By Richard Acello

This July, delegates to an international conference will meet in Geneva, Switzerland, to consider recommendations aimed at improving the risk governance of nanotechnology. The conference, sponsored by the International Risk Governance Council (IRGC), is designed to improve the understanding and assessment of risk issues and design innovative, efficient, and balanced governance strategies.

In advance of the conference, scientists have been working on a comprehensive survey designed to provide a portrait of nanotechnology governance across 27 economies from around the globe. Experts from industry, academia, government and non-governmental organizations gathered in Geneva in January for a workshop to develop strategies and to review the IRGC’s “Survey on Nanotechnology Governance.”

The report was authored by Mike Roco, a senior adviser for the National Science Foundation, a federal agency that funds research in the United States, and Emily Litten, nanotechnology project manager for IRGC, an independent foundation in Switzerland. The Swiss Federal Agency for Development and Cooperation, the U.S. Department of State and Swiss Reinsurance Co. (Swiss Re) funded the survey.

“Societal relationships and the governance of science may either accelerate or dampen the development of emerging technologies, in particular nanotechnology,” Roco said. “Nanotechnology operates at the first level of organization of atoms and molecules, so the implications of its development will be broader than in other emerging technologies, both positive and with potentially unexpected consequences. For this reason, nanotechnology has to be addressed in the cultural, economic and societal context.”

Governance of nanotechnology is in a race with development that has accelerated as applications such as nanocoatings become more sophisticated. Those applications may soon be leapfrogged by second-generation “active nanostructures,” such as nanobiotech assemblies, according to Roco.

“In the last two or three years, industry has entered nanotechnology in a significant way,” Roco said. “It has become a subject of international competition and the public is a lot more aware of its development.”

The Roco-Litten report targets deficits in nanotechnology governance. Its recommendations fall into four categories of risk research, stakeholder engagement, risk communication, and governance approaches.

Should a “supranational” governance policy for nanotech products – one that involves a number of nations – be adopted by the IRGC, it would have to overcome traditional cultural differences to R&D in the U.S. and Europe. The U.S. operates on a “risk assessment” model that assumes all risks cannot be known in advance; Europe is more likely to embrace a “principle of precaution” approach that seeks to discover all the consequences of nanotechnology prior to its widespread use.

Prior to the IRGC’s July meeting, Roco said, the group hopes to arrive at a consensus on the types of governance applicable to each stakeholder group and issue final recommendations by the fall of 2006. Though an international scheme of governance is destined to encounter nationalist, competitive appetites for nanotech development, a U.S.-based environmentalist said she believes it’s worth the effort. “Markets respond to demand, but they also respond to rejection,” said Jennifer Sass, senior scientist in health and environmental programs with Natural Resources Defense Council in Washington, D.C. “Good governance approaches are consistent with good marketing and business strategies. It’s essential they go hand in hand.”

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Four focus areas for recommendations

• Risk research recommendations include advancing studies of hazard, exposure and risk of nanoproducts; requiring input on the environmental, health and safety impacts to research and development projects; developing specific plans for environmental impact, chemical toxicity and pollution control; and “green” design and manufacturing, among others.
• Recommended stakeholder engagements include regular workshops; social scientist participation at the R&D level; and international dialogue between ethical advisory committees.
• Communication of risk recommendations seek a balanced disclosure of positive and negative evidence; encouragement of independent sources of information; communication of secondary unanticipated consequences; and periodical re-evaluation of risk to be disseminated to the public.
• Governance approaches include a “supranational body” to supervise international rules; a role for the United Nations in resolving conflicting national policies; self-regulation through voluntary peer review of decision making processes; government labeling of nano-related products; and national, international and supranational cohesiveness on regulatory schemes, definitions and nomenclatures, best practices, common assessment policies and testing periods.

Toshiba unveils MEMS tool for biotech use

TOKYO – Toshiba Corp. has developed a MEMS-based technology for injecting nanoparticles in cells. The technology is said to have advantages over conventional techniques that use laser beams, including the ability to simultaneously manipulate numerous cells.

The MEMS component produces subtle vibrations that cause nanoparticles in a liquid to adhere to cell surfaces. Continuous vibration gets converted to thermal energy that affects cell surfaces, resulting in injection of nanoparticles into the cells.

Toshiba has fabricated a nanoparticle manipulator with a water-repellent MEMS-based diaphragm. It tested the technology by placing a water droplet containing yeast cells and nanoparticles on a vibrating diaphragm. Vibrations caused the nanoparticles to adhere to cells, and once immobile, heat up, affecting the cell surface.Click here to enlarge image

Toshiba said it expected applications to include medical analytical tools for studying and manipulating cells. The company unveiled the technology at the 2005 IEEE International Electron Devices Meeting in December in Washington, D.C.

300 volunteers in Pacific Northwest to test energy-monitoring technology

RICHLAND, Wash. – About 300 volunteers on Washington’s Olympic Peninsula, in Yakima, Wash., and in Gresham, Ore., will test equipment that is expected to make the electrical grid more reliable while offsetting huge investments in new transmission and distribution equipment.

Pacific Northwest National Laboratory said that it launched a regional initiative in January to test and speed adoption of GridWise, its collection of smart technologies designed to make the power grid more resilient and efficient. GridWise uses miniaturized sensors, software and advanced analytical tools to monitor energy use in home appliances. The technology can sense when the grid is being strained, and shut down appliances to avoid outages.

The year-long study is funded primarily by the Department of Energy. Utilities, appliance manufacturers and technology companies also are supporting the effort to demonstrate the devices and assess the resulting consumer response.

Gold nanoparticles show potential for Alzheimer’s treatment

SANTIAGO, Chile and BARCELONA, Spain – Chemists at the University of Chile in Santiago and the University of Barcelona in Spain have identified a new approach for the possible treatment of Alzheimer’s disease that they say has the potential to destroy beta-amyloid fibrils and plaque, which are hypothesized to contribute to the mental decline of Alzheimer’s patients. The researchers say the new technique could halt or slow the disease’s progress without harming healthy brain cells.

Using test tube studies, the scientists attached gold nanoparticles to a group of beta-amyloid fibrils, incubated the resulting mixture for several days and then exposed it to weak microwave fields for several hours. The energy levels of the fields were six times smaller than that of conventional cell phones and unlikely to harm healthy cells, the researchers said.

The fibrils dissolved and remained dissolved for at least one week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers. The research appeared in the Jan. 11 issue of Nano Letters.

UCLA-Bologna team’s nanomotor relies on sunlight for power

LOS ANGELES and BOLOGNA, Italy – Chemists at Italy’s University of Bologna, University of California, Los Angeles, and the California NanoSystems Institute have designed and constructed a nanomotor that does not consume fuels. Instead, their nanomotor is powered only by sunlight.

The nanomotor is a multi-component molecular-scale system called rotaxane, a mechanically interlocked molecule consisting of one or more rings trapped on a rod by bulky stoppers at either end. It was designed, assembled and run by the research groups at UCLA and the University of Bologna.

The nanomotor system operates in a fashion that is analogous to a four-stroke engine: light excitation and subsequent transfers of an electron (“combustion”); displacement of the ring along the rod (“piston displacement”); removal of the electron (“exhaust removal”); and relocation of the piston. A full cycle is carried out in less than one-thousandth of a second. Image courtesy of UCLAClick here to enlarge image

It works continuously without any external interference, and operates without consuming or generating chemical fuels or waste, said Fraser Stoddart, UCLA’s Fred Kavli Professor of NanoSystems Sciences and the director of the institute. The research was published Jan. 31 in Proceedings of the National Academy of Sciences.

Nanomix, Pitt use detectors to spot gene mutations linked to diseases

PITTSBURGH and EMERYVILLE, Calif. – Researchers at the University of Pittsburgh and at sensor maker Nanomix have developed devices made of carbon nanotubes that can find mutations in genes causing hereditary diseases. The researchers used nanotubes’ electrical properties to find a particular mutation in the gene that causes hereditary hemochromatosis, a disease in which too much iron accumulates in body tissues.

“The size compatibility between the detector and the detected species – DNA molecules in this case – makes this approach very attractive for further development of label-free electronic methods,” said Alexander Star, an assistant professor of chemistry at Pitt.

Label-free electronic detection of DNA has several advantages over state-of-the-art optical techniques, including cost, time, and simplicity, they said. They reported their findings in the Jan. 16 issue of Proceedings of the National Academy of Science.

DNA self-assembling properties used to mass-produce nanostructures

DURHAM, N.C. – Duke University scientists have used the self-assembling properties of DNA to mass-produce nanometer-scale structures in the shape of grids on which patterns of molecules can be specified. They said the achievement represents a step toward mass-producing electronic or optical circuits at a scale 10 times smaller than the smallest circuits now being manufactured.

Instead of using silicon as the platform for tiny circuits, Duke researchers used DNA strands to create grids. The smallest features on these square DNA lattices are approximately 5 to 10 nanometers, according to the scientists, compared with about 65 nanometers in silicon circuits created using photolithography.

Duke University scientists demonstrated that they could mass-produce grids with infinitesimal patterns by making batches of trillions of separate grids showing the letters “D,” “N” and “A.” Image courtesy of Duke UniversityClick here to enlarge image

To demonstrate their ability to mass-produce grids, the scientists created batches of trillions of separate grids with the letters “D,” “N” and “A” written with a protein that can be seen through atomic force microscopy. They were able to create the grids by using the binding properties of DNA to ensure that large numbers of DNA strands would assemble themselves in specified patterns. Their work appeared in the Jan. 23 issue of Angewandte Chemie.

Nanoparticle catalyst offers cleaner manufacturing method

BETHLEHEM, Pa. and CARDIFF, Wales – Materials scientists in the United States and chemists in Wales have uncovered secrets of the “nanoworld” that promise to lead to cleaner methods of producing, among other things, flavorings and perfumes. The researchers reported their results Jan. 20 in the journal Science.

Christopher Kiely of Lehigh University in Pennsylvania determined the structure of a type of gold-palladium nanoparticle, which is the active component of a new environmentally friendly catalyst that promotes the oxidation of primary alcohols to aldehydes. The catalyst system was developed by a group headed by Graham Hutchings at Cardiff University in Wales.

The chemical, pharmaceutical and perfume industries rely on expensive and environmentally harsh oxidation reactions to manufacture products such as vanilla. The new catalyst, consisting of gold-palladium nanoparticles dispersed on a titanium oxide support, allows this reaction to take place using oxygen under mild solvent-free conditions.

Studies fail to include basics for assessing toxicity

By Candace Stuart

Vicki Colvin has a question for colleagues who study nanoparticles and how they may affect people and the environment. “Exactly what do you mean by size?”

When chemists, toxicologists or other researchers report the dimensions of an engineered nanoparticle, are they measuring the core, the core plus a coating, or perhaps the core, a coating and attachments that help nanoparticles adhere to cells? What happens after exposure to water, or to blood?

“We want to know how particle size changes as it marches through the body,” Colvin said at a workshop designed to identify roadblocks to nanobiotech commercialization. Size, composition, shape and other characteristics help distinguish the scores of different engineered nanoparticles that exist today. They also help determine their wanted – and unwanted – properties. “Can I take a material that is active (potentially harmful) and make it safe?” she asked. “How can I engineer a safe nanoparticle?”

Colvin, a chemistry and chemical engineering professor and director of the Center for Biological and Environmental Nanotechnology at Rice University, is not alone in her quest. The federal agencies that may decide to impose environmental, health and workplace regulations on industry face a mishmash of toxicological data that often lacks basic information about nanoparticle size, surface area and other characteristics.

Rice University researchers Vicki Colvin and Mark Wiesner explore the two sides of nanotechnology: its use for remediation as well as its possible toxic effects. Photo by George CraigClick here to enlarge image

Toxicologists and other scientists studying nanomaterials say these gaps make it difficult if not impossible to compare studies and get an accurate picture of how nanoparticles interact with the body.

Reporting basics like size will go a long way toward ensuring that regulations are based on sound rather than spotty science, they say. Scientists will be able to see the relationships between a nanoparticle’s size or surface area or charge, for instance, and how it behaves in the body to predict which traits could be harmful. That knowledge may help them design benign nanoparticles.

“It was kind of where dioxins and PCBs were in the ’60s,” said Nigel Walker, a staff scientist with the National Toxicology Program (NTP) of his initiation into nanotechnology about three years ago. NTP, part of the National Institutes of Health’s environmental sciences division, has launched a program to evaluate potential health hazards of nanomaterials. Dioxins, a byproduct of combustion processes, and polychlorinated biphenyls, an industrial chemical, were found to be cancer-causing pollutants that required costly cleanups once their toxicity was discovered.

“We introduced a technology without understanding the implications and then spent 30 years trying to eliminate or reduce the risk,” Walker said. He recognized that with nanotechnology he and other scientists had an opportunity to spot troublesome nanoparticles early in the commercial process, before they cause damage. “Now we can make sure we can prevent that. We can choose the kinds of experiments that reduce the risk. We can be at the forefront.”

Their size makes nanoparticles promising candidates for medical applications. They are small enough to fit within cells and also can roam undetected by biological sentries such as the blood-brain barrier or the liver, according to Scott McNeil, director of the National Cancer Institute’s Nanotechnology Characterization Laboratory. As coordinator of pre-clinical characterization of nanomaterials, McNeil is helping the NCI in its goal of developing nano-based therapies and diagnostics for cancer.

His team has already begun tests on gold nanoparticles, liposomes, dendrimers and buckyballs. Each nanoparticle offers benefits: Branch-shaped dendrimers and spherical liposomes can transport drugs into cells. Contrast agents can be put in the hollow centers of buckyballs for tumor imaging. Gold particles known as nanoshells can attach to cancer cells, and when exposed to harmless near ultraviolet light, heat up and kill the cells.

Preliminary research on gold nanoparticles suggests that nanoparticles grow larger in the presence of plasma. Researchers consider the results a trend until their studies undergo further review. Image courtesy of the Nanotechnology Characterization LaboratoryClick here to enlarge image

“These can leach into tumors because they are smaller than the pores of the blood vessel wall,” McNeil said. Nanoparticles are also smaller than the filter mechanisms in the spleen and liver that capture and eliminate other foreign matter. That leaves nanoparticles free to circulate until they find their cancer target.

Nanoparticles pose a risk, though, if they are or become toxic and the body’s defense systems can’t detect and eliminate them, McNeil and Walker pointed out. For medical applications – where tissue is deliberately exposed to nanoparticles – it is critical to understand how cells react to the presence of various types and forms of nanoparticles during various stages of exposure. Unintended exposure through the skin, lungs and other pathways also needs to be considered.

“Size will be a critical component for toxicology,” Walker said. Studies on ultrafine particles, which are typically a byproduct of combustion, suggest a link between particle size and toxicity, for instance. “But size is contextual. How do you report size? What kind of methodology do you use? What is the tool?”

The Nanotechnology Characterization Laboratory is collaborating with the Food and Drug Administration and the National Institute of Standards and Technology to find methods for analyzing nanomaterials in various stages: before exposure to any biological environment, exposure in test tubes and other in vitro environments, and exposure within living organisms, or in vivo environments. They accept applications for materials from manufacturers on a quarterly basis, but will only take materials that can be produced in sufficient quantities.

“We don’t accept material for characterization unless they can produce a gram of material. We don’t want to have multiple industrial batches,” McNeil said. Batches can vary in purity, for instance. “We want to make sure we have the same stuff in the lab as in the animal.”

McNeil’s team follows a methodical system to plot the physical attributes of each type of nanoparticle. But nanoparticles rarely are used in their natural, or “naked,” form. Many nanomaterials that function in the dry world of chemistry need to be “dressed” to work in the wet world of biology. They also often have antibodies or other biomolecules attached to their surface that complement molecules on a cancer cell’s surface. The attachments help the nanoparticles latch onto target tumor cells.

“We attempt to have a baseline characterization so we can have some familiarity with that category of nanoparticle,” McNeil said. Each time it is dressed, or functionalized, it is studied again. “Each one would be unique in its behavior. Functionalizing it changes its properties.”

Designers can use the ability to alter properties in their favor. A nanoparticle’s surface charge can make it less biocompatible, for instance. Adding a coating that neutralizes charge may solve the problem, though. In what McNeil characterizes as a possible trend, his team noticed naked gold nanoparticles get larger when placed in plasma. To better understand gold nanoparticles’ blood-contact properties, they plan to add molecules that could stop proteins from absorbing on the surface. That also may be a way to keep the gold nanoparticles from growing larger.

The National Toxicology Program is studying buckyballs and carbon nanotubes, semiconductor nanocrystals called quantum dots and metal oxides such as the sunscreen ingredient titanium dioxide. It is developing a program based on dendrimers, too. NTP, which agreed to take on the initiative at Colvin’s request, allocated between $1.5 million and $2 million in the past year for the program, Walker said.

Veeco’s BioScope II allows scientists to image molecular features within living systems. Photo courtesy of Veeco InstrumentsClick here to enlarge image

Walker said the NTP is more or less starting from scratch after scouring the toxicology literature and finding it lacking. But accurately measuring nanoparticles in their various states may prove difficult. Microscopy tools for measuring an electron-dense nanoparticle may not be as suitable for gauging less electron-dense coatings or attachments. Tools using probes may compress flexible structures.

Craig Prater, a fellow at Veeco Instruments who has been integral in the commercialization of several of its microscopy products, said today’s tools can adequately measure nanoparticle size, even in the wet world of biology. Prater helped launch Veeco’s nanobio atomic force microscope, the BioScope. The BioScope II, introduced in December, can be used to image molecules within living cells.

He’s also involved in a project with Dow Chemical Co. to develop ways to better understand nanoparticles’ structure-function relationships. The goal of the Veeco-Dow partnership is to provide a predictive mechanism that will allow manufacturers to efficiently design nanoparticles that perform exactly as desired.

“If we can understand the structure-function and surface chemistry connection to toxicity, that will help us accelerate the design of consistently safe nanoparticles,” Prater said. “All of the chemical companies and scientists take that responsibility seriously.”

But reliable predictions depend on sound data, and scientists like Walker, McNeil and Colvin warn that, for the most part, good fundamental information is not available now. The haphazard reporting of basic characteristics like size threatens to hamper commercialization. “We need to do a better job of describing material,” Walker said. “This will be a roadblock.”

In an effort to get consistency in nanoparticle reporting, Walker contacted funding agencies and editors of key scientific journals and asked that grants or acceptance of a paper be contingent on reporting basic information such as size and methodology. Colvin has been prodding the academic research community to agree to some accepted norms. McNeil hopes to develop voluntary standards for industries and toxicologists based on a consensus process.

It’s the chance to avoid another dioxin or PCB incident.

“If we could provide the structure-activity tools,” Walker said, “then we could say (to nanoparticle designers), ‘You really don’t want to go there with this one.’ They could make an informed decision. The further we can get to providing that assessment upfront, the better it will be for everybody.”

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Online sources of information

everal organizations offer searchable databases and inventories on nanoparticles and their health and environmental implications. Here are a few:

International Council on Nanotechnology
http://icon.rice.edu/research.cfm

U.S. National Institute for Occupational Health and Safety
http://www2a.cdc.gov/niosh-nil/index.asp

European Union’s NanoSafe project
http://www.nanosafe.org/

Wilson Center’s Project on Emerging Nanotechnologies
http://www.nanotechproject.com/index.php?id=18

On Jan. 19, a mix of industrial, government and academic researchers and officials gathered on the campus of Rice University in Houston to discuss one of the stumbling blocks facing nanobiotechnology. The participants joined forces at the one-day workshop to identify gaps in the nation’s measurement system that impede innovation, and to suggest potential solutions.

The National Institute for Standards and Technology organized the workshop as part of a nationwide assessment. NIST was on a mission to address unmet or emerging needs for new or better tools and services that could give the United States a competitive edge. As part of the Department of Commerce, NIST is expected to drive technological innovation and economic growth in the nation.

“We hope this will serve as a catalyst for action,” said James Whetstone, chief of NIST’s Process Measurement Division, as he encouraged participants to help the agency prioritize key innovations and pinpoint barriers.

NIST has overseen about a dozen workshops focusing on topics like nanotechnology, photonics and biotechnology – all broad-based technologies that could create significant economic gains and contribute to national needs. Fact-gathering workshops will continue into at least March. NIST will compile its findings and produce a report by mid-June.
– Candace Stuart

Dear Small Times:

After reading Patti Glaza’s column, “Oh Canada! Sing your praises for your nanotech successes” (Small Times Magazine, January/February 2006) I came away disappointed. I met with Ms. Glaza on her recent tour of Canadian nanotech companies. In fact, we spent an hour and half together over a private lunch arranged a month in advance by a Canadian trade organization.

I arranged my air travel for this meeting, representing our company, the province, and to ensure that Small Times would have a clear understanding of what Canada’s “rising nano stars are doing to promote their success.” Indeed, to gain this understanding is why Small Times attended this event in the first place. So, you can imagine my surprise when I read the assertion that Canada is doing nothing to promote its nanotech success, especially when Small Times just attended an event to promote that very subject!

So what’s happening here? After reviewing the Small Times Web site, I discovered that since 2001, Small Times posted, or reported on, a total of three press releases issued by Micromem Technologies. But since 2004, Micromem has issued over 25 press releases – all sent to Small Times as well as other media outlets.

I believe that the press has a responsibility to report the news. My conclusion is that Small Times is either ignoring that responsibility, or doing a very poor job of it.

Sincerely,
Cynthia Kuper
Micromem Technologies
Toronto, Ontario

I suspect no one in the nanotech community is thanking disgraced stem cell researcher Hwang Woo Suk for duping the world about his breakthroughs in cloning. But maybe we should.

The journal Science retracted two papers in January submitted by Hwang and his collaborators at Seoul National University in South Korea and the University of Pittsburgh after discovering that the evidence had been faked. In the first paper, published in February 2004, he claimed to have cloned human embryos. Sixteen months later he reported that he developed a more efficient method for creating new lines of human embryonic stem cells. A whistle-blower blew his cover.

The potential for therapeutic cloning and stem cell-based approaches to overcome diseases such as diabetes or conditions such as paralysis tantalizes researchers with dreams of glory. Hwang gained star status in his native Korea, where he was deemed a candidate for a Nobel Prize. The government issued a stamp in his honor, and gave $43.35 million in the past decade for his research, Reuters reported in February.

Lots of promise. Lots of hype. Lots of temptation and potential for fraud. Sound familiar?

Nanotechnology had a lesser fall from grace in late 2002 when it was discovered that Bell Labs’ physicist Jan Hendrik Schon had fabricated data in molecular electronics studies. Eight papers that appeared in Science in 2000 and 2001 were retracted. The fraud was discovered when his work was proven irreproducible.

The stakes are higher now. Nanotechnology’s profile has been raised with bona fide advancements in cancer therapies, fuel and solar cells, advanced materials and even golf balls. Concerns about its possible toxicological and environmental effects are now part of the public discourse.

The large amounts of federal funding for nano in not only the U.S., Europe and Japan but also in China, Korea and elsewhere have stoked competition among nations. Many countries bet that nanotech, like stem cell research, will lead to huge economic gains as well as social good. The pressure to succeed is great. The mechanisms to ensure honesty and integrity are challenged.

“I have pointed out in the past that even unusually rigorous peer review of the kind we undertook in this case may fail to detect fraud,” said Donald Kennedy, Science’s editor-in-chief, as he announced the retraction of Hwang’s work. Nanotechnology is likely to prove equally difficult to police because of its interdisciplinary nature and novelty.

Since Kennedy’s announcement, Science has implemented a screening test that detects whether images submitted by researchers have been altered. It’s a start. Better yet, maybe Hwang’s professional nose dive will serve as a wakeup call to researchers, their institutions and the governments and corporations that fund them to keep ambitions in line – so concocted results never cross the desk of a journal editor to begin with.

One way to prevent fraud is to reward honesty. Providing sound research on the toxicology of nanoparticles motivates some of the scientists who have taken on the task, as shown in our special report. They recognize that by understanding nanoparticles’ properties, designers can engineer around potential problems. There’s personal satisfaction, if not always glory, in such an approach.

Rewards can be monetary, too. Few people can afford to devote their lives to micro and nanotechnology without receiving compensation in return. Who and how much? We unveil our first salary survey in this issue, based on responses from more than 800 salaried workers.

Candace Stuart is editor-in-chief at Small Times. She can be reached at [email protected].