Paving the Way for Nanotech

Nanotechnology has been billed as the next great technological revolution--sometimes referred to as the "second Industrial Revolution." It holds great promise in a number of areas, including medicine, energy, and materials science. But as the science advances and applications begin to emerge, researchers and policymakers fear that unintended health and environmental implications and a backlash of negative public opinion will stop the field in its tracks.

To guard against such a backlash, a push is under way to make sure that, as the science moves forward, issues related to the environmental and safety implications and the ethical concerns of nanotechnology also are studied. This latter group of studies was the topic of discussion at an Institute of Medicine workshop held in Washington, D.C., on May 27. Sponsored by IOM's Roundtable on Environmental Health Sciences, Research & Medicine, the meeting assessed the current state of research on nanotech implications.

"There are a number of uncertainties related to nanotechnology, but we've faced uncertainties before with emerging technologies," roundtable Chairman Paul G. Rogers, partner at Hogan & Hartson LLP, said at the opening of the workshop. He noted that the science community needs to make the science understandable so that informed policy decisions can be reached. To do this, communication will be key.

"It's important to get the public involved up front," said Kenneth Olden, director of the National Institute of Environmental Health Sciences at the National Institutes of Health. "We should anticipate that not every nanomaterial that is made will be benign" and be on guard to prevent harmful materials from being released into the public, he noted.

The public must have access to the facts so that they can educate themselves, Olden said. Otherwise, he added, they will not accept the resulting technological advances and will miss out on their benefits.

With the federal investment in nanotechnology at nearly $1 billion per year, the nascent field is maturing and moving from the laboratory to the marketplace, where it is predicted to have a revolutionary impact. Nanotechnology is already being used to make products that include sunscreens, tennis balls, stain-resistant fabrics, and electroconductive coatings.

Currently, the estimated total amount of nanoparticles in commerce is a few thousand tons, reported Vicki L. Colvin, associate chemistry professor and executive director of the Center for Biological & Environmental Nanotechnology at Rice University. This is not a significant amount of material, but as future concepts such as high-tech battle suits (C&EN, Aug. 11, 2003, page 28) become realities, the quantity will grow, she explained.

"We are at an optimal time to study these problems," Colvin pointed out. "We are at the birth of a new market. We can shape this area with knowledge as it develops."

"We should anticipate that not every nanomaterial that is made will be benign."

PERHAPS THE BIGGEST challenge in trying to shape the emerging market and inform the public is the limited data on the toxicity and bioavailability of engineered nanoparticles, Olden said. For the available environmental and health data to increase, a better toxicity screening process needs to be in place. "Toxicology assessments will be expensive and daunting unless we can develop new strategies to identify toxicity on a large scale, not on a single material as is now done," he said.

The small number of publications evaluating the toxicity of engineered nanoparticles is evidence of the difficulty in screening these materials. According to Colvin, only 50 peer-reviewed research papers on environmental and health effects of engineered nanoparticles have been published. The situation is better for naturally occurring nanoparticles, where Colvin noted that there are about 500 publications. By far, the most work in this area has been on incidental nanoparticles such as ultrafine soot and carbon black--for which there are more than 10,000 peer-reviewed publications.

The large number of papers on incidental nanoparticles came from industry studies looking at manufacturing by-products, Colvin explained. These nanoparticles have a high concentration in the environment and typically have a complex composition, an ill-defined surface chemistry, and a diameter less than 100 nm.

In contrast, engineered nanoparticles are relatively new and are not yet present in the environment in high quantities. These particles also differ from incidental nanoparticles in that they are typically very pure in composition, have a controlled surface chemistry, and are much smaller in diameter.

The novel properties of nanoparticles give rise to an important deviation from the traditional paradigm of evaluating particles' health risks. "The current paradigm says that health effects associated with inhalation exposure to particles are related to the mass of the material depositing in the lung," said Andrew D. Maynard, senior service fellow at the National Institute for Occupational Safety & Health.

When it comes to nanoparticles, however, the factors that contribute to the health risks include surface area, surface chemistry, and size-deposition probability and translocation, Maynard said. "But these factors do not include particle mass," he pointed out. This observation illustrates the need for a change in philosophy when dealing with nanoparticles, he said.

Another unique aspect of nanoparticles is their behavior, Colvin noted. Studies have shown that nanoparticles cannot be assumed to behave like a bulk material or a single molecule of the same composition, she explained. She also discussed three important lessons of nanoparticles' behavior that she has learned from the emerging data on fullerenes.

First, the physical size of nanoparticles is not constant, as they tend to form colloidal aggregates. Another point is that the surface of the nanoparticle influences its properties, and derivatizing the surface can significantly alter the toxicity. Finally, the properties of the nanoparticle will change as its surface interacts with the environment.

THESE OBSERVATIONS illustrate how hard it can be to determine the toxicity of nanoparticles. Based on the limited published data, the relative toxicity of engineered nanoparticles is worrisome, said John M. Balbus, director of the Environmental Health Program at Environmental Defense--a nonprofit, environmental activist organization.

For example, Balbus noted that the data available on fullerenes show that the particles are translocated to the brain, cause membrane lipid peroxidation, and prevent bacterial growth in an aqueous aquarium environment (C&EN, April 5, page 14). In addition, he added, carbon nanotubes that have been placed directly into the tracheas of rats have been found to cause the animals to suffocate (C&EN, April 28, 2003, page 30). Thus far, scientific studies do not paint a reassuring picture of the environmental and health safety of these engineered nanoparticles, he said.

Many more questions must be answered before the toxicity can be confidently determined, Balbus noted. "What we don't know far exceeds what we do know," he said. In light of this, he questioned whether current Environmental Protection Agency regulations under the Toxic Substances Control Act (TSCA) are sufficient to handle the developing use of engineered nanoparticles.

Under TSCA, engineered nanoparticles are not viewed as new compounds unless they have a unique composition. For example, TiO₂ nanoparticles are handled the same way with respect to regulation as bulk TiO₂, even though the two forms have different properties. This situation shows that new regulations need to be developed, Balbus said.

A model that could be used to regulate these novel materials is the one used by the European Commission, Balbus pointed out. The commission uses an algorithm that gives nonsoluble particles a higher risk assessment priority because these particles have the potential to bioaccumulate. Although the success of this proactive stance has yet to be demonstrated because it is still being implemented, it is an option worth considering, he explained.

Another model is to work within the existing regulatory framework until a new framework can be developed. This is what is happening in Canada, said Paul Glover, director general of the Safe Environments Program at Health Canada. He noted that Canada is using horizontal management to address this problem, an approach where all the players--government, industry, and researchers--work together not as individual departments and agencies but as a multidisciplinary team.

The U.S. is also taking steps to develop an effective framework for dealing with nanotechnology, noted E. Clayton Teague, director of the National Nanotechnology Coordination Office at the National Nanotechnology Initiative. NNI--which provides a long-term R&D focus for nanotechnology and coordinates the relevant federal agencies in this area (C&EN, April 19, page 30)--is funding research into the environmental and health implications of nanotechnology. About 11% of NNI's funding is being used to study applications and implications in this area, he said.

Teague also said the federal agencies are working together as part of the National Environmental & Health Implications working group to develop standards such as best practices and a common nomenclature for the emerging field.

"The train has yet to leave the station," Maynard told the audience. "We have the opportunity to work hand-in-hand with people in industry" to ensure that regulations and policies are developed that allow the public to get the maximum benefits of nanotechnology.

TARGETING TUMORS

Nanomedicine Moves Beyond The Bench

BETHANY HALFORD

Although most of the scientific talks at a recent Institute of Medicine forum on implications of nanotechnology were devoted to precautionary tales of nanotech's negative impact on human health, University of Michigan environmental health professor Martin A. Philbert gave attendees a glimpse of how nanomedicine could transform cancer diagnosis and treatment.

Philbert has been developing a range of biological nanosensors called PEBBLEs (probes encapsulated by biologically localized embedding) in collaboration with University of Michigan chemistry professor Raoul Kopelman (C&EN, Jan. 29, 2001, page 31). PEBBLEs are nanoprobes made of sensing molecules trapped in a chemically inert matrix. They can be used to monitor various chemicals inside living cells without doing any damage.

The researchers are currently trying to make more sophisticated PEBBLEs that go beyond sensing applications. The idea, Philbert says, is to make one PEBBLE that can image a tumor and then, in a slightly different mode, kill that tumor as noninvasively as possible.

"The concept is simple, but the implementation is very difficult," Philbert tells C&EN. Creating PEBBLEs that can safely perform such varied tasks, he says, is like a battle between physics, chemistry, materials science, and biology: "In order to get a very good medical therapy, you have to conquer each of those domains and have them work together."

Despite the technical challenge, the researchers have already seen some promising in vivo results using PEBBLEs to treat certain types of brain tumors in rats. They hope to publish the work within the next few months.