# News this Week

Science  18 Dec 2009:
Vol. 326, Issue 5960, pp. 1598
1. Breakthrough of the Year

# Ardipithecus ramidus

1. Ann Gibbons

A rare 4.4-million-year-old skeleton has drawn back the curtain of time to reveal the surprising body plan and ecology of our earliest ancestors.

See references and Web links on Ardi.

Only a handful of individual fossils have become known as central characters in the story of human evolution. They include the first ancient human skeleton ever found, a Neandertal from Germany's Neander Valley; the Taung child from South Africa, which in 1924 showed for the first time that human ancestors lived in Africa; and the famous Lucy, whose partial skeleton further revealed a key stage in our evolution. In 2009, this small cast got a new member: Ardi, now the oldest known skeleton of a putative human ancestor, found in the Afar Depression of Ethiopia with parts of at least 35 other individuals of her species.

Ever since Lucy was discovered in 1974, researchers wondered what her own ancestors looked like and where and how they might have lived. Lucy was a primitive hominin, with a brain roughly the size of a chimpanzee's, but at 3.2 million years old, she already walked upright like we do. Even the earliest members of her species, Australopithecus afarensis, lived millions of years after the last common ancestor we shared with chimpanzees. The first act of the human story was still missing.

Now comes Ardi, a 4.4-million-year-old female who shines bright new light on an obscure time in our past. Her discoverers named her species Ardipithecus ramidus, from the Afar words for “root” and “ground,” to describe a ground-living ape near the root of the human family tree. Although some hominins are even older, Ardi is by far the most complete specimen of such antiquity. The 125 pieces of her skeleton include most of the skull and teeth, as well as the pelvis, hands, arms, legs, and feet. (The 47-million-year-old fossil of the early primate called Ida is also remarkably complete, but she is not a direct ancestor to humans, as initially claimed during her debut this year.)

When the first fossils of Ardi's species were found in 1994, they were immediately recognized as the most important since Lucy. But the excitement was quickly tempered by Ardi's poor condition: The larger bones were crushed and brittle, and it took a multidisciplinary team 15 years to excavate Ardi, digitally remove distortions, and analyze her bones.

Ardi's long-awaited skeleton was finally unveiled in 11 papers in print and online in October (Science, 2 October, pp. 60–106). Her discoverers proposed that she was a new kind of hominin, the family that includes humans and our ancestors but not the ancestors of other living apes. They say that Ardi's unusual anatomy was unlike that of living apes or later hominins, such as Lucy. Instead, Ardi reveals the ancient anatomical changes that laid the foundation for upright walking.

Not all paleoanthropologists are convinced that Ar. ramidus was our ancestor or even a hominin. But no one disputes the importance of the new evidence. Only a half-dozen partial skeletons of hominins older than 1 million years have ever been published. And having a skeleton rather than bits and pieces from different individuals not only provides a good look at the whole animal but also serves as a Rosetta stone to help decipher more fragmentary fossils. As the expected debate over Ardi's anatomy and relations to other primates begins, researchers agree that she and the other specimens of her species provide a wealth of new and surprising data on some of the most fundamental questions of human evolution: How can we identify the earliest members of the human family? How did upright walking evolve? What did our last common ancestor with chimpanzees look like? From now on, researchers asking those questions will refer to Ardi.

## Body of evidence

Ardi's biggest surprise is that she was not transitional between Australopithecus and a common ancestor that looked like living chimpanzees and gorillas. Standing 120 centimeters tall, Ardi had a body and brain only slightly larger than a chimpanzee's, and she was far more primitive than Lucy. But she did not look like an African ape, or even much like the known fragments of more ancient apes.

When researchers studied her face and teeth, they found derived features that tie Ardipithecus to all later hominins, including Lucy's species and us. For example, Ardi's muzzle juts out less than a chimpanzee's does. Even males of her species lacked the large, sharp, daggerlike upper canines seen in chimpanzees. The base of her skull is short from front to back, as in upright walkers, rather than elongated, as in quadrupedal apes.

In addition, Ardi's pelvis convinced her discoverers that she did indeed walk upright—long the defining trait for being a member of the human family. The upper blades of Ardi's pelvis are shorter and broader than in living apes, lowering her center of gravity so she could balance on one leg at a time while walking, for example. But she didn't walk as well as humans or Lucy. Her pelvis was useful for both climbing and upright walking, making her a “facultative” biped, according to her discoverers.

Ardi's remarkably complete hand and foot bones add to this picture. Her wrist joints were not as stiff as those of African apes, and the bones of her palm were short, indicating that she did not knuckle-walk like chimpanzees or swing beneath tree branches, the discoverers say. Yet Ardi's foot was more rigid than a chimpanzee's, suggesting that it was an odd mosaic used for both upright walking on the ground and careful climbing and walking atop branches in the trees. Indeed, Ardi's long curving fingers and opposable big toe suggest she grasped tree branches.

If so, our ancestors began walking upright while still living primarily in a woodland rather than in more open, grassy terrain, as once believed. The international discovery team went to great lengths to reconstruct the scene where Ardi took her first steps, collecting 150,000 specimens of fossil plants and animals from Aramis and nearby. After using radiometric methods to tightly date the fossil-bearing sediments to 4.4 million years ago, the team concluded that Ardi lived on an ancient floodplain covered in sylvan woodlands, climbing among hackberry, fig, and palm trees, and coexisting with monkeys, kudu antelopes, and peafowl.

## Human relations

At face value, Ardi is a hominin—if you define hominin on the basis of traits in the face, skull, and teeth. Many researchers who have read the descriptions of Ardipithecus or seen casts of the fossils agree on this. But since Lucy's discovery, the gold standard for identifying a hominin has been walking upright. Among primates, only humans and our closest relatives were habitual bipeds. On this point, Ardi stands on shakier ground.

The pelvis, which provides the pivotal evidence for upright walking, is fragmentary and crushed—parts of it have been called “Irish stew”—and outside researchers want to review its reconstruction. The discoverers note, however, that the interpretation of upright walking rests on traits in the foot and on the best-preserved portions of the original pelvis, not the reconstruction.

A few outside researchers who have already seen the cast of the pelvis agree that it shares some key traits with later hominins, such as the shape and size of a large opening known as the sciatic notch. Yet Ardi's hands and feet are so primitive that some researchers strongly question whether she really walked upright more often than other apes or was less able to climb and swing beneath branches. The next steps will be to further compare Ardi's bones with those of more ancient apes and to see how her unique anatomical features affected how she moved.

Many researchers also challenge the papers' forceful argument that Ardi reveals the basic body plan of the common ancestor of humans and chimpanzees. They point out that Ardi lived perhaps 1 million to 3 million years after that ancestor—plenty of time for evolutionary change. Some also question the social implications of Ardipithecus males' reduced canines, which the discovery team interprets as implying less male-male aggression than is seen in chimps.

The debate reveals how hard it is to identify upright walking in such an early hominin. Must Ardi walk upright like an australopithecine to be admitted to the human family? Or is it enough that she walked upright in an intermediate manner, if her face, skull, and canines align her with later protohumans? Ardi is already prompting some to ask whether habitual upright walking is essential to being a hominin. Perhaps some ancient apes became hominins head first.

There's precedent for new hominin fossils provoking controversy and redefining what it means to be a member of the human family. Many thought a big brain and tool use emerged in concert with upright walking—until Lucy, with her chimp-sized brain, proved that upright walking came first.

As researchers ponder the definition of a hominin, they also wonder exactly where Ardi fits in our family tree. The discovery team suggested as one hypothesis that Ardipithecus gave rise to Lucy's genus Australopithecus, which is generally thought to have led to our own genus, Homo. But they also noted that Ardi could have been a side branch, an extinct lineage that was a sister species to our direct ancestors. As the study of Ardi widens to include new collaborators, the team is granting requests to view the casts and will return to Aramis to search for more fossils.

In the year of the bicentennial of Darwin's birth, it seems fitting that researchers finally broke through the 4-million-year barrier to understanding our origins. Models for our earliest ancestors can now be informed by plenty of fresh data and at least one body of hard evidence.

2. Breakthrough of the Year

# The Runners-Up

1. The News Staff

This year's runners-up for Breakthrough of the Year include new gamma-ray observations, the long-sought receptor for a key plant hormone, mock monopoles, a drug that increases life span, ice on the moon, gene-therapy successes, insights into the properties of graphene and how to use it to make novel devices, Hubble's rebirth, and the first x-ray laser.

## Opening Up the Gamma Ray Sky

See references and Web links on the gamma ray sky.

Like a lighthouse blinking in the night, a pulsar appears to flash periodically as it spins in space, sweeping a double cone of electromagnetic radiation across the sky. Since the discovery of the first pulsar 4 decades ago, astronomers have detected hundreds more of these enigmatic objects from the pulsing radio waves they emit. Now, astronomers have opened a new channel of discovery—the highly energetic gamma ray spectrum—to find pulsars that radio observations could not detect. The advance, part of a torrent of recent gamma ray observations, is giving researchers an improved understanding of how pulsars work, along with a rich haul of new pulsars that could help in the quest to detect gravitational waves.

The findings come from the Fermi Gamma-ray Space Telescope, which has been mapping the gamma ray universe since it was launched by NASA in June 2008. Combing through data the telescope collected in its first few months, an international team discovered 16 new pulsars; strong gamma ray pulsations from eight previously known pulsars with spin times of milliseconds, proving that these objects pulse brightly at gamma wavelengths as well as in the radio range; and high-energy gamma rays from the globular cluster 47 Tucanae indicating that the cluster harbors up to 60 millisecond pulsars.

Those Fermi results might be just the beginning. Armed with their new knowledge of pulsar behavior, researchers are checking whether some of the unidentified gamma ray sources Fermi has detected might be pulsars. In November alone, teams of astronomers in the United States and France discovered five new millisecond pulsars by training ground-based radio telescopes on candidate objects Fermi had pointed out—a much more targeted search technique than scanning the sky blindly with ground-based radio telescopes.

Gamma ray beams of pulsars are believed to be wider than their radio beams, so in principle a space-based gamma ray telescope should be more likely to encounter and discern a pulsar's sweep than a radio telescope on Earth is. However, Fermi's forerunner—the Compton Gamma Ray Observatory, which flew from 1991 to 2000—did not have much luck finding these objects. What has made the difference is Fermi's high sensitivity, which enables it to detect pulsations that would have been too faint for Compton.

Already, the discoveries are shedding new light on the physics of pulsars. Researchers know that pulsars are fast-spinning neutron stars with powerful magnetic fields that accelerate particles to near–light speed and shoot them out from the poles. Those hot jets of matter give off gamma rays. But how are the magnetic fields structured, and exactly where do the particle beams emanate from? In one type of model, the jets erupt from the polar caps on the surface of the neutron star; in another, the beam originates above the poles, thousands of kilometers out in space.

An analysis of the gamma ray emission from the pulsars Fermi observed dealt a severe blow to the polar cap model, astrophysicists say. Instead, the observations suggest that the bulk of the emission comes from a location in the outer magnetosphere. Such detailed examination of how pulsars work would be impossible through radio observations alone, because radio waves make up only a minute fraction of the pulsar's total energy; gamma rays represent a much more substantial chunk of its radiation.

Astrophysicists say the pulsar results herald further discoveries about many other types of cosmic objects. The more than 1300 gamma-ray sources Fermi has detected include starbursting galaxies, gamma ray bursts, and the black holes at the center of galaxies. In November, teams at two ground-based gamma ray telescopes, in combination with Fermi, solved a long-standing mystery by tracing cosmic rays, highly energetic particles from space, to their birthplaces inside exploding stars (Science, 20 November, p. 1047). The new pulsars themselves could help researchers detect gravitational waves—ripples in the fabric of spacetime, which should cause apparent changes in the rotation rate of the most rapidly spinning pulsars.

See references and Web links on the gamma ray sky.

## ABA Receptors

See references and Web links on plant ABA receptors.

Although “Fight or Flight” is not in their behavioral repertoire, plants have their equivalent of an adrenaline rush: a chemical called abscisic acid (ABA). High concentrations of ABA keep seeds dormant and help curtail water loss and inhibit root and other vegetative growth when times are tough. The receptors for this key plant hormone have long eluded plant biologists, sending them down false trails and leaving research in disarray. But in May, two independent teams, taking different approaches, identified the same family of proteins as the receptors. By late fall, several other groups had confirmed the connection between ABA and the PYR/PYL/RCAR proteins. As one leader in the field put it: “The ABA receptor field finally has a success.”

One team, based in Germany, homed in on these receptors by looking for proteins that bind to enzymes called ABI1 and ABI2, known to help spur ABA activity. They found two, calling each a “regulatory component of ABA receptor” (RCAR). A second team, based in California, tracked down an ABA receptor by figuring out what pyrabactin, which revs up ABA activity, interacts with. This group called the receptor PYR1. Both teams discovered that their receptors were part of the same 14-member protein family.

Other researchers from China, Japan, Europe, and the United States have supported these results. Several have obtained crystal structures of ABA bound to its receptor or ABA and the receptor interacting with the PP2C phosphatases that must be shut down to allow ABA to function. The structures show that PYR/PYL/RCAR proteins pair off, making a gated pocket that ABA nestles into. ABA changes the shape of the pair of molecules so that the “gate” closes and creates a binding surface for a PP2C.

These results are a boon for plant biology—and possibly beyond. The PP2C and the ABA receptors both belong to highly conserved families of proteins whose roles in other organisms may become clearer now that their function in plants has been nailed down.

See references and Web links on plant ABA receptors.

## Mock Monopoles Spotted

See references and Web links on mock monopoles.

In Dr. Seuss's famous children's book How the Grinch Stole Christmas, the curmudgeonly protagonist snaps, “If I can't find a reindeer, I'll make one instead!” Physicists have taken a similar approach to the pursuit of a long-sought particle called a magnetic monopole. They still haven't found such a creature, but this year two teams created ripples, or “quasiparticles,” inside magnetic crystals that act like monopoles.

As far as physicists know, every magnet has a north pole and a south pole. However, theorists have speculated about fundamental particles that have only one or the other. In 1931, the British theorist Paul Dirac argued that the existence of such monopoles would explain the quantization of electric charge. Monopoles are also predicted by “grand unified theories” that treat the electromagnetic, the weak, and the strong forces as different aspects of one thing.

The monopoles reported in September exist only in materials such as holmium titanate and dysprosium titanate, which are known as spin ices. Within them, the gyrating and magnetic holium or dysprosium ions sit at the corners of four-sided pyramids, or tetrahedra, just as hydrogen ions do in ice. At low temperatures, two ions in each tetrahedron point their north poles inward toward the tetrahedron's center and two point their north poles outward. Flipping one ion then creates one imbalanced tetrahedron with three ions pointing in and another tetrahedron with only one ion pointing in. Flip more spins and the imbalances can shuffle about independently, acting like monopoles.

Such “spin systems” provide a playground for theorists and experimentalists alike. The observed monopoles illustrate the richness of such systems in a simple way.

See references and Web links on mock monopoles.

## Live Long and Prosper

See references and Web links on rapamycin.

It's not Ponce de León's vision of the fountain of youth: the secretion of a dirt-dwelling bacterium from Easter Island. But this year researchers showed that the compound, called rapamycin, boosts longevity in mice, the first time any drug has stretched a mammal's life span.

Doctors prescribe rapamycin to battle kidney cancer and to stymie rejection of transplanted organs. After the U.S. National Institute on Aging added the drug to its list of molecules that might increase rodent life span, the three U.S. labs that test such candidates started feeding rapamycin to mice when they were 600 days old, comparable to 60-year-old people. The rapamycin-rich diet added between 9% and 14% to the rodents' life span. Researchers had achieved similar feats in worms and flies, but the result was a first in mammals—and especially encouraging because the animals were already past their prime.

The drug's mechanism has scientists puzzled. Rapamycin curbs the TOR biochemical pathway, which is involved in everything from protein synthesis to cell division. However, the drug didn't thwart any specific cause of death: The mice suffered the full range of old-age infirmities such as ulcers and heart failure. And because the mice didn't become skinny, the researchers doubt that rapamycin works similarly to calorie restriction (CR)—an extreme diet that can increase longevity in mice and some other lab organisms—although other scientists think there might be a connection.

Meanwhile, another study released this year brought us closer to answering the big question about CR: whether it's effective in humans. The first primate trials, on rhesus monkeys, started 20 years ago. Now the animals are starting to die from age-related causes, and the early results indicate that they are outlasting their well-fed contemporaries.

Rapamycin undermines the immune system, and only zealots can stick to CR. So neither is likely to be a practical life extender. But they might lead researchers to more palatable alternatives for slowing aging or at least increasing how long we remain healthy.

See references and Web links on rapamycin.

## An Icy Moon Revealed

See references and Web links on lunar ice.

Planetary scientists finally proved this year that a barren, often boiling-hot body like the moon can harbor water ice. The finding renewed prospects for reading an eons-long environmental record and for literally fueling the exploration of the solar system.

An icy moon hadn't been a totally outrageous idea. Radar probing of Mercury from Earth in the early 1990s had revealed what seemed to be water ice buried beneath the floors of impact craters on Mercury. The deposits appeared only in polar craters whose rims cast permanent shadows across their floors, ensuring the required perpetual cold. Perhaps, scientists reasoned, over the eons a bit of the water from impacting comets and icy asteroids got frozen into the permanently shadowed craters. Orbiting radar eventually hinted at ice in polar lunar craters, too, but that notion remained controversial, even after an orbiting instrument in 1998 detected high polar concentrations of hydrogen that could be part of buried water molecules.

In the end, it took slamming a 2-ton spent rocket stage into a permanently dark, frigid crater called Cabeus at 7200 kilometers per hour to coax a few liters of water into sight. The $80-million Lunar Crater Observation and Sensing Satellite (LCROSS) mission returned clear spectroscopic signatures of water vapor, ice, and water-derived hydroxyl in the impact plume. LCROSS also returned evidence for a source of the moon's water. Its sensors detected molecules such as carbon monoxide, methane, and methanol that had been buried with the water ice. Those are just the sort of compounds found in comets and icy asteroids, so at least a few spots on the moon may have retained a trace of the bodies that have been bombarding the moon for eons. Icy stores of lunar water might hold records of lunar impacts over billions of years. Astronauts might drink the water, grow food with it, or even split its molecules into hydrogen and oxygen for rocket fuel. One problem: Someone would have to figure out how to conduct coring and mining operations on the moon at just 40° above absolute zero. See references and Web links on lunar ice. ## Gene Therapy Returns ### Web Links See references and Web links on gene therapy. Gene therapy—repairing malfunctioning cells by mending their DNA—offers an elegant solution to diseases caused by a single flawed gene. Since the first human study began in 1990, however, the field has struggled with technical challenges and setbacks such as the death of a volunteer in a trial. But this year, gene therapy turned a corner, as researchers reported success in treating several devastating diseases: • Leber's congenital amaurosis (LCA), a rare form of inherited blindness that strikes in infancy. Researchers in the United States and the United Kingdom injected one eye of LCA patients with a harmless virus carrying a gene coding for an enzyme needed to make a light-sensing pigment. In the first completed trial, the light sensitivity of all 12 partially blind patients improved. Four children gained enough vision to play sports and stop using learning aids at school. (Another team using a similar approach gave full color vision to squirrel monkeys born with red-green colorblindness.) • X-linked adrenoleukodystrophy (ADL), a brain disorder that usually kills boys before they're teenagers. The disease involves a flaw in a gene that makes a protein that helps maintain the myelin sheath around nerves. A French team inserted a corrective gene into the blood cells of two 7-year-old boys with ADL, and some of the cells began making the missing protein and apparently migrated into their brains. Two years later, the progressive brain damage typical of ADL has stopped. The trial is also the first to carry the gene into cells with a disabled HIV virus, which should be less likely than older vectors to cause cancer. • “Bubble boy” disease: severe combined immunodeficiency (SCID) due to a lack of an enzyme called adenosine deaminase. In January, Italian researchers gave an update on an 8-year-old trial for children with the disease. Eight of 10 patients no longer need enzyme-replacement therapy and are living normal lives. None suffered serious side effects from the therapy. (Gene therapy for a related disease, X-linked SCID, restored the immune systems of 19 infants but caused leukemia in five of them, one of whom died.) Clinical results for other genetic diseases are expected out soon, and more trials using the new, safer vectors are gearing up. See references and Web links on gene therapy. ## Graphene Takes Off ### Web Links See references and Web links on graphene. Progress in materials science often plods. Graphene soars. Since 2004, when researchers in the United Kingdom discovered a simple way to peel the single-atom-thick sheets of carbon atoms off chunks of graphite, researchers have scrambled to study this ultimate membrane. This year they took it to a new level, with a string of discoveries that include new fundamental insights and ways to make large graphene sheets and turn them into novel devices. Much of graphene's fascination lies in the way it conducts electrons. Its near-perfect atomic order—a chicken wire–like lattice of carbon atoms—allows electrons to flow through it at ultrafast speeds. That property enables physicists to use it as a simple test bed for some of the unusual features of quantum mechanics. Last month, for example, separate research groups in New York and New Jersey confirmed that graphene's electrons exhibit the fractional quantum Hall effect, in which electrons act collectively as if they are particles with only a fraction of the charge of an electron. This behavior was spotted decades ago in some multilayer semiconductors but never before in such a simple material. Simplicity reigned elsewhere as well. In May, researchers at the University of Texas, Austin, reported that they had made graphene films up to a centimeter square by growing them atop thin copper foils. A team at Cornell University modified their technique to grow graphene on silicon wafers. The two advances open the door for making large arrays of graphene-based electronic devices. Progress on such devices also surged. In January, researchers at IBM reported building graphene transistors that can switch on and off 26 billion times per second, far outpacing conventional silicon devices. Researchers at the Massachusetts Institute of Technology chipped in with a graphene frequency multiplier for electronic signals, which could lead to new applications in communication and sensing. And elsewhere, researchers turned out everything from a graphene-based scale capable of weighing small molecules to a superfast graphene photodetector. Simple or not, researchers are making it look easy with graphene. See references and Web links on graphene. ## Hubble Reborn ### Web Links See references and Web links on the HST. It was an aging workhorse that almost got put out to pasture. But this fall, the Hubble Space Telescope began snapping the best images of its 19-year career, thanks to a successful servicing mission in May that has extended the instrument's life by another 5 years. The mission capped a long battle within NASA to keep Hubble alive after former NASA Administrator Sean O'Keefe announced the cancellation of a planned 2004 shuttle flight to service the telescope. NASA officials pondered sending a robot to make the necessary repairs, but many experts saw that as an unrealistic proposition that would doom Hubble. Proponents of maintaining the telescope's operations heaved a sigh of relief in 2006 when O'Keefe's successor, Michael Griffin, asked the agency's astronauts to buckle up for a final journey to refurbish the instrument. In May, a seven-member crew on board the shuttle Atlantis traveled 500 kilometers above Earth, making five spacewalks over 11 days to carry out a set of complex and risky maneuvers. By the end, they had checked off all the tasks on their list: replacing the Wide Field Camera 2 with the new Wide Field Camera 3, which offers more than 10 times the image resolution; installing the Cosmic Origins Spectrograph, which enhances Hubble's ability to take ultraviolet spectra; and making fixes to two existing devices, the Advanced Camera for Surveys and the Space Telescope Imaging Spectrograph. On 9 September, NASA released the results of the effort: spectacular images of the Butterfly Nebula, the Omega Centauri globular cluster, and other stellar wonders. Hubble was back in business. Now, scientific work using Hubble data is picking up pace: In recent months, for example, the instrument has delivered the most detailed pictures yet of the nearby spiral galaxy, M83, which should help researchers learn more about star birth in its core. See references and Web links on the HST. ## First X-ray Laser Shines ### Web Links See references and Web links on the x-ray laser. In April, a new type of light flashed into existence. Physicists at SLAC National Accelerator Laboratory in Menlo Park, California, turned on the world's first x-ray laser, a 130-meter beast called the Linac Coherent Light Source (LCLS) that is powered by the lab's 3-kilometer, straight-shot particle accelerator. The machine is the heart of a$420 million user facility, and after 3 years of construction, researchers needed less than 2 hours to fire it up.

The LCLS is a tool, but it deserves the appellation “breakthrough” because it takes a qualitative stride far beyond its predecessors. For decades, scientists have used x-rays to probe the atomic-scale structure of materials. Shining a billion times brighter than any previous source, the LCLS produces pulses of x-rays as brief as 2 millionths of a nanosecond, short enough to snap stop-action images of chemical reactions in progress. Simply put, the LCLS is the first device to combine atomic-scale spatial and temporal resolution. It also pumps out x-rays in a coherent quantum wave, allowing researchers to borrow techniques developed for conventional lasers.

Experiments with the LCLS began in October. Scientists hope to determine the structure of a protein from a sample of one molecule or rip out the inner-shell electrons from all the atoms in a material to see how the stuff reacts. Given that x-ray sources called synchrotrons are already workhorses for structural biologists and material scientists, some question what exactly the newfangled LCLS will be good for. But the fact that scientists are asking “What can we do with this?” shows that the LCLS is something completely new that may produce dramatic advances nobody has foreseen.

See references and Web links on the x-ray laser.

3. Scorecard

# Rating Last Year's Areas to Watch

Science's editors clearly foresaw this year's burgeoning of plant genome sequences, progress on emissions reductions in the run-up to the U.N. conference in Copenhagen, and the continued failure to spot dark matter. Last year's other predictions will take more time to come to fruition.

(For this year's predictions, see page 1606.)

## Plant genomics

The genome sequences of cucumber, sorghum, and two strains of maize saw print in 2009, a cause for celebration. Cassava and oil palm were sequenced as well, and there has been progress on numerous other plants, although perhaps not as much as Science forecast.

## Ocean fizz

The inevitable acidification of the ocean by rising atmospheric carbon dioxide garnered more public attention in 2009, but—as anticipated—not much. The expected bad news about generally harmful effects on living things kept coming, and hot spots of particularly rapid acidification turned up, but nothing pushed world attention across a threshold. Climate negotiations in Copenhagen got no boost from outcries over the one sure greenhouse impact.

## Neuroscience in court

In March, defense attorneys in a child custody case in southern California submitted as evidence—but later withdrew—fMRI scans purportedly showing that their client was telling the truth. In November, defense attorneys for a convicted murderer in Illinois used fMRI scans to argue that their client should be spared the death penalty because of a brain disorder. After much deliberation, the jury decided otherwise. Interest in using neuroimaging in court cases continues to grow, but 2009 wasn't the watershed year we predicted.

A new American president pledging to pass greenhouse gas restrictions, growing international momentum, and increasingly clear climate science might well have paved the way for a historic global agreement on emissions at the U.N. conference in Denmark. But the U.S. Senate and international negotiators couldn't get their act together before the meeting, which ended after this issue went to press. Emissions limits will get other chances in 2010, but the looming U.S. congressional elections and the continuing partisanship in Washington remain major obstacles to any global agreement.

## Darkness visible

As predicted, dark matter remained murky. Two years ago, the ATIC balloon experiment reported an excess of electrons and positrons from space at a particular energy, which might be a sign of dark matter particles annihilating each other. This year, the orbiting Fermi Gamma-ray Space Telescope saw no such excess. The Fermi spectrum wasn't exactly what astrophysicists expected, however, and data from the orbiting PAMELA particle detector still show an increase in the ratio of positrons to electrons. These could be signs of dark matter, but the case is hardly clear.

## Defining species

Darwin would have been pleased with progress in the genetics of speciation in the year of his 200th birthday celebration. The number of speciation genes has jumped from five in 2006 to about 15, depending on how a speciation gene is defined, with discoveries in mammals and yeast as well as the usual fruit flies. Researchers also succeeded in pinning down other DNA, including several regulatory regions involved in helping to define new species, and worked on understanding genome wide influences on speciation.

## Tevatron's triumph

It didn't find the Higgs boson as we all but predicted it would, but the aging atom smasher at Fermi National Accelerator Laboratory (Fermilab) in Batavia, Illinois, scored a victory of sorts. The U.S. Department of Energy announced that it plans to run the Tevatron through 2011, which should allow physicists at Fermilab either to spot signs of the most-coveted particle or to rule out its existence in the most likely range of masses. Physicists at the European particle physics laboratory, CERN, near Geneva, Switzerland, are finally starting up the more-powerful Large Hadron Collider, so the race for the Higgs will likely come down to the wire in 2012.

4. Breakdown Revisited

# Trying to Stay Afloat

1. Jeffrey Mervis,
2. Eliot Marshall

The global financial crisis made 2009 a tough year for many U.S. academic institutions dependent on state funding or endowments. But it has also been a banner year for thousands of individual scientists, whose labs have benefited from billions of dollars in U.S. government stimulus funding.

When last year's financial crisis (Science's “Breakdown of the Year” for 2008) swept the globe, doomsayers predicted a calamity for research. They were partly right: 2009 has been a tough year for many U.S. academic institutions dependent on state funding or endowments. But it has also been a banner year for thousands of individual scientists, whose labs have benefited from billions of dollars in U.S. government stimulus funding (Science, 27 November, p. 1176). And in much of the rest of the world, research institutions so far seem to be weathering the storm.

California, the most populous state, is in especially dire shape. “Win a Nobel, get a pay cut,” Elizabeth Blackburn quipped to reporters after learning that she had won the 2009 medicine prize for her work on telomeres. Blackburn, an Australian-born biochemist at the University of California (UC), San Francisco, suffered a 4% salary cut this summer (in the form of an 11-day furlough). She and thousands of other faculty members in the 10-university UC system were taxed to help erase an $813 million deficit caused by a continued drop in support from a state fighting to stave off bankruptcy. Anticipating an even larger state deficit next year, UC regents last month increased tuition fees for next year by 32%, to$10,300, further eroding what was once one of the country's best bargains in higher education.

California is not alone in its misery. A survey last month of the 188-member Association of Public and Land-grant Universities (APLU) found that 87% of respondents had suffered cuts in state funding, an important source of revenue for many public universities, with the decreases averaging 11.4%. Those hardest hit have eliminated departments and laid off tenured professors. Private universities—including Harvard, Stanford, and Yale, some of the world's wealthiest—have reduced staff and services and halted long-planned construction (Science, 27 February, p. 1157) after their endowments shrank by 20% to 27%. But so far, they have avoided faculty layoffs.

“Those publics that have historically had high state support and relatively low tuition, like California, have been hurt the most by a decline in state support,” says Robert Berdahl, president of the 62-member Association of American Universities and former chancellor of the system's flagship institution, UC Berkeley. “And those privates that have been most dependent on endowments have also been hurt badly.”

At the same time, some institutions are managing to stay afloat—or even thrive. The University of Michigan has kept its $5.4 billion annual budget in balance despite a drop in state funding by judicious trimming—planting fewer bulbs and trees at the Ann Arbor campus, for example—and by finding additional sources of revenue. Another flagship state university, the University of Texas (UT), Austin, has avoided cuts to its educational programs and become a buyer of prime research talent. “The department is growing, and we're part of a cohort of new people; … it's a fabulous feeling,” William Hanks told The New York Times last month, explaining why he and his wife, Jennifer Johnson-Hanks, both cultural anthropologists, had decided to leave UC Berkeley for UT Austin. Research universities in Europe and Asia have reported fewer direct impacts from the recession, as many top private institutions there depend far less on endowments than their U.S. counterparts do and are less prone to financial shocks. But changes may be coming. This summer, a new government in Japan froze a planned multibillion-dollar growth in research spending and seems poised to slash support for science as part of its plan to shrink recession-triggered budget deficits (Science, 20 November, p. 1046). In Europe, Portugal and Italy have already experienced university funding reductions of 10% to 20%. Ireland faces possible cuts of 6% to 10% in university funding in the next 2 years, according to the European University Association, which also notes that eastern European universities are under heavy pressure. So what's in store for 2010? A majority of respondents to the APLU survey are bracing for another round of state cuts. “Many people think that the state funding will never quite recover, especially in places that have been hurt the worst,” says Berdahl. And facing growing political opposition to more tuition hikes, university administrators aren't sure how best to buffer themselves against the continuing economic storms. 5. Breakthrough of the Year # Areas to Watch In 2010, Science's editors will be watching for developments with induced pluripotent stem cells, the Alpha Magnetic Spectrometer, "exome sequencing," disrupting the metabolism of tumor cells, and human space flight. IPS CELLS. Last year's Breakthrough of the Year, the ability to reprogram adult skin cells into induced pluripotent stem (iPS) cells that can be coaxed to develop into various mature cell types, promises to usher in a new wave of research. Using these methods, researchers can create cells from individual patients and examine them for physiological and genetic abnormalities or use them to test potential therapies. Scientists have already created iPS cells from people with type 1 diabetes, Parkinson's disease, and at least a dozen other disorders. Look for the number to grow in 2010 as more researchers get in on the act and, with luck, start gaining new insights into these conditions. See references and Web links on IPS cells. COSMIC EYE. An innovative space-based particle physics experiment called the Alpha Magnetic Spectrometer (AMS) will finally be delivered to the international space station in July. Nobel physicist Samuel Ting led the inter national team behind AMS, which will analyze cosmic rays for evidence of antimatter, dark matter, and strangelets. Originally due for launch in 2003, it was grounded by the Columbia disaster, a situation that looked permanent. But in 2008, the U.S. Congress passed a bill mandating that NASA launch the$2 billion instrument.

See references and Web links on AMS.

EXOME STUDIES. In 2010, scientists will sequence the protein-coding DNA of thousands of people's genomes in hopes of finding new genes underlying human diseases. Such “exome sequencing” studies are already revealing the genetic causes of mysterious hereditary illnesses. They might also fill in the gaps left by so-called whole genome association studies, which use DNA chips to scan the genome for disease risk markers. Although wildly popular in recent years, these studies have failed to explain much of the heritability of common diseases and traits. Some researchers are betting that rarer variants found through sequencing will unveil this genetic “dark matter.”

See references and Web links on exome sequencing.

BIOCHEMISTRY BEATS CANCER? Will a metabolic quirk of cancer cells first noticed in the 1920s finally pay off with new treatments? To break down glucose, tumor cells often switch from the usual oxygen-demanding pathway to an oxygen-free alternative called glycolysis. Disrupting the cells' unorthodox metabolism has already become the talk of conferences, the business plan of at least one biotech start-up, and the goal of several clinical trials.

See references and Web links on cancer metabolism.

HUMAN SPACE FLIGHT. Out with the old, in with … to be determined. With the U.S. spaceshuttle fleet slated to be mothballed in September 2010 after nearly 3 decades of service, President Barack Obama must pick NASA's next launcher capable of carrying humans. He could go with the current Ares rocket design, call for a variant based on an existing expendable launcher, or ask commercial companies for a cheaper option. Obama also plans to decide whether to shoot for the moon, an asteroid, or a martian moon in the next decade.

See references and Web links on the future of human space flight.

6. Virus of the Year

# The Novel H1N1 Influenza

1. Martin Enserink,
2. Jon Cohen

For years, scientists have been warning about the potential for an influenza pandemic on the order of the 1918 Spanish flu. But the pandemic that erupted last spring looks nothing like the one health officials have been preparing to combat.

For years, scientists have been warning that an influenza pandemic could strike at any moment, triggering a global catastrophe on the order of the 1918 Spanish flu. They imagined the culprit would surface in Asia—and, since 2003, have worried that the avian influenza strain H5N1 might be it. Health officials worldwide drafted one preparedness plan after another.

But the pandemic that erupted last spring looks nothing like the one in the plans. Not only did it begin in North America, but the swine virus behind it is a novel form of an H1N1 strain already circulating in humans. And although the new H1N1 is unusually dangerous for the young and for pregnant women, in most otherwise healthy people it causes a disease no more severe than seasonal flu. Scientists have repeatedly warned that this relatively mild virus could mutate or swap genes with cousins and become deadlier. But for now, it looks as if this H1N1, which mysteriously jumped from swine to humans, will go down in history more for causing confusion than catastrophe.

Not everything went wrong. The virus was discovered in humans earlier than it might have been, thanks to new technologies and border-surveillance programs set up in the wake of 9/11. Mexico, the hardest hit country, at first openly discussed its unfolding epidemic and mounted an aggressive response. Scientists characterized the new virus and distributed tests to detect it at record speed, sharing findings nearly in real time. Regulatory bodies rushed to approve new vaccines and drugs. And information campaigns, aided by the Internet, have kept the public apprised of the pandemic's course and of efforts to prevent and treat disease.

Yet the novel H1N1 virus ultimately revealed more weaknesses than strengths in the world's ability to combat pandemic influenza. As a symbol of the depth of the confusion, the World Health Organization (WHO) held an awkwardly prolonged backroom debate about whether the outbreak even merited the “pandemic” designation, and officials floated a cornucopia of names for the virus, none of which has stuck. But the problems were far more than symbolic.

Because of flimsy flu surveillance in pigs, the virus went undetected for years. By the time it was discovered, it had been circulating in humans for months—far too late to be contained with quarantines and antiviral drugs (stockpiled by WHO for that purpose), as mathematical models suggested could be done if a new pandemic virus were spotted early enough. Against the advice of WHO, many countries instituted useless travel bans and quarantines, and Egypt went so far as to kill all its pigs—even though not a single case of pig-to-human transmission had been found.

But the biggest wake-up call has been with vaccines, the cornerstone of pandemic preparedness plans. Almost as soon as the virus was isolated, public health labs and manufacturers kicked into high gear. Unfortunately, they hit one snag after another. Given the pandemic's April debut, no one expected the vaccine to arrive in time for the Southern Hemisphere's winter. But for the Northern Hemisphere as well, it came too little, too late. Most countries did not start vaccination programs until October or November, when the pandemic's second wave was in full swing.

The distribution of vaccines proved equally vexing. Despite lofty rhetoric at international meetings about global equity, poor countries were last in line. So far, WHO has received promises of a mere 200 million or so vaccine doses to help the poor, and delivery didn't start until early December. Moreover, the United States failed to stretch the supply of vaccines by using immune-enhancing adjuvants. European countries that did use adjuvants insisted on a two-dose regimen despite evidence that a single dose protects people over 10 years of age. So far, the global disparities have failed to ignite much political indignation. But if the new H1N1 had been a major killer, many public health experts believe the wealthy world's behavior would have created diplomatic mayhem.

Mistrust of the vaccine also reached a new high. Celebrities have denounced it, proudly proclaiming that they would not give it to their H1N1-vulnerable children—and many others have followed their advice. The Internet has fueled rumors about the vaccine, ranging from the simply false (“It hasn't been tested on humans”) to the paranoid (“It's a WHO-led plot to depopulate the world”).

In the final analysis, this anticlimactic pandemic might be best remembered as a trial run for the truly vicious killer that may come one day. And it has demonstrated that if influenza's Big One had struck in 2009, we would have been in a world of hurt.

7. 2010 U.S. Budget

# Congress Takes Care of Science In Quiet Finish to a Busy Year

1. Jeffrey Mervis

Congress has quietly passed a 2010 spending bill that gives several U.S. science agencies pretty much what they expected, including a 2.3% bump for the National Institutes of Health (NIH) and a 6.7% increase for the National Science Foundation (NSF).

The lack of fireworks stems in part from the lawmakers' preoccupation this year with other issues—from health care reform to the war in Afghanistan. But another factor was the $18 billion investment in research approved in February as part of the$787 billion stimulus package to revive the sagging economy (Science, 27 November, p. 1176). That windfall postponed until next year most of the usual battles over each agency's annual appropriations.

Acting last week only days before the expiration of a temporary spending extension, the House of Representatives and the Senate approved a $450 billion omnibus bill covering six of the 12 annual spending bills for the fiscal year that began on 1 October. In addition to NIH and NSF, the legislation funds the National Oceanic and Atmospheric Administration and the National Institute of Standards and Technology within the Department of Commerce. Several science agencies had already received their 2010 budgets in standalone legislation passed earlier this fall. At press time, Congress was still working on the final 2010 spending bill, which would fund the Department of Defense. Within NSF's overall budget of$6.926 billion, legislators trimmed $115 million from a 10.5% increase requested for research activities, leaving it at$5.62 billion. Even so, they suggested that NSF seek additional time for U.S. astronomers on the twin Gemini telescopes in Hawaii and Chile built by a consortium of countries. They bumped up the Administration's requested 2% boost for education by $15 million, to$873 million, saying the extra money should be used to help elementary school students learn math and science.

Congress also took the unusual step of telling the White House that its request for 2011—to be unveiled on 1 February—should be larger than it had signaled last spring. A report accompanying the bill said that NSF needs at least a 7% boost if the agency's budget is to stay on track for a 10-year doubling by 2016. That calculation excludes $3 billion in one-time funding that NSF received from the stimulus package, most of it already allocated in grants that run for as long as 5 years. The$692 million increase for NIH, to $31 billion, tops the Administration's$450 million request, which was low-balled because of the $10.4 billion in stimulus money that NIH received. Biomedical lobbyists were relieved that conferees dropped House-approved language removing funding for three NIH grants to study HIV risks among sex workers and alcoholics. A controversial$3 billion project to track the health of 100,000 children from the womb to age 21 received up to $194 million—enough to enable researchers to continue with a pilot study and prepare for a full launch in 2011. Within NASA, legislators met the Administration's request for science, including$441 million to prepare the James Webb Space Telescope for a 2014 launch. But they called for a project review after noting a $95 million cost overrun in the past 6 months alone. Lawmakers provided$25 million to begin work on a replacement to the Orbiting Carbon Observatory, which landed in the ocean earlier this year, and set aside $15 million to start work on a robotic mission to Jupiter's moon Europa. They even asked NASA what it would cost to launch the Europa mission in 2018, 2 years ahead of the current schedule. In October, Congress gave a 2.7% hike, to$4.9 billion, to the Department of Energy's (DOE's) Office of Science, which received a $1.6 billion infusion of stimulus money that it spent on “shovel ready” research projects and facilities. Legislators told DOE's new energy research agency, ARPA-E, to exhaust its$400 million in stimulus funding before asking for an annual appropriation. Toward that goal, agency officials this month announced a $100 million competition for far-out ideas to improve vehicular battery storage, carbon capture, and the conversion of carbon dioxide into liquid transportation fuels. ARPA-E's inaugural competition, which covered all aspects of clean energy, distributed$151 million to 37 grantees, leaving roughly $150 million for a third round sometime next year. 8. Academic Freedom # Terrorism Charges Against Grad Student Raise Questions 1. Greg Miller Last month a sociology graduate student at the University of Minnesota, Twin Cities, was charged with conspiracy under the Animal Enterprise Terrorism Act after he refused to testify before a grand jury that is apparently investigating a laboratory break-in at the University of Iowa in 2004. His academic adviser and 1600 others have signed an online petition urging the government to drop the charges against him, arguing that his academic freedom is at stake. The student, Scott DeMuth, 22, studies radical activist groups. In the course of his research, he and his advisers say, he has promised confidentiality to his subjects. Compelling him to break this promise and reveal anything he might know about the Iowa raid—which caused more than$400,000 in damages—would violate social scientists' code of ethics, his supporters argue.

The case raises a number of questions, not the least of which is whether DeMuth is a promising young researcher trying to uphold the ethical standards of his field or an activist trying to use his academic ties as a cover for allegedly breaking the law.

In an interview with the Associated Press (AP), DeMuth denied that he was involved with the Iowa break-in or that he has ever been an animal-rights activist. DeMuth does, however, belong to Earth Warriors are OK!, a prisoner support group for people accused of illegal acts related to environmental and animal-rights activism, according to the AP and other sources. In an e-mail to Science, DeMuth defended his decision not to testify before the grand jury, but he did not respond to questions or requests for an interview.

As an undergraduate at the University of St. Thomas in St. Paul, Minnesota, DeMuth conducted research on the Minnehaha Free State struggle, a 1998 protest in which environmental and Native American activists camped illegally on land slated for a rerouted highway. DeMuth interviewed participants and presented his findings at meetings of the Midwest Sociological Society in 2008 and 2009, says his undergraduate adviser, sociologist Lisa Waldner.

Some of the activists involved in the Minnehaha protests have also been involved in public events supporting people jailed for animal-rights activities, says David Pellow, DeMuth's graduate adviser. “We're surmising that [the government] believes that from this project he may have interviewed people who were involved or know people who were involved in the Iowa vandalism,” Pellow says.

In mid-November, DeMuth and former girlfriend Carrie Feldman, 20, were subpoenaed to appear before a grand jury in Davenport, Iowa. Both refused to testify and were jailed for contempt of court. Two days later—just as the statute of limitations was expiring on the Iowa raid—DeMuth was charged with conspiracy under the Animal Enterprise Terrorism Act, a 2006 law that gives investigators and prosecutors more power in pursuing crimes by animal-rights activists. (DeMuth was released pending his trial; Feldman remains in jail but has not been charged.) The indictment doesn't mention the Iowa incident explicitly but lists a time period and location that match. Whether DeMuth stands accused of participating in the raid, helping to plan it, or playing some other role is unclear. Clifford Cronk, the assistant U.S. attorney involved with the case, said he was not permitted to comment.

A motion filed by Cronk to block DeMuth's release does mention the lab break-in and claims that FBI agents have found evidence that DeMuth is “an anarchist who has been engaging in illegal anti-government activities” and is “a part of the movement identified as the Animal Liberation Front,” which claimed credit for the Iowa raid.

DeMuth's academic advisers paint a different picture. “He's a really bright young man,” says Pellow. “He was a star undergraduate student, and he's got several projects … building on that work.”

Pellow and Waldner argue that DeMuth's role as an activist shouldn't necessarily undermine his credibility. It's not uncommon for sociologists to participate in the groups they study, Waldner says: “Some people argue that participant observation is not a valid research strategy because of the objectivity issue. Other folks argue it's the only way to understand the viewpoint of the people you're trying to study.”

The petition for DeMuth cites portions of the code of ethics of the American Sociological Association (ASA) that deal with confidentiality between researchers and subjects. The ASA has not taken a position on DeMuth's case, says the association's executive officer, Sally Hillsman: “We don't know enough about the specifics.” But she adds that confidentiality is crucial for research in areas such as domestic violence, police brutality, and other illegal behavior.

However, she notes that conflicts can arise between the sociologists' code of ethics and legal obligations. Many sociologists avoid getting into a bind by telling subjects up front that they do not want to hear anything about future illegal activities, Hillsman says.

Those who choose otherwise may face consequences, and DeMuth seems determined to protect his sources, even if it means going to jail. The government's case against him should become clearer as his trial, scheduled for 1 March 2010, approaches.

9. Scientific Integrity

# A Dark Tale Behind Two Retractions

1. Robert F. Service*

The notices published in Science last month and online in the Journal of the American Chemical Society (JACS) in September were brief: Two papers from a prominent chemistry lab were being retracted because the results couldn't be replicated. Part of the story behind the retractions is anything but straightforward, however. It involves an extortion attempt and a threat of suicide.

The papers were published in 2004 from the laboratory of Peter Schultz, a chemist at The Scripps Research Institute in San Diego, California. They extended pioneering work in Schultz's lab on a method for incorporating non-native amino acids into proteins (Science, 20 April 2001, p. 498). Conventional proteins are made up almost exclusively of 20 amino acids that are coded for by DNA, though hundreds of other amino acids occur naturally. Schultz and his colleagues offered biologists a way to incorporate some of these nonstandard amino acids, which could then serve as novel chemical handles to manipulate proteins of interest. Today, dozens of these chemical handles are used by everyone from drug-makers to cell biologists looking for new ways to understand how proteins function.

In 2004, Zhiwen Zhang, then a postdoc in Schultz's lab, and several other co-authors reported in Science that they had extended the technique to introduce an unnatural amino acid that came preloaded with a specific sugar group (Science, 16 January 2004, p. 371). Such sugar groups are common appendages on glycoproteins. But because the sugars are difficult to express uniformly and to purify, understanding their role has long been viewed as a major challenge. The Science paper offered researchers the possibility of systematically studying the effect of different ways proteins are modified. On 11 November 2004, Zhang, Schultz, and their colleagues published a second paper in JACS reporting the incorporation into a protein of a sugar-loaded amino acid that's a core unit in glycoproteins central to inflammation and cellular recognition.

At about the time of the Science paper, Eric Tippmann joined the Schultz lab as a postdoctoral assistant. Like Zhang, Tippmann worked on efforts to extend the technique of incorporating unnatural amino acids into proteins. A few months after Tippmann's arrival, Zhang left the Schultz lab to take a tenure-track position as an assistant professor of pharmacology at the University of Texas (UT), Austin. Tippmann says he became interested in Zhang's work because fellow students and postdocs told him they were having trouble replicating it. Tippmann says he reviewed Zhang's work closely in the fall of 2006. In September 2006, Tippmann spoke at a Schultz group meeting outlining reasons why he thought Zhang's work was likely incorrect.

Schultz says the concerns raised were serious enough that he asked a group of lab members to try to replicate the work in Zhang's Science paper in addition to several other important discoveries Zhang had made. That task, however, was complicated by the fact that Zhang's lab notebooks, describing his experiments in detail, were missing. Schultz says that in the early fall of 2006, the notebooks were in Schultz's office. But at some point after that they were taken without his knowledge and have never resurfaced.

After considerable effort, Schultz says his students were able to replicate most of the work. The biggest exception was the work that served as the basis for the 2004 Science and JACS papers. “It was clear the glycosylated amino acid work could not be reproduced as reported. So we tried to figure out what was going on,” Schultz says.

In the midst of this process, events took an ominous turn. On 1 March 2007, Zhang received an e-mail that listed the author as “michael pemulis,” who claimed to have discovered “fraud” in multiple papers. If Zhang did not send $4000 via overnight mail to a post office box in San Diego, the e-mail sender said he or she would reveal this “fraud” to faculty at Scripps and UT Austin. “They will investigate you. … pete will retract all your post-doctoral work. you lose job. … Texas will fire you before you tenure,” the e-mail states. “I was scared to death,” Zhang recalls. He immediately contacted Schultz, who in turn contacted Richard Lerner, president of Scripps. At Lerner's urging, Schultz and Zhang then contacted the San Diego Police Department, which forwarded their case to its electronic crimes unit. About a month later, in April 2007, Zhang says the officer in charge of the case told him that they had a suspect and asked whether he wanted to press charges. Zhang says he decided not to do so in hopes the situation would blow over. It didn't blow over. In November 2007, an anonymous letter was sent to officials at several institutions, including Scripps; UT Austin; the University of California, Berkeley; and Science's editorial department. The letter stated that it was from “a member of PGS [Peter G. Schultz] lab” and called the 2004 Science paper a “fake.” “I feel like leaving science or committing suicide,” the letter stated. Zhang says that when he saw the letter, “my jaw dropped again.” The disturbing events haven't stopped. Zhang says over the past 2 years, he has received several anonymous phone calls at his UT Austin office phone number in which the caller hasn't said anything and then hangs up. Zhang says he's tried calling the number that pops up on his caller ID, but a recording on the other end says it is a long distance calling card center in Mississippi. Zhang says he and his family have become unnerved: “We don't feel safe anymore.” The stress has gotten so high, that his wife and children moved away from Texas some time ago and have since been in virtual hiding. “It's horrible,” Zhang says. “I'm just trying to be a good scientist. This is not science.” The events, Schultz says, affected him deeply as well. “It put me in a situation where I felt there was an extra burden on me to find out what was going on, given the threats,” he says. Today, after years of effort, Schultz says he feels he and his students are starting to understand what may have gone wrong with the original experiments. Although still preliminary, it appears that the problem might be with the enzyme that they thought was binding to the unnatural amino acid and incorporating it in the protein. A test with a different glycosylated amino acid shows that it actually binds the unnatural amino acid not in the normal “active site” but at another site. Here it then prompts a conventional natural amino acid to be incorporated in the active site, giving a false positive reading. In the end, Schultz says, Tippmann was right to have doubts. “There was something wrong with the work.” That meant the Science and JACS papers needed to be retracted. Zhang says Schultz contacted him in July and suggested that the papers be pulled. Zhang was preparing for his tenure review at UT Austin and says he was concerned that retracting the papers would prove damaging to his chances of receiving tenure. Nevertheless, after Schultz and Zhang talked it over, they agreed to retract both papers. After receiving signed agreement from each of the authors, a process that took several weeks, Schultz sent the retractions to Science and JACS on 11 August. JACS quickly accepted the retraction. But editors at Science informed Schultz that the journal's editorial practice requires that they get signatures directly from all authors wishing to retract a paper. During that process, Zhang informed Science's executive editor, Monica Bradford, of the extortion e-mail and the missing lab notebooks. In response, Science's editor-in-chief, Bruce Alberts, called Schultz to suggest that the retraction letter in Science should state that the lab notebooks were missing through no fault of the authors; that wording helped explain why they had trouble replicating the experiments. In the end, the retraction was published on 27 November. The summer brought other developments. On 7 August, Tippmann, now a lecturer at the University of Cardiff in the U.K., co-authored a paper that laid out several reasons why Zhang's original glycosylated amino acid experiments could not have worked. And in October, Zhang was told he would be denied tenure by UT Austin. For his part, Tippmann says he's sorry that Zhang has had to undergo this ordeal, but that his involvement has been entirely limited to the science, and he had nothing to do with the missing notebooks, the March 2007 e-mail sent to Zhang, or the November 2007 letter. Schultz says he and his Scripps colleagues will continue to search for answers. Lerner concludes: “There was somebody who did this, really turned lives upside down, and made doing science a lot harder than it had to be.” • * With reporting by Michael Torrice. 10. U.S. Science Policy # Chair of Science Panel to Leave Congress 1. Jeffrey Mervis Saying that “it's time to do something else,” the chair of the House Science and Technology Committee announced this week that he will retire at the end of 2010. Ending a 26-year career in Congress, Representative Bart Gordon (D–TN) leaves Democratic Party leaders scrambling to defend a seat in a Republican-leaning district and research lobbyists wondering how his successor will take to the role of spokesperson for science. The 60-year-old Gordon, who joined the committee as a freshman in 1985 and has been chair since 2007, helped turn a 2005 National Academies report into 2007 legislation that has provided a blueprint for research and education programs at the Department of Energy and the National Science Foundation. He says reauthorizing the America COMPETES Act next year is his highest priority. The second-ranking Democrat, Representative Jerry Costello (D–IL), has already declared his interest in becoming chair. One of the less-visible members of the committee, Costello has been active on national transportation issues and has championed the FutureGen carbon sequestration and storage project in his southwestern Illinois district. 11. ScienceNOW.org # From Science's Online Daily News Site HIV Outwits Yet Another Microbicide The largest study ever conducted of a microbicide designed to prevent HIV infection has resulted in yet another case of high hopes being dashed about a promising product. Earlier in the year, a smaller study of the same vaginal gel gave a hint that it might offer modest protection, but the new results put the question to rest. A Cheap Way to Chop Up Nitrogen Nitrogen atoms are needed to make many important chemicals, from drugs to fertilizers. But getting those atoms into chemicals is challenging because nitrogen molecules are tough nuts to crack. They consist of two atoms sharing a stubborn triple bond, which chemists can break up only by scorching them with temperatures of up to 500°C. And that results in the simple chemical ammonia, which needs further processing to produce more complicated compounds. Now chemists have devised a new way to split molecular nitrogen and synthesize a common fertilizer. A Mind That Touches the Past Imagine planning your schedule for the week and seeing the days on the calendar appear before you as a spiral staircase so real you feel like you could touch it. That's what it's like to have spatial-sequence synesthesia, a condition in which people perceive numbered sequences as visual patterns. Now researchers have shown that individuals with the condition have superior memories, recalling dates and historic events much better than the average person can. Better Nanotubes May Be on the Way In the world of nanotechnology, few things get as much billing as nanotubes. Experts say that these cylinders composed of one-molecule-thin sheets could someday be used in everything from superstrong jet engines to cancer cures. Now researchers think they've found a way to make large amounts of an elusive type of nanotube that could provide even more impressive applications. Read the full postings, comments, and more on sciencenow.sciencemag.org. 12. Evolution # Spineless Fish and Dark Flies Prove Gene Regulation Crucial 1. Elizabeth Pennisi Almost 3 years ago, biologists got into a tussle over what drives morphological evolution: changes in the protein-coding portions of genes or changes in the DNA regions that regulate gene activity. At the time, some researchers felt there was little hard evidence to support the idea that regulatory changes were indeed important (Science, 8 August 2008, p. 760). Now, on page 1663 and in last week's Science Express (www.sciencemag.org/cgi/content/abstract/science.1182213), two teams not only independently report that changes in regulatory DNA were responsible for an adaptation in natural populations of fish and insects, but each group has also pieced together details of the underlying genetic alterations in those animals. “They provide beautiful and convincing examples of how [certain] regulatory elements can be lost or modified to reduce [gene] expression, ultimately causing morphological change,” says Hopi Hoekstra, an evolutionary biologist at Harvard University and one of the chief skeptics. In one case, the same piece of regulatory DNA was lost in different freshwater fish populations, each time causing the loss of pelvic spines. In the other case, the darkening of a fruit fly took place through an accumulation of small mutations in regulatory DNA. Taken together with other discoveries of noncoding regions involved in evolution, “there is broad support now” that changes in regulatory DNA can generate morphological variation, says Günter Wagner, an evolutionary developmental biologist at Yale University. The fish study took place at Stanford University, where David Kingsley has spent the past decade tracking down the genetic basis for why three-spined sticklebacks (Gasterosteus aculeatus) that live in salt water have spines jutting from their belly whereas some of their freshwater counterparts do not. In salt water, the pelvic spines help make the stickleback difficult for a predator to swallow, but the protuberances become a hindrance in fresh water as they could serve as handholds onto which dragonflies and other carnivorous insects grab. In 2004, Kingsley and his colleagues tracked the disappearance of the pelvis in multiple populations of freshwater sticklebacks primarily to a gene called Pitx1. The gene is expressed during development in many places in both fish types. But it's active in the pelvic region of the saltwater animals and not in the freshwater ones, Kingsley's team found. Yet the gene's coding region is virtually unchanged between fresh- and saltwater fish, suggesting regulatory DNA is the difference. The new work confirms that suspicion. When Kingsley, his graduate student Yingguang Frank Chan, now at the Max Planck Institute for Evolutionary Biology in Plön, Germany, and their colleagues studied fish with and without a pelvis, they determined that DNA upstream of Pitx1 was responsible for silencing the gene. They broke that DNA into fragments and determined exactly which piece, an enhancer called Pel, turned Pitx1 on in the pelvis. When the researchers compared the sequence of Pel in saltwater sticklebacks and freshwater ones from nine different lakes, they found the latter populations each had various amounts of missing DNA bases in the enhancer region, including an apparently key 488-base region that is absent in most of the lake fish. “The fact that multiple alleles, with unique mutations, were observed is surprising and emphasizes the tinkering nature of the evolutionary process,” says Patricia Wittkopp, an evolutionary biologist at the University of Michigan, Ann Arbor. To confirm Pel's importance, the researchers added a saltwater stickleback's version of the enhancer and Pitx1 to the fertilized eggs of freshwater sticklebacks that don't normally sport pelvic spines. The resulting transgenic freshwater fry developed the structures. For the insect study, evolutionary biologists Sean Carroll and Mark Rebeiz of the University of Wisconsin, Madison, and their colleagues followed up on work into why the normally yellow abdomens of fruit flies (Drosophila melanogaster) have become dark in some African populations living at high elevations. Earlier work done by collaborators John Pool of the University of California, Berkeley, and Charles Aquadro of Cornell University suggested that this color change was due to a change in the activity of a gene called ebony. The new work narrows down the cause to an enhancer upstream of the gene. By dissecting the function of this region in different Drosophila populations, ones with either dark or light abdomens, the researchers identified five mutations that reduced ebony expression to varying degrees. Three of those mutations are present in Drosophila with light abdomens, but the dark flies from high altitudes also have two newer mutations. These two have the biggest effects on squelching ebony expression, but all five mutations combine to create the full color change. The work “leads to two very important conclusions about classic evolutionary genetic questions,” says William Cresko, an evolutionary biologist at the University of Oregon, Eugene. One is that a “big” evolutionary step—a color change—actually can come about because of several little steps: multiple mutations in the enhancer. Secondly, it shows that adaptive mutations sometimes exist unnoticed in a population. Others are also in hot pursuit of evolutionary changes based on regulatory elements. Wittkopp is homing in on mutations in a regulatory region that change body color between two closely related species of fruit flies (Science, 23 October, p. 540). And Hoekstra's group has a regulatory region in its sights that seems to underlie mouse color changes (Science, 28 August, p. 1095). But developing a broad understanding of the relative roles of shifts in gene regulation versus changes in the proteins encoded by genes “will require many more case studies from across a wide array of taxa,” cautions Cresko. Given how much work the two new studies took, he adds, it may require a “quantum leap” in technology for that to be possible. 13. France # Sarkozy's 'Grand Loan' Bets That Research Will Pay Off 1. Martin Enserink PARIS—On Monday, president Nicolas Sarkozy announced a €35 billion investment plan that he pledged would make France's science more productive, its population smarter, its economy more competitive, and its environment cleaner. The plan was originally envisioned as an economic stimulus similar to the one passed by the United States earlier this year but has been rebranded as an investment in the “France of tomorrow” because Sarkozy is betting heavily on research, higher education, and innovation. It sets aside almost €8 billion to establish a handful of elite academic centers, and €3.5 billion for turning research into products and services. Almost two-thirds of the €35 billion will be borrowed money—hence the nickname the “Grand Loan”—and economists have warned that Sarkozy is imperiling France's long-term fiscal health. Some researchers, meanwhile, dismiss the plan as a PR stunt. Most of the money will be in the form of capital endowments to universities from which they can only use the annual interest. Thus, the net increase for science is several hundred millions of euros annually, says physicist Bertrand Monthubert, secretary-general for research and higher education in the minority Socialist Party. That's barely enough to offset years of neglect, says Monthubert, who calls the plan “a mirage.” Sarkozy largely followed recommendations issued in November by a panel chaired by two former prime ministers, socialist Michel Rocard and conservative Alain Juppé. The stimulus plan's centerpiece are endowment-style funds for five to 10 “Campuses of Excellence,” to be selected by an international jury and modeled on academic hotbeds in the United States. Each will consist of a number of universities, research institutes, and so-called Grandes Écoles in close geographical proximity; they are expected to work closely together or even merge. One explicit goal is to create universities that score better in controversial academic charts such as the Shanghai ranking. France's poor showing is a source of political embarrassment. “The goal is simple: we want the best universities in the world,” Sarkozy said on Monday during a press conference from the Elysée Palace. The endowments will allow the chosen universities to attract top talent by making long-term funding commitments, says Alain Beretz, president of the University of Strasbourg. But critics worry that dozens of smaller, regional universities will be left by the wayside. “It's fine to have a pyramid, but you can't ignore the base,” says Laurent Bouvet of the University of Nice, who specializes in—and blogs about—higher education policy. Sarkozy's plan does reserve €1 billion for “laboratories of excellence” outside the elite; universities were hoping for more, says Lionel Collet, president of the University of Lyon 1 and chair of the Conference of University Presidents. In his speech, Sarkozy tried to reassure financial markets and the European Union that the country's debt won't spiral out of control. On the contrary, he said, the Grand Loan will result in a more competitive economy and a healthy tax revenue stream. Indeed, the plan puts a strong emphasis on technology transfer, an area in which France is lagging. There will be a €1 billion national fund to help exploit publicly funded science and €2 billion for new technology innovation institutes. Research would also benefit from other parts of the plan; a €5 billion investment in “sustainable development,” for example, will promote so-called fourth-generation nuclear reactors and alternative energy sources. 14. ScienceInsider # From the Science Policy Blog The world may be focused on Copenhagen this week, but next spring all eyes will be on the U.S. Senate as it gets down to brass tacks on climate change. This week's ScienceInsider offers a comprehensive look at the political climate for that debate—interviews with the key players, analysis of the biggest issues, and a look at where the votes are. Learn whether the so-called world's greatest deliberative body may take meaningful steps to reduce global warming. Ireland's funding allocation for science, technology, and innovation is being cut by 4.4% in 2010. And in a major change of policy, research will be funded through a single stream from one government department. Harvard University is temporarily halting construction on a$1 billion life sciences complex in Allston, several kilometers away from the main Cambridge campus.

In a continuing battle with the facility's governing board, scientists at the Australian Synchrotron are again working on a 9-to-5 schedule rather than around the clock. The partial strike could severely hamper research efforts.

U.K. Science Minister Paul Drayson announced that Britain will create its own space agency. No news yet on the body's name or spending power.

Carlos Pérez del Castillo, a career civil servant from Uruguay, was named chair of the new board of the Consortium Board of the Consultative Group on International Agricultural Research Centers, a network of 15 agricultural research organizations from around the world.

For these stories and more, go to blogs.sciencemag.org/scienceinsider.

15. Geology

# Peril in the Pamirs

1. Richard Stone

Concerns about the risk of a calamitous flood from a mountain lake in Central Asia have scientists racing to improve evacuation plans and find an engineering fix.

DUSHANBE—Once a month, Kadam Maskaev flies by helicopter to Lake Sarez, a jewel high in the Pamir Mountains in western Tajikistan. “Just knowing that nature is creating this wondrous lake before our eyes—it's a kind of magic,” he says. Sarez is special, but there's nothing mystical about it, and Maskaev is no starry-eyed pilgrim. He's deputy director of Tajikistan's emergency situations committee, and Sarez is his chief concern.

The lake was born nearly a century ago, when a mountainside crumbled during a magnitude-7.4 earthquake. The 567-meter-high landslide blocked an alpine river, forming the world's tallest dam. Since then, the valley behind it has filled with 17 billion cubic meters of snow and glacier melt. Maskaev and others fear that the natural dam could someday give way, unleashing a wall of water from the 56-kilometer-long lake on villages along the Bartang and Panj rivers and the great waterway they feed: the Amu Darya, Central Asia's largest river.

The possible trigger for such a catastrophe would be another major earthquake shaking the region. A large temblor is virtually certain: The Pamirs are a seismic hot spot, and a quake of magnitude 7 or greater rattles the faults around Sarez every century or so. But a severe jolt in itself almost certainly would not directly bring down Usoi Dam, named after a village buried in the landslide on 18 February 1911. The scenario that Maskaev and other scientists worry about is a landslide into the lake, which could trigger a tsunami-like wave that would flow over and perhaps breach the dam. Just such a disaster claimed about 2000 lives in Italy in 1963. Scientists concur that the probability of a reprise at Sarez is low. But the consequence “would be a catastrophe,” says Sharifov Gul, a chief engineer in Tajikistan's water ministry.

Adding uncertainty over how much force Usoi might withstand, a few years ago water began trickling in greater volumes through the upper part of the dam. That reassures some experts and unsettles others. “In the short term, that may relieve pressure. But in the mid- to longer term, it could have a destabilizing impact by increasing fissures in the dam,” says Igor Zonn, director general of the Engineering Research Center on Water Management, Land Reclamation, and Ecology “Soyuzvodproject” in Moscow. “In either scenario,” Zonn contends, “the risk remains high for settlements downstream.”

With the sword of Damocles hanging over as many as 5.5 million people in the Amu Darya basin—including settlements in eastern Tajikistan and northern Afghanistan, Turkmenistan, and Uzbekistan—authorities are taking no chances. Tajikistan has installed a sophisticated warning system at Sarez, and officials throughout the region are crafting evacuation plans. The countries have their work cut out for them. “I'm not aware of any regional preparedness plans which would adequately address the potential risks,” says Sergei Vinogradov, an expert on water law at the University of Dundee in the United Kingdom.

Reducing the threat is a daunting challenge. Shoring up Usoi Dam is not feasible, experts concluded at a workshop last September in Nurek, Tajikistan's gateway to the Pamirs. Rather, they agreed on the urgent need to draw down the lake, which last year reached its highest-ever water level. “The overwhelming international scientific consensus is that to guarantee long-term safety of the dam and lake, the water level should be reduced by 50 to 100 meters,” says Roger Roschnik, a project manager at Stucky, a company in Renens, Switzerland, that developed the warning system. Several ideas have been floated for lowering the waterline. Meanwhile, researchers have proposed taking cores from Usoi. “Nobody knows what the dam looks like inside,” says Maskaev. Scientific drilling, proponents say, would allow more robust estimations of the structure's stability.

As experts mull next steps, Maskaev's team is hewing to its prime directive: keeping vigil as the waters of Sarez rise.

## One family's nemesis

Scientists have cast a wary eye on Sarez from the start. In 1913, Russian engineers dispatched to the disaster zone found the Murghab River backing up behind roughly 2 cubic kilometers of rubble, a pile of mostly shale and sandstone nearly three times as tall as the Hoover Dam on the Colorado River. The team enlisted a local man, Kabul Kurbonbekov, to monitor the newborn lake, which had already submerged the village of Sarez in the summer of 1912. The post of chief observer has passed from one generation to the next and now belongs to Kurbonbekov's great-great-grandson: Maskaev.

Concerns about Usoi's integrity have waxed and waned. An early fear was that a large earthquake would cause the 5-kilometer-long dam to fail. Most experts now discount that prospect. Usoi is stronger than any humanmade dam, calculations suggest. “I consider the dam safe, taking into account its dimensions and the time it has had to consolidate,” says geologist Jean Schneider of the University of Natural Resources and Applied Life Sciences in Vienna.

The trouble spot, researchers say, is not Usoi but an unstable slope along Lake Sarez about 4 kilometers east of the dam. Imperceptible to the naked eye, a section of the lake's right bank is slipping about 10 centimeters a year toward the lake. There is a “relatively high possibility” that a strong earthquake would trigger a sudden collapse as the bank's saturated underwater portion liquefies in the shear zone, sending tens to hundreds of millions of cubic meters of debris plunging into Lake Sarez, says Kyoji Sassa, a disaster prevention specialist at Kyoto University in Japan and executive director of the International Consortium on Landslides.

The displacement would create a seiche wave, a kind of tsunami observed in lakes and other enclosed basins. A seiche wave at Sarez could wash over Usoi Dam, whose crest at its lowest point now sits only 38 meters above the lake's surface, says Sassa.

Just such a disaster occurred in Italy on the evening of 9 October 1963, when heavy rain triggered a massive landslide into a reservoir behind Vajont Dam north of Venice. The debris spawned a towering seiche that sent some 50 million cubic meters of water spilling over the 262-meter-high dam. The torrent, abetted by the tornado-force blast of air it displaced, obliterated five villages in its path.

The situation in Tajikistan is not nearly as precarious as it was in Italy. The reservoir's banks at Vajont were crumbling before the tragedy, suggesting that the terrain was unstable. Even if a major earthquake were to collapse Sarez's right bank, some researchers say the odds are against a disastrous seiche. “The probability is 1 in a million,” asserts Jörg Hanisch of JorgeConsult in Hannover, Germany, who served on a panel that oversaw installation of the Stucky monitoring system by FELA Management in Diessenhofen, Switzerland. “The risk of even a partial outbreak is exaggerated,” adds Schneider. “The dam will only possibly be overtopped in the far future.” But Sassa and others argue that the threat is significant. The nightmare scenario is that the force of a tremendous seiche (the one at Vajont was approximately 250 meters tall) could breach and sweep away a large chunk of Usoi Dam—releasing, in minutes, much of Lake Sarez.

“Ten years ago, I was not as concerned about the risk of Usoi failing,” says Maskaev. Since then, two things have changed. The 9/11 attacks revealed a vulnerability of any dam: Terrorists could blast a hole in Usoi with a hefty, well-placed bomb or by ramming a plane into it. Then in 2004, Maskaev's team noticed a marked increase in water seeping through the dam some 100 meters below the lake's surface.

The water is clear, which means it's not washing out debris and is unlikely to be weakening Usoi. “Internal erosion can be excluded,” says Hanisch, who notes that such seepage is necessary for long-term stability of natural rockslide dams. Maskaev has a different take: “The filtration regime of the dam is changing, and that makes me nervous.”

## Planning for the worst

Whatever goes down at Lake Sarez, Maskaev's team will be the first to know. A five-person detachment keeps an eye on the lake around the clock from a station anchored with steel cables to a stable perch 150 meters above Usoi—out of the path of any seiche. “It's a perfectly safe place,” Maskaev says.

Instrumentation has improved considerably since Great-Great-Grandpa Kurbonbekov's day. Stucky's $2 million monitoring system features strong-motion accelerographs for detecting tremors, GPS to track movements of the right bank and the dam, and radar and pressure-cell sensors to monitor water levels in Sarez and in the Bartang River, downstream of Usoi. Although data are beamed by satellite to Dushanbe, a decision to evacuate would not wait for word from Tajikistan's capital. The warning system would trip if its detectors registered, for instance, a magnitude-5 or greater earthquake, a 25-centimeter rise in Sarez's level over 24 hours, or a 1-meter surge in the Bartang River below the dam. Sirens would sound in 17 villages, and the residents of Barchidiv, the village nearest the dam, would have 17 minutes—“enough time,” Maskaev assures—to reach provisioned shelters on higher ground. As they grab their children and food, villagers would listen for a radio advisory confirming a real emergency. The Bartang valley population “is very well prepared and has gone through a number of evacuation drills,” says Goulsara Pulatova, senior adviser to the U.N. International Strategy for Disaster Reduction's office in Dushanbe. Further downstream, however, preparedness falls off sharply. In Soviet days, evacuation plans were drawn up for settlements along the Amu Darya, all the way to the Aral Sea, says Maskaev. Renewed concerns over Sarez have prompted officials to dust off and revise these plans. Last summer, for instance, Termez, a major city in Uzbekistan on the Afghan border, held an evacuation drill. The conference in Nurek drew experts from Turkmenistan, which for years hadn't dispatched delegations to Sarez workshops, and from Afghanistan, which is seeking to set up a warning system on its side of the border. Evacuation plans alone are insufficient for addressing the threat, cautions Michael Glantz of the University of Colorado, Boulder. Another need, he says, is contingency plans for rehabilitation and reconstruction in the event of a disaster. In addition, he says, Tajikistan may want to consider moving people permanently out of harm's way. ## Waiting game Experts have for now ruled out buttressing Usoi against a seiche. A more promising idea, they say, is to partly drain Sarez. If the lake level were lowered several dozen meters, says Hanisch, “even the highest imaginable wave could not overtop the dam.” Finding an engineering solution is easier said than done. The “best option,” according to Sassa, is to tunnel through bedrock on Sarez's left flank and drain lake water via a conduit. Bearing in mind the immense pressure of 6 trillion tons of water, “it would require some very careful engineering to ensure a controlled release of water and that things didn't get out of control,” says Philip Micklin, a geographer at Western Michigan University in Kalamazoo. The project's estimated$500 million cost could be defrayed by building a 250-megawatt hydropower plant where water exits the tunnel. “Such a project would contribute to the social and economical development of the region,” says Roschnik, who notes that Stucky is conducting a feasibility study with the World Bank's International Finance Corp.

Tapping Sarez could also defuse mounting tensions over regional water supplies in Central Asia (see sidebar, p. 1616). At the World Water Forum in Istanbul last March, Tajikistan President Emomali Rahmon proposed establishing an international consortium to construct a pipeline from Sarez to neighboring Uzbekistan. “Sarez has enough volume to provide drinking water for all of Central Asia,” says Gul. A consortium has yet to materialize. “So far it's all just talk,” Gul says. “The main problem is money.”

An alternative strategy would be to construct a spillway, similar to one that army engineers in Pakistan built to drain a lake formed by the Hattian Bala landslide, a 68-million-cubic-meter rockfall set off by the 2005 earthquake in Kashmir. Such a trench, however, would dramatically increase the hazard of a seiche wave breaking the dam, says Hanisch. Most experts favor the tunnel, which is also Tajikistan's preferred solution, Maskaev says.

As engineers mull ideas for defanging Sarez, scientists are eager to peer inside the megadam. At the September conference, Maskaev proposed taking cores from at least three sites at Usoi. In the late 1980s, engineers were preparing to drill. But the Soviet collapse in 1991 scotched that plan, and newly independent Tajikistan lacked the cash and expertise to carry it out. Both deficits remain. “We're waiting for offers of help,” Maskaev says. Some researchers are not sold on the idea. “Drilling would not offer a comprehensive integrated picture of the dam's structure,” says Zonn.

One initiative gaining steam is a research campaign. Sassa and colleagues from five countries are planning a detailed look at Usoi next summer, with results ready for a conference in Tajikistan in 2011 to mark the Sarez centennial. By then, says Roschnik, “we should have started working on a long-term solution.” If they succeed, Maskaev would be more than happy to wind up the family business—and continue to admire Sarez, for its beauty alone.

16. Geology

# Burdened by Soviet Legacy, Nations Spar Over Water Rights

1. Richard Stone

As scientists worry about the prospect of a catastrophic flood from Lake Sarez in the Pamir Mountains (see main text), agricultural communities on the plains below face a very different problem: increasing competition for fresh water, a situation that might be eased, experts say, if Lake Sarez could be tapped and its surplus water distributed.

DUSHANBE—As scientists worry about the prospect of a catastrophic flood from Lake Sarez in the Pamir Mountains (see main text, p. 1614), agricultural communities on the plains below face a very different problem. This arid region in Central Asia has inherited a set of resource blunders made decades ago by the Soviet Union. And since the Soviet collapse in the 1990s, competition for fresh water has increased. The situation might be eased, experts say, if Lake Sarez could be tapped and its surplus water distributed. But that won't happen anytime soon. For now, regional water problems are growing more intense.

Water scarcity is not the only woe. The people of Ferghana Valley in northwest Tajikistan are trying to bail out of a vast inundation, the belated consequence of a Soviet project called the Kayrakkum Dam, completed in 1956. As its reservoir filled, the water table of the surrounding land rose, infiltrating homes and spoiling crops. Engineers installed a drainage system to pump water back into the Kayrakkum reservoir. But now many of the pumps have broken down. Across 30,000 waterlogged hectares, sewage is backing up, salt has risen to the surface and is ruining fields, and homes are riddled with mildew, says civil engineer Akhrorov Akhatjon of the Ferghana Valley Water Resources Management Project. “The problem is getting worse,” he says. The government lacks the resources to fix the drainage system, and villagers are too impoverished to relocate. A handful of people have had the means to rebuild homes on 3-meter-high foundations, but most simply endure the swampy conditions. “We're worried about the disease risk of poor sanitation,” Akhatjon says. “It's a perilous situation.”

Along the Tajik-Uzbek border, meanwhile, a perpetual squabble over water and energy resources is growing tenser. In winter as hydropower reservoirs in Tajikistan drop too low to generate power, Uzbekistan has accused Tajikistan of siphoning electricity from Central Asia's shared grid. This month, Uzbekistan pulled out of the grid—a move that has provoked talk of retaliation. “If [Uzbeks] don't want to give us electricity during winter, why should we give them water?” asks Sharifov Gul, a chief engineer in Tajikistan's water ministry.

Turning off the spigot is easier said than done. The source of most of Central Asia's water is rivers flowing from glacier fields in mountainous Kyrgyzstan and Tajikistan. There's little now that either country can do to stem the flow into Kazakhstan, Turkmenistan, and Uzbekistan. But that could soon change. Tajikistan is building the world's tallest artificial dam, Roghun, on the Syr Darya River. The 3.6-gigawatt hydropower station would make Tajikistan self-sufficient in electricity. Uzbekistan has opposed the 335-meter-high dam, arguing that Tajikistan might use Roghun to restrict downstream releases. That could devastate agriculture in Uzbekistan, whose cotton and wheat fields depend on irrigation from the Syr Darya and the Amu Darya. Gul insists that's not Tajikistan's intention: In fact, he says, Roghun could supply electricity to neighboring countries.

The most notorious example of poor management, perhaps, is the diversion of water a half-century ago from the Amu Darya and Syr Darya to irrigate cotton fields in Turkmenistan and Uzbekistan. The irrigation canals constantly hemorrhage water through their beds, while a substantial fraction of water also evaporates. By the 1970s, the Amu Darya no longer reached the Aral Sea. The shrinking sea grew saltier and fisheries were devastated; a Kazakh effort is replenishing part of the sea (Science, 14 April 2006, p. 183).

A fresh concern is the retreat of Central Asia's glaciers as temperatures rise. Both the Amu Darya and Syr Darya depend on glacier runoff to provide a stable flow in summer, says Daene McKinney, a civil engineering professor at the University of Texas, Austin. “Decreased glacier mass will likely cause this high level of dependable base flow to become more erratic, requiring more efficient water management,” he says. The Amu Darya is expected to be the hardest hit, says Victor Dukhovny, director of the Scientific Information Centre of the Interstate Commission for Water Coordination of Central Asia in Tashkent. As a result, he says, there is already a “strong movement to water saving.”

In a taste of hardships to come, Central Asia experienced a prolonged drought last year that resulted in water shortages. In response, Tajikistan stepped up construction of Roghun, a project started by the Soviets in the 1970s. It spent \$150 million this year and plans a similar expenditure in 2010, and now has a 7000-strong work force at the site. To speed up the project, Tajikistan President Emomali Rahmon this month called on every Tajik family who could afford it to buy shares in Roghun.

The most urgent need at present, argues Dukhovny, is stronger water governance to mediate the struggle between hydropower companies intent on controlling water and agricultural concerns that have an inalienable right to water. Ministers of Central Asian nations meet every 3 months to discuss how to divvy up water under an existing treaty. But as resources grow scarcer, transboundary disputes are bound to grow more frequent. Because “international water law is very weak,” Dukhovny says, it might take the intervention of the U.N. Security Council to forge a lasting solution.

17. Marine Sciences

# U.S. Poised to Adopt National Ocean Policy

Faced with more action in the ocean, a new federal council will try to improve planning and resolve conflicts.

Stellwagen Bank National Marine Sanctuary shelters a rich array of marine mammals, including the highly endangered North Atlantic right whale. Spanning the mouth of Massachusetts Bay, the sanctuary is also a busy thoroughfare for cargo ships traveling to Boston. For decades, that's been a deadly combination for the whales. But a recent modification to the shipping lanes, which keeps vessels away from the area where right whales are most likely to congregate, has reduced the risk of collision by 56%. And it's made the trip only 15 minutes longer.

Such compromises—this one was worked out by the U.S. Coast Guard, port officials, and sanctuary staff—are relatively rare, however. And the growth of offshore aquaculture, wind farms, and other activities will intensify the competition for ocean space and resources. This week, a White House task force took a significant step toward better planning in federal waters by describing how to balance economic growth with improved protection of federal waters. Its report lays the groundwork for implementing the country's first national ocean policy. “Ocean planning is starting to catch on,” says marine ecologist Larry Crowder of Duke University in Durham, North Carolina. “It's nothing less than phenomenal.”

There's a pressing need for better planning. States control their waters out to 3 nautical miles; beyond that, some 20 federal agencies have responsibilities for more than 140 laws that apply to federal ocean waters and the Great Lakes. Sometimes those agencies have conflicting missions or don't communicate well. In the course of adjusting the shipping routes through Stellwagen, for example, the sanctuary staff and the Coast Guard learned of a pending request to build two liquefied natural gas (LNG) terminals that would have been dangerously close to the proposed route.

Both a 2003 report from the privately funded Pew Oceans Commission and a 2004 report from the congressionally mandated U.S. Commission on Ocean Policy called for better coordination (Science, 23 April 2004, p. 496). “Having an intelligent approach to spatial planning could really fundamentally change the way we do things in the sea,” says Elliott Norse of the Marine Conservation Biology Institute in Bellevue, Washington.

Several states are moving toward comprehensive planning in their waters, and Australia has used it to protect the Great Barrier Reef. The national Committee on Ocean Policy created by President George W. Bush fell far short of resolving such inherent conflicts as exist between the Department of Interior, which is in charge of oil and gas leases, and the National Oceanic and Atmospheric Administration (NOAA), which is responsible for fisheries and marine sanctuaries. “Nothing drove the agencies to get out of their bunkers and work toward a common goal,” says Christopher Mann of the Pew Charitable Trusts in Washington, D.C.

In June, President Barack Obama asked officials from several agencies to take a fresh look at how to improve the health of the oceans. Their report recommends formation of a National Ocean Council, comprised of senior representatives from 24 federal agencies and co-chaired by the president's science adviser and the head of the Council on Environmental Quality (CEQ). They would provide “high-level policy direction to make sure there's sustained engagement from agencies,” says Nancy Sutley, who heads CEQ. Mann is optimistic that this will help reduce conflicts.

The report also laid out nine priorities for managing the oceans, including focusing on ecosystems, managing for resiliency and climate change, and improving ocean-observing systems. “I was very pleased with the interim report,” says Robert Gagosian of the Consortium for Ocean Leadership, an advocacy group in Washington, D.C. “There's so much science in it.”

More science will clearly be needed. Regional ecosystem assessments will become a priority, says Gagosian, as will integrating the current patchwork of ocean-observing systems. “The amount of data coming in 24-7 will be tremendous,” he says. Even routine survey work on wind resources or bathymetry “could spin off interesting scientific points,” adds physical oceanographer David Farmer of the University of Rhode Island, Narragansett. A case in point: The companies building the LNG terminals agreed to install hydrophones to monitor the amount of background sounds and the noise from the terminals. These data could also be used to study how whales are affected.

All the data gathering and analysis will cost money, of course, and major budget increases are unlikely in a tight economy. NOAA Administrator Jane Lubchenco hinted at a Senate hearing last month that she may need to redirect existing resources to meet the new approach. State agencies are in a similar fiscal bind.

But money isn't the first order of business for ocean advocates. Their immediate goal is an executive order, expected by the spring, to create the national ocean policy. Then the new council will spend 6 to 12 months deciding how the planning process should work and how much it might cost.

18. Cancer Research

# Melanoma Drug Vindicates Targeted Approach

1. Ken Garber*

A mutation-targeted molecular therapy has shown promise against one of the most devastating types of cancer, but how it works is unclear.

Metastatic melanoma is one of the worst cancers. Average survival time at diagnosis is about 9 months, and many oncologists take a nihilistic attitude toward treatment. “They see patients with metastatic disease, and they say, ‘Well, you might as well make out your will; there's really nothing for you,’” says Jeffrey Weber of the Moffitt Cancer Center in Tampa, Florida. The U.S. Food and Drug Administration approved the only metastatic melanoma drug, dacarbazine, in 1975. That drug has a 15% response rate, and all efforts to improve on that rate have failed.

Until this fall, “the skepticism that we would ever be able to break the back of this problem was particularly high,” says William Kaelin, a cancer researcher at the Dana-Farber Cancer Institute in Boston. So the 70% response rate reported in September in a phase I trial for a drug from the Berkeley, California, biotech company Plexxikon shocked the field. “It's an astounding leap,” says trial principal investigator Keith Flaherty of Massachusetts General Hospital in Boston. “Way out of the ballpark of what … we've ever seen with melanoma therapies in the past.” Patient numbers, though, are small, and the compound is not a magic bullet: Patients relapse, on average, after about 9 months, and a survival benefit has yet to be proven. But the Plexxikon compound, PLX4032, is changing the psychological landscape in the melanoma field. Researchers are scrambling to understand why it works in order to design new treatments for other cancers.

PLX4032 is a targeted molecular therapy, one of many now in development. It binds to and inactivates the BRAF protein, which is mutated in about 60% of melanomas. (A single mutation accounts for most of these.) Mutant BRAF turns on signaling in a pathway in cells that controls proliferation, and the drug's efficacy validates the theory that targeting this pathway would destroy tumors. Skepticism had been widespread. “There were many who thought, ‘Well, BRAF mutations, who cares?’” says Flaherty. “ ‘These tumors have so many mutations that there's no one oncogene that's going to be so important.’”

Melanoma trials of other compounds targeting BRAF and a downstream protein, MEK, did not succeed. K. Peter Hirth, the CEO of Plexxikon, says that PLX4032 works because it's “clean”: It binds to the mutant form of BRAF much better than it does normal, “wild-type” BRAF. “You really need to have more than 90% pathway inhibition” of BRAF signaling to shut it down, he says. Because it binds preferentially to a target that exists only in tumors, the drug can be given in high doses to patients before serious side effects appear.

PLX4032 is “unlike any targeted therapy anytime in the past,” says David Solit, a researcher at the Memorial Sloan-Kettering Cancer Center in New York City. “It seems to be inhibitory of the pathway … only in tumors with the mutation. And that could lead to a change in the way we try to design drugs.”

But how the drug works remains unclear. “Why is it so selective for just the mutant?” asks Solit. One possibility is that the drug at high doses binds to wild-type BRAF or other RAF family members in a way that allows the signaling pathway to be active in normal cells instead of shutting it down. For example, a group from the biotech company Genentech presented data at the Molecular Targets and Cancer Therapeutics meeting in November in Boston showing that the same RAF inhibitors that block the pathway in BRAF mutant cells activate the pathway in nonmutant cells. Three other research groups have recently reported similar activating activity for RAF inhibitors in normal cells.

That pathway activation in normal cells could explain why side effects don't show up at high doses, speculates Frank McCormick, a cancer researcher at the University of California, San Francisco: “You don't have to worry about side effects of shutting down the pathway.”

Pathway activation in normal cells may help, but it could also account for a worrisome side effect. Some PLX4032 patients develop skin lesions known as keratoacanthomas. Researchers suspect the drug might be activating the pathway in skin cells predisposed to growth, hence the tiny lesions. They're benign, but they hint that long-term drug treatment could convert precancerous growths into nonmelanoma cancer.

Regardless of how it works, PLX4032 validates the theory that targeting early “driver” mutations is a feasible way to treat common cancers. “The hope was that by understanding the molecular biology, and in particular identifying the driver mutations, we would make progress,” says Kaelin. “This is a very significant step forward.”

BRAF mutations are also found in about 10% of colorectal cancers, and less frequently in lung and other cancers—in about 7% of all tumors overall. In theory, PLX4032 should work in all of them. A clinical trial in colorectal cancer is nearly complete.

Whether other cancer mutations can be practically targeted remains to be seen. Cancer genome sequencing efforts suggest that mutations are high in number and low in frequency (Science, 5 September 2008, p. 1280). Many drugs might prove necessary for any single tumor type, one for each driver mutation. Kaelin anticipates “drips and drabs of different mutations” in different cancers. “But I'm hoping there are at least a few more of these … highly prevalent mutations waiting to be discovered.” And drug resistance is inevitable, as PLX4032 confirms. “It's going to have to be … combinations of two or three drugs that can really effectively kill the tumors,” says McCormick. Still, the melanoma results allow researchers to go forward with some confidence. Says Kaelin, “This is a hopeful piece of data that we're on the right track.”

• * Ken Garber is a freelance writer in Ann Arbor, Michigan.

19. Genomics

# Ecological Genomics Gets Down to Genes—and Function

1. Elizabeth Pennisi

The promise of genomics has been luring ecologists into the once-alien world of molecular biology.

KANSAS CITY, MISSOURI—A decade ago, many ecologists and molecular biologists were barely on speaking terms. As universities devoted ever more space and resources to molecular biology, ecologists felt they got the short end of the stick. And those who wanted to incorporate new molecular techniques into their studies were hamstrung by grants too small to pay for the new technologies.

But in recent years, ecologists and molecular biologists have been finding common ground—to the benefit of both disciplines. “Ecology needs better grounding in mechanisms, particularly molecular mechanisms. And those [researchers] who focus on the molecular level often do so at the expense of reality,” says Jack Schultz, an ecologist at the University of Missouri, Columbia. “These two areas really need each other.” Now, says Schultz, “when you walk around, you see people [doing] genomic studies on all kinds of organisms.”

Some of the results of this detente were on display last month, when about 90 researchers and students gathered* to discuss progress in ecological genomics—the application of genomic techniques and resources to the study of ecology. Some are applying tools such as microarrays or RNA interference to their favorite study animal or plant. Others are developing genetic maps and databases of gene fragments for non-model organisms, with the goal of eventually sequencing those genomes. These efforts are pinpointing genes involved in ecologically relevant traits, and researchers are beginning to figure out the roles those genes play in an organism's function and evolution. “It's not enough to identify a list of candidate genes for adaptation; you now need to integrate a functional approach,” says Jay Storz, an evolutionary biologist at the University of Nebraska, Lincoln.

## How bees are like us

May Berenbaum, an entomologist at the University of Illinois, Urbana-Champaign, has long been interested in innovations in the arms race between insect herbivores and their hosts. Her work has focused on genes for cytochrome P450, a family of enzymes that break down toxins. (One particular P450 enables a black swallowtail caterpillar, for example, to feast on the normally toxic wild parsnip and its relatives.) For many years, Berenbaum tracked down P450 genes one at a time, but now that several genomes have been sequenced, she can use computer programs to search for typical P450 sequences across an organism's entire genome and verify them with more detailed studies. More than 7000 P450 genes are now listed in public databases; insects generally have scores of them, and some plants have hundreds.

As she described at the meeting, Berenbaum noticed something strange when she looked over the P450 counts for the honey bee, mosquito, fruit fly, and red flour beetle genomes. Honey bees had a mere 48, compared with 87 in the fruit fly, 112 in the mosquito, and 144 in the beetle. “How could they function with so few [toxin] metabolism genes?” she wondered.

She ruled out the possibility that the small number was attributable to the fact that female worker bees have just one set of chromosomes instead of the usual two: Nasonia vitripennis, a small parasitoid wasp, has the same unusual genetic system, yet it has 90 different P450 genes. Berenbaum next tried activating the honey bee's detoxification genes by exposing the insects to a chemical that usually triggers P450 gene activity. She got no response. It was as if honey bees didn't often encounter toxins.

At first this finding didn't make sense. Honey bees gather nectar from a wide range of plants, and nectar contains a variety of toxins, so Berenbaum expected that the bees would have a robust, readily activated detoxification program. But as she thought about it more, Berenbaum hit on a possible explanation: Honey bees rarely eat “raw” food. Instead, they collect nectar and pollen and process it into honey and bee bread in the hive. Sitting in the warm hive, nectar's toxins break down, nectar is dewatered, and its sugar profile and pH change as it is transformed into honey. The transformation likely renders the food less harmful. The honey bee “is the only other organism [besides humans] that prepares its food,” says Berenbaum. “They use social behavior, as do we, to deal with toxic foods.”

The work “is an exciting example of genome-enabled research—particularly the potential for comparisons between genomes of different species that have different lifestyles,” says Erica Bree Rosenblum, an evolutionary biologist at the University of Idaho, Moscow.

## How deer mice live the high life

Several talks at the meeting indicated how evolutionary biologists are coming to depend on genome sequence data to provide important insights into the evolution of specific traits. “Genomic technology [has] provided us with the means of identifying the genetic basis of adaptation and speciation,” says Storz. “The future lies in obtaining a more mechanistic understanding of those processes.”

Storz's group has already begun to go down that path. They have characterized changes in genes for hemoglobin—a component of blood that transports oxygen—that enable deer mice, Peromyscus maniculatus, to thrive at oxygen-poor high altitudes. A survey of the sequenced genomes of the lab mouse, human, and lab rat revealed that the organization of the hemoglobin genes was conserved and “showed where in the genome these genes were located,” says Storz. Two copies of the gene for the alpha globin subunit appeared together in one location; two copies of the beta globin subunit appeared together in another spot. He used the sequences and their locations to track down those same genes in the deer mouse.

At the meeting, Storz and his colleagues described how hemoglobin genes were quite different in mice living at high altitudes compared with those at low altitudes. These genes were more different than were other genes from the two locations, indicating that they experienced selection pressures in high- and low-altitude environments that other genes did not.

Based on the sequences of these subunit genes, Storz and his colleagues pinpointed five amino acid changes in the alpha globin subunits and four in the beta globin subunits associated with altitude. They purified hemoglobin from deer mice of known genetic makeups and tested how well each version of hemoglobin grabbed onto oxygen. The versions from mice living on the peaks had high oxygen affinity—which made taking in oxygen in the rarefied mountain air more efficient. Now Storz and his colleagues are making artificial hemoglobins with different combinations of the changes they see in the high-altitude mice to see which changes are most important.

“What [Storz] is doing is really at the cutting edge, the foreground, of ecological, evolutionary and functional genomics,” says Theodore Morgan, an evolutionary biologist at Kansas State University in Manhattan. “He's able to link not only the genotype with the phenotype, but he's also able to establish a mechanistic link [in] how the different alleles of hemoglobin are changing between the high altitudes and low altitudes.”

## How lizards lighten their skin

Rosenblum has also used genomics to probe mechanisms that underlie the adaptations organisms make to their environment. Her animals of choice are three species of lizard in White Sands, New Mexico—a large patch of white gypsum surrounded by dark desert scrub. Over the past 10 years, Rosenblum and her colleagues have determined that the three species have different mutations of the Mc1r pigment gene that cause normally brown skin to be quite pale. When mutated, Mc1r causes less brown pigment to be produced, helping the lizards blend in with the white sand.

She was puzzled that the mutations have different effects in two of the lizards. In the eastern fence lizard (Sceloporus undulatus), the blanched color was passed on as a dominant trait, whereas in the little striped whiptail lizard (Aspidoscelis inornata), it was a recessive trait. This difference probably affected how quickly the mutation spread in the White Sands populations of each species. When she tested the effect of each mutation on the function of the Mc1r protein in cell cultures, she discovered that the fence lizard's defective protein does not integrate well into the cell membrane, where it normally sits. The whiptail lizard's defective protein settles into the membrane just fine, however, but it doesn't pass signals along very well. “Even though we have the same gene, we have different [ways] the function is compromised,” she reported at the meeting.

The lightened skin also changes other skin-color patterns—in particular, the yellow, orange, blue, and green that lizards rely on for social cues. So Rosenblum wondered how these changes have affected courtship and territorial behavior. She and her colleagues tested whether White Sands males react differently to each other compared with males from the surrounding desert. They also looked at the White Sands males' preferences for females of like or different color. White males were more aggressive toward other white males and more attentive to the white females, Rosenblum found: “The lizards, in a couple of thousand generations, can tell the difference.” But the color changes also had an unexpected effect: White males tended to court the desert scrub males—most likely because the desert scrub males' blue belly patches were about the same size as the White Sands females' belly patches, which made them look like White Sands females. “We have a link between natural and sexual selection,” she adds. “Therefore, a single mutation can have important effects for both adaptation and the early stages of speciation.”

As the work with lizards, deer mice, and honey bees shows, ecologists have converged on genomics from very different perspectives. Yet once genomics has helped them find specific genes and identify selective pressures, their interests broaden to include physiology, cell biology, and interactions with the environment. As Michael Herman of Kansas State University points out, those in this field “are spanning all levels of biological organization.”

• * The Ecological Genomics Symposium was held 13 to 15 November in Kansas City, Missouri.