some four dozen strong, for personal news and computing and engineering esoterica. One of her closest friends is Erika Abbas, now a quality manager at E Ink in Cambridge, who was in the audience when Lavik presented her thesis proposal. Lavik described her plan to design a scaffold patterned after a rat’s spinal cord, build the scaffolds out of a biodegradable polymer often used for suture thread, and seed them with neural progenitor cells from mice. (Neural progenitor cells, also called neural stem cells, are immature cells that can develop into neurons and supporting cells in the right environment.) A surgeon would remove a section of the spinal cord from a number of lab rats and implant scaffolds in some, and then Lavik and her colleagues would track the rats' recovery.
The reaction from Lavik’s thesis committee, as Abbas remembers it, was: “This is way too much. You’re never going to finish all that.” The committee suggested that she design a scaffold, add cells, and see whether the cells would grow on it in a petri dish. “But,” says Abbas, “Erin said, ‘No, that’s not the whole story. I want to go to the end.’”
Lavik spent two years designing the treatment strategy. Because she would have to injure the rats and eventually kill them, she says, “it was really important to me that I thought the study we were doing was necessary.”
The idea of a scaffold was not new, but Lavik spent months creating a design that satisfied her. To mimic the anatomy of a spine, she used suture thread to bind a porous piece of spongy polymer fabric to a plastic cylinder less than a quarter-inch long. Like a flower stem, the cylinder contained many tiny open channels inside.
The next challenge was deciding how big to make the channels. Lavik had to reckon with the shape of a spinal cord nerve cell: a rounded cell body with a long thin tendril, called an axon, that carries nerve impulses. Should the channels in the scaffold be large enough to accommodate the cell body, providing protection, or should they be skinny, so only the axons could enter? She decided to make the channels small, reasoning that they would protect the axons from being overwhelmed by scar tissue, which is faster-growing but too large to enter the channels. Once she'd designed the scaffold, Lavik had to work through the technical barriers to manufacturing several dozen identical copies, and then figure out how long to culture the cells before implanting them.
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It was both exhilarating and nerve-racking, Lavik recalls, to see some of the rats start walking again. |
In the fall of 1999, a surgeon in Boston excised four millimeters from one side of the spinal cords of 50 white female laboratory rats. He made the cuts at the ninth and tenth thoracic vertebrae, about midway down the back. In some of the rats, he implanted scaffolds with cells; in others, only scaffolds or only cells; and in a few rats, nothing at all. Soon after, Lavik and her colleagues began their tests. They measured how well the rats could walk, whether they could hold themselves up on a slanted board, whether they could feel the pain of a little pinch on the foot on the injured side.
It was both exhilarating and nerve-racking, Lavik recalls, to see some of the rats start walking again. What if these were the rats that hadn’t received implants? What if the recovery had nothing to do with the treatment? Lavik and her colleagues had followed the standard experimental protocol of “blinding” themselves to which rats were which, so that their bias would not influence the results, and they had no way to reassure themselves until the study was over. “We just hoped—really, really hoped—that the animals that were walking were part of the treatment group,” she says.
They were. The rats with the scaffold-plus-cells implants recovered much more function than any of the others. Among the untreated rats, three in ten learned to walk again. The recovery rate for rats implanted with cells alone was similar, fewer than two in ten. Of the scaffold-only rats, slightly more than half walked again. But of the scaffold-plus-cells rats, seven out of ten regained significant ability to walk. “We were blown away,” says Lavik. (The video clip of two rats is at www.pnas.org/cgi/content/full/052678899/DC1/1.)
Lavik’s thesis advisor, Robert S. Langer, was surprised too: “I thought she'd do well, but that was a pretty spectacular outcome.” Langer, the Germeshausen Professor of Chemical and Biomedical Engineering at MIT and a superstar in the discipline, calls Lavik’s research “very original, very good work.”
A collaborator of Lavik's, D. Michele Basso, a professor of physical therapy at Ohio State University, comments, “Can we put a scaffold in and get functional recovery? The answer is yes. But it’s not really clear why there was this functional effect or how to maximize it. For every question we answer, we usually get ten more.”
Lavik believes most of the recovery came from the effects of the scaffold itself, since post-mortem tests showed that none of the implanted cells had developed into neurons. She speculates that the channels protected the rat’s own spinal cord tissue against the intrusion of scar tissue as it grew. “I think we had tissue preservation but very limited regeneration,” she says. But she is confident that the rats' recovery was not a fluke—the improvement rates for the scaffold-plus-cells rats were statistically significant—and she believes the scaffold could be scaled up for use in humans.
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Lavik is not the only scientist at Yale to make dramatic progress in the field of spinal-cord repair. |
Achieving functional recovery in rats, let alone humans, is difficult because so many factors affect neurological injury and recovery. Swelling, scarring, and biochemical signals that instruct cells to commit “neuronal suicide” cause secondary injury weeks or even months after an accident. Post-injury bleeding also causes damage, because blood harms neurons. Lavik and Basso are trying to find out whether quick repair of ruptured blood vessels after an injury improves recovery.
Lavik is not the only scientist at Yale to make dramatic progress in the field of spinal-cord repair. Yale neurologist Stephen M. Strittmatter has discovered another impediment to spinal-cord recovery—and through it, one of the most promising possibilities for repair. Strittmatter, holder of the Vincent Coates Chair in Neurology, found that after an injury, the body actually blocks repair: a protein called Nogo inhibits the regeneration of axons. He and his colleagues have identified compounds that block the axonal receptors for Nogo. In their experiments, axons grew back in rats whose brains or spinal cords had been damaged, and the rats that received treatment regained significant ability to walk. Strittmatter says that the research on rats may lead to clinical trials for spinal cord injuries and stroke.
Also at Yale, Charles A. Greer in the neurosurgery department and Jeffery Kocsis in neurology are trying to capitalize on the one place in the central nervous system where neurological regeneration is the norm: the nose. Receptor cells in the lining of the nose die and are replaced every 45 to 60 days, year after year. When Greer’s and Kocsis’s teams took cells from the olfactory system and injected them into rodent spinal cords, axons regenerated.
Lavik’s scaffold might play a role here. Lavik is working with a neurosurgery resident (whom Greer supervises) to find out whether using a scaffold to implant the olfactory cells will raise the rate of regeneration. A scaffold will also allow researchers to introduce growth factors, proteins that activate cells to develop or multiply.
In 2004, Wired magazine nominated Lavik for one of its Rave Awards, which honor “the mavericks, the dreamers, the innovators” who are “paving the way to tomorrow.” Among the winners were Talking Head David Byrne, Lord of the Rings filmmaker Peter Jackson, and Apple CEO Steve Jobs. Although Lavik didn’t win, she got a kick out of the awards ceremony. “People spent the whole time being very, very cool,” she says. “That’s how the scientists found each other—because we were not hip.”
Hip and not hip, of course, are in the eye of the beholder. Lavik skied on MIT’s varsity Nordic team, skated on its intramural ice hockey team, and played flute for its marching band. She traveled for a month in India during graduate school. (“Technically, I was writing my thesis.”) She has written four plays. In her latest, a work in progress called Galileo Walking among the Stars, four famous dead scientists build a spaceship to explore the heavens. (She consulted her MIT listserv for details on the next generation of space-flight propulsion systems.) The Ensemble Studio Theatre of New York City chose the play for a staged reading in 2003.
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Lavik has already created two unusual undergraduate courses. |
Lavik likes to cook, particularly the flamboyantly rich dishes of her Norwegian paternal heritage, such as rommegrøt (sour-cream porridge). She also bakes wedding cakes. The shelves in her office hold textbooks on tissue engineering, a box of biscuits for her beloved red mongrel, Wally, and a thick stack of Martha Stewart Weddings. Lavik and Erika Abbas, who are conversant in terms like “ganache” and “rolled fondant,” have made a half-dozen cakes together for their friends' weddings. Abbas describes Lavik as fearless when it comes to the defining moment of producing a wedding cake: stacking the layers. “If you hesitate, you’re lost,” Abbas says. Lavik doesn’t hesitate. “That may be why she does so many things. She just says, ‘One, two, three, go!’”
Lavik takes the same approach to teaching. She has already created two unusual undergraduate courses. One is an upper-level biomaterials course in which, instead of learning laboratory techniques in a prescribed order, students work on solving a design problem—creating an artificial artery using two kinds of living cells—and learn bench skills as needed. The other is a freshman writing seminar that will focus on the science and ethics of stem-cell research. She is also supervising three graduate students. Teaching, she says, is “a tremendous rush. The only thing cooler than making a discovery is watching someone you’re teaching make a discovery.”
But she is still discovering. In addition to her spinal-cord research, Lavik is researching retinal degeneration, the leading cause of blindness in industrialized countries. She is working on designing a polymer delicate enough to hold artificial rods and cones and to be implanted within existing eye tissue. In experiments on lab rats, she is trying to replace lost photoreceptors in the retina by implanting a spongy scaffold seeded with retinal stem cells.
In her quest to repair the body, Lavik has come to value its inherent wisdom: “We try to do simple things and let the body take over as much as possible,” she says. “Biology is much smarter and more complex than we can be. The body has four billion years of R&D.  |
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