For Science, Nanotech Poses Big Unknowns

By Rick Weiss
Washington Post Staff Writer
Sunday, February 1, 2004

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.

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.

"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.

"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?"

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.

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."

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.

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.

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."

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."

© 2004 The Washington Post Company