Inside nanotechnology’s little universe of big unknowns
Heather Millar
A PAIR OF SCIENTISTS, sporting white clean-suits complete with
helmets and face masks, approach a prefab agricultural greenhouse in a
clearing at Duke University’s Research Forest. Inside are two long rows
of wooden boxes the size of large horse troughs, which hold samples of
the natural world that surrounds them—the pine groves and rhododendron
thickets of North Carolina’s piedmont, which at this moment are alive
with bird song.
Looking a lot like the government bad guys in
E.T., the two
men cautiously hover over a row of boxes containing native sedges, water
grasses, and Zebra fish to spray a fine mist of silver nanoparticles
over them. Their goal: to investigate how the world inside the boxes is
altered by these essentially invisible and notoriously unpredictable
particles.
The researchers are part of a multidisciplinary coalition of
scientists from Duke, Stanford, Carnegie Mellon, Howard, Virginia Tech,
and the University of Kentucky, headquartered at Duke’s Center for the
Environmental Implications of NanoTechnology (CEINT), that represents
one of the most comprehensive efforts yet to measure how nanoparticles
affect ecosystems and biological systems.
So far the questions about whether nanoparticles are an environmental
risk outnumber the answers, which is why the Duke scientists take the
precaution of wearing clean-suits while dosing the boxes—no one’s sure
what exposure to a high concentration of nanoparticles might do. Among
the few things we
do know about them are that they sail past the blood-brain barrier and can harm the nervous systems of some animals.
The regulation of nanoparticles has been recommended for more than a
decade, but there’s no agreement on exactly how to do it. Meanwhile, the
lid has already been lifted on nanotechnology. The use of man-made
nanoparticles has spread into almost every area of our lives: food,
clothing, medicine, shampoo, toothpaste, sunscreen, and thousands of
other products.
Regulatory structures, both here and abroad, are completely
unprepared for this onslaught of nanoproducts, because nanoparticles
don’t fit into traditional regulatory categories. Additionally,
companies often shield details about them by labeling them
“proprietary”; they’re difficult to detect; we don’t have protocols for
judging their effects; and we haven’t even developed the right tools for
tracking them. If nanotechnology and its uses represent a frontier of
sorts, it’s not simply the Wild West—it’s the Chaotic, Undiscovered,
Uncontrollable West.
And yet, when I visit the boxes on a warm spring day filled with the
buzzing of dragonflies and the plaintive call of mourning doves, they
look perfectly benign and could easily be mistaken for a container
garden. But there are hints that more is going on: each “mesocosm” (a
middle ground between microcosm and macrocosm) is studded with probes
and sensors that continually transmit data to CEINT’s central computer.
As I instinctively squint my eyes to try and locate evidence of the
silver nanoparticles inside each box, I realize I might as well be
staring down at these research gardens from another arm of the galaxy.
The scale of these two worlds is so disparate that my senses are
destined to fail me.
AS WITH MANY THINGS that are invisible and difficult to understand—think
subatomic particles such as the Higgs boson, muons, gluons, or
quarks—any discussion of nanoparticles quickly shifts into the realm of
metaphor and analogy. People working in nanoscience seem to try to outdo
each other with folksy explanations: Looking for a nanoparticle is like
looking for a needle in the Grand Canyon when the canyon is filled with
straw. If a nanoparticle were the size of a football, an actual
football would be the size of New Zealand. A million nanoparticles could
squeeze onto the period at the end of this sentence.
But what is a nanoparticle? The very simplest explanation is that a
nanoparticle is a very small object. It can consist of any bit of
matter—carbon, silver, gold, titanium dioxide, pretty much anything you
can imagine—that exists on the scale of nanometers. One nanometer equals
one-billionth of a meter. A nanoparticle may range in size from one
nanometer to one hundred nanometers, although the upper boundary remains
a matter of debate among scientists.
Nanoparticles exist in nature, but they can also be manufactured. One
way is top-down: grinding up things that are big until they are really,
really small, an approach used in nanolithography for electronics. Or
you can make them from the bottom up, following instructions that read
like a chemistry textbook: mixing one chemical with another by pyrolysis
(heating a material in a partial vacuum), or with electrolysis (running
a current through a liquid), or by other means.
But what do they look like? Raju Badireddy, a postdoctoral
researcher, is happy to satisfy my curiosity. He greets me with a smile
at the door to one of CEINT’s basement labs and guides me around his
little domain. For much of his work, Badireddy uses a “dark field”
microscope that excludes certain wavelengths of light, reducing the
“noise” in the image to provide unparalleled clarity. Sensing my
anticipation, he doses a slide with silver nanoparticles similar to
those in the mesocosm boxes in the forest, and slips it under the lens.
As I look into the scope, it fairly takes my breath away. There are
so many dots of light that I’m reminded of staring up at the Milky Way
on a trip across the Tibetan Plateau years ago. Yet the silver dots
throb and undulate as if alive. Here and there, giant spheres of dust,
as large as Goodyear blimps, porpoise through the nanoparticles. I pull
back from the oculars, feeling as if I’ve intruded upon something
private. This world is so close—it’s even inside me—yet it looks so
other, so mysterious.
Scientists don’t really have a full theoretical foundation to explain
reality at this scale. But all agree that one of the most important
aspects of nanoparticles is that they are all surface. Consider a
conventional chemical process: When one element is reacting with
another, it’s really just the surface molecules that are involved in the
lock-and-key dance of classical chemistry. The vast majority of the
molecules remain interior, and stable. But there are many fewer
molecules in a nanoparticle, so most of the molecules are on the
outside, thus rendering nanoparticles more reactive.
Myriad surface imperfections cause randomness to dominate the nano
world. If you hit a billiard ball with a clean shot at the macro level,
you can have a good idea where it will go. But at the nano level, a
billiard ball might shoot straight up, or even reverse direction. These
bits of matter are hot to trot: ready to react, to bond, and to do so in
unpredictable ways.
This makes life at the nano scale more chaotic. For instance,
aluminum is used everywhere to make soda cans. But in nanopowder form,
aluminum explodes violently when it comes in contact with air. At the
macro level, gold is famously nonreactive. At the nano level, gold goes
the opposite way, becoming extremely reactive. Bulk carbon is soft. But
at the nano level, if you superheat it, the molecules bend into a tube
that is very strong and semiconductive. In the nano world, gravity fades
to the background, becoming less pronounced, the melting temperature of
materials changes, and colors shift. At 25 nanometers, spherical gold
nanoparticles are red; at 50 nanometers they are green; and at 100
nanometers they’re orange. Similarly, silver is blue at 40 nanometers
and yellow at 100 nanometers.
So chemistry and physics work differently if you’re a nanoparticle.
You’re not as small as an atom or a molecule, but you’re also not even
as big as a cell, so you’re definitely not of the macro world either.
You exist in an undiscovered country somewhere between the molecular and
the macroscopic. Here, the laws of the very small (quantum mechanics)
merge quirkily with the laws of the very large (classical physics). Some
say nanomaterials bring a third dimension to chemistry’s periodic
table, because at the nano scale, long-established rules and groupings
don’t necessarily hold up.
These peculiarities are the reason that nanoparticles have seeped
into so many commercial products. Researchers can take advantage of
these different rules, adding nanoparticles to manufactured goods to
give them desired qualities.
Scientists first realized that nanomaterials exhibit novel properties
in 1985, when researchers at Rice University in Houston fabricated a
Buckminsterfullerene, so named because the arrangement of sixty carbon
atoms resembles the geodesic domes popularized by architect Richard
Buckminster Fuller. These “Buckyballs” resist heat and act as
superconductors. Then, in 1991, a researcher at the Japanese technology
company NEC discovered the carbon nanotube, which confers great strength
without adding weight. Novel nano materials have been reported at a
feverish pace ever since.
With these engineered nanoparticles—not even getting into the more
complex nanomachines on the horizon—we can deliver drugs to specific
cells, “cloak” objects to make them less visible, make solar cells more
efficient, and manufacture flexible electronics like e-paper.
In the household realm, nanosilica makes house paints and clothing
stain resistant; nanozinc and nano–titanium dioxide make sunscreen, acne
lotions, and cleansers transparent and more readily absorbed; and
nanosilicon makes computer components and cell phones ever smaller and
more powerful. Various proprietary nanoparticles have been mixed into
volumizing shampoos, whitening toothpastes, scratch-resistant car paint,
fabric softeners, and bricks that resist moss and fungus.
A recent report from an American Chemical Society journal claims that
nano–titanium dioxide (a thickener and whitener in larger amounts) is
now found in eighty-nine popular food products. These include: M&Ms
and Mentos, Dentyne and Trident chewing gums, Nestlé coffee creamers,
various flavors of Pop-Tarts, Kool-Aid, and Jell-O pudding, and Betty
Crocker cake frostings. According to a market report, in 2010 the world
produced 50,000 tons of nano–titanium dioxide; by 2015, it’s expected to
grow to more than 200,000 tons.
AT FIRST some in the scientific community didn’t think that the unknown
environmental effects of nanotechnology merited CEINT’s research. “The
common view was that it was premature,” says CEINT’s director, Mark
Wiesner. “My point was that that’s the whole point. But looking at risk
is never as sexy as looking at the applications, so it took some time to
convince my colleagues.”
Wiesner’s team at CEINT chose to study silver nanoparticles first
because they are already commonly added to many consumer products for
their germ-killing properties. You can find nanosilver in socks, wound
dressings, doorknobs, sheets, cutting boards, baby mugs, plush toys—even
condoms. How common is the application of nanoparticles? It varies, but
when it comes to socks, for example, hospitals now have to be cautious
that the nanosilver in a patient’s footwear doesn’t upset their MRI
(magnetic resonance imaging) machines.
Wiesner and his colleagues spent several months designing the
experiments that will help them outline some general ecological
principles of the unique nanoverse. He knew they wanted to test the
particles in a system, but a full-scale ecosystem would be too big, too
unmanageable, so they had to find a way to container-ize nature. They
considered all sorts of receptacles: kiddie pools (too flimsy), simple
holes in the ground (too dirty, too difficult to harvest for analysis),
concrete boxes (crack in winter). Finally, they settled upon wooden
boxes lined with nonreactive, industrial rubber: cheap to build, easy to
reuse, and convenient to harvest.
They built thirty boxes and a greenhouse to hold them. The large
number would make it easier to replicate experiments, and to answer the
spectrum of questions being posed by CEINT’s interdisciplinary team. The
ecologists were interested in community diversity and how the biomass
shifts over time. The biologists wanted to know whether the
nanoparticles become concentrated as they move up the food chain. The
toxicologists wanted to track where the particles went and how fast they
got there. The chemists wanted to know about reactivity.
Whatever the goal of the experiment it houses, each mesocosm features
a slanted board upon which a terrestrial ecosystem slowly gives way to
an aquatic one. It’s a lot more complicated than a test tube in a lab,
but it remains an approximation. The team had hoped to run streams
through the mesocosms, but the computing power and monitoring vigilance
necessary to track nanoparticles in the streams proved prohibitive.
In 2011, the team dosed the boxes with two kinds of nanosilver made
on campus: one coated in PVP, a binder used in many medicines, and the
other coated in gum arabic, a binder used in numerous products,
including gummi candies and cosmetics. Both coatings help to stabilize
the nanosilver. In some boxes, the researchers let the silver leach
slowly into the box. In other boxes, they delivered the silver in one
big pulse. In some, they introduced the silver into the terrestrial part
of the box; in others, they put the silver into the water.
Then the researchers watched and waited.
READING THROUGH DESCRIPTIONS of nanoparticle applications can make a
person almost giddy. It all sounds mostly great. And the toxicology
maxim “Dose makes the poison” leads many biologists to be skeptical of
the dangers nanoparticles might pose. After all, nanoparticles are
pretty darn small.
Yet size seems to be a double-edged sword in the nanoverse. Because
nanoparticles are so small, they can slip past the body’s various
barriers: skin, the blood-brain barrier, the lining of the gut and
airways. Once inside, these tiny particles can bind to many things. They
seem to build up over time, especially in the brain. Some cause
inflammation and cell damage. Preliminary research shows this can harm
the organs of lab animals, though the results of some of these studies
are a matter of debate.
Some published research has shown that inhaled nanoparticles actually
become more toxic as they get smaller. Nano–titanium dioxide, one of
the most commonly used nanoparticles (Pop-Tarts, sunblock), has been
shown to damage DNA in animals and prematurely corrode metals. Carbon
nanotubes seem to penetrate lungs even more deeply than asbestos.
What little we know about the environmental effects of
nanoparticles—and it isn’t very much—also raises some red flags.
Nanoparticles from consumer products have been found in sewage
wastewater, where they can inhibit bacteria that help break down the
waste. They’ve been found to accumulate in plants and stunt their
growth. Another study has shown that gold nanoparticles become more
concentrated as they move up the food chain from plants to herbivores.
“My suspicion, based on the limited amount of work that’s been done,
is that nanoparticles are way less toxic than DDT,” says Richard Di
Giulio, an environmental toxicologist on the CEINT team. “But what’s
scary about nanoparticles is that we’re producing products with new
nanomaterials far ahead of our ability to assess them.”
As a society, we’ve been here before—releasing a “miracle technology”
before its potential health and environmental ramifications are
understood, let alone investigated. Remember how DDT was going to stamp
out malaria and typhus and revolutionize agriculture? How asbestos was
going to make buildings fireproof? How bisphenol A (BPA) would make
plastics clear and nearly shatterproof? How methyl tertiary-butyl ether
(MTBE) would make gasoline burn cleanly? How polychlorinated biphenyls
(PCBs) were going to make electrical networks safer? How genetically
modified organisms (GMOs) were going to end hunger?
The CEINT scientists are trying to develop a library that catalogues
all the different kinds of engineered nanoparticles. They’re designing
methods for assessing potential hazards, devising ways to evaluate the
impact nanoparticles have on both terrestrial and aquatic ecosystems,
and creating protocols that will help shape environmental policy
decisions about nanoparticles.
Wiesner says the boxes in the forest provide “ground truth” for
experiments in the lab. Sometimes, he says, environmental research leads
to generalizations that become so abstracted that they have no
relationship to reality. The example he likes to give is Freon: if you
were to study the toxicology of Freon in the traditional way, you’d
never get to the ozone hole. “Nature changes things,” Wiesner says. “So
we need to be able to understand those transformation processes, and we
need to understand them in complex systems.”
The first large set of CEINT experiments ended about a year ago, and
the team spent most of last year figuring out where the nanoparticles
went, what they did, and how they added up. They superimposed a grid on
each box, then harvested the plants and animals section by section. They
clipped the grasses, sorted them by type, and ground them up. They took
bore samples of the soil, the water, and the rocks. They anesthetized
and flash froze the vertebrates. Then they started measuring the
nanoparticle concentrations in the plants, the animals, and core-sample
slices.
But consider the magnitude of the scientific problems that face the
scientists at CEINT, or anyone else trying to answer a multitude of
questions as nanotech applications gallop into the market and man-made
nanoparticles begin to litter our world. Just try tracking something a
billion times smaller than a meter in even a modestly sized ecosystem,
say, a small wetland or a lake. Do carbon nanotubes degrade? And if not,
then what? And how do you tell the nanotubes from all the other carbon
in your average ecosystem? Even if we did regulate nanoparticles, how
would we detect them? There’s no “nanoprobe” that could find them today,
and given the challenges of developing such a thing, the team at CEINT
considers it unlikely that there will be one any time soon. Thus,
gathering evidence of nanoparticles’ effects—whether positive or
negative—turns out to be a titanic task. Simply finding them in the
experiment samples seems about as complicated as finding that needle in a
haystack the size of the Grand Canyon.
LEE FERGUSON, a chemistry professor who directs the nanoparticle
analysis, meets me in the basement of the CEINT building and leads me on
a tour of all the hulking, pricey instruments the researchers use.
Despite the cutting-edge aura of this machinery, none of it is fully up
to the task of locating and analyzing the proverbial nanoneedle.
“With nanoparticles, we’re playing catch-up as a scientific
community—not only to ask the right questions, but to have the right
tools to investigate them,” Ferguson says as he pushes through a door
into the first lab. “We were well prepared to answer questions about
PCBs—we’d spent half a century refining the chemistry and the
instruments that were used to analyze the molecules in those chemicals.
But simply
measuring nanoparticles is a challenge. It’s one thing
if they’re concentrated, but if you’re looking for nanoparticles in
soil, for instance, you just can’t find them.”
He spends the next hour showing me how the CEINT team has
back-engineered methods to detect and characterize nanoparticles. The
fluorometer aims three lasers at carbon nanotubes. Another instrument
uses ultrasonic waves to flush out its tiny quarry. Across campus, huge
electron microscopes train electron beams on the nanoparticle samples,
projecting their images onto a charge-coupled device camera, like the
ones used on the Hubble Telescope, and atomic force microscopes form
images of them by running a probe over samples like a hypersensitive,
high-tech record player.
As the team’s methods continue to advance, their experiments have
resulted in some surprising data. “After we dosed the water, we took
some of it to the lab and exposed fish to it,” says Wiesner’s research
assistant, Benjamin Espinasse. “Some of the particles turned out to be
more toxic in the lab. And the reverse also happened: some things didn’t
appear to be toxic in the lab, but they were more toxic in the boxes.
It seems that the organic matter in the mesocosms changed the coatings
of the particles, making them more toxic or less toxic,” Espinasse
continues. “We could never have imagined that.”
While CEINT has only published the results of the preliminary
mesocosm experiments, the team has been able to make a few conclusions:
When the nanoparticles come in a burst, they tend to stay in the soil.
But if they bleed into the system slowly, they filter into the water
column. Regardless, nanoparticles seem to have a tendency to stick
around—that was also the case with DDT.
Meanwhile, CEINT has begun a new set of experiments in the boxes:
testing nanoparticles that have been combined with various other
substances.
“The materials we most see now are nanomaterials incorporated into
other products: textiles, foams, mattresses, nanotubes in display
screens,” Wiesner explains. “How it will get out into the environment
will be very different than just the pristine particle.”
And then there are the nanobots to plan for. “As we get closer to
even simple nanobots, we will need to understand how to do research on
them, too,” Wiesner says. Although they remain a marvel of the future,
scientists are working toward nanomachines that may someday be able to
replicate red blood cells, clean up toxic spills, repair spinal cord
injuries, and create weapon swarms to overwhelm an enemy. Researchers
are already working on simple versions of nanobots using the chemical
principles of attraction and repulsion to help nanostructures arrange
and build themselves in a process akin to the way DNA works: a strand of
DNA can only split and rebuild in one particular way, and the desired
structure is preserved, no matter how many times the DNA replicates.
As if trying to figure out the effects of simple nanoparticles
weren’t enough of a futuristic challenge, concerns surrounding nanobots
that replicate like DNA are so theoretical they’re spoken about in
narratives resembling science fiction. Sun Microsystems founder Bill Joy
famously warned that, if released into the environment, self-assembling
and self-replicating nanomachines could spread like pollen or bacteria,
and be too tough and too small to stop before invading every part of
the biosphere, chewing it up and reducing all life on earth to “gray
goo.” In nanotech circles, this is called the “gray goo problem,” but no
one really knows if this vision is prophetic or simply hysterical.
DOWN THE BASEMENT HALLWAY, postdoc Badireddy motions to me to join him
at a computer monitor next to the dark field microscope in his lab. He
clicks on a movie he’s made from images he’s captured. It shows silver
nanoparticles interacting with bacteria.
At first, the nanoparticles don’t seem to be doing much. Then, all of
a sudden, they start to clump to the outside of a bacterium. The
nanoparticles build up and build up until the bacterium’s cell membrane
bursts. Then the nanoparticle clumps dissolve into small units before
clumping back up again and attacking more bacteria. “The whole cycle
happens in about thirty minutes,” Badireddy says. “It’s so fast. If you
leave the nanoparticles overnight, when you come back in the morning,
all the bacteria are ground mush.”
If you’re looking for stink-free athletic socks, maybe this is a good
thing. But could that same process someday turn out to have some sort
of nasty biological effect? We just don’t know yet.
“The fact that they re-cycle suggests they might persist for a long
time,” Badireddy says as we watch the movie a second time. “They might
enter the food chain. And then, who knows what will happen?”
Is nanotechnology a panacea or Pandora’s box? Listen to a conversation with Heather Millar.
