From the issue dated September 10, 2004
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The Dark Side of SmallAs nanotechnology takes off, researchers scramble to assess its risks
On the big screen this summer, small science nearly squashed Spider-Man. In the sequel to the 2002 blockbuster, ultraminiature materials called "nanowires" transmogrify a brilliant physicist into a rampaging villain who pummels the superhero to within a millimeter of his life. If the plot sounds far-fetched, consider that we all can harness the superpower of nanotechnology, for just $49.50 plus shipping and handling. That's what it costs to buy a pair of comfort-waist pleated khakis from Eddie Bauer, endowed with nanoparticles that are advertised to knock out stains and wrinkles. Welcome to the brave new little world of nanotechnology, the fast-approaching revolution that proponents say will play an increasingly important role in all our lives. Store shelves are starting to sag with products touting nanotech components, such as transparent sunscreens, self-cleaning windows, and tennis balls that keep their bounce. Soon, the fruits of nanotechnology may slash the power required to propel cars down the road and may fundamentally improve the way doctors treat cancer. "We see it as having virtually unlimited potential to transform the way we produce, deliver, and use energy, not to mention its likely effect on medical technology and national security," said U.S. Energy Secretary Spencer Abraham at a nanoscience conference in June. But the small world is arriving before scientists have had an opportunity to test whether nanoparticles will harm people or the environment. The federal government has ramped up spending on the development of nanotechnology to nearly a billion dollars this year, with more than half of that going to researchers at universities. But less than 1 percent of the total is going to investigate the toxicity of the materials. Simply put, our knowledge about nanotechnology's risks is as slim as the particles themselves. "We don't have the information to be able to quantify the potential for hazards, and we don't really have methods for assessing those hazards -- and indeed we don't have a common language for being able to talk about these substances," concluded Lynn R. Goldman, a professor of environmental health at the Johns Hopkins University and a former official at the Environmental Protection Agency, who spoke at a meeting of the National Institute of Medicine this spring. Indeed, of the few tests conducted so far at universities and federal labs, several have raised red flags, showing that some nano-size molecules can damage the lungs and even the brains of animals. While the Food and Drug Administration has ruled that the nanoscale titanium dioxide particles in some sunscreens are no different from the larger titanium dioxide particles already present in products, initial studies suggest that, ounce for ounce, the nano-size particles are more toxic to lung tissue than their larger siblings. As academic, corporate, and government scientists race to develop nanotechnology's myriad benefits, those who study its risks are playing catch-up and will not have time to assess many new materials before they reach consumers. At the same time, the absence of reliable information has allowed science-fiction plots -- such as Michael Crichton's novel Prey -- to dominate public discussions about nanotechnology, a trend that worries researchers who watched scare scenarios close down markets for genetically modified foods. "The perception that nanotechnology will cause environmental devastation or human disease could itself turn the dream of a trillion-dollar industry into a nightmare of public backlash," said Vicki L. Colvin, a professor of chemistry at Rice University, when she testified last year before Congress. Nano, Nano Everywhere Although the buzzword "nanotechnology" has entered the lexicon of Hollywood and Madison Avenue, many researchers consider the term so broad that it verges on meaningless. It takes its root from "nanometer," a unit of length that is one millionth of a millimeter. For scale, a water molecule is about a third of a nanometer wide. A virus particle might reach 150 nanometers in size, while a red blood cell looms large at 7,000 nanometers in width. An arbitrary definition of nanotechnology -- not universally accepted -- is that it deals with human-built structures measuring 100 nanometers or less. As a species, we have been making nanoparticles from the dawn of time, albeit without any intention. Fires generate a bevy of carbon-containing molecules in the nanometer range. Stop at a red light behind a diesel bus and you'll inhale a good dose of nano-size specks, some of which have been shown to cause microscopic lung damage. But nanotechnology represents something new because researchers are creating novel, highly refined structures with specific properties, such as the ability to conduct electricity or to glow when illuminated by a laser. And each week, scientific journals report advances in developing nanomaterials that could dramatically help people or the environment. Last month, for example, researchers from Banaras Hindu University, in Varanasi, India, and Rensselaer Polytechnic Institute described a process for building large filters out of carbon nanotubes, hollow cylinders only a few nanometers across, made of carbon atoms. The team demonstrated how such fine sieves could filter bacteria and poliovirus particles out of drinking water. Earlier in the summer, a team from Emory University and the Georgia Institute of Technology reported using quantum dots -- nano-size semiconductor particles -- to detect cancers in living mice. By bonding antibodies to the quantum dots, the researchers made particles that could travel through an animal's bloodstream to attach to cancer cells. Then they detected the location of the tumors by shining a tissue-penetrating light on the mouse, which caused the quantum dots to emit a signal. In the long run, researchers plan to make such systems capable of killing cancer cells after they detect them. In many cases, nanotechnology research does not involve the creation of new chemicals. Carbon nanotubes are, after all, another form of the carbon present in diamonds or pencil graphite. But the properties of the particles can change drastically as they shrink in size. A quantum dot two nanometers wide glows in blue light, for example, while the same type of quantum dot shines in red if it measures six nanometers wide. The difference illustrates the gargantuan task facing toxicologists who want to know whether nanoparticles can harm people. There are so many different kinds of materials and so vast an array of sizes that researchers need some overarching framework to tell what class of nanoproducts might cause harm and therefore deserves the most scrutiny. A Fish Tale At this point, though, scientists can't even draw the plans for such a framework. While thousands of papers have come out touting different developments in nanoscience, fewer than 50 papers have examined how engineered nanoparticles might affect people or the environment. "We're guessing on a lot of this," says Ms. Colvin, who directs the Center for Biological and Environmental Nanotechnology at Rice. For the past 10 years, academic institutions of all stripes have been scrambling to get a share of nanotech research money. And the pot is quickly growing. Last month, for example, the National Science Foundation announced that as part of its nanotechnology portfolio for next year, it will be giving out $81.5-million. Proposals are due in November and the money will support roughly 130 grants. "Every university and its brother has a nanotech center and is trying to do nanotech one way or another," says Ms. Colvin. Originally, nanotech researchers didn't want to explore potential problems. "The academic community was very negative about this kind of stuff," she says, "because most of the nanotech people like myself, who make nanomaterials, want our stuff to save the world. We don't want to find out that it's toxic." But she has detected a turning point, as the government has started making modest sums available for studying the effects of nanotechnology. "Just in the last year," she says, "I've seen this enormous transition in how it's handled in the research community and the level of interest." The studies that have come out so far have not painted a glowing picture of the technology. This spring Eva Oberdörster, an adjunct scientist at Duke University who lectures at Southern Methodist University, made headlines with potentially disturbing news about highly touted nanoparticles called buckyballs, after the inventor R. Buckminster Fuller. Made of 60 carbon atoms bonded together like a molecular soccer ball, the particles are also called fullerenes. Ms. Oberdörster put a solution of fullerenes into a tank with large-mouthed bass and later examined different organs in the fish. She found signs of oxidative damage in their brains and speculated that the nanoparticles had stimulated the production of free radicals, highly reactive compounds that can damage cells. Normally, she says, particles can't get into the brains of fish -- or people -- because a protective structure called the blood-brain barrier keeps out harmful materials. But past experiments have shown that nano-size particles can slip through that barrier by traveling up nerve cells into the brain. As Ms. Oberdörster was conducting the bass studies, she noticed that the tanks containing fullerenes had noticeably clearer water than did the control tanks. The molecules, it seems, killed off beneficial bacteria in the fish tanks. The results show that fullerenes could prove useful in the future as powerful new antimicrobial agents. However, nobody has examined whether fullerenes could harm natural bacteria living in rivers and oceans if the particles were released in the environment, says Ms. Oberdörster. Because hers was the first study to examine how fullerenes affect fish, Ms. Oberdörster cautions against drawing any broad conclusions from the work so far. "This was just scratching the surface," she says. "It was very limited in scope. We used only one nanomaterial." But it has opened scientists' eyes, she says: "It's made people aware that there may be some consequences to these nanomaterials." Size Matters For Ms. Oberdörster, studying extremely small particles is something of a family business. Her father, Günter Oberdörster, has spent decades analyzing how the lungs react to ultrafine materials. (Her brother is also a toxicologist.) Dr. Oberdörster, a professor of toxicology in environmental medicine at the University of Rochester, just received a $5.5-million, five-year grant from the Defense Department to study the effects of nanoparticles. His previous work suggests that particles of this size can be more destructive than bigger ones with exactly the same composition. The Rochester team, for example, looked at titanium dioxide particles, which are used as pigments in white paint and also in some sunscreens. When rats and mice inhaled particles ranging in size from 12 nanometers up to 250 nanometers, the smaller particles caused more inflammation than did an equal weight of larger particles. The discovery points out a flaw in the way researchers and government agencies generally assess doses in toxicology studies and safety regulations. The standard way is to measure the mass of a material, but that quantity is not so critical in the nanoworld. When particles get extremely small, what matters most is their surface area because almost all of the particle is exposed surface. Dr. Oberdörster found that the amount of surface area, rather than the mass of the particles, predicted how much inflammation they would cause in the lungs. The smaller particles react differently from larger ones, he says, because nano-size materials evade the normal defense system in the lungs, the macrophage cells that gobble up irritants and clear them out. Once nanoparticles get deep into the lungs, they can cross over into the bloodstream and from there into any organ. At this point, he says, it is unlikely that people will inhale the nano-size titanium dioxide on the market because the particles are suspended in liquid sunscreens. But he wonders about other routes of exposure. "We don't know how well these particles translate across the skin," he says. Some tests on cadavers have shown that nano-size particles can slip through the skin, especially when it is flexed, as might happen when a person bends an arm. "It's probably possible that these nanoparticles will be able to penetrate the skin, but to what degree, that is still open," says Dr. Oberdörster. It is not even clear to what extent gloves can protect lab workers from exposure to nano-size particles. At this point, researchers are still very much in the dark, he says. "I'm not saying that nanoparticles are bad in general, but we just need to test for the potential pitfalls." After considering safety data submitted by manufacturers, the Food and Drug Administration ruled in 1999 that nano-size titanium dioxide in sunscreens was not a new product, and there was no evidence of any safety concern. But some toxicologists question that ruling, given nanoparticles' large surface area and the unusual way that they have behaved in certain studies. The FDA declined numerous requests to explain its decision regarding nano-size titanium dioxide. Damage to Lungs The FDA's decision is "probably not correct," says Vincent Castranova, an adjunct professor at West Virginia University and chief of the health-effects laboratory in the pathology and physiology research branch of the National Institute for Occupational Safety and Health, or Niosh. Mr. Castranova and his colleagues have explored the health effects of carbon nanotubes, which are attracting considerable interest for potential use in electronics, aerospace materials, batteries, and fuel cells. Companies now manufacture carbon nanotubes at the rate of tons per year, but several have advertised that they will step up production quickly in the future, as demand for the materials grows. The Niosh team was interested in how carbon nanotubes would affect lung tissue if the particles were inhaled. In a study run by Anna A. Shvedova, an adjunct associate professor at West Virginia and a senior staff scientist at the institute, the researchers put carbon nanotubes into the lungs of mice and found scar tissue forming within a week, faster than the scarring from any other material they have tested. In another study, Ms. Shvedova and co-workers found that carbon nanotubes generated dangerous free radicals in cultures of human skin cells. The oxidative damage caused by the nanotubes triggered the deaths of the cells, her team reported in the Journal of Toxicology and Environmental Health last year. "Our hazard identification would say these are materials of potential concern," says Mr. Castranova. He and Ms. Shvedova hypothesize that the real culprit may be iron trapped within the nanotubes, an unwanted byproduct of the fabrication process. At present, most nanotubes contain such contaminants, but manufacturers are trying to create cleaner structures, and the Niosh team plans to test the more refined molecules as they become available. Heavy metals can also cause a problem with quantum dots, the ultrasmall particles that could play a role in cancer treatment and other medical applications. Current quantum dots have cores of toxic elements such as cadmium and selenium, prompting some researchers to worry about their effects. Warren C.W. Chan, an assistant professor of biotechnology at the University of Toronto, and colleagues at the University of California at San Diego found that uncoated cadmium-selenium quantum dots did indeed kill cultures of rat-liver cells. But by coating the quantum dots, the researchers reduced their toxicity. That fact highlights how nanotechnology can follow a different path from that of previous technologies, says Rice's Ms. Colvin. In the past, drug companies or biotech firms have waited to test their products for problems until late in the process. At that point, toxicology researchers would give the green light to products or put up a permanent stop sign, preventing them from ever reaching the marketplace. "The paradigm shift really is not seeing toxicology as a gatekeeper but seeing toxicology as a point of information that allows you to generate more biocompatible materials," says Ms. Colvin. She is hoping to team up nanomaterial producers with toxicologists early on so the latter can help steer the former toward making safer particles. In some cases, that might mean adding a surface coating to a nanomaterial. In other cases, such as with buckyballs, it could involve breaking one of the carbon-carbon bonds and adding another molecule that alters the properties of the fullerene. Nanoscale Support for Research Almost everybody involved in nanotechnology says it is too soon to tell whether and how these materials might harm people or the environment. "Very little is known," says Mr. Castranova. "It's sort of a virgin territory." He and others argue that the federal government has devoted far too little money to studying the potential dangers of nano-technology. "We can't test all those materials with the amount of resources we're spending," he says. E. Clayton Teague, director of the national nanotechnology-coordinating office, says the federal government is spending a little over $10-million a year to assess the risks that nanomaterials pose to human health and the environment. That amounts to 1 percent of the total federal expenditure on nanotechnology. Because researchers are still in the early stage of developing nanotechnology, says Mr. Teague, the amounts allocated for toxicology make sense. "It's unclear that if you poured more money into it, it would move faster," he explains. But toxicologists disagree, saying that the lack of resources is holding back research. The available money "is not enough," says Dr. Oberdörster. "If you really forge ahead with nanotechnology -- which is no question what we will do and what we should do- -- you can't forget that there may indeed be something which is not as we expect it to be." As criticism grows, the White House last month called on agencies to support research into how nanotechnology will affect human health and the environment. But at this point, the administration has pledged no new money for that effort beyond what it had previously planned. With the low level of support for risk research, the nanotech industry is speeding far ahead of researchers' ability to test the newly created materials. So products will enter the marketplace well before they have been examined for safety. In one scenario, the Rice center has estimated that tons of fullerenes packed into fuel cells could be arriving at people's homes within four to five years. That prospect -- and nightmarish fears about nanotech disasters -- has led some groups to call for moratoria on nanotech products. While such draconian steps have not won the support of scientists, the British Royal Society this summer issued a report saying, "Until more is known about environmental impacts of nanoparticles and nanotubes, we recommend that the release of manufactured nanoparticles and nanotubes into the environment be avoided as far as possible." Academics who work on nanomaterials worry that the gap between testing and product development could send nanotechnology down the same hole that recently doomed genetically modified crops. Bad publicity about the potential risks of such products caused people, especially in Europe, to rise up against what had been dubbed "Frankenfoods." "We like to hold up GM foods as the poster child of what not to do," says Kristen Kulinowski, executive director of education and public policy at Rice's center. The lessons that she draws: "Don't minimize the public's concerns. Don't sweep potential problems under the rug. Don't try to lull people into a false sense of security." At this point, public perceptions remain fairly positive about nanotechnology, according to a recent poll conducted by North Carolina State University. But people also remain mostly uninformed about it. That ignorance may come to haunt researchers, as more developers of popular culture start casting nanotechnology as the next übermonster. Plots in video games and movies have already started the trend, which will only grow when the novel Prey meets the big screen. David Rejeski, director of the foresight and governance project at the Woodrow Wilson International Center for Scholars, says that the public is "going to get much more information from films and television shows and games than they ever will from a National Academy study." So for the moment, with little research exploring potential risks, the public may draw its knowledge about the nanotechnology they will soon be buying from films like Spider-Man 2. And that prospect is making scientists' skin crawl. THE WORLD OF THE ULTRASMALL The U.S. government spent close to $1-billion this year on research and development in nanotechnology -- the science of extremely minute products hat could revolutionize medicine, transportation, and many other aspects of modern society. Some nanoparticles are so small that thousand could fit inside a red blood cell. But researchers expect big dividends from the tiny technology: Some estimates predict that the nanotech market will reach $1-trillion in a decade.  MRI SCAN: STONE; CAR: NOAH BERGER; SPACE SHUTTLE: THE IMAGE BANK; QUANTUM DOTS: H. FISCHER, A. SINGHAL, W. JIANG, U. OF TORONTO; GOLD PARTICLES; D.W. GOODMAN, TEXAS A&M; NANOTUBES: R.E. SMALLEY, SCIENCE; BLOOD CELLS: STONE; HAIR: RON BOARDMAN, FRANK LANE PICTURES; FEA: STONE.
SOURCE: Chronicle reporting
Chronicle graphic by Robert Bryson
http://chronicle.com Section: Research & Publishing Volume 51, Issue 3, Page A12 | |||||||||||||||
Copyright © 2004 by The Chronicle of Higher Education