Monday, June 11, 2012

Small Wonder

Partnering with an engineer, a pathologist goes in a new direction.

The yellow-and-black signs outside Dr. Agnes Kane’s pathology laboratory read “CAUTION: Cancer hazard.” Nodding at the ominous-looking postings, Kane explains, “because of their toxicity similar to asbestos, we handle these materials as if they were carcinogens.” Meanwhile, across the Providence River, at the School of Engineering, Professor Robert Hurt is hard at work creating the very materials that Kane is so gingerly studying: nanoparticles.

Smaller than 1,000th the width of a human hair—so small that you need an electron microscope to see them— nanoparticles’ practical applications may be enormous: making implants more biocompatible; diagnosing and treating cancers; cleaning up oil spills. That said, the history of science is filled with promising solutions that create additional unforeseen problems of their own. No one is more aware of this than Kane, chair of Brown’s Department of Pathology and Laboratory Medicine. She has spent her career on, and helped guide the Department’s focus on, the human health effects of environmental and occupational exposures. She and Hurt tick off some examples demonstrating this law of unintended consequences:

“Corn ethanol,” says Hurt, referring to the fact that 40 percent of the corn grown in America is used to create this alternative fuel. “Then you raise the corn prices for food.”

Kane nods. “Use more fertilizer? Contaminate our water supplies. There’s always these trade-offs.”

One of modern history’s most devastating trade-offs was of a common mineral that makes an excellent flameretardant building material. Its usefulness notwithstanding, asbestos can cause devastating cancers and fatal lung problems both for those who mine it and for those who live and work in buildings that contain it.

Small, Novel...but Safe

Selenium-carbon nanocomposite particles
synthesized as a novel chemotherapy agent

From the time Kane joined Brown’s pathology department as a founding member in 1982, she has studied the mechanisms by which asbestos injures cells and causes cancer. When, in 2004, she gave a talk about this research to a group of colleagues, Hurt approached her afterward. The asbestos fibers that Kane showed in her talk reminded Hurt of the carbon nanofibers he had been developing. “We were not working on health effects at the time,” Hurt says. “We were doing traditional nanoscience, trying to make new things that had never been made before.”

But when Hurt told Kane about his carbon nanofibers, “I immediately asked him if I could have some,” Kane recalls. Her worrisome discovery—that the particles were similar to asbestos in several key ways—has changed the direction of both her own and Hurt’s careers and of the pathology department’s research and teaching.

Now Kane and Hunt work side-by-side to create innovative nanotechnology and, simultaneously, assess the materials’ safety and toxicity. “It’s a new paradigm to try to consider the implications of the technology as you develop the technology,” says Hurt. “We haven’t done a lot of that in the past. We just develop technology and we field it and then we worry about what its implications might be. So it’s kind of fun to do these things together.”

In 2007, their collaboration gave rise to the Institute for Molecular and Nanoscale Innovation (IMNI), an interdisciplinary organization comprising more than 60 faculty in nine departments. Kane heads IMNI’s NanoHealth Initiative, which studies the environmental and health effects of nanotechnology.

Training the Next Interdisciplinarians

With curly chin-length gray hair and blue eyes, Kane—known to friends and colleagues as “Aggie”—smiles often and laughs readily. Her unassuming manner and commitment to collaboration, teaching, and mentorship have won her numerous teaching awards and devotees.

“If it weren’t for Aggie, I wouldn’t be doing what I’m doing,” says Luba Dumenco, a lecturer in pathology and director of the Medical School’s preclinical curriculum. “She’s always valued teaching incredibly highly.” Just recently, Dumenco struck up a conversation with another mom at the local skating rink.The woman happened to be a neonatologist who had trained at Brown’s medical school. “I told her I was teaching at the med school, and she said, ‘Do you know Dr. Aggie Kane? She was our favorite! We loved her!’” Dumenco says with a laugh. “She cares a lot about the students.She does a wonderful job and they’re very lucky to have her.”

The breadth of students that Kane reaches each year has grown as a result of her partnership with Hurt. In 2009, they secured a grant from GAANN, or Graduate Assistance in Areas of National Need, to fund interdisciplinary training in nanotechnology. Between six and eight doctoral students study nanotoxicology and nanomedicine with co-mentors in engineering or physical sciences and biological science. Kane and Hurt also co-teach an undergraduate and graduate course called “Small Wonders: Science, Technology, and Human Health Impacts of Nanomaterials.” For their final projects, students working together in interdisciplinary teams are required both to use nanotechnology to solve some real-world problem and to address—and minimize—their solution’s potential environmental and health impacts. “I look at this as training the next generation of environmental scientists and engineers,” Kane says.

But first they have to learn how to talk to each other. When Kane and Hurt began collaborating, “it took us a while to learn each other’s languages,” says Kane, “because medicine has its own vocabulary, as well as engineering.” Kane might, for example, say “mitochondria,” or “epigenetics,” and get a blank stare in return. “And so we would just keep asking each other questions, any time we didn’t understand something,” she recalls. “It took us quite some time to learn enough to communicate effectively.”

Their newest collaboration is funded by the Gulf of Mexico Research Initiative, which was established in the wake of the Deepwater Horizon disaster. Hurt has set out to design nanoparticles called nanosorbents, which by capturing and sequestering pollutants like oil, may be safer and more effective than existing methods of cleaning up oil spills. The Deepwater Horizon cleanup team—like the Exxon Valdez team before it—relied on Corexit, a dispersant which causes oil to suspend in the water as tiny particles rather than accumulate on the surface as oil slicks.

“They used it in enormous amounts in the Deepwater Horizon cleanup,” says Hurt, but “it’s not clear if it’s a good idea to use very large amounts of chemicals in a marine environment.”

But it’s not clear whether nanosorbents are a good idea, either. As Hurt designs the particles, Kane and her team set out to answer two questions. “First, will they work?” she asks. “And then, will they be toxic to the organisms?”

“They might be worse,” Hurt acknowledges. “We don’t know.”

Engineering Prevention

To begin to answer these questions, Kane has a small steel tank in her lab. Like a miniature wave pool, the open-air tank bubbles with seawater maintained at exactly 72 degrees. Soon this will be home to a small colony of brine shrimp, tiny marine organisms that, as larvae in the wild, are eaten by small fish, which, in turn, are used as bait to catch larger fish, which are eaten by people. As such, the brine shrimp are a good “indicator species” for study.

“We don’t want to have these kinds of dispersants accumulate up the food chain,” says Kane, peeking at the churning water.

A tube runs from a beaker into the basin, helping to aerate the water. As the shrimp grow in the lab, Kane and her colleagues will release oil and Hurt’s nanoparticles into the water with them to see what happens. Will they stop swimming? Will they die? Will their RNA reflect toxicity or injury? If so, Kane says, she is confident that her colleagues can alter the nanoparticles to reflect her findings.

“Engineers are very clever,” she says with a smile. “If we can identify the specific properties that are associated with the toxic effects, they can design [the nanoparticles] or process them to eliminate those properties or reduce those properties and reduce their toxicity.” And part of the excitement of studying nanoparticles is the ability to intervene now, in the very early stages—to prevent environmental and health disasters, rather than clean them up after the fact.

“When you think about what happened with the widespread use of asbestos throughout the 20th century— and we’re still suffering the consequences because of the long latent period of those diseases—the fact that those fibers persist in the buildings and in the environment and we’re still being exposed,” says Kane, “that’s a very expensive lesson. We do not want to repeat that tragedy again.”

by Beth Schwartzapfel ’01
Photographs by Karen Philippi
Courtesy of Brown Medicine Magazine