Issue Date: November 28, 2016
Superfund research center studies asbestos from all angles
Ads in which a lawyer talks about compensation for asbestos exposure and mesothelioma have been a television mainstay in the U.S. for a long time. Watching those, one might assume that the science of asbestos—how it’s formed, how it’s transported in the environment, and how it causes lung cancers—is a closed book. It turns out, however, there’s still lots to learn about the long, thin fibrous material.
Prized for its flame and heat resistance, asbestos was used for decades in products such as floor and ceiling tiles, wallboard, electrical insulation, and brake linings. Once the mineral’s link to mesothelioma was established, the use of asbestos in the U.S. plummeted but never completely stopped. Many other countries banned new uses of asbestos minerals (see page 28).
Still, asbestos waste lingers at various sites across the globe, and buildings containing the material continue to age and decay. By some estimates, as many as 35 million homes in the U.S. harbor it.
“Asbestos kills at least 10,000 people a year in this country and many, many more worldwide,” says Christopher Weis, toxicology liaison at the National Institute of Environmental Health Sciences (NIEHS). “There’s ongoing exposure to asbestos that needs to be measured and studied—both general exposures in the ambient environment and specific areas of exposure.”
Enter the Penn SRP center, an NIEHS-funded research program that focuses exclusively on the challenges still posed by asbestos. It’s lengthier, formal name, the Superfund Research & Training Program at the University of Pennsylvania: Asbestos Fate, Exposure, Remediation & Adverse Health Effects, describes its purpose. The largest NIH-funded program dedicated to studying asbestos, Penn’s SRP center aims to answer a multitude of scientific questions about the fibrous material, including how it is transported in the environment, how best to remediate it, and how exposure causes health effects.
The center grew out of a relationship between professors at Penn’s Center of Excellence in Environmental Toxicology and the Community Advisory Group for the BoRit Superfund Site in Ambler, Pa. That site and the nearby Ambler Piles Superfund Site are the largest industrial waste sites for asbestos in the U.S. Another site in Libby, Mont., is larger, but it was a vermiculite mine that happened to contain large amounts of asbestos rather than being a designated asbestos manufacturing facility.
The Ambler sites, located just north of Philadelphia, were dumps for asbestos-containing waste from nearby facilities that manufactured asbestos-containing construction materials such as tiles, shingles, and pipes. The type of asbestos used there is chrysotile, a member of the curvy-shaped serpentine class of minerals. The last of the factories closed in 1987. The defunct facilities left behind huge piles of asbestos-containing materials that had accumulated over decades. At the Ambler Piles site, the color and height of some of the heaps earned them the nickname “White Mountains.”
Edward Emmett, an occupational medicine expert at Penn and onetime director of community outreach at Penn’s environmental toxicology center, is a member of the community advisory group for the BoRit site. In this role, he hears a lot about the community’s concerns about cleanup and remediation efforts. He realized there were scientific questions in those concerns.
“Communities can identify the issues, but they’re not good at identifying the precise scientific questions that need to be answered to help,” Emmett says. “We took those issues and formulated them into questions.” Six of them to be precise. The SRP center is organized around those questions. The goal is to make its findings relevant to Ambler and to other asbestos-contaminated sites around the world.
One of the SRP center’s six projects, led by plant biologist Brenda Casper, aims to figure out how best to revegetate the Ambler site. The asbestos piles are capped with a thick layer of soil intended to contain the asbestos. The right plants can help hold that soil in place. “The question is what types of soil additives to use and what types of plants to plant,” Casper says.
Rocky outcrops that contain serpentine minerals related to the chrysotile asbestos occur throughout the eastern U.S. “The first thing we did was go to serpentine sites to see if the plants that grew there would be better at growing on asbestos.”
Casper’s team planted seeds from grasses growing on the serpentine rocks in asbestos-containing soil. “We expected these seeds to do a lot better than commercial seeds we buy,” she says. But they didn’t. Apparently, the grasses evolved to handle the high metal content of the serpentine rocks, so they tolerate well the serpentine soil but do not grow rapidly regardless of soil type.
As Casper’s team continues looking for plants to hold the soil in place, another group worries about whether buried asbestos can migrate through the soil. Geophysicist Douglas J. Jerolmack is studying the transport of asbestos and other fibers through water and soil. He had to start almost from scratch because little was known about the diffusion and aggregation behavior of asbestos and other rod-shaped colloids.
“When you look at research on the behavior of different species of asbestos, there was a lot of fundamental work on materials characterization and aggregation all through the 1970s,” Jerolmack says. “After asbestos got declared hazardous, fundamental research on asbestos just stopped.” Many modern-day materials characterization techniques haven’t been applied to asbestos, he says.
So his team started by looking at the diffusion of chrysotile asbestos fibers in water. Chrysotile is the most common type of asbestos in commercial use. The researchers found that fiber diffusion is size-dependent and agrees with predictions about how rod-shaped particles diffuse randomly (Environ. Sci. Technol. 2015, DOI: 10.1021/acs.est.5b03839).
Then they looked at how asbestos fibers cluster together. They compared the aggregation behavior of chrysotile asbestos fibers to that of glass spheres and glass rods—model objects. The glass rods had the same mass, size, aspect ratio, and surface charge as the asbestos fibers. “We found that the glass rods behaved identically to the asbestos fibers, and both of them were fundamentally distinct in their growth and aggregate structure from anything that had been reported before,” Jerolmack says.
They both behaved differently from the glass spheres, leading Jerolmack to believe that shape plays a significant role in aggregation behavior. He also thinks that the results may be applicable to other rod-shaped materials, such as carbon nanotubes, which are also an inhalation concern.
Jerolmack’s ultimate goal is to be able to do field studies in Ambler.
“There are so many open questions that I didn’t feel the wise thing to do first was a field campaign,” he says. “We need to be educated in the way we go about sampling in the environment. We could start taking samples willy-nilly, but it’s hard to isolate low concentrations of asbestos fibers in soil and water. Based on what we’ve learned, we now have an idea of how solution chemistry may influence the aggregates.” His team is using that information to design a field sampling campaign to see whether any of the capped asbestos in Ambler has migrated.
The Ambler community is worried about whether the asbestos can migrate through groundwater to nearby Wissahickon Creek.
“We don’t have any reason to believe right now that there’s been significant migration of the asbestos fibers through groundwater,” Jerolmack says. There have been some reports of asbestos fibers in the water, but because there are naturally occurring outcrops in the area, it’s not clear whether those fibers come from the Superfund site or natural sources, he adds.
The main reason the SRP center’s scientists and the surrounding community are concerned about asbestos’s containment and migration is its potential health effects. As a result, the center has focused four of its six projects on studying these.
One of the health-related projects is taking a historical look at the incidence of asbestos-related diseases in Ambler. Frances K. Barg, Emmett, and coworkers are mining census data from 1930, a period of peak asbestos production in Ambler, to determine who among the people who lived in the area later developed an asbestos-related disease.
“We know who was there and where they were living. Did they work with asbestos? Did they live in a family with someone who did?” Emmett says. “We’re looking to see what happened to those people. What did they die of?”
The historical approach Emmett, Barg, and the team is using is necessary because “less than 1% of the mesotheliomas from asbestos occur in the first 15 years following exposure,” Emmett says. “The rate increases until about 45 years after exposure and then it flattens out.”
The availability of census records, which are released after 72 years, is a key piece of the study. “We know exactly the names, family name, spouses, time of birth, whether they worked in the factory,” Emmett says.
One of the goals is to determine the importance of community exposure compared with occupational exposure. Does living in a community with asbestos lead to an increase in asbestos-related disease even for people who don’t work with asbestos? If so, what factors contribute to that increase? Emmett and his team have been able to track down death records for about 2,000 people, just over half of the cohort, so far.
As the ethnographic study highlights, the long latency period for asbestos-related diseases is a challenge for studying such conditions. Joseph R. Testa, a geneticist at Fox Chase Cancer Center, is leading a project at the Penn center for developing animal models that can make it easier to study mesothelioma and potential prevention measures.
Testa’s mesothelioma work predates the Penn center. By studying families with multiple cases of mesothelioma, he has discovered genetic mutations that can contribute to the development of the disease. He’s identified mutations or deletions of the BAP1, CDKN2A, and NF-2 tumor suppressor genes as being important for mesothelioma development.
Now he’s using those mutations to genetically engineer mouse models of the disease. One type of mouse has a BAP1 mutation. The other has both CDKN2A and NF-2 mutations.
Testa uses the mice with two mutations to test potential protective agents because those mice develop mesothelioma quickly after asbestos exposure. “If they don’t have a mutation, it takes about a year for the mesothelioma to become symptomatic,” Testa says.
One limitation of the mouse models is that the researchers deliver the asbestos by injection into the peritoneal space of the abdomen instead of by inhalation, which is the usual exposure route for humans. Nonetheless, with the mouse models, they see that crocidolite, a type of asbestos that’s characterized by its needle like structure, is very carcinogenic. Chrysotile, though not as bad as crocidolite, is also carcinogenic in the mice.
Another Penn researcher, Melpo Christofidou-Solomidou, is using the mouse models to study asbestos fiber toxicity, which is strongly connected to inflammation. She’s also evaluating antioxidants as a way to combat inflammatory processes in the lungs and other agents that might prevent lung cancers. She is especially interested in finding botanicals with protective properties. Botanicals could be nontoxic and attack multiple disease-related molecular pathways simultaneously, she says.
At the moment, she’s got her sights set on the most bioactive component of the lignan component of flaxseed, a biphenolic called secoisolariciresinol diglucoside (SDG). In cell studies, SDG acts as a free-radical scavenger and decreases the release of inflammatory agents. It also activates Nrf-2, a gene that regulates the transcription of antioxidant enzymes.
Christofidou-Solomidou envisions using SDG as a prophylactic dietary supplement for people who know they have been or may be exposed to asbestos. But she acknowledges that such hopes are still premature. “A lot more studies need to happen. We have to go from mice to primates to man,” she says. “There’s a long regulatory pathway.”
Diagnostic tools such as biomarkers are needed to help identify people who could benefit from intervention. Ian A. Blair, who is the director of the Penn SRP center, and coworkers are using high-resolution mass spectrometry to identify biomarkers of asbestos-related disease. They have analyzed blood serum samples from asbestos-exposed shipyard workers to identify potential lipid and protein biomarkers of mesothelioma. They are focusing most closely on a protein called high-mobility group box-1, or HMGB-1, which is involved in inflammation. Other researchers have shown that the acetylated form of this protein is predictive of mesothelioma.
“We’re developing a way to look at all the different acetylation states of HMGB-1,” Blair says. The protein has 43 lysine residues as possible acetylation sites. Blair and his team want to be able to look at all the possible combinations of acetylation to see which ones are important.
They hope to eventually combine multiple biomarkers into a single assay. “Hopefully, along the way we’ll discover a biomarker that’s specific to asbestos exposure but not mesothelioma,” Blair says. Such a marker could give people advance notice of whether they’re at risk for these diseases that take so long to manifest themselves.
All this research is done with the needs of the community in mind, says Trevor M. Penning, deputy director of Penn’s SRP center and director of the Center of Excellence in Environmental Toxicology.
“We pride ourselves on a model called community first communication. If we’re doing community-engaged research, the community has a right to know about the results of our findings as soon as they’ve been vetted, rather than waiting for them to trickle down through peer review.”
As far as Penning is concerned, the center’s interdisciplinary training activities are as important as its research. “The individuals working on these projects come from different cultures and different perspectives on how to do their science,” he says. “We put in place curricula and cross-training to allow these trainees to feel comfortable with the different components of working on Superfund hazardous waste.”
And perhaps most important is the assistance the center can provide in policy decisions. “Often when we do bench-related science, we don’t think about the impact of what we’re doing in terms of public health policy and remediation strategies,” Penning says. The research coming out of Penn’s asbestos center, scientists there hope, could have near-term impact on the local governments that look after the Ambler sites.
But Penning sees the center’s impact reaching the national level as well. “Congress needs to be informed that we have these problems that are going to impact public health,” he says. “We’re not allowed to lobby because we get federal dollars, but we can certainly provide persuasive information that might help in the decision-making process.”
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