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SCIENCE ROUNDUP
Contents of this Issue:
Unthinkable Crimes
The Blossoming of Epigenetics
Time to Rewrite the Textbooks
A Decision on Stem Cells
Flu’s Clues
Visualizing Microarrays
Batten Down the Hatches?
Digging into Seismicity in Central Europe
Taking the Long View on Ecology
All in the Family
Dino Makeover
Vibration Predation
Threatened Treasures
Brain Researchers Unite!
Superconductivity Heats Up
Toward New Energy Sources
How the Brain Makes Faces
Tool for the 21stCentury
During the third quarter of 2001, Science provided the stage for dramatic
reporting both of cutting-edge scientific research and of events at the
intersection of science and global society. Here’s a review of some of
the more notable stories.
Unthinkable Crimes
http://www.sciencemag.org/cgi/content/summary/293/5538/2182a
In the wake of the terrorist attacks of 11 September, the magnitude of the
crime initially seemed beyond comprehension. Yet the attacks, wrenching as
they were for the U.S. and the world, inevitably brought to mind the still
greater horrors that might ensue if terrorist groups were to use weapons
of mass destruction. A news article in the 21 Sep 2001 issue of Science
reviewed the state of U.S. and international antiterrorist programs, and
explored the plausibility of terrorist threats related to mass
destruction’s “unholy trinity” -- nuclear, chemical, and biological
weapons. Bioweapons formed the focus of a timely editorial in the
following week by C. F. Chyba
(http://www.sciencemag.org/cgi/content/summary/293/5539/2349), titled
“Biological Security in a Changing World.”
The Blossoming of Epigenetics
http://www.sciencemag.org/content/vol293/issue5532/index.shtml#specialintro
The depression among some researchers upon learning that humans have only
around 50% more genes than the common laboratory roundworm is being lifted
by a flurry of new work in understanding the complex epigenetic regulation
of our genome -- a topic reviewed in Science’s 10 Aug 2001 special issue.
Review and Viewpoint articles covered DNA methylation in mammals and other
organisms, histone modifications, and the known epigenetic phenomena of
X-chromosome dosage compensation, imprinting, and centromere function.
Reports in the same issue by Lo et al.
(http://www.sciencemag.org/cgi/content/short/293/5532/1142) and Noma et
al. (http://www.sciencemag.org/cgi/content/short/293/5532/1150) described
new findings in regulation of histone modifications, which has emerged as
one of the primary mechanisms for control of gene expression. And an
accompanying feature on the Science Functional Genomics Web site
(http://www.sciencegenomics.org/resources/res_epigenetics.shtml) offered
links to a collection of online epigenetics resources, and an archive of
articles and reviews published in Science over the past several years.
One key arena for epigenetic study lies in exploring the feasibility of
cloning organisms by nuclear transfer. In a landmark report in the 6 Jul
01 issue, Humpherys et al.
(http://www.sciencemag.org/cgi/content/short/293/5527/95) examined
imprinted gene expression in cloned mice and in the embryonic stem cells
from which the mice were derived. The epigenetic state of the stem cells
turned out to be highly unstable, which resulted in variation in imprinted
gene expression in the derived mice. These results could help explain many
abnormalities found in cloned organisms -- and may also serve to dampen
enthusiasm for human cloning, which would require exquisite control over
the genome’s epigenetic state. As Rideout et al. pointed out in their
review of the topic in the epigenetics special issue
(http://www.sciencemag.org/cgi/content/short/293/5532/1093),
“even apparently healthy cloned animals may have subtle gene expression
abnormalities that were not severe enough to cause lethality or an obvious
postnatal phenotype” -- but that may become tragically apparent later on.
Time to Rewrite the Textbooks
Everyone is taught that, in eukaryotic cells, transcription of DNA into
RNA occurs only in the nucleus and translation of RNA into protein occurs
only in the cytoplasm. Apparently, everyone has been mistaken. In the 10
Aug 2001 Science, Iborra et al.
(http://www.sciencemag.org/cgi/content/short/293/5532/1139) offered the
most convincing evidence yet that some proteins -- an estimated 10 to 15%
-- are made inside the nucleus. To visualize new protein translation, the
researchers exposed cells to molecules of the amino acid lysine that were
tagged with fluorescent or radioactive markers. They observed similar
incorporation of the tagged molecules into new proteins both in the
cytoplasm and, surprisingly, at pinpoint sites in the nucleus. What’s
more, the nuclear accumulation was time dependent, and was slowed by
chemicals known to inhibit protein synthesis in eukaryotic cells -- clear
indicators that translation was taking place in the nucleus. Purified
nuclei that had been removed from the cell also showed the ability to
fashion proteins, a confirmation that the nucleus wasn’t simply importing
proteins from the cytoplasm. As M. W. Hentze noted in an accompanying
Perspective (http://www.sciencemag.org/cgi/content/short/293/5532/1058),
the work opens up entirely new avenues of study on how proteins are
constructed in the cell -- and “future research on translation, whether in
the nucleus or the cytoplasm, is likely to be full of suspense and
surprises.”
A Decision on Stem Cells
On August 9, George W. Bush, in his first televised address as President,
announced that he would allow the federal government to fund research on
human embryonic stem cells. Science provided full coverage and analysis of
the announcement in a 17 Aug 2001 News Focus
(http://www.sciencemag.org/cgi/content/short/293/5533/1242). The feature
covered both the announcement and its immediate aftermath -- especially
concern among scientists regarding the originally reported 64 stem cell
lines worldwide. Also included: a full transcript of Bush's address
(http://www.sciencemag.org/cgi/content/short/293/5533/1244) and a profile
of the administration’s newly appointed bioethics point man, Leon Kass
(http://www.sciencemag.org/cgi/content/short/293/5533/1243).
As impressive as their theoretical potential to differentiate into any
human cell is, key issues such as how stem cells actually form, what roles
they play in the body, and what limitations, if any, there are to their
ability to migrate remain largely obscure. A study by Ourednik et al.
(http://www.sciencemag.org/cgi/content/short/293/5536/1820) published in
the 7 Sep 2001 issue cast some light on all three questions. A traceable
clone of human neural stem cells was implanted in developing primate
forebrains to study the cells’ differentiability and migratory patterns.
The researchers found that the cells divided into two separate
subpopulations -- one dedicated to producing differentiated cells and the
other set aside in a secondary “reservoir.” Yet both subpopulations had
the ability to migrate through the large expanse of the primate cerebrum,
suggesting that stem cell transplants could someday be successful in
brains larger than those of rodents.
Flu's Clues
The virulence of different strains of the influenza virus, one of
humankind’s most enduring pathogenic enemies, constitutes a fascinating
and controversial puzzle. A pair of studies in the 7 Sep 2001 issue put
together some of the pieces using the tools of comparative genomics and
molecular biology. Hatta et al.
(http://www.sciencemag.org/cgi/content/short/293/5536/1840) examined the
H5N1 influenza A virus -- the “Hong Kong” flu that was fatally transmitted
from birds to humans in 1997. Comparing that lethal virus to a close but
nonlethal relative suggested that substitutions of two amino acids in the
viral genome principally determined the variation in virulence between the
two strains.
Digging further into the past, Gibbs et al.
(http://www.sciencemag.org/cgi/content/short/293/5536/1842) constructed a
molecular history of the H1 influenza hemagglutinin gene, the principal
antigen on the surface of the virus capsule. They concluded that the 1918
“Spanish flu” pandemic, the most deadly ever for humans, resulted from a
virus with a rare recombination event in its hemagglutinin gene --
although an accompanying Perspective by R. G. Webster
(http://www.sciencemag.org/cgi/content/short/293/5536/1773) suggested that
the proposed rearrangement was “definitely a stretch for influenza
virologists” in view of the extreme rarity of such recombination events.
Those differences notwithstanding, an Editorial in the same issue
(http://www.sciencemag.org/cgi/content/short/293/5536/1729) pleaded for
building up stockpiles of antiviral drugs to combat the next influenza
pandemic -- for, as noted in a second, sobering Perspective by Laver and
Garman (http://www.sciencemag.org/cgi/content/short/293/5536/1776), a
“worldwide epidemic (pandemic) of type A influenza could occur at any
time.”
Visualizing Microarrays
The increasing popularity of microarray studies as a way to examine gene
expression carries its own quandary: How do you view and analyze the huge
volumes of data churned out by each experiment? In the 14 Sep 2001 issue,
Kim et al. (http://www.sciencemag.org/cgi/content/short/293/5537/2087)
borrowed an answer from geology -- make a topo map. The group compiled
data from 553 gene expression microarray experiments on C. elegans, and
presented an innovative three-dimensional “terrain map” to view the data
-- each “mountain” representing a gene expression cluster, revealing
relationships between genes that may not have been seen when testing
specific hypotheses. “Fly-over” movies of several of these gene-expression
terrains are available as supplemental material on Science Online. In the
same issue, Zhu et al.
(http://www.sciencemag.org/cgi/content/short/293/5537/2101) reported a
different milestone in array studies: the creation of a nearly complete
microarray of the entire proteome of the laboratory yeast S. cerevisiae on
a single microscope slide.
Batten Down the Hatches?
As residents of the U.S. East and Gulf Coasts well know, the number of
Atlantic hurricanes has been above average in recent years. In a report
published on 20 Jul 2001, Goldenberg et al.
(http://www.sciencemag.org/cgi/content/short/293/5529/475) suggested just
how much: Charting the variability of hurricane activity since the
mid-20th century, the study noted a 2.5-fold increase in hurricane
activity for the past six years relative to the preceding quarter-century.
And that increase, they suggest, isn’t just a temporary fluke, but instead
traces to a combination of increased North Atlantic sea-surface
temperatures and vertical wind shear that’s likely to persist for another
10 to 40 years. In a Perspective
(http://www.sciencemag.org/cgi/content/short/293/5529/440), however, L.
Bengtsson disagreed, arguing that meteorological records are “too short
and too incomplete” to allow such a conclusion. Either way, all agreed
that the U.S. coastal population boom during the previous lull in
hurricane activity has greatly increased the possible damage costs from
any single hurricane.
Digging into Seismicity in Central Europe
The Rhine graben is a lengthy rift valley, bounded by active extensional
faults, that runs north-south through much of Germany and Switzerland. The
faults are known to have failed in catastrophic earthquakes in the past --
the largest being a magnitude 6.5 event that struck the area of Basel,
Switzerland, in 1356. But earthquake-linked faults in the region have been
notoriously difficult to study in detail owing to the infrequency of such
events. Meghraoui et al.
(http://www.sciencemag.org/cgi/content/short/293/5537/2070), reporting in
the 14 Sep 2001 issue, applied the techniques of paleoseismology to finger
the fault responsible for the 1356 quake. Using remote sensing to narrow
down the list of candidate structures, they zeroed in on a 50-meter-high
fault scarp south of Basel as a promising candidate; then, they explored
the fault’s history by digging trenches into the base of the fault. The
trenching revealed sedimentary layers that had been substantially
separated along the fault’s trace -- and radiocarbon dating suggested that
displacement along the fault amounted to nearly 2 meters, in not one but
three major seismic events over the past 8500 years. Although the data
imply a relatively long “recurrence interval” for the fault in question
(on the order of 1500 to 2500 years), the study offered a sobering new
glimpse at the seismic hazards in central Europe -- an area dotted with
vulnerable “critical facilities” such as chemical and nuclear plants.
Taking the Long View on Ecology
http://www.sciencemag.org/content/vol293/issue5530/index.shtml#specialintro
Although systematic recordkeeping has been introduced and implemented only
in the past century, ecologists have increasingly come to appreciate that
gleaning long-term trends -- both over history’s long haul and in modern
experiments spanning decades rather than years -- is an important step for
understanding current conditions and predicting the future of complex
ecosystems. The 27 Jul 2001 special issue of Science chronicled some
recent efforts to piece together how ecosystems work over long time
scales. An extensive news article by Jocelyn Kaiser examined the
granddaddy of all ecology-through-time projects, the NSF-funded Long Term
Ecological Research (LTER) network, a program whose big-science approach
to ecology has paid off with some impressive successes. Review articles
explored a variety of areas in which a long-term perspective is essential,
such as reconstructing ancient coastal ecosystems through historical
records and studying variations in plant and population dynamics over
time. And a Viewpoint article turned the focus to the future: the
“emerging imperative” of accurate ecological forecasting, and how
long-term studies can aid in such efforts. An online supplement
(http://www.sciencemag.org/feature/data/ecology2001.shtml) offered links
to general ecological resources, LTER programs in the U.S. and abroad,
resources on population ecology and ecological forecasting, and more.
All in the Family
“I seem to have misplaced an elephant” is not a phrase one hears often --
but that’s just what Roca et al. argue that scientists have been doing for
more than 100 years, in a 24 Aug 2001 report
(http://www.sciencemag.org/cgi/content/abstract/293/5534/1473). The group
described variations in the DNA sequence of four nuclear genes gathered
from dart-biopsy samples of 195 free-ranging African elephants within the
species Loxodonta africana -- variations substantial enough to suggest
that two groups of the elephants have evolutionarily diverged. Result: The
addition of a second species of African elephant, dubbed L. cyclotis.
That’s not all that has been evolving in the pages of Science over the
last quarter. In the 21 Sep 2001 issue
(http://www.sciencemag.org/cgi/content/short/293/5538/2239), Gingerich et
al. described the discovery of skeletons of two primitive whales with
well-developed limbs. These findings may be an important “missing link” in
whale evolution, as they lend credence to the claim that whales are not
just related to, but descended from, artiodactyls -- the group that
includes even-toed, hoofed mammals.
Dino Makeover
Watching dinosaurs stalk across the silver screen, it’s easy to forget
that what we know about them comes from interpretation of fossils -- and
that recreating nonfossilized structures, such as skin and muscle, can be
a very difficult task. In a study published in the 3 Aug 2001 issue
(http://www.sciencemag.org/cgi/content/short/293/5531/850), Witmer rose to
the challenge in grand style. By studying the position, in closely related
species such as birds and crocodiles, of the small nasal aperture of the
skin with respect to the larger underlying nasal bone cavity, and
comparing fine structures on the bones of the extinct reptiles with those
of living relatives, Witmer deduced that the fleshy part of the dinosaurs’
nostrils were likely located in front of the nasal cavity, out toward the
front of the dinosaur’s snout, rather than high and back as commonly
portrayed. As is noted in the accompanying news article by Eric Stokstad
(http://www.sciencemag.org/cgi/content/short/293/5531/779a), the
difference isn’t just aesthetic -- an up-front nasal opening could mean
both enhanced airflow and a better sense of smell and taste for the
animals.
Vibration Predation
Sea water is often dark or cloudy, and harbor seals haven't evolved the
echolocation employed by other sea mammals. How do they track their prey
over a distance? Dehnhardt et al.
(http://www.sciencemag.org/cgi/content/short/5527/102) provided an answer
in the 6 Jul 2001 Science: In stylishly simple experiments, the group
established that the seals use their whiskers to detect hydrodynamic
trails left by the moving prey. Dehnhardt et al. trained seals to track
small, propeller-driven submarines, and showed that, when tracking the
sub, the seals followed a curved trail taken by the submarine rather than
making a straight line for the sub’s current position. Only when their
whiskers were masked were they unable to track the sub. Normally, seals’
whiskers are extremely sensitive, and vibrate at characteristic
frequencies based on swim speed and other factors. Dehnhardt et al.
speculated that the vortices left in the wake behind prey, which can
persist for more than three minutes, change the whiskers’ vibration
frequency, signaling that dinner is nearby.
Threatened Treasures
http://www.sciencemag.org/content/vol293/issue5527/index.shtml#newsfocus
As the “cradle of civilization,” ancient Mesopotamia was home to some of
the earliest human societies; today, the same lands, located in modern-day
Iraq, are home to some of the most sought-after archeological treasures
known. But the political turmoil of the area has raised severe threats for
archeology in the once great Fertile Crescent. A ten-page news focus in
the 6 Jul 2001 issue of Science surveyed the past, present, and future of
archeology in Iraq, with articles focusing on the immediate dangers to
artifacts in the country, looting networks at work in the desert, the
efforts of archeologists determined to stop the destruction, and new
excavations that could help revitalize study of the greatness that was
Mesopotamia.
Brain Researchers Unite!
This quarter in Science was remarkable for articles that linked previously
disparate areas of research on two devastating neurological diseases:
--Shimura et al (13 Jul 2001;
http://www.sciencemag.org/cgi/content/short/293/5528/263) connected two
areas of research into Parkinson's disease (PD) that had been proceeding
along separate tracks. It has been known for several years that families
with one inherited form of PD carried a mutation in the PARKIN gene, which
codes for the E3 ubiquitin ligase parkin, and that victims of another
familial PD variant showed missense mutations in the gene encoding the
alpha-synuclein protein. Shimura et al. closed the loop, reporting that
parkin is in fact the ligase that adds ubiquitin groups to a form of
alpha-synuclein -- and thereby, in the words of an accompanying
Perspective by C. Haass and P. J. Kahle, “targets that protein for
destruction in the cell's garbage dump, the proteasome.” The paper, note
the Perspective authors, offers “provocative evidence” to reconcile
variations in brain pathology between two forms of PD to different
problems in a common pathway.
--In the 24 Aug 2001 issue, two groups working independently on
Alzheimer's disease (AD) -- Lewis et al.
(http://www.sciencemag.org/cgi/content/short/293/5534/1487) and Gotz et
al. (http://www.sciencemag.org/cgi/content/short/293/5534/1491) --
demonstrated that amyloid-beta protein interacts with tau protein to
increase the formation of neurofibrillary tangles in the mouse brain. As
noted in a related Perspective by V. M.-Y. Lee
(http://www.sciencemag.org/cgi/content/short/293/5534/1446), the two
studies together provide the first compelling evidence that “a causal
connection” links the two dominant pathologies of Alzheimer’s, amyloid
plaques and tau tangles.
Superconductivity Heats Up
The dream of “killer apps” for superconductivity, such as large
superconducting cables, has long been stymied by a nagging fact: The
“critical temperature” of most superconducting materials (the temperature
below which the materials actually do superconduct) tends to be extremely
cold -- on the order of tens of Kelvins. The discovery fifteen years ago
of higher-temperature superconducting behavior in copper-oxide planes (the
so-called planar cuprates) spurred excitement and a huge amount of
subsequent work, but thus far, even for these promising materials, the
record critical temperature of 133 K, reached eight years ago, still has
not been surpassed. Now two papers by Schoen et al., in the 28 Sep 2001
issue of Science, have opened up a different road toward high-temperature
superconductivity -- one paved in fullerene. The group found that these
remarkable spherical molecules of sixty carbon atoms (also known by the
nickname “buckyballs”) can, using a method called field-effect doping,
have their superconducting temperature tweaked up from 52 K to a
comparatively balmy 117 K. As noted in an accompanying Perspective by E.
Dagotto (http://www.sciencemag.org/cgi/content/short/293/5539/2410), it
seems likely that, using the techniques and materials of the Schoen et al.
studies, researchers will easily break the current critical-temperature
record of 133 K -- and that the studies could spur a renewed “race toward
room-temperature superconductivity.”
Toward New Energy Sources
Extracting cheap, efficient power from the sun is the holy grail of
renewable energy. But although solar cells made of organic materials have
the potential to be substantially cheaper than current, dominantly
inorganic photovoltaics, it’s been tough to achieve high enough
efficiencies to make organic devices commercially worthwhile. In the 10
Aug 2001 issue of Science, Schmidt-Mende et al.
(http://www.sciencemag.org/cgi/content/short/293/5532/1119) took a big
step in the direction of practical, efficient organic photovoltaics. By
exploiting the self-organizing properties of liquid crystals, the group
was able to combine two organic compounds in a photovoltaic device that
achieved nanoscale separation between electron-accepting and electron
“hole”-accepting parts of the cell. Result: A easy-to-fabricate cell with
a highly efficient separation of charge carriers -- and a “quantum
efficiency” well above that of most organic photovoltaics. An accompanying
Perspective by J. Nelson
(http://www.sciencemag.org/cgi/content/short/293/5532/1059) provided a
gloss on this elegant work, and placed it in the context of other
solar-cell studies.
Another possible route to efficient solar energy is harnessing the sun’s
photons to dissociate molecular hydrogen from water or other
hydrogen-containing solvents, and using the harvested hydrogen in a fuel
cell. The trick for such a scheme lies in fashioning a small-molecule
catalyst to repeatedly act as midwife to the hydrogen-liberating reaction.
In the 31 Aug 2001 issue, Heyduk and Nocera
(http://www.sciencemag.org/cgi/content/short/293/5535/1639) showed that
they could photogenerate molecular hydrogen from pure hydrohalic acids,
such as condensed HCl, using a cleverly designed dirhodium catalyst.
Although it’s not exactly “hydrogen from water,” and although the system
needs improvement, as noted in a Perspective by J. K. McCusker
(http://www.sciencemag.org/cgi/content/short/293/5535/1599), the work does
clear an important hurdle on the path toward sustainable hydrogen-driven
energy.
How the Brain Makes Faces
For years, neuroscientists have debated the question: Does the brain
organize information of different types, such as human faces, in discrete
physical areas, or modules, devoted to that kind of data? Or can a given
class of information be processed in many different brain areas, each
capable of handling numerous data types? A pair of articles in the 28 Sep
2001 Science, both using the neuroimaging technique known as functional
magnetic resonance imaging (fMRI), arrived at strikingly divergent answers
to the question. Haxby et al.
(http://www.sciencemag.org/cgi/content/short/293/5539/2425) found that
categories of objects such as faces, bottles, and cats each evoked a
unique brain response that was distributed among different areas across a
large region of ventral extrastriate cortex. In a separate study, however,
Downing et al. (http://www.sciencemag.org/cgi/content/short/293/5539/2470)
provided compelling evidence for the modular view: pictures of the human
body -- whether photos, line drawings, silhouettes, or stick figures --
drew a strong response from a highly circumscribed zone of the lateral
occipital cortex. Reconciling these apparently contrasting views poses a
challenge for the field, as is discussed in a Perspective by J. D. Cohen
and F. Tong (http://www.sciencemag.org/cgi/content/short/293/5539/2405).
Tool for the 21st Century
http://www.sciencemag.org/content/vol293/issue5537/index.shtml#specialintro
Over the past 50 years, no machine has done more to shape the way people
work -- especially in science -- than the computer. But where is
scientific computing headed? Science suggested some answers in a special
issue on 14 Sep 2001. News articles covered the increased R&D effort at
semiconductor giant Intel, the need for improved “science only” search
engines (and how some researchers and companies are meeting that need),
and developments in that most speculative realm of computer science,
quantum computing, which also formed the subject of a Viewpoint article in
the issue. Other Viewpoints discussed applications of computer science in
visualizing complex life-science data sets and signaling pathways; the
“invisible barrier” of inherent physical limitations facing silicon-based
circuitry; machine learning; and social themes, including the potentially
troubling impact of the Digital Millennium Copyright Act on scientific
openness and communication. An online supplement
(http://www.sciencemag.org/feature/data/compsci/index.shtml) offered links
to additional Web resources on computer science.
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