# News this Week

Science  16 Apr 2004:
Vol. 304, Issue 5669, pp. 368
1. GENOMICS

# New Global Database Lends a Hand to Gene Hunters

1. Dennis Normile

TOKYO—Genetics researchers received a new tool today. A database of annotated, full-length human complementary DNAs (cDNAs), compiled by an international team led by Japanese researchers, has been opened for public access. The database is expected to be a boon for research related to drug development, gene hunting, molecular evolution, and comparative genomics.

“This unique database should prove very valuable for understanding the human transcriptome [all the messenger RNA transcribed from genes],” says Sumio Sugano, a molecular biologist at the University of Tokyo's Institute of Medical Science and one of the organizers of the effort. cDNA embodies the protein-coding sequences of genes, as captured from messenger RNA expressed in different tissue. It represents actual protein-encoding genes and doesn't have to be inferred, as is the case when working with the genomic sequence data.

The new database pools and builds on information from six major cDNA projects, including the Mammalian Gene Collection of the U.S. National Institutes of Health, the German Human cDNA project, work at the Chinese National Human Genome Center in Shanghai, and three projects in Japan. Takashi Gojobori, deputy director of the Japan Biological Information Research Center in Tokyo, says that scientists involved in the various projects were looking for ways to make their work more accessible to all researchers and to augment the value of individual collections, for example, which focus on cancer-related cDNAs or cDNAs of genes with unknown functions. “One project can't cover everything, but put them all together and they are very complementary,” he says.

Japanese researchers took the lead in creating the database because of the large number of projects here and because Gojobori, who is also a professor of bioinformatics at the National Institute of Genetics in Mishima, got a 5-year, $22 million grant in 1999 as one of a number of Millennium Projects focusing on genetics. Additional support came from cDNA projects in China, Germany, and the United States. To create the initial data set, the six centers pooled information on more than 41,000 cDNAs. To validate, standardize, and annotate the cDNAs, Gojobori hand-picked 100-plus genome scientists from 40 institutions in 12 countries for a 10-day session in summer 2002. The event was called the “Human Full-Length cDNA Annotation Invitational,” or “H-Invitational,” Gojobori says, “because we wanted only the best genome scientists to participate to ensure a high standard of quality.” The resulting database (http://www.h-invitational.jp/) includes data on more than 20,000 unique cDNA sequences, including everything known about function, structure, tissue expression patterns, disease relationships, and orthologs in common experimental animals. Researchers who want a copy of a particular cDNA clone can contact the appropriate institute. And that is just a down payment. A second annotating marathon held last November produced data on 15,000 additional clones, which will be uploaded as soon as they are processed. The database is also prepared to accept submissions. Analysis of the annotated data has already led to the identification of several thousand previously unidentified candidate genes. And Stefan Wiemann, a molecular biologist at the German Cancer Research Center in Heidelberg and head of the German cDNA consortium, expects the database and the clones together to help researchers “investigate the roles of proteins on a large scale.” Gojobori imagines the database as the ultimate repository of information on cDNAs and sees it as one of Japan's major contributions to the field. Japan was late getting started on its contribution to human genome sequencing efforts, contributing only about 6% of the total. In contrast, the three Japanese projects contributed about 60% of the cDNA data going into the H-Invitational Database. “I think Japanese researchers wanted to make a unique contribution to genomic efforts,” he says. 2. FRANCE # Jobs Promised, Strike Aborted 1. Barbara Casassus* 1. Barbara Casassus is a writer based in Paris. PARIS—French researchers are popping the champagne corks: Their biggest crisis in decades is over. Last week, as expected, the French government caved in to scientists' demands on jobs (Science, 9 April, p. 191). Education and Research Minister François Fillon has pledged to create 550 permanent scientific posts—200 for researchers and 350 for engineers and technicians—and 1000 university jobs this year in what he terms “an exceptional and immediate effort.” He has promised more jobs in 2005. The government had already agreed to “unfreeze” €294 million from the 2002 and 2003 budgets and reinstate 120 full-time civil service jobs. “This is a big day for French research,” says Alain Trautmann, a cell biologist at the Cochin Institute and spokesperson for the protesters. “We have stopped the hemorrhage, … but we will remain vigilant and mobilized.” The protesters have aborted their calls for strike action, and the administrative resignations of lab directors have been withdrawn. But the government may have trouble keeping researchers happy as it struggles to rein in a ballooning public deficit. And some tough negotiations are expected over a law to reform research, due to be unveiled at the end of the year; a number of controversial proposals will be on the table, including financing R&D projects rather than labs. 3. ARCHAEOLOGY # Oldest Beads Suggest Early Symbolic Behavior 1. Constance Holden Two recently announced finds from Africa may strengthen the argument that humans were well on their way to complex, symbolic thinking by 75,000 years ago—long before the “creative explosion” of painting and jewelry began 40,000 years ago in Europe. The new discoveries are both of beads, made of snail shell in South Africa and ostrich eggshell in east Africa. Each may be more than 30,000 years older than any previously discovered personal adornment, although one set has not yet been fully dated. On page 404 of this issue, a team led by Christopher Henshilwood of the University of Bergen in Norway and the State University of New York, Stony Brook, reports finding in South Africa what it calls the world's oldest beads: perforated shells of the snail Nassarius kraussianus. The team recovered the beads from a Middle Stone Age (MSA) layer at Blombos Cave that has been dated to about 75,000 years ago by applying thermoluminescence and optically stimulated luminescence techniques to burnt stone and sand. The team says that the beads are the most sophisticated in a series of suggestive finds from this layer at Blombos, including two pieces of ochre with incised cross-hatchings (Science, 15 February 2002, p. 1278) and finely crafted bone tools. The east African beads, two carved doughnut-shaped pieces of ostrich shell, come from an MSA deposit extending to 110,000 years ago. They were found almost 4 years ago in Tanzania's Serengeti National Park but were announced only last month at the Paleoanthropology Society meeting in Montreal. Scientists say both are important finds, assuming they're genuine. “If the dates hold up,” says archaeologist Randall White of New York University, “we now seem to be seeing a trail of representational objects that is increasingly older as we move back [from Europe] into Africa.” The amazing burst of advanced art seen in cave paintings and jewelry in Europe beginning about 40,000 years ago has led some archaeologists, most notably Richard Klein of Stanford University, to suggest a “big bang” in human behavior at around this time, perhaps spurred by a genetic change that also affected language. But Henshilwood and others point to a small but growing record of earlier artistic objects from Africa. They argue that modern behavioral traits, such as the use of external symbols, developed gradually over a couple of hundred thousand years, not suddenly after our ancestors emerged from Africa. The bead discoveries show “that early cultural complexity, and thus likely modern human behavior, was widespread in Africa far earlier than in Europe,” says archaeologist Curtis Marean of Arizona State University in Tempe, a co-author of the ostrich shell presentation. But not everyone finds the beads so persuasive. White, for example, is not convinced that the holes in the Nassarius shells were humanmade. “I'm disturbed by the fact that there are no tool traces,” he says. Klein agrees that the holes, which occur on the weakest, most bulbous part of the shell, could well be accidental. Henshilwood counters that the holes were “almost certainly” made by a “sharp stone point” and that worn areas on the lips of the holes could have come only from having been suspended on something. He adds that in this particular stratum of the cave, “there are only 41 shells, and every single one of them is a bead … [with holes] all in exactly the same place.” Klein argues, however, that the wear around the holes could be from rubbing on the ground rather than on a thread or rope. As for the ostrich eggshells, their beadlike nature is beyond doubt, but their dating is not. Part of the uncertainty stems from the fact that there were only two of them, 35 millimeters across, and small objects can easily get mixed into lower layers. Klein says that without a large collection of such artifacts, the only way to be sure of their age is to date them directly. But principal investigator John Bower of Iowa State University and the University of California, Davis, says that the upper deposits were “sterile archaeologically,” which rules them out as the source of the beads. Bower says that the geology puts the beads in the MSA layer, which ranges from 45,000 to 110,000 years old. No specific dates have yet been obtained—carbon dating the beads would destroy them—but the team is awaiting the results of tests on associated fragments of shell, tooth, and bone. Despite excitement over the beads, Klein is not ready to change his view that there was a relatively abrupt change in humans' wiring some 40,000 years ago, because evidence for earlier creativity is extremely sparse compared with the abundance of cultural objects found later. But Marean and Henshilwood say that's because few African MSA sites have as yet been explored. The beads, insists Henshilwood, are only “part of a whole repertoire of other behaviors” that will emerge with more time—and more excavations. 4. GLOBAL CHANGE # A Slowing Cog in the North Atlantic Ocean's Climate Machine 1. Richard A. Kerr Oceanographers, who have begun to watch the slow churnings of the ocean much the way meteorologists observe the daily weather in the atmosphere, believe they have seen a new shift in ocean “climate.” The giant vortex of an ocean current, or gyre, tucked into the northwestern North Atlantic appears to have slowed. The weakening of this subpolar gyre in the 1990s may have been just a random fluctuation in one part of the complex of ocean currents that carries warm waters into the high North Atlantic. If so, this single cog in the Atlantic “conveyor belt” of north-south currents could soon recover. Or the subpolar gyre might continue to slow through this century as the whole conveyor belt brakes under the arresting hand of global warming. That would be no climate catastrophe—notwithstanding next month's climate disaster movie The Day After Tomorrow, which depicts chilling consequences of a breakdown of the conveyor. But the effects could be real enough, including a cooling of northern Europe, fewer Atlantic hurricanes, and more drought in the Sahel of Africa. The record of subpolar gyre behavior is decades shy of revealing what may be in store, but “there may well be a consequence” for the conveyor, says oceanographer Jochem Marotzke of the Max Planck Institute for Meteorology in Hamburg, Germany. This latest hint of global change comes from what might be described as an ocean weather satellite. To take a snapshot of atmospheric weather, meteorologists measure atmospheric pressure so they can map out the centers of high and low pressure around which the winds blow. In the ocean, the highs and lows around which currents circle to form gyres are palpably manifest in the height of the sea surface at their centers. In a 15 April online report in Science (www.sciencemag.org/cgi/content/abstract/1094917), oceanographers Sirpa Häkkinen of NASA's Goddard Space Flight Center in Greenbelt, Maryland, and Peter Rhines of the University of Washington, Seattle, give satellite measurements of sea surface height over the far northern North Atlantic. The measurements were made by the U.S.-French TOPEX/Poseidon radar-altimeter satellite. During the decade of observations between 1992 and 2002, the interior of the subpolar gyre, which is most intense between Labrador and Iceland just south of Greenland, rose by about 4 to 9 centimeters depending on location, Häkkinen and Rhines report. With a shallower and thus weaker low, the gyre should have slowed by more than 1 centimeter per second per decade, or about one-fifth of its flow. That's what seems to have happened: A set of current meters that was moored in the western edge of the gyre for 2 years in the mid-1990s recorded a slowing as the satellite altimetry showed a shallowing. “I think that is quite convincing,” says Marotzke. If the subpolar gyre continues to slow, oceanographers wonder what effect it could have on the conveyor belt, which they variously term the thermohaline circulation or the meridional overturning circulation (MOC). The gyre and the Labrador Sea that it encompasses make up “the Grand Central Station of global circulation,” says Rhines. “There's so much happening there.” On the broadest scale, the MOC carries warm surface waters from the South Atlantic into the far northern North Atlantic. The most obvious warm-water route is the Gulf Stream, whose northernmost branch abuts the southern edge of the subpolar gyre. The MOC also sinks cold, saltier water that moves southward in currents at mid depths and along the ocean bottom. Some of that sinking occurs in the Labrador Sea. The forces driving the subpolar gyre are varied. The wind has immediate as well as delayed effects; anything affecting the buoyancy of surface water—heating or cooling, and evaporation or the addition of fresh water—can influence the sinking of surface waters; and the effects of these forces elsewhere in the Atlantic can propagate into the gyre. In the case of the 1990s slowing, Häkkinen and Rhines deduce that surface waters within the gyre lost less heat to the atmosphere in the 1990s, warming and expanding waters there and thus raising the sea surface and slowing the gyre. Oceanographers can't say whether the subpolar gyre's heating-induced slowing will continue. “We don't claim to show there is an irreversible global warming effect” on the gyre, says Rhines. Researchers have only two snippets of record before the launch of TOPEX/Poseidon in 1992, so they have no way to tell whether they're seeing a long-term, greenhouse-induced slowing of the gyre or just random natural variations. Even if the subpolar gyre were to continue to slow, there's no agreement that it would make much difference to the MOC or climate around the Atlantic. On page 400, ocean modelers Andrew Weaver of the University of Victoria, British Columbia, and Claude Hillaire-Marcel of the University of Quebec in Montreal argue from published modeling and paleoclimate records that global warming might in fact shut down the sinking of surface waters in the gyre's Labrador Sea, as happened in 1995. But that needn't slow the MOC as a whole, they say, and would have a minor climate effect downwind in Europe. That scenario is less dramatic than an inundated New York City freezing up one summer's night, as Hollywood has it in The Day After Tomorrow, but likely closer to the truth. 5. BEHAVIORAL ECOLOGY # Why Male Bowerbirds Decorate As Well As Dance 1. Virginia Morell* 1. Virginia Morell is a writer in Ashland, Oregon. What do female satin bowerbirds want? It's a puzzle that the males of this species face every Australian spring, when the choosy ladies make their rounds, evaluating the males' efforts to impress through their elaborately decorated mating arenas, or bowers, and their dances and songs. Eventually, each female mates with one male—presumably one that she's judged to be the best. Researchers say that the dances and songs are the best indicators of a suitor's physical condition. So why do males apparently need a swanky bower as well as a spunky dance to attract mates? In this week's issue of Nature, behavioral ecologist and graduate student Seth Coleman and his colleagues at the University of Maryland, College Park, show that the males are actually sending messages to two different audiences: young, inexperienced females and older, wiser ones. Although the females ultimately want the same thing—a genetically top mate—they can't be wooed in the same way, so the males have devised different methods to present their qualifications. “People are just beginning to think about these kinds of mixed messages,” says Michael Ryan, an evolutionary biologist at the University of Texas, Austin. “We often think animals are directing their displays only at one audience when, in fact, they may be sending multiple messages to multiple audiences.” This study, notes behavioral ecologist Jack Bradbury of Cornell University, presents a “brilliant experimental way to evaluate [such] multicue decision-making.” Even to an uninitiated observer, there's no missing the advertisement of a male satin bowerbird display. Unlike the mottled green female, the males are colored a brilliant purple-blue, with blue eyes and strongly contrasting yellow beaks. They build that same color scheme into their physical displays, constructing U-shaped arenas of yellow straw on yellow straw mats, which they then decorate with as many blue objects as they can find, such as feathers, glass, and bits of plastic. When a female comes courting, she stands inside the bower and watches as the male struts, arches his wings, and screeches his love tunes. Because she will raise their offspring alone, she needs to make a careful choice, says Coleman. “That's the only thing that the male contributes: his genes. So she needs to be a good judge.” The dance and song are the best measure of male quality because although males can steal blue objects from one another's bowers, “another male can't steal this [behavioral] trait.” So why decorate a bower? To find out, Coleman outfitted about 90 wild males and females at Wallaby Creek, New South Wales, with colored plastic leg bands to identify each one. Males at 14 of the 28 bowers in the study were each then given 50 strands of blue plastic from an old tarp as well as 20 small blue plastic tiles. After the males arranged these items in their bowers, Coleman glued them in place to prevent the birds from stealing from one another. He then recorded their trysts on automatic video cameras to compare the mating success of males with enhanced bowers to those that had only their own treasures to show off. From previous studies, the team knew that females have three stages of decision-making. A female first visits several bowers when the males are not present to study the decorations. If she's pleased, she returns when the males are home to listen to their songs and watch their dances. And if she's happy with one male's performance, she builds a nest and returns to mate with him. Younger females are handicapped in their evaluations, however, because a male's intense singing and dancing often frightens them away. Coleman found that females of every age returned to the most heavily decorated bowers, showing that the bowers played some role in each female's choice. But older females watched the male's entire show and mated with the one that gave the most demanding performance, basing their final decision on the best indicator of physical quality. In contrast, younger 1- and 2-year-old females lost their hearts to males who'd been given the extra treasure—and weren't necessarily the best at song and dance. The fear factor in young females may thus explain the male's determination to collect as many blue objects as possible. “That's the best way he has to communicate his fitness to these younger birds,” says Coleman, noting that because blue items are rare in the natural environment, they can also be “good indicators” of the male's overall quality. For wooing young female bowerbirds, it seems, blue bling bling is just the thing. 6. BEHAVIORAL ECOLOGY # Songbirds Check Compass Against Sunset to Stay on Course 1. Erik Stokstad Songbirds can migrate for thousands of kilometers at night and in poor weather yet still end up in the right place. How do they do it? In lab experiments, birds can remember landmarks, check the stars or the sun, or follow a magnetic compass. Now, in a logistical tour de force, three researchers have shown for the first time what happens in the wild. After radio-tracking individual birds across the U.S. Midwest for hundreds of kilometers, the group reports on page 405 that night-flying thrushes set their course using a magnetic compass, which they calibrate to the setting sun before takeoff each evening. The new evidence is “extraordinarily straightforward and convincing,” says John Phillips of Virginia Polytechnic Institute and State University in Blacksburg. Most of what's known about bird navigation comes from lab experiments. Researchers place a bird inside a small, vertical funnel, then alter the magnetic field, the orientation of polarized light, or other cues. By watching in which direction the birds attempt to hop out, scientists try to discern which cues the birds rely on most. But these “cue-conflict” studies have often yielded conflicting results. “What was needed was a clean experiment with birds in the wild,” says Phillips. About 20 years ago, William Cochran, then at the Illinois Natural History Survey, attempted just that. He radio-tracked two migratory birds for 6 days, and they appeared to use the sunset to calibrate a magnetic compass. Calibration would help navigation, he reasoned, because magnetic field lines vary from place to place and don't always point toward true north. Birds might wander off course if they didn't double-check their bearings. Cochran had put the work aside, but when Martin Wikelski of Princeton University and Henrik Mouritsen of the University of Oldenburg in Germany approached him about the idea, the trio decided to test it. They captured several dozen gray-cheeked thrushes and Swainson's thrushes near Champaign, Illinois, and glued small radio transmitters to them. Before releasing the birds, they exposed some to “false” magnetic fields, rotated 80° to the east, during sunset. The researchers followed the birds as they flew through the night, tracking them using a meter-tall antenna mounted on top of a battered 1982 Oldsmobile. “It's quite a chase,” Wikelski says. Many nights, the team was delayed when suspicious police officers pulled over the electronics-laden car. Control birds flew northerly, but those that had been in the altered magnetic field flew westward for the entire night. The next evening, after sunset, the experimental birds corrected their course and headed north. The birds seem to calibrate their compass at sunset, perhaps from the position of the sun or the pattern of polarized light it creates in the sky. They may set their course by comparing the twilight cues with the orientation of the magnetic field lines. However, it's not certain that once airborne, the birds actually fly by their magnetic compass, Phillips notes; after getting their bearings at dusk, they might keep their eyes on the stars. This work may explain why birds don't get lost when they cross the equator. That had been an enigma because birds can't tell magnetic north from south. Instead, they check the inclination of the field lines relative to the ground; the angle becomes steeper near the poles. A bird using only its magnetic compass would risk getting turned around near the equator, but calibrating it to the sunset would keep it on track. Of course, the position of the sunset changes with latitude and season, but Wikelski thinks that birds may be able to correct for that through a biological clock that tells them the time of year. 7. CHINA # Underground Detector Proposed to Join Hunt for Gravitational Waves 1. Ding Yimin* 1. Ding Yimin writes for China Features. With reporting by Elena Giorgi in Pasadena, California. BEIJING—Using Einstein's name as a selling point, a team of Chinese scientists hopes to build an underground physics facility that will let them join the global search for gravitational waves. The project, if approved, would also mark a significant milestone in China's support for fundamental research that doesn't promise an economic payoff. Gravitational waves were posited by Einstein in his 1915 general theory of relativity. But these subtle ripples in spacetime, postulated to originate in violent events such as supernovas and the collision of black holes, have never been observed. The China Einstein Gravitational Wave Observatory (CEGO) would complement existing observatories such as LIGO in the United States and VIRGO in Europe, as well as LISA, a space-based antenna being developed jointly by NASA and the European Space Agency, and DECIGO, a similar antenna under consideration by the Japan Aerospace Exploration Agency. China's effort is led by geophysicist Tang Keyun of the Chinese Academy of Sciences' (CAS's) Institute of Geology and Geophysics. Tang has spent a decade chasing solar eclipses for evidence of a graviton, a hypothetical particle responsible for gravity. According to one theory, the moon's juxtaposition between Earth and the sun during a total eclipse should alter, however infinitesimally, the sun's pull on Earth. Although apparatus set up by Tang and colleagues in China (1997), Zambia (2001), and Australia (2002) failed to detect any clear evidence of a dip in gravity, the group plans to continue its monitoring of total solar eclipses next year in South America and in 2008 and 2009 in China. In the meantime, Tang is pushing the idea of an L-shaped underground interferometer, up to 5 kilometers on a side. He chose its name, he says, “because there are many more Chinese who know Einstein than know gravitational waves.” The experiment would fill a geographic gap in the ground-based observatories that would help scientists triangulate any recorded measurements. It would also operate at frequencies below those of LIGO and VIRGO and above LISA's. Finally, its location 500 meters underground would eliminate the confounding effect of seismic noise at the surface. And CEGO would be only the first step, he says: “Our goal is to build an underground facility capable of hosting multiple interferometers.” U.S. scientists involved in LIGO are intrigued by China's plans. “The low-frequency interferometers would complement the performance of the present instruments,” says physicist Riccardo De Salvo, who met Tang during the latter's recent visits to the California Institute of Technology (Caltech) in Pasadena, the scientific home of the$365 million U.S. instrument. “And the optimized sensitivity [of an underground facility] would provide much greater insight into phenomena like the genesis of the large galactic black holes.”

De Salvo had already proposed that an aboveground, low-frequency interferometer be installed in parallel with planned upgrades to LIGO, which began operations in 2002. So when he heard about Tang's plans, “the synergy was obvious.” Last month De Salvo and colleagues attended a workshop on gravitational wave observatories that Tang put on in Beijing.

LIGO's director, Caltech physicist Barry Barish, says it's “much too early” to know what will become of Tang's project. But he's happy to share with the Chinese his team's knowledge of building and operating such observatories. He's written letters of support for CEGO to China's Ministry of Science and Technology, CAS, and the National Natural Science Foundation of China, which will ultimately make the call on whether to fund the facility, and he plans to ask the U.S. National Science Foundation to fund a series of scientific exchanges with Chinese scientists in fields—from laser interferometry, precision optics, advanced control, and high-vacuum systems to seismic isolation and crystal materials—essential to the project's success. “I wrote the letters to let the Chinese know that other scientists take the project seriously,” Barish says.

To get more bang for the research buck, DST has identified five areas in which South Africa has distinct advantages: astronomy and Earth observation, indigenous knowledge, bioscience and bioresources, paleontology, and the Antarctic, islands, and oceans. The government, which has earmarked $16 million for these niche areas, puts a premium on attracting foreign scientists—and support. The strategy is paying dividends. South Africa is now involved in several major research collaborations, ranging from the construction of the largest optical and infrared telescope in the Southern Hemisphere (see p. 378) to a multidisciplinary project to study the genetics, genome, and habitat of the coelacanth, a living fossil that has plied the waters off southern Africa unchanged for 70 million years. With the government setting the priorities, some scientists were bound to feel left out in the cold. According to medical biochemist Wieland Gevers, the government has turned a deaf ear to his funding requests for the Institute of Infectious Disease and Molecular Medicine, a new biomedical research facility that he founded on the University of Cape Town campus in 2001. So far, its funding has come from grants that its 25 staff scientists brought with them or from private donations. “It's a paradox,” Gevers says. “We're in a country with more than 5 million people infected with HIV, the highest rate of tuberculosis, and malaria on its borders, yet we can't get support for a major new institute for infectious diseases.” Instead, he complains, funding is lavished on projects with little relevance to the country's immediate needs: “It's money going into the stars.” Adam disputes that characterization. He notes that the leveraging strategy used to land big astronomy projects in South Africa has also won international collaboration in health research. “In the past couple of years, we pumped a lot of cash into the whole bio area,” he says. “If you look at the growth area, it's not astronomy, it's biotech.” Mokhele notes that in 2001 NRF launched a strategy for responding to South Africa's development challenges. With broad titles such as “Unlocking the future: Advancing and strengthening strategic knowledge” and “Sustainable livelihoods: The eradication of poverty,” the categories are intended to draw in scientists from a range of disciplines. “Instead of saying, ‘This is chemistry, physics, sociology, or psychology,’ we're saying, ‘Here are the challenges that we're responding to. How does your scholarship and research respond to them?’” Mokhele explains. Many South African researchers insist that they are eager to pick up that gauntlet. “Fairly ordinary scientists can actually make a huge difference in whether things succeed or fail here,” says astronomer Patricia Whitelock of the South African Astronomical Observatory. And in stark contrast to how things were a mere decade ago, black researchers will have just as large a role as their white peers in keeping the scientific community—and the country—afloat. 9. 10 YEARS AFTER APARTHEID # New South Africa Puts Emphasis on Reclaiming Humanity's Past 1. John Bohannon* 1. John Bohannon writes from Oxford, U.K. Some of the world's most famous archaeological sites are to be found in South Africa, but so far few blacks have entered the field ELANDS BAY, SOUTH AFRICA—It might not look like prime real estate, but this rocky outcrop studded with prickly fynbos bushes and boulders has been a penthouse of sorts since the dawn of humanity. From the cool shade of a rock shelter in the sandstone face, the earliest known Homo sapiens could enjoy an unobstructed view of the Verlorenvlei River valley and the moving feast—a dozen varieties of antelope—that grazed on the grassy banks. Archaeologists have unearthed a treasure-trove of artifacts under the packed dirt of the shelter's floor. Among the finds are the remains of a cooking hearth, a trash pile that consists mostly of seafood shells, and fragments of ostrich eggshell etched with geometric patterns, which some claim are the oldest examples of symbolic expression ever found. The deepest layer being uncovered is estimated to be almost 100,000 years old. Closer to the present surface, the accumulated dirt has yielded stone tools of increasing sophistication. And painted on the walls with red ochre possibly as many as 20,000 years ago are graceful images of antelopes next to human handprints. Under this sheltering stone ceiling is “the oldest record of human cultural evolution in the world,” says Cedric Poppenpoel, an archaeologist at the University of Cape Town (UCT), who is directing the excavation. And this is only one of a plethora of sites in South Africa that reveal not only the origins of human culture but also the evolutionary transition from ape to human. Some 1200 kilometers to the northeast, the Sterkfontein cave near Johannesburg has offered up one of the richest sources of early hominid remains in the world, with over 600 specimens so far including the famous “Little Foot,” a 3-million- to 4- million-year-old skeleton of an australopithecine, our recent apelike ancestor. “Sterkfontein is unusually good for producing whole skeletons,” says Phillip Tobias, a paleoanthropologist at the University of the Witwatersrand in Johannesburg, probably because our unfortunate ancestors either fell or climbed down into the cave and couldn't get back out again. As a result, he says, researchers have the unique opportunity to study a “diversity of specimens cheek by jowl.” From Verlorenvlei to Sterkfontein and hundreds of sites in between, South Africa has become “probably the best place in the world to study where we came from,” says John Parkington, a prehistoric archaeologist at UCT. “It is certainly one of the cradles of humanity” where many of the key fossils for the modern theory of human ancestry have been unearthed. Hoping to build on its natural endowment of Paleolithic riches, the South African government has designated human origins research as one of its priorities for basic research funding, although so far it has limited support mostly to the handful of well-known sites. But some experts see an equally important task in transforming the demographics of their white- dominated research community. Bringing South Africa's ancient wonders to light didn't always receive such encouragement. During the apartheid era, “I received absolutely no financial support from the government” for excavations, says Tobias. Strongly influenced by the conservative Dutch Reform Church, the apartheid government was loath to fund research on evolution “that contradicted the Bible,” he says. Moreover, Tobias and other researchers were often cut off from their colleagues overseas by the antiapartheid movement's academic boycott. This made it “often impossible to attend conferences or to publish in many journals.” Perhaps no one has a better perspective on how things have changed here than Poppenpoel. In 1962, at the age of 17, Poppenpoel entered the field of archaeology at the only level allowed to blacks under apartheid: as a laborer. He was hired by Barbara Anthony, an archaeologist now retired from Harvard University. As they excavated a remote Stone Age site in the Western Cape province, “she continuously fed me with information and books,” Poppenpoel recalls, and within a year he “fell in love with archaeology.” After the dig, Anthony brought Poppenpoel to the South African Museum in Cape Town, where he helped her sort and analyze artifacts. One day at the museum he was approached by Raymond Inskeep, a renowned UCT archaeologist, who later moved to the University of Oxford, U.K. “He asked me if I'd like to go to the University of Cape Town to study archaeology.” Poppenpoel was thrilled but anxious: “There had never been a single black archaeology student there.” To get around the apartheid ban on him studying there, Inskeep arranged for the archaeology department to employ Poppenpoel as a staff member, providing a loophole for him to attend classes. He completed the undergraduate course of study, “although of course I was never given the degree.” Everything changed 10 years ago with the arrival of democracy. With all barriers dropping away, Poppenpoel dove into a master's thesis and is now in the home stretch of a Ph.D. It will be an extraordinary thesis: As the principal investigator at the Verlorenvlei site, he is in charge of one of the most important early human sites in the world. Poppenpoel's success story is all too rare here. The ranks of paleoanthropologists and archaeologists in South Africa remain almost entirely white. “Very little has changed since the end of apartheid,” laments Parkington. Part of the problem could be a lingering taint of colonialism. “Archaeology and anthropology were born in colonial circumstances” when white foreigners arrived, grabbed material, and “left nothing behind,” Parkington says. If this work is never taken on by black researchers, he adds, “it would be a great shame.” One serious barrier to black students, most of whom are from financially struggling families, is the lack of job prospects. Because the study of prehistory “never became part of the public consciousness,” says Parkington, “the whole field has been in decline,” with the number of museum and university positions “shrinking since the 1980s.” Over the past decade, the need for new student scholarships and faculty positions “has not been met.” Tobias agrees but predicts that prospects could soon improve. “There hasn't been a flood of black students yet,” he says, but the numbers are improving, at least at the undergraduate level. This is one area where the rest of Africa is coming to South Africa's rescue. Tobias notes that black paleoanthropologists from the rest of Africa are coming here as visiting faculty members, providing black students with badly needed role models. And in terms of the job market, he adds that the government's renewed support of the field—which is still largely at the planning stage—is already having “wonderful knock-on effects,” such as the construction of the Human Evolution Research Institute at the University of the Witwatersrand. Looking ahead, Parkington sees a need to “democratize” the science: “We should have a cast of Little Foot in every school's classroom so that children are proud of what they have here.” The government is doing its part to promote such feelings at a higher level, for example by rejoining UNESCO and successfully nominating 13 Paleolithic caves as World Heritage sites. It has also placed rock-art images of human figures in the center of the new national crest. “I'm enormously optimistic about the future,” says Tobias, who is retiring after a 60-year career. He was one of a minority of scientists here who were openly critical of the apartheid government's racist policies. With apartheid finally behind them, “South Africa will be a world center for the study of human evolution,” and inevitably, says Tobias, black researchers will be leading the way. In a very real sense, he says, “we are all Africans.” 10. 10 YEARS AFTER APARTHEID # Astronomers Attempt to Stay in the Big League 1. Charlene Crabb* 1. Charlene Crabb is a science writer based in Paris. The South African government has made the controversial decision to invest heavily in astronomy, as an inspiration to the nation's youth SUTHERLAND, SOUTH AFRICA—With its shiny metal dome and white walls, the Southern African Large Telescope (SALT) looks like an alien spaceship that just touched down among the dry scrub and rust-red rocks in this corner of the Karoo plateau in western South Africa. Even more incongruous is how SALT arrived on the political scene. In 1998, only a few years after the country's first democratic election and while grappling with urgent problems such as poverty, homelessness, and AIDS, the South African government made a stunning proposal: It would finance half the cost of a$20 million, world-class 10-meter optical telescope if international partners stumped up the rest. Barely 2 years later, the groundbreaking ceremony for SALT took place.

The government remains steadfast in its commitment to keeping astronomy a national priority. South Africa has made a serious bid to host another international collaboration, a radio astronomy project called the Square Kilometre Array (SKA), and participates in a third, the High Energy Stereoscopic System (HESS), a gamma ray telescope soon to be commissioned in neighboring Namibia. Gambling that such investments will keep South Africa a leader in the high-profile world of astronomy, the government also hopes that they will spark interest in science among young people (see sidebar at right), create opportunities for industry, and lure scientific resources to southern Africa.

“There's no way we can pay for our astronomy program on our own,” says Rob Adam, director general of the Department of Science and Technology. “That would be mad. So we say to the rest of the world, ‘Look, we have wonderful viewing conditions here, we have industry that can build much cheaper than anywhere else, plus we can maintain facilities.’” Out of that deal, Adam says, “we get high-cost infrastructure on our table.”

South Africa is hoping to get back to where it once was: at the forefront of astronomy in the Southern Hemisphere. For example, a 1.9-meter optical telescope, predating World War II and standing a few hundred meters from SALT, was once the largest of its kind in the Southern Hemisphere. By the 1970s, however, 4-meter telescopes were cropping up in Chile, Australia, and other locales, rendering South Africa's scope nearly “obsolete and irrelevant,” says SALT project scientist David Buckley.

The dismantling of apartheid opened the door to international funding and collaboration. In 1996, scientists at the McDonald Observatory near Fort Davis, Texas, paid a visit to the Cape Town headquarters of the South African Astronomical Observatory. They wanted to drum up interest in building a Southern Hemisphere equivalent of the Hobby-Eberly Telescope (HET), then under construction at the McDonald Observatory.

The timing was right. Astronomers were hungry for a new telescope, and crucially, the new government was eager to support a flagship project that would buoy one of its top scientific communities. Plus, HET's revolutionary design—a spherical mirror tilted at a fixed angle, optics to correct for the mirror's poor focusing ability, and a device to track star movement so that the mirror could remain stationary—meant that a world-class 10-meter telescope could be built for $20 million, roughly the cost of a conventional 3-meter instrument. (Inflation has since increased the cost to$30 million.)

Scheduled for completion early next year, SALT improves on the HET design. Its main mirror, like its cousin's, consists of an array of 91 hexagonal segments, but in SALT each is equipped with a dozen edge sensors as well as three positioners that will keep the segment properly aligned with its neighbors. South African astronomer Darragh O'Donoghue has revamped the optics that correct the spherical aberration caused by the main mirror's shape; the current image is 240% sharper and quadruples the field of view. With this “gigantic African eye,” as President Thabo Mbeke has called it, SALT astronomers can search for planets orbiting nearby stars or probe distant galaxies for clues to the early history of the universe.

The South African government didn't put all its astronomical eggs in one basket. “We decided to look at the whole spectrum open to ground-based astronomy,” says Adam. South Africa was approached in 1997 by an international consortium to participate in the HESS telescope, a high-energy gamma ray telescope in central Namibia. Gamma rays from space collide with atoms in the upper atmosphere, creating showers of secondary particles. These particles give off a faint blue light, Cherenkov radiation, which follows the path of the original gamma ray down to Earth's surface. Phase I of HESS, four 11-meter optical telescopes, will be inaugurated in September; the project may shed light on the mysterious origin of very high energy cosmic rays.

Currently, South Africa is in the throes of bidding to host SKA, a $1 billion international project to create a million square meters—1 square kilometer—of receiving surface for radio waves in the 0.15- to 20-gigahertz range. The vast surface, 100 times the size of the biggest receiving surface in existence, will consist of small antennas arranged in a dense core fanning out in an increasingly diffuse array extending as much as 10,000 kilometers from the central cluster, with some dishes on other continents. The widespread network will yield unprecedented resolution. Although the number, design, and distribution of antennas will not be finalized until 2007, the site for the core, an area that must be entirely free of cell phone, television, and radio transmissions, is expected to be chosen next year. South Africa has nominated three such sites in remote parts of the Northern Cape, SALT's home province. A half-dozen other countries are also putting in bids, including Australia, Argentina, and China. But reservations remain about financing such projects when there are so many pressing problems in South Africa. “There is a sense that we should not be building [SALT], given the national challenges,” says Khotso Mokhele, president of the National Research Foundation. “We're riddled with AIDS, multiple-drug-resistant tuberculosis, unemployment, crime—all sorts of things. And many people say, ‘Why not take the money and respond to those challenges?’ We say to them, ‘Yes, we'll work ceaselessly and selflessly to respond to those challenges. But at the same time, we can still allow ourselves to see SALT as a project we want to fund.’” Part of this commitment to big astronomy rests on the belief that the projects have tangible returns, such as spurring South Africa's economy and technological development. “People enjoy talking about dark matter, dark energy, and the big bang. And the science is exciting, but the more pragmatic side is, what will it do for South Africa?” says Justin Jonas, managing director of the Hartebeesthoek Radio Astronomy Observatory. So far, South African industry has made about 60% of SALT's components. And there are potential commercial spin-offs: Extremely fast switching devices used in HESS to detect rapid Cherenkov flashes are now being adapted for use in commercial sterilization systems, because such rapid switching generates ozone, a powerful disinfectant. The big astronomy projects will also address another national challenge: improving science education in rural areas and among blacks. SALT's budget pays for a science teacher at the local high school in Sutherland, a teaching specialty that did not exist here until the new telescope came to town. And observatory staff members train teachers and give talks to children in other communities. So while South African astronomers are gazing at the heavens, they are also working to solve problems closer to home. “We see astronomy as something driving the national development agenda,” says senior astronomer Patricia Whitelock of the South African Astronomical Observatory. “It's not just astronomy, not just science for scientists. It's an icon of South African achievement, something young Africans can aspire to be part of.” 11. 10 YEARS AFTER APARTHEID # South Africa's Own Shooting Star 1. John Bohannon* 1. John Bohannon writes from Oxford, U.K. CAPE TOWN, SOUTH AFRICA—Thebe Medupe takes a stroll under the brilliant southern sky, a protective hand on the shoulders of two of his astrophysics graduate students. Although Medupe turned 30 years old this year, his smooth, round face and unconstrained grin make him look more like a classmate of the two youngsters than their supervisor. It wasn't long ago that he was in their position, but they will not face the kind of obstacles that stood in his way. In 1986, Medupe was 13 years old and living in a village with no running water outside Mafikeng in northern South Africa. This was the year that Halley's Comet came whipping through the solar system, firing Medupe with a passion for astronomy. Straightaway he built his own telescope—using a metal pipe that he cut and fitted with a pair of lenses borrowed from his school—and meticulously mapped the surface of the moon. “I was determined to become an astronomer,” recalls Medupe. Apartheid began to crumble just as Medupe was applying to universities, enabling him to become the first black astronomy student at the prestigious University of Cape Town (UCT). He stayed on to earn a cum laude distinction for his master's thesis and complete a Ph.D. on the interior structure of stars, and now he works at the South African Astronomical Observatory in Sutherland, where he continues to study stellar interiors. Medupe has also taken on a mission: to attract black students into his field. Astronomy is one of the research communities in South Africa in which black scientists are most underrepresented, with only three among the country's 50 astronomers. Medupe sees two major barriers to transforming these demographics. There is little public outreach to attract black students into astronomy, he says, and those who do take it up “have no black role models to encourage them to go further.” Medupe is tackling both these problems at once. “Thebe is an inspiration,” beams Brian Warner, head of UCT's astronomy department. “During apartheid,” Medupe says, “we were told that Africans have never been interested in science, and certainly not astronomy.” To put the lie to this misrepresentation, Medupe teamed up with a pair of filmmakers and in 2002 traveled across Africa, visiting remote villages and collecting cosmological mythologies. The making of the film, called Cosmic Africa, transformed Medupe. “I know so much about the stars, yet I know so little about my own continent and how my own people are connected to the sky,” he explains. The film has won praise at festivals in South Africa and later this month will be aired at the Hayden Planetarium in New York City. Meanwhile, Medupe is guiding as many black astronomy students into postgraduate research as he can. In 2000, he set up a theoretical astrophysics research program back home at North West University in Mafikeng. When it started, the program didn't even have a room allocated to it—it “really was theoretical,” quips Medupe. Four years later the program has plenty of room, including a new computer lab, and Medupe oversees a budding group of two master's and two Ph.D. students. And this year, Medupe is helping run a national program to pluck out the brightest astronomy students—particularly black postgrads at disadvantaged universities—and give them year-round access to the best teaching and research resources. Medupe has high hopes that his efforts will bear fruit. “My dream is to start seeing top-quality black astronomy graduates running the facilities here,” he says, “and participating on an equal basis with astronomers from around the world.” It's unclear when that vision will be realized, but Warner believes it is inevitable. “You want to keep your standards high and hire on the basis of skill. So we need to increase the number of qualified black students.” In spite of Medupe's unbridled optimism, one thing still frustrates him. “I go to international astronomy conferences, and I'm almost always the only black face in the crowd.” If he gets his way, Medupe will change that. 12. 10 YEARS AFTER APARTHEID # Earth Sciences Seek Niche Apart From Mining Industry 1. John Bohannon* 1. John Bohannon writes from Oxford, U.K. Powerful mining interests have long set the agenda for South African earth sciences. But perhaps not for much longer CAPE TOWN, SOUTH AFRICA—Tshifhiwa Mabidi faces the same challenges as do graduate students everywhere, such as having a lot to learn in very little time. For her master's degree in geology here at the University of Cape Town (UCT), she is compiling a geological treasure map: an enormous database on minerals that she will use to test the predictive power of models used to zero in on precious metals such as gold, silver, and platinum. She looks over the computer algorithms she will soon have to learn how to use and grimaces. Before embarking up this mountain of learning, however, she's heading out into the field with a group of visiting German geologists to conduct magnetic and electrical soundings of Earth's crust. “It's completely unrelated to my master's thesis,” she admits with a smile and a shrug, “but it will be a very good experience.” Such opportunities are a sign of the changing times as earth sciences departments try to cast off their historical role as a training ground for the country's powerful mining industry. The German team that Mabidi will join is part of an international project called Inkaba ye Africa that aims to transform South Africa's earth sciences community into a basic research powerhouse. “The problems that Inkaba is taking on are exciting,” says Kevin Burke, an earth scientist at the Carnegie Institution of Washington. But Inkaba faces an uphill struggle: The mining industry continues to snap up the lion's share of top students, both black and white. In a cramped office down the hall from Mabidi, her mentor, Maarten de Wit, is a blur of activity. He has just returned from a scientific meeting in France and is about to head out into the field with another German group. A geologist at UCT since 1989, de Wit has been South Africa's driving force behind Inkaba ye Africa. Since 2002 he has helped pull together 15 government and academic institutions in South Africa and Germany into a consortium. And Inkaba is more than just an idea now: The two governments signed up to the$14 million program in January.

The scale and complexity of Inkaba ye Africa are what set it apart from most earth science efforts. The plan is to survey a cone-shaped sector of Earth, extending from the core out to space and enclosing South Africa and much of the surrounding ocean. The idea is to uncover the evolution of its components—magma, rock, and water systems—going back 200 million years, when the Gondwana supercontinent began to break apart. The challenge is to explain how changes that have occurred deep beneath Earth's crust have influenced South Africa's current air, sea, and land features. That, de Wit predicts, should shed light on everything from the distribution of minerals and Earth's fluctuating magnetic field to the causes of climate change, natural hazards, and even human ancestry. In the Xhosa language—one of 11 spoken in South Africa—Inkaba means “navel” and figuratively conveys a sense of total interconnectedness.

So why South Africa? “Because it is, quite simply, the best natural earth systems laboratory in the world,” de Wit claims. Brian Horsfield of the Earth Science Center (GFZ) in Potsdam, the main German coordinator of Inkaba, agrees: “The sheer magnificence of South African geology was the initial reason for the GFZ to set up shop down there.” The bulk of the country's landmass consists of a chunk of crust called the Kaapvaal Craton that has remained stable for over 3.5 billion years within a shifting bed of younger rocks. As a result, de Wit says, southern Africa has “the longest and best-preserved geologic record in the world.” Embedded in this island of stability are hundreds of kimberlites, magma pipes as many as a few kilometers wide that act like rock elevators, bringing samples from the lower mantle and perhaps even the core itself up close to the surface. People have been keenly interested in South Africa's kimberlites for more than a century because they are a rich source of diamonds. And South Africa's ancient geologic store is also one of the richest for gold and platinum.

Blasting in the world's deepest mines—some of which plunge 3 kilometers—has unexpected consequences. South Africa is now the only place in the world with anthropogenic tectonic activity, generating earthquakes up to magnitude 5 on the Richter scale across a 10,000 km2 area—four times the size of Rhode Island—on an almost daily basis. By studying how fractures start and propagate through rock, Inkaba aims to improve mine safety and better understand the fundamentals of earthquake physics.

But that is just the beginning. For example, one project is focusing on a hole in Earth's magnetic field drifting toward South Africa's west coast. Scientists are concerned that this anomaly could be a sign that the direction of Earth's magnetic field could be about to flip, as has happened several times in the planet's history. Because the field is generated by Earth's liquid core, Inkaba scientists want to discover whether it is due to an upwelling of magma at the core-mantle interface thousands of kilometers beneath South Africa. Normally, different kinds of earth scientists remain isolated from each other, says Hartwig Frimmel, a UCT earth scientist who serves as one of three Inkaba coordinators, but not in the Inkaba project. Because much of the data collecting will be done offshore, these geophysicists will be rubbing elbows onboard with geochemists and climate modelers working on an entirely different part of the Inkaba project.

For every section of Inkaba, money has been set aside to support black graduate students. This strategy for capacity building has already been tested on a smaller scale. Before Inkaba, de Wit and UCT geochemist Marian Tredoux were part of a project with several U.S. groups that focused on determining the geologic history of the Kaapvaal Craton. The initiative recruited several black students who have gone on to pursue basic research. Collaborations such as Inkaba have lasting benefits for black South Africans, says Tredoux, by giving them the chance to study abroad and work with Western counterparts. De Wit holds up a photo of his department's current final-year undergraduates and points out proudly that all but one of the 13 are black and half are women.

But how many of South Africa's black earth science students will stick with academia is another question. The UCT geology department recently advertised a faculty position explicitly for a black geologist. Despite the pool of talent on hand, says Frimmel, “not a single black applicant came forward.” Part of the reason is a revolution taking place within the mining industry. As part of its black empowerment strategy, the government passed legislation in 2002 calling for at least 26% of the industry to be run by black South Africans within 10 years. To meet this demand, the industry is snapping up top black students by offering salaries with which academia can't compete.

Such career prospects tantalize students like Mabidi. The 23-year-old grew up in Venda, one of the “homelands” cordoned off by the apartheid government in the 1960s where blacks were forced to live in appalling poverty. She was lucky to move from her village to the town of Thohoyandou, the local capital, where she had access to education, including a geology degree at nearby the University of Venda, one of South Africa's historically black colleges. When asked what she will do after obtaining her master's degree, Mabidi does not hesitate: “I will almost certainly go into mining.”

Tredoux isn't surprised. Many students “are sending money home to their families. I've found students nearly starving themselves to save,” she says. Until there is a substantial black middle class in this country, says Tredoux, efforts at changing the color of the earth sciences faculty will continue to be “three steps forward, two steps back.” But in the meantime, if Inkaba ye Africa achieves even half of its goals, the black Ph.D. students who do manage to avoid the lure of mining will find themselves in a golden age of South African earth science.

13. EVOLUTION OF DEVELOPMENTAL DIVERSITY MEETING

# The Genes That Change the Cichlid Jaws

1. Elizabeth Pennisi

COLD SPRING HARBOR, NEW YORK—From jellyfish to kangaroos, the Evolution of Developmental Diversity meeting held here 31 March to 4 April covered evolutionary, developmental, and genetic aspects of a menagerie of organisms.

Sometimes it doesn't take much to send an organism down a different path, one that leads to a new species. Cichlids are 5- centimeter- to 50-centimeter-long fish from East African Rift Valley lakes such as Lake Malawi. There, it took a mere million years or so for about 1000 species to evolve, all with different lifestyles, eating habits, and mating and breeding strategies. These differences enable the plethora of types to live together comfortably.

A gene that controls multiple components of skull development may have made possible some of these adaptations, says R. Craig Albertson, an evolutionary biologist at the Forsyth Institute in Boston, Massachusetts. He and his colleagues have evaluated the genetic underpinnings of the different mandible styles by breeding two cichlid species: Labeotropheus fuelleborni, with big bones and a short snout—good for foraging on the lake floor—and Metriaclima zebra, which has a long, narrow mouth for sucking in and snapping up prey in midwater.

When he first crossed the two species, which are close enough to interbreed, Albertson got jaws that were midway in size and shape between those of the two parents. He then bred the progeny of these intermediates with each other and did a genetic analysis to determine quantitative trait loci: places along the genome, typically containing one gene, that are responsible for the resulting variation. He looked for loci involved with the height, width, and overall shape of various skull bones, including the two distal and proximal elements of the mandible. The distal element juts out and supports the teeth. The proximal element extends backward from the distal element; it has a bony process that curves upward toward the eye and is the anchor point for jaw muscles.

Late last year, he reported that this analysis indicated that just two hotspots control the height and length of the jaw. In addition, the mandible's height and length change in inverse proportion. He doesn't have a particular gene from any of these hotspots in hand, but the evidence is growing that each of these hotspots—and likely a single gene within them—is capable of remaking a jaw.

When one of these genes alters the proximal element, it also reduces the height of the bony process, which, as a result, can't support such big muscles. Then there is a domino effect, as this reshaping of the proximal element seems to influence the dimensions of the distal element, which in turn can affect the teeth. The work makes a key point, comments Richard Behringer, a genomicist at the University of Texas M. D. Anderson Cancer Center in Houston: “You can make one change, and something big happens.”

Albertson's team has now found developmental evidence of this domino effect. Just 1 week into development, a cartilaginous proximal element with a tall “bony” process has a short jaw. Even at this early stage, the gene in charge of shaping this precursor bone indirectly dictates the distal element's position, Albertson reported at the meeting. “It's just tagging along and doing what the proximal element tells it to do,” he explains.

The work “suggests that the entire jaw is evolving as a single unit,” says F. Bryan Pickett, a biologist at Loyola University in Chicago. And that modularity could help explain the rapid evolution of these fish in the face of intense competition for food and space. Says Pickett, “It might give you a way to [change] rapidly.”

14. EVOLUTION OF DEVELOPMENTAL DIVERSITY MEETING

# Japanese Catch of the Day

1. Elizabeth Pennisi

COLD SPRING HARBOR, NEW YORK—From jellyfish to kangaroos, the Evolution of Developmental Diversity meeting held here 31 March to 4 April covered evolutionary, developmental, and genetic aspects of a menagerie of organisms.

Japanese researchers have taken a big first step toward making one of their native fish a worldwide tool for genomicists. Last week, an extensive draft genome of this fish, called medaka, was released to the public. And Hisato Kondoh of Osaka University is ready to take advantage of the sequence data. He and his colleagues have gathered an extensive collection of mutant medaka. F. Bryan Pickett, a biologist at Loyola University in Chicago, calls the group's detailed catalog about these mutants a “valuable innovation” that should help researchers determine the functions of new medaka genes. Although some consider medaka the piscine equivalent of Drosophila—both have a century-old history as tools for geneticists—“it hasn't had the attention it deserves,” says Chris Amemiya, a genomicist at Benaroya Research Institute at Virginia Mason in Seattle, Washington, in part because there were no strong U.S. proponents for sequencing this species.

But medaka has advantages over the zebrafish and puffer, the two other fish with sequenced genomes, Kondoh points out. Several inbred medaka strains now exist, simplifying genetic studies. Medaka is also an amenable lab animal. Females brood their eggs on their bellies, providing researchers with easy access to genetically identical young. During the month these fish breed, a pair can produce 1000 eggs, plenty for most studies. The young also develop much more slowly than zebrafish, he adds, providing a longer window for embryological work.

For their first go-around, Kondoh and his colleagues have chemically treated enough fish to alter 70% of their genes, which they will study in mutant offspring. Among those identified so far appear to be 350 mutants with developmental defects and 2000 that die during development, he reported. The screen should expand rapidly now, he notes, because three more groups have joined the effort. “With this [screen], you are likely to get a lot of new things,” comments Nipam Patel, an evolutionary development, or evo-devo, biologist at the University of California, Berkeley.

The work has already yielded some bizarre results, and the draft genome is helping the researchers home in on the genes responsible. At the meeting, Kondoh described one mutant, called totoro, in which both males and females have abdomens filled with immature eggs. Another, called finless, lacks a tail and swims by thrusting its body from side to side. “And this is just the tip of the iceberg,” says Amemiya. He's quite pleased with these results, noting that “all these kinds of [mutants] that are available for medaka will absolutely complement [studies] of zebrafish.”

15. EVOLUTION OF DEVELOPMENTAL DIVERSITY MEETING

# RNAi Takes Evo-Devo World by Storm

1. Elizabeth Pennisi

COLD SPRING HARBOR, NEW YORK—From jellyfish to kangaroos, the Evolution of Developmental Diversity meeting held here 31 March to 4 April covered evolutionary, developmental, and genetic aspects of a menagerie of organisms.

In 1998, geneticists working on the worm Caenorhabditis elegans, one of the first beasts to have its genome sequenced, struck gold. They discovered a simple way to find out the functions of many of its 20,000 sequenced genes. A stampede ensued, with researchers racing to try the procedure, called RNAi, in their favorite study organisms. “Here you had a technique that you could use on nonmodel organisms,” for which no other good methods exist for knocking out genes, points out Nipam Patel, an evo-devo biologist at the University of California (UC), Berkeley. At the meeting, at least a half-dozen evo-devo biologists reported new results made possible through RNAi. From planaria and jellyfish to beetles and crickets, RNAi is unearthing the roles of certain genes in development and evolution—information that can also help illuminate human genes.

RNAi—the “i” stands for interference—works by neutralizing specific RNAs, essentially shutting down the gene that generated them. It's like using a mutation to knock out a gene, but easier. By observing how this shutdown affects an organism, researchers can deduce the gene's purpose.

Using this technique, Alejandro Sánchez Alvarado, a developmental biologist at the University of Utah School of Medicine in Salt Lake City, has zeroed in on a gene shared by many plants and animals, showing that in the planarian worm it can make or break the ability of stem cells to regenerate heads and other parts of the body. Others have discovered differences in the location and function of developmental genes shared by fruit flies, beetles, crickets, and spiders—differences that likely played a role in the evolution of these invertebrates. RNAi “has really opened new avenues of investigation of genes whose functions we think we know and genes whose functions we don't know,” says Sánchez Alvarado.

For years Sánchez Alvarado has been painstakingly tracking down genes involved in planaria regeneration. These small worms can regrow a head in a matter of days and a whole body in not much longer. They depend on stem cells called neoblasts not only to build new body parts but also to maintain status quo in their tissues.

“Before the introduction of [RNAi], no functional assays were available to study the molecular biology of neoblasts,” he recalls. But already his group has used RNAi to study 1200 genes, and it's gotten intriguing results for about 240. “It seems like they are on the verge of understanding how neoblasts work,” says Richard Behringer, a genomicist at the University of Texas M. D. Anderson Cancer Center in Houston. He hopes the research on planaria can help elucidate human stem cells, those highly coveted cells that give rise to many different types of tissue.

A gene called piwi suggests that the planaria studies can do just that. Scientists already knew that stem cells use this same gene in other organisms—evidence that stem cells are evolutionarily quite old and so essential that their genes haven't changed much. The piwi gene is active in stems cells, and signs of its activity disappear when the stem cells are destroyed by radiation. Utah's Peter Reddien put RNA in the planaria's food. Although the stem cells continued to function, “regeneration failed once piwi was disabled,” he reported.

Other RNAi work presented last week is helping demonstrate the role developmental genes played in reshaping organisms as they evolved. Susan Brown, a geneticist at Kansas State University in Manhattan, has been examining the activity and function of genes that help define the segments of the Drosophila embryo. In this fruit fly, segmentation happens early in development, and all segments form at the same time. In other insect species, however, such as the red flour beetle, most segments form one at a time, each one helping elongate the embryo's body. At the meeting, she reported that one common segmentation gene called runt may help explain the different developmental pathways observed in these two insects.

In fruit flies, runt plays a role in early, simultaneous segmentation, as mutant embryos lacking that functional gene are half the normal size and are missing every other segment. When Brown gave beetles low concentrations of RNAi against runt, their embryos looked just like these mutant fly embryos. But when she upped the dose of RNAi, “we got unexpected results,” she reported. Very few segments formed, suggesting that because this beetle and the fruit fly diverged from a common ancestor, the function of this gene, and perhaps others, diverged along with developmental pathways. She's not sure how the difference in RNAi dosage works, however.

Some development genes seem to work the same in both fruit flies and evolutionarily divergent insects. Studies reported by Taro Mito of the University of Tokushima in Japan suggest that crickets use genes such as one called eve, which is involved in patterning the anterior part of the body, in much the same way as Drosophila does.

RNAi is not a panacea for functional studies, however. Sometimes the inserted RNA disrupts the function of genes other than its target, says UC Berkeley's Patel. Other times, it fails to turn off the target gene. Nonetheless, the use of this technique is sure to grow, says UC Berkeley's John Gerhart: “It's almost become a requirement if you are going to do evo-devo.”

16. SPACE SCIENCE

# Gravity Probe to Give Einstein a Pricey High-Precision Test

1. Charles Seife

NASA is about to launch a satellite to obtain a result that physicists have been expecting for almost 90 years

When ships, satellites, and spacecraft need a stationary point to steer by, they take aim at the stars. Gravity Probe B (GP-B) is no exception. In this case, though, it would be more appropriate for the satellite to guide the guide star.

The \$700 million satellite, scheduled for launch on 19 April, is about to make a measurement so precise that the infinitesimal drift of its guide star—a binary in the constellation Pegasus—would ruin the experiment. To orient the craft, astronomers on the ground will have to measure the star's motion and take it into account. Only then can GP-B perform its mission: to measure an as-yet-unseen consequence of Einstein's theory of general relativity. The incredible precision needed has made the satellite expensive and controversial.

“This test of general relativity is very simple in concept, but when you get down to the technical details, excessive perseverance was needed, to say the least,” says co-principal- investigator Brad Parkinson, an aerospace engineer at Stanford University in California.

GP-B is NASA's oldest experimental project; it was proposed in 1961 by Stanford scientists and received its first NASA funding 3 years later. Its roots go back to 1915, when Einstein combined space and time into a mathematical object that behaves like a rubber sheet. A massive object such as a star or a planet sitting on the sheet creates a dimple (Science, 24 May 2002, p. 1418). A spacecraft floating near that object would tend to fall into the dimple—attraction that we perceive as gravity.

Two consequences of that theory, the warping of space and the warping of time, have been measured with great precision. In 1976, for example, GP-A tested how a 2-hour suborbital rocket flight altered a sensitive atomic clock. But a third, more subtle effect has eluded physicists. “The spinning of the Earth or the sun or other massive body drags spacetime along with it, something we have never seen in any definitive way,” says Kip Thorne, a theorist at the California Institute of Technology in Pasadena. This so-called frame-dragging effect is the reason for GP-B.

GP-B is a very sensitive measurer of twist. Its heart is a concrete-mixer-sized Thermos bottle filled with liquid helium. Inside the Thermos are four incredibly smooth golf-ball-sized quartz spheres—the most nearly perfect spherical objects ever created by humans—each of which is set spinning around its axis 10,000 times a minute by carefully controlled squirts of helium. These spheres act as gyroscopes that, absent external influences, will always point in the same direction. “The gyros are 1 million times better than the best inertial navigation gyroscopes,” says Stanford physicist Francis Everitt, co-PI of the GP-B mission.

As the spinning Earth drags spacetime along with it, the satellite's gyroscopes—themselves embedded in spacetime—will twist a bit as well. By keeping a careful watch on the gyroscopes' orientation with respect to the (corrected) guide star, scientists can deduce whether this frame-dragging effect changes the direction in which the gyroscopes point. (Scientists will also have to correct for skewing due to the warping of spacetime by Earth. This “geodetic effect” is actually much greater than the twist due to frame dragging.) The expected change in angle is so tiny—41 thousandths of an arc second, roughly the breadth of a penny in Los Angeles as viewed by an observer in Washington, D.C.—that a small hiccup in the satellite or a flaw in the gyroscope would wipe out any hope of seeing the frame-dragging effect.

Such a finely tuned instrument is expensive, and GP-B's hefty price tag almost doomed it several times—especially because it is designed to verify a theory almost nobody doubts. Indeed, it had to fight for its survival up to the last minute; cost overruns and failed engineering tests made NASA officials consider scrapping the whole project (Science, 21 March 2003, p. 1827). And if the satellite fails, there's no plan to replace it.

But if GP-B does fail, physicists might be able to spot frame dragging in other ways. In the late 1990s, x-ray astronomers thought that they saw hints of the effect in the swirling clouds of infalling gas around massive spinning neutron stars and black holes. Each disk-shaped cloud acts something like a gyroscope; the frame-dragging effect would cause the disk to wobble around the black hole, creating fluctuations in the x-rays that stream from those disks. Frame dragging could explain the observed fluctuations, says Wei Cui, an astronomer at Purdue University in West Lafayette, Indiana—but so could other models that don't invoke it, and it's unlikely that x-ray astronomers will get a definitive answer anytime soon. “This is the difference between this line of work and what Gravity Probe B will measure,” he says. “That will be a direct measurement.”

Another possibility would be to add a third spacecraft to a pair of existing satellites known as LAGEOS. Scientists bounce lasers off these satellites to make precise measurements of the motion of tectonic plates. Frame dragging should shift the satellites' orbits, which themselves act like giant gyroscopes. So by measuring the orbits with great precision and accounting for variations in Earth's gravitational field, “you should see [frame dragging]—not at GP-B precision, but good enough,” says Thorne.

LAGEOS could come in handy as a reality check if GP-B's results don't match Einstein's theory—an outcome few expect. “If it's not agreeing with general relativity, there will be extreme excitement in the community,” says Thorne.

With luck, GP-B should yield a result in a little more than 18 months. Says Anne Kinney, director of NASA's astronomy and physics division, “My expectation is that it will be in all the textbooks.”