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SCIENCE ROUNDUP
Contents of this Issue:
Breakthrough of the Year: Genomes
Wild about the Weed (Arabidopsis genome)
Moving Ahead, Cautiously, in Stem Cell Research
News from Out There (planetary science and astrophysics)
The Science of the Very Small (nanotechnology)
Another Look at Vision Development
Memory, Amnesia, and . . . Tetris?
Malaria's Deadly Challenge
Progress in Cellular Immunology
Looking Back at the Younger Dryas
Winding Up the "Pathways" Journey
Exploring the Roots of Disease
Cholesterol's Ins and Outs
An RNA Precursor?
Special Issue: Dendrites
In the fourth quarter of 2000, *Science* brought readers insights
on stem cells, gamma ray bursts, nanomotors, and Parkinson's
disease -- as well as a roundup of the big research breakthroughs
(and pitfalls) of 2000. Here are some of the highlights of the past
three months.
Breakthrough of the Year: Genomes
*Science* ended 2000 with its annual review, "Breakthrough of
the Year" (22 Dec. 2000) -- and, though it's always tough to select
among many compelling scientific accomplishments, this year one
area seemed to stand out: genomes. The online publication of
huge volumes of genome data, the announcement of a finished
draft of the human genome, landmark papers on *Drosophila* and
*Arabidopsis*, the emergence of microarray technology for study
of gene expression and proteomics: All have the potential to
reshape biomedicine, and place humankind on some ethical *terra
incognita*, in the coming century (http://www.sciencemag.org/cgi/content/full/290/5500/2220).
Runners-up
(http://www.sciencemag.org/cgi/content/full/290/5500/2221)
included:
--the extraordinary revelations on the function of the cell's protein
factory, the ribosome, published in *Science*, *Nature*, and
*Cell* during 2000;
--a spectacular Eurasian fossil find that provided the first
undisputed evidence that humans left Africa at least 1.7 million
years ago;
--advances in the use of plastics and other organics in electronic
and laser applications;
--further progress in stem cells and cloning;
--evidence for the importance of water on and Mars and Europa; and
--new observations in cosmology, cellular receptors, planetary
geology, and "quantum weirdness."
Rounding out the presentation were predictions of top stories for
2001
(http://www.sciencemag.org/cgi/content/summary/290/5500/2222);
an assessment of *Science*'s year-end 1999 predictions for 2000
(http://www.sciencemag.org/cgi/content/summary/290/5500/2223);
a review of the Wen Ho Lee snafu
(http://www.sciencemag.org/cgi/content/summary/290/5500/2224b),
tagged the "Meltdown of the Year"; and a discussion of the
"Controversy of the Year," the debate surrounding biomedical
research ethics
(http://www.sciencemag.org/cgi/content/summary/290/5500/2225).
In keeping with genomics as 2000's Breakthrough of the Year,
*Science Online* launched a new feature, the *Science*
Functional Genomics Web Site, with links to news, research, and
resources for genomic and post-genomic science and the biotech
business (http://www.sciencegenomics.org/).
Wild about the Weed
One notable event in genome-studies history took place near the
end of 2000, when the first complete plant genome sequence -- that
of the mustard weed, *Arabidopsis thaliana* -- was published in
*Nature*. *Science* marked the occasion in its 15 Dec. 2000
issue with news, commentary, and research on this crucial model
organism. News stories reviewed the effort to sequence the weed's
complex genome, the plant's importance not only in molecular
biology but also in ecological and evolutionary studies, and the
insights the sequencing process has allowed on the mysterious
chromosomal structures known as centromeres
(http://www.sciencemag.org/content/vol290/issue5499/#newsfocus).
An editorial by Caroline Dean
(http://www.sciencemag.org/cgi/content/short/290/5499/2071)
noted the potential for plant science inherent in the *Arabidopsis*
sequence -- and also the need to balance future funding between
understanding the mustard weed and sequencing other plant
genomes. A Policy Forum by C. Somerville and J. Dangl
(http://www.sciencemag.org/cgi/content/short/290/5499/2077)
overviewed the "2010 Project," an ambitious program with the
goal of knowing the function of all plant genes within ten years.
And a trio of research articles drawing on the new data explored
the comparative genomics
(http://www.sciencemag.org/cgi/content/abstract/290/5499/2105),
gene expression
(http://www.sciencemag.org/cgi/content/abstract/290/5499/2110),
and molecular evolution
(http://www.sciencemag.org/cgi/content/abstract/290/5499/2114)
of *Arabidopsis*.
Moving Ahead, Cautiously, in Stem Cell Research
Even as it noted the extraordinary progress in genomics, *Science*
continued to publish groundbreaking work in the area cited as
Breakthrough of the Year for 1999: stem cell research. In the
1 Dec. 2000 issue, reports by Brazelton et al.
(http://www.sciencemag.org/cgi/content/abstract/290/5497/1775)
and Mezey et al.
(http://www.sciencemag.org/cgi/content/abstract/290/5497/1779)
independently showed that cells from bone marrow transplanted
into genetically altered mice can migrate to the brain. Most
remarkable, however, a small percentage of migrated cells (tagged
using expression of a green fluorescent protein in one case and a
genetic marker in the other), once they reached the brain area, were
found to express proteins characteristic of neurons -- a sign that
bone marrow had, in effect, become brain. A News Focus by
Gretchen Vogel
(http://www.sciencemag.org/cgi/content/short/290/5497/1672)
examines the implications of these discoveries in detail, and the
larger ethical debate on research using stem cells from human
embryos.
News from Out There
During the 2000 fourth quarter, new insights emerged in the pages
of *Science* into planetary geology and astrophysics, covering
settings ranging from Earth's near neighborhood to the edges of
the observable universe:
-- Brown et al. (13 Oct. 2000;
http://www.sciencemag.org/cgi/content/abstract/290/5490/320)
presented the first detailed scientific discussion of the Tagish Lake
meteorite. The presence of scores of eyewitnesses (coupled with
the serendipitous collection of the meteorite by a local resident,
who carefully preserved the specimen in his freezer) allowed a
thorough treatment of the probable orbit, pre-atmospheric mass,
and composition of an extremely primitive meteorite -- one that, as
J. N. Grossman writes in an accompanying Perspective
(http://www.sciencemag.org/cgi/content/short/290/5490/283),
could prove to be the most important recovered fall since the
Allende and Murchison events three decades ago.
-- A study of isotopic ages for impact melts in lunar meteorites by
Cohen et al. (1 Dec. 2000;
http://www.sciencemag.org/cgi/content/abstract/290/5497/1754)
suggests that the moon underwent six to ten major impact events
between 2.76 and 3.92 billion years ago, and thus provided new
evidence for the "lunar cataclysm hypothesis" -- the idea that
large-scale impacts early in its history resurfaced much of the
moon and created the prominent lunar basins. The pulse of activity
on the moon, as noted in a News Focus in the same issue
(http://www.sciencemag.org/cgi/content/short/290/5497/1677),
suggests an even more wrenching bombardment on the Earth, with
profound implications for the origin and early evolution of life.
-- The possible importance of water in early martian history (with
all of its implications for the possibility that life once existed on
the Red Planet) received another boost in the 8 Dec. 2000 issue
(http://www.sciencemag.org/cgi/content/abstract/290/5498/1927).
Malin and Edgett offered a series of impressive high-resolution
images from the Mars Global Surveyor spacecraft that include
huge, layered outcrops -- which, the authors argued, could
represent stands of sedimentary rock originally laid down in lakes
and shallow seas that formed in the crater-swept martian landscape
billions of years ago.
-- On 6 Oct. 2000, Zapatero Osorio et al.
(http://www.sciencemag.org/cgi/content/abstract/290/5489/103)
reported that, using optical and near-infrared imaging and
spectroscopy, they had determined that several objects of five to
fifteen Jupiter masses in a star cluster near the sigma-Orionis were
too cool to be stars, and thus might be planets. The kicker: If so,
these would be "planets without orbits" -- unassociated with a
particular star, and floating freely within the cluster. A news
article
(http://www.sciencemag.org/cgi/content/short/290/5489/26a)
highlighted the controversy stoked by the finding.
-- Finally, looking out to the edges of the observable universe,
papers by Amati et al.
(http://www.sciencemag.org/cgi/content/short/290/5493/953) and
Piro et al.
(http://www.sciencemag.org/cgi/content/short/290/5493/955) in
the 3 Nov. 2000 issue provided new glimpses into one of the
universe's most violent events: gamma ray bursts, which produce
more energy in a second than an average star will throw off in 10
billion years, and which are generally thought to stem from the
collapse of a supermassive star into a black hole. As discussed in
an accompanying news feature
(http://www.sciencemag.org/cgi/content/short/290/5493/926), the
observations point to a revised hypernova model in which the
supermassive star collapses not once, but *twice*.
The Science of the Very Small
*Science* also zoomed in on the efforts of researchers studying
affairs at very small length and time scales. A special section,
"Issues in Nanotechnology" (24 Nov. 2000;
http://www.sciencemag.org/content/vol290/issue5496/#specialintro),
reviewed the investigations of scientists in the diminutive world
of nanometer-scale electromechanical systems, fabricated
materials, and other devices reaching down to the molecular scale.
Also during the quarter, *Science* published pathbreaking
research on nano-world observations and developments, including:
a new method for making extremely strong carbon nanotube fibers
so plastic they can actually be tied into knots (17 Nov. 2000;
http://www.sciencemag.org/cgi/content/short/290/5495/1310);
surprising, near-molecular-scale observations of the process of
surface alloying -- characterized in a companion Perspective as
"direct observation of a nanomotor" (24 Nov. 2000;
http://www.sciencemag.org/cgi/content/short/290/5496/1520), and
with a nifty set of online movies
(http://www.sciencemag.org/cgi/content/full/290/5496/1561/DC1);
and imaging of magnetic precession at nanometer spatial and
picosecond temporal resolution (20 Oct. 2000;
http://www.sciencemag.org/cgi/content/summary/290/5491/466),
with the presentation again supplemented by a striking video clip
on *Science Online*
(http://www.sciencemag.org/feature/data/1053788.shl).
Another Look at Vision Development
For more than 30 years, it's been a core premise underlying studies
of vision development: the structures in the brain's visual cortex
that respond to stimulation from one eye or the other -- known as
ocular dominance columns -- are not pre-existent neural "tracks,"
but form and are shaped in response visual activity. But a study in
the 17 Nov. 2000 threw down the gauntlet against that widely held
view. Crowley and Katz
(http://www.sciencemag.org/cgi/content/short/290/5495/1321),
examining ocular dominance columns in ferrets at various stages
of development, found that the columns were well established even
in adults that had had all visual stimulation cut off at birth -- an
indication that retinal activity is less important in shaping the
formation of these crucial neural structures than previously
thought. An accompanying news article
(http://www.sciencemag.org/cgi/content/short/290/5495/1271)
reviewed the controversial finding and the questions that it raises.
Memory, Amnesia, and . . . Tetris?
Exploring the nature of memory sometimes entails enlisting some
unusual tools. In a fascinating study published in the 13 Oct. 2000
*Science*, Stickgold et al.
(http://www.sciencemag.org/cgi/content/abstract/290/5490/350)
employed the computer game Tetris, whose rotating, falling
geometrical blocks are familiar to overworked grad students
everywhere. In the study, both normal subjects and amnesiacs --
patients with damage to the brain's hippocampal region that
prevented them from building new stored, or "declarative,"
memories -- were taught the game in intensive sessions during the
day, and then were awakened that night during their initial, light
sleep and asked what sensations they had experienced during the
sleep period. Most of the normal subjects reported seeing images
like the shapes of the falling Tetris blocks. More surprising, the
amnesiacs reported seeing the same shapes -- even though they had
no recollection of playing the game at all. The study suggests new
insights on how the brain converts transient perceptual memories
into stored declarative memories.
Malaria's Deadly Challenge
Malaria kills between one and three million persons per year -- a
death toll greater than that of any infectious disease except AIDS
and tuberculosis. Yet, until recently, the broad scientific research
and funding communities showed less interest in understanding
and fighting the deadly malarial pathogen *Plasmodium
falciparum* than those grim numbers would suggest. After
decades of neglect, however, the fight against malaria is moving to
the front ranks of the world's scientific problems, as international
funding and aid organizations are now pouring money into malaria
studies. A special news focus (20 Oct. 2000;
http://www.sciencemag.org/content/vol290/issue5491/#newsfocus)
examined the forces reinvigorating the fight against malaria -- and
how studies of the genome of *P. falciparum* and its main vector,
the *Anopheles* mosquito, could lead to new treatment and
prevention strategies. A month later, in the 20 Nov. 2000 issue, a
set of Policy Forums
(http://www.sciencemag.org/content/vol290/issue5496/#policyforu
m) debated the pro's and con's of emphasizing genomics as a tool
in the battle against malaria.
Progress in Cellular Immunology
The "rich and diverse army" of immune-system cells that has
evolved over billions of years formed the subject of the fourth
quarter's first Special Issue of *Science* (6 Oct. 2000;
http://www.sciencemag.org/content/vol290/issue5489/#specialintro).
News stories focused on how two different cutting-edge
technologies -- computer modeling and microarrays -- are shedding
light on the workings of cellular immunology. And Review and
Viewpoint articles covered some of the scientific frontiers of
cellular immunology, overviewing recent research on inhibitory
receptors, the relationship between B cells and T cells, the
dynamics of T cell responses and T cell memory, and how the
immune system handles pathogenic invasions at surfaces such as
the skin and the mucous membranes.
Looking Back at the Younger Dryas
For paleoclimatologists, one of the most argued-about Holocene
events is the cooling around thirteen millennia ago known as the
Younger Dryas (named for the sudden reappearance in the
Scandinavian fossil record of *Dryas octopetala*, a cold-tolerant
flower). The event, a thousand-year interruption in the warming
that led to Holocene deglaciation, has been documented in North
Atlantic marine and ice cores -- but was the Younger Dryas limited
to the Northern Hemisphere, or was it a global phenomenon?
Bennett et al. (13 Oct. 2000;
http://www.sciencemag.org/cgi/content/short/290/5490/325)
offered data that strongly support the former view. Studying fossil
pollen in radiocarbon-dated sediments from four lakes in southern
Chile, they found evidence only of steady warming in the region,
and a steady southward-migration of cold-tolerant species, with no
reversal during the period corresponding to the Younger Dryas (or,
for that matter, any other time). D. T. Rodbell discussed the
findings in an accompanying Perspective
(http://www.sciencemag.org/cgi/content/summary/290/5490/285).
A 22 Dec. 2000 study of the precipitation history of the Amazon
basin, by Maslin et al.
(http://www.sciencemag.org/cgi/content/abstract/290/5500/2285),
however, points to other Southern Hemisphere changes during the
Younger Dryas period: the study suggests that the Amazon's
discharge then dropped to some 60% below modern values -- a dry
Younger Dryas indeed.
Winding Up the "Pathways" Journey
The climate system also formed the subject of the quarter's first
essay in "Pathways of Discovery" -- *Science*'s yearlong
exploration of the history and future of some key scientific
disciplines. P. J. Crutzen and V. Ramanathan (13 Oct. 2000;
http://www.sciencemag.org/cgi/content/summary/290/5490/299)
looked at the evolution of atmospheric science, from Torricelli's
invention of the barometer, in the mid-17th century, to
sophisticated numerical models run on massively parallel
computers, at the dawn of the 21st. A month later, E. R. Kandel
and L. R. Squire (10 Nov. 2000;
http://www.sciencemag.org/cgi/content/summary/290/5494/1113)
reviewed the incredible development of cellular and molecular
neuroscience since Ramon y Cajal's advancing of the "neuron
doctrine" in the early 1900s. And M. J. Rees (8 Dec. 2000;
http://www.sciencemag.org/cgi/content/summary/290/5498/1919)
wound up the Pathways journey with a whirlwind tour through
perhaps the strangest science of all, cosmology: the realm of black
holes, neutron stars, dark matter, and superstrings.
Exploring the Roots of Disease
The deep structure and potential treatment of celebrated diseases
were the subject of several fascinating *Science* reports over the
past three months:
--Orth et al. (24 Nov. 2000;
http://www.sciencemag.org/cgi/content/short/290/5496/1594)
illuminated the signal-transduction havoc wrought by one of
history's most notorious killers, *Yersinia pestis* -- the pathogen
responsible for the Black Death, which routed Europe and Asia
during the 14th century. As is discussed in an accompanying news
article
(http://www.sciencemag.org/cgi/content/summary/290/5496/1475)
, one of the *Yersina* bacterium's first acts is to inject into the
body's macrophage cells a protein called YopJ, which in turn rips
apart the proteins that the macrophage uses to communicate the
infection's presence to the body's other immune cells.
--The food-borne pathogen *Listeria monocytogenes*, by contrast,
rather than injecting a disruptive protein to foil the immune
system, actually enlists the aid of unwitting macrophages in its
attack, according to research published on 3 Nov. 2000 by Decatur
and Portnoy
(http://www.sciencemag.org/cgi/content/short/290/5493/992).
After being consumed by the macrophage and trapped within an
interior vacuole for later destruction, *Listeria* uses its own pore-
forming protein, listeriolysin O, to burrow through the vacuole
wall. Because of an unusual sequence in the protein molecule,
however, the pore-forming protein degrades quickly after rupturing
the vacuole, which allows *Listeria* to take up residence and
multiply within the macrophage without destroying the host cell --
and protected from the body's other immune defenses.
--Kordower et al.
(http://www.sciencemag.org/cgi/content/short/290/5492/767), on
27 Oct. 2000, reported progress in the treatment of another
scourge: Parkinson's disease, which afflicts some one million
Americans, as noted in the accompanying Perspective by L. Olson
(http://www.sciencemag.org/cgi/content/summary/290/5492/721).
The Kordower et al. study was also an advance in gene therapy: In
two primate models of the disease, the researchers used a lentiviral
vector to introduce a gene expressing glial cell line-derived growth
factor (GDNF), which in turn prevented degeneration of dopamine
neurons, allowed some neuronal regeneration -- and resulted in
reduced motor defects.
Cholesterol's Ins and Outs
A package of articles on 1 Dec. 2000 explored the state of the art
in cholesterol studies. Simons and Ilkonen
(http://www.sciencemag.org/cgi/content/short/290/5497/1721)
reviewed recent findings in the cell biology of cholesterol, and at
how a new focus on the cellular processes regulating influx, efflux,
and synthesis of cholesterol could lead to new progress in
controlling cholesterol disease. Berge et al., in a report in the same
issue
(http://www.sciencemag.org/cgi/content/short/290/5497/1771),
focused on the genetic mutations and associated proteins
responsible for a rare form of inherited cholesterol disease. Their
findings, as noted in a companion Perspective by Allayee et al.
(http://www.sciencemag.org/cgi/content/short/290/5497/1709),
provide "important insights" into cholesterol trafficking in the
body -- and also suggest potential targets for drugs to decrease
serum cholesterol. Findings released three weeks later on
Niemann-Pick C disease, an ailment related to faulty cellular
management of cholesterol, shed additional light on cholesterol
transport (22 Dec. 2000;
http://www.sciencemag.org/content/vol290/issue5500/twis.shtml#
290/5500/2209c).
An RNA Precursor?
Just how different was the chemistry of life at the dawn of the
biotic era? Schoening et al. (17 Nov. 2000;
http://www.sciencemag.org/cgi/content/short/290/5495/1347)
examined the tantalizing possibility that one of the fundamental
molecules of modern life, ribonucleic acid (RNA) -- the basic
machine of the protein synthesis on which all life depends -- may
have been preceded in the "prebiotic soup" by simpler genetic
materials. In laboratory experiments, the group synthesized and
studied an RNA analog based on the tetrose sugar threose, which
they dubbed "TNA"; what's more, they found that TNA strands
can form stable double-helices both with each other and with
strands of RNA and DNA. The potential importance of this
finding, as noted in a Perspective by L. Orgel
(http://www.sciencemag.org/cgi/content/summary/290/5495/1306),
is that tetrose sugars like threose, which can be assembled
directly from two identical two-carbon fragments, would likely
form more readily in a prebiotic world than pentose sugars like
ribose, which have a more complex structure. Thus, in principle,
TNA is one candidate for "an alternative genetic material for
primitive life forms" -- though many questions remain.
Special Issue: Dendrites
Dendrites have been called "the brains of the neuron" -- and
studies of these beautiful and complex, branching structures are
yielding new insights into the biochemical processes that shape
thought and memory. A special issue of *Science* (27 Oct. 2000;
http://www.sciencemag.org/content/vol290/issue5492/#specialintro)
updated readers on recent progress in dendrite research --
including a news feature on the role of protein synthesis in dendrite
function, and reviews on the dynamics of dendrite signaling,
quantitative models, how the dendrites process information from
thousands of synapses, and the structural changes and plasticity in
dendrites that may underlie memory and learning.
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