# News this Week

Science  21 Dec 2012:
Vol. 338, Issue 6114, pp. 1516
1. # Around the World

1 - Karachi and Peshawar, Pakistan
Six Polio Campaign Workers Killed
2 - Singapore, Hong Kong, Taiwan, and South Korea
East Asian Students Still Excel in Math, Science
3 - Austin
More Changes at Texas Cancer Agency
4 - Bremen, Germany
German Court OKs Macaque Research

## Karachi and Peshawar, Pakistan

### Six Polio Campaign Workers Killed

Six vaccination campaign workers were killed and others injured in attacks in Pakistan on 17 and 18 December, prompting the country's health officials to suspend the country's 3-day mass vaccination campaign in greater Karachi. Vaccinations are going ahead in Peshawar, a city in the northwestern part of the country. Three apparently coordinated attacks in poor Karachi neighborhoods claimed five victims. One volunteer was killed in Peshawar. Taliban insurgents have repeatedly threatened campaign workers, but when Science went to press, no one had claimed responsibility for the attacks.

Pakistan is one of the world's three remaining polio hotspots (Science, 3 August, p. 517). The killings occurred as the country is making significant progress against the disease; there have been only 56 cases so far this year, down from 173 this time in 2011. The worst reaction to these “horrible, awful” events would be to let this opportunity be squandered, says Bruce Aylward of the World Health Organization, who leads the global effort to eradicate polio.

## Singapore, Hong Kong, Taiwan, and South Korea

### East Asian Students Still Excel in Math, Science

The latest results from the Trends in International Mathematics and Science Study (TIMSS) released last week show that fourth- and eighth-grade students from Singapore, Hong Kong, Taiwan, and South Korea have retained—and in some cases widened—their lead over the rest of the 63 countries that took the tests in 2011. “Revolutionary results require revolutionary changes,” says Michael Martin, co-director of the International Study Center at Boston College that administers the quadrennial TIMSS as well as PIRLS, a similar test of reading and literacy skills. Those changes are more likely to occur, he says, in countries that have a centralized education system and can move quickly to embrace the latest thinking on how to improve schooling.

U.S. students placed 11th in fourth-grade math, ninth in eighth-grade math, seventh in fourth-grade science, and 10th in eighth-grade science. Fourth-graders showed significant gains in math, whereas U.S. scores in the other three categories remained flat. http://scim.ag/TIMSS2011

## Austin

William Gimson, the executive director of the troubled $3 billion Cancer Prevention and Research Institute of Texas (CPRIT), stepped down last week. The agency also announced a new chief scientific officer to replace Alfred Gilman, the Nobel laureate who quit in protest over the agency's peer review procedures. Gimson explained in a letter to CPRIT's board that after 8 months of controversy, he has “been placed in a situation where I feel I can [no] longer be effective.” His resignation follows the departure of CPRIT Chief Commercialization Officer Jerald Cobbs in November. Last week, the Travis County district attorney launched a criminal investigation into CPRIT's funding of several commercialization awards. CPRIT's new chief scientist is Margaret Kripke, a cancer immunologist and former executive vice president at the University of Texas MD Anderson Cancer Center in Houston. She told reporters that her first task will be to rebuild CPRIT's “really terrific” peer review system, which lost many reviewers when Gilman left in October. http://scim.ag/CPRITchanges ## Bremen, Germany ### German Court OKs Macaque Research A long-running legal fight over animal research in Germany ended last week when a court ruled that University of Bremen neuroscientist Andreas Kreiter could continue his research on macaques. In 2008, Bremen authorities refused to renew Kreiter's license for animal research, claiming that the knowledge gained from the experiments did not justify the suffering endured by the macaques, which have electrodes implanted into their brains. Kreiter and the university sued, and in 2009 a court ruled in their favor. The city-state of Bremen appealed—but the latest ruling, made on 11 December, found that the authorities were not justified in denying Kreiter his license, and ruled out further appeals. Research organizations welcomed the ruling as a fundamental decision in favor of the “freedom of research” clause in German law. (Kreiter had been allowed to continue his research during the court battle.) Activists opposed to the research have vowed to continue their fight through political means. 2. # Newsmakers ## Three Q's What is time and how would you explain it to an 11-year-old? That's the second Flame Challenge that actor Alan Alda and the Center for Communicating Science at Stony Brook University in New York have posed to scientists. Answers are due 1 March and will be judged by thousands of children. (Read the full interview at http://scim.ag/AldaFlame.) Q:Does the Flame Challenge reflect the center's mission? Yes. Can I explain something to an 11-year-old with the 11-year-old judging how well I do? That's fun for everybody. But the scientist is really being challenged to see if he or she can remember what it's like not to know what they now know so intimately. To break it all down and yet not take forever getting through it, that's a real challenge. Q:Isn't this year's question particularly difficult? It sure is! The first question—what is a flame?—came from me and my memories of when I was an 11-year-old. But this year's question comes from current 11-year-olds. And they're asking a much deeper question. Q:So the judgment is done by vote? The top vote wins. The children are very careful about dismissing the answers that they think are too short and not informative enough. They don't mind it if a scientist speaks colloquially. But they don't want the answers to be silly. Last year, one kid said, “We're 11, we're not 7!” ## Lubchenco to Leave NOAA Marine scientist Jane Lubchenco, the head of the U.S. National Oceanic and Atmospheric Administration (NOAA), announced on 12 December that she will leave the job at the end of February. She plans to “return to my family and academia” in Oregon, she said in a message to NOAA staffers. “[W]onderful as Skype is for staying in touch, it is not a viable long-term arrangement!” Lubchenco has contended with some difficult challenges during her time at NOAA, including one of the world's worst oil spills in the Gulf of Mexico and the reform of major science satellite programs that were behind schedule and over budget. She also battled critics in Congress, who sank her efforts to reorganize NOAA's climate science programs and called for her firing over changes in fisheries regulation. “Our fishing community has suffered under Jane Lubchenco's leadership,” said Representative John Tierney (D–MA). But Lubchenco got high marks from environmentalists for her efforts to forge a national oceans policy that put an emphasis on using science to inform policy. http://scim.ag/Lubchenco 3. # Random Sample ## Let Me Hear You Scream The growls and screams of hardcore/metal bands like Bitterness Exhumed (pictured) sound painful, but those vocal pyrotechnics might be less damaging to the singer than you might expect. There's not much scholarly work on what happens in the throats of heavy metal singers when they perform, says musicologist Marcus Erbe of the University of Cologne in Germany. So Erbe, who has been doing field work in the heavy metal, death metal, and hardcore band scene in Germany for several years, teamed up with linguist Sven Grawunder of the Max Planck Institute for Evolutionary Anthropology in Leipzig and ear, nose, and throat physician Michael Fuchs of the Leipzig University School of Medicine to investigate. The researchers used an endoscope to make videos of vocalists emitting growls, screams, and other standard-fare sounds of the genre. Initial results from six participants indicate that the performers—whose range rivals that of classical opera singers—produce their characteristic sounds with not only the true vocal folds but also with the vestibular folds and aryepiglottic folds, which are located higher in the larynx. And part of the desired sound comes from vibrating mucus in the singers' throats—which might also help protect their voices. Several participants have voice-intensive day jobs as counselors or teachers, but none reported any voice problems, Fuchs says. Grawunder also plans to compare the sounds with those found in, for example, unusual consonants in various languages and Tuvan throat singing in Siberia. Metal performers push the human voice to its limits, says musicologist Michael Custodis of the University of Münster who is not part of the project. To use high-quality scientific methods to study that process “is fantastic.” ## They Said It “It's like judging the bottles in a wine contest by the labels only without tasting their content.” —Political economist Alberto Baccini of the University of Siena in Italy, speaking about a major government effort to evaluate Italian scientists and research institutions. http://scim.ag/Italyex 4. # The Top 10 ScienceNOWs of 2012 At the end of every December, ScienceNOW takes a look back at some of our favorite stories of the year. These aren't necessarily the biggest scientific advances (see our Breakthrough of the Year, p. 1524). They're simply the funniest, wackiest, and most popular items we've run. ## Turtle Sex—Preserved for the Ages If anything could be more embarrassing than dying while having sex, it might be being preserved in flagrante delicto for millions of years so that members of an advanced species could dig you up, gawk at you, and write a journal paper about your final romantic encounter. For a group of ancient turtles, this nightmare came true. ## The Physics of Spilled Coffee Here's some news you can use. Physicists have figured out how coffee spills from your mug—and how to keep it from sloshing all over your keyboard. One hint: Watch the acceleration. ## Old Termites Blow Themselves Up To Protect the Nest Elderly termites do not go softly into that good night. When another species of termite or a predator approaches, the termites activate explosive crystals on their backs and go boom. Secretions released by the blast kill opponents—and save the nest. ## Clues to Species Decline Buried In Pile of Bird Excrement Talk about a pile of … well, excrement. By digging into a 2-meter-deep mound of bird poop laying at the bottom of a five-story-high chimney and deposited over 48 years, researchers have uncovered new clues about why the chimney swift and other species like it have begun to disappear. ## Landscape of Dead Bodies May Have Inspired First Mummies Three thousand years before the ancient Egyptians began mummifying their dead, hunter-gatherers known as the Chinchorro adopted the practice in Chile's Atacama Desert. Their inspiration, according to this study, was seeing corpses rising from the sand during their daily journeys. ## Meet ‘Amasia’: The Next Supercontinent In about a hundred million years, you may be able to take a train from South America to Australia. That's because most, not all, of today's continents will be merged into a giant landmass called Amasia. If you can't wait, flying is still your best option. ## It's Official: Physics Is Hard Finally, science has proved what most of us always suspected: Physics is difficult. One of the most common goals in the field—finding an equation that describes how a system changes over time—is defined as “hard” by computer theory. Just don't expect to get out of that pop quiz. ## A Million-Year Hard Disk Pity the humans that come across our nuclear waste repositories tens of thousands of years hence. How will they know what they are? Enter a sapphire disk engraved with platinum that can store information for more than a million years. Now we just need to decide what language to write it in. ## Mysterious Fairy Circles Are ‘Alive’ Footprints of the gods? Signs from extraterrestrials? Namibia's so-called fairy circles have long puzzled scientists. One researcher thinks he has finally come close to solving the mystery. ## And the number one story is … It's a public nuisance, and one that's been hard to fix. But now, by utilizing a bit of non-Newtonian physics, a group of college students may have hit upon a solution. One of our “silly”-est stories of the year is also our most popular. To find out what it is, visit: http://scim.ag/top10_12 5. Breakthrough of the Year # The Discovery of the Higgs Boson 1. Adrian Cho Science has chosen the finding of the Higgs boson as its Breakthrough of the Year. No recent scientific advance has generated more hoopla than this one. On 4 July, researchers working with the world's biggest atom smasher—the Large Hadron Collider (LHC) in Switzerland—announced that they had spotted a particle that appears to be the long-sought Higgs boson, the last missing piece in physicists' standard model of fundamental particles and forces. The seminar at which the results were presented turned into a media circus, and the news captured the imagination of people around the world. “[H]appy ‘god particle’ day,” tweeted will.i.am, the singer for pop group The Black Eyed Peas, to his 4 million Twitter followers. Yet, for all the hype, the discovery of the Higgs boson easily merits recognition as the breakthrough of the year. Hypothesized more than 40 years ago, the Higgs boson is the key to physicists' explanation of how other fundamental particles get their mass. Its observation completes the standard model, perhaps the most elaborate and precise theory in all of science. In fact, the only big question hanging over the advance is whether it marks the beginning of a new age of discovery in particle physics or the last hurrah for a field that has run its course. The Higgs solves a basic problem in the standard model. The theory describes the particles that make up ordinary matter: the electrons that whiz around in atoms, the up quarks and down quarks that make up the protons and neutrons in atomic nuclei, the neutrinos that are emitted in a type of radioactivity, and two sets of heavier cousins of these particles that emerge in particle collisions. These particles interact by exchanging other particles that convey three forces: the electromagnetic force; the weak nuclear force, which spawns neutrinos; and the strong nuclear, which binds quarks. But there's a catch. At first blush, the standard model appears to be a theory of massless particles. That's because simply assigning masses to the particles makes the theory go haywire mathematically. So mass must somehow emerge from interactions of the otherwise massless particles themselves. ### Multimedia That's where the Higgs comes in. Physicists assume that empty space is filled with a “Higgs field,” which is a bit like an electric field. Particles interact with the Higgs field to acquire energy and, hence, mass, thanks to Albert Einstein's famous equivalence of the two, encapsulated in the equation E = mc2. Just as an electric field consists of particles called photons, the Higgs field consists of Higgs bosons woven into the vacuum. Physicists have now blasted them out of the vacuum and into brief existence. That feat marks an intellectual, technological, and organizational triumph. To produce the Higgs, researchers at the European particle physics laboratory, CERN, near Geneva, built the$5.5 billion, 27-kilometer-long LHC. To spot the Higgs, they built gargantuan particle detectors—ATLAS, which is 25 meters tall and 45 meters long, and CMS, which weighs 12,500 tonnes. The ATLAS and CMS teams boast 3000 members each. More than 100 nations have a hand in the LHC.

Perhaps most impressive is the fact that theorists predicted the existence of the new particle and laid out its properties, right down to the rates at which it should decay into various combinations of other particles. (To test whether the particle really is the Higgs, researchers are measuring those rates now.) Physicists have made such predictions before. In 1970, when only three types of quarks were known, theorists predicted the existence of a fourth, which was discovered 4 years later. In 1967, they predicted the existence of particles that convey the weak force, the W and Z bosons, which were found in 1983.

Particle theorists offer various explanations of their knack for prognostication. Particle collisions are inherently reproducible and free of contingency, theorists say. Whereas no two galaxies are exactly the same, all protons are identical. So when smashing them, physicists need not worry about the peculiarities of this proton or that proton because there are none. Moreover, theorists say, in spite of its mathematical complexity, the standard model is conceptually simple—a claim that nonphysicists might not buy.

The standard model ultimately owes its predictive power to the fact that the theory is based on the notion of mathematical symmetry, some theorists say. Each of the three forces in the standard model is related to and, in some sense, necessitated by a different symmetry. The Higgs mechanism itself was invented to preserve such symmetry while giving mass to force-carrying particles like the W and the Z. Simply put, symmetry arguments are powerful predictive tools.

No matter the reason for particle physicists' predictive prowess, with the Higgs boson apparently in the bag, they have no similar prediction to test next. They have plenty of reason to think the standard model is not the final word on fundamental physics. The theory is obviously incomplete, as it doesn't incorporate the force of gravity. And the theory itself suggests that interactions between the Higgs and other particles ought to make the Higgs hugely heavy. So physicists suspect that new particles lurking in the vacuum may counteract that effect. But those arguments aren't nearly as precise as the one necessitating the Higgs boson.

In fact, scientists have no guarantee that any new physics lies within the reach of the LHC or any conceivable collider. The standard model could be all of the inner workings of the universe that nature is willing to reveal. The discovery of the Higgs is a breakthrough. Will particle physicists ever score a similar breakthrough again?

6. Breakthrough of the Year

# The Runners-Up

A remarkable new method to prepare single strands of ancient DNA and view their genomes topped the list of this year's runners-up for Breakthrough of the Year, along with important discoveries into transcription activator–like effector nucleases, neutrino physics, Majorana fermions, the production of eggs cells from stem cells, and brain-machine interfaces. Other notable advances involve the Encyclopedia of DNA Elements, the Mars Curiosity rover, and the use of x-ray lasers to determine protein structure.

## A Home Run for Ancient DNA

Two years ago, paleogeneticists made our short list for Breakthrough of the Year for publishing the complete sequence of the nuclear genome of the Neandertals. In 2011, the same lab shared our spotlight for piecing together the genome of the Denisovans, an archaic human that lived in Siberia at least 50,000 years ago. But those ancient DNA sequences and others were blurry snapshots next to the high-resolution genomes that researchers can now sequence from living people. Much of the fragile DNA from fossils is degraded into single strands that automatic sequencers can't copy. Researchers were resigned to deciphering only parts of the code of ancient genomes, whether from archaic humans, animals, or pathogens.

This year, however, a persistent postdoc developed a remarkable new method that enabled his team to revisit the Denisovan DNA and sequence it 31 times over. The resulting genome, of a girl who lived in Siberia's Denisova Cave, reveals her genetic material in the same sharp, rich detail that researchers typically get from the DNA of living people. This technological feat promises to give a major boost to the field of ancient DNA, as researchers begin to apply the method to other samples and species.

Ancient DNA researchers typically have adapted the tools used to sequence DNA from living humans, which start with samples of double-stranded DNA. But ancient DNA usually breaks into single strands. So postdoc Matthias Meyer at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, set out to sequence single-stranded ancient DNA from scratch. He failed at first, but then managed to bind special molecules to the ends of a single DNA strand, holding it in place for sequencing. As a result, using only 6 milligrams of bone from the Siberian girl's pinky finger, Meyer and colleagues were able to copy 99.9% of her genome at least once and 92% of the genome 20 times—the benchmark for reliably identifying nucleotide positions.

The results confirmed that Denisovans interbred with the ancestors of some living humans; people living in parts of island Southeast Asia have inherited about 3% of their nuclear DNA from Denisovans. The genome literally offers a glimpse of the girl, suggesting that she had brown eyes, brown hair, and brown skin. It also allowed the team to use DNA to estimate that the girl died between 74,000 and 82,000 years ago—the first time researchers had used genomic information to date an archaic human. The high quality of the genome gives researchers a powerful new tool to fish for genes that have recently evolved, providing a “near-complete” catalog of the handful of genetic changes that separate us from Denisovans, who were close kin to Neandertals.

These details are all the more remarkable because the Denisovans are so poorly known from fossils: Only a tiny scrap of finger bone and two molars have been reliably assigned to them so far. In contrast, the Neandertals are known from hundreds of fossils but from a much less complete genome.

Neandertal experts may catch up soon. Meyer and colleagues have been trying “Matthias's method” on fossil samples that previously failed to yield much DNA. A detailed Neandertal genome comparable to the Denisovan one is expected in 2013.

Related References and Web Sites

## Genomic Cruise Missiles

This year, genome engineers got their hands on some potentially powerful new tools that promise to put the modification of DNA within easy reach of biologists studying a variety of organisms, including yeast and humans. One of these tools, called TALENs (for “transcription activator–like effector nucleases”), can destroy or alter specific genes in zebrafish, Xenopus toads, and livestock. A TALEN is a protein that cuts DNA in specific places, and the ensuing repair modifies the target gene. One group of researchers used the technique to create a miniature pig useful for studying heart disease. Others are modifying the genomes of rats, crickets, and even human cells from patients with disease. Crystal structures of these effector proteins attached to DNA have revealed how the proteins find their targets. And at least three teams have come up with a way to make many of these proteins fast and cheaply. This progress has prompted more investigators to give this approach a try.

Such a boom in genome engineering was unthinkable just a few years ago. For most higher organisms, changing or deleting DNA has generally been a hit-or-miss proposition. Researchers could not readily control where an added gene would insert itself into a genome or which DNA they delete in so-called knockout experiments. As a result, pinpointing what specific genes do and correcting disease genes in people have posed major challenges.

A decade ago, a new technology called zinc finger nucleases provided a way to target specific genes. Researchers leaped to develop this tool. But zinc fingers proved difficult to make, and one company holds all the key patents. So excitement swelled again in 2009, when two teams discovered a one-to-one correspondence between the repetitive regions of transcription activator–like effector proteins and the DNA bases they attach to, thus providing a new way to target genes. In 2012, studies drove home that TALENs work as well as zinc fingers do but are far easier and cheaper to make. Some researchers now think TALENs will become standard procedure for all molecular biology labs.

Meanwhile, another gene-targeting technology is beginning to make a name for itself. One drawback of zinc finger nucleases, TALENs, and another genome-editing tool called meganucleases is that they must be reengineered for each new DNA target. These proteins have two parts: the DNA targeting section and the DNA-cutting section. The new technology substitutes RNA—which is simpler to make than a piece of a protein—for the DNA targeting section. It also makes use of a bacterial protein called Cas9, which is part of a natural bacterial defense system called CRISPR, to do the cutting.

Researchers have shown in a test-tube that they can combine these two RNAs into a single one that both matches the DNA target and holds Cas9 in place. Using this system, they were able to cut specific target DNA, demonstrating the potential of Cas9 to work like TALENs. Now, those researchers are trying this approach in organisms other than bacteria, and other genome engineers are quite excited about their prospects, suggesting that it may one day challenge zinc finger nucleases and TALENs as the core genome engineering technology.

Related References and Web Sites

## Crash Project Opens a Door in Neutrino Physics

Sometimes it's not the result itself so much as the promise it holds that matters most. This year, physicists measured the last parameter describing how elusive particles called neutrinos morph into one another as they zip along at near–light speed. And the result suggests that in the coming decades neutrino physics will be every bit as rich as physicists had hoped—and may even help explain how the universe evolved to contain so much matter and so little antimatter.

Born in certain nuclear interactions, neutrinos come in three types or flavors that change into one another in so-called neutrino oscillations. The rates and extents to which the flavors mix depend on six parameters: the three differences between the neutrinos' masses, and three “mixing angles.” In March, the 250 researchers with the Daya Bay Reactor Neutrino Experiment in China reported that last unknown parameter, the mixing angle known as Θ13 (pronounced “theta one three”), equals 8.8°, give or take 0.8°.

The result itself is remarkable, as it's not every year that physicists measure a new fundamental parameter. The real excitement, however, stems from the result's broader implications. The measurement proves that all three mixing angles are greater than zero. That fact, in turn, implies that the oscillations of antineutrinos might differ from those of neutrinos, something that would not be possible had Θ13 equaled zero.

That's a big deal. Such a difference would be an example of an asymmetry between matter and antimatter known as CP violation. Physicists have already observed CP violation among particles called quarks, but they know that it isn't pronounced enough to explain why particles of normal matter vastly outnumber particles of antimatter in the universe. Physicists think that if there is CP violation among neutrinos, then it may be more analogous to the effect that created the matter-antimatter imbalance in the universe.

In fact, researchers in the United States, Japan, and Europe are engaged in experiments in which they use particle accelerators to fire neutrinos hundreds of kilometers through Earth to huge particle detectors. Current efforts seek to pin down, for example, the masses of the neutrinos and not just the differences between them. And scientists in all three regions are planning bigger experiments to search for CP violation among neutrinos. The Daya Bay result gives those efforts an enormous shot in the arm.

The result also marks a coup for Chinese physicists. The Daya Bay team studied the neutrinos emanating from the reactors at the Daya Bay Nuclear Power Plant and two neighboring plants in Shenzhen. In making a definitive measurement, they beat out teams working at reactors in France and South Korea and accelerator-based experiments in Japan and the United States.

The measurement of Θ13 wasn't the only result in particle physics this year. Researchers working with the world's largest atom smasher, the Large Hadron Collider (LHC) in Switzerland, discovered the Higgs boson, the last piece of physicists' standard model. But if LHC researchers do not find new particles beyond those in the standard model, then neutrino physics could be the future of particle physics—as the fact that neutrinos even have mass isn't part of the standard model. If so, the Daya Bay result may mark the moment when the field took off.

Related References and Web Sites

## Piercing a Frigid Underworld

The depths of Antarctica are about to be brought to light. In February, after 14 years of off-and-on drilling through 4 kilometers of East Antarctic ice, Russian scientists stopped just short of the surface of a mysterious subglacial lake likely cut off from the rest of the planet for millions of years. This month, the team returns to Lake Vostok with plans to bring back samples of ice—and, they hope, to discover signs of long-buried indigenous life. U.S.-led and U.K.-led teams are embarking on their own expeditions to study subglacial Antarctic waters. The U.S. team will head to the Whillans Ice Stream, where Antarctic ice joins the Southern Ocean; the U.K. team, to Lake Ellsworth, also on the Western Antarctic Ice Sheet.

## Cancer Immunotherapy

Recently developed drugs that harness the body's immune system to fight cancer have beaten back the disease in a small subset of tumor-ridden patients. Researchers predict that combining two such immunotherapies that target different pathways could pack an even more powerful punch. In 2013, look for early results from clinical trials that pair two antibodies that thwart pathways that tumor cells co-opt to hide from the immune system, and for reports on human studies that combine this brake-lifting strategy with treatments that rev up the body's immune response.

## Plant Power

Expect basic plant research to pay off this year, with farmers making use of drought-resistant crops and companies selling the first algae-based diesel fuel. Researchers expect to pin down details of the molecular and genetic components that interact to regulate the growth of plants. Mechanical forces will prove to play a key role in this regulation. Melding genomic, developmental, and ecological studies should help reveal how natural variation can succeed—or fail—to enable plants to adapt to climate change.

9. Breakthrough of the Year

# Scorecard: Rating Last Year's Areas to Watch

The predictions of Science's editors were spot on for this year, involving the long-sought Higgs boson, faster-than-light neutrinos, how metabolism influences the reprogramming of mature cells, whole-genome sequencing, potential targets for reversing cognitive and behavioral symptoms, and the Mars Science Laboratory.

## The Higgs Boson

We said that at the rate physicists were collecting data with the world's biggest atom smasher, the Large Hadron Collider, it was “all but a mathematical certainty” that they would either find the long-sought Higgs boson or rule out its existence. It appears that physicists have bagged their prize (see p. 1524). Nature was generous. Math works.

Related References and Web Sites

## Faster-Than-Light Neutrinos

As suggested, last year's claim that particles called neutrinos travel faster than light fell apart—but in an unexpectedly spectacular way. Physicists had reported that neutrinos were making the 730-kilometer trip from CERN in Switzerland to the OPERA particle detector in Italy 60 nanoseconds faster than they should at light speed. This February, however, they found that the time discrepancy had been caused by a loose cable connection. In March, two leaders of the 200-member OPERA team stepped down after a vote of no confidence.

Related References and Web Sites

## Stem-Cell Metabolism

Scientists made progress this year in understanding the way stem cells use energy and the molecules needed for cell function as they differentiate into various tissues. They uncovered more details about how metabolism influences the reprogramming of mature cells into embryolike ones. It's also increasingly clear that the metabolism of embryolike stem cells resembles that of cancer cells. However, there's plenty more to discover about the complicated pathways and their influence on aging, disease, and regenerative medicine. Keep watching.

Related References and Web Sites

## Genomic Epidemiology

This year has shown that whole-genome sequencing of infectious bacteria can help scientists understand and even control disease outbreaks. Researchers used the technique to discover how Clostridium difficile spread went on a rampage in hospitals around the world and to track outbreaks of resistant Staphylococcus aureus and Klebsiella pneumoniae bacteria within a single hospital; in the last two cases, they think their genomic sleuthing may have saved lives.

Related References and Web Sites

## Treating Intellectual Disability

As we predicted, in 2012 animal studies turned up more potential targets for reversing cognitive and behavioral symptoms in autism and related disorders. And clinical trials continued, with researchers reporting encouraging findings with arbaclofen and bumetanide, drugs that enhance certain effects of the neurotransmitter GABA, in people with fragile X syndrome and autism, respectively. Closely watched clinical trials for fragile X with mGluR5 antagonists, which inhibit a receptor for glutamate, another neurotransmitter, should release findings in 2013.

Related References and Web Sites

## Curiosity to Mars

The Mars Science Laboratory has indeed proved worth watching. Its “7 minutes of terror” descent through the martian atmosphere ended in a safe, spot-on landing (see p. 1529) followed by—so far—months of productive scientific work by the Mini Cooper–sized Curiosity rover. Who could ask for more?

Related References and Web Sites

10. Breakthrough of the Year

# A Year On, the H5N1 Debate Remains Infectious, With No End in Sight

1. David Malakoff

Two controversial studies that showed how to make the H5N1 avian influenza virus transmissible among mammals have left scientists wondering which kinds of studies are worth the risk and how potentially dangerous results should be reviewed and safely communicated to the public and public health experts.

Fiasco. Essential. Inevitable.

Those are just a few of the words that scientists and national security experts have used to describe the global controversy that engulfed influenza researchers this year. The drama began in late 2011 after two science teams showed how to make the H5N1 avian influenza virus—which typically kills birds—transmissible among mammals, potentially opening the door to a deadly human pandemic. Some say the storm—which is still far from over—has exposed long-standing flaws in efforts to prevent dangerous agents from escaping from unsafe laboratories or falling into the hands of terrorists, and highlighted the need for tighter oversight of “dual-use” research that can be used for good and evil. But others fear the episode is fueling a regulatory overreaction that could harm international collaboration and put an end to U.S. funding for potentially valuable science.

There's one thing that all sides appear to agree on: Nobody wants to repeat the highly publicized meltdown that sowed confusion and contention among scientists, government officials, the media, and the public. “In many ways, it's been a debacle,” Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases, told Science earlier this year.

Fauci should know. His agency funded the two controversial studies, which raised dual-use concerns after the results were submitted to Nature and Science. As word leaked out, researchers helped fan the flames when an author of one the studies—virologist Ron Fouchier of Erasmus MC in Rotterdam—told reporters from Science and other outlets that his team had engineered a virus that might kill millions. Such suggestions ultimately helped persuade the U.S. National Science Advisory Board for Biosecurity (NSABB), which advises the government on the security risks associated with biological research, to recommend against fully publishing the studies.

That recommendation did little to quell the debate, however, with some scientists calling it misguided while others argued that it didn't go far enough. The New York Times even called on the government to destroy the “doomsday” virus and halt funding for similar research. To help ease fears, in January influenza researchers announced a voluntary, temporary moratorium on H5N1 experiments that might make the virus more dangerous to humans. And some asked NSABB to reconsider its recommendation. In March, it did—and a majority of the members changed their minds, in part because they learned that Fouchier's virus was less lethal than originally believed. Some were also encouraged by the release of a new U.S. policy designed to help funders and scientists spot problematic dual-use studies before they begin—potentially heading off future conflicts. With NSABB's blessing in hand, Science and Nature finally published the studies.

The end of story, however, isn't settled. The voluntary moratorium on H5N1 research—which was originally planned to last just 60 days—is still in place with no end in sight. A long-promised follow-up to the March dual-use policy, designed to help U.S. university officials implement the rules, has yet to appear. And this month, U.S. officials introduced a new plot line, unveiling draft guidelines that would bar government funding for H5N1 studies that would enable the virus to gain functions, such as the ability to easily infect humans, which might not naturally evolve. The rules could also require such “gain-of-function” studies to be kept secret.

Not surprisingly, that draft is getting a mixed reception from researchers, with some worrying that it will end U.S. funding for a whole subset of possibly useful studies. Meanwhile, even supporters of such controls say they'll have only a limited effect if other nations don't adopt similar rules. “This is a global issue—lots of laboratories can do this type of research, and the U.S. can't be effective acting alone,” says microbiologist and biosecurity expert Ronald Atlas of the University of Louisville in Kentucky.

The end result: More than a year after the H5N1 controversy erupted, there is still no clear international consensus on which kinds of studies are worth the risk, or how potentially dangerous results should be reviewed or safely communicated to the public and public health experts. Until the confusion clears, experts warn, more messy public battles over finding the right balance between science and security are probably, well, inevitable.

11. # The Year in News

Here are some of the people, places, and events that helped shape the world of science in 2012.

## The Year in News, 2012

### January

Baikonur Cosmodrome, Kazakhstan: Russia's Fobos-Grunt sampling mission fails to escape Earth's orbit on way to martian moon.

### January

Washington, D.C.: Obama administration proposes dismantling Commerce Department and scattering its scientific components across the federal government.

### January

New Delhi: India celebrates going 1 year without a case of polio; no new cases reported in 2012.

### January

London and Washington, D.C.: Flu researchers announce a 60-day moratorium on risky H5N1 studies in a letter to Nature and Science. The moratorium remains in effect.

### February

Antarctica: A team of Russian scientists finishes drilling 3770 meters through the Antarctic ice to reach the surface of buried Lake Vostok.

### March

Bethesda: Reversing an earlier decision, the National Science Advisory Board for Biosecurity approves publication of two controversial papers on H5N1's ability to trigger a pandemic.

### March

Washington, D.C.: U.S. government announces rules designed to reduce risk of harmful consequences from experiments using 15 pathogens and toxins.

### April

Paris: Contact is lost with Europe's 10-year-old Earth-observing satellite Envisat.

### April

Washington, D.C.: Jim Yong Kim elected as first scientist/physician to lead the World Bank.

### May

Boston: Autopsies of four military veterans find signs of the same neurodegenerative disease found previously in U.S. football players.

### June

Galapagos Islands: Centenarian Lonesome George, the last of a subspecies of giant tortoise in the Galapagos Islands, succumbs to apparent heart failure.

### June

Rio de Janeiro, Brazil: Lack of major commitments dooms Rio+20 conference on sustainable development.

### July

Meyrin, Switzerland: Physicists at CERN report they've probably found the Higgs boson, the particle that conveys mass to other fundamental particles.

### July

Washington, D.C.: Two studies published in Science failed to find arsenic in bacterial DNA, refuting controversial work reported in 2010.

### July

Phnom Penh: A mysterious syndrome that killed dozens of children is identified as hand, foot, and mouth disease after patients test positive for Enterovirus 71.

### July

Tokyo: Panel finds that anesthesiologist Yoshitaka Fujii fabricated a record-setting 172 papers.

### August

Bethesda: The National Heart, Lung, and Blood Institute launches massive clinical trial to test whether blocking inflammation can prevent heart disease.

### August

Pasadena, California: NASA's Curiosity rover lands safely on Mars and begins 2-year mission.

### August

Indianapolis and New York: Long-awaited clinical trial results for bapineuzumab and solanezumab fail to show cognitive benefits for Alzheimer's disease patients.

### August

Kyoto, Japan: Mathematician Shinichi Mochizuki invites colleagues to poke holes in his proof of the abc conjecture.

### September

Hinxton, U.K.: Results from the Encyclopedia of DNA elements (ENCODE) project identifying a high percentage of human DNA with some functionality generate praise and controversy.

### September

Livermore, California: National Ignition Facility fails to meet its own deadline for achieving a self-sustaining fusion reaction.

### September

Saudi Arabia and Qatar: Two cases, one fatal, of a new coronavirus related to SARS triggers worries about a wider outbreak.

### September

Hunan province, China: In a nationwide uproar, critics say that a U.S.-funded study involving genetically modified (GM) golden rice used Chinese children as guinea pigs.

### September

Caen, France: Study claiming that GM maize causes tumors and early death in rats generates headlines—and widespread criticism from food safety agencies.

### September

Alaska: Shell begins exploratory oil drilling in Alaska's Chukchi Sea, the first in more than 2 decades. But technical problems cut the project short.

### October

L'Aquila, Italy: Six scientists and a government official are found guilty of manslaughter and sentenced to 6 years in prison for making reassuring statements before a deadly April 2009 earthquake.

### November

Sacramento: California's cap-and-trade program, the broadest in the nation, began auctioning permits to businesses in an effort to regulate release of greenhouse gases.

### December

Brussels: E.U. officials endorse a unified patent system that they hope will take effect in 25 countries in 2014.