"No Small Risk," Feature Article, September 2006

Focus on Nanotechnology

no small risk

As nanotech products race to the marketplace, researchers are still trying to determine if they could endanger human health.

by Jeffrey Winters, Associate Editor

for German consumers, the name on the bottle of bathroom product promised wondrous, futuristic power: Magic Nano. Spray the contents on your tub or tiles, and soapy buildup would be repelled. For the vast majority of people who couldn't distinguish AFMs and fullerenes from ATMs and Listerine, everyday items such as Magic Nano are what the much-hyped nanotech revolution represents—simple items that make their lives easier.

In spite of its long presence in the research community, nanotechnology is just now beginning to make its mark in the marketplace. Products from the AccuFlex Evolution Golf Shaft to the Zelens Fullerene C-60 Day and Night Cream contain (or at least claim to contain) ingredients that have been designed on the scale of less than a micrometer. Such engineered nanoparticles are the first wave of what most consider to be a tide of nanotechnology expected to wash across the economy.

This German bathroom product made headlines when dozens of users became sick. The product was removed from the market.

Within days of the introduction of Magic Nano to store shelves in a new aerosol form in the spring, however, reports began surfacing that dozens of users were reporting breathing difficulties, and six were hospitalized with pulmonary edemas. Though no one was permanently injured, the product's manufacturer, Kleinmann GmbH of Sonnenbühl, Germany, pulled Magic Nano from store shelves immediately, and the ETC Group, an Ottawa-based environmental organization, called for a moratorium on all nanotechnology research.

Nanotechnology had its first public relations fiasco. That Magic Nano appeared to have no actual nanoscale material in it was lost in the hubbub.

"The question of public perception is uppermost in the minds of many who are seeking to cash in on nanotechnology," said Kristen Kulinowski, the executive director for policy at the Rice University Center for Biological and Environmental Nanotechnology in Houston and director of the International Council on Nanotechnology, which maintains an extensive database on nanotech research. "Part of the problem is that we have a lot of products that are labeled 'nano this' or 'nano that' which don't have any ostensible nanotechnology in them whatsoever. If there's a hazard associated with one of those, the chance that there's a backlash against legitimate nano products before they even make it to market is even stronger."

Even so, while some have chided the media and the public for blowing the Magic Nano case out of all proportion, before the incident, no one in government or industry had bothered to check whether the product's claim of nanoscale properties was valid.

More importantly, the true nature of risk from nanotechnology is far from understood. Some studies suggest that even passive nanostructures—that is, particles and other material that have no active parts or control systems—may have some serious effects on human health. But experts in the nascent field of nanotoxicology are almost unanimous in their belief that it's still far too early to tell just how extensive the problems could be.

"We still have an opportunity to think proactively about risk," Kulinowski said. "I have hope that we've raised these issues early enough. I think we'll get some good data, but it will take some time to sort out what it all means."

That deliberative instinct is running up against the relentless drive to commercialize nanotechnology.

If there are dangers to be found, who will uncover them first—researchers in the lab or consumers in the marketplace?

Great, Good, or Gray Goo

From its first conception back in the mid-1980s, nanotechnology has been seen as both enormously promising and potentially dangerous. Indeed, in some of his first publicized writings on the field, Eric Drexler considered the possibility of a self-replicating nanoscale machine running out of control and reproducing so virulently that it consumed everything available. Such an outcome was dubbed the gray goo scenario.

Though it seems an unlikely endpoint for nanotechnology (or for humanity, for that manner) the gray goo scenario has alarmed some serious thinkers. Bill Joy, cofounder of Sun Microsystems, wrote about the prospect of gray goo in his famous April 2000 essay for Wired magazine called "The Future Doesn't Need Us."

"An immediate consequence of the Faustian bargain in obtaining the great power of nanotechnology is that we run a grave risk—the risk that we might destroy the biosphere on which all life depends," Joy wrote, adding, "The gray goo threat makes one thing perfectly clear: We cannot afford certain kinds of accidents with replicating assemblers."

More recently, author Michael Crichton used a rampaging cloud of nanorobots as the monster in one of his thrillers.

This pessimistic or alarmist view of nanotechnology is not the common one, however. To the extent that people have heard of the field—and a 2004 survey funded by the National Science Foundation found that more than 80 percent of the public had heard little or nothing about nanotechnology—nano has been played up as a field that not only has the potential to do great things for humanity, but is making headway toward that goal in real time.

Fullerenes, such as the iconic 60-atom buckyball (above), have been found to damage sensitive lung tissues (below) when inhaled. Researchers don't yet know whether nanoparticles pose a major health risk.

For those who are informed about nanotechnology, said David Rejeski, director of the Project on Emerging Nanotechnology at the Woodrow Wilson International Center for Scholars in Washington during Congressional testimony last November, "They are generally optimistic about nanotechnology's potential contribution to improve quality of life. The key benefits the public hopes for are major medical advances, particularly greatly improved treatments for cancer, Alzheimer's, and diabetes."

Part of this optimistic push can be seen in the sheer numbers of products that are trading on the promise of nanotechnology. The Wilson Center keeps track of products that claim to rely on engineered nanoscale ingredients. The list (which can be accessed at http://www.nanotechproject.org/ index.php?id=44) contains a fairly wide range of products, including clothing, cosmetics, and children's toys.

All these products, it should be noted, contain what has been called first-generation nanotechnology. Such products have only passive structure at the nanoscale and their effects, such as waterproof coatings, are seen primarily at the macro level. In a scheme first laid out by M.C. Roco, an ASME Fellow who is senior advisor on nanotechnology to the National Science Foundation, the second generation of nanotech will employ active structures in the form of electronics, sensors, and adaptive structures.

After that will follow a generation of nanotechnological devices that are actual systems of nanostructures—essentially, machines made of nanoscale parts—and a final generation made of designed molecules should arrive in the 2020s. That date sounds futuristic, but according to this timeline, engineers now in their 40s will have to grapple with fourth-generation nanotechnology before they retire.

Indeed, there's a big push at the federal level to bring active, adaptive nanotech to reality. The National Nanotechnology Initiative, a multi-agency, multibillion dollar research effort, this year was scheduled to begin focusing on more active nanosystems with an emphasis on energy, medicine, and agriculture.

Nanotechnology may soon begin to deliver on its enormous promise. New nanoparticle-based treatments for cancer are close to the trial stage. But some experts in environmental health and toxicology are concerned that the rush toward commercializing and marketing nano-derived products may skip one crucial step: ensuring their safety.

Size Matters

Fullerenes—the class of molecules represented by the 60-atom buckminsterfullerene—were discovered in 1985. Within a few years, buckyballs and carbon nano- tubes were the focus of intense research. But as early as 1992, toxicological research had indicated that nanoparticles could, under certain circumstances, move into vital regions of the lungs when inhaled and cause long-term respiratory problems. Another experiment from the mid-1990s showed that a weak solution of fullerene-derived molecules could disrupt the activity of HIV in rats; unfortunately, a slightly more concentrated solution killed the rats quite swiftly.

Among the first to give nanoscale particles close scrutiny is Günter Oberdörster, an environmental medicine researcher at the University of Rochester in New York. A specialist in ultrafine particle toxicity, Oberdörster saw a similarity between minuscule particles in the normal environment, such as soot, and these newer molecules.

"Both ambient ultrafine particles and engineered nanoparticles are of the same size, less than 100 nm," Oberdörster said, "and their interaction with cells and the biokinetics are based on similar principles."

Some of the results of Oberdörster's experiments have been horrific—and headline-grabbing. In one study, rats exposed to less than 60 micrograms per cubic meter of nanoscale Teflon particles began bleeding in their lungs; many died within 30 minutes of exposure.

That Teflon—thought of as remarkably inert on the familiar scale—can create such damage when turned into a nanomaterial points out one of the looming difficulties in characterizing the risks involved with nanoscale particles. Size matters.

Titanium oxide nanoparticles (below) are found in some sunscreens. Recent research indicates such particles could penetrate skin cells.

That, of course, is the basis of why nanomaterials can be so prodigiously useful. Change the size of titanium dioxide particles, for instance, and you can completely alter the way they interact with light. Unfortunately, this also means that materials engineered at different nanoscale sizes may interact with human tissues in different ways.

"As you go down from the micron to the nanoscale, you're engineering new properties that don't occur at the larger scales," said Nigel Walker, a researcher with the National Toxicology Program of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. "The history that one may have on bulk material that is bigger in nature cannot necessarily extrapolate down to the smaller material."

Similarly, material characteristics that have little bearing on health effects in bulk materials, such as surface area, may become important when trying to measure the hazard from trace amounts of nanomaterials. Indeed, nanotoxicologists may well have to use a separate and unique set of metrics for determining what the safe exposure to various nanomaterials is.

"The measurement challenge is huge with nano," said Andrew Maynard, chief science advisor to the Wilson Center's nanotechnology project. "We're trying to understand how people are being exposed, what they are being exposed to and also what's being released to the environment. Because these materials are so complex, we need to use very complex methodologies—much more complex than toxicologists are used to using. We're finding that the ways that toxicologists are used to characterizing materials just aren't good enough when it comes to engineered nanomaterials."

NPT's Walker agrees. "There are not going to be any new manifestations of toxicity, but the ways which they can occur can be very different," Walker said. "More importantly, the metrics which are associated with the exposure and response relationship are much more different. Up until now, we've functioned in a world where mass-based exposure is what all the regulations are based on. There are no real regulations based on other metrics, such as surface area or number of particles."

What's more, the precision control that engineers have in making nanoscale materials may also amplify their effect. Naturally occurring nanoscale material, such as particles formed in combustion exhaust, are formed over a wide range of sizes. Any given particle size will make up only a small part of the overall sample, diluting the potential ill effects. Nanoengineered materials ideally come in a tight range of sizes; if that size happens to create health problems, it will show up in far smaller doses than would be needed in a natural material. One researcher likened it to the difference between a broad-spectrum light and a laser beam.

A Coordinated Strategy

As the scope of the issue has become clear, toxicologists have begun to deal with the fact that the exact nature of the danger from nanoscale materials is far from clear. Without a systematic approach to determining the toxicological risk, researchers, workers, and even consumers may be unaware that an engineered material could pose harm.

Over the past three years, then, the toxicological community has started a coordinated strategy to measure the risk. In 2004, a working group studying environmental and health implications was established within the National Nanotechnology Initiative.

Estimates of the federal funding last year devoted to actual health risk assessment range from $11 million to $38 million. Even that money is being spent in a somewhat undirected manner, according to a recent Wilson Center study. While silver, titanium, and zinc-based material make up nearly half the nano products to have reached consumers thus far, more than three-quarters of the money spent on health research has focused on carbon-based molecules such as nanotubes and buckyballs.

Without a systematic
approach to determining the risk, people may be unaware that an engineered material could pose harm.

Instead of letting individual researchers follow their own interests, Maynard and others say, a directed and systematic framework needs to be established. Research that helps lay out the basic parameters of the problem—figuring out which characteristics of nanoscale particles are most important, or setting up standards for handling nanoscale material in a laboratory—is certainly important. But so, too, is research into materials, such as titanium dioxide nanoparticles found in some sunscreens, which are making their way into the hands of consumers right now.

One recent plan for taking comprehensive action called for a $50 million a year research effort that could last up to 10 years. Whether such a commitment will be made on the part of the federal government remains to be seen.

In the face of the suggested risk and the daunting task in successfully characterizing it, the simplistic choice would be to turn away from nanotechnology altogether. But even Oberdšrster, whose experiments have had some gruesome results, says that to do so would be a mistake.

"I think there is too much hype around nanotechnology," he said. "Certainly, we need to thoroughly evaluate potential adverse effects, but we should not overreact and raise unnecessary fears by, for example, interpreting results from inappropriate testing as demonstrating a significant risk of a specific nanomaterial."

In essence, you can paraphrase Defense Secretary Donald Rumsfeld and place the health risks from nanotechnology in three categories: the known knowns, the known unknowns, and the unknown unknowns. Unfortunately, researchers say, that last bin is still by far the biggest.

The specter that the vast promise of nanotechnology could be betrayed by a rush to commercialization is one that hangs over the nanotoxicology community. Kulinowski said the example of the pesticide DDT, which was introduced with great fanfare only to be pulled from the market when it was shown that it had horrible side effects, was worth remembering. "I don't want the same thing to happen with nanotechnology," she said.

"I fully anticipate that there will be classes of nanomaterials that will not be suitable for commercialization," Kulinowski added. "I think that we're going to find the limits of what we can do and what we shouldn't do with nano. But we need to keep asking the questions and not be satisfied until—until we're satisfied."