For Science, Nanotech Poses Big Unknowns

By Rick Weiss

Nanotechnology, the hot young science of making invisibly tiny machines and materials, is stirring public anxiety and nascent opposition inspired by best-selling thrillers that have demonized the science -- and new studies suggesting that not everything in those novels is fantasy.

The technology, in which scientists manufacture things less than 1,000th the width of a human hair, promises smaller computers, stronger and lighter materials, even "nanobots" able to cruise through people's blood vessels to treat diseases. Billions of dollars are being pumped into the field, and products with science-fiction-like properties have already begun to hit the market.

But studies have also shown that nanoparticles can act as poisons in the environment and accumulate in animal organs. And the first two studies of the health effects of engineered nanoparticles, published in January, have documented lung damage more severe and strangely different than that caused by conventional toxic dusts.

The risks of nanoparticles may ultimately prove to be minor and avoidable, experts say. Nonetheless, in a move that industry supporters blame on a conflation of facts with popular fiction -- such as Michael Crichton's best-selling thriller "Prey," in which rogue nanoparticles wreak deadly havoc -- activists have begun to organize against the science.

Some in California are trying to block construction of a nanotech factory, noting that no government agency has developed safety rules for nano products. Others want a global moratorium on the field until the risks are better understood.

Now, realizing that public perception may be at a tipping point, the fledgling industry and government agencies are taking a novel tack, funding sociologists, philosophers and even ethicists to study the public's distrust of nano. Supporters of the approach say these experts will serve as the industry's conscience and ensure that the science moves forward responsibly. Others suspect it is an effort to defuse nano's critics.

Both sides agree the stakes are huge. Government officials have called nanotechnology the foundation for the "next industrial revolution," worth an estimated trillion dollars within the coming decade. But if nano's supporters play their cards wrong, experts say -- by belittling public fears as "irrational" or blundering into a health or environmental mishap -- the industry could find itself mired in a costly public relations debacle even worse than the one that turned genetically engineered crops into "Frankenfood."

"We can't risk making the same mistakes that were made with the introduction of biotechnology," said Rita Colwell, director of the National Science Foundation, the nation's largest funder of nanotechnology research. "We have to do this benignly and equitably."

The struggle for public trust will be challenging, officials confess, given the frightening tales that have been spun about nano in recent years.

It started in 2000, when Bill Joy, co-founder of the computer giant Sun Microsystems, wrote a chilling and widely read article warning that self-replicating nanomachines could eventually overwhelm the human race and digest the living world into a mass of "gray goo" -- a scenario that many scientists, but not all, reject.

Then came "Prey." And in Dan Brown's No. 1 best-selling novel, "Angels & Demons," the Catholic Church denounces nanoscience as evil. (It has not, although Britain's Prince Charles has expressed alarm about the science.)

In December it seemed the industry might at last be shaking off its negative image: In an Oval Office ceremony, President Bush hailed the technology and signed a $3.7 billion bill to boost the research. But even as the president was signing that bill, researchers at the National Science Foundation across the Potomac were attending a meeting on nano's social and environmental risks.

It is too soon to say whether nano will wean society from dirty technologies or simply produce its own versions of the asbestos, diesel soot and DDT debacles that are the legacy of the last industrial revolution. The science is still new, and the rhetoric on both sides remains defensive and polarized.

"This is a genuine opportunity for an engaged dialogue," said Davis Baird, who, as chairman of the University of South Carolina's philosophy department and associate director of the university's Nanocenter, is part of the nascent effort to separate nanomythology from fact.

"But it's going to be tricky," Baird said. " 'Risk' is a more subtle concept than broad sections of the public appreciate."

Burgeoning Industry

Nanotechnology started off as little more than a clever means of making incredibly small things. IBM scientists made headlines in 1990 by painstakingly arranging 35 xenon atoms to spell out the company's three-letter name, creating the world's smallest corporate logo. Cornell University scientists followed with an invisibly small "nanoguitar." Its strings, each just a few atoms across, could be plucked by laser beams to play notes 17 octaves higher than those produced by a conventional guitar -- well above the human hearing range.

Novelties though they were, these feats proved that with new tools in hand scientists could arrange atoms as methodically as masons arrange bricks -- and in doing so build materials never made in nature.

Now the field is taking off.

Last year alone, hundreds of tons of nanomaterials were made in U.S. labs and factories. Microscopically thin sheets of tightly woven carbon atoms are being wrapped around the cores of tennis balls to keep air from escaping. New fabrics have been endowed with nanofibers that keep stains from settling in. Some sunscreens have ultraviolet-absorbing nanoparticles so small they cannot reflect light, making them invisible. Tennis rackets and airplane bodies are being made with nanomaterials whose atoms have been carefully arranged to make them especially strong.

"This technology is coming, and it won't be stopped," said Phillip J. Bond, the Department of Commerce's undersecretary for technology.

Bond may be right. But it won't be for some people's lack of trying.

Foremost among those activists is Pat Mooney of the Winnipeg-based ETC Group, which has called for a moratorium on commercial production of nanomaterials until its risks are better elucidated and regulations put in place.

It is a radical stand , but industry knows it ignores Mooney at its peril. He spearheaded much of the opposition to agricultural biotechnology -- opposition so successful that it made biotech giant Monsanto Co.'s name synonymous with "PR failure" and resulted in European restrictions on imported crops that continue to cost the United States hundreds of millions of dollars in lost trade every year.

"I do think there is a growing sense that they have to address these issues more seriously than they did in the past," Mooney said.

Scientists have known for years that tiny particles such as soot or metal powders can, when inhaled, cause lung disease, cancer and other ailments. But the laws of chemistry and physics work differently when particles get down to the nanoscale. As a result, even substances that are normally innocuous can trigger intense chemical reactions -- and biological damage -- as nanoscale specks.

Gold, for example, is a famously inert metal. But nanoparticles of gold are extremely chemically reactive, with the potential to disrupt biological pathways.

"The smaller the particles, the more toxic they become," said Vyvyan Howard, a University of Liverpool pathologist who studies the health effects of environmental aerosols.

The first two studies to look for such problems appeared in the January issue of the journal Toxicological Sciences, and the results, experts said, are less than reassuring.

In the first study -- sponsored by NASA, an agency that hopes to make great use of nanomaterials -- Chiu-Wing Lam of Wyle Laboratories in Houston and his colleagues washed three kinds of carbon nanotubes into the lungs of mice and examined them as much as three months later. Nanotubes are incredibly strong, microscopic tubules made of carbon atoms; some are already being produced in factories.

All three types caused lung granulomas -- abnormalities that interfere with oxygen absorption and can progress to fatal lung disease. And although each mouse got just one exposure, the lesions got worse over time, with some progressing to tissue death. On average the reactions were worse than those in mice given equal amounts of quartz particles, which toxicologists use as their "serious damage" standard.

Carbon nanotubules, the team concluded, "can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures."

The other study was led by David Warheit at DuPont Co.'s Haskell Laboratory near Newark, Del., and involved similar exposures in rats. Surprising the scientists, 15 percent of the animals getting the highest dose died from lung blockages within 24 hours -- an outcome the group had never seen for any lung toxin. Warheit said in an interview he did not believe the deaths were indicative of any "inherent pulmonary toxicity" of nanotubes. But his other results were surprising, as well: All the surviving rats developed granulomas, yet without the inflammatory responses that usually accompany those lesions.

"The response in the body was quite unique," said Vicki Colvin, director of the Center for Biological and Environmental Nanotechnology, a federally funded research center at Rice University that also gets support from the university and industry. "They behaved differently than other carbon-based ultrafine particles."

"This is a very unusual lesion," Warheit agreed. "The question is, why did that happen?"

Warheit, whose company hopes to profit from nanotechnology, is optimistic that nanomaterials will prove relatively nontoxic. He and Lam note that more realistic tests, in which the particles are inhaled, have yet to be done. Those tests are expensive, both noted, and no one has expressed a willingness to fund them.

Inhaled particles do not always stop at the lungs. Experiments by University of Rochester toxicologist Gunter Oberdoerster showed that nanoparticles can make their way from a rat's throat into its brain, apparently via the nasal cavities and olfactory bulb.

"Who knows how they interact with cells there?" Oberdoerster asked. "Maybe they do something bad and lead to brain diseases."

Other scientists have wondered at recent meetings whether nanoparticles can cross the placenta and get into a developing fetus.

Scientists in France recently showed that carbon nanotubes -- thousands of which could fit inside a cell -- can easily penetrate living cells and even make their way into the nucleus, the inner sanctum where DNA resides.

The researchers hope to harness this capacity and use nanotubes as vehicles to deliver drugs into cells. But the approach could easily backfire, they conceded.

In many instances, for reasons that remain unclear, the nanotubes themselves killed the cells.

Environmental Effects

The effects of nanoparticles in nature are similarly unclear. Depending on whom you ask, the strange chemistry of nanomaterials could save or destroy the environment.

Tom Kalil, special assistant to the chancellor for science and technology at the University of California at Berkeley, is among the optimists.

"Recent results suggest that nanoscale particles could play a very important role in environmental cleanup, dramatically reducing the costs associated with remediating Superfund sites," Kalil said. Engineered nanospheres, which resemble tiny molecular cages, can trap polychlorinated biphenyls (PCBs) and toxic metals, he said. And researchers are designing nanopore materials that can filter out bacteria, viruses and toxins from water.

But not all nanoparticles are so green.

Titanium dioxide, for example, is a generally nonreactive substance used in many products, including skin lotions and house paints. Increasingly, however, it is being made in the form of nano-size particles. And tests show that they are highly reactive, generating chemically "hot" free radicals that can literally burn up bacteria. That has some experts worrying about impacts on soil ecology if the particles are released.

Robin Davies, a British scientist with Soil Environment Services Ltd. in Newcastle upon Tyne, said even slight changes in bacterial populations can have major effects on soil chemistry and on its ability to support plant life. Knocking out soil microbes, he said, "can both create serious environmental pollution and also impoverish the soil for many decades."

No one knows how much "nanolitter" is being released into the environment, experts said, and disposal rules have yet to be crafted.

Even more distressing to activists, nanotechnology is starting to be exploited on a large scale in the great outdoors. Last summer, for example, under contract to the Bureau of Indian Affairs, Utah-based Sequoia Pacific Research Co. sprayed a proprietary "nanostructured solution" on 1,400 acres in New Mexico to try to stabilize the soil after forest fires destroyed the local vegetation. Company officials will not reveal the ingredients in their product, saying only that it does not contain engineered nanoparticles. It works, they said, by triggering cross-reactions among naturally occurring nanoparticles in the soil.

But activists are upset that what appears to have been the world's largest environmental release of a product designed to operate on the nanoscale occurred without federal review or impact studies.

Scientists also want to know what happens to nanoparticles months and years after their release. Researchers at Rice University's CBEN have shown that like many other nonbiodegradable pollutants, they accumulate in living things over time, with ever-increasing concentrations in microbes, in the worms that eat those microbes, and in animals higher up the food chain.

CBEN researchers emphasized that accumulation does not necessarily mean harm, and others dismiss the idea that nanoparticles pose an environmental threat. Clark University risk specialist Roger Kasperson said that reminds him of the early days of the atomic era, when experts similarly unburdened by data predicted that nuclear power plants could never melt down and that electricity would become too cheap to meter.

"Critics of nuclear power were called irrational," said Kasperson, who directs the Stockholm Environment Institute, an international research organization focused on sustainable development. "The starting point to me is to acknowledge that we don't know what the risks of nano are, and we don't know what the benefits are, and we won't for some time."

Incomplete Data

Everybody agrees that if nanotechnology is going to be the next industrial revolution, it would be nice if it were a cleaner revolution than the last one. Nobody wants to read Rachel Carson writ small.

"In the old industrial revolution, we learned too late," said David Rejeski, director of the Foresight and Governance Project at the Washington-based Woodrow Wilson International Center for Scholars. "We ended up chasing waste streams, and we still are."

But the regulatory schemes that came into being as a result of that mess are not designed to cope with the challenges of nanopollution.

Currently, companies seeking regulatory approval to manufacture or release potentially toxic substances are required to answer two basic questions: "What is it?" and "How much of it will there be?" But neither question works well for nanotechnology, because substances that are nontoxic in bulk form can be deadly when produced on the nanoscale.

"We're so keyed in to the composition of the substance when we think of toxicology, but on the nanoscale the [particle] size and surface chemistry will probably be the most important feature," CBEN director Colvin said. "That's an interesting paradigm shift."

Even when huge amounts of nanoparticles are made and packed together, the underlying presence of all those microscopic particles can make big materials behave in strange ways.

"There's no doubt from everything we've found that even in aggregates, nanoparticles still express their nanoparticleness, if you will," said Howard, the University of Liverpool aerosol expert.

This truth has not been integrated into the regulatory world. Take the growing number of factories in the United States making carbon nanotubes, which are made of graphite but behave very differently from ordinary graphite.

Like all factories, nanotube facilities must submit "material safety data sheets" describing the substances they handle and assuring that appropriate measures are in place to keep human exposures below mandated thresholds.

But the data sheets that nanotube factories are filing to regulators are simply for graphite.

"You can't simultaneously proclaim a product is new and has all these novel properties and at the same time claim that it can be regulated as if it were nothing different," said Eric Drexler, chairman of the Foresight Institute in Palo Alto, Calif., a nonprofit educational organization focused on advanced technologies. "You can't have it both ways. If these have new properties, they have to be examined and regulated that way."

Mooney said he has been struck by the wide variation in precautions different countries have demanded. In some factories, he said, workers are using high-tech air filtering equipment to guard against inhaling nanoparticles or contaminating the plant. At others, he said, workers wear cheap face masks with pore sizes so large as to offer no real protection.

"It's like having a basketball net over your head to protect you from mosquitoes," he said.

Federal officials acknowledge they have not developed safety standards for nanoproducts, and the agencies are still getting up to speed on the topic.

Norris Alderson, director of the Food and Drug Administration's office of science, said the agency had so far approved six nano-based products: two drugs, two medical devices and two sunscreen lotions. But he did not know whether special safety tests had been required. Pressed for those details, an agency representative called back to report that, in fact, no nano-based products have been approved. No explanation for the confusion was offered.

At the Environmental Protection Agency, after repeated requests for access to an officer in charge of nano-related environmental reviews, an official at the agency said there was no one with any information to provide, and "as of now there are no specific regulations."

Many industry representatives and some independent experts argue that it is too soon to slap restrictions on nano.

"There is a long-term concern, but where is the immediate concern?" asked Thomas Theis, director of physical sciences at IBM Research in Yorktown Heights, N.Y., who sits on two key federal advisory committees dealing with nano. "We have the Environmental Protection Agency. We have OSHA [the Occupational Safety and Health Administration]. That's their function."

But virtually everyone agrees that much more research is needed than is currently being funded to answer questions about toxicity.

"It's clear we are underinvesting in this area," Kalil said.

Only this year, for example, is the EPA considering proposals for what would be its first funded studies on the potential impacts of nanoparticles on the environment.

The agency's request for proposals, published last year, begins candidly, "There is a serious lack of information about the human health and environmental implications of manufactured nanomaterials."

Potential Shock Waves

It will be years before the first studies of nanotechnology's health and environmental impacts come together into a body of evidence, but government and industry officials know that public opinion could solidify long before then. In Berkeley, residents and some members of the city health commission have been staging protests against plans to build a nanotech "molecular foundry" in the hills above town, sending a shiver down the spines of some nano advocates.

Government and industry officials say they are aware of nanotech's societal and environmental implications and can be trusted to be taking them seriously.

Mihail Roco, chief of nanotechnology for the National Science and Technology Council, a Cabinet-level group that advises the president on matters of science, likes to note that he convened the first federal meeting on the societal implications of the science in 2000, two years before Greenpeace came out with its report on the same subject and three years before Mooney's ETC Group published its 80-page manifesto about the threats posed by nano.

Yet most of the social concerns addressed at that meeting -- and at a similar meeting Roco convened in December -- were related not to the direct health or environmental risks of nanotechnology but to the likely social and economic disruptions as the technology invades older manufacturing sectors and displaces workers. Much of the emphasis has been on how to beef up science and engineering curricula in schools to handle nanotechnology's workforce needs.

Roco also has said repeatedly that about 10 percent of the current nano budget in this country is devoted to environmental issues. But experts familiar with the numbers say that figure is deceiving. Almost all that money is going to study how nanotechnology may profitably be used to address existing environmental problems -- an important question, scientists said, but one quite different than that of how nanotech may negatively affect the environment.

And although the nano spending bill that Bush recently signed calls for social and environmental concerns to be addressed, efforts to include a minimum dollar amount for such studies lost out in the final draft.

Some observers have been heartened by the government's recent funding of social scientists and ethicists as representatives of the public interest to make sure the new science is introduced responsibly and safely. But ethics cannot substitute for solid scientific assessments of risk, critics note. And even some of the social scientists who have received those grants say they are skeptical about their roles.

"They're very concerned about public perceptions," said one recipient, speaking on condition of anonymity. "But a lot of it's about, 'How can we make sure people are not afraid so we can go ahead with this?' " Still, nano advocates express confidence that the industry will be straight with the public. "The big companies get it," said Kristen Kulinowski of Rice University.

If nothing else, there's always the fear of repeating history. No nanotech company, she said, wants to be the next Monsanto.

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