2006年《科学》十大进展
---Breakthrough of the Year 2006
- The Poincaré Conjencture--Proved (庞加莱猜想)
- DIGGING OUT FOSSIL DNA (化石DNA)
- SHRINKING ICE (冰川融化)
- NEITHER FISH NOR FOWL (鱼迈出的第一步)
- THE ULTIMATE CAMOUFLAGE (隐形技术)
- A RAY OF HOPE FOR MACULAR DEGENERATION PATIENTS (黄斑病变患者的希望)
- DOWN THE BIODIVERSITY ROAD (生物多样性)
- PEERING BEYOND THE LIGHT BARRIER (显微学的新前沿)
- THE PERSISTENCE OF MEMORY (记忆形成)
- MINUTE MANIPULATIONS (新的一类小RNA)
1 The Poincaré Conjencture--Proved (庞加莱猜想)
The solution of a century-old mathematics problem turns out to be a bittersweet prizeTo mathematicians, Grigori Perelman's proof of the Poincaré conjecture qualifies at least as the Breakthrough of the Decade. But it has taken them a good part of that decade to convince themselves that it was for real. In 2006, nearly 4 years after the Russian mathematician released the first of three papers outlining the proof, researchers finally reached a consensus that Perelman had solved one of the subject's most venerable problems. But the solution touched off a storm of controversy and drama that threatened to overshadow the brilliant work. Perelman's proof has fundamentally altered two distinct branches of mathematics. First, it solved a problem that for more than a century was the indigestible seed at the core of topology, the mathematical study of abstract shape. Most mathematicians expect that the work will lead to a much broader result, a proof of the geometrization conjecture: essentially, a "periodic table" that brings clarity to the study of three-dimensional spaces, much as Mendeleev's table did for chemistry. While bringing new results to topology, Perelman's work brought new techniques to geometry. It cemented the central role of geometric evolution equations, powerful machinery for transforming hard-to-work-with spaces into more-manageable ones. Earlier studies of such equations always ran into "singularities" at which the equations break down. Perelman dynamited that roadblock. "This is the first time that mathematicians have been able to understand the structure of singularities and the development of such a complicated system," said Shing-Tung Yau of Harvard University at a lecture in Beijing this summer. "The methods developed … should shed light on many natural systems, such as the Navier-Stokes equation [of fluid dynamics] and the Einstein equation [of general relativity]."
Unruly spaces Our bodies, and most of the familiar objects they interact with, have three dimensions. Their surfaces, however, have only two. As far as topology is concerned, two-dimensional surfaces with no boundary (those that wrap around and close in on themselves, as our skin does) have essentially only one distinguishing feature: the number of holes in the surface. A surface with no holes is a sphere; a surface with one hole is a torus; and so on. A sphere can never be turned into a torus, or vice versa. Three-dimensional objects with 2D surfaces, however, are just the beginning. For example, it is possible to define curved 3D spaces as boundaries of 4D objects. Human beings can only dimly visualize such spaces, but mathematicians can use symbolic notation to describe them and explore their properties. Poincaré developed an ingenious tool, called the "fundamental group," for detecting holes, twists, and other features in spaces of any dimension. He conjectured that a 3D space cannot hide any interesting topology from the fundamental group. That is, a 3D space with a "trivial" fundamental group must be a hypersphere: the boundary of a ball in 4D space. Although simple to state, Poincaré's conjecture proved maddeningly difficult to prove. By the early 1980s, mathematicians had proved analogous statements for spaces of every dimension higher than three--but not for the original one that Poincaré had pondered. To make progress, topologists reached for a tool they had neglected: a way to specify distance. They set about recombining topology with geometry. In 1982, William Thurston (now of Cornell University) theorized that every 3D space can be carved up so that each piece has a unique uniform geometry, and that those geometries come in only eight possible types. This hypothesis became known as the geometrization conjecture. If true, Thurston's insight would solve the Poincaré conjecture, because a sphere is the only one of the eight geometries that admits a trivial fundamental group. In 1982, Richard Hamilton (now of Columbia University) proposed a possible strategy for proving it: Start with any lumpy space, and then let it flow toward a uniform one. The result would be a tidy "geometrized" space à la Thurston. To guide the flow, Hamilton proposed a geometric evolution equation modeled after the heat equation of physics and named it "Ricci flow" in honor of Gregorio Ricci-Curbastro, an early differential geometer. In Ricci flow, regions of high curvature tend to diffuse out into the regions of lower curvature, until the space has equal curvature throughout. Hamilton's strategy works perfectly in 2D surfaces. Slender "necks," like the one seen on the cover of this issue, always expand. In 3D spaces, however, Ricci flow can run into snags. Necks sometimes pinch off, separating the space into regions with different uniform geometries. Although Hamilton did a great deal of pioneering work on Ricci flow, he could not tame the singularities. As a result, the whole program of research seemed to run aground in the mid-1990s. In 2000, when the Clay Mathematics Institute named the Poincaré conjecture as one of its $1 million Millennium Prize problems, most mathematicians believed that no breakthrough was in sight. The breakthrough In fact, Perelman was already well on his way to a solution. In 1995, the 29-year-old St. Petersburg native had returned to Russia after a 3-year sojourn in the United States, where he had met Hamilton and learned about Ricci flow. For the next 7 years, he remained mostly incommunicado. Then, in November 2002, Perelman posted on the Internet the first of three preprints outlining a proposed proof of the geometrization conjecture. To experts, it was immediately clear that Perelman had made a major breakthrough. It was in the title of the first section of the first paper: "Ricci Flow as a Gradient Flow." Perelman had spotted an important detail that Hamilton had missed: a quantity that always increases during the flow, giving it a direction. By analogy with statistical mechanics, the mathematics underlying the laws of thermodynamics, Perelman called the quantity "entropy." The entropy ruled out specific singularities that had stymied Hamilton. To reach a safe harbor, however, Perelman still had to identify the remaining types of singularities that might cause problems. He had to show that they occurred one at a time instead of accumulating in an infinite pileup. Then, for each singularity, he had to show how to prune and smooth it before it could sabotage Ricci flow. Those steps would be enough to prove Poincaré. To complete the geometrization conjecture, Perelman had to show, additionally, that the "Ricci flow with surgery" procedure could be continued for an infinitely long time. In 2003, when Perelman revisited the United States to lecture on his work, many mathematicians doubted that he could have pulled off all of these feats. By 2006, however, the mathematical community had finally caught up. Three separate manuscripts, each more than 300 pages in length, filled in key missing details of Perelman's proof. Two of the papers--one authored by Bruce Kleiner and John Lott of the University of Michigan, Ann Arbor, the other by John Morgan of Columbia University and Gang Tian of the Massachusetts Institute of Technology in Cambridge--stopped short of the geometrization conjecture, because Perelman's explanation of the final step had been too sketchy. (Both groups are still working on it.) They did, however, include enough math to nail down the Poincaré conjecture. The third paper, by Huai-Dong Cao of Lehigh University in Bethlehem, Pennsylvania, and Xi-Ping Zhu of Zhongshan University in Guangzhou, China, was less circumspect. Cao and Zhu claimed to have "the first written account of a complete proof of the Poincaré conjecture and the geometrization conjecture of Thurston." This summer, the International Mathematical Union (IMU) decided to award Perelman the Fields Medal, traditionally considered the highest honor in mathematics.
Anticlimax In the ensuing months, hard feelings have abounded. Certain mathematicians claimed that their quotes were distorted in the New Yorker, and Yau threatened to sue. Kleiner and Lott complained that Cao and Zhu had copied a proof of theirs and claimed it as original, and the latter pair grudgingly printed an erratum acknowledging Kleiner and Lott's priority. This fall, the American Mathematical Society attempted to organize an all-star panel on the Poincaré and geometrization conjectures at its January 2007 meeting in New Orleans, Louisiana. According to Executive Director John Ewing, the effort fell apart when Lott refused to share the stage with Zhu. Ewing still hopes to organize such an event "at some time in the future." For the time being, however, the animosity continues to make it hard for mathematicians to celebrate their greatest breakthrough of the new millennium. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites PoincaréConjecture Shing-Tung Yau 2 DIGGING OUT FOSSIL DNA (化石DNA) This year, on the 150th anniversary of the discovery of the Neandertal type specimen, researchers in Europe and the United States transformed the study of this ancient human by sequencing more than 1 million bases of Neandertal DNA. In November, two groups, one decoding 65,000 Neandertal bases and the other a million bases, showed that researchers can now find sequence changes between modern and ancient humans, differences that may reveal key steps in our evolution. The studies concluded that Neandertals diverged from our own ancestors at least 450,000 years ago--approximately the time suggested by fossil and mitochondrial DNA studies. One group's data also suggest that Neandertals and modern humans may have interbred. In the works are a very rough draft of the complete Neandertal genome sequence and, as more fossils become available to sequencers, the development of bacterial libraries containing DNA from several Neandertals.This breakthrough owes a large debt to earlier sequencing feats that demonstrated the potential of a new approach called metagenomics for deciphering ancient DNA, both human and nonhuman, and of faster sequencing technologies. For metagenomics, a technique developed for assessing microbial diversity, all the DNA in a sample is sequenced, and then sophisticated computer programs pull out only the target DNA based on its similarity to the sequence of a closely related extant organism. In January 2006, researchers combined metagenomics with a new rapid sequencing technique called pyrosequencing, which uses pulses of light to read the sequence of thousands of bases at once, to get a whopping 13 million bases from a 27,000-year-old mammoth. The same sample also yielded another 15 million bases from bacteria, fungi, viruses, soil microbes, and plants--DNA that will provide clues about this giant mammal's environment. With those two advances, ancient DNA sequencing is off and running. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites National Geographic: Neanderthals NOVA: Neanderthals on Trial Timeline in the Understanding of Neanderthals Glaciologists nailed down an unsettling observation this year: The world's two great ice sheets--covering Greenland and Antarctica--are indeed losing ice to the oceans, and losing it at an accelerating pace. Researchers don't understand why the massive ice sheets are proving so sensitive to an as-yet-modest warming of air and ocean water. The future of the ice sheets is still rife with uncertainty, but if the unexpectedly rapid shrinkage continues, low-lying coasts around the world--including New Orleans, South Florida, and much of Bangladesh--could face inundation within a couple of centuries rather than millennia. This disturbing breakthrough rests on decades of measurements by airborne laser altimeters and orbiting radars, and, more recently, by a pair of satellites that measure ice mass directly by its gravitational pull. Different techniques and even different analyses of the same data disagree about just how much ice volume is changing. All of them, however, now show that both Greenland and Antarctica have been losing ice over the past 5 to 10 years. In the north, Greenland is shedding at least 100 gigatons each year. In the south, the figure is less certain but lies in the range of tens of gigatons per year or more. Current ice sheet losses aren't raising sea level faster than 0.1 meter per century, but researchers fear that the rate could rise to a meter per century or more in the near future. As recently as 5 years ago, they assumed that global warming would simply melt more and more ice from the ice sheets, as it is melting mountain glaciers. But it turns out the ice isn't just melting faster, it is moving faster. Radar mapping shows that in recent years, glaciers carrying ice away from the sheets have sped up by as much as 100%. In West Antarctica, warming ocean waters seem to have attacked the floating tongues of ice that hold back the ice sheet's outlet glaciers. Around southern Greenland, something else seems to be quickening the pace of outlet glaciers, perhaps lubrication by increasing amounts of surface meltwater seeping to a glacier's base. Now glaciologists are wondering how the next chapter will play out. Will the relatively strong warming around the ice continue, or will it be weakened by natural variations of climate? Will the ice sheets adjust to the new warmth by eventually slowing their ice loss? And will more glaciers succumb to the spreading warmth? A few more breakthroughs are definitely in order. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites National Snow and Ice Data Center The West Antarctic Ice Sheet Initiative 4 NEITHER FISH NOR FOWL (鱼迈出的第一步)Paleontologists made a major splash this year with the debut of a fossil fish that long ago took a deep breath and made some tentative but ultimately far-reaching steps onto land. With its sturdy, jointed fins, the 375-million-year-old specimen fills an evolutionary gap and provides a glimpse of the features that helped later creatures conquer the continents. All limbed vertebrates, known as tetrapods, evolved from lobe-finned fishes some 370 million to 360 million years ago. Many of these sophisticated fishes had skeletons with modifications, such as enlarged bones in their fins, that would ultimately prove useful for weight-bearing limbs. The new species is the most tetrapodlike fish yet discovered. Three specimens were found during a 2004 field expedition to Ellesmere Island in the far north of Nunavut, Canada. They were named Tiktaalik roseae for "large freshwater fish" in the Inuktitut language and a donor who helped fund the expedition, respectively. With fins and scales, the 3-meter-long Tiktaalik is clearly a fish. It had a flat head with eyes on top and lived in shallow streams. What makes Tiktaalik unique among fish is that each of the front fins has a wrist and elbow, providing flexible motion. Also unlike other fish, Tiktaalik sported a neck--the oldest one known in the fossil record--and could move its head. Achieving that flexibility required losing a bone called the operculum, which modern fish use to pump water over their gills. Tiktaalik still had well-developed gills, and it probably used its neck and stout limbs to push its head above water to inhale. Another feature that makes Tiktaalik close kin to tetrapods is its robust, overlapping ribs. Although their function isn't completely clear, researchers think they could have helped support its body out of water and aided in breathing. Forays onto land would have offered an escape from sharks and other predators, as well as insects to eat. Tiktaalik isn't a perfect tetrapod, of course--among other traits, it lacks fingers and toes--but it was certainly a big step in the right direction. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites Tiktaalik roseae Science veered toward science fiction this year as physicists cobbled together the first rudimentary invisibility cloak. Although far from perfect--the ring-shaped cloak is invisible only when viewed in microwaves of a certain wavelength traveling parallel to the plane of the ring--the device could usher in a potentially revolutionary approach to manipulating electromagnetic waves. The disappearing act began in May, when two independent analyses predicted that it should be possible to ferry electromagnetic waves around an object to hide it. All that was needed was a properly designed shell of "metamaterial," an assemblage of tiny metallic rods and c-shaped rings. The waves churn the electrons in the rods and rings, and the sloshing affects the propagation of the waves. Both analyses specified how to sculpt the properties of the metamaterial and left it to experimenters to design the materials to meet those specs. In October, the team that made one of the predictions did just that--almost. Physicists at Duke University built a ring instead of an all-concealing sphere. They made some approximations that rendered the cloak slightly reflective. Still, the thing whisked microwaves around a plug of copper, proving that the method works. Cloaks for visible light are likely years off, as researchers must figure out how to make metamaterials that work at such short wavelengths. Even then, the cloak would be a bust for spying because it would be impossible to see out of it. The real breakthrough may lie in the theoretical tools used to make the cloak. In such "transformation optics," researchers imagine--?la Einstein--warping empty space to bend the path of electromagnetic waves. A mathematical transformation then tells them how to mimic the bending by filling unwarped space with a material whose optical properties vary from point to point. The technique could be used to design antennas, shields, and myriad other devices. Any way you look at it, the ideas behind invisibility are likely to cast a long shadow. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites First Demonstration of a Working Invisibility Cloak The year brought good news to the many people suffering from the vision-robbing disease known as age-related macular degeneration (AMD).In October, The New England Journal of Medicine published the results of two clinical trials showing that treatment with the drug ranibizumab improves the vision of roughly one-third of patients with the more serious wet form of AMD and stabilizes the condition of most of the others. Other approved treatments can only slow the progression of AMD. Vision loss in the wet form of AMD is caused by the growth and leakage of abnormal blood vessels in the macula, the central region of the retina. Ranibizumab, a monoclonal antibody fragment produced by Genentech Inc. does better than other treatments because it specifically targets a protein called VEGF that stimulates that vessel growth. The U.S. Food and Drug Administration approved ranibizumab for AMD treatment this year, but researchers are also looking at a related antibody made by Genentech. That drug, known as bevicizumab, is approved for treating certain cancers but so far not for use in AMD. If it works, however, it could be a cheaper alternative to ranibizumab, which costs $1950 per monthly dose. AMD researchers are making progress on another front as well. Over the past year and a half, they have uncovered several genes that influence an individual's susceptibility to the eye disease. One of them is the gene for VEGF itself, and another makes a protein that might also help regulate blood vessel growth. In addition, several groups have zeroed in on genes encoding proteins involved in inflammation, which can damage tissues if not controlled properly. Identifying those genes could help physicians determine whether a person is at high risk for AMD and thus should take preventive steps such as consuming more antioxidants and not smoking. And by shedding light on the causes of AMD, genetic studies should also provide targets for devising even better therapies. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites Medline Plus: Macular Degeneration Age-Related Macular Degeneration Macular Degeneration Parternship It doesn't take much to send an organism down speciation's path. Several studies these past 12 months have uncovered genetic changes that nudge a group of individuals toward becoming a separate species by giving them an edge in a new environment. The year's results speak to the power of genomics in helping evolutionary biologists understand one of biology's most fundamental questions: how biodiversity comes about. For Florida beach mice, a single base difference in the melanocortin-1 receptor gene accounts for up to 36% of the lighter coat color that distinguishes the beach mice, evolutionary biologists reported in July. For cactus finches, the activity of the calmodulin gene is upregulated, causing their relatively long beaks, researchers reported in August. Genes help drive speciation in other ways as well. Since the late 1930s, researchers have realized that as two incipient species diverge, the sequences of two or more interacting genes can evolve along different paths until the proteins they encode no longer work together in any crossbred offspring. Working with Drosophila melanogaster and a sister species, D. simulans, evolutionary geneticists have pinpointed the first such pair of incompatible genes, demonstrating in transgenic flies the genes'killing effects in hybrids of the two species. In October, a separate team found another fast-evolving gene and is homing in on its partner. They both seem to be nuclear pore proteins that are no longer compatible in fruit-fly hybrids. In September, fruit-fly researchers found that hybrids had problems because a particular gene was in a different place in the two species, likely because of duplication and loss of the original copy in one of them. But in at least one case, hybrids do just fine. In June, evolutionary biologists detailed the most convincing case yet of a species that arose through hybridization. They bred two species of passion vine butterflies and got the red and yellow stripe pattern of a third species (image above). The pattern proved unattractive to the parent species, helping to reproductively isolate the hybrid. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites Evolution 101 Kimball's Biology Pages: Speciation Evolution in Action [Requires Flash Player] FlyBase Biologists got a clearer view of the fine structure of cells and proteins this year, as microscopy techniques that sidestep a fundamental limit of optics moved beyond proof-of-principle demonstrations to biological applications. The advances could open a new realm of microscopy. An ordinary microscope cannot resolve features smaller than half the wavelength of the light used to illuminate an object--about 200 nanometers for visible light. For years, physicists and engineers have devised schemes to get around the "diffraction limit," and this year, researchers used those techniques to do some real biology. In April, researchers in Germany used a technique known as stimulated emission depletion (STED) to study the tiny capsules in nerve cells called synaptic vesicles. Each vesicle releases its load of neurotransmitter when it merges into the cell membrane. The team showed that a protein in the vesicle remains clumped after the merger, suggesting that the clumps do not form from scratch when the process reverses to form new vesicles. The researchers tagged the proteins with a fluorescent dye and zapped the specimen with laser light to excite a spot as small as the diffraction limit allows. Then, by applying a pulse from a second beam with a dark "hole" in the middle, they squeezed the fluorescent spot down to a much smaller pinpoint of light. By scanning the beams across the sample and recording the level of fluorescence, the researchers assembled an image with a resolution of tens of nanometers. The team followed up with two other biological studies. In August, another team imaged proteins within cells using a simpler technique known as photoactivated localization microscopy (PALM). The researchers used a fluorescent tag that had to be turned on with a pulse of light of one wavelength before it could be excited to fluoresce by light of another wavelength. By applying the first laser at a very low level, the researchers could turn on one tag molecule at a time. The molecule still produced a blurry spot when viewed through the microscope, but the researchers could nail down its position very precisely by finding the center of the blob. Repeating the process over and over, the team mapped proteins in cells with nanometer resolution. Two other groups introduced similar techniques this year. Just how widely the techniques will be used remains to be seen. PALM is too slow to track dynamic processes, and STED requires fluorescent tags that can withstand intense excitation. Still, researchers are optimistic that more applications will follow, now that the diffraction limit is no longer a limit. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites STED Microscopy New Microscope Sharpens Scientists' Focus How the brain records new memories is a central question in neuroscience. One attractive possibility involves a process called longterm potentiation (LTP) that strengthens connections between neurons. Many neuroscientists suspect that LTP is a memory mechanism, but proving it hasn't been easy. Several findings reported this year strongly bolstered the case. Scientists discovered LTP in the early 1970s, when experiments with rabbits showed that a brief barrage of electrical zaps could bolster synaptic connections between neurons in the hippocampus, a brain region tied to memory. Later studies revealed that drugs that block LTP, when given to an animal before it learns a new task, prevent new memories from being formed. But some predictions of the LTP-memory hypothesis have been harder to test. One is that it should be possible to observe LTP in the hippocampus when an animal learns something. In January, Spanish scientists reported just such an observation in mice conditioned to blink upon hearing a tone. In August, another research team described LTP in the hippocampus of rats that had learned to avoid an area where they'd previously received a shock. A study published in August addressed another prediction: that abolishing LTP after learning should erase what was learned. Researchers injected a compound that blocks an enzyme needed to sustain LTP into the hippocampus of rats after they'd been trained to avoid a "shock zone" in their enclosure. The treatment eradicated both LTP and the memory of the shock zone's location. Although the new results add to evidence that LTP is a molecular mechanism of memory, much work remains. For example, researchers still haven't figured out how the many forms of LTP identified in brain tissue relate to different kinds of memory. And they may have a while to wait for the ultimate test, which some call the "Marilyn Monroe criterion": inducing LTP at select synapses to create the vivid memory of an event, such as an evening with the voluptuous movie star, that never happened. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites Learning, Memory, and Long-Term Potentiation How Memory Works: Long-Term Potentiation The Molecular Basis of Learning and Memory Small RNA molecules that shut down gene expression have been hot, hot, hot in recent years, and 2006 was no exception. Researchers reported the discovery of what appears to be a new and still-mysterious addition to this exclusive club: Piwi-interacting RNAs (piRNAs). Abundant in the testes of several animals, including humans, piRNAs are distinctly different from their small RNA cousins, and scientists are racing to learn more about them and see where else in the body they might congregate. PiRNAs made their grand entrance last summer, when four independent groups released a burst of papers describing them. In a sense, their sudden prominence is not surprising. The Piwi genes to which piRNAs bind belong to a gene family called Argonaute, other members of which help control small RNAs known as microRNAs (miRNAs) and small interfering RNAs (siRNAs). Scientists already believed that the Piwi genes regulate the development and maintenance of sperm cells in many species. With the discovery of piRNAs, they may be close to figuring out how that happens. Particularly intriguing to biologists is the appearance of piRNAs: Many measure about 30 RNA bases in length, compared with about 22 nucleotides for miRNAs and siRNAs. Although that may not sound like much of a difference, it has gripped biologists and convinced them that piRNAs are another class of small RNAs altogether. Also striking is the molecules' abundance and variety. One group of scientists found nearly 62,000 piRNAs in rat testes; nearly 50,000 of those appeared just once.
But beyond characterizing what piRNAs look like and finding hints that they can silence genes, scientists are mostly in the dark. Still to be determined: where they come from, which enzymes are key to their birth, and perhaps most important, what they do to an organism's genome. Stay tuned. ----------------------------------------------------------------------------------------- Papers and Articles
Interesting Web Sites The RNA World Website Selected Labs Gregory Hannon (Cold Spring Harbor Laboratory) Thomas Tuschl (Rockefeller University) David Bartel (MIT) Robert Kingston (Massachusetts General Hospital/Harvard Medical School) Haifan Lin (Yale Stem Cell Center) |
