NEWS & VIEWS
the incidence of spontaneous oocyte activation. This allows a set of uniform oocytes with
high levels of MPF to be generated, which
can then be activated in a controlled manner.
Byrne and colleagues’ success2 in generating
primate-derived embryonic stem-cell lines
followed the introduction of these changes to
the SCNT protocol (Fig. 1). However, further
work is required to unravel the mechanisms
underlying this achievement.
An entirely different approach to SCNT can
also lead to embryonic stem-cell lines. This
procedure involves reprogramming adult
cells directly by inducing the expression of
just four gene transcription factors in the cells.
Using this method, researchers5,6 have reprogrammed skin cells of adult mice to generate a
few cells that have many of the characteristics
of embryonic stem cells.
There is so far no sign that this approach
could be effective in human cells. But even
if it could be applied to generating patientspecific cells, there are other limitations on its
use in humans. For example, viral vectors were
used to introduce the genes encoding the four
transcription factors into the genome of the
mice. Because of the potential risks associated
with using viral vectors, this procedure would
be unacceptable for use in treating humans.
Moreover, many of the embryonic stem-celllike cells generated in this way eventually
developed into tumours, probably because misregulation of one of the four introduced genes
— Myc — can lead to cancer. But a modified
approach to direct reprogramming that does
not involve cancer-causing genes or the use of
viruses is likely to be the ultimate method of
choice for producing human stem cells.
What are the implications of Byrne and colleagues’ findings2 for applications in humans?
When considering the potential of stem cells
derived from adult cells, great emphasis is often
placed on the fact that derivatives of such cells,
if returned to a patient suffering from a degenerative disease, would not be rejected by their
immune system. Realistically, a careful examination of resources and the time required to
produce differentiated cells for treatment purposes suggests that large-scale use of stem cells
would be impractical.
In our haste to use patient-specific cells in
therapy, however, we tend to overlook the fact
that they are of great value for basic research
and drug discovery. For example, such cells
could provide new ways to study inherited
diseases. If the diseased tissue cannot easily
be recovered from the patient, production of
patient-specific cells is the only potential means
of obtaining cells with the condition. Such cells
could be used to identify causative mutations.
Or they could be compared with their healthy
counterparts to identify the molecules and
molecular mechanisms underlying the disease
symptoms. This information could then form
the basis for high-throughput screens to identify small-molecule drugs that could prevent
such disease-associated changes at a molecular
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NATURE|Vol 450|22 November 2007
level. Ultimately, this approach might lead to
treatments for neurodegenerative diseases,
some cancers and psychiatric disorders.
■
Ian Wilmut and Jane Taylor are at the Centre for
Regenerative Medicine, Chancellor’s Building,
University of Edinburgh, 49 Little France
Crescent, Edinburgh EH16 4SB, UK.
e-mails: [email protected];
[email protected]
1. Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J.
& Campbell, K. H. S. Nature 385, 810–813 (1997).
2. Byrne, J. A. et al. Nature 450, 497–502
(2007).
3. Mitalipov, S. M. et al. Hum. Reprod. 22, 2232–2242
(2007).
4. Whitaker, M. Physiol. Rev. 86, 25–88 (2006).
5. Okita, K., Ichisaka, T. & Yamanaka, S. Nature 448, 313–317
(2007).
6. Takahashi, K. & Yamanaka, S. Cell 126, 663–676
(2006).
MATERIALS SCIENCE
Purity rolled up in a tube
Fotios Papadimitrakopoulos and Sang-Yong Ju
Before carbon nanotubes can fulfil their potential in device applications,
better ways must be found to produce pure samples of them. A promising
approach involves wrapping them up in a shell of polymer.
Formed simply by rolling up a two-dimensional sheet of graphite (graphene), singlewalled carbon nanotubes — SWNTs — are
wonder materials of modern materials science.
They are phenomenally strong and stiff, and,
unusually, are excellent conductors of heat
along the tube’s axis, yet good thermal insulators across it. But it is their electrical characteristics that excite the most interest: depending
on the precise way they are rolled up, they can
be either semiconductors or fully conducting
metals.
And there’s the rub. SWNTs can generally
be fabricated only in batches that vary widely
both in the diameter of the individual tubes
and in the orientation of their graphene lattice
relative to the tube axis — the property known
as chirality (Fig. 1). Separating out different
conformations to produce a ‘pure’ nanotube
sample is a thorny problem, but one that
must be solved if nanotubes are to fulfil their
electrifying potential.
Writing in Nature Nanotechnology, Nish
et al.1 show how the selection of a specific
nanotube chirality can be greatly improved by
using a polyfluorene-based conjugated polymer as a wrapping agent. Chen et al.2, writing
in Nano Letters, verify that finding, and achieve
further enrichment by using related conjugated
polymers to preferentially wrap nanotubes with
less variation in their mean diameter. Quite
apart from the importance of these techniques
for nanotube separation, this work1,2 allows
a peek at future polymer–nanotube architectures, which could be poised to revolutionize photovoltaic, sensor and flexible-display
technologies in their own right.
So how does this chirality enrichment work?
Just like graphite3, SWNTs have a smooth surface, and interactions with this surface can be
used to organize many chemical species. The
interaction between SWNTs and species containing aromatic groups, such as polyfluorene,
has been argued4 to proceed first by interactions
a–1
a–2
7a–1
5a–2
(7,5)
(7,5)
(10,5)
(10,5)
Figure 1 | Roll up. The diameter and chirality
(orientation of the graphene lattice with
reference to the tube axis) of a single-walled
carbon nanotube can be described by a
two-dimensional ‘rolling vector’ based on
unit vectors (ā, ā) along two axes of the
unrolled graphene lattice. The conformation
is determined by joining the origin and
end point of the rolling vector.
between the electrons of the graphene lattice
and the aromatic groups, followed by a stage
of close packing that depends strongly on the
underlying chirality of the SWNTs.
Polyfluorene’s chemical structure falls into
the basic category of ‘hairy rod’ conjugated
polymers (Fig. 2a). The hairs take the form of
short side-chains, formed of several CH2 groups
and one CH3 group, which are attached to a
fluorene backbone, the rod. Additional aromatic groups inserted between the fluorene
groups make the polymer repeat-unit longer.
The polyfluorene chains are organized into
planes such that one side-chain is aligned
between adjacent chains and one extends
upwards to interact with the solvent and impart
solubility to the structure (Fig. 2b).
The overall result is a smooth surface that
encircles the equally smooth surface of the
SWNTs and thus can guide the wrapping
process (Fig. 2c). Crucially, however, these
two smooth surfaces have fine corrugations.
As the latest papers describe1,2, when the
NEWS & VIEWS
NATURE|Vol 450|22 November 2007
polymer sheet is rigid, only selected nanotube
chiralities match the ‘corrugations’ of the
polymer sheet, kick-starting the wrapping
process and facilitating chirality enrichment.
Nish et al.1 also show that, depending on
the nanotube diameter required (between 0.5
and 1.4 nanometres), two, three or four polyfluorene chains are needed to wrap up a SWNT
completely. Both sets of authors find1,2 that
selective chirality enrichment is influenced
by the length of the side-chains and the precise structure of the polymeric repeat. These
features give the polyfluorene sheet rigidity,
leading to better recognition of the nanotube
corrugation. Chen et al.2 also demonstrate that
the ratio of polymer to nanotubes is a decisive
factor for chiral selectivity, indicating that the
formation of such superstructures is dynamic
rather than static.
The precise organization and directionality
of aromatic surfactants in processes for sorting
SWNTs has been a focus of intense theoretical
study5. Recent experiments6 have also shown
that a chiral biporphyrin chemical group can
be used to separate certain SWNTs into optically active nanotube fractions, depending
on whether the tube is rolled up in a righthanded or a left-handed way. Such separation
a
b
Fluorene
c
Nanotube
Figure 2 | Hairy rod as guiding hand.
a, Polyfluorene’s chemical structure consists of
a fluorene backbone connected by additional
aromatic groups (red circles). As the authors
show1,2, both this conformation and the sidechains of the structure are crucial to rigidify
(green side-chain) the polyfluorene structure and
also to make it soluble (pink side-chain).
b, c, This allows several polyfluorene chains
to bind together and form a rigid sheet that
selectively interacts (c) with specific nanotube
diameters and chiralities.
adds credence to the idea of an assembly
process in which aromatic adsorbates seem to
‘communicate’ with the underlying chiral
side-wall corrugation.
MICROBIOLOGY
Woodworker’s digest
Andreas Brune
Termites digest wood with the help of their intestinal microorganisms. The
first metagenomic analysis of the inhabitants of a termite gut provides
insight into this feat of biomass-to-energy conversion.
The gut of wood-feeding termites is a tiny but
astonishingly efficient bioreactor, in which
microbes catalyse the conversion of lignified
plant cell walls to fermentation products that
drive the metabolism of their host. Molecular
phylogenetic data have revealed the presence
of hundreds of microbial species in this microlitre-sized environment, but little is known
about their functional diversity. On page 560
of this issue, Warnecke et al.1 report an analysis
of the metagenome of bacteria in the largest
part of the gut — the hindgut paunch — of
a termite species of the genus Nasutitermes
(Fig. 1, overleaf).
Metagenomics is the burgeoning study of
the entire genetic material from particular
environments, and allows investigation of
microorganisms that cannot be cultured in
the laboratory. In this case, Warnecke et al.
compiled an enormous amount of (unavoidably highly fragmented) sequence data from
the total genomic DNA of the inhabitants of
the termite hindgut paunch, and compared
those data with known gene sequences in
public databases. Such sequence comparisons
offer a wealth of information, but nevertheless
can be deceptive. So, crucially, the authors also
identified the major proteins secreted into the
hindgut fluid, and went further by confirming
the catalytic properties of selected gene products by expressing the genes in the bacterium
Escherichia coli.
The main structural polysaccharides of
wood (lignocellulose) are cellulose and various
hemicelluloses: both are efficiently digested by
termites. In lower (more primitive) termites,
hydrolysis of cellulose and hemicelluloses
is catalysed by flagellate protozoa housed in
the hindgut paunch; bacteria are also present.
Higher termites, which include Nasutitermes
and most termite species worldwide, lack
flagellates. Instead, their hindgut is host to a
largely bacterial community, although the
involvement of the bacteria in cellulose and
hemicellulose digestion has not been clear2.
The metagenomic analysis1 of the Nasutitermes hindgut reveals a rich diversity of
bacterial genes encoding hitherto unknown
glycosyl hydrolases. These enzymes constitute
more than 100 families of proteins that cleave
So what’s next? Clearly, the work of Nish
et al. and Chen et al. provides a starting point
for future investigations of specific polymer–
nanotube interactions that take into account
the atomic characteristics of both structures.
If talented chemists, physicists and surface
scientists club together, the result could be
nanotubes that not only are enriched in a specific chirality, but also interact with polymeric
substrates to produce nanocomposites with
specific desired properties. A whole new world
of devices is poised to take advantage of what
might emerge from such efforts.
■
Fotios Papadimitrakopoulos and Sang-Yong
Ju are in the Nanomaterials Optoelectronics
Laboratory, Polymer Program, Department
of Chemistry, Institute of Materials Science,
University of Connecticut, Storrs,
Connecticut 06269-3136, USA.
e-mail: [email protected]
1. Nish, A., Hwang, J.-Y., Doig, J. & Nicholas, R. J. Nature
Nanotech. 2, 640–646 (2007).
2. Chen, F., Wang, B., Chen, Y. & Li, L.-J. Nano. Lett. 7,
3013–3017 (2007).
3. Tao, F. & Bernasek, S. L. Chem. Rev. 107, 1408–1453
(2007).
4. Zheng, M. et al. Nature Mater. 2, 338–342 (2003).
5. Lu, J. et al. J. Am. Chem. Soc. 128, 5114–5118 (2006).
6. Peng, X. et al. Nature Nanotech. 2, 361–365 (2007).
the glycosidic bond between carbohydrates, or
between a carbohydrate and non-carbohydrate
entity. The authors’ sequence analysis suggests
that many of the gene products fall within the
glycosyl hydrolase families specializing in the
degradation of cellulose and hemicelluloses.
For several gene products, they also demonstrate cellulase activity in vitro. So far, bacteria
with such cellulolytic power have not been
isolated from the hindgut of higher termites;
until recently, even their activity had remained
undetected because the enzymes are not
soluble but are associated with the particulate
fraction of the gut content3.
Many of the genes identified by Warnecke
et al.1 could be assigned to one of two groups
of bacteria — the fibrobacters and spirochetes — known to be abundant in the hindgut of Nasutitermes species. The fibrobacters
from termite guts have not been cultured in
the lab, but are known to be distant relatives
of the fibre-degrading bacteria found in the
intestines of cows and other ruminant animals4. The implication that members of the
spirochetes are involved in cellulose digestion, however, was unexpected. This result is
of similar importance to the earlier, equally
surprising discovery that termite-gut spirochetes can carry out reductive acetogenesis5 (a
mode of energy metabolism that results in the
reduction of carbon dioxide to acetate). This
finding answered the long-standing question
regarding the identity of the organism responsible for one of the key metabolic activities in
termite guts6.
Warnecke et al.1 show that almost all of the
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