Managing Safely The Gigantic Future of Very Small Things (Fall 2007 Trust Magazine article)

Pew is no longer active in this line of work, but for more information, visit the Project on Emerging Nanotechnologies on PewHealth.org.

The Project on Emerging Nanotechnologies supports nano development—and the public's health as this new science matures

While sitting in his home office not long ago, Paul Alivisatos was startled to hear one of his daughters racing up the stairs from the TV room. She burst in, her eyes big. “Dad! Dad!!” the youngster exhaled. “The bad guy is taking over the world. And he's a nanotechnologist!”

Oh just terrific, he thought.

Alivisatos is a nanotechnologist of the first rank: a professor of both chemistry and nanotechnology at the University of California at Berkeley and associate director for physical sciences at the Lawrence Berkeley National Laboratory, up the hills just east of campus. A stickler for safety in his 25-person research team, he oversees the national lab's “lessons learned” program that scrutinizes every accident or near-miss.

Nanotechnology deals with matter at the level of the molecule on the scale of nanometers. A nanometer is a billionth of a meter. A nanometer is to a meter as a marble is to the Earth, noted Jennifer Kahn in an article in National Geographic. A man's beard grows a nanometer, she added, in the time he raises a shaver to his face.

Here are other ways of looking at it. A sugar molecule is a nanometer across, and it would take 300 trillion of them to cover the surface of a penny. The common cold virus is about 20 times wider than a sugar molecule and a human hair 80,000 times wider. The unaided human eye can see items as small as 10,000 nanometers.

Nanotechnologists produce and use distinct components— nanoparticles, string-like nanotubes, nanocircuits and nanofilms (components that may not be more than 100 nanometers in size)—and assemble them into machines. Perhaps 100 groups within half a mile of Alivisatos's own lab spaces are involved, not to mention many other universities, research institutes and private companies and labs around the country.

Indeed, an immense worldwide effort is underway to design and build chemical, electronic and mechanical systems from the atom up. Lux Research, which analyzes trends in technology, estimates that 15 percent of global industrial output, about $2.6 trillion worth, will have some nanotech content by 2014. At last count in mid-2007, more than 500 consumer products already claim to have something derived from nanotechnology in their composition, and the number is doubling every year or so. Components include silicon nanoparticles in electronic switches; tiny blobs of zinc oxide in sunscreens; carbon nanotubes, stronger and lighter than steel, embedded in lightweight tennis rackets or bicycle frames for stiffness; nano-motes of hydroxyapatite in toothpaste to beef up enamel; and sub-cellular-sized capsules for delivery of medicine a few molecules at a time where the body needs them most.

Alivisatos's group in Berkeley has spawned important advances in the burgeoning field. Among its core claims to fame is development of quantum dots—clusters of 100 to several thousand atoms. The electronic, crystalline innards of quantum dots absorb and emit light of colors that can be selected almost at will just by slightly adjusting their sizes and thus the wavelengths of photons and electrons that resonate inside them. In their energy behavior, they have been compared to artificial atoms. But more practically, they are like colored sticky notes affixed to molecules or viruses and can highlight active genes and metabolic processes inside living tissue. Non-biological applications include high-efficiency solar power cells.

While polls show only a tiny percentage of Americans have a glimmer of what nanotechnology is, the new science's practitioners, it would seem, have made the grade into at least one animator's axis of technovillains, thus joining such staple, perverse Prometheans as atomic physicists, genetic engineers and builders of giant robots that shoot death rays out of their eyes.

And there stood the professor's anxious little daughter. “So, we had a little talk about what I do,” he said. She seemed satisfied. It was only a cartoon.

Yet, and yet . . . . Alivisatos sat in a recent interview in his underground office below one of U.C. Berkeley's chemistry halls, with the tools of nanotech in the next room over. “We are making building blocks at the same size as those that compose our bodies,” he says. Mankind's inventions are, like life itself, getting complicated all the way down. The lines dividing the living from the mechanical are blurring. For instance, a manufactured thing can be so small that it can pass right through the pores in our cells' membranes. Sooner or later, if one is not careful, nanoparticles or other nanodevices could possibly cause serious trouble—like monkey wrenches and power tools applied randomly to the gears, nuts, switches and relays in a bustling factory. “We have to do this right,” he says.

That is a feeling broadly shared among scientists as well as public interest groups. Many are concerned that the potential risks in a new technology flooding the marketplace with products—while in its infancy—will not get the public-health scrutiny they merit.

Such concerns are why the Woodrow Wilson International Center for Scholars (an arm of the Smithsonian Institution), in partnership with Pew, embarked in 2005 on the Project on Emerging Nanotechnologies (PEN), which is devoted equally to making sure the technology's benefits can be realized and to addressing potential concerns.

“This is the new industrial revolution,” says PEN's director, David Rejeski, who served for six years at the White House Office of Science and Technology Policy and as the representative of the U.S. Environmental Protection Agency to the White House Council on Environmental Quality. “My hope is that if you have enough smart people thinking ahead, you can maximize benefits and minimize risks. But there will always be some risk.”

At Harvard University earlier this year, he described PEN's determination to help nanotechnology move forward rapidly and also warned about the risk. “Somewhere out in the fast-growing world of nanosciences is an accident waiting to happen,” he said. “This mishap will chill investment, galvanize public opposition and generally lead to a lot of hand-wringing on the part of governments who are betting large sums of money on the nanotech revolution. Will it be just bad luck or bad practices? Probably the latter.”

PEN's aim is to ensure that the right risk research is being undertaken by the U.S. Government and that oversight mechanisms are working for the environment, consumers and business.

In its first two years, the project helped support the development of an agreement between the DuPont Corporation and the consumer-activist organization Environmental Defense to craft a voluntary standard for recognizing and dealing with risks from nanoscale materials. The result, a “Nano Risk Framework” tool, is now being distributed industry-wide.

PEN also developed the first inventory of nanotech research activities in the United States, listing more than 800 companies, labs at universities or federal agencies and elsewhere engaged in nanotech-related work, and developed a Google-world “mashup” map showing their zip codes.

Last May, it produced the first systematic analysis of the federal government's policy approach to nanotechnology. Authored by J. Clarence (Terry) Davies, senior advisor at PEN and senior fellow at Resources for the Future (he co-authored the plan that created the EPA), the report says that regulatory oversight of nanotechnology is urgently needed; it calls for immediate action to identify and minimize any adverse effects of nano materials and products on health or the environment. The report spells out more than 25 steps the EPA, Congress, the president, the U.S. National Nanotechnology Initiative and the nanotechnology industry as a whole should take to improve the oversight of developments in the field.

William D. Ruckelshaus, who twice served as an EPA administrator, commented on the report, saying, “Nanotechnology holds tremendous potential— for breakthroughs in medicine, in the production of clean water and energy, and in computers and electronics. It may be the single most important advance of this new century. But with its ability to fundamentally change the properties of matter, nanotechnology also may pose both the greatest challenge and biggest opportunity for EPA in its history. EPA needs to seriously consider the constructive and thoughtful changes that Davies puts forward in his report.”

PEN's staff have been active in disseminating the project's message. Rejeski testified before Congress twice in just one 10-month period, and other members of the staff have met with their counterparts in Congress and in federal agencies, including the Food and Drug Administration, the EPA, the National Science Foundation and the National Institutes of Health.

PEN's Web site has proven useful, too. Recent statistics show about 840 unique users per day, with an average user session of 22 minutes. As of early fall, the first 10 PEN reports had been downloaded 26,823 times.

Andrew D. Maynard, Ph.D., PEN's chief science advisor, was the lead author of an article in the journal Nature last year that set forth five “grand challenges” for research into nanosafety. “The specter of possible harm, whether real or imagined,” the team wrote, threatens to slow the development of nanotechnology unless sound, independent and authoritative information is developed on what the risks are and how to avoid them. They called for industry, government and research organizations to take “unprecedented pre-emptive action” to realize the potential of nanotechnology while minimizing potential risks.

The challenges that Maynard and his co-authors enunciated to get the job done are:

• Develop instruments to assess exposure to engineered nanomaterials in air and water, within the next 3 to 10 years.
• Develop and validate methods to evaluate the toxicity of engineered nanomaterials, within the next 5 to 15 years.
• Develop models for predicting the potential impact of engineered nanomaterials on the environment and human health, within the next 10 years.
• Develop robust systems for evaluating the health and environmental impact of engineered nanomaterials over their entire life, within the next five years.
• Develop strategic programs that enable relevant risk-focused research, within the next 12 months.

The paper received a warm reception but, nearly a year later in late summer 2007, Maynard laments that measurable progress has been scarce, particularly on the fifth challenge with its one-year deadline. Nonetheless, he notes that the European Union's 7th European Research Framework called for similar programs. And last April, the European Commission called for public consultation on a nanosafety initiative and related research.

In the United States, he says, the federal National Nanotechnology Initiative is still working on its list of research priorities, a “process that looks systematic, on paper, but is by no stretch of the imagination a research strategy that will deliver results.

“Yet, with the rapidity with which nanotech is moving into products, it is a pretty important timeline—we don't have the luxury of dallying over what to do while people are already being exposed to these materials.”

The special feature of nanoscience's products, and the reason some worry they need special scrutiny from the start, is not merely that they are small. Often, new properties emerge at very small dimensions that are not simple extrapolations of their behavior as bulk matter (or even as more routine bits of dust). These include quantum effects in atomic behavior and interactions, dramatically increased mobility or chemical reactivity, color and electrical conductivity. Regulations that govern exposure to toxic materials as a function of their total burden, or mass, may need revision for particles so small that a fifth of their atoms are on their surfaces, vastly increasing their rates, per ounce, of chemical impact.

Many avenues of basic research reveal how nanoparticle behavior brings special safety challenges. At the University of Rochester's Department of Environmental Medicine, a team led by Günter Oberdörster, D.V.M., Ph.D., tracked the paths of nanoparticles inhaled by rats. His team found the motes can travel from the respiratory tract to the liver in just four hours, passing easily through the thin walls of blood vessels. Some penetrated the olfactory nerves in nasal passages. Over the course of a week, they migrated up the slender fibers to the olfactory bulb in the brain, circumventing the blood-brain barrier that repels most unwanted molecules from the central nervous system. They penetrated tissues as a breeze goes through a fence. “It means [we need] some additional regulatory concepts in nanotoxicology,” says Oberdörster. “We need better assays or ways to assess it. The ones we have are very valuable, but we need more.”

The campaign to set up robust safety systems during nanotech's infancy runs somewhat counter to history. More commonly, societies waited until bodies began to pile up before thinking about regulations. The Food and Drug Administration was born in large part because muckraking writers, including Upton Sinclair in his 1906 book The Jungle, exposed the horrors not only of industrial exploitation of immigrant labor but also of the filthy conditions in meatpacking plants. Seat belts, padded dashes and air bags may be standard today, but for its first half-century-plus, the auto industry had hardly anybody checking the safety of its products. Rates of highway carnage for the last several decades have steadily dropped, largely in response to safety requirements.

“I'm crossing my fingers that there is no nanoparticle out there that is truly dangerous,” says chemist Vicki Colvin, director of the Center for Biological and Environmental Technology at Rice University. “History is littered with really good technologies that got really obliterated by accidents or other problems—like with DDT. The public reaction to an environmental problem [drastic decline in some bird species and thinning of eggs due to DDT contamination] forced a complete shutdown.” It has taken decades for DDT to work its way back, under careful controls, as a potent weapon against malaria.

The only good parallel to putting up safety curtains during an industry's infancy comes from genetic engineering and biotechnology, another new arrival on the scene. Novel organisms created by swapping genes among species, or by designing entirely new genes for them, are unevenly monitored. GMOs, or genetically modified organisms, regularly trigger public outcry in many countries. With nanotech, Colvin says that public agencies, especially in the United States, have an even higher obligation of vigilance. “It is really a government initiative . . . through billions of dollars of investment in R&D,” she says. She is referring to the National Nanotechnology Initiative, created in the Clinton administration and embraced in the Bush administration, with nearly $1.44 billion in federal nanotech research in the 2008 budget alone.

As for safety, right now “federal agencies and companies are all looking to existing regulations to work for nanotechnologies, without a lot of coordination,” says PEN director Rejeski. “But will they? And if not, what options do we have? Given the novel properties of many nanomaterials, do we have the right tests and are we even asking the right questions? For the past two years, PEN has undertaken a comprehensive review of what federal agencies already have on the books, including the EPA and FDA, for instance, and looked beyond existing regulations for new solutions.”

European countries, especially the United Kingdom, are moving ahead more aggressively than the United States to impose controls on nanoscale science and technologies. There, the precautionary principle of regulation— an assumption that new products and practices are considered a potential threat until shown they are not—holds greater sway, says chemist Kristen Kulinowski, director of the International Council on Nanotechnology at Rice University.

Three years ago, a report from Britain's Royal Society, its foremost science body, flatly recommended that release of manufactured nanoparticles and nanotubes into the environment be avoided as far as possible.

Until proven otherwise, it said, all should be regarded as hazardous. It urged that all agencies immediately review their regulations to find any gaps through which threats from nano products or research might sneak.

In America, Kulinowski says, “the attitude is somewhat more relaxed. Agencies are mostly saying they don't need any more authority for nano than they already have for any potentially hazardous substance.” Last July, the Food and Drug Administration, after long gestation, released a report that Commissioner Andrew von Eschebach said would foster “the continued development of innovative, safe and effective FDA-regulated products that use nanotechnology materials.”

Yes, he acknowledged, such materials “present challenges,” but they are “similar to those the FDA faces for products of other emerging technologies,” and the rules in place, along with appropriate research to keep up with the science, appear adequate.

It is not as though nanosciences have no top-level scrutiny in this country. Papers on potential hazards have emerged from U.S. labs, and virtually every technical agency has held workshops on them and formed special offices to watch for any developing perils.

But among the recommendations that the PEN program made back in 2005 was that at least $100 million in the subsequent two years go into safety-related research. And while federal overseers of the national nanotech program said they were spending $40 million to $100 million every year on such matters, PEN analysts put the true figure at only about $11 million. For instance, an internal National Science Foundation budget analysis claimed a $24-million expenditure on risk-related research in 2005, but PEN's closer look at the figures found only $19 million went to research relevant in any way to understanding potential risks, and only $2.5 million to work that could be considered highly relevant.

Maynard's 2006 Nature article proposed specific, short-term nano safety budgets for U.S. agencies, including $46 million for the National Institute for Occupational Safety and Health and $20 million for the EPA.

Although no nanotech accident has occurred, there has been a false alarm. In March 2006, the German manufacturer of a spray for sealing ceramic tiles—called Magic Nano— pulled the product from the market after several buyers ended up in the hospital with fluid in the lungs and nearly 100 had bad but less severe reactions. All recovered, but the incident looked like the first nanoinduced public health crisis that some had been predicting. Several groups called the episode a wake-up call to regulate nanotechnology more carefully, but independent tests could not confirm anything nano about the spray. It now seems that a solvent in the product caused the lung distress and that the nano label was a mere marketing tool.

PEN's science adviser Maynard keeps track of new nano products and perked up upon discovery of a nano-kayak. Perhaps some new lightweight material in its hull, stiffened with nanotubes? Nope. “It was just a very small, one-person kayak,” he says. Labeling works the other way around, too: Many products that contain nanotech don't mention it in their sales literature—raising questions about truth in labeling and potentially hampering surveillance.

As for real nano and its potential hazards, scrutiny so far has focused on the most easily foreseen problem areas. These are mainly nanoparticles dispersible in the environment, typically in the air or water, or via medicines or cosmetics that people might take in orally or through the skin.

But in the long run—years, decades and even centuries to come—vigilance may need to aim at more exotic issues.

It's worth a look back to see how the long future of nanotech may unfold. The field's historians trace its origins to a talk titled “There's Plenty of Room at the Bottom,” by Caltech physicist Richard Feynman in 1959. He noted that no physical laws forbid manufacturing of goods from the bottom up, atom by atom. More than mere chemistry, he envisioned atomic-scale factories complete with automated assembly lines, lathes, forges, coils, jigs and drill presses as tiny as the smallest organelle sub-units in living cells, but not necessarily bathed in watery environments. He supposed they could be developed through a series of miniaturizations. Big tools would make smaller copies of themselves, which in turn would make a yet-smaller generation, and so on. (Such self-reproducing machines had been imagined before, notably by mathematician and computer pioneer John von Neumann.)

In the 1980s and 1990s, engineer K. Eric Drexler, then at the Massachusetts Institute of Technology, began fleshing out Feynman's ideas. He forecast a dawning age of molecular manufacturing, drawing parallels between its operation and the biological machinery of living cells. Drexler's was in large part an optimistic look forward. But he also mused, in his 1986 book Engines of Creation, that microbe-like, self-copying micromachines might run amok. They might consume raw materials from all available sources and spread across the earth in a smothering, planet-wide infection he called “gray goo.” This grabbed the public imagination, eliciting a response from PEN (not a danger) and a repudiation of its possibility from Drexler.

Nonetheless, the future is long, human and machine-aided inventiveness hard to predict, and the potential profits from truly conquering the nanoscale, mass manufacture of materials and products enormous. “Molecular manufacturing will be as big as the invention of computers, as big as the industrial revolution,” says Chris Phoenix of the Center for Responsible Nanotechnology in Brooklyn, N.Y. Its greatest impacts, he adds, will arise from its eventual ability to transform the nature of industry and the speed with which ideas become products. One forecast is, within decades or even less, the presence of tabletop nanofactories “with many zillions of manufacturing stations and a smaller order of zillions of assembly stations that put together tabletop products that are perfect, down to the atom.” It won't be a question of how many nanoparticles can stand on the head of a pin, but how many supercomputers can be housed there.

For now, the field's safety perils may be different from and perhaps frightening compared to those of other new fields. They are not, however, dramatically beyond the scale of hazards to which industrial societies are accustomed. “Our goals are to stimulate research, oversight and foresight,” says Rejeski. “Will it slow down innovation? I don't think so. I'm very optimistic. We are addressing safety and environmental issues so much earlier than with other technologies. The intention is to move nanotechnology into the marketplace without significant speed bumps.”

The Project on Emerging Nanotechnologies is located in Washington, D.C. Its Web site, www.nanotechproject.org, features nine topic areas: business; environmental health and safety; environment and green nano; looking ahead; multimedia/ podcasts; perspectives series; policy; public perceptions; risk; and research. In addition, Andrew Maynard has a new blog: Click here for blog.

Charles Petit, science writer for U.S. News & World Report for 26 years, now freelances, with recent credits in National Geographic, Smithsonian Magazine, Nature, and The New York Times. His honors include awards from the American Association for the Advancement of Science (for newspapers and for magazines) and the Science-in-Society prize from the National Association of Science Writers, an organization he later headed as president.

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In the PEN report Nanotechnology: A Research Strategy for Addressing Risk, Andrew Maynard proposed a comprehensive framework for systematically exploring possible risks. He concluded with these recommendations:

Changes need to be made in risk-research responsibility within the federal government. There should be top-down authoritative oversight, and nanotechnology risk research must shift to federal agencies with a clear mandate for oversight and research into environment, health and safety issues.

• Adequate funding must be provided for highly relevant risk research. Agencies must have sufficient budget to develop critical knowledge, and there should be investment to inform the public's understanding of risk.
• A short-term strategic risk-research plan should be developed and implemented. Top priorities involve nanotechnologies in or close to commercial use, with long-term research into predictive toxicology to provide the scientific basis for addressing new risks.
• Mechanisms should be developed for joint government-industry riskresearch funding.
• Nanotechnology risk research must be coordinated internationally. There should be mechanisms to facilitate the free exchange of information on research needs, activities and priorities, and mechanisms for sharing costs and resources.
• An interagency oversight group should be established with authority to set, implement and review a strategic risk-research framework. This group would set and implement the agenda, assure the allocation of appropriate resources and direct efforts to provide a strong scientific basis for regulatory decisions.
• A rolling, independent assessment of long-term research needs and strategies should be established.

The full description of these recommendations, as well as the full report, is available at the project's Web site, under reports.