- In his novel Prey, Michael Crichton portrayed a future
threatened by minuscule, self-replicating robots that begin to consume
the planet. That's still in the realm of science fiction, but not everyone
believes that nanotechnology is inherently safe. The Prince of Wales, for
instance, warned us a year ago that the unleashing of small-scale "nano"
particles on an unprepared world could result in a Thalidomide-like health
disaster.
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- It is not easy to dismiss such fears over the possible
health effects of nanotechnology - the science of the very small, at the
scale of a billionth of a metre. There may be no evidence of risk, but
that does not mean that the risk is zero. In fact, only now are scientists
beginning to shed some light on exactly how the specially engineered nanoparticles,
which are the basic ingredients of nanotechnology, might affect our health
if they managed to end up in the wider environment.
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- Much of this research is based on the round assembly
of 60 carbon atoms known as the buckyball, or fullerene. This nanoparticle
is considered important because it is a building block for all sorts of
new materials and medicines. Buckyballs have remarkable characteristics.
If you shoot one of these virus-sized particles at a steel plate at 15,000mph,
it bounces back unharmed. Squash one, and it becomes twice as hard as diamond.
They're hollow, so you can put other molecules, such as drugs, inside them.
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- But studies suggest that the properties that may make
fullerenes useful may also make them toxic. The first evidence came earlier
this year when Eva Oberdorster, an American toxicologist at the Southern
Methodist University in Dallas, published a study showing how, after two
days of swimming in water containing buckyballs, largemouth bass fish suffered
damage to the fat membranes in their brains. Their livers had responded
as though there was a toxin present.
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- Now, scientists at Rice University, Houston, have pinpointed
what could be the mechanism causing this damage. Rice's breakthrough study,
published in the journal Nano Letters, is the first to look at the toxic
effects on individual human cells exposed to fullerenes, and the first
to indicate the cause. "People have shown there's a hazard, but this
is the first work about how that hazard comes to be. It's important for
the community to understand how, because then you can change it,"
says Kristen Kulinowski, the director of Rice's Centre for Biological and
Environmental Nanotechnology.
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- The Rice researchers exposed human liver and skin cells
to solutions containing different concentrations of fullerenes. Four types
of solution were tested. One contained plain buckyballs; in the other three,
researchers modified the buckyballs by attaching other molecules to their
sides.
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- They measured how many cells died within 48 hours, and
repeated the tests until they found the exposure level for each solution
that killed half the cells. The plain buckyballs destroyed half the cells
in a concentration of about 20 parts per billion, but a concentration of
10 million times more was needed to make the modified fullerenes as toxic.
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- All atoms and molecules are surrounded by their own particular
halo of electrons, but in the buckyball's case, the structure of this halo
seems to be very disruptive to biological systems. "The fullerene
has what is known as a high electron affinity, which means it likes to
pluck electrons from other molecules it comes into contact with,"
says Dr Kulinowski.
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- When a molecule loses one electron, it's often left with
a lonely partner electron. Such a molecule - a free radical - is highly
reactive in its desperation to pair off. "The proposed mechanism is
that these free radicals attack the cells in their search for extra electrons
and damage the cell membranes," Kulinowski says. In essence, free
radicals punch holes in the membranes.
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- The buckyballs, however, remain stable because the energy
from the extra electrons they pick up seems to spread evenly over the ball-like
structure. This is one of the reasons why fullerenes are so incredibly
strong.
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- A research team at the University of Michigan has discovered
a similar hole-punching effect with another, larger nanoparticle called
a dendrimer, which is used in nanomedicine to deliver drugs or imaging
agents to specific parts of the body via the blood. The team found that
the size of the nanoparticle seemed to make a difference, with the smallest
dendrimers having no adverse effects.
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- A member of the team, Professor Mark Banaszak Holl, says
that if the presence of nanoparticles can produce holes in cell membranes,
it makes it easy for all sorts of molecules, including the nanoparticle
itself, to get inside the cell. "This provides a physical mechanism
via which nanoparticles can be toxic to cells - even if the material the
nanoparticle is made from would normally not cause chemical toxicity,"
he explains. This work was published in the journal Bioconjugate Chemistry
last summer.
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- Encouragingly, both the Michigan and Rice groups have
found that modifying the surface of these nanoparticles by attaching other
molecules makes them far more body-friendly, and this may be a way to tune
toxicity. "Attaching small molecules to the buckyball surface disrupts
the electronic structure and therefore makes it less accommodating to extra
electrons, so it doesn't produce as many free radicals," Kulinowski
says.
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- However, she warns against drawing any general conclusions
about engineered nanoparticles. We need to wait, she says, until scientists
have properly investigated the relationship between structure and function
for a wide range of nanoparticles.
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- A great deal more work is also needed to see what happens
inside the whole body, where cellular repair mechanisms, whole-organ and
whole-body processes come into play. "Every cell in the body is surrounded
by a membrane. If you put therapeutic nanoparticles in the bloodstream
and they started punching holes in the cells lining the blood vessels,
it would seem to be a bad thing. But we just don't know," says Ken
Donaldson, Professor of Respiratory Toxicology at the University of Edinburgh.
"Some membranes have pores in them already. It could mean nothing
or it could mean a lot," he says.
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- Donaldson's interest in engineered nanoparticles comes
by way of his work on asbestos, coal-mining dust and car pollution particles.
It is well established that inhaling very small particles can cause inflammation
in the lungs. This immune response, Donaldson suggests, is to do with the
large surface area of the lungs that is exposed. It may have evolved as
a way to deal with invasion by bacteria. "Inflammation in the lungs,
unlike in the skin, for example, is not a trivial matter as it doesn't
take too much lung inflammation to compromise your breathing," he
says.
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- Nanoparticles add another dimension because, being a
similar size to viruses, they can get into the bloodstream through the
lungs and can enter the brain directly via inhalation through the nose.
This is quite new, and there is not a lot of hard data, according to Donaldson.
He's concerned about links that have been found between welding and Parkinson's
disease, because there is research showing that inhaled metals from welding-fume
nanoparticles end up in the brain.
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- In Oberdorster's experiment, it seems that the buckyballs
got into the fish brains by entering the bloodstream through the gills.
However, she points out that despite the changes she found in their bodies,
the fish appeared to be functioning normally. "They could eat just
fine, and when I tried to catch them with a net, they were doing all the
proper escape behaviours," she says. "We think the damage was
as debilitating as having a very bad migraine."
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- She says it is possible that the brain tissue might repair
itself because there are cells in the brain that help the mending process,
but the only way to find this out would be to carry out a follow-up study.
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- In the fish livers, the buckyballs had switched on genes
related to inflammation and involved in breaking down contaminants. This
is a standard response to a toxic substance, and it suggests that the fish
were trying to change the fullerenes into their constituent parts to get
rid of them. "If the body could deal with buckyballs like any other
toxicant, that would be really nice; you wouldn't have to worry about them
accumulating in the body," says Oberdorster. This is being investigated.
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- With the nanotechnology industry poised to make all kinds
of nanoparticles in huge quantities, these toxicology results are timely,
for the public and for the thousands of workers in the industry exposed
to such materials.
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- But a lot more needs to be understood before we can relax
about the possible effects of nanoparticles on human health.
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- THE BENEFITS OF DOWNSIZING
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- By Steve Connor
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- Nanotechnology is the science of the very small, on a
scale of millionths of a millimetre - a thousand times smaller than the
micro-devices used in electronics.
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- Nano-scale materials are already used for some mobile
phones and for the ultra-thin coating on self-cleaning glass. There are
also plans to develop nanotechnology for delivering drugs to the target
tissues in the body, to build biology implants to help the blind to see,
and to clean contaminated ground.
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- Scientists can already manipulate atoms with "nano"
microscopes. They have also made nano-scale machines - even works of art
- smaller than the width of a human hair.
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- A reasonable fear is that when particles are constructed
on the nanoscale, it will be easier for them to penetrate the body - through
the skin and lungs, say - and so pose new health threats. Viruses are an
example of naturally occurring nano-scale particles.
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- © 2004 Independent Digital (UK) Ltd
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- http://news.independent.co.uk/world/science_technology/story.jsp?story=595304
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