"I sit before you today with very little hair on my head. It fell out a few weeks ago as a result of the chemotherapy I've been undergoing. Twenty years ago, without even this crude chemotherapy, I would already be dead. But 20 years from now, nanoscale missiles will target cancer cells in the human body and leave everything else blissfully alone. I may not live to see it. But I am confident it will happen." Richard Smalley spoke these words on Jun 22, 1999. He died of non-Hodgkin's lymphoma on October 28, 2005. The 62-year-old Nobel Prize-winning chemist was a nanotech pioneer.
A tsunami is unnoticeable in the open ocean—a long, low wave whose power becomes clear only when it reaches shore and breaks. Technological revolutions travel with the same stealth. Spotting the wave while it's still crossing the ocean is tricky, which explains why so few of us are aware of the one that's approaching. Nanotechnology has been around for two decades, but the first wave of applications is only now beginning to break. As it does, it will affect everything from the batteries we use to the pants we wear to the way we treat cancer.
The main thing to know about nanotechnology is that it's small. Really small. Nano, a prefix that means "dwarf" in Greek, is shorthand for nanometer, one-billionth of a meter: a distance so minute that comparing it to anything in the regular world is a bit of a joke. This comma, for instance, spans about half a million nanometers. To put it another way, a nanometer is the amount a man's beard grows in the time it takes him to lift a razor to his face.
Nanotechnology matters because familiar materials begin to develop odd properties when they're nanosize. Tear a piece of aluminum foil into tiny strips, and it will still behave like aluminum—even afer the strips have become so small that you need a microscope to see them. But keep chopping them smaller, and at some point—20 to 30 nanometers, in this case,—the pieces can explode. Not all nanosize materials change properties so usefully (there's talk of adding nano-aluminum to rocket fuel), but the fact that some do is a boon. With them, scientists can engineer a cornucopia of exotic new materials, such as plastic that conducts electricity and coatings that prevent iron from rusting. It's like you shrink a cat and keep shrinking it, and then at some point, all at once, it turns into a dog.
Substances behave magically at the nanoscale because that's where the essential properties of matter are determined. Arrange calcium carbonate molecules in a sawtooth pattern, for instance, and you get fragile, crumbly chalk. Stack the same molecules like bricks, and they help form the layers of the tough, iridescent shell of an abalone.
It's a tantalizing idea: creating a material with ideal properties by customizing its atomic structure. Scientists have already developed rarefied tools, such as the scanning tunneling microscope, capable of viewing and moving individual atoms via an exquisitely honed tip just one atom wide.
"Nano's going to be like the invention of plastic," says Paul Alivisatos, associate director of physical sciences at Lawrence Berkeley national Laboratory's new nanofabrication center. "It'll be everywhere: in the scalpels doctors use for surgery and in the fabrics we wear." Alivisatos already owns a pair of stain-resistant nanopants from the Gap, made from fibers treated with fluorinated nanopolymer. "I spilled coffee on them this morning, and it rolled right off."
On a table in a lab at Rice University, André Gobin, a graduate student, is working with two slices of raw chicken. He nudges the slices together so they touch and dribbles greenish liquid along the seam. The liquid is a solution of nanoshells: minuscule silica beads covered, in this case, with gold. Switching on an infrared laser, Gobin deftly traces the beam down the length of the green line. Tweezing the chicken up, he dangles what is now a single piece of meat.
Someday soon surgeons may be able to use a nanoshell treatment like this to reconnect veins that have been cut during surgery. "One of the hardest things a doctor has to do during a kidney or heart transplant is reattach cut arteries," says Gobin. "They have to sew the ends together with tiny stitches. Leaks are a big problem." With Gobin's nanoshell solution a surgeon could simply meld the two ends and get a perfect seal. It would make grafting veins as easy as soldering wire.
Although much of nanotechnology's promise remains unrealized, investment in the field is booming. The U.S. government allocated more than a billion dollars to nanotechnology research in 2005—more than twice what it spent on sequencing the human genome when that project was at its height. Japans and the European Union have spent similar amounts, and even smaller countries are hurrying to get a foot in the door. A Korean company has used nanosilver-based antibacterials in refrigerator interiors. The same material can be incorporated in bandages. The hopes is the same on all fronts: to get the jump on a growing global market that the National Science Foundation estimates will be worth a trillion dollars by 2015.
One reason for the rapid global spread of nanotechnology is that the entry cost is comparatively low. Countries that missed out on the computer revolution because they lacked the capital to build vast, high-tech factories that make silicon chips are less likely to miss the nanotech wave.
"It's science you can do in a beaker," says Stephen Empedocles, vice president of Nanosys, a company that's developing cheap solar nanostructures. Traditionally the manufacture of solar-energy cells has required a multimillion-dollar fabrication facility that cooks sheets of glass at extremely high temperatures until the atoms order themselves into a receptive latticework. Solar nanostructures, on the other hand, grow like rock candy. You can "mix them up in a beaker with a hundred dollars' worth of starter chemicals," Empedocles says, and then paint them on window glass to turn an entire building into a solar-energy generator. Or, they might be embedded in the plastic body of a cell phone or a laptop computer.
For a hundred dollars, in fact, anyone can buy nanoparticles—specifically a gram (.04 ounce) of carbon nanotubes—online. Place the order, and you'll receive a small ziplock bag of what looks like soot tucked inside a cardboard FedEx envelope along with some safety instructions. (They recommend gloves to keep the carbon slivers off the skin and a respirator to keep the tiny black specks from entering the lungs.)
There's not much you can do at home with a thimbleful of carbon nanotubes. But some of their mysteries are revealed in another Rice University lab, where Matteo Pasquali holds up a test tube containing a few dark threads so stiff that they seem to have been starched and ironed. These are fibers spun from carbon nanotubes—several billion of them—which, in theory, should be stronger than Kevlar, the material in bulletproof vests.
For now, however, the threads are only about as tough as the acrylic found in an ordinary sweater. The reason the threads are weak, Pasquali believes, is because some portion of the billion nanotubes bundled together have hidden breaks. A photo taken through a microscope shows fibers that look like pale gray hairs, some perfectly straight, others frayed and curling. "We have split ends," Pasquali says with a sigh. "We need a nanotube conditioner."
Carbon has proved a useful element in nanotechnology. One of the science's building blocks is a molecule that contains 60 carbon atoms arranged in a sphere. A molecule of C60 looks like the geodesic dome invented by Buckminster Fuller, thus its nickname: buckyball.
Richard Smalley and colleagues discovered the buckyball in 1985, and in 1996 Smalley and two others earned a Nobel Prize in chemistry for the deed. Until his recent death, Smalley was a bucky fanatic. He renovated his house, close to the Rice University campus in Houston, with a glass skylight shaped like half a buckyball, with precisely proportioned steel struts representing the bonds between atoms.
Smalley was openly proselytical about the merits of buckyballs and a particular fan of their relatives, carbon nanotubes. ("Fifty to a hundred times stronger than steel and one-sixth the weight!" he often pronounced as though reporting the achievements of a precocious child.)
Because of their light, stiff composition, merely sprinkling carbon nanotubes into epoxy strengthens the glue by more than 30 percent. The tubes have also begun turning up in high-end sporting equipment. They strengthen tennis rackets, mountain-bike handlebars, frames for racing bikes, and golf-club shafts. Carbon nantubes also show promise for use in transparent conductive films for displays on computers, cell phones, PDAs, and automatic teller machines.
Smalley was also an ardent advocate of nanotubes as a solution to the world's impending engery crisis. His plan was to replace old copper and aluminum power lines with wires spun from carbon nanotubes. Nanotubes can carry far more current than traditional metal wires—over a billion amps of current per square centimeter (0.16 square inches)—and, unlike metal wires, they lose very little of that energy as heat. In theory, the nanotube power lines would carry electricity over thousands of miles. Rather than relying on local coal-fired power plants, cities could use energy generated by giant solar farms in deserts or by wind farms off coasts. "This is the great getting-up morning of nano," Smally said. "If Mother Nature allows it, we could restring the electrical grid of the world."
Not everyone is so sure. Carbon nanotubes come in three types. They all conduct electricity, but only one does it especially well. And so far no one has come up with a way to make those nanotubes very long. Right now, the longest electricity-conducting nanotube in existence measures a fraction of an inch.
At the root of the problem is the fact that there are two ways to make nanoparticles: "top down," where a bulk material gets chopped down into nanosize bits, and "bottom up," where molecules grow under controlled conditions, as in crystals, and then snap together into particular configurations based on their charge and molecular chemistry.
Bottom-up constructions—which long carbon nanotubes would require—are where the real power of nano lies. But they're also far more complicated, subject to all the laws of bonding that limit the ways atoms and molecules can be arranged. Getting carbon to curl into a perfectly aligned tube rather than a thick, twisted scroll is exceedingly complex.
Scientists are still relatively ham-fisted when it comes to the finer points of bottom-up assembly, particularly compared with a far more prolific nanofactory: the human body.
The human body makes quick and constant work of assembling raw materials like calcium and keratin to create elaborate structures like bones and skin. Compared with the work a blood cell does, scientists are "pretty much inept," admits Jim Heath, a Caltech chemist who is developing nanoscale sensors capable of detecting and diagnosing cancers. "But we're learning. We've come a long way in the past two years."
Heath's goal is to identify cancers early, when they are still just a few thousand cells strong and far easier to treat. Unlike HIV or malaria, which produce unique antibodies identifiable from a simple blood test, cancers are difficult to spot. Nonetheless, they do leave what Heath calls a fingerprint: a change in the number and type of proteins that regularly circulate in the blood.
Determining which combination of proteins makes up the unique signature of a particular cancer is an ongoing project. "To diagnose one cancer reliably in early stages, we probably need to measure 20 or 25 different proteins," Heath says. "So to develop a test that would identify 20 different cancers, we'd need about 500 measurements. And we would want to be able to do that easily, with just a finger prick of blood."
Heath has already developed nanosize sensors called nanowires that can electronically detect a few protein molecules along with other biochemical markers that are early signs of cancer. Heath's strategy is to coat a collection of nanowires with different compounds, each of which binds to one particular marker. When the marker, which can be a protein, an antibody, or DNA, latches on, it changes the conductivity of the nanowire, creating a tiny but measurable alteration in current. Heath has combined tens of thousands of these sensors onto a single chip, which allows him to detect cancer-signifying molecules in blood while their concentration is still low. The chips also allow him to identify what types of cancer are present. Currently, heath reports, his chip can detect between 20 and 30 relevant biomolecules. He plans to begin using the chip to detect brain cancers this summer.
Richard Smalley was one scientist who followed Heath's progress carefully. Smalley's non-Hodgkin's lymphoma was a relatively slow-moving cancer, but even when he was in remission, between a hundred million and billion cancer cells circulated in his body (a number that doctors consider relatively low).
One of the advantages of treating cancer in an early stage is that the cells are less likely to have mutated and become resistant. Drug resistance is one of the trickiest things about cancer, which adapts so rapidly that medications can rarely keep up. "You don't want a killing mechanism to be fancy," Smalley said. It needs to be fast and thorough.
But targeting a brute-force treatment is difficult, says Jennifer West, a bioengineer who is treating tumors in mice using gold nanoshells. Difficult because things that kill cancer cells typically kill healthy cells as well. "That's what we'd like to avoid," West says, Her approach relies on the fact that tumors grow blood vessels so quickly to keep up with the rapidly multiplying tumor cells that they don't have time to knit tightly and instead leak like rusted pipes. West's gold nanoshells are about 120 nanometers in diameter—a cancer cell is 170 times bigger. So the nanoshells are minute enough to seep through the cracks in the tumor capillaries and become lodged in the tumor.
To kill the tumor, West activates the shells with infrared rays that pass harmlessly through the skin but heat the gold, killing the adjacent tumor cells. Because the cancer cells die, they don't develop the resistance that can plague drug-based cures.
Moreover, because the nanoshells lodge only in the tumor and are nontoxic unless activated by infrared light, West expects her treatment to be nearly side-effect free—particularly compared with treatments like chemotherapy and radiation. As part of the FDA approval process, West has injected mice with increasingly large doses of nanoshells. Not a single mouse has died. "We injected mice with increasingly large doses of nanoshells. Not a single mouse has died. "We haven't even been able to induce any adverse effects," she says with a shrug. "If we had injected these mice with the same amount of table salt, they would have keeled over long ago.
Unfortunately, the very thing that makes nanoshells such a promising therapy—their ability to move easily through the body and to interact with different cells—is a downside when it comes to the problem of nanoparticle pollution.
In 2004 Eva Oberdörster, a toxicologist at Sothern Methodist University in Dallas, reported that largemouth bass exposed to water containing buckyballs at a concentration of 500 parts per billion suffered brain damage. And people are similarly vulnerable. After exposing lab-grown human skin and liver cells to an even weaker solution—a mere 20 parts per billion—Rice University chemist Vicki Colvin found that fully half the exposed cells died.
Results like these are troubling, in part because of the rapidly growing number of products already on the market that contain nanoparticles. "With nanomaterials, it's not enough to look at the properties of the bulk material," Colvin warns. "Whether you're working with gold or lead, the toxicity will be hard to predict." There is some evidence, for example, that the nanoscale particles of titanium dioxide used in sunscreen, depending on the way they are nanosized, can produce high amounts of free radicals when exposed to sunlight. Free radicals can damage cells, making some more likely to turn cancerous.
Colvin's concern is that companies are currently optimizing their particles for processability rather than for human health. A recent study found that buckyballs could be made less toxic fairly easily—by attaching inert molecules known as hydroxyl groups. The more hydroxyl groups attached, the less dangerous the buckyballs became. For the most thoroughly coated, the safe exposure level went up by a factor of ten thousand.
But it's hard to get funding for this kind of research, Colvin says. "Funding managers want a sexy story at the end of the day. They want to be able to say that they're helping to cure cancer. It doesn't sound as glorious when your finding is that a certain particle you were hoping to use ought to have hydroxyl groups put on it in order to be safe."
Still, researchers are making important advances. They are finding new ways to use nanosize sensors in water purification systems that will filter everything from bacteria to industrial pollutants like arsenic. The key feature of the new filters is the fact that nanoparticles have a vast amount of surface area for their weight: One ounce (28.3 grams) of nanobeads, for instance, contains a staggering 300,000 square feet (27,871 square meters) of surface area. Because the chemical reactions that neutralize pollutants take place on the surface of the beads, the greater the available area, the more effective the filter.
The potential impact of nanofilters is substantial. Many regions in China have drinking water that contains dangerously high levels of arsenic and other industrial pollutants. Because of this, Colvin predicts that Asia will be a test bed for point-of-use water treatment systems that utilize nanoparticles to eliminate toxic chemicals. "Right now, nanoscale iron is a bit too expensive to be used to treat wastewater," she says. "But it's the best way to clean up concentrated arsenic, and I expect the cost will come down soon."
Because nanotech applications are so potentially useful, Colvin doesn't think research should be stopped, or even slowed. But she does think that a larger proportion of government money should be directed toward safety and related questions—like whether nanoparticles could accumulate undetected in the water and food chains.
Such safety issues are key, given the speed with which the nanotech tsunami is moving. Corporations will invest more than four billion dollars in nanotech this year alone, and a recent nanotech conference in Japan drew a crowd of 30,000.
Meanwhile, commercial applications continue to spread. Homeowners now have the option of installing windows manufactured by PPG Industries, a company that uses nanoscale particles of titanium dioxide to make glass that doesn't streak and never needs washing. Food companies have begun experimenting with nanopackaging that changes color when food spoils or contains bacteria like E. coli. The prefix has even trickled over into popular culture, where it's the advertising hit du jour, with GM hawking a "nano" Hummer, and Apple its iPod Nano digital music player.
"What's amazing is how quickly this is evolving," Colvin says. "Even ten years ago, a lot of these applications would have seemed pretty unrealistic."
The boom left Richard Smalley downright nostalgic: "Nano is a baby that's all growed up," he mused shortly before his death. Perhaps, but we've still got some interesting years ahead.