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Tiny Bit Of Caution

A Look At The Potential Hazards Of Nanotechnology

Let's talk about nano. And I don't just mean Apple's svelte little music player, although that is a piece of it. I mean the whole nanotech revolution going on across the world. Nanotechnology is helping to create everything from advanced computer chips to stain-resistant pants. Already we are rapidly fulfilling Sir Arthur Clarke's third law that "any sufficiently advanced technology is indistinguishable from magic.” But as society revels in nanotech's magical powers, we need to keep our heads about us and use them to avoid the potential dark sides of this new alchemy.

"Nano” is a prefix, meaning it's a word-piece that we can stick in front of other words to make them longer and more complicated. Of course it also makes them more specific. A nanometer, for instance, is one billionth of a meter, a size considered by most scientists to be really, really small. So fastening "nano” to the front of "technology” or "particle” means we are talking about them on this incredibly tiny scale, usually less than 100 nanometers in size. For comparison, a sheet of paper is about 100,000 nanometers thick. Your hair could be 50,000 to 180,000 nanometers thick if you are a brunette or as thin as 15,000 to 50,000 nanometers if you are blond, still far too big to be considered close to nano-scale.

Some better if more abstract comparisons: a chain of ten carbon atoms is about one nanometer long and the spiral shape of a DNA strand is two nanometers wide. This is the size that we now manufacture, manipulate, and control with nanotechnology. Because the size is so small, because the changes affected by nanotechnology are so precise and fundamental, the potential effects can be staggering.

"Nanotechnology is the base technology of an industrial revolution in the 21st century," Michiharu Nakamura, Executive VP of Hitachi, explains to Nanotechnology Now. Stan Williams, Director of Quantum Science Research at HP Labs and nanotech pioneer agrees, telling BusinessWeek, "Every industry that involves manufactured items will be impacted by nanotechnology research. Everything can be made in some way better—stronger, lighter, cheaper, easier to recycle—if it's engineered and manufactured at the nanometer scale."

In other words, now that we realize how powerful the "nano” prefix can be, we want to stick it in front of everything. Ten years ago we put it in front of manufacturing and built a really tiny guitar complete with 6 strumable strings, each 100 atoms wide. Although the very cool nanoguitar could play notes way beyond our hearing range, a cure for cancer it was not. It was a showpiece, a practice for better things to come and nanomanufacturing and nanofabrication have come a dramatic way since then. Today nanomaterials are used in our clothing, sunscreen, dental work, eyeglasses, cosmetics, water filters, and innumerable other specialized and everyday products. Three to four new nanotech products hit the marketplace every week.

The medical community is eager for their nano as well. "With nanotechnology we'll be able to build surgical tools that are molecular, both in their size and in their precision,” says Ralph Merkle, a nanomedicine researcher at Paolo Alto Research Center, in a House of Representatives subcommittee meeting. "For the first time we'll be able to intervene at the scale where the damage actually occurs and to reverse that injury." Researchers are already testing nanotherapies for diseases, and using nanoparticles to deliver drugs and target cancers. Like the shrinking submarine injected into a patient in the 1966 film Fantastic Voyage, scientists are even dreaming up injectible nanorobots to detect and treat diseases, repair cells, and connect nanocomputers for controlling nerves.

We've been joining all of these wonderful and fascinating nano- words and it's really exciting every time because the results are almost like magic. Except now a few people are realizing that we left one word out. We should have put together "nanotoxicology.”

The new field of nanotoxicology addresses the unique toxic effects of nanoparticles. Nanoparticles fall into one of three categories based on how they are made. First, there are naturally occurring nanoparticles - tiny specks typically produced in volcanic eruptions or atmospheric phenomena. Second, combustion derived nanoparticles such as diesel soot are produced by burning and released into the air. Finally, manufactured nanoparticles are the ones we make on purpose, usually with a core of carbon or metal-oxide and often coated with polymers that adjust their behavior. Carbon nanotubes are an emerging subtype of manufactured nanoparticles with unique properties due to their tubular shape.

But wait. Volcanic eruptions, smoke, and soot are on most people's list of bad-for-you things. So how could our miraculous manufactured nanoparticles be so similar? More importantly, if they are so similar, can manufactured nanoparticles also be bad for you? Of course they can. And to complicate things further still, nanoparticles can be toxic even when their larger counterparts are not.

There are different rules in effect when dealing in the extremely small world of nanotechnology. Gravity matters very little. Forces between atoms or molecules become extremely important and the weird science of quantum mechanics rules.

Materials at the nanoscale can have different properties compared to how we perceive them on a large scale. For instance, gold and platinum are inert on a large scale, leading to their use in many medical applications, but both can set off chemical reactions at a nanoscale. In shrinking to nanosize, copper becomes clear, aluminum can burn, and gold turns to liquid at room temperature. Really. These counterintuitive quantum effects contribute to some of the fascinating magical properties of nanotechnology and give rise to unique benefits never imagined at larger sizes. Or unique hazards never before expected.

The Greeks termed asbestos the "miracle mineral” because of its astonishing resistance to heat and its soft, workable properties. In and of itself, asbestos is not harmful as long as it's kept large and intact. But just like a dry board will release dust and splinters when it is broken, when asbestos is handled it releases a myriad of tiny needle-like shards into the air. These asbestos fibers can be as small as 10 nanometers across, allowing new interactions not possible on a large scale.

By the first century AD, the Greeks and Romans knew that slaves involved in weaving asbestos cloth often contracted a sickness in their lungs. For the last fifty years we have known that asbestos causes lung cancer. More recently, researchers sprinkled asbestos fibers onto human lung cells and through a powerful microscope videotaped one of the miniscule fibers as it drifted gently through a cell, bent slightly as its tip met some DNA, then flicked off a large chunk of DNA as it moved on. Even more often, the needle-like fibers tangled in cells' machinery, fouling proper cell division. Damage like this will usually either kill a cell or push it towards becoming cancer. Such physical interactions with DNA would be impossible at any size but nanoscale. Simply put, an asbestos fiber is dangerous because it's so small.

Carbon nanotubes are arguably one of the most fascinating nanostructures developed. They are the strongest and stiffest substance on earth, making material scientists and nanoengineers giddy with possibilities. The quantum mechanical properties of carbon nanotubes give them unique electrical conduction properties that current computer chips can only dream of. Their versatile structure also allows drugs to be attached to the outside, hidden inside the tube, or trailed behind the tube, propelling them to the forefront of the drug delivery field, especially for cancer treatment.

But let's also remember that a carbon nanotube is roughly the same size and shape as an asbestos fiber. What implications could that have when injecting nanotubes into people? Results from various scientific studies on cells have been confusing the experts. Some reports indicate nanotubes to be highly toxic while others show no problems at all.

Although nanotubes were first discovered in 1952, the first pilot studies of nanotube toxicity in living animals have just come out this year. While the first few mice don't show any drastic problems, there haven't been enough mice studied to make solid conclusions about more general health effects. These studies are also so new the mice have only been watched for a few months. For comparison, it can take victims exposed to asbestos over twenty years to develop lung cancer. In contrast to these first mouse reports, recent and prominent study from the University of Edinburgh found that carbon nanotubes have "asbestos-like” toxicity and cause inflammation and lesions when implanted in a mouse's abdomen.

Mouse test results also disagree on details such as how long the nanotubes stay in the body and what organs they collect in. These disagreements are not surprising since the research teams use different nanotube formulations at different times in different animals, and there is still no standard measure for nanotoxicology researchers to use when comparing their data.

Imagine one fisherman tells you he just caught the biggest fish of his life while another says he just caught a little fish and threw it back. So whose fish was really bigger? Only when we measure the fish can we see that the first angler caught a record-breaking 18 inch brook trout while the deep sea fisherman threw back a 4 foot long swordfish. In the same way, the nanotechnology industry needs a ruler. No one's hiding results, no one screwed up, but until there is a standard that everyone can agree on, nanotoxicologists will continue to produce contradictory and irreconcilable data.

"Without relevant data, innovators are forced to rely on ‘reasonable worst-case scenarios',” explains Jim Hutchison in a recent University of Oregon press release. According to Hutchinson, a U. Oregon nanotechnology researcher and proponent of "green chemistry” in nanotechnology, "The lack of information on material safety hinders innovation and places companies at considerable risk of failure.”

Hutchinson and other researchers across the country are now sounding the call to explore the environmental risks associated with the manufacture and use of nanotechnology products. For now, we can take comfort in knowing that our bodies and ecosystems have evolved to handle usual amounts of naturally occurring nanoparticles in our environment. Even manmade nanomaterials are unlikely to be harmful in low enough doses. But, like seemingly harmless snowflakes, we should not underestimate the powers of nanoparticles when they gang up. Already hundreds of tons of nanomaterials enter our environment annually and we know very little about their effects.

Because of their size, nanoparticles from industry or excreted by medical patients are likely to pass through our waste treatment facilities. In fact, nanoparticles are so small that they have almost no inside. As soon as you get through the front surface, you're already going out the back. This extremely high proportion of surface area permits chemical reactions that contribute to oxidative damage. Published reports suggest this allows nanomaterials to enter or kill bacteria critical in maintaining a normal ecosystem.

Once in the environment and in bacteria, it is unknown if they are passed up the food chain. Looking to larger creatures, some nanoparticles have proved toxic to aquatic invertebrates, especially filter-feeders. Researchers have found increased oxidative damage in the brains of fish living in water containing certain common nanoparticles. Although little is known about the effects of environmental nanoparticles on humans, we do know that oxidative damage is implicated in several diseases including atherosclerosis, Parkinson's disease, Alzheimer's disease, and cancer.

The emerging theme from nanotoxicology studies is our amazing lack of knowledge on the subject. As we saw with studies in cells and mice, for each study warning of the possible environmental hazards there is another suggesting that nanoparticles really aren't that bad. Here's the problem: Nanotoxicology is so new and under-funded that no one has set up industry standards to use when comparing results. In 2006, only $39 million of the NIH's $1.05 billion dollars in nanotech funding went to investigate toxic effects. With this dramatic funding discrepancy, and without a reliable ruler, it's not surprising that most analysts have to simply conclude that "further study is needed.” We can't afford to continue this trend.

Nanotech is now only in its infancy as companies and countries are rallying to expand the industry faster. At a 2004 luncheon for the National Nanotechnology Initiative, U.S. Senator Ron Wyden (D-OR) expressed our country's commitment to nanotech. "Nanotechnology is going to change America on a scale equal to, if not greater than, the computer revolution. Harnessing the power of nanotechnology is one of the keys to ensuring that our nation continues to be an economic powerhouse in this new century." By 2014 an estimated $2.6 trillion worth of goods will incorporate nanotechnology. Like it or not, nanotech is going to be a huge piece of our lives, so we better make sure it's safe.

Personally, I'm thrilled by the nearly magical promise of the nanotech industry. I see the power in small and I believe that over time this power's contribution to our society will be life-changing. So the next question is: should we step on the gas or hit the brakes? Businesses and countries face clever and fierce competitors. They must innovate faster and produce more efficiently in order to survive. In the face of nanotech's many unknowns, I find myself wanting to yell, "Slow down!” Yet I don't believe these words are an accurate answer to our complicated problem. For instance, when I believe that nanotech has such tremendous potential in the treatment of cancer, how can I yell "Slow down” when there are still cancer patients waiting? Is slowing down even ethical?

Right now, nanotech's excitement lies in its wonderful possibilities while its danger lies in the unknown. So far, we have excelled in identifying good applications of nano's power, but are far behind in considering the negatives. The best way to balance this pairing is not to slow down searching the nanoworld for benefits, but to open our eyes and look around for the bad guys hiding there too. We first need to mentally step back from this dazzling fireworks show and acknowledge that real danger could exist. Because we don't understand everything, we can't predict everything.

The next essential step is to go back to middle school science class. The core of all science, the whole reason science works, is objective comparison against standards and controls. Scientists should carry a ruler. Nanotech and especially nanotoxicology researchers need to agree on a set of standards to combine and interpret their research.

Our governments, hospitals, corporations, and scientists are making a tremendous push to harness the power of the nanotech revolution. Every week we stick ‘nano' in front of something new, making it a bigger part of our lives. Finding the balance between wonder and watchfulness is the key. Since we know that new nanotechnology is inherently unpredictable, we have the responsibility to be vigilant as we wrap ourselves in its magic.

Chris Hubert is a graduate student in Molecular and Cellular Biology at the University of Washington.

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