This month in Science Roundup:
Science's 125th Anniversary
Genomes to Vaccines
The Trypanosomatid Genomes
The Drug Discovery Gamble
Memory Insights
Mammals in Peril
Red Light Lures
First Stars in the Universe
Warming Oceans
Paleoecosystem Collapse Down Under
Dinosaurs Walking
Lithography on a Wire
Nanoscience in China
Toward Solid-State Quantum Computing
Science's 125th Anniversary
http://www.sciencemag.org/sciext/125th/
In a special collection of articles published beginning 1 Jul 2005, Science Magazine and its online companion sites celebrated the journal's 125th anniversary with a look forward -- to the most compelling puzzles and questions facing scientists today. In a special News section titled "What Don't We Know?" Science explored 125 questions that point to gaps in our basic scientific knowledge -- ranging from "What is the universe made of?" to "Why do humans have so few genes?" Science's Next Wave ( http://nextwave.sciencemag.org/ ) profiled four young scientists building their careers grappling with some of these conundrums. The Science of Aging Knowledge Environment ( http://sageke.sciencemag.org/ ) surveyed several big questions confronting researchers on aging, and the Signal Transduction Knowledge Environment (http://stke.sciencemag.org/ ) highlighted classic Science articles that have had a big impact in the field of cell signaling. Rounding out this anniversary collection was a special forum hosted on Science Online inviting readers to comment on Science's 125 questions -- or to nominate their own.
Two pairs of studies reported in the 1 Jul 2005 Science described genome analyses that offer new insights into important human and animal pathogens -- insights that should aid in the development of drugs and vaccines to help fight them.
Two Reports presented the genome sequence of two species of apicomplexan -- a diverse group of disease-causing parasitic protozoa. Gardner et al. ( http://www.sciencemag.org/cgi/content/short/309/5731/134 ) presented the sequence of Theileria parva, a tick-borne parasite responsible for the death of 1 million cattle in sub-Saharan Africa each year. Pain et al. ( http://www.sciencemag.org/cgi/content/short/309/5731/131 ) presented a comparison with the newly generated sequence of the related parasite T. annulata. Although both Theileria genomes are comparable in size and metabolic complexity with those of other parasites, they unexpectedly carry no obvious genes that account for the parasites' ability to transform host white blood cells. Nevertheless, mining the new sequence data should offer insights into the parasites' basic metabolic pathways and prove useful in the search for drug or vaccine candidates. An accompanying Perspective by D. S. Roos ( http://www.sciencemag.org/cgi/content/short/309/5731/72 ) highlighted the studies.
Two other studies focused on the bacterial pathogen group B Streptococcus (GBS), a major cause of life-threatening infections in newborn babies. Because antibiotics have only shown limited effectiveness in combating GBS disease, Maione et al. ( http://www.sciencemag.org/cgi/content/short/309/5731/148 ) sought to develop a broadly effective vaccine. The researchers analyzed the genome sequences of 8 GBS strains and identified and tested surface proteins common to all the strains and likely to be recognized by the immune system. They found that a combination of four of the proteins was able to protect mice against the 12 strains responsible for the majority of GBS disease in humans. Meanwhile, Lauer et al. ( http://www.sciencemag.org/cgi/content/short/309/5731/105 ) screened the genomes of multiple GBS strains and found that strep B bacteria have hollow, hairlike structures called pili that have previously gone unrecognized in these microbes. The pili are composed of antigens that can be used to immunize mice against GBS infection, a finding that suggests that pili may play an important role in the bacteria's virulence.
The Trypanosomatid Genomes
http://www.sciencemag.org/sciext/tryp/
The so-called "Tritryp" parasites -- Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major -- cause chronic and ultimately fatal infections in humans and livestock, primarily in developing countries. Although all three organisms and their diseases, which include African sleeping sickness and Chagas disease, have been studied for more than 100 years, few safe therapies exist. A special section of the 15 Jul 2005 Science presented the genomes of these notorious parasites and explored other fundamental aspects for their biology from metabolic and biochemical pathways to transcription and DNA repair; a related STKE Perspective investigated the role of host cell signaling in T. cruzi invasion. These studies allow better understanding of the genetic and evolutionary bases of the life cycle similarities and differences among the tritryp pathogens. And it is the hope that this wealth of information will provide the much-needed forward thrust for the design of new diagnostics, drugs, and vaccines. A related Editorial by G.A.M. Cross and a Viewpoint article by Morel et al. discussed the challenges in helping developing countries address neglected diseases.
The Drug Discovery Gamble
http://www.sciencemag.org/sciext/drugdisc05/
Identifying new medicines and bringing them to market is a huge gamble -- and the stakes are high. Researchers are working at the frontiers of science, combining knowledge with educated guesses, and their companies are betting millions on untested compounds, most of which never even make it into the pipeline. A special section of the 29 Jul 2005 Science examined the daunting world of drug discovery and the scientists who are braving it. Eight News stories as well as related articles on Science's Next Wave ( http://nextwave.sciencemag.org/ ) and Signal Transduction Knowledge Environment ( http://stke.sciencemag.org/ ) explored a variety of topics, including the debilitating effect of mergers and acquisitions on productivity and morale, the expansion of pharmaceutical research in China, the application of genetic and systems biology approaches to find new drug targets, and the unlikely paths to success of inventors of top-selling drugs. A related Editorial by J. Avorn discussed how an emphasis on science over advertising and other marketplace signals could foster more useful pharmaceutical innovation.
Two reports in Science this month provided insights into the formation, loss, and recovery of memory.
--SantaCruz et al. ( 15 Jul 2005; http://www.sciencemag.org/cgi/content/short/309/5733/476 ) investigated the role of neurofibrillary tangles (NFTs) in memory loss. NFTs occur in the brains of people with Alzheimer's and other neurodegenerative diseases and are twisted bundles of protein at least partially composed of deposits of the protein tau. The team studied mice that overexpressed tau and found that the animals developed age-related NFTs, neuronal loss and behavior impairments such as losing the ability to navigate a water maze. Remarkably, when the researchers turned off tau production, the mice recovered some of their lost memory despite significant neuron loss, brain atrophy, and continued growth of NFTs. This suggests that tangle pathology may be irrelevant to memory loss. A ScienceNOW story by C. Tran ( http://sciencenow.sciencemag.org/cgi/content/full/2005/714/1 ) highlighted the report.
--Leutgeb et al. ( 22 Jul 2005; http://www.sciencemag.org/cgi/content/short/309/5734/619 ) examined the role of the hippocampus in memory formation. By recording the neural activity of rats placed in various settings, the team showed that hippocampal neurons have independent coding schemes for spatial and nonspatial information. Changes in spatial location are represented as changes in the location of firing and firing rate of active cells, whereas nonspatial changes are represented by changes in firing rate while the location of firing remained constant. These independent encoding schemes may enable simultaneous representation of spatial and episodic memory information. An accompanying Perspective by G. Buzsáki ( http://www.sciencemag.org/cgi/content/short/309/5734/568 ) discussed the study.
Because resources for protecting biodiversity are limited, conservation goals are typically set for relatively small regions. However, a global view of patterns of species distributions would be extremely useful for establishing conservation priorities. In a Report in the 22 Jul 2005 Science, Ceballos et al. ( http://www.sciencemag.org/cgi/content/short/309/5734/603 ) presented the first global analysis of the conservation status of all known land mammals. According to their study, 25% of known mammal species are at risk of extinction. Moreover, to maintain 10% of the ranges of existing terrestrial mammals, more than 15% of Earth's land must be protected.
In a related study published online on Science Express (21 Jul 2005), Cardillo et al. ( http://www.sciencemag.org/cgi/content/abstract/1116030 ) explained why large mammals may be more threatened than their smaller relatives. In a statistical analysis of extinction risk in nearly 4000 mammals, the researchers found that the main risk factors for mammals smaller than 3 kilograms were environmental, such as proximity to agriculture or human populations. In larger species like elephants, however, extinction risk is driven by a combination of environmental factors and intrinsic biological constraints such as small litters and long gestation times.
The new studies, highlighted in a News story by E. Stokstad ( http://www.sciencemag.org/cgi/content/short/309/5734/546a ) suggest that a variety of approaches to conservation will be necessary in different areas and for different species.
Bioluminescence -- visible light made by living organisms -- is common throughout the ocean ecosystem. In creatures ranging from bacteria and plankton to crustaceans and fish, blue is the preferred color of such bioluminescence because blue wavelengths travel farther than those of other colors and are thus easier to detect in water. In a Brevium in the 8 Jul 2005 Science, Haddock et al. ( http://www.sciencemag.org/cgi/content/short/309/5732/263 ) reported their discovery that at least one marine invertebrate glows red. The Erenna siphonophore -- a deep-sea relative of the jellyfish -- sports tentacles with numerous side branches called tentilla that consist of stinging cells attached to a central stalk. Inside immature tentilla are spots that produce blue-green bioluminescence. Upon closer examination, the researchers found that over time, fluorescent compounds cover these blue spots, absorbing the glow and re-emitting the energy as red light. Because mature tentilla also display a rhythmic flicking behavior, the researchers suspect that that the creature uses them not for defense, but as lures to attract fish. This is at odds with the prevailing view that deep-living creatures cannot see red light. A ScienceNOW story by C. Tran ( http://sciencenow.sciencemag.org/cgi/content/full/2005/707/2 ) highlighted the curious find.
The first stars in the universe are believed to have formed shortly after the Big Bang and are likely to have been massive yet short-lived. Models of early star formation posit that the first stars formed from a primordial hydrogen-helium gas cloud and contained no metals (carbon and heavier elements like iron). Their demise is believed to have spawned a second generation of stars that recorded the elemental compositions of their progenitors. The recent discovery of "hyper metal poor" stars led to hopes that the earliest generation of stars, the so-called Population III, had been found. Now, a report in the 15 Jul 2005 Science (published online 2 Jun 2005) by Iwamoto et al. ( http://www.sciencemag.org/cgi/content/short/309/5733/451 ) suggests otherwise. The researchers described computer modeling of the elemental abundance of the two most iron-poor stars known today. The detailed abundance patters indicates that these stars are actually second-generation objects that formed from the supernovae of an earlier population of stars. Their results also suggest that stellar masses in the early universe may have included first-generation stars with only 25 times the mass of the Sun and that these lower-mass stars are responsible for the elemental abundance patters now observed in the second-generation stars. An accompanying Perspective by T. C. Beers ( http://www.sciencemag.org/cgi/content/short/309/5733/390 ) highlighted the report.
Observations have shown that about 84% of the total heating of the Earth system over the last 40 years has gone into warming the oceans. Now a Report by Barnett et al. ( http://www.sciencemag.org/cgi/content/short/309/5732/284 ) in the 8 Jul 2005 Science (published online 2 Jun 2005) substantially strengthens the evidence that human activities are responsible for the observed ocean warming. Focusing on the upper 700 meters of each ocean -- where the greatest temperature changes are found, and where scientists have the best understanding of ocean behavior -- the researchers examined the patterns of warming on an ocean-by-ocean basis, as a function of amount, location, and time. They compared the observational data to simulations from two independent climate models and show that changes in solar radiation and volcanic forcing cannot explain the observed pattern of ocean changes. However, if the release of greenhouse gases and sulfate aerosol particles is factored in, both models accurately reproduce the observed warming pattern in each ocean basin. As noted in an accompanying Perspective by G. C. Hegerl and N. L. Bindoff ( http://www.sciencemag.org/cgi/content/short/309/5732/254 ), further study of the world's oceans is still needed to better understand ocean variability, to quantify the likelihood of sudden ocean change, and to predict future changes in ocean biogeochemistry and ecosystems.
Paleoecosystem Collapse Down Under
Most of Australia's largest mammals became extinct 50,000 to 45,000 years ago, shortly after humans colonized the continent. But experts have long debated whether human activity or abrupt climate change was to blame for the these extinctions. Resolving the issue has been difficult because of the lack of well-dated environmental records. Now, in a Report in the 8 Jul 2005 Science, Miller et al. ( http://www.sciencemag.org/cgi/content/short/309/5732/287 ) provides the best evidence to date that human occupation was the driving force. The team assembled a 140,000-year record of ancient vegetation from three distinct sites in Australia based on the carbon isotope ratios of emu eggshells and wombat teeth. The record suggests that emus and wombats experienced a sudden change in diet from grasses to shrubs shortly after the proposed human arrival. Because earlier dramatic climate changes did not produce similar diet shifts, human-induced vegetation change -- possibly due to fires -- seems a more plausible explanation for the animals' eventual demise. An accompanying Perspective by C. N. Johnson ( http://www.sciencemag.org/cgi/content/short/309/5732/255 ) highlighted the study.
Paleontologists have long assumed that giant 4-legged dinosaurs called sauropods evolved from smaller bipedal ancestors and began walking on all fours only as their bodies grew too large to be carried on two feet. Now a Report in the 29 July 2005 Science suggests that sauropods actually had quadrupedal beginnings. Reisz et al. ( http://www.sciencemag.org/cgi/content/short/309/5735/761 ) examined the oldest dinosaur embryos so far discovered -- found inside fossilized eggs recovered from South Africa and dating to about 190 million years ago. The embryos' features indicate that they are Massopondylus dinosaurs -- not sauropods, but members of their closest kin, the prosauropods. The large skulls, long horizontally held necks, and proportionately long forelimbs of the embryos indicate that they hatched as quadrupeds. Interestingly, the body proportions of adult Massopondylus (and most other adult prosauropods) are characterized by a small head, short forelimbs, and robust caudal vertebrae -- all indicative of bipedal locomotion. This raises the possibility that the later sauropods evolved by preservation of the early developmental state. An accompanying News story by E. Stokstad ( http://www.sciencemag.org/cgi/content/short/309/5735/679 ) highlighted the report.
The goal of molecular electronics is to construct electronic circuit elements from individual molecules. In traditional macroscopic circuits, elements like resistors are connected to electrical "leads" on either end of the device. But how can you connect leads to either end of a molecule? One approach is to fabricate a nanoscale-gap between two electrodes followed by insertion of a molecule into the gap, but existing procedures have been imprecise, low-yielding, and difficult to control. In a Report in the 1 Jul 2005 Science, Qin et al. ( http://www.sciencemag.org/cgi/content/short/309/5731/113 ) described a new method called on-wire lithography that allows mass production and provides convenient and reproducible control over the size of the gap. First, a nanowire is fabricated from two long metal segments with a short segment made of a different metal in between. Once one side of the wire is coated with silica to stabilize it, the short middle segment is etched away leaving a nanogap between the two longer segments. The team successfully created gaps as small as 5 nanometers and showed that nanogaps can be bridged with conductive polymers. As noted in an accompanying Perspective by C. R. Martin and L. A. Baker ( http://www.sciencemag.org/cgi/content/short/309/5731/67 ), "the ease with which devices can be prepared, characterized, and manipulated bodes well for on-wire lithography to become an important tool in the molecular-electronics toolbox."
Science's yearlong "Global Voices of Science" essay series continued in the 1 Jul 2005 issue with an essay by Chunli Bai ( http://www.sciencemag.org/cgi/content/short/309/5731/61 ), Executive Vice President of the Chinese Academy of Sciences. Since China's communist regime opened up to foreign investment in 1978, China has become one of the world's fastest growing economies and has embraced a national strategy for rejuvenating the country through education and science. Among the fields that have enjoyed particularly rapid development in the past decade are nanoscience and nanotechnology, which involve understanding and building structures on the scale of atoms and molecules ( see the accompanying online slideshow at http://www.sciencemag.org/sciext/globalvoices/ ). Chinese researchers are contributing increasingly more consequential discoveries and advances, especially in the field of nanomaterial fabrication. With an estimated 3000 researchers now engaged in nanoscience R&D, Dr. Bai is confident that China will become a leading contributor to the nano era.
In a related Policy Forum, M. H. A. Hassan ( http://www.sciencemag.org/cgi/content/short/309/5731/65 ) discussed how investments by governments of developing countries in nanoscience and nanotechnology are paving the way for better science and solutions to problems of basic living -- from affordable information and communications technologies to improved water quality and cheaper food production.
Toward Solid-State Quantum Computing
In addition to mass and charge, electrons have magnetic properties directly related to their magnetic spin. These spins can combine into quantum states of different spin "parity", and such states may be useful as quantum bits or qubits -- the basic storage units of information in quantum computers. Proposals for solid-state quantum computing have so far relied on two-qubit "quantum gates" as the elementary units needed to perform computations, but controlling the coupling interaction between qubits presents a significant challenge for real implementations. In a Report in the 22 Jul 2005 Science, Engel and Loss ( http://www.sciencemag.org/cgi/content/short/309/5734/586 ) proposed a solid-state protocol that does not require interacting two-qubit gates. Instead, their scheme involves a double quantum dot system, in which electrons are allowed to leak from one dot to another. Using a nanowire acting as a charge detector, the researchers were able to sense the presence of the spin states and measure the total spin component of the system via a spin-to-charge conversion. As noted in accompanying Perspective by J. C. Egues ( http://www.sciencemag.org/cgi/content/short/309/5734/565 ) the new protocol should permit the manipulation of quantum dot qubits for quantum computation.