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+ By Corinna Wu
Peril in Small Places

Peril in Small Places

What dangers lurk in our expanding use of nanotechnology?

Advertisers have always lured consumers with promises of the latest technology. Nowadays, the terms “space-age” and “new-and-improved” have given way to “nano.” An ad for a cutting board boasts that its “surface with nano-silver coating protects sliced food from bacteria and germs.” A line of cookware features “a revolutionary and technologically advanced ceramic non-stick Nano-GlazeTM on the inside and outside of every vessel.” Shampoo is “luxuriously enriched with light-weight ingredients and leverages the latest molecular nanotechnology.”

More than 1,000 consumer products now use nanotechnology – a $254 billion market in 2009 – and that number could grow 10-fold in the next decade, researchers say. Global research and development in the field have already garnered 4,000 patents. What some call an investment “gold rush” will reach $1 trillion by 2015, according to the International Center for Technology Assessment. Numerous medical products using nanotechnology have been commercialized. Nanotechnology in various uses is showing up around the world in manufacturing, oil fields, military installations, and private homes. It holds the promise of cleaner energy, cleaner water, and biomedical advances. Indeed, it’s well on the way to becoming a “general-purpose technology,” according to a recent report issued by the World Technology Evaluation Center Inc.

The wonder of nanotechnology is the abundance of materials, devices, and systems made possible by controlling and manipulating matter at the atomic and molecular levels. But with that wonder comes concern that these now ubiquitous nanoparticles could spread new hazardous pollutants that threaten health and the environment. “We’re trying to say, ‘These are new materials. We don’t know if there’s a problem, so let’s ask now,’” says Sally Tinkle, senior science adviser at the National Institute for Environmental Health Sciences, part of the National Institutes of Health. With prodding from the National Research Council and other institutions, inquiry into the health and environmental effects of nanotechnology has gone hand in hand with research on potential applications. The work is interdisciplinary, and engineers play a critical role. By helping to figure out what makes a nanoparticle toxic, they can, for instance, design nanoparticles that kill cancer cells yet don’t harm healthy tissues, or that remove pollutants from soil without poisoning wildlife.

So far, engineered nanomaterials (ENM) are not known to have caused any disease or serious environmental hazard, according to a presentation earlier this year by Andre Nel of the University of California-Los Angeles Medical School and David Grainger of the University of Utah. “However, there is experimental evidence of ENM hazard,” they reported.


Birth of a Science

Ever since Cal Tech physicist Richard Feynman, in 1959, suggested the possibility of manipulating atoms and molecules and of shrinking machines to nanoscale, nanotechnology has fired the scientific imagination. Norio Taniguchi of Japan is credited with the first use of the term “nano-technology” in 1974. Six years later, at the Massachusetts Instititute of Technology, Eric Drexler seized on Feynman’s earlier work and theorized that molecular engineering could produce “great advances in computational devices and in the ability to manipulate biological materials.” In 1985, Rice University’s Richard Smalley discovered a 60-atom carbon structure in the shape of a soccer ball – or geodesic dome. The versatile Buckminsterfullerene, or “buckyball,” opened the way for a variety of practical applications.

Carbon nanotubes followed. Scientists quickly saw that the shape of these sheets of carbon graphite, rolled into tiny hollow tubes, could be filled with other compounds and used as a delivery system for medicine, carrying drugs directly to cells. They were also found to be good conductors of electricity and to contain properties that make them useful in solar panels. Other types of nanoparticles – dendrimers and liposomes, ceramic nanoparticles, silica-coated micelles – pushed the field of nanotechnology into everyday products.

In years past, lifeguards at the beach seemingly all had noses coated with a trademark white cream of zinc oxide. Now the sunblock contains titanium dioxide nanoparticles so small it’s transparent. Bound to cotton fibers, nanosilver particles act as anti-microbials, keeping socks smelling fresh. Added to implants, they can help prevent bacterial films from forming. Carbon nanotubes, mixed into materials, yield composites that are as light as plastic yet stronger than steel. Environmental engineers are testing whether nanoparticles that bind to pollutants will make cleanup of contaminated sites faster and cheaper. And because nanoparticles are small enough to be inserted into human cells, researchers hope they can be used to detect and destroy cancer tumors.

Tinker Bell and Darth Vader

So the promise of nanotechnology is great. But researchers, recalling lessons learned from such fiascoes as DDT’s effect on the environment and that of chlorofluorocarbons on the ozone layer, are busy trying to grasp nanotechnology’s possible dangers. “The thing that makes a knife unique is that it cuts, but the fact that it cuts can make it dangerous as well,” says Mark Wiesner, director of the Center for the Environmental Implications of Nanotechnology (CEINT) at Duke University. In his presentations on the topic, Wiesner says he has used a slide showing Tinker Bell and Darth Vader – symbolic of the bright side of applications and the dark side of the implications.

Researchers at Rice University, birthplace of the buckyball, were among the first to probe nanotechnology’s dark side. Their approach wasn’t popular 10 years ago, says Kristen Kulinowski, a chemist and external affairs director at Rice’s Center for Biological and Environmental Nanotechnology. Other researchers said it was too soon, and worried that discussing risk might jeopardize funding for basic research. “It wasn’t too soon, because even then, there were a lot of products in the marketplace or in the workplace that weren’t necessarily identified as nanotech but were actually nanoscale materials. It wasn’t just something that was happening in esoteric research labs around the world,” she says.

There’s a growing recognition that health and safety must be an integral part of nanomaterial design.

Since then, two fields have emerged – nano safety and nano toxicity – examining potentially hazardous material compositions and properties. According to the presentation by UCLA’s Nel and Utah’s Grainger, there’s now a recognition that potential environmental, health, and safety impacts should be an “integral part of ENM design” and not a “post facto add-on or imposed cleanup cost.” Where potential hazards are identified, it’s important to consider “product safety disclosure.”

The validity of such concerns is gaining wider recognition. The President’s Council of Advisors on Science and Technology identified two categories of potential risk: nanomaterials derived from bulk materials known to threaten health and the environment, like heavy metals, and those made of nontoxic materials that become risky when miniaturized and aerosolized. PCAST called for a strengthening of research into environmental, health, and safety risks, warning that a lack of public confidence could stymie growth of the field.


Similar to Asbestos?

Nanoparticles are being used increasingly to strengthen construction materials like steel and concrete. They can also keep windows cleaner, kill bacteria on walls, make materials fire resistant, and make solar panels more efficient, according to research led by Rice engineering Prof. Pedro Alvarez. But some of the same properties that make the nanomaterials useful could cause problems. For example, titanium dioxide particles that work to prevent bacterial films from forming on windows or solar panels could also endanger beneficial bacteria in the environment. Possibly worse, titanium dioxide appears to be carcinogenic in rats when inhaled.

Animal tests have pointed to acute lung inflammation and possible cancer resulting from nanoparticles.

For all the potential in medicine from nanotechnology, it’s not fully known how nanoparticles will act inside the body. Carbon nanotubes (CNT) can encapsulate drugs, but they’re not water soluble, so their surface will have to be chemically changed. Then, because of their shape, nanotubes can get stuck in tissue. Research with mice has shown that when inhaled, nanotubes can move through the lining of the lungs, raising concern that they could act like asbestos fibers, which can cause mesothelioma, a cancerous tumor. Animal studies have shown that even relatively low doses of CNT can cause acute lung inflammation.

Nanosilver is useful in controlling infections, since it is toxic to harmful bacteria such as E. coli and Staphylococcus aureus, which has become resistant to many antibiotics. That’s why nanosilver has been incorporated into fabrics and plastics to minimize bacterial growth. But nanosilver has a downside. It is also toxic to the types of bacteria used in sewage treatment plants to convert raw sewage into less harmful compounds.

“You can’t say, ‘Nanoparticles are harmful.’. .  You have to be very specific.”  —Rice University’s Kristen Kulinowski

Yet, research into nano risks is tricky. “It is impossible to generalize about nanomaterials,” says Kulinowski. Nanoparticles’ chameleon-like behavior makes them hard to get a handle on. “You can’t say, ‘Nanoparticles are harmful,’ or ‘These nanoparticles are harmful.’ You have to be very specific...It’s tough for researchers to grapple with that, and it’s tough from a communications perspective to get that across.”  

So, researchers have been studying nanoparticles in the lab as well as in more complex environments, with the aim of developing a framework to assess risks. In a forest next to Duke University, CEINT researchers maintain 32 “mesocosms” -- wooden boxes containing a small pond, soil, plants, and fish. Each represents a small wetland ecosystem, with terrestrial and aquatic components. CEINT researchers hope the mesocosms will help reveal how nanoparticles behave in a complex, natural environment.

Instruments on the mesocosms monitor parameters such as pH, water level, and redox potential, and a webcam trained on the site shows what’s happening during daylight hours. By taking sediment and water samples, researchers can analyze how nanoparticles are taken up by the plants and fish in the experimental setups.

CEINT opened two years ago, with funding from the National Science Foundation and Environmental Protection Agency, but its development dates back more than a decade to when interest in nanotechnology started taking off. Director Wiesner, who had previously worked with Smalley at Rice, says Duke was an ideal site because it had a top medical school as well as ecological research programs. “No one was looking at true ecological issues: how it might affect cycling, how things move through the environment,” he says. In the lab, researchers are studying more than 60 types of nanoparticles of different compositions, sizes, and shapes. In the mesocosms, they’ve tested silver nanoparticles, carbon nanotubes, and titanium dioxide nanoparticles.

At the University of Florida in Gainesville, the particle science and technology building is just a two-minute walk from the health science center. Yet, a decade ago, they were worlds apart. In 1999, Florida’s engineers began looking into biomedical applications of nanoparticles and quickly found that not much was known about the fate of the materials in the body. After they began to explore those issues, they spent nine months brainstorming and bringing people together, says Brij Moudgil, director of the UF Particle Engineering Research Center.

Six years ago, they formally launched a nano-toxicology program, which includes materials scientists, chemical engineers, ecologists, toxicologists, and biomedical scientists.

Engineers on the Team

“The communities which are interested in toxicology and those who have been dealing with particles, as a whole, have been very far apart,” Moudgil says. “The particle people have been more oriented toward materials, chemicals, minerals, and those kinds of industries. Toxicology is in the domain of biology -- life scientists.

“The motivations and the drivers of the engineering community and the clinical faculty are very different,” he continues. “Unless those things get reconciled and you’re on the same plane, you don’t get workable and fruitful relationships. So we’ve learned some tricks over the years, what clicks for them. At the same time, they learn how the engineering faculty work and what are the drivers for them, so we’re sensitized to each other’s needs and we try to help each other out.”

Now, they find that the physical proximity of the engineers and doctors fosters that close relationship, Moudgil says. “My research team members can synthesize particles in two minutes and deliver those particles to my colleagues in the medical center for testing.” Instead of waiting for E-mails to be answered, the researchers can just walk over and resolve any issues in a timely fashion.

For engineers, the scope of further work in nanosafety and nanotoxicity is vast. They will play a key role in manufacturing to ensure uniformity of the particles used, in characterizing materials, in developing safe particles for different applications, and in developing coatings to reduce hazards.

While research on nanohazards has shot upward in recent years, scientists and engineers continue to grapple with some basic questions. They’re still learning the right way to measure nanoparticles, and what’s important to measure: surface area, mass, chemical properties. This is key, researchers say, because it is surface area, more than size, that makes nanomaterials potentially toxic. “Even though people have been working with nanomaterials for a decade -- and the concentration in EHS has only been in the last five years -- that’s still very young science,” says Tinkle of the National Institute of Environmental Health Sciences. “Good science takes time, so it’s going to be a while before we can really answer these questions.”

And there’s the rub: The explosion of engineered nanomaterials is outpacing efforts by scientists to identify potential hazards. The result is a cloud of uncertainty hanging over the rapidly expanding field. This uncertainty, according to PCAST, “threatens to undermine confidence and trust amongst investors, businesses,and consumers, and could jeopardize the success of nanotechnology.”


Corinna Wu is a freelance writer based in Oakland, Calif., who specializes in science.




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