News this Week

Science  15 Aug 1997:
Vol. 277, Issue 5328, pp. 897
  1. NEUROSCIENCE

    Worm Longevity Gene Cloned

    1. Wade Roush

    A GENE THAT HELPS CONTROL THE LIFE-SPAN OF THE NEMATODE C. ELEGANS ENCODES THE WORM VERSION OF THE INSULIN RECEPTOR, THEREBY PROVIDING A POSSIBLE LINK BETWEEN AGING AND GLUCOSE METABOLISM

    While our canine companions age as much in 1 year as we do in 7, the clock runs even more rapidly for the lowly worm known as Caenorhabditis elegans. The tiny nematodes of this species age the equivalent of 5 human years for every day they spend grubbing in the dirt searching for tasty bacteria, usually dying when they are 14 days old. The worms do, however, have a way to put aging on hold—one that humans might envy: In times of stress, such as when overpopulation leads to overcrowding and food scarcity, they can store fat, stop eating, and enter the so-called “dauer” phase (from the German for durable), a state of suspended animation that can last for 2 months or more. In human terms, that's like having yourself cryogenically preserved until the year 2297. Now, a Boston-based research team has new results that help explain just how nematodes extend their lives—and suggest a tantalizing connection to aging in mammals.

    Parallel paths.

    Changing a proline (P) to a leucine (L) In the human insulin receptor leads to diabetes and obesity, while the same mutation in daf-2 leads to increased fat deposition in the worm.

    SOURCE: G. RUVKUN

    In this week's Science, geneticist Gary Ruvkun and his colleagues at Massachusetts General Hospital (MGH), Harvard Medical School in Boston report that they have cloned and sequenced a gene that, when damaged, can block or enhance the ability of C. elegans to make the switch to the dauer stage (see page 942). The gene, called daf-2 (for dauer-formation defect 2), is one of a bushel of genes harvested over the last decade that help the worm enter suspended animation. But daf-2's newly decoded gene sequence is particularly revealing. The protein it encodes appears to be the worm equivalent of the human insulin receptor, the molecule that “listens” for the hormone insulin, which is secreted in response to a rise in blood sugar, and passes its metabolism-enhancing signal to our cells' interiors. The similarity implies that the very system the worm uses to monitor and alter its metabolism has become part of the switch that shifts its metabolism into “suspend” mode, drastically lengthening its life when times are bad.

    Simply finding an analog to the human insulin receptor in C. elegans is a surprise, says Jim Thomas, a geneticist at the University of Washington in Seattle who also studies dauer initiation. He notes that scientists “weren't anticipating that the fundamental genetic circuitry that regulates glucose metabolism in mammals would be evolutionarily that ancient”—apparently dating to a time before nematodes and mammals diverged, perhaps some 700 million to 800 million years ago.

    But beyond providing yet another example of evolution's parsimonious ways, the finding raises a tantalizing possibility: that changes in glucose metabolism could be the key to slowing the aging process in higher organisms, including humans. If some of the same genetic circuitry triggered in the worms by the DAF-2 signal accounts for the life-span extension seen in rats and mice under conditions of caloric restriction, “that would be a phenomenal discovery,” says Don Riddle, a geneticist at the University of Missouri in Columbia, who studies dauer initiation. It might spur the design of drugs that could stretch human life-spans by tricking cells into entering a dauerlike stage, even when they aren't being starved.

    When Riddle decided to study the dauer initiation of C. elegans in 1974, researchers already knew that worms enter the dauer phase when they detect pheromones secreted by neighboring worms—a sign of excess population density and increased competition for food. Riddle wanted to find out how the biochemical alarms set off when chemosensory neurons in a worm's cuticle detect these pheromones lead to such specific tissue changes as increased fat deposition around the intestines and a thickened cuticle. In screens for mutant worms that either can't become dauers or enter the dauer stage inappropriately, Riddle, Thomas, Ruvkun, and other researchers turned up nearly three dozen genes, including daf-2. Their proteins seem to make up at least two parallel “signal transduction pathways,” biochemical bucket brigades that supply genes with information about conditions inside and outside the organism.

    In 1992, molecular geneticists Cynthia Kenyon of the University of California, San Francisco (UCSF), and Pamela Larson in Riddle's lab provided a clue to what daf-2's pathway does. They found that worms with minor mutations in the gene live two to three times as long as normal, but without becoming dauers. Those findings uncoupled life-span extensions from the other changes that occur in dauers, says Kenyon, suggesting that the daf-2 pathway can regulate longevity without input from the other pathway—the alarm system triggered by the pheromones.

    Last year, Ruvkun's group found more intriguing clues about the connection between daf genes and the longevity of C. elegans. The MGH team cloned another gene, daf-23, and found that it encodes a so-called PI3 kinase. This familiar type of membrane-bound protein transmits signals from receptors into the cell by activating so-called “second messenger” molecules, which pass on signals that ultimately reach the nucleus and alter gene activity. PI3 kinases are among the many molecules in mammalian cells known to be altered when insulin binds to its receptor, suggesting that daf-23's arm of the dauer pathway regulates metabolism.

    The team knew that daf-23 mutations have effects much like those in daf-2, so Ruvkun and lab members Koutarou Kimura, Heidi Tissenbaum, and Yanxia Liu reasoned that the proteins encoded by the two genes might be partners in the same arm of the dauer pathway. But when they set out to clone daf-2, bad luck slowed their hunt: The gene lay in the 10% of worms' DNA that has not been sequenced by the C. elegans genome project. But their persistence in tracking daf-2 paid off. A comparison of the finished gene sequence with the databases showed that the DAF-2 protein shares 35% of its amino acid sequence with the human insulin receptor and 34% with the insulin-like growth factor-1 receptor—enough to indicate that the three share a common evolutionary origin, and, presumably, similar functions. Moreover, the researchers found that DAF-2 regulates metabolism as its mammalian cousin, the insulin receptor, does.

    Putting their findings together into a single scenario for the daf-2/daf-23 pathway, Ruvkun's group proposes that during times of plenty, C. elegans maintains high levels of an insulin-like hormone, which binds to DAF-2. This, in turn, may trigger DAF-23 to activate the second messenger, passing an “okay to burn fuel” signal to the cell interior. But when the worms grow so numerous that they threaten to overtax their food supply, two things happen: Increased pheromone concentrations trip individual worms' chemosensory alarms, and internal insulin levels decrease, a sign of plummeting glucose availability. The two signals together push the worms into the dauer stage.

    Mice fed meager diets may go through parallel physiological calculations, suggests S. Michal Jazwinski, a geneticist studying aging at Louisiana State University Medical Center in New Orleans. The caloric restriction pushes the mice into a high-efficiency state, in which normal 2-year life-spans increase by up to 40%. “They metabolize as much glucose on a per-gram basis as other animals, but they can utilize that glucose more efficiently,” Jazwinski explains. As a result, they show fewer of the changes, such as oxidative tissue damage, thought to lead to aging. If human cells could be fooled into making a dauerlike transition to efficient energy use, Jazwinski speculates, it might eventually be possible to soften the ravages of aging.

    The existence of a food-sensitive, longevity-inducing mechanism in species as distantly related as nematodes and rodents suggests that nature has long been experimenting with such inhibitors of aging. “You could imagine that in a primitive metazoan, a way evolved for the animal to make it through bad times, and that core regulatory ability still exists in different organisms but is expressed in different ways,” says UCSF's Kenyon.

    Ruvkun speculates that the high incidence of diabetes among humans may be an indirect legacy of this adaptation. Like the defects seen in the long-lived daf-2 worms, minor variations in the genes encoding insulin, its receptor, or other components of its signaling pathways might be advantageous during times of famine, thus gaining a selective advantage. Such variations, however, also underlie some forms of diabetes.

    Indeed, even if the long-lived worms don't show the way to vastly extending the human life-span, they offer researchers a new model system in which to study insulin signaling. That, Riddle, Ruvkun, and other researchers point out, may improve biologists' chances of designing treatments for diabetes, the seventh leading cause of death in the United States. “Not everything we find will be directly applicable,” says Jazwinski, “but now that we're generating findings more and more quickly, the odds are in our favor.”

  2. TECHNOLOGY

    Quantum Cells Make a Bid To Outshrink Transistors

    1. James Glanz

    Electrical engineers are heading straight for a bruising encounter with the laws of physics as they continue to shrink transistors. Even the most gung-ho circuit builders know that heat overload and quantum effects, such as the elusive behavior of electrons on very small scales, will eventually stop them from packing more and more transistors onto a single computer chip. But 6 years ago, a pair of electrical engineers, Craig Lent and Wolfgang Porod at the University of Notre Dame in Indiana proposed a scheme for dodging those limits—even exploiting them.

    Domino theory.

    The interactions between many quantum-dot cells, each with four dots, create this adder, designed by Craig Lent and P. Douglas Tougaw

    SOURCE: C. LENT AND P. D. TOUGAW

    They realized that when transistor sizes bottom out, the quantum fuzziness of very small scales might actually be the key to shrinking electronics still further. They proposed that dominolike arrays of “quantum dots,” in which electrons would quantum-mechanically “tunnel” from dot to dot, might one day outshrink transistors. The notion met with incredulity in the electrical engineering world, where more conventional schemes relying on quantum dots have yet to demonstrate their practicality (Science, 17 January, p. 303). A paper on page 928 of this issue shows, however, that Lent and Porod's quantum-dot dominoes—called quantum-dot cellular automata (QCA)—really do work, at least one at a time.

    Tunnel vision.

    Electrons tunnel between aluminum islands (indicated by red circles) microns apart in a quantum-dot cell.

    A. ORLOV, ET AL.

    The paper, by Alexei Orlov and several colleagues at Notre Dame—including Lent—describes the first functioning model of a single, four-dot QCA cell. “We showed that this little thing goes click clack,” says Lent. Spanning 8 microns, several times the size of today's smallest transistors, and working only when cooled all the way to 15 millikelvin to keep thermal noise from rattling electrons out of their dots, the cell “is just the first baby step” for the technology, says co-author Gary Bernstein.

    Some researchers are hanging on to their earlier skepticism, saying that the QCA approach is conceptually flawed and won't work when it is extended to an entire system of cells. But the group's working QCA has impressed others. “This is a key demonstration that the concept could work,” says Pierre Petroff, a materials scientist at the University of California, Santa Barbara (UCSB). The remaining hurdles—though daunting—are largely technical, says Terry Fountain, in the department of physics and astronomy at University College London. “The Lent-Porod approach does constitute a new and promising possibility to shrink computer architectures,” Fountain says, which could, in principle, reduce circuit areas by factors of as much as 50,000 compared to the smallest feasible transistors.

    Existing chips are etched with thousands or millions of transistors, in which electrical currents are switched on and off with electric fields—or, equivalently, voltage biases—in semiconducting materials based on silicon. Conduction channels, or “wires,” link the transistors and other components of a chip to create the physical basis of binary logic—the electronic 1s and 0s that are further manipulated in computations. But within the next decade or two, as the size of the smallest circuit features drops from today's 1/3 of a micron to less than 1/10 of a micron, the physical limits facing conventional electronics will assert themselves.

    For one thing, the proliferating interconnections will start to wipe out the gains due to smaller sizes. For another, the heat generated by electrical resistance will be harder to dissipate. And finally there is the wavelike, quantum-mechanical nature of particles on tiny scales, a fuzziness that lets electrons tunnel and escape through the walls set up to channel them—the narrower the walls, the easier the tunneling.

    In principle, at least, QCA cells do away with all of these problems. Each cell consists of a square arrangement of four quantum dots—minute islands of a material that has a higher affinity for electrons than the surrounding material. Two electrons inhabit each cell. Their mutual repulsion forces them into opposite corners, like boxers between rounds; the two possible configurations stand for binary 0 and 1. The electrons rely on tunneling to move from dot to dot, which they do under the influence of adjacent cells. Like neurons in the retina of the eye, they process information by interacting with their neighbors rather than by sending impulses to some central location, which is why they are called cellular automata.

    When a cell at the end of a row is forced into state 1, for example, the next cell will flip into the same state, since that ensures the maximum distance between electrons in the two cells. The rest of the cells will quickly fall into line, passing the 1 down the “wire.” Such wires could be intertwined to perform more complicated operations in which one state can be contingent on several others (see diagram).

    Since each signal passes down the line without any current, little heat is generated, and because each cell passes information directly only to nearby cells, which can then send the results to the next cluster for further processing, the interconnection problem is eased. And the smaller the dots are made, the better they confine electrons, keeping thermal fluctuations from dislodging them; indeed, extremely small cells could operate at room temperature. “Things only get better as you shrink them down,” says Lent. “It could go down to molecular levels.”

    But would this theorist's dream fall to pieces in a real experiment? Some critics had predicted that the electrons would leak away through interactions with defects and free charges in the surrounding material, rather than remain stably confined. Others had questioned whether the dots could be made accurately enough for the tunneling to work as designed.

    To test the scheme, the Notre Dame group used a tightly focused electron beam to lay out a single QCA—an array of four aluminum dots on a silicon dioxide surface. They put the device through its paces by using voltage biases to force electrons either up or down on one side of the cell (call it the right side) and checking whether the electrons on the left side responded. They found that electrons did move to the opposite corner on the left side, remaining there for periods of minutes. “We can sit there and watch it,” says co-author Greg Snider, “and, no, [the charge] doesn't leak off.”

    In a complicated set of measurements in which one pair of dots actually probed the other, Snider and co-workers also determined the electrical potential—an indicator of how charges are distributed—on the left pair as the switching took place. The fluctuations in the potential compared favorably with theory, suggesting that electrons really were tunneling between dots and were not, say, being drawn randomly from defects in the crystal lattice. “I think it is a very important breakthrough,” says Tamás Roska, a professor at the Computer and Automation Institute in Budapest. “These are not easy experiments,” adds UCSB's Petroff. “But I have no doubt [that the switching was observed].”

    He notes, however, that QCA's longer term prospects remain controversial because of questions about how well large systems of the dots will function—even if they can be accurately fabricated in much smaller sizes, which would require new techniques. Rolf Landauer of IBM's T. J. Watson Research Center has persistently questioned whether “exactly two” electrons will stay confined in each cell—crucial for such a device to work properly—and whether slight defects in the system will play havoc with its computations. A more vociferous critic, Supriyo Bandyopadhyay of the electrical engineering department at the University of Nebraska, Lincoln, says “fundamental flaws” in the scheme will prevent the arrays from working even if they are built perfectly. For example, the system may get permanently stuck at a wrong answer on its way to the right one, he and his collaborators say, as the electron states reach an impasse akin to traffic gridlock on downtown streets.

    Lent says the group has addressed some of these doubts and is studying others. His detailed calculations show, for instance, that running an array at slightly slower than its maximum speed—so-called “adiabatic switching,” an approach suggested by Landauer—gets around the wrong-answer problem, just as conservative drivers have a slower commute, but cause fewer traffic snarls than heavier-footed motorists. Still, he says, “One is rightfully concerned about overselling a technology.” Whether the click clack of his group's dots will turn out to be first footsteps leading computer science into the realm of the very small remains to be seen.

  3. PHYSICS

    Microwaves Steal the Blush From Ruby

    1. Charles Seife
    1. Charles Seife is a writer in Riverdale, New York.

    Rubies are red, and they usually stay that way. But in the 28 July Physical Review Letters, researchers at Wayne State University in Detroit report that they have made rubies a little less red and more transparent with nothing more than a magnet and a bath of microwaves.

    A lock on absorption.

    Electrons that normally absorb light by jumping to a higher energy level (left) are stymied when microwaves couple two lower levels.

    LIZ CARROLL

    The feat, called electromagnetically induced transparency, had already been demonstrated in gases. But “this is the first work in solid-state materials,” says electrical engineer Yang Zhao, one of the researchers. He and others say it might eventually lead to more efficient lasers and to optical switches for computers.

    Color, in rubies and most other materials, arises because electrons in the material absorb specific wavelengths of light. The absorption takes place when a photon of light with the right energy kicks an electron from a low-energy level into a higher one. To clear a path through an absorbing material, electrons must be prevented from jumping up to the higher energy level—not an easy task.

    Researchers working with gases had already demonstrated a way to shackle these jumping electrons: Use electromagnetic fields to link the lower energy level—the electrons' jumping-off point—with another level at a similar energy. To apply this strategy to rubies, Zhao and his colleagues cooled the material to 2.4 degrees above absolute zero to “sharpen” the energy levels. Then they placed it in a magnetic field, which split each of the energy levels into two closely spaced levels through what is known as the Zeeman effect. Each pair of levels corresponds to a particular direction of electron spin—up or down.

    Once Zhao and his colleagues had split the energy levels, they applied a microwave field that had just the right energy to “couple” two of the lower energy levels by flipping the electrons' spins back and forth, forcing them to jump between the levels. By providing two competing paths for electrons to jump from a lower to a higher level, the coupling stymied the transition. “When you have light taking two paths and hitting a screen, at certain parts of the screen, the light cancels out,” explains Scott Shepard, a physicist at Texas A&M University in College Station. “This is a very similar canceling out; the wave functions cancel.” Because the electrons can't jump into the high-energy band, the ruby fails to absorb the wavelengths of light that would normally do the kicking.

    The team was able to reduce absorption by about 20%. Other researchers have gotten much better results in gases. But “work in atomic vapors mainly demonstrates the principle,” Zhao says: “Work in solid state may lead to real devices.” Atac Imamoglu, a physicist at University of California, Santa Barbara, agrees. Even though the work is at a very early stage, he thinks that “several avenues [of possible application] are interesting.” The ability to vary the transparency of an optical medium, he says, might be useful for storing bits in a quantum computer or creating switches for an optical computer. By cutting down on the amount of light absorbed in a laser's light-generating medium, he says, it could also lead to lower powered lasers.

  4. NEUROBIOLOGY

    Schizophrenia Clues From Monkeys

    1. Elizabeth Pennisi

    For decades researchers have tried, without much success, to stitch the patchwork of schizophrenia symptoms into a single picture. One in every hundred people suffers from this brain disorder, with manifestations that range from delusions and hallucinations, to lack of behavioral inhibition and cognitive problems—such as inability to make even simple decisions. Now, researchers from Yale University School of Medicine in New Haven, Connecticut, have taken a step toward understanding some of the brain changes involved in this disease.

    Monkey do.

    PCP-treated monkeys can't figure out how to retrieve a treat from this cube.

    JANE TAYLOR/YALE UNIV.

    On page 953, pharmacologist Robert Roth and his colleagues report that they can create cognitive problems in vervet monkeys by treating the animals with phencyclidine (PCP), a drug of abuse better known as “angel dust.” Other researchers have studied how the drug affects behavior in animals, but they have not, for the most part, tested the animals on complex tasks such as those impaired in schizophrenia. What's more, the Roth team's results suggest that the more severe the cognitive deficits, the bigger the changes in dopamine—a neurotransmitter already known to be involved in schizophrenia—in the prefrontal cortex of the monkeys' brains. And they found the monkeys' problems can be partially reversed by a drug used to treat the condition in humans.

    “I'm quite impressed,” comments psychopharmacologist Klaus Miczek from Tufts University in Boston. “The combination of a complex behavioral test and the neurochemistry is very nice.” Indeed, comments John Hsiao, a psychiatrist at the National Institute of Mental Health in Rockville, Maryland, “depending on how good a model [the PCP-treated monkey] is, this could be a tremendous advance.” Studies of these monkeys may help clarify why cognitive problems arise in schizophrenia patients and could also help researchers evaluate therapies for improving cognitive function.

    The Yale group decided to try PCP on the monkeys, because they knew the drug causes schizophrenic symptoms in people, particularly when used repeatedly. For the experiments, J. David Jentsch, a graduate student in Roth's lab, administered PCP twice daily to 15 monkeys for 2 weeks. A week later, he evaluated six of the animals—and an equal number of controls—with a behavioral test, in which each monkey was presented with a transparent cube that contained a slice of banana and was open on one side.

    Instinctively, both PCP-treated and untreated monkeys grabbed for the banana by reaching straight for it. They all succeeded as long as the cube opening faced them. When the cube was rotated, untreated monkeys quickly figured out that they needed to reach in from the side. But the PCP-treated monkeys, like animals whose prefrontal cortex is damaged, kept grabbing for the banana from the front, even though their hands kept banging into the cube wall. People with schizophrenia show a similar lack of behavioral inhibition. “They can't stop themselves, even though they know it is wrong,” says Jentsch.

    To look for chemical changes that might underlie this behavior, the Yale team sacrificed the other nine PCP-treated animals, as well as four controls. Then, to get an indication of dopamine usage, they measured the amounts of both dopamine and one of its breakdown products in various regions of the prefrontal cortex. The PCP treatment proved to be “very selective” in its effects, Roth notes, reducing dopamine usage in only two sections. One was the dorsal-lateral prefrontal cortex, which is responsible for working memory—essential if the monkey is to remember that it had already tried to grab the banana from the front. The other section was the prelimbic cortex, a section of the brain thought to control behavioral inhibition. “There's a direct and significant relationship in the degree of inhibition of dopamine [usage] and the degree of cognitive impairment,” says Jentsch.

    In a final test of the PCP monkey as a model for schizophrenia's cognitive symptoms, the Yale team evaluated the effects of clozapine, a drug used to treat the condition, on the surviving PCP monkeys. The drug improved their ability to figure out how to get the banana out of the cube, they report. This result highlights the power of using the PCP-treated monkey to study these deficits, says Roth. “There are other animal models of prefrontal cortical dysfunction, but they are not pharmacologically reversible,” he points out.

    The new work also fits with the growing view that dopamine's role in schizophrenia is more complicated than originally thought. Because many antipsychotic drugs block dopamine receptors, decreasing dopamine function, researchers once thought the symptoms were caused by an excess of this important nervous-system chemical. But this and other recent work suggest that while dopamine concentrations increase in some brain areas in schizophrenia, they decline in others—a result similar to what happened in the prefrontal cortex of the PCP-treated monkeys. “You can have both high and low dopamine at the same time,” says Jentsch.

    The Yale group hopes that continued work with the PCP-treated monkeys will lead to a better understanding of how dopamine is affected in the animals. And from those findings, says Jentsch, “we may be able to extrapolate what's going on in schizophrenia.”

  5. CONSERVATION

    Droppings Give the Lowdown On Stress in the Spotted Owl

    1. David A. Malakoff
    1. David A. Malakoff is a writer in Bar Harbor, Maine.

    Sitting in the woods and waiting for an owl to poop might seem like an unrewarding research assignment. But such field work has enabled researchers to show, for the first time, that disturbing a wild bird's habitat by logging can measurably increase the animal's stress. This preliminary finding—fiercely challenged by at least one biologist—has raised new doubts about the adequacy of governmental efforts to protect the northern spotted owl, a threatened species that lives in old-growth forests in the northwestern United States.

    The work, reported in this month's issue of Conservation Biology by animal physiologist Samuel Wasser of the University of Washington, Seattle, and wildlife biologists Kenneth Bevis, Gina King, and Eric Hanson of the state's Yakama Indian Nation, demonstrates a potentially valuable new technique for monitoring stress in beleaguered wildlife. While biologists can monitor an animal's stress by measuring stress hormones in blood, capturing a wild creature and drawing its blood can itself trigger a powerful stress response, biasing a study's results. “The question is how does one measure stress in a wild animal without inducing it,” says Steven Monfort, a researcher with the National Zoological Park's Conservation and Research Center in Front Royal, Virginia.

    Wasser and his colleagues had a solution: Scoop up the owl's feces, which also contain stress hormones. Like a time capsule, the fecal sample holds hormonal evidence of a bird's stress before a researcher's arrival might have triggered a reaction. Wasser and others pioneered the fecal-sampling technique in the mid-1980s to monitor stress and reproductive hormones in wild animals such as baboons, but it has never been used with an endangered bird. The technique “offers a very promising way to measure the physiological effects of habitat disturbance,” says Rocky Gutierrez, a biologist at Humboldt State University in Arcata, California.

    Gutierrez and other biologists believe that high stress levels in a wild animal can signal trouble. Stress hormones—released in response to disturbances such as loud noises or threats from predators—often cause dramatic physiological changes, such as a faster heart beat, which can help an animal survive a crisis. But repeated triggering of the stress response can be harmful, at least in the laboratory. Experimental animals pushed into a state of chronic stress produce fewer young, are less resistant to disease, and die prematurely.

    In recent years, some biologists have wondered whether such chronic stress is contributing to the decline of some endangered species, such as the spotted owl. Researchers estimate that owl populations are shrinking by 4% per year, despite federal efforts to protect the bird's habitat, including regulations that limit logging in 28-hectare circles around active nests.

    To test this theory, Wasser and his colleagues measured levels of the stress hormone corticosterone in fecal samples collected from 16 pairs of spotted owls nesting on the Yakama Indian Reservation in Washington and from about 150 other owls scattered across the Pacific Northwest. They found that male owls living within 0.41 kilometers of a major logging road or a patch of forest that had been clear-cut within the last 10 years had corticosterone levels almost two times higher than those of owls living more than 3 kilometers away. They also found that males living near clear-cut areas had significantly higher corticosterone levels than those of owls living near areas that had been selectively logged with methods that leave some trees standing. While female owls did not exhibit the same stress pattern, the researchers did find that hormone levels in all females, even those not nesting, rose during the 45-day period in which young owls get ready to leave the nest.

    Wasser says the results—which he emphasizes are preliminary—raise some questions about the efficacy of federal regulations designed to protect the owl. “The fecal-hormone measure allows you to get a handle on three very important questions,” he says. “First, are we protecting a big enough area around owl nests? If the data hold up, that suggests the circles are too small. Second, does the logging technique make a difference to the owl? The answer appears to be yes. Third, when should you restrict timber harvest during the reproductive season? It appears to be that 45-day period when the young are popping their heads out the nest.” Currently, Wasser notes, logging near nests is often restricted for a longer period.

    Wasser believes the technique could help biologists monitor how owls and other endangered species are faring under the federal government's Habitat Conservation Plans (HCPs). The 50- to 100-year-long agreements set aside prime habitat for a region's endangered species, while opening other areas to logging and other types of development. By monitoring fecal hormones, Wasser believes land managers could gain an “early warning” that a conservation plan needs tinkering. He notes, however, that a controversial new federal policy of “no surprises” (Science, 13 June, p. 1636), which bars the government from making major changes to an HCP once it's been hammered out, could limit the usefulness of such monitoring.

    One prominent spotted owl biologist fiercely challenges the new study. “It is an interesting idea, but I don't trust the results,” says Eric Forsman of the U.S. Forest Service's Forest Science Laboratory in Corvallis, Oregon. He says the study's sample size is too small for the researchers to conclude that factors other than logging or roads (such as prey availability) aren't responsible for the measured stress differences. More important, he says, so far “there is no evidence that this stress translates into a significant effect on reproduction or survival.”

    Wasser, however, believes that future owl studies will confirm the link between chronic stress and impaired reproduction seen in laboratory studies. And one senior federal wildlife manager dismisses the criticism. “You always have dueling biologists,” says David Frederick, Washington state supervisor for the U.S. Fish and Wildlife Service in Olympia, which helped fund Wasser's study. “There are extraordinarily few data out there on disturbance, and now we have a tool that will help us address that issue.”

  6. PHYSICS

    Curve Throws X-rays for a Loop

    1. Charles Seife
    1. Charles Seife is a science writer in Riverdale, New York.

    High-energy x-rays are a great way to probe matter, but it's hard to control a beam of them, since they shoot straight through ordinary lenses without bending. Now, researchers have developed the most efficient way yet to bend a powerful x-ray beam. Inspired by the famous “whispering gallery” just under the dome of St. Paul's Cathedral in London, Jene Golovchenko and Chien Liu of Harvard University drastically bent a beam of short-wavelength, high-energy x-rays by making it follow a curving wall of polished silicon. Other physicists say the device, described in the 5 August issue of Physical Review Letters, might someday become a crucial component of an x-ray laser.

    Kissing the wall.

    An 18-millimeter-long silicon barrier deflects high-energy x-rays.

    SOURCE: C. LIU, J.A. GOLOVCHENKO/PRL

    Scientists already have ways of manhandling an x-ray beam: bouncing it off a “grazing incidence” mirror at a very shallow angle, like skipping a stone on water, or channeling it through thin layers of artificial crystals. But these techniques only deflect the beam by a few degrees. The Harvard researchers have had better luck by imitating the acoustics of St. Paul's, where a beam of sound waves—a whisper, for instance—travels around the circular gallery by bouncing repeatedly along the curved walls, so that it is clearly audible to someone listening close to the wall at the far side of the dome.

    The same principle can work for radiation. Earlier this year, a group led by A.V. Vinogradov at the Lebedev Physics Institute in Russia reported constructing a whispering gallery that bends lower energy x-rays, with wavelengths of about 70 angstroms. But higher energy x-rays take even more finesse to control, because they are more likely to penetrate a surface instead of skip off it.

    To make their high-energy whispering gallery, Golovchenko and Liu polished an 18-millimeter-long silicon wafer, which they bent into an arc. When they fired a beam of 0.7 angstrom x-rays at a shallow angle toward one end of the arc, the photons grazed the wafer's surface. Almost all were reflected and then hit the wafer again, farther down the curve. The process was repeated down the length of the wafer, with the beam bouncing nearly 100 times against the wall. At the end of the line, the rays had been deflected by 13 degrees.

    “This is the shortest wavelength example of a whispering gallery by far,” says Malcolm Howells, a physicist at California's Lawrence Berkeley National Laboratory. It will take some work to translate the proof-of-principle into a useful piece of equipment, however. “At the moment, it's more a lab curiosity than anything else,” says Donald Bilderback, a physicist at Cornell University. “But, as with all new ideas, until you wrestle with it, you don't know what will come from it.”

    Howells, for example, envisions building a racetrack-shaped whispering gallery to trap x-rays in a future x-ray laser. “You could return the x-rays and feed some back into the laser,” he says. “Nobody's actually done that, but I foresee the possibility of a laser resonator.”

  7. GENOMICS

    Drug Firms Back Move to Link Databases

    1. Nigel Williams

    Because the world's major biological databases are constructed differently, it is virtually impossible to devise search programs to tap into them all effectively. A user has to hop from one to the other using each database's search engine to retrieve information that comes in a variety of different formats. That may soon change, however. A group of leading pharmaceutical companies last week put their considerable weight behind the development of common standards for the interface between biological databases, based on an approach popular in the computer industry. But bioinformatics specialists who run some key databases used by academic researchers say they are not enamored of the interface standards chosen, although they may now be forced to adopt them.

    The strategy was agreed to at a meeting in Philadelphia, attended by representatives of pharmaceutical giants such as Smith Kline Beecham, Glaxo Wellcome, and Zeneca, together with a number of software companies and representatives of databases, including the European Bioinformatics Institute (EBI) in Cambridge, U.K., and the Genome Data Base at Johns Hopkins University. The participants unanimously agreed on a fast-track plan to bring life sciences databases under standards drawn up by the world's largest software consortium, the Object Management Group (OMG). “The pharmaceutical industry is fed up by the lack of standards between biological databases,” says the EBI's head of services, Graham Cameron.

    The OMG was set up 8 years ago to tackle the problem of incompatible databases. The OMG's approach, dubbed the Common Object Request Broker Architecture (CORBA), does not impose an external set of rules for the contents of databases to which everyone must adhere. Instead, CORBA defines interfaces that allow different databases to communicate with each other no matter what their format. Software companies then use these interfaces to devise programs that allow researchers to access data in otherwise incompatible locations. “The idea behind CORBA is that database managers will never entirely agree on common formats for data entry in databases,” says Eric Neumann of the biological software company NetGenics.

    The EBI has already championed the CORBA approach, winning funds from the European Union to study its application to biological databases in collaboration with other European partners. The Philadelphia meeting, chaired by Cameron, agreed to work toward getting the OMG to establish a life sciences “task force” by the end of the year to hammer out the details of applying CORBA to life sciences databases. Seven task forces in various business areas already exist.

    Cameron is concerned, however, that biologists may not back a move to CORBA in the belief that other standards may ultimately be more useful for life scientists. “The plan is by no means a done deal,” he says. Researchers at the National Center for Biotechnology Information (NCBI) in Bethesda, Maryland, for example, are not convinced that CORBA will provide the best solution for biologists. “CORBA is one among many technologies,” says head of applications development, Jim Ostell. “There's no real reason why a number of other standards couldn't be applied, but given the critical mass of interest in CORBA it's a reasonable choice,” he adds. NCBI will be looking at CORBA alongside other potential technologies for linking databases.

    Supporters of CORBA will ultimately have to convince skeptics to use the standards, but they are optimistic. “The best outcome would be standards to which software developers and database managers adhere. It could do us all a great deal of good,” says Cameron.

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