The Runners-Up

Science  19 Dec 2008:
Vol. 322, Issue 5909, pp. 1768
DOI: 10.1126/science.322.5909.1768

The first direct detections of exoplanets topped the list of this year's runners-up for Breakthrough of the Year. Other notable discoveries included cancer genes, new high-temperature superconductors, and a new water-splitting catalyst.

2 Seeing Exoplanets

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Seeing might be believing, but for scientists belief rarely depends on seeing. The right squiggles coming out of an instrument are usually enough to confirm that they have caught their quarry, however infinitesimal, insubstantial, or bizarre. Astronomers searching for planets circling other stars, however, may have been getting just a tad impatient with their progress toward their ultimate goal: recognizing a habitable, even an inhabited, planet beyond our own solar system. For that, they'll need to see their target. But all exoplanet detections had been of the squiggly variety.

Now, astronomers have seen exoplanets for the first time—a half-dozen candidates have been announced in the past few months. To some, the new observations may simply have replaced squiggles with dots. But the faint pinpricks of light from far-off worlds have captured the public's imagination and will give astronomers new clues to what those distant planets are made of and how they were formed. Key to these direct detections have been big telescopes and the latest technology to pick out a vanishingly faint planet from its host star's overwhelming glare.

Previous, indirect detections of more than 300 exoplanets had provided breakthroughs of their own. For 13 years, astronomers have been finding exoplanets using ground-based telescopes to monitor the subtle wobble a planet gravitationally induces in its star. This workhorse radial-velocity technique is especially useful for finding massive “hot Jupiters” searingly close to their star. No light is seen from the planet, however. Another method, called microlensing—in which a planet's gravity momentarily brightens a background star by bending its passing light—is particularly good for detecting planets more distant from their stars and in principle could spot lightweights with masses down to that of Earth. But microlensing is a one-off event; once the fleeting alignment with the star is over, no sign of the planet will ever be seen again.


If a planet happens to orbit across the face of its star as viewed from Earth, however, the repeated tiny dimming of the total light of the star plus the planet can reveal the presence of the planet. At the same time, starlight passing through the outer planetary atmosphere can reveal clues about composition. Already, water, methane, and—just last month—carbon dioxide have been detected in transiting exoplanets. Those compounds, plus molecular oxygen, are the key markers of an inhabited planet. But only hot Jupiters—unlikely abodes of life—are liable to transit their stars and be detected using current technology.

That leaves direct detection. The chore is simple enough: Separate the light from a planet from the light of its nearby star. The hitch is that the star is millions of times brighter than any planet, and Earth's turbulent atmosphere churns the light of star and planet together. To solve the latter problem, astronomers can move their telescopes above the atmosphere to Earth orbit. Or they can correct the incoming telescopic image using so-called adaptive optics, in which precisely controlled warping of a mirror many times a second straightens out distorted light. Coping with the vast difference in brightness between planet and star requires a coronagraph in the telescope to physically block out the star or “virtual coronagraph” software to remove starlight from the image. It also helps to search for very young and therefore still hot planets at infrared wavelengths, in which case the star-planet contrast will be much smaller.

With more than 5 years of observations using the latest technology, astronomers are suddenly busting down the doors to announce candidates for directly detected exoplanets. Published last month, the most secure—and surely the most stunning—are three objects orbiting a star called HR 8799, 128 light-years from Earth. Judged to have five to 10 times the mass of Jupiter, they orbit at least 24 to 68 times farther from their star than Earth orbits from the sun. That makes them among the most massive exoplanets discovered and by far the most distant from their star. New detection techniques typically start by finding such oddballs. These are giving theorists fits; they don't see how planets could have formed that far out.

Other direct detections came one per star. Last month, another group also reported detecting a planet of roughly three Jupiter masses orbiting the star Fomalhaut, one of the brightest stars in the sky. A third group announced a single candidate exoplanet last September but must await confirmation that it is orbiting the star rather than just passing through. And a fourth group announced late last month what would be—at eight times the sun-Earth distance from its star—the imaged planet closest to its star.

Astronomers are already starting to analyze the light of some of the new finds for clues to their physical and chemical nature. That should keep planetary formation theorists busy. The chance to directly study potentially inhabited planets is further off. Imaging Earth-like exoplanets in Earth-like orbits is probably still decades and certainly billions of dollars away.

See Web links on exoplanets

3 Cancer Genes

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Researchers this year turned a searchlight on the errant DNA that leads tumor cells to grow out of control. These studies are revealing the entire genetic landscape of specific human cancers, providing new avenues for diagnosis and treatment.

Tumor cells are typically riddled with genetic mistakes that disrupt key cell pathways, removing the brakes on cell division. Thanks to the completion of the human genome and cheaper sequencing, researchers can now systematically survey many genes in cancer cells for changes that earlier methods missed. Results from the first of these so-called cancer genome projects came out 2 years ago, and the output ramped up in 2008.

Leading the list were reports on pancreatic cancer and glioblastoma, the deadliest cancers. By sequencing hundreds or thousands of genes, researchers fingered dozens of mutations, both known and new. For example, a new cancer gene called IDH1 appeared in a sizable 12% of samples from glioma brain tumors. A separate glioma study revealed hints as to why some patients' tumors develop drug resistance. Other studies winnowed out abnormal DNA in lung adenocarcinoma tumors and acute myeloid leukemia.


The expanding catalog of cancer genes reveals an exciting but sobering complexity, suggesting that treatments that target biological pathways are a better bet than “silver bullet” drugs aimed at a single gene. Genome projects for at least 10 more cancers are in the works.

See Web links on cancer genes

4 New High-Temperature Superconductors

Physicists discovered a second family of high-temperature superconductors, materials that carry electricity without resistance at temperatures inexplicably far above absolute zero. The advance deepened the biggest mystery in condensed-matter physics.

In February, a group in Japan reported the first material, fluorine-doped lanthanum iron arsenic oxide (LaFeAsO(1-x)Fx), which is superconducting up to a “critical temperature” of 26 kelvin. Within 3 months, four groups in China had replaced the lanthanum with elements such as praseodymium and samarium and driven the temperature for resistance-free flow up to 55 kelvin. Others have since found compounds with different crystal structures and have bumped the critical temperature up to 56 kelvin.


For a critical temperature, that's not so hot. The record is 138 kelvin for members of the other family of high-temperature superconductors, the copper-and-oxygen, or “cuprate,” compounds discovered in 1986. Still, the iron-based materials have created a stir, in part because they might help solve the enduring mystery of how the cuprates work. The $64,000 question is whether the two families work the same way. So far, evidence points in both directions.

5 Watching Proteins at Work

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After studying proteins for more than a century, biochemists pushed the boundaries of watching the molecules in action—and received surprises at every turn.

Scientists have long debated how proteins bind to their targets. Most think the shape of a target molecule forces a protein to wiggle into a complementary profile. But it's also possible that proteins in solution wiggle among many slightly different conformations until one finds its target. Computational biologists in Germany and the United States offered bold new support for that upstart idea when they crunched extensive experimental data and showed how one long-studied protein seems to dance among dozens of conformations. In another surprise, a U.S. team tracked individual proteins and found that a single random molecular event can switch a bacterial cell from one metabolic state to another.


Zooming out to the large scale, proteomics researchers in Germany simultaneously monitored the abundance of up to 6000 proteins in yeast cells and quantified how the expression of individual proteins differed between two different cell types. Their technique could lead to new insights into development and disease. Finally, proteomics researchers in Sweden revealed that different tissues in the body likely get their unique characteristics by controlling not which proteins are expressed but how much of each gets made.

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6 Water to Burn

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Renewable energy sources, such as wind and solar power, have plenty going for them. They're abundant and carbon-free, and their prices are dropping. But they're part-timers. Even when the sun is shining and the wind is blowing, there is no good way to store excess electricity on an industrial scale. Researchers in the United States reported this year that they've developed a new catalyst that could begin to change that picture.

The catalyst, a mixture of cobalt and phosphorus, uses electricity to split water into hydrogen and oxygen. Hydrogen can then be burned or fed to fuel cells that recombine it with oxygen to produce electricity. Researchers have known for decades that precious metals such as platinum will split water. But platinum's rarity and high cost make it impractical for large-scale use. The cobalt version isn't all the way there yet, either—it still works too slowly for industrial use—but just getting a cheap and abundant metal to do the job is a key step. Now, if researchers can speed it up, on-again-off-again renewables could have a future as fuels that can be used anywhere at any time.

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7 The Video Embryo

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The dance of cells as a fertilized egg becomes an organism is at the center of developmental biology. But most microscopes allow only partial glimpses of the process. This year, scientists observed the ballet in unprecedented detail, recording and analyzing movies that traced the movements of the roughly 16,000 cells that make up the zebrafish embryo by the end of its first day of development.

Researchers in Germany made the movies with a new microscope they designed. It uses a laser beam to scan through a living specimen, capturing real-time images and avoiding the bleaching and light damage that have usually limited such videos to just a few hours. The researchers then used massive computing power to analyze and visualize the recorded movements. They also ran the movies backward to trace the origin of cells that form specific tissues, such as the retina. A movie of a well-known mutant strain of fish revealed for the first time exactly what goes wrong as the embryo develops.


The zebrafish movies are freely available on the Internet, and the developers say they hope the Web site will develop into a full-blown virtual embryo—a sort of developmental biology YouTube with contributions from labs around the world.

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8 Fat of a Different Color

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This year, researchers finally uncovered the mysterious roots of so-called brown fat. Hardly blubber, the energy-using tissue turns out to be one step away from muscle.

Anatomists first noted the distinction between our two fat types more than 400 years ago. White fat is the energy-caching padding that vexes doctors and dieters. If white fat is a quilt, brown fat is an electric blanket. Thanks to plentiful mitochondria, it burns fat molecules to generate heat that warms the body.


Scientists long assumed that both fat varieties developed from the same kind of progenitor cell. Then a team led by U.S. scientists discovered that they could morph brown fat into muscle and vice versa. The researchers knew that the gene PRDM16 spurs specialization of brown fat. So when they turned down PRDM16 in brown-fat precursor cells, they expected white fat cells to result.

Instead, the cells stretched out into tube-shaped muscle cells that could even twitch. Reflecting their altered identity, the cells switched off a raft of genes characteristic of brown fat and switched on genes typical of muscle. Coercing cells that had already begun differentiating into muscle to fashion PRDM16 triggered the reverse transformation, yielding brown fat. Using a technique called lineage tracing, the researchers identified the descendants of the muscle cell clan in mice. They included muscle and brown fat cells but not white fat cells.

The discoveries could mark a step toward antiobesity treatments that melt away bad white fat, either by firing up existing fat-burning brown cells in the body or by transplanting new ones.

See Web links on brown fat

9 Proton's Mass ‘Predicted’

Starting from a theoretical description of its innards, physicists precisely calculated the mass of the proton and other particles made of quarks and gluons. The numbers aren't new; experimenters have been able to weigh the proton for nearly a century. But the new results show that physicists can at last make accurate calculations of the ultracomplex strong force that binds quarks.

In simplest terms, the proton comprises three quarks with gluons zipping between them to convey the strong force. Thanks to the uncertainties of quantum mechanics, however, myriad gluons and quark-antiquark pairs flit into and out of existence within a proton in a frenzy that's nearly impossible to analyze but that produces 95% of the particle's mass.


To simplify matters, theorists from France, Germany, and Hungary took an approach known as “lattice quantum chromodynamics.” They modeled continuous space and time as a four-dimensional array of points—the lattice—and confined the quarks to the points and the gluons to the links between them. Using supercomputers, they reckoned the masses of the proton and other particles to a precision of about 2%—a tenth of the uncertainties a decade ago—as they reported in November.

In 2003, others reported equally precise calculations of more-esoteric quantities. But by calculating the familiar proton mass, the new work signals more broadly that physicists finally have a handle on the strong force.

10 Sequencing Bonanza

New genome-sequencing technologies that are much faster and cheaper than the approach used to decipher the first human genome are driving a boom in sequencing.


See Web links on gene sequencing

This year, using “sequencing by synthesis” technology from 454 Sequencing, which “grows” fluorescently labeled DNA on microscopic beads, researchers produced the mitochondrial genomes of extinct cave bears and of a Neandertal, and 70% of the genome of a woolly mammoth. A preliminary draft of the full Neandertal genome is in the works. Another new technology, developed by Solexa (now part of Illumina), made its debut in the scientific literature with the descriptions of the first genomes of an Asian, an African, and a cancer patient, shedding new light on early human migrations and candidate genes that may underlie malignancies. Illumina's technology sequences DNA in massively parallel reactions on glass plates. A proof-of-concept paper by Pacific Biosciences, a company that sequences single DNA molecules, provided an exciting glimpse of even faster sequencing. Now the goal is to make it more accurate.

Costs continue to drop; at least one company boasts that genomes for $5000 are in reach.

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