Online the Higgs Boson Eas- That Empty Space Is ﬁ Lled with Tions of Other Particles

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NEWSFOCUS THE DISCOVERY OF THE Higgs Boson

NO RECENT SCIENTIFIC ADVANCE HAS act by exchanging other particles that con- Higgs, researchers at the European particle generated more hoopla than this one. On vey three forces: the electromagnetic force; physics laboratory, CERN, near Geneva, built 4 July, researchers working with the world’s the weak nuclear force, which spawns the $5.5 billion, 27-kilometer-long LHC. To biggest atom smasher—the Large Hadron neutrinos; and the strong nuclear, which spot the Higgs, they built gargantuan particle Collider (LHC) in Switzerland—announced binds quarks. detectors—ATLAS, which is 25 meters tall that they had spotted a particle that appears But there’s a catch. At first blush, the and 45 meters long, and CMS, which weighs to be the long-sought Higgs boson, the standard model appears to be a theory of 12,500 tonnes. The ATLAS and CMS teams last missing piece in physicists’ standard massless particles. That’s because boast 3000 members each. More model of fundamental particles and forces. simply assigning masses to the than 100 nations have a hand The seminar at which the results were pre- particles makes the theory go in the LHC. sented turned into a media circus, and the news haywire mathematically. So Perhaps most impressive captured the imagination of people around the mass must somehow emerge is the fact that theorists pre- world. “[H]appy ‘god particle’ day,” tweeted from interactions of the oth- dicted the existence of the will.i.am, the singer for pop group The Black erwise massless particles new particle and laid out its Eyed Peas, to his 4 million Twitter followers. themselves. properties, right down to Yet, for all the That’s where the Higgs the rates at which it should hype, the discovery of comes in. Physicists assume decay into various combina- Online the Higgs boson eas- that empty space is fi lled with tions of other particles. (To sciencemag.org ily merits recognition a “Higgs field,” which is a bit test whether the particle really For an expanded as the breakthrough like an electric fi eld. Particles inter- is the Higgs, researchers are mea- version of this sec- of the year. Hypoth- act with the Higgs field to acquire energy suring those rates now.) Physicists have made tion, with podcast, video, links, and more, see www. esized more than and, hence, mass, thanks to Albert Einstein’s such predictions before. In 1970, when only sciencemag.org/special/ 40 years ago, the Higgs famous equivalence of the two, encapsulated three types of quarks were known, theorists btoy2012 and science- boson is the key to in the equation E = mc2. Just as an electric fi eld predicted the existence of a fourth, which was on December 24, 2012 careers.org. physicists’ explanation consists of particles called photons, the Higgs discovered 4 years later. In 1967, they pre- of how other funda- fi eld consists of Higgs bosons woven into the dicted the existence of particles that convey mental particles get their mass. Its observa- vacuum. Physicists have now blasted them out the weak force, the W and Z bosons, which tion completes the standard model, perhaps of the vacuum and into brief existence. were found in 1983. the most elaborate and precise theory in all of That feat marks an intellectual, technologi- Particle theorists offer various explana- science. In fact, the only big question hang- cal, and organizational triumph. To produce the tions of their knack for prognostication. Parti- ing over the advance is whether it marks the cle collisions are inherently reproducible and

beginning of a new age of discovery in par- free of contingency, theorists say. Whereas www.sciencemag.org ticle physics or the last hurrah for a ﬁ eld no two galaxies are exactly the same, all that has run its course. protons are identical. So when smash- The Higgs solves a basic prob- ing them, physicists need not worry lem in the standard model. The about the peculiarities of this pro- theory describes the par- ton or that proton because there ticles that make up ordi- are none. Moreover, theorists nary matter: the electrons say, in spite of its math- that whiz around in ematical complexity, the Downloaded from atoms, the up quarks standard model is con- and down quarks that ceptually simple—a make up the pro- claim that nonphysi- tons and neutrons cists might not buy. in atomic nuclei, The standard the neutrinos that model ultimately are emitted in a owes its predictive type of radioactiv- power to the fact that ity, and two sets the theory is based on of heavier cous- the notion of math- ins of these parti- ematical symmetry, cles that emerge in some theorists say. particle collisions. Each of the three forces These particles inter- in the standard model is related to and, in some Pieced together. In this par- sense, necessitated by a dif- ticle collision, it appears that ferent symmetry. The Higgs a Higgs boson decays into two mechanism itself was invented

electrons and two positrons (red). to preserve such symmetry while MCCAULEY CERN/L. TAYLOR/T. CREDIT:

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giving mass to force-carrying particles like theory is obviously incomplete, as it doesn’t In fact, scientists have no guarantee that the W and the Z. Simply put, symmetry argu- incorporate the force of gravity. And the the- any new physics lies within the reach of the ments are powerful predictive tools. ory itself suggests that interactions between LHC or any conceivable collider. The stan- No matter the reason for particle physi- the Higgs and other particles ought to make dard model could be all of the inner workings cists’ predictive prowess, with the Higgs the Higgs hugely heavy. So physicists suspect of the universe that nature is willing to reveal. boson apparently in the bag, they have no sim- that new particles lurking in the vacuum may The discovery of the Higgs is a breakthrough. ilar prediction to test next. They have plenty counteract that effect. But those arguments Will particle physicists ever score a similar of reason to think the standard model is not aren’t nearly as precise as the one necessitat- breakthrough again? the ﬁ nal word on fundamental physics. The ing the Higgs boson. –ADRIAN CHO

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 auto- on December 24, 2012 matic 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 Deniso-

van DNA and sequence it 31 times over. www.sciencemag.org 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 techno- logical feat promises to give a major boost to the fi eld of ancient DNA, as researchers Single-minded. Postdoc Matthias Meyer (above) developed a new method to prepare single strands of ancient begin to apply the method to other samples DNA; the technique gave researchers an unprecedented view of an ancient girl’s genome. Downloaded from and species. Ancient DNA researchers typically have of the genome 20 times—the benchmark for evolved, providing a “near-complete” cata- adapted the tools used to sequence DNA reliably identifying nucleotide positions. log of the handful of genetic changes that from living humans, which start with sam- The results confi rmed that Denisovans separate us from Denisovans, who were ples of double-stranded DNA. But ancient interbred with the ancestors of some liv- close kin to Neandertals. DNA usually breaks into single strands. ing humans; people living in parts of island These details are all the more remark- So postdoc Matthias Meyer at the Max Southeast Asia have inherited about 3% of able because the Denisovans are so poorly Planck Institute for Evolutionary Anthro- their nuclear DNA from Denisovans. The known from fossils: Only a tiny scrap of pology in Leipzig, Germany, set out to genome literally offers a glimpse of the finger bone and two molars have been sequence single-stranded ancient girl, suggesting that she had brown reliably assigned to them so far. In DNA from scratch. He failed at eyes, brown hair, and brown skin. contrast, the Neandertals are known from first, but then managed to bind It also allowed the team to use hundreds of fossils but from a much less special molecules to the ends DNA to estimate that the girl died complete genome. of a single DNA strand, hold- between 74,000 and 82,000 years Neandertal experts may catch up soon. ing it in place for sequencing. As ago—the fi rst time researchers had Meyer and colleagues have been trying a result, using only 6 milligrams of used genomic information to date “Matthias’s method” on fossil samples that bone from the Siberian girl’s pinky fi n- an archaic human. The high quality of the previously failed to yield much DNA. A ger, Meyer and colleagues were able to copy genome gives researchers a powerful new detailed Neandertal genome comparable to

CREDIT: MAX PLANCK INSTITUTE FOR EVOLUTIONARY ANTHROPOLOGY MAX PLANCK INSTITUTE FOR EVOLUTIONARY CREDIT: 99.9% of her genome at least once and 92% tool to fish for genes that have recently the Denisovan one is expected in 2013.

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GENOMIC CRUISE MISSILES

This year, genome engineers got their hands on some potentially powerful new tools that promise to put the modifi cation of DNA within easy reach of biologists studying a variety of organisms, including yeast and humans. One of these tools, called TALENs (for “transcrip- tion activator–like effector nucleases”), can destroy or alter specifi c genes in zebrafi sh, Xenopus toads, and livestock. A TALEN is a protein that cuts DNA in specifi c places, and the ensuing repair modifi es the target gene. One group of researchers used the technique to create a miniature pig useful for studying heart disease. Others are modify- ITALIAN QUAKE VERDICTS ing the genomes of rats, crickets, and even human cells from patients RATTLE RESEARCHERS with disease. Crystal structures of these effector proteins attached to DNA have revealed how the proteins fi nd their targets. And at least three teams have come up with a way to make many of these proteins Can scientists risk talking publicly about risk—especially when lives fast and cheaply. This progress has prompted more investigators to are on the line? It’s a question that many researchers began asking give this approach a try. this year as Italian prosecutors pressed manslaughter charges against Such a boom in genome engineering was unthinkable just a few four scientists, two engineers, and a government offi cial accused of years ago. For most higher organisms, changing or deleting DNA conducting superfi cial analyses and making misleading public state- has generally been a hit-or-miss proposition. Researchers could ments about earthquake hazards in the days before a deadly 2009 temblor struck the city of L’Aquila, killing more than 300 people. In October, each of the seven defendants was found guilty and sentenced to 6 years in prison; all are appealing the convictions, a pro- on December 24, 2012 cess that could take years. The verdicts shocked and enraged many researchers—and prompted them to revisit a long-standing challenge: how to communicate with the public and policymakers about risk, especially in technical areas with high uncertainty and the potential for great loss of life. From bioterrorism and disease outbreaks to hurricanes and earth- quakes, researchers are called upon by government offi cials to help

forecast the probability of dangerous events and devise plans to keep www.sciencemag.org the public safe. They often struggle to translate nuanced statistical models into plainspoken, practical advice. Should a 40% probability that an event might occur make it “low-risk” in common parlance, for instance—or should that be a “medium” risk? And what differ- Model porker. Researchers used ence would that make to a person trying to decide whether to fl ee an TALENs to make pigs useful for oncoming storm, or a government offi cial trying to prepare for a pos- studying heart disease. sible bioterror attack? Until now, the answers to such questions were largely academic, Downloaded from or at least low-risk from a legal perspective. After the Italian verdicts, not readily control where an added gene would insert itself into a however, some scientists worry that the words they utter might land genome or which DNA they delete in so-called knockout experi- them in prison. “I’m afraid that many scientists are learning to keep ments. As a result, pinpointing what specifi c genes do and correcting their mouths shut,” earth scientist Thomas Jordan of the University of disease genes in people have posed major challenges. Southern California in Los Angeles, told Science earlier this year. “This A decade ago, a new technology called zinc fi nger nucleases won’t help those of us who are trying to improve risk communication provided a way to target specific genes. Researchers leaped to between scientists and the public.” develop this tool. But zinc fi ngers proved diffi cult to make, and one Some science groups are working to make sure researchers don’t company holds all the key patents. So excitement swelled again in go silent. National academies of science in Europe, for example, are 2009, when two teams discovered a one-to-one cor- collaborating on efforts to extract lessons from the L’Aquila case, respondence between the repetitive regions of tran- with an eye toward heading off similar legal jeopardy elsewhere. scription activator–like effector proteins and the “Probability-based statements are per se fraught with uncertainty,” DNA bases they attach to, thus providing a new the French and German academies noted in a statement earlier this way to target genes. In 2012, studies drove home year. But “scientists cannot—and should not—absolve themselves” that TALENs work as well as zinc fi ngers do but of the responsibility to communicate clearly, it added. The risk that are far easier and cheaper to make. Some research- scientists ultimately decide to say nothing, such efforts suggest, may ers now think TALENs will become standard proce- be the greatest risk of all. dure for all molecular biology labs. –DAVID MALAKOFF Meanwhile, another gene-targeting technology is beginning

to make a name for itself. One drawback of zinc ﬁ nger nucleases, OF RECOMBINETICS CREDITS (TOP TO BOTTOM): SANDRO PEROZZI/AP; COURTESY

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TALENs, and another genome-editing tool use of a bacterial protein called Cas9, which demonstrating the potential of Cas9 to work called meganucleases is that they must be is part of a natural bacterial defense system like TALENs. Now, those researchers are reengineered for each new DNA target. These called CRISPR, to do the cutting. trying this approach in organisms other than proteins have two parts: the DNA targeting Researchers have shown in a test-tube bacteria, and other genome engineers are section and the DNA-cutting section. The that they can combine these two RNAs into a quite excited about their prospects, suggest- new technology substitutes RNA—which is single one that both matches the DNA target ing that it may one day challenge zinc ﬁ nger simpler to make than a piece of a protein— and holds Cas9 in place. Using this system, nucleases and TALENs as the core genome for the DNA targeting section. It also makes they were able to cut speciﬁ c target DNA, engineering technology.

CRASH PROJECT OPENS A the neutrinos emanating from the reactors at the Daya Bay Nuclear Power Plant and two DOOR IN NEUTRINO PHYSICS neighboring plants in Shenzhen. In making a defi nitive measurement, they beat out teams Sometimes it’s not the result itself so much as analogous to the effect that created the matter- working at reactors in France and South the promise it holds that matters most. This antimatter imbalance in the universe. Korea and accelerator-based experiments in year, physicists measured the last param- In fact, researchers in the United States, Japan and the United States. eter describing how elusive particles called Japan, and Europe are engaged in experi- The measurement of θ13 wasn’t the only neutrinos morph into one another as they ments in which they use particle accelera- result in particle physics this year. Research- zip along at near–light speed. And the result tors to fi re neutrinos hundreds of kilometers ers working with the world’s largest atom suggests that in the coming decades neu- through Earth to huge particle detectors. Cur- smasher, the Large Hadron Collider (LHC) in trino physics will be every rent efforts seek to pin down, for example, Switzerland, discovered the Higgs boson, the bit as rich as physicists had hoped—and may even help explain how the universe evolved to on December 24, 2012 contain so much matter and so little antimatter. Born in certain nuclear interactions, neutrinos come in three types or fl avors that change into one another in so- called neutrino oscillations. The rates and extents to which the fl avors mix depend on

six parameters: the three differences between www.sciencemag.org 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 8.8º, give or take 0.8º. The result itself is remarkable, as it’s not Downloaded from 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 was fast! Construction of China’s Daya Bay Reactor Neutrino Experiment began in 2007. With 2 months’ That’s a big deal. Such a difference would worth of data, it scooped competitors in Japan, France, Korea, and the United States. be an example of an asymmetry between matter and antimatter known as CP viola- the masses of the neutrinos and not just the last piece of physicists’ standard model. But tion. Physicists have already observed CP differences between them. And scientists in if LHC researchers do not ﬁ nd new particles violation among particles called quarks, but all three regions are planning bigger experi- beyond those in the standard model, then neu- they know that it isn’t pronounced enough to ments to search for CP violation among neutrino physics could be the future of particle explain why particles of normal matter vastly trinos. The Daya Bay result gives those efforts physics—as the fact that neutrinos even have outnumber particles of antimatter in the uni- an enormous shot in the arm. mass isn’t part of the standard model. If so, verse. Physicists think that if there is CP vio- The result also marks a coup for Chi- the Daya Bay result may mark the moment

CREDIT: SUN ZIFA/COLOR CHINA PHOTO/AP IMAGES SUN ZIFA/COLOR CREDIT: lation among neutrinos, then it may be more nese physicists. The Daya Bay team studied when the ﬁ eld took off.

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GENOMICS BEYOND GENES home in on different cell compartments, as if they have fi xed addresses where they operate, A decadelong, $288 million study reported rosis and Crohn’s disease. suggesting that they play a role in the cell. Crit- this year in more than 30 papers showed the When these papers were published in ics argue, however, that it was already known human genome to be quite a bustling place, September, the media went wild. ENCODE that a lot of RNA was made, and that many of biochemically speaking. The work—called was hailed in The New York Times as a “stun- these RNAs may be spurious genome prod- the Encyclopedia of DNA Elements ucts that serve no purpose. Likewise, (ENCODE)—builds on the Human one ENCODE researcher found 3.9 Genome Project, which deciphered ENCODE million regions across 349 types of the order of the bases that are our by the Numbers cells where proteins called transcrip- DNA’s building blocks and found tion factors bind to the genome—but 147 that less than 2% of those bases again, it’s unclear how much of that defi ned genes. 80% binding is functional. ENCODE researchers took an Nonetheless, ENCODE stands 20,687 intensive look not just at genes out as an important achievement but at all of the DNA in between. 18,400 that should ease the way for more Their results drive home that much 1640 insights into the genome. By com- of the genome that at one time was bining these data with sampling dismissed as “junk DNA” actu- >30 from another data-intensive effort, ally seems to play an essential role, 442 the 1000 Genomes Project, research- often by helping to turn genes on ers discovered that 8% of our DNA $288 or off. They pinpointed hundreds million appears with little variation through- of thousands of landing spots for out the human population—a strong proteins that infl uence gene activ- sign that it was important for our ity, many thousands of stretches of DNA that ning resource” and “a major medical and evolution. Overall, ENCODE’s newly dis- code for different types of RNA, and lots of scientifi c breakthrough” with enormous and covered functional regions overlap with 12% on December 24, 2012 places where chemical modifi cations serve immediate implications for human health. of the specifi c DNA bases linked to higher to silence stretches of our chromosomes, The Guardian called it “the most signifi cant or lower risks of various diseases, suggest- concluding that 80% of the shift in scientists’ understanding of the way ing that the regulation of genes—not just the genome was biochemically our DNA operates since the sequencing of makeup of the genes themselves—might be at active. These details pro- the human genome.” the heart of these risks. Scientists have used vide a much better road But several scientists in the blogosphere this information to home in on relevant genes map for investigators try- called the coverage overhyped and blamed the and cell types in several disorders. Experi-

ing to understand how journals and ENCODE leaders for overplay- ments can now unearth the molecular basis www.sciencemag.org genes are controlled. Some ing the signiﬁ cance of the results. For exam- of these connections and, from there, identify researchers have already used ple, ENCODE reported that 76% of DNA is potential treatments. If that potential is real- these insights to clarify genetic risk factors for transcribed to RNA, most of which does not ized, then ENCODE will have earned its acco- a variety of diseases, including multiple scle- go on to help make proteins. Various RNAs lades as a “stunning resource.”

Planck Maps the Cosmic Downloaded from AREAS TO WATCH Microwave Background One Cell at a Time The European Space Agency’s Planck satellite will produce the most pre- Single-cell DNA sequencing burst onto the scene this year, with advances cise map yet of the afterglow of the big bang, the cosmic microwave back- in microfl uidics, the isolation of rare cells, and the ability to decipher ground radiation (CMB). The discovery of the CMB in 1965 bolstered the these tricky one-shot genomes—milestones that should help break the notion that the universe was born in an explosive big bang. Measurements fi eld wide open in 2013. Even more exciting, some say, are prospects for of tiny variations in its temperature in 1992 supported the idea that the learning about how cells—particularly brain cells—work by studying the universe expanded at greater than light speed in a brief spurt of “infl a- RNA in individual, intact cells. tion.” And the precise mapping of those variations in 2003 helped nail In the coming year, single-cell down the composition of the universe: 5% ordinary visible matter, 22% sequencing promises to reveal as-yet invisible dark matter, and 73% space-stretching dark energy. Planck a lot about how cancer cells will test the now-standard cosmology in greater detail—and could fi nd evi- vary within a tumor and how dence that the relatively simple scenario isn’t quite the whole story. many copies of genes reside in each cell. Expect continued Connectomes progress in developing this In 2013, the Human Connectome Project will get into full swing. This technology for medical diagnostics for cancer and prenatal applications. $38.5 million effort, funded by the U.S. National Institutes of Health, aims Meanwhile, several groups are assessing what genes are doing by measur- to scan the brains of 1200 healthy adults, including 300 pairs of twins, to ing in individual cells the messenger RNA that carries their instructions to investigate individual variations in the connections between brain regions

a cell’s protein factories. and how they might account for individual differences in cognition and CREDITS TO BOTTOM): DENNIS (TOP KUNKEL MICROSCOPY INC./VISUALS UNLIMITED/CORBIS

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SCARY ENGINEERING TAMES Engineers got a break when mission planners asked them to have Curiosity touch MARTIAN TERROR down up close and personal with the geo- logically intriguing central mound of Gale It looked like a wreck waiting to happen, but setting a massive rover down on inclined crater, a tight spot that no previous mission the new “sky crane” landing system designed slopes that would stymie a legged lander. could have targeted. Instead of streaking in to deliver the massive Curiosity rover safely Instruct the platform to cut the cables on as uncontrolled as a bullet, Curiosity revived onto Mars performed flawlessly on touchdown and fl y away, and you’ve a “heritage” concept from the days of the 5 August (PDT). Curiosity landed a got a safe landing—in principle. Apollo moon program, when astronaut- mere 2.4 kilometers from the center To make it all work in prac- bearing capsules guided themselves during of the bull’s-eye after a 563-million- tice, engineers test, test, and test reentry into Earth’s atmosphere. Sensing kilometer journey from Earth— again. But Curiosity engineers had any deviations from its intended fl ight path, even though engineers had no way a problem: Their EDL system—a the Curiosity entry vehicle would fi re side to test Curiosity’s “entry, descent, and blazing meteor- landing” (EDL) system from beginning to like entry, a para- end under martian conditions. chute descent, and the Curiosity mission engineers at NASA’s Jet sky-crane landing, Propulsion Laboratory in Pasadena, Califor- all designed to slow nia, pulled off a stunning EDL after thinking their spacecraft from far outside the box. Six times before, NASA a hypervelocity speed had landed intact spacecraft on Mars (and of 21,240 kilometers once it didn’t work out so well). Three land- per hour to a stand- ers came down like 1950s sci-fi spaceships, still 7 minutes later— rockets blazing and landing on legs. The three couldn’t be tested on rovers bounced onto Mars inside NASA’s Earth. Earth’s gravity version of a beach ball. But Curiosity— and atmosphere are too on December 24, 2012 clamped inside its entry vehicle—weighed different from those of in at 3.3 metric tons, too massive for either of Mars. So they tested Safe and sound. Bold design and exhaustive testing by NASA the traditional approaches. components sepa- engineers helped deliver the Curiosity rover safely to Mars. So Curiosity engineers considered rately as much as they how their earthly brethren move big things could, for example, by around. Taking their inspiration from cranes opening the parachute in the world’s largest thrusters to correct its course as it plunged and helicopters, they created the sky crane: a wind tunnel. Then they tested the system end toward the surface. The rover’s spot-on land-

platform festooned with retrorockets with the to end millions of times in a computer. In ing reassured planners that NASA can now www.sciencemag.org rover, wheels deployed, dangling 7.5 meters the end, reality played out as the simulations send a rover to collect samples on Mars and below at the end of three cables. The scary- did—a sign that NASA had taken one more later land a second mission in the same spot looking contraption could handle a landing step toward solving the far weightier prob- to pick up the samples and loft them into mass too large for a beach ball, while safely lem of landing astronauts on Mars. Mars orbit for eventual return to Earth.

behavior. Several other projects are zooming in to examine neural connec- patients. Researchers predict that combining two such immunotherapies that Downloaded from tivity at the cellular level. Advocates and critics have debated how much target different pathways could pack an even more powerful punch. In 2013, these maps will advance our understanding of brain function. By this time look for early results from clinical trials that pair two antibodies that thwart next year, far more data will help inform the debate. 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 treat- Piercing a frigid underworld ments that rev up the body’s immune response. 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, Plant Power Russian scientists stopped just short of the surface of a mysterious subgla- Expect basic plant research to pay off this year, with farmers making use of cial lake likely cut off from the rest of the planet for millions of years. This drought-resistant crops and companies selling the ﬁ rst algae-based diesel month, the team returns to Lake Vostok with plans to bring back samples fuel. Researchers expect to pin down details of the molecular and genetic of ice—and, they hope, to discover signs of long-buried indigenous life. components that interact to regu- U.S.-led and U.K.-led teams are embarking on their own expeditions to late the growth of plants. Mechani- study subglacial Antarctic waters. The U.S. team will head to the Whillans cal forces will prove to play a key Ice Stream, where Antarctic ice joins the Southern Ocean; the U.K. team, to role in this regulation. Melding Lake Ellsworth, also on the Western Antarctic Ice Sheet. genomic, developmental, and eco- logical studies should help reveal Cancer Immunotherapy how natural variation can suc- Recently developed drugs that harness the body’s immune system to ﬁ ght ceed—or fail—to enable plants to

CREDITS (TOP TO BOTTOM): CERN; WIKIMEDIA COMMONS cancer have beaten back the disease in a small subset of tumor-ridden adapt to climate change.

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FIRST PROTEIN STRUCTURE researchers from Germany and the United States determined the structure of the inactive FROM AN X-RAY LASER “precursor” form of an enzyme that’s key for the survival of the single-celled parasite that One hundred years ago, physicists showed stay of structural biology. When many copies causes African sleeping sickness, Trypano- how x-rays ricocheting through a crystal of a molecule are arranged in an orderly array soma brucei. To produce micrometer-sized could reveal the crystal’s atomic-scale struc- called a crystal lattice, they scatter the x-rays crystals of the enzyme, they overexpressed ture. This year, scientists pushed such “x-ray from an incoming beam in concert. The pat- it in cultured cells. They dropped the crystals diffraction” nearly to its ultimate limit when, tern of scattering reveals the structure of the through the beam of the LCLS, which turned for the fi rst time, they used an x-ray laser to crystal, including that of the molecule. Using on in 2009. A pulse of x-rays would obliter- circular particle accel- ate a crystal even as it produced a diffraction erators called synchro- pattern. Adding up 178,875 individual pat- trons to generate x-rays, terns, researchers determined the precursor’s biologists have deter- structure, which includes a kind of molecular mined tens of thousands safety cap that deactivates it. That information of protein structures. could help scientists fi nd a drug to tie up the Some proteins, such active form of the enzyme. as those found in cell With just one new structure in the bag, it’s membranes, do not not yet clear that x-ray free-electron lasers readily form crystals (XFELs) will compete with synchrotrons in big enough to be stud- structural biology. For one thing, researchers ied with synchrotrons, were not able to determine the structure of however. So, scientists the enzyme de novo from the diffraction data hope they can probe alone, but had to use the known structure of the those tough cases with active enzyme as a starting point. For another, new x-ray lasers, an XFEL serves far fewer users than a syn- on December 24, 2012 which are powered chrotron does. Still, the “diffraction before by straight-shot destruction” approach takes a qualita- linear accel- tive step past what synchrotrons can erators and do. Earlier this year, researchers in shine a billion Japan turned on their own XFEL, times brighter and researchers in Europe are build- In sum. Researchers used 178,875 individual laser pulses to generate this than synchro- ing one that should power up in 2015. diffraction pattern and decipher the structure. tron sources. In The grand goal is to push x-ray dif- www.sciencemag.org November, researchers fraction to its ultimate limit and use an x-ray determine the structure of a protein. The unveiled the fi rst protein structure revealed laser to decipher a protein structure by zap- advance shows the potential of x-ray lasers with such a laser. ping individual molecules. It’s not certain that to decipher proteins that conventional x-ray Working with the Linac Coherent Light can be done, but some researchers say the new sources cannot. Source (LCLS) at SLAC National Accelera- result suggests that objective may not be too X-ray diffraction has long been the main- tor Laboratory in Menlo Park, California, far out of reach. Downloaded from BRAIn-MACHINE INTERFACES dimensions—a 58-year-old woman who had been unable to speak or move her limbs for start to GET A GRIP 15 years manipulated a robotic arm with her thoughts, reaching out to grasp a bottle and This week researchers in Pennsylvania ous objects, removing plastic cones stacked take a sip of coffee. A tetraplegic man, 66, reported that a 53-year-old woman paralyzed on a base and restacking them one by one also learned to touch and grasp objects. from the neck down by a genetic neurode- on another base, for example. The demon- All of this work builds on more than a generative condition had learned to manip- strations represent the most complex move- decade of research with monkeys and other ulate a robotic arm with her thoughts. Sur- ments yet performed by a paralyzed human animals. And that work continues to advance. geons had implanted two 4×4-millime- patient using a brain-machine interface In 2011, researchers described a prosthetic ter grids of hair-thin electrodes in her (BMI), as such sophisticated pros- system that provides tactile feedback by brain to capture signals from an area thetics are often called. stimulating the somatosensory cortex, the involved in planning hand move- By demonstrating more fluid brain region responsible for the perception ments. A computer translated those and natural movements, this case of touch. And in April of this year, a team signals into commands to move the study improves on another impres- used signals from electrodes implanted in the robotic arm, which was engineered sive report earlier this year. In that motor cortex of the brain to stimulate mus- to have nearly all the same movement study—the first published demonstra- cles in the temporarily paralyzed arms of two capabilities as the real thing. In videos, the tion that paralyzed human patients can use a monkeys, enabling the animals to pick up

woman uses the arm to grasp and move vari- BMI to execute complex movements in three rubber balls and place them in a chute. Such NASS, CFEL KAROL CREDIT:

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MAJORANA FERMIONS, years ago, theorists suggested that the collec- tive motion of electrons in nanoscale wires quasi-here AT LAST adjacent to a superconductor may form “quasiparticles” Nanoscience is more than just a fashion- standing of fermions, particles such as elec- that for all intents and pur- able buzzword. It’s already paid off in bil- trons that show a type of angular momentum poses behave as if they lions of dollars worth of products including known as spin, with Albert Einstein’s equa- were a fundamental Majo- better batteries and baseball bats. This year, tions of relativity that impact particles trav- rana particle themselves. researchers in the fi eld delivered a different eling near the speed of light. Majorana’s The race was on. This year, type of value: their fi rst-ever likely particle insights implied the existence of a new type a team of physicists and chem- discovery, known as Majorana fermions. of fermion that could act as their own anti- ists in the Netherlands crossed the line show- ing compelling evidence that the Majorana quasiparticles exist. The discovery has already prompted efforts to use the new particles to build a stable quantum computer. Such computers operate on quantum bits, or qubits. Unlike regular bits of digital information repre- sented as 0s and 1s in calculations, qubits can be virtually any combination of a 0 and 1— say, 57% 0 and 43% 1, or 12% 0 and 88% 1. As a result, quantum computers have the potential to store and process information in ways that conventional digital machines can’t hope to match. For some types of calculations, crunching just 300 qubits could on December 24, 2012 generate an answer that today’s best super- computers would struggle to solve. However, current qubit technology is far too fussy for practical computing. The slight- est bump in temperature or other outside Particle detectors. At the heart of each device in this array is an indium antimonide nanowire, one end is gold- infl uence typically wipes out the informa- coated and the other is a superconductor (blue). Majorana fermions are produced at the ends of the nanowires. tion stored in a standard qubit. Theoretical

calculations show that Majorana fermions www.sciencemag.org Speculation about the existence of Major- matter and annihilate themselves. should be able to “remember” their quantum ana particles dates back more than 7 decades, Physicists have long suspected that neu- state even when buffeted by outside forces. when a young Italian physicist named Ettore trinos are Majorana fermions. Thus far, So now the Dutch team and others are hot on Majorana crunched some equations in the they’ve been unable to nail down the case. the trail to see whether that is the case. If it emerging fi eld of quantum mechanics. His And prospects for fi nding other Majorana is, nanoscience may soon be able to add to mathematics united the quantum under- fermions long seemed remote. But a few its bragging rights. Downloaded from fi ndings hint at the tantalizing possibility that it may one day be possible to reanimate paralyzed limbs in people. As hopeful as these developments are, it will be years before large numbers of people can benefi t from BMIs. The robotic arms are experimental and extraordinarily expensive, and patients use them only in the lab, aided by a team of technicians. And the movements enabled by BMIs aren’t nearly as fast and graceful as the movements made by unin- jured individuals. Advances in the algorithms that decode neural signals and convert them into commands a computer or prosthetic limb can understand should help with that. Progress in that area continues apace, but for hundreds of thousands of patients paralyzed by strokes, spinal injuries, and other condi- Reach for the future. This year saw impressive advances in brain-controlled prosthetic devices.

CREDITS (TOP TO BOTTOM): TU DELFT 2012; THE JOHNS HOPKINS UNIVERSITY APPLIED PHYSICS LABORATORY (JHU/APL) CREDITS (TOP TO BOTTOM): TU DELFT 2012; THE JOHNS HOPKINS UNIVERSITY APPLIED PHYSICS LABORATORY tions, it can’t come quickly enough.

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MAKING EGGS implanted those clusters in the ovaries or kid- neys of host mice, and several weeks later from Stem Cells they were able to extract mature oocytes. The scientists used normal mouse sperm Researchers have been trying for more than mine which genes are turned on and which to fertilize the oocytes in vitro and then a decade to make egg cells in the laboratory. are turned off. Although pluripotent cells— implanted the resulting embryos into foster This year, they took an important step toward including ES cells—are capable of becoming mothers. The foster mothers gave birth to that goal, as lab mice gave birth to the fi rst live any kind of cell in the body, turning them into normal mice, which were then able to go on pups born of eggs derived from mouse embry- germ cells in the lab has proved diffi cult. and have offspring of their own. (The recipe onic stem (ES) cells. The technique, devel- In 2011, the same lab also works with induced pluripo- oped by researchers in Japan, in Japan reported that tent stem cells, which are derived still requires a mouse to host it had turned ES cells from adult cells that have been the developing eggs during into fertile sperm. In reprogrammed to behave like a key part of their matura- 2012, researchers there embryonic cells.) tion, so it doesn’t achieve showed that a similar The technique doesn’t yet the big prize: deriving egg process can produce work with human cells—and cells entirely in vitro. But it eggs. First, they treated the requirement for ovarian tis- does demonstrate that ES cells the stem cells with a sue and a live host for part of the can give rise to fertile oocytes, and it gives sci- cocktail of growth fac- development makes it impracti- entists a way to learn more about how these tors and proteins to Growing potential. Fertilized cal and ethically problematic to complex and powerful cells develop. form what they call pri- lab-derived egg cells yielded try. But having a better way to Egg and sperm cells, also known as germ mordial germ cell-like embryos—and live mice. study the genes and other factors cells, have a particularly complicated devel- cells, which resemble that infl uence egg cell develop- opment. They undergo meiosis, a special kind the precursors of egg and sperm cells found ment could already help researchers under- of cell division that leaves them with half the in early embryos. They then mixed the cells stand some kinds of infertility—and could normal number of chromosomes. They also with ovarian tissue. The cells formed clusters lead to better ways to make these elusive but on December 24, 2012 reset the genomic imprinting that helps deter- that resemble miniature ovaries. The scientists powerful cells in the lab.

SCORECARD embryolike stem cells resembles that of cancer cells. However, there’s plenty more to discover about the complicated pathways and their infl u- RATING LAST YEAR’S AREAS TO WATCH ence on aging, disease, and regenerative medicine. Keep watching. www.sciencemag.org The Higgs boson Genomic epidemiology We said that at the rate physicists were col- This year has shown that whole-genome sequencing of infectious bacteria lecting data with the world’s biggest atom can help scientists understand and even control disease outbreaks. smasher, the Large Hadron Collider, it was Researchers used the technique to discover how Clostridium diffi - “all but a mathematical certainty” that they cile spread went on a rampage in hospitals around the world and would either fi nd the long-sought Higgs boson or rule out to track outbreaks of resistant Staphylococcus aureus and Klebsiella its existence. It appears that physicists have bagged their pneumoniae bacteria within a single hospital; in the last two cases, they prize (see p. 1524). Nature was generous. Math works. think their genomic sleuthing may have saved lives. Downloaded from

Faster-than-light neutrinos Treating intellectual disability As suggested, last year’s claim that particles called neutrinos travel faster As we predicted, in 2012 animal studies turned up more potential targets than light fell apart—but in an unexpectedly spectacular way. Physi- for reversing cognitive and behavioral symptoms in autism and related dis- cists had reported that neutrinos were making the 730-kilometer trip orders. And clinical trials continued, with researchers reporting from CERN in Switzerland to the OPERA particle detector in Italy 60 encouraging fi ndings with arbaclofen and bumetanide, drugs nanoseconds faster than they should at light speed. This February, that enhance certain effects of the neurotransmitter GABA, however, they found that the time discrepancy had been caused by in people with fragile X syndrome and autism, respectively. a loose cable connection. In March, two leaders of the 200-member Closely watched clinical trials for fragile X with mGluR5 antag- OPERA team stepped down after a vote of no confi dence. onists, which inhibit a receptor for glutamate, another neurotransmitter, should release fi ndings in 2013. (6109) 338 Stem-cell metabolism , Scientists made progress this year in understanding the Curiosity to Mars SCIENCE way stem cells use energy and the molecules needed The Mars Science Laboratory has indeed proved worth watching. , for cell function as they differentiate into various tis- Its “7 minutes of terror” descent through the martian atmo- ET AL. sues. They uncovered more details about how metabo- sphere ended in a safe, spot-on landing (see p. 1529) fol- lism infl uences the reprogramming of mature cells into lowed by—so far—months of productive scientifi c work by embryolike ones. It’s also increasingly clear that the metabolism of the Mini Cooper–sized Curiosity rover. Who could ask for more? CREDIT: HAYASHI HAYASHI CREDIT:

1532 21 DECEMBER 2012 VOL 338 SCIENCE www.sciencemag.org Published by AAAS BREAKTHROUGH OF THE YEAR 2012 | NEWSFOCUS

A YEAR ON, the h5n1 debate remains infectious, with no end in sight

Fiasco. Essential. Inevitable. voluntary, temporary moratorium on H5N1 experiments that might on December 25, 2012 Those are just a few of the words that scientists and national security make the virus more dangerous to humans. And some asked NSABB experts have used to describe the global controversy that engulfed infl u- to reconsider its recommendation. In March, it did—and a majority of enza researchers this year. The drama began in late 2011 after two sci- the members changed their minds, in part because they learned that ence teams showed how to make the H5N1 avian infl uenza virus—which Fouchier’s virus was less lethal than originally believed. Some were also typically kills birds—transmissible among mammals, potentially open- encouraged by the release of a new U.S. policy designed to help funders ing the door to a deadly human pandemic. Some say the storm—which is and scientists spot problematic dual-use studies before they begin— still far from over—has exposed long-standing fl aws in efforts to prevent potentially heading off future confl icts. With NSABB’s blessing in hand,

dangerous agents from escaping from unsafe laboratories or falling into Science and Nature fi nally published the studies. www.sciencemag.org the hands of terrorists, and highlighted the need for tighter oversight of The end of story, however, isn’t settled. The voluntary morato- “dual-use” research that can be used for good and evil. But others fear rium on H5N1 research—which was originally planned to last just the episode is fueling a regulatory overreaction that could harm inter- 60 days—is still in place with no end in sight. A long-promised follow-up national collaboration and put an end to U.S. funding for potentially to the March dual-use policy, designed to help U.S. university offi cials valuable science. implement the rules, has yet to appear. And this month, U.S. offi cials There’s one thing that all sides appear to agree on: Nobody wants to introduced a new plot line, unveiling draft guidelines that would bar repeat the highly publicized meltdown that sowed confusion and conten- government funding for H5N1 studies that would enable the virus to gain tion among scientists, government offi cials, the media, and the public. functions, such as the ability to easily infect humans, which might not Downloaded from “In many ways, it’s been a debacle,” Anthony Fauci, head of the U.S. naturally evolve. The rules could also require such “gain-of-function” National Institute of Allergy and Infectious Diseases, told Science earlier studies to be kept secret. this year. Not surprisingly, that draft is getting a mixed reception from Fauci should know. His agency funded the two controversial stud- researchers, with some worrying that it will end U.S. funding for a whole ies, which raised dual-use concerns after the results were submitted subset of possibly useful studies. Meanwhile, even supporters of such to Nature and Science. As word leaked out, researchers helped fan the controls say they’ll have only a limited effect if other nations don’t fl ames when an author of one the studies—virologist Ron Fouchier of adopt similar rules. “This is a global issue—lots of laboratories can do Erasmus MC in Rotterdam—told reporters from Science and other out- this type of research, and the U.S. can’t be effective acting alone,” says lets that his team had engineered a virus that might kill millions. Such microbiologist and biosecurity expert Ronald Atlas of the University of suggestions ultimately helped persuade the U.S. National Science Advi- Louisville in Kentucky. sory Board for Biosecurity (NSABB), which advises the government on the The end result: More than a year after the H5N1 controversy erupted, security risks associated with biological research, to recommend against there is still no clear international consensus on which kinds of stud- fully publishing the studies. ies are worth the risk, or how potentially dangerous results should be That recommendation did little to quell the debate, however, with reviewed or safely communicated to the public and public health experts. some scientists calling it misguided while others argued that it didn’t Until the confusion clears, experts warn, more messy public battles over go far enough. The New York Times even called on the government to fi nding the right balance between science and security are probably, destroy the “doomsday” virus and halt funding for similar research. well, inevitable. To help ease fears, in January influenza researchers announced a –DAVID MALAKOFF CREDIT: CDC CREDIT:

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JUNE

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

JANUARY Bethesda, Maryland: The National Washington, D.C.: U.S. government Institutes of Health decides to revise announces rules designed to reduce the original design for the National risk of harmful consequences from Children’s Study after spending experiments using 15 pathogens nearly $800 million to plan the and toxins. monitoring of 100,000 children. APRIL Galapagos Islands: Centenarian Lonesome George, the last giant tor- toise in the Galapagos Islands, suc- cumbs to apparent heart failure.

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

Washington, D.C.: Obama admin- istration proposes dismantling Rio de Janeiro, Brazil: Lack of major Commerce Department and scatter- Paris: Contact is lost with Europe’s commitments dooms Rio+20 confer- on December 25, 2012 ing its scientiﬁ c components across Gran Sasso, Italy: Faulty wiring is 10-year-old Earth-observing satellite ence on sustainable development. the federal government. found to have caused the anomalous Envisat. faster-than-light neutrino results JULY announced in September 2011 by Washington, scientists in Italy. D.C.: Jim Yong Kim elected as MARCH ﬁ rst scientist/

physician to lead www.sciencemag.org Mariana Trench, the World Bank. Paciﬁ c Ocean: Filmmaker James MAY Cameron’s one- New Delhi: India celebrates going man sub dives 1 year without a case of polio; no to the bottom new cases reported in 2012. of Challenger Meyrin, Switzerland: Physicists at Deep, the ﬁ rst solo visit to Earth’s CERN report they’ve probably found Downloaded from London and Washington, D.C.: deepest domain. the Higgs boson, the particle that Flu researchers announce a 60-day conveys mass to other fundamental moratorium on risky H5N1 studies Washington, D.C.: U.S. Department particles. in a letter to Nature and Science. of Energy shelves $1.5 billion Long The moratorium remains in effect. Baseline Neutrino Experiment, asks London: U.K. government expects Fermilab for cheaper alternatives. to spend more than $100 million to FEBRUARY Amsterdam: Australia and South subsidize publication in open access Africa chosen as co-hosts for the journals of research it funds. $2 billion Square Kilometre Array.

Mongstad, Norway: Work begins on $1 billion carbon capture and storage facility, the largest such test site in the world. Bethesda: Reversing an earlier deci- Antarctica: A team of Russian sci- sion, the National Science Advisory Boston: Autopsies of four military Northeastern U.S.: One species of entists fi nishes drilling 3770 meters Board for Biosecurity approves publi- veterans fi nd signs of the same North American bats infected with through the Antarctic ice to reach cation of two controversial papers on neurodegenerative disease found white-nose syndrome fi ghts the

the surface of buried Lake Vostok. H5N1’s ability to trigger a pandemic. previously in U.S. football players. disease by hibernating alone. IMAGES; NADEEM OOZEER; RESEARCH INSTITUTE PRESSCERN; ANGELA SERVICE; GEORGE/WIKIMEDIA COMMONS; CDC; ESA; REX FEATURES/AP CDC; AP PHOTO/ARCTIC AND ANTARCTIC AGENCY; CREDITS (CHRONOLOGICAL): AP PHOTO/RUSSIAN ROSCOSMOC SPACE CONSERVATION OF ENVIRONMENTAL VON LINDEN/NEW YORK DEPARTMENT WIKIMEDIA COMMONS/MINGLEX; WIKIMEDIA COMMONS; CERN; RYAN

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Washington, D.C.: New U.S. law is Kyoto, Japan: Alaska: Shell begins exploratory NOVEMBER expected to funnel up to $20 billion Mathematician oil drilling in Alaska’s Chukchi in BP civil fi nes from the 2010 Gulf Shinichi Mochizuki Sea, the fi rst in more than oil spill to restoration and research. invites colleagues 2 decades. But technical problems to poke holes in cut the project short. Washington, D.C.: Two studies his proof of the published in Science failed to fi nd abc conjecture. OCTOBER arsenic in bacterial DNA, refuting controversial work reported in 2010. SEPTEMBER

Hinxton, U.K.: Results from the Sacramento: California’s cap-and- Encyclopedia of DNA elements trade program, the broadest in the (ENCODE) project identifying a nation, began auctioning permits to high percentage of human DNA businesses in an effort to regulate with some functionality generate release of greenhouse gases. praise and controversy. Washington, D.C.: BP to pay L’Aquila, Italy: Six scientists and a $2.5 billion for research and resto- Phnom Penh: A mysterious syn- government offi cial are found guilty ration efforts as part of guilty plea drome that killed dozens of chil- of manslaughter and sentenced in criminal case from oil spill. dren is identifi ed as hand, foot, and to 6 years in prison for making mouth disease after patients test reassuring statements before a Brussels: The European Commis- positive for Enterovirus 71. deadly April 2009 earthquake. sion’s approval to market Glybera to treat a rare disease called lipo- Tokyo: Panel fi nds that anesthesi- Livermore, California: National protein lipase defi ciency makes it ologist Yoshitaka Fujii fabricated a Ignition Facility fails to meet its the fi rst gene therapy drug in the on December 25, 2012 record-setting 172 papers. own deadline for achieving a self- Western world. sustaining fusion reaction. AUGUST Tilburg, the Saudi Arabia and Qatar: Two Netherlands: Bethesda: The National Heart, cases, one fatal, of a new corona- Investigators Lung, and Blood Institute launches virus related to SARS triggers say social psy- massive clinical trial to test whether worries about a wider outbreak. chologist

blocking infl ammation can prevent Diederik Stapel www.sciencemag.org heart disease. Hyderabad, India: The U.N. has committed Convention on Biological Diversity fraud in at least announces a doubling, to 55 of his 137 papers. $10 billion a year, of aid to developing countries by 2015. Cape Town: Disappointing results from fi rst phase III trial of a Cambridge, U.K.: First articles malaria vaccine dim prospects for appear in eLife, a new open access RTS,S vaccine. Downloaded from Hunan province, China: In a journal backed by the Howard Hughes nationwide uproar, critics say that a Medical Institute, the Wellcome Trust, DECEMBER U.S.-funded study involving geneti- and the Max Planck Society. cally modifi ed (GM) golden rice used Pasadena, California: NASA’s Chinese children as guinea pigs. Curiosity rover lands safely on Mars and begins 2-year mission.

Tokyo: Scientists complete technical design for proposed International Linear Collider, a $10 billion facility Austin: Nobelist Alfred Gilman that Japan hopes to host. Indianapolis and New York: Long- Caen, France: Study claiming that resigns from $3 billion Cancer awaited clinical trial results for GM maize causes tumors and early Prevention and Research Institute Brussels: E.U. offi cials endorse bapineuzumab and solanezumab death in rats generates headlines— of Texas along with dozens of peer a unifi ed patent system that they fail to show cognitive benefi ts for and widespread criticism from food reviewers to protest agency’s peer hope will take effect in 25 countries

CREDITS (CHRONOLOGICAL): AP PHOTO/HENG SINITH; NASA IMAGES; AP PHOTO/SETH WENIG; COURTESY OF SHINICHI MOCHIZUKI; DAMIEN JEMISON/LLNL; INTERNATIONAL RICE RESEARCH INSTITUTE/WIKIMEDIA SHINICHIOF MOCHIZUKI;INTERNATIONAL DAMIEN JEMISON/LLNL; CREDITS (CHRONOLOGICAL): SINITH;AP PHOTO/HENG NASA IMAGES; AP PHOTO/SETH WENIG; COURTESY COMMONS; MIKESJOURNAL © AUGUST 2006; REY.HORI/KEK UNIVERSITY; TILBURG COMMONS; WIKIMEDIA AGENCY; KATZ/LIAISON SHELLEY COMMONS; WIKIMEDIA IMAGES; AFP/GETTY Alzheimer’s disease patients. safety agencies. review practices. in 2014.

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