Taming high-tech particles: cautious steps into the nanotech future.

There are countless ways in which particles having microscopic dimensions could transform medicine and science. From the tiniest of circuits to the finest of filters, technologies made with such nanomaterials just might be the solution for shrinking the computer chip or removing microscopic contaminants from water. These particles, which have dimensions of billionths of a meter, might deliver drugs to targets inside individual cells or perhaps serve as components in sensors that detect chemical and biological agents.

Enthusiasm for an anticipated windfall of such nanotech inventions has been running high. The technology appears to be a new industry in the making. However, as nanomaterials approach commercial development, some researchers are beginning to look at the potential consequences of putting the new materials into the environment or the body. These scientists' goal is to launch preemptive strikes against any problems that might arise down the line.

One of the hot spots of this effort is Rice University in Houston--an institution known for its nanoscience research. Last fall, the university opened a center focused on developing new nanotechnologies that can solve environmental problems and offer new medical therapies.

A couple of years ago, during discussions about the proposed nanotechnology center, Rice's Vicki Colvin showed a slide demonstrating one of the field's many new wonders. Published by Paul Alivisatos' research group at the University of California, Berkeley, the image showed semiconductor particles, called quantum dots, serving as brightly glowing tags in mammalian cells (SN: 10/24/98, p. 271).

Suddenly, Colvin recalls, she and her colleagues paused. It had occurred to them that if nanosize particles could get inside cells for beneficial purposes, then these agents might get inside cells when no one wanted them there. Quantum dots contain cadmium compounds known to be toxic in bulk amounts.

From that moment on, says Colvin, researchers planning to work in Rice's new Center for Biological and Environmental Nanotechnology began thinking about what environmental and health consequences such new, tiny materials might pose. At the center, scientists have the opportunity to simultaneously develop new technologies and consider whether their methods or materials might contribute to health or environmental hazards down the line.

For example, as researchers succeed in making nanoscale substances soluble in water for drug delivery or other biomedical applications, they're also potentially enabling these particles to move freely in groundwater, says Rice's Mark Wiesner, who studies nanomaterials' environmental uses and impacts.

With early information on potential risks, researchers could guide the development of these materials as they speed toward industrial production so as to make the coming industry safe as well as effective.

"The concerns about what bad things could result from nanotechnology are largely speculative at this point," comments Rice's Neal Lane, who was President Clinton's science advisor. But "when you're dealing with a new science and a new technology, it's prudent to think ahead and make sure that you're taking whatever protective steps are necessary to ensure bad things don't happen," Lane says.

Now, at the Rice center and elsewhere, the first studies of nanomaterials' behavior in the environment and the body are under way. Scientists discussed some of this early research at a workshop last December at Rice. Few indications of problems have turned up yet among the limited results so far, they report. "We think that most nanoparticles will probably be relatively inert" in the biological realm, says Rice bioengineer Jennifer West, "but the actual toxicity studies on a wide variety of nanoparticles haven't really been done." And, she adds, "I think there will be some nanoparticles that will prove to be toxic."

FORECASTING THE FUTURE When a proposal for the center was submitted to the National Science Foundation, some reviewers questioned whether safety studies weren't a little premature, says Wiesner.

But "that's the whole point," he says. "We want to get at it when it's very, very early."

In making his case for probing potential negative consequences of emerging materials, Wiesner points to two historic examples: chlorofluorocarbons (CFCs) and DDT. Both were hailed as miracles when introduced, but serious problems became associated with them much later.

Developed in the 1930s, CFCs were particularly useful as refrigerants because they're not flammable or toxic. In the 1970s, however, scientists learned that the chemicals were destroying Earth's protective ozone layer.

DDT, a powerful insecticide for managing lice, disease-carrying mosquitoes, and crop pests, is another product developed in the 1930s. "The benefits perceived at that time were obvious to everyone. It was going to reduce the incidence of malaria," says Wiesner. "But no one saw the consequences of it accumulating through the food chain." The chemical's stability enabled it to build up in animals by passing from insects to the birds and fish that eat them. Use of DDT was restricted by the United States 30 years ago.

With hard lessons like these as incentives, investigators try to anticipate problems posed by technologies that have not yet been implemented. "We can't foresee all of the possibilities, but we do know that certain sorts of materials like to go certain places, and that sets off certain warning bells," says Wiesner.

To study nanomaterials' behaviors in the environment, Rice researchers place them in laboratory-simulated natural microcosms and then monitor their movements. The scientists are examining widely used nanomaterials, such as nanosize silicon crystals, iron particles, and carbon nanotubes, which are hollow cylinders just a few nanometers wide. All these materials are already being manufactured by small start-up companies, notes Wiesner. "We're using materials that we know exist right now and are likely in the relatively near term to be produced in sizeable quantities," he says.

One test examines whether the nanomaterials would pass through filters in a water-treatment plant. Other tests determine whether the substances bind to various common contaminants such as pesticides or PCBs. If contaminants are attracted to the nanomaterials, the new particles could enable already present chemicals to become more mobile and possibly cause more harm.

Other investigations ask whether bacteria take up the nanomaterials and if so, whether this might open a route for the particles to move into and up the food chain.

Meanwhile, to predict how new nanomaterials will act in the body, Rice scientists expose living cells to the substances while noting such specifics as how the nanomaterials interact with proteins. They are concerned that when a protein attaches to the surface of a nanomaterial, the protein's shape and function can change, says West.

"It's very early to make predictions ... but I think it's important at this stage that we start to really investigate this," says West. Researchers, she adds, need to "screen more materials for toxicity, screen more materials for their ability to piggyback on different synthetic molecules, and investigate their effects not just in cell culture but also in living animals."

TUBES ALONG THE NANOFRONT One of the most promising aspects of nanotechnology rests on carbon nanotubes. These tiny cylinders of carbon have a tantalizing portfolio of properties. For example, they are very strong and can act as conductors or semiconductors. Chemists can even tune nanotubes' electronic properties by filling them with other molecules (SN: 2/019/02, p. 93).

Since the discovery of carbon nanotubes in 1991, researchers have been exploring their potential as components of miniscule electronic circuits, movable parts in tiny machines, models for biological channels in the body, and drug-delivery vehicles, to name just a few possibilities. During the Rice conference, Patrick Bernier of the University of Montpellier in France discussed one such possibility: using carbon nanotubes to store enough hydrogen to make them useful for fueling future generations of cleaner automobiles. Manufacturing of tiny tubes could be scaled up soon to industrial quantities. Bernier notes that it's not yet certain this can be done efficiently enough for some potential nanotechnologies, such as hydrogen storage. However, small companies have recently started making enough carbon nanotubes for some nanotube product development. These include the Rice spin-off firm Carbon Nanotechnologies in Houston and Nanoledge in Montpellier, which was cofounded by Bernier.

Yet, even with industrial use of nanotubes in view, toxicology experiments have been scarce. Researchers haven't determined what would happen if people breathed in nanotubes or received them in medical treatments.

In Bernier's lab, however, immunologist Silvana Fiorito, has begun to compare the effects that various carbon structures have on rat cells. Her experiments investigate what might happen if nanotubes were used in medical implants, such as artificial joints. When blended with polymers, the nanotubes could make such implants stronger, she says. However, there's also the possibility of nanotubes leaking out into body tissues and causing problems.

Fiorito has found that graphite particles 1 micrometer in diameter stimulated the cells to produce nitric oxide--an indicator of an immune response. However, when she added carbon nanotubes to cells, they didn't produce nitric oxide. The cells accepted the nanotubes without developing inflammation.

Soccer-ball-shape cages of carbon atoms--fullerenes--didn't provoke inflammation either. Fiorito labels these results as preliminary and says that she doesn't know why some forms of carbon are more readily tolerated by cells.

One of the biggest concerns about carbon nanotubes, which resemble asbestos fibers in shape, is that they might harm people's lungs. As a precaution, many researchers working with carbon nanotubes wear masks during procedures that could generate airborne plumes of the material.

Last year, a team of researchers in Warsaw carried out experiments to explore whether carbon nanotubes act in lung tissue the way asbestos does. In the April 15, 2001 Fullerene Science and Technology, the researchers reported subjecting guinea pigs to soot that did or didn't contain carbon nanotubes. Four weeks later, data from pulmonary-function tests didn't differ substantially between the groups. Autopsies didn't reveal significant differences in the animals' inflammatory reactions, either. On the basis of this initial evidence, the researchers suggested that "working with soot containing carbon nanotubes is unlikely to be associated with any health risk."

IT'S NOT EASY BEING GREEN While researchers are studying how certain nanomaterials move through and interact with the environment and the body, they're also trying to identify the most environmentally friendly ways of manufacturing the materials. If methods that save energy and don't use hazardous organic solvents are developed during an industry's infancy, they can save money and protect the environment later on.

It's a good time to do this sort of research, says James Tour, another member of Rice's roster of nanoscience researchers. "You hate to mess things up and then backtrack. The chemical industry has done that in the past, and it's a whole lot easier to think about it up front."

Furthermore, adds Wiesner, it's important to instill this kind of forward-looking thinking into today's graduate students, who will be the ones developing nanomaterial-based technologies in the coming decades. As Wiesner sees it, if students "leave with ... a good sense of being cautious and thoughtful about where a material is going to end up in the environment," the odds drop drastically that nanomaterials will become this century's CFCs.