News this Week

Science  20 Dec 2013:
Vol. 342, Issue 6165, pp. 1422
  1. Around the World

    1 - Silver Spring, Maryland
    FDA Tackles Farm Antibiotic Use
    2 - Sydney, Australia
    Port Plans Cast Shadow on Iconic Reef
    3 - Beijing
    China Scores Lunar Touchdown
    4 - Luxembourg
    Court Strikes Down GM Potato Approval

    Silver Spring, Maryland

    FDA Tackles Farm Antibiotic Use

    Treat with care.

    U.S. will limit livestock drugs.

    CREDIT: HUMANE SOCIETY OF THE UNITED STATES/WIKIMEDIA COMMONS

    In an effort to slow the evolution in farm animals of drug resistance, which could spread to humans, the U.S. Food and Drug Administration (FDA) last week announced changes in the use of antibiotics for livestock and poultry. It asked companies producing antibacterial drugs that it considers medically important to humans to voluntarily change their labels, removing claims of improved growth and feed efficiency.

    These antibiotics would then require prescriptions from a veterinarian, who could approve use for treating sick animals or preventing disease in those considered "at risk." FDA gives drug producers 3 years to make the change, and many companies support the plan.

    The American Society for Microbiology applauded the move in an e-mail, calling it "a major step to address antibiotic resistance comprehensively." But others doubt that voluntary action will be enough to protect public health. "The FDA may care whether companies call it growth promotion or disease prevention, but the bacteria do not," said Keeve Nachman, an environmental health scientist with the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, in a statement. http://scim.ag/FDAfarm

    Sydney, Australia

    Port Plans Cast Shadow on Iconic Reef

    The ecologically embattled Great Barrier Reef (GBR) may soon be host to one of the world's largest coal ports—if a proposed construction project gets the go-ahead from Australia's Marine Park Authority. Port construction would involve dredging at Abbot Point and dumping up to 3 million cubic meters of dredge spoils at an unspecified location within the GBR ecosystem, which is listed as a UNESCO World Heritage Site. Federal Environment Minister Greg Hunt approved the project on 10 December, but because it falls within the marine park boundary, a park authority permit is required.

    "The development would clearly damage the health of the GBR," asserts fisheries veterinarian Matt Landos of the University of Sydney. He says "lessons have not been learnt" from the 2010 to 2011 dredging south at Gladstone Harbour, which released toxic metals from the seabed, caused outbreaks of fish disease, and killed dolphins and turtles.

    UNESCO warned earlier this year that further gas and coal development could put the reef on the "in danger" list. No decision had been made as Science went to press.

    Beijing

    China Scores Lunar Touchdown

    Ready to rove.

    China's Yutu rover on the moon.

    CREDIT: AN XIN/IMAGINECHINA VIA AP PHOTO

    After a 12-day voyage, China's lunar probe Chang'e-3 landed at the Sea of Rains (also known as Mare Imbrium) in the moon's northern hemisphere on 14 December. The event, broadcast live on national television, was the first soft landing on the moon in 37 years.

    "Everything has gone fantastically well," says Wu Ji, director of the National Space Science Center in Beijing. "The lander kicked up much less dust than expected." The Communist Party hailed the mission as a "new glory" of the Chinese people.

    After 8 hours charging up with the spacecraft's solar panels, the rover Yutu (Jade Rabbit) rolled down the lander's ramp and onto the moon's surface. "It was quite nerve-racking," says Jia Yang, the spacecraft's deputy chief engineer at the Beijing Institute of Spacecraft System Engineering. He says that Yutu is taking a "nap" now to avoid damage from the scorching lunar heat. It will then start its 3-month mission exploring the composition of the lunar surface and crust.

    Luxembourg

    Court Strikes Down GM Potato Approval

    Hot potato.

    A 2010 protest in Germany against genetically modified potatoes.

    CREDIT: WIKIMEDIA COMMONS

    In another setback for genetically modified (GM) crops in the European Union, the General Court last week annulled the authorization to grow and sell a GM potato called Amflora. The ruling won't affect the potato's cultivation or sale, because its manufacturer withdrew from the European market last year. But it may hinder the approval of a GM maize variety, which the European Commission tried to drive forward last month after a lengthy deadlock.

    The potato is engineered to produce a starch used in paper pulp, glue, and animal feed. Based on advice from the European Food Safety Authority, the European Commission authorized it in March 2010. But it did not submit the final decision to the relevant committee of member states' representatives. Hungary challenged that decision in court, with support from Austria, France, Luxembourg, and Poland.

    Environmental groups are now calling on the commission to withdraw its proposal to approve Pioneer's GM maize 1507, which they say followed a similarly flawed procedure. A commission spokesman says its legal services will analyze the ruling and its possible consequences. http://scim.ag/GMannul

  2. Random Sample

    By the Numbers

    80%—Proportion of data from publicly funded research that's inaccessible 20 years after publication thanks to problems such as old e-mail addresses and obsolete storage devices, according to a study in Current Biology this week. http://scim.ag/datalost

    They Said It

    "They should make at least a fraction of what some Wall Street trader makes."

    —Billionaire entrepreneur Yuri Milner at an award ceremony for winners of the Breakthrough Prizes in Physics and Life Sciences, where he announced a new $3 million prize for mathematics.

    A Makeover for Big Screen Dinos

    CREDIT: COURTESY OF TWENTIETH CENTURY FOX

    The world of Patchi the Pachyrhinosaurus is no Jurassic Park. The computer-animated protagonist of the new movie Walking with Dinosaurs inhabits a fictional land informed by recent science. That's the verdict from paleontologist Steve Brusatte of the University of Edinburgh in the United Kingdom, who was among a handful of dino consultants on the film.

    As a budding scientist, Brusatte was enraptured by the original Walking with Dinosaurs, a 1999 BBC miniseries that inspired the current movie reimagining. "When I look at the film, I'm very happy with how they portrayed the dinosaurs," he says. "The point of the film isn't to present new science, but it incorporated new science to tell the story."

    That story follows Patchi as he grows from a punchy underdog of a hatchling to an unlikely leader of his migrating herd. Viewers accustomed to the traditional "scaly lizard" image may find the feathery meat-eating dinosaurs jarring. And the volatile environment of the Late Cretaceous, just a few million years before the dino-obliterating asteroid, adds to the drama, as characters struggle to survive in a world of wildfires, volcanic eruptions, and fluctuating temperatures and sea levels. The parental care lavished upon young Patchi and the communal lifestyle of his herd also find support in the fossil record, Brusatte says. All in all, sticklers for scientific accuracy will be pleased, he predicts—provided they can "get beyond the fact that these things are talking."

    ScienceLIVE

    We will return on Thursday, 9 January, at 3 p.m. EST for a live chat with experts on preserving threatened large carnivores to stabilize ecosystems. http://scim.ag/science-live

  3. Newsmakers

    Three Q's

    Bourguignon

    CREDIT: © JEAN-FRANÇOIS DARS

    The European Commission announced this week that French mathematician Jean-Pierre Bourguignon will be the new president of the European Research Council (ERC), the European Union's main funding agency for basic research. After 19 years directing the Institute of Advanced Scientific Studies in Paris, Bourguignon joins the agency at the dawn of the European Union's new 7-year research program, Horizon 2020, which will dramatically increase ERC's budget.

    Q:Why did you decide to take the job?

    J.-P.B.:[One reason] is that I'm a very convinced European. If you ask scientists what the greatest success for science in the European Union is, many will say: the ERC. So being involved in that was very natural to me.

    Q:Will you make changes in ERC's existing grants?

    J.-P.B.:There have been two rounds of Synergy Grants [a grant for small interdisciplinary groups of researchers that started in 2012]. What I have seen from the outside doesn't give me a very good impression of it. … So this program needs to be reviewed very, very carefully.

    Q:What do you tell those countries that have fared poorly in the competition for grants?

    J.-P.B.:The answer isn't obvious at all. Sometimes the level of science [in a country] just isn't high enough; then that has to be addressed in itself. But we must absolutely not go to the situation where every country gets out of the ERC what they put into it—the principle of juste retour, as the French call it. That would be the worst idea. Extended interview at http://scim.ag/BourgERC.

  4. Cancer Immunotherapy

    1. Jennifer Couzin-Frankel

    This year marks a turning point in cancer, as long-sought efforts to unleash the immune system against tumors are paying off—even if the future remains a question mark.

    Domino effect.

    One such treatment, with the antibody in pink at the top, works by blocking a protein receptor, in purple, on a T cell. That sets off a chain reaction that allows T cells to target a tumor cell (bottom left).

    History's path is unchartable when it's not yet past but present, when we are still standing in the middle of it. That's what made Science's selection of this year's Breakthrough of the Year such a topic of internal debate, even anxiety. In celebrating cancer immunotherapy—harnessing the immune system to battle tumors—did we risk hyping an approach whose ultimate impact remains unknown? Were we irresponsible to label as a breakthrough a strategy that has touched a tiny fraction of cancer patients and helped only some of them? What do we mean when we call something a breakthrough, anyway?

    Ultimately, we concluded, cancer immunotherapy passes the test. It does so because this year, clinical trials have cemented its potential in patients and swayed even the skeptics. The field hums with stories of lives extended: the woman with a grapefruit-size tumor in her lung from melanoma, alive and healthy 13 years later; the 6-year-old near death from leukemia, now in third grade and in remission; the man with metastatic kidney cancer whose disease continued fading away even after treatment stopped.

    As the anecdotes coalesce into data, there's another layer, too, a sense of paradigms shifting. Immunotherapy marks an entirely different way of treating cancer—by targeting the immune system, not the tumor itself. Oncologists, a grounded-in-reality bunch, say a corner has been turned and we won't be going back.

    With much pressure these days to transform biological insights into lifesaving drugs, there's a lesson to be learned from immunotherapy's successes: They emerged from a careful decoding of basic biology that spanned many years. The early steps were taken by cancer immunologist James Allison, now at the University of Texas MD Anderson Cancer Center in Houston. In the late 1980s, French researchers who weren't thinking about cancer at all identified a new protein receptor on the surface of T cells, called cytotoxic T-lymphocyte antigen 4, or CTLA-4. Allison found that CTLA-4 puts the brakes on T cells, preventing them from launching full-out immune attacks. He wondered whether blocking the blocker—the CTLA-4 molecule—would set the immune system free to destroy cancer.

    Allison's rationale was untested. He and his colleagues changed the conversation, in the words of one cancer researcher, "to consider immunosuppression as the focal point, and manipulation of immunosuppression as the target."

    Doing so took time. CTLA-4 was discovered in 1987. In 1996, Allison published a paper in Science showing that antibodies against CTLA-4 erased tumors in mice. Pharmaceutical companies shied away from cancer immunotherapy, wary of past flops but also of a strategy very unlike the standard zapping of a tumor. So the job of getting anti–CTLA-4 into people fell to a small biotechnology company, Medarex, in Princeton, New Jersey. In 1999, it acquired rights to the antibody, taking the leap from biology to drug.

    Arsenal.

    New antibody therapies, depicted here, are stimulating the immune system to destroy cancer cells.

    CREDIT: V. ALTOUNIAN/SCIENCE

    Crucial results didn't come for another 11 years. In 2010, Bristol-Myers Squibb—which had bought Medarex for more than $2 billion—reported that patients with metastatic melanoma lived an average of 10 months on the antibody, compared with 6 months without it. It was the first time any treatment had extended life in advanced melanoma in a randomized trial. Nearly a quarter of participants survived at least 2 years.

    The numbers for another antibody are so far even better and the side effects milder. In the early 1990s, a biologist in Japan discovered a molecule expressed in dying T cells, which he called programmed death 1, or PD-1, and which he recognized as another brake on T cells. He wasn't thinking of cancer, but others did. One, oncologist Drew Pardoll at Johns Hopkins University, met with a leader of Medarex at a Baltimore coffee shop. He urged the company to test an anti–PD-1 antibody in people.

    The first trial, with 39 patients and five different cancers, began in 2006. By 2008, doctors were jolted by what they saw: In five of the volunteers, all of them with refractory disease, tumors were shrinking. Survival in a few stretched beyond what was imagined possible.

    Still, understanding what these therapies were doing inside the body was a challenge. Other cancer treatments either work or they don't, and the answer is nearly instantaneous. With both anti–CTLA-4 and anti–PD-1, physicians saw some tumors grow before vanishing months later. Some patients kept responding even after the antibody had been discontinued, suggesting their immune system had been fundamentally changed. Some, particularly those on anti–CTLA-4, developed unnerving side effects, inflammation of the colon, for example, or of the pituitary gland. All of these were the fine points of a new template, one whose vagaries physicians were just beginning to understand. The learning curve would be steep.

    It was steep in another area of immunotherapy as well. For years, Steven Rosenberg at the National Cancer Institute had harvested T cells that had migrated into tumors, expanded them in the lab, and reinfused them into Tpatients, saving some with dire prognoses. The technique worked only when doctors could access tumor tissue, though, limiting its application.

    Then in 2010, Rosenberg published encouraging results from so-called chimeric antigen receptor therapy, or CAR therapy—a personalized treatment that involves genetically modifying a patient's T cells to make them target tumor cells. One group, led by Carl June at the University of Pennsylvania, began reporting eye-catching responses to CAR therapy: patients with pounds of leukemia that melted away. At a meeting in New Orleans this month, June's team and another at Memorial Sloan-Kettering Cancer Center in New York reported that the T cell therapy in their studies put 45 of 75 adults and children with leukemia into complete remission, although some later relapsed. CAR therapy is now the focus of numerous clinical trials. Researchers hope that it, like the antibodies, can target an assortment of cancers.

    Engineered T cells are still experimental, but the antibodies are slowly going mainstream. At least five major drug companies, their early hesitancy gone, are developing antibodies such as anti–PD-1. In 2011, the U.S. Food and Drug Administration approved Bristol-Myers Squibb's anti–CTLA-4 treatment, called ipilimumab, for metastatic melanoma. The cost is high: The company charges $120,000 for a course of therapy. In 2012, Suzanne Topalian of Hopkins, Mario Sznol of Yale University, and their colleagues reported results for anti–PD-1 therapy in nearly 300 people, and they provided an update earlier this year. Tumors shrunk by about half or more in 31% of those with melanoma, 29% with kidney cancer, and 17% with lung cancer.

    This year brought even more encouragement. Bristol-Myers Squibb reported this fall that of 1800 melanoma patients treated with ipilimumab, 22% were alive 3 years later. In June, researchers reported that combining ipilimumab and anti–PD-1 led to "deep and rapid tumor regression" in almost a third of melanoma patients. Drugs blocking the PD-1 pathway have not yet been proven to extend life, although survival rates so far have doctors optimistic that they do.

    For physicians accustomed to losing every patient with advanced disease, the numbers bring a hope they couldn't have fathomed a few years ago. For those with metastatic cancer, the odds remain long. Today's immunotherapies don't help everyone, and researchers are largely clueless as to why more don't benefit. They are racing to identify biomarkers that might offer answers and experimenting with ways to make therapies more potent. It's likely that some cancers will not yield to immunotherapy for many years, if ever.

    Even in the fluid state oncology now finds itself, this much is certain: One book has closed, and a new one has opened. How it will end is anyone's guess.

  5. 2013 Runners-Up

    Genetic Microsurgery for the Masses

    A gene-editing technique called CRISPR touched off an explosion of research in 2013, leading Science's editors to name it a runner-up for the 2013 Breakthrough of the Year.

    Molecular scalpel.

    To home in on the right DNA, the Cas9 protein links up with guide RNA that has a target-specific sequence. Once attached, Cas9 has two active sites that cut the DNA in the right place.

    CREDIT: K. SUTLIFF/SCIENCE

    In the 1920s, the introduction of a microscope into the operating room touched off a revolution in surgical procedures. Suddenly, doctors could fix ears, blood vessels, and other parts of the human body with exhilarating precision and ease. Now, biologists operating on the genome are gaining similar abilities, thanks to a bacterial protein called Cas9. That protein, coupled with RNA designed to home in on specific DNA sequences, gives researchers the equivalent of a molecular surgery kit for routinely disabling, activating, or changing genes.

    This technology, called CRISPR, has become red hot in the past year, with more than 50 publications in 10 months. One CRISPR “how-to” website now attracts about 900 visitors each day. Since January, more than a dozen teams have manipulated specific genes in mice, rats, bacteria, yeast, zebrafish, nematodes, fruit flies, plants, and human cells, paving the way for understanding how these genes function and possibly harnessing them to improve health. One team even reported using the approach to disable HIV hiding in T cells. CRISPR also has the potential of modifying multiple genes simultaneously, and it simplifies the job of making mouse models of disease.

    Such genetic microsurgery was a dream a decade ago. Researchers could not readily control where an added gene would insert itself into a genome or which DNA would be deleted in so-called knockout experiments. That changed about 10 years ago, when labs began studying proteins called zinc finger nucleases. Their composition dictated which DNA sequence was cut, allowing researchers to cut DNA at will. Zinc fingers proved difficult to make. Then, just as that technology was beginning to take hold, another approach, based on a plant pathogen, provided an easier alternative. The rush to harness that system, called TALENs (for transcription activator-like effector nucleases), prompted Science to recognize genome editing as one of the major achievements of 2012.

    CRISPR, which stands for clustered regularly interspaced short palindromic repeats, takes genome editing to the next level. The name comes from repetitive stretches of DNA that bacteria have evolved as part of an adaptive immune system against viruses called bacteriophages. To fight these viruses, bacteria link the protein Cas9 to RNA that matches the virus's genome. The complex cuts the viral DNA, disabling it. In 2012, researchers first used labmade CRISPR complexes for genome editing in a test tube. Others immediately recognized CRISPR's potential. With TALENs or zinc finger nucleases, each new gene targeted requires a custom protein be built. CRISPR substitutes RNA—which is simpler to make than a piece of a protein—for the DNA-targeting section.

    Researchers are eagerly tinkering with CRISPR technology; they are modifying the Cas9 protein so that it nicks instead of cuts the DNA. Biochemists are also working out the structures of the Cas9 complexes. And a few labs are exploring whether other Cas proteins might work better than Cas9. To take CRISPR from basic research to medicine—harnessing it to fix a broken gene or disable a bad one, for example—researchers must show that each CRISPR construct hits only its target and no others. For now, CRISPR RNA will sometimes latch on to DNA that doesn't exactly match up. But CRISPR researchers are already finding ways to sharpen their targeting.

    Both CRISPR and TALENs were unanticipated outcomes of basic research unrelated to genome editing. So CRISPR could easily be displaced by an even slicker genome-editing tool. But for now, with companies forming and new studies coming out practically every week, the CRISPR craze is in full swing.

  6. 2013 Runners-Up

    CLARITY Makes It Perfectly Clear

    A new brain-imaging technique that turns brain tissue transparent made the short list of runners-up for Science's Breakthrough of the Year.

    Crystal clear.

    A new method of making tissue transparent will help neuroscientists explore the postmortem brain in 3D.

    CREDIT: KWANGHUN CHUNG AND KARL DEISSEROTH/HOWARD HUGHES MEDICAL INSTITUTE/STANFORD UNIVERSITY

    A new window on the brain opened this year, promising to fundamentally change the way labs study the intricate organ. Called CLARITY, it turns brain tissue as transparent as glass by removing the fatty, light-scattering lipid molecules that form cellular membranes. CLARITY replaces the lipids with molecules of a clear gel but leaves all neurons, other brain cells, and their organelles intact, putting the intricacies of the brain on display.

    Previous attempts to create see-through brains rendered them too fragile to work with, but CLARITY leaves tissue sturdy enough for scientists to infiltrate it repeatedly with labels for specific cell types, neurotransmitters, or proteins; wash them out; and image the brain again with different labels. Researchers say the advance could speed up by 100-fold tasks such as counting all the neurons in a given brain region and could make traditional methods of imaging postmortem brain tissue irrelevant. At present, however, the technique is limited to small amounts of tissue: Just clarifying a 4-mm-diameter mouse brain takes about 9 days.

  7. 2013 Runners-Up

    Human Cloning at Last

    Researchers announced they had derived stem cells from cloned human embryos, a long-awaited research coup that Science's editors chose as a runner-up for Breakthrough of the Year.

    Long-sought.

    Cloned human embryos, which can be used to make patient-specific stem cell lines.

    CREDIT: OREGON HEALTH & SCIENCE UNIVERSITY

    After more than a decade of failed attempts, it finally worked. This year, researchers announced that they had cloned human embryos and used them as a source of embryonic stem (ES) cells—a long-cherished goal. Able to develop into any tissue while providing a perfect genetic match to the cell that was cloned, the ES cells could prove a powerful tool for research and medicine. However, concerns about destroying embryos and the emergence of a cheaper, easier rival technique might keep human cloning for stem cells from becoming standard practice.

    The cloning technique, called somatic cell nuclear transfer (SCNT), is the same one used to clone Dolly the sheep 17 years ago. Scientists remove the nucleus from an egg cell and then fuse the remaining cell material with a cell from the individual to be cloned. They then give the fused cell a signal to start dividing, and when things go right an embryo develops. Scientists have used SCNT to clone mice, pigs, dogs, and other animals, but human cells proved trickier to work with. Years of trying—and a high-profile fraud—yielded nothing more than a few poor-quality embryos, unable to produce ES cells.

    At the Oregon National Primate Research Center in Beaverton, however, researchers finally cloned monkey embryos and derived ES cells from them in 2007. In the process, they discovered a number of tweaks that made SCNT more effective for primate cells, including human ones. The final recipe worked surprisingly well, yielding ES cells in about one in 10 tries. One key ingredient seems to be caffeine, which appears to help stabilize key molecules in the delicate human egg cells.

    How important the technique will be in the long run is an open question. In the years since human cloning was first attempted, researchers found that they can make patient-specific stem cells by "reprogramming" adult cells into induced pluripotent stem (iPS) cells. That method, which scientists adapted to human cells in 2007, eliminated the need for human eggs and does not involve embryos, two aspects that make SCNT controversial and expensive. But some experiments have suggested that, at least in mice, ES cells from cloned embryos might be of better quality than iPS cells. Now, investigators will be able to compare the two types of human stem cells side by side.

    The feat also raises concerns about cloned babies. But that seems unlikely for now. Despite hundreds of tries, the Oregon researchers say, none of their cloned monkey embryos have established a pregnancy in surrogate females.

  8. 2013 Runners-Up

    Dishing Up Mini-Organs

    In research that Science's editors chose as a runner-up for Breakthrough of the Year, scientists coaxed cells called pluripotent stem cells to grow into tiny "organoids"—liver buds, mini-kidneys, and even rudimentary human brains—in the lab.

    Self-organized.

    A cross section of a lab-grown mini-brain shows neural stem cells (red) and neurons (green).

    CREDIT: MADELINE A. LANCASTER

    Left alone in a lab dish, pluripotent stem cells run riot. They differentiate into a disorganized mass of tissues: beating heart cells, neurons, even hair and teeth. It's still a challenge to coax stem cells to grow into specific tissues, let alone into organized structures. This year, researchers did just that, in spectacular style, growing a variety of "organoids" in the lab: liver buds, mini-kidneys, and, most remarkably, rudimentary human brains.

    The brains, grown by Austrian researchers, differ in important ways from the real thing. Because they have no blood supply, they stop growing once they reach the size of an apple seed. Cells at the core, starved of oxygen and other nutrients, die off. But the organoids mimic developing human brains to a surprising degree, developing eye tissue and layers that, under the microscope, resemble those in the brain of an early human fetus.

    Inspired by previous work that had grown mini-guts from stem cells, the researchers began by encouraging human embryonic stem cells and induced pluripotent stem (iPS) cells to become neural stem cells. Then they suspended clumps of the cells in a gelatinous material called Matrigel and let them grow in a bioreactor, which rotates to help nutrients reach the cell clusters.

    To the scientists' surprise, after a few weeks they saw darker pigmented cells that seemed to resemble early eye development. On closer inspection, they found evidence that the organoids had developed layers identifiable as forebrain, midbrain, and hindbrain, all typical of fetal brains. They also saw evidence for an outer subventricular zone, which is present in human brains but not mouse ones.

    The mini-brains have already yielded insights into microcephaly, a condition in which the brain doesn't grow to its full size. When the team started with iPS cells derived from a microcephaly patient, the resulting organoids were smaller than normal because stem cells stopped dividing too soon. With further development, researchers hope to use the mini-brain technique to investigate other brain diseases.

  9. 2013 Runners-Up

    Cosmic Particle Accelerators Identified

    This year, astronomers traced high-energy particles called cosmic rays back to their birthplaces in the debris clouds of supernovae—a feat that Science's editors chose as a runner-up for Breakthrough of the Year.

    Boom!

    Supernova remnants such as the Jellyfish Nebula can boost particles to enormous energies.

    CREDIT: NASA/DOE/FERMI LAT COLLABORATION, TOM BASH AND JOHN FOX/ADAM BLOCK/NOAO/AURA/NSF, JPL-CALTECH/UCLA

    For decades, physicists thought they knew where many of the immensely energetic protons and atomic nuclei that whiz in from space as cosmic rays get their start: in the wreckage of exploded stars, or supernovas. Now they're sure. This year, researchers with NASA's orbiting Fermi Gamma-ray Space Telescope produced the first direct evidence of such particles revving up in cloudlike supernova remnants within our galaxy.

    When a star explodes, material ejected from it crashes into a tenuous sea of gas between the stars. That interstellar medium is so thin that few particles collide directly. However, particles from the supernova can rebound off magnetic fields in space, twisting them up to form a lingering collisionless shock that slingshots other particles to higher energies. In the late 1970s, theorists realized that as protons and nuclei circulate repeatedly through such a shock, they may accelerate to colossal energies—hundreds of times higher than particle accelerators have reached.

    But tracing cosmic rays to supernova remnants hasn't been easy. Because they're electrically charged, protons and nuclei swirl in interstellar magnetic fields. So by the time they reach Earth, cosmic rays do not point back to their birthplaces. The Fermi team had to find another way to show that supernova remnants accelerate the particles.

    If protons are accelerated in a supernova remnant, then a few proton-proton collisions should still occur. Such collisions produce fleeting particles called pi-zero mesons, each of which quickly decays into a pair of high-energy photons. Those pi-zero decays should then produce a telltale hump in the energy spectrum of photons from a supernova remnant, when it's plotted in a particular way. After 5 years of collecting data, Fermi researchers spotted that signature of proton acceleration in two supernova remnants. They had to tease it out of the overwhelming glare of photons that ricochet off high-energy electrons, which do not have such a spectral bump. Others had looked for the signature, but Fermi is the first experiment to see it clearly.

    Astrophysicists still don't know many details of how the particles and magnetic fields interact, and they suspect that the highest energy cosmic rays originate from other sources outside our galaxy. Still, there's now no doubting that supernova remnants do indeed spew cosmic rays.

  10. 2013 Runners-Up

    Newcomer Juices Up the Race to Harness Sunlight

    Up-and-coming solar cell materials called perovskites made such rapid progress this year that the editors of Science picked them as a runner-up for Breakthrough of the Year.

    Sunny side up.

    Solar cell materials known as perovskites burst on the scene promising cheap, high-efficiency solar power.

    CREDIT: PIRANHA PHOTOGRAPHY/OXFORD PHOTO

    A rising star lit up the world of solar power research this year. Cheap, easy-to-make crystals called perovskites proved capable of converting more than 15% of the energy in sunlight to electricity. That's up from 3.8% just 4 years ago, and it's already better than a couple of other solar cell technologies that researchers have been working on for decades.

    Perovskite solar cells still lag behind the silicon panels that dot rooftops worldwide. Those typically achieve about 20% efficiency, and the best performers in research labs reach 25%. But silicon solar cells and other high-performance solar materials rely on semiconductors that must be grown at high temperatures in expensive fabrication facilities. Not so with perovskites. The versions used for solar cells thus far are made simply by mixing inexpensive precursor compounds in solution and then drying them on a surface. Surprisingly, this procedure produces perovskites with such high crystalline quality that two groups reported using them to make lasers, an application for which near-perfect crystals are de rigueur.

    Crystalline quality is central to a solar cell's ability to produce power. When sunlight strikes a cell, it energizes electric charges. This propels them through the material to the electrodes, where they are collected and sent through wires as an electric current. Defects in semiconductor crystals act as speed traps. Perovskites offer a cheap route to fewer traps.

    But perhaps the best news about perovskite solar cells is that it may be possible to integrate them with conventional silicon solar cells, layering the newbies right on top of silicon panels. Perovskites excel at snagging the higher energy photons in sunlight—the blues and greens—while silicon does better at grabbing the lower energy red and infrared photons. So putting the two together in a hybrid could achieve an efficiency of as much as 30%. Solar researchers around the globe are racing to marry the two materials.

    They're also coping with potential problems. Solar cell perovskites are fragile and readily break down when exposed to water or air. The current varieties also contain lead, an environmental toxin. To make a viable technology, researchers will have to find ways to encapsulate the materials, and find safer replacements. If the rapid progress so far can be sustained, perovskites' star has only begun to rise.

  11. 2013 Runners-Up

    To Sleep, Perchance to Clean

    In work that Science's editors named a runner-up for Breakthrough of the Year, researchers studying mice have found experimental evidence that sleep helps to restore and repair the brain.

    Brainwashing.

    Fluid-filled channels (pale blue) between neurons expand and flush out waste while mice sleep.

    CREDIT: JEFF ILIFF AND MAIKEN NEDERGAARD

    Why do we sleep? Questions of biology don't get much more fundamental than that. This year, neuroscientists took what looks like a major stride toward an answer.

    Most researchers agree that sleep serves many purposes, such as bolstering the immune system and consolidating memories, but they have long sought a "core" function common to species that sleep. By tracking colored dye through the brains of sleeping mice, scientists got what they think is a direct view of sleep's basic purpose: cleaning the brain. When mice slumber, they found, a network of transport channels through the brain expands by 60%, increasing the flow of cerebral spinal fluid. The surge of fluid clears away metabolic waste products such as β amyloid proteins, which can plaster neurons with plaques and are associated with Alzheimer's disease.

    Until this discovery, researchers thought the brain's only way to dispose of cellular trash was to break it down and recycle it inside cells. If future research finds that many other species undergo this cerebral housekeeping, it would suggest that cleaning is indeed a core function of sleep. The new findings also suggest that sleep deprivation may play a role in the development of neurological diseases. But with a causal role far from certain, it's too early for anyone to stay awake worrying.

  12. 2013 Runners-Up

    Your Microbes, Your Health

    Researchers have found that bacteria living inside the human body play vital roles in determining how the body responds to challenges as different as malnutrition and cancer—a realization that Science's editors named a runner-up for Breakthrough of the Year.

    Gut sense.

    Microbes may be key players in malnutrition and other aspects of health.

    CREDIT: LYLE CONRAD/CDC

    One hundred trillion cells bearing 3 million different genes—that's the roster of microbes that live inside your body. They're not just passengers; if animal studies hold up, these unseen multitudes profoundly affect the body's response to the environment, illness, and medical treatment. This year, researchers started pinpointing specific ways in which the microbiome promotes health and disease.

    • In 2008, nearly 300,000 infants in China got kidney stones from milk formula tainted with melamine, a plastics additive that was used illegally to bulk up the formula's apparent protein content. This year, scientists found that a bacterium may be to blame. A study showed that rats exposed to melamine developed fewer kidney stones when they were given antibiotics. The reason: The treated rats lacked Klebsiella, which converts melamine to a form that collects in the kidney. About 1% of infants carry Klebsiella—about the same percentage of infants on milk formula who got sick, suggesting this microbe may play a role in human toxicity as well.

    • In Malawi, researchers studied unusual cases in which one twin developed a malnutrition syndrome called Kwashiorkor but the other did not. They sampled the children's microbes for 3 years, tracking how the bacterial populations changed before, during, and after treatment with a nutritional supplement. They also implanted fecal material from each twin into the guts of germ-free mice and then monitored the animals over several weeks. Mice that received bacteria from the Kwashiorkor children developed Kwashiorkor-like symptoms; other mice did not. The researchers discovered that the malnourished children's microbial portfolio had not matured properly. As a result, they suggest, the children were less able to process amino acids containing sulfur and thus were more prone to malnutrition.

    • This year, researchers traced several links between gut microbes and cancer. Three anticancer therapies proved to need gut bacteria to be effective; the bacteria help prime the immune system to respond to drug treatment. A mouse study showed that a liver cancer often associated with obesity can arise because of a DNA-damaging bacterial byproduct that builds up in obese mice. Finally, new results confirmed earlier hints that a gut bacterium called Fusobacterium plays a role in stimulating colorectal tumors.

    • In a study of obese mice, the animals lost weight and had better insulin control—even on a high-fat diet—when researchers boosted the amount of the mucus-eating gut bacterium Akkermansia muciniphila in their guts. Obese mice, as well as obese people and people with type 2 diabetes, typically have reduced numbers of these bacteria. The same bacterium also seems to play a role in the weight loss that accompanies gastric bypass surgery.

    The year also saw more tantalizing hints of microbial influences on immune system function. The autoimmune disease rheumatoid arthritis, for example, may be associated with a bacterium called Prevotella copri. In mice, increases in the bacterium Lactobacillus johnsonii in the gut account for much of the protection against allergies and asthma provided by exposure to indoor/outdoor dogs and, to a lesser extent, cats.

    The studies make it increasingly clear that personalized medicine will need to take our microbial guests into account to be most effective.

  13. 2013 Runners-Up

    In Vaccine Design, Looks Do Matter

    In work that Science ranked as a runner-up for Breakthrough of the Year, researchers used structural biology—the study of the molecules of life—to design the key ingredient of a vaccine against a dangerous childhood disease.

    Packed punch.

    The RSV F protein best displays the red area needed to trigger potent antibodies in its coiled state (left) before fusing with a cell.

    CREDIT: JASON MCLELLAN/NIAID VACCINE RESEARCH CENTER

    For decades, researchers have hoped that structural biology—the near-atom-level study of the molecules that make up living organisms—would help them design better vaccines. This year, they finally found convincing proof that the approach can deliver big-time payoffs.

    Respiratory syncytial virus (RSV) hospitalizes millions of infants each year with pneumonia and other lung diseases, and it has defied many a vaccine developer. For children at high risk of developing severe RSV disease—which worldwide kills 160,000 kids each year—a monoclonal antibody on the market, palivizumab, can cut the risk of hospitalization in half. But palivizumab must be used repeatedly and costs nearly $1000 a dose, placing it far out of reach of many.

    Antibodies that have 10- to 100-fold more potency than palivizumab recently have been isolated, and in May, a research team at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) reported that it had crystallized one of them in action. The antibody binds to a protein on RSV's surface, dubbed F, that the virus employs to fuse with cells during the infection process. Using x-ray diffraction techniques to study the crystal structure of the bound antibody, the researchers mapped precisely where it attaches to the F protein. Other potent, novel antibodies allowed the team to analyze the vulnerable site on the F protein in even finer detail.

    In November, the same NIAID group described the next step: using the findings from their structural analyses to design an RSV F protein that could serve as an immunogen (the main ingredient of a vaccine). The F protein is like a jack-in-the-box: coiled up before it fuses with a cell and "sprung" afterward. The coiled, prefusion state best displays the vulnerable site. To teach an immune system to make potent antibodies, the researchers reasoned, a vaccine would have to contain the F protein locked into a prefusion configuration that features a full-monty view of the vulnerable site.

    The investigators engineered just such a prefusion F protein and injected it into animals. Their strategy was vindicated: The protein stimulated production of highly potent antibodies. Overnight, it became a leading candidate in the race to develop an RSV vaccine. It has yet to go into humans, but the NIAID researchers hope to have a product ready for testing in 18 months.

    Three other studies published this fall exploited similar strategies to design a vaccine for another intractable infection, HIV. By mapping antibody-binding sites on an HIV surface protein, researchers identified features that may be essential to a successful vaccine. They designed a novel, "near native" version of the surface protein that displayed those features to best advantage. The investigators still have yet to prove that their putative immunogen can stimulate antibodies capable of tripping up the myriad variants of HIV in circulation, but they hope to follow in the footsteps of the RSV colleagues, who tested many versions of their artificial proteins in animal experiments to find the best one.

    Now that structural biology has proven its value to vaccine design, many researchers hope the groundbreaking work will point the way toward vaccines for hepatitis C, dengue, West Nile, and other viruses that have perfected the art of dodging immune attack. Similar up-close-and-personal analyses of viruses might also reveal why so many viral diseases have eluded effective treatment for so long.

    J. Cohen, “HIV Surface Proteins Finally Caught Going Au Naturel,” Science 342, 6158 (1 November 2013).

    J. Cohen, “Structural Biology Triumph Offers Hope Against a Childhood Killer,” Science 342, 6158 (1 November 2013).

    J.-P. Julien et al., “Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer,” Science 342, 1477 (31 October 2013).

    J. S. McLellan et al., “Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus,” Science 342, 6158 (1 November 2013).

    J. S. McLellan et al., “Structure of RSV Fusion Glycoprotein Trimer Bound to a Prefusion-Specific Neutralizing Antibody,” Science 340, 6136 (31 May 2013).

  14. How We Did in 2013 and …

    Science editors rate how well they predicted scientific areas worth watching in 2013.

    Graphic 1. One Cell at a Time

    Though not yet routine and nowhere near the clinic, single-cell DNA sequencing is yielding important discoveries such as unexpected variation in supposedly similar cells, including brain cells.

    Graphic 2. Planck Maps the Cosmic Microwave Background

    As expected, Europe's Planck spacecraft mapped the cosmic microwave background with unprecedented accuracy. But the Planck team's analysis merely confirmed the standard theory of what the universe is made of and how it evolved. Planck researchers will get one more shot at a major discovery—see "Cosmic history, with a twist" on page 1443.

    Graphic 3. Connectomes

    The $40 million Human Connectome Project released the first raw data in its 5-year quest to learn how millimeter-scale variations in the connections between human brain regions might account for individual differences in cognition and behavior. Other researchers this year mapped a speck of mouse brain synapse by synapse.

    Graphic 4. Piercing a Frigid Underworld

    In January, Russian drillers retrieved a core of ice frozen from Lake Vostok, a pocket of water buried nearly 4000 meters below the Antarctic ice sheet. Scientists were eager to see what sort of microbial life the lake might harbor after millions of years of isolation. But the cells they spotted may have ridden down to Vostok on contaminated drills; more sampling could be necessary.

    Graphic 5. Cancer Immunotherapy

    It's our Breakthrough of the Year—enough said.

    Graphic 6. Plant Power

    This year, seed companies introduced drought-tolerant crops and scientists pinpointed new regulators of plant growth and development. Two teams also homed in on a gene that can fend off Ug99, or wheat stem rust, a global threat. Scientists are hard at work developing new varieties adapted to anticipated future conditions. But two expected payoffs from basic research—commercial algae-based fuels and forecasts of how plants will fare under climate change—have not yet materialized.

  15. … Areas to Watch in 2014

    Science editors forecast science news to look out for in the year ahead.

    CREDIT: C. BICKEL/SCIENCE

    Space ghosts. This year, physicists finally detected elusive particles called neutrinos coming from beyond our solar system. Now, the question is whether they will prove to be a useful tool for probing the universe. The observations from IceCube, a massive array of particle detectors sunk into 1 cubic kilometer of ice at the South Pole, completed a 40-year quest for cosmic neutrinos. But IceCube's main aim is to pinpoint their sources in the sky and usher in the field of neutrino astronomy, and it remains to be seen if it can collect enough of the ghostly particles for that. The IceCube team's first earnest attempt to map the neutrino sky should come within months, so scientists may soon know whether the array is big enough to serve as a neutrino telescope or whether something more is needed.

    Clinical genomes. In 2014, more and more researchers—and even some doctors—will be requesting a patient's entire genome sequence or a subset of it, the protein-coding DNA known as the exome. The results could help diagnose rare diseases and identify cancer treatments. Several studies will explore whether sequencing should become part of newborn screening and even guide the medical care of healthy people. In perhaps the most ambitious clinical sequencing project yet, the United Kingdom will embark on a 4-year plan to sequence the genomes of 100,000 patients, most of them with cancer and rare diseases, to guide their treatments. Looming over these efforts is a debate over whether patients should be notified when the sequencing reveals "incidental" results—medically important findings unrelated to their illness.

    Cosmic history, with a twist. The afterglow of the big bang—the so-called cosmic microwave background (CMB) radiation—may soon yield another revelation about how the universe began. That primordial radiation could contain traces of gravity waves that rippled through the universe in the first sliver of a second. Those traces would take the form of swirling patterns in the polarization of the microwaves as the CMB is mapped across the sky. The swirls, called B modes, could yield clues to how the universe underwent a faster-than-light growth spurt known as inflation. Researchers with the European Space Agency's spacecraft Planck, which took data from August 2009 to October 2013, should release a polarization map of the whole sky within months. But some researchers say Planck may not have the resolution to spot the swirls and may get scooped by ground-based efforts.

    CREDIT: GLOBALP/ISTOCKPHOTO

    Bye-bye, chimps? One way or another, chimpanzees may be leaving U.S. research labs. In June, the National Institutes of Health announced plans to retire all but 50 of its 360 research chimps and phase out much of the chimp research it supports. The U.S. Fish and Wildlife Service, meanwhile, has recommended that captive chimps be listed as endangered, which would limit any research that isn't in their best interest. And just this month, an animal rights group known as the Nonhuman Rights Project launched a legal effort to have chimpanzees declared legal persons and freed from captivity. Its first three lawsuits, filed in three New York courts, were dismissed, but it plans to appeal (http://scim.ag/NHRPchimps). Scientists who study the animals may soon have to move on to other creatures—or abandon their research entirely.

  16. Notable Developments

    Find out what Science staff considered the top breakup, breakdowns, breakout, and genomes of the year, as well as 2013's top fossil, politico, vertebrate, and invertebrate.

    Fossil of the Year: Dmanisi Skull Gives New Face to Early Human Ancestors

    CREDIT: GURAM BUMBIASHVILI/GEORGIAN NATIONAL MUSEUM

    Researchers unveiled the most complete skull of an early human ancestor this past November—and proved once again that a single fossil can transform our picture of human ancestors. The stunning 1.8-million-year-old remains of a mature male had a remarkably small brain and a large, jutting jaw. That's just the opposite of what researchers expected to find for members of our genus Homo at this time. Four skulls of our direct ancestor, Homo erectus, found in the same sliver of time and place—at Dmanisi in Georgia—had bigger brains and less conspicuous mugs. As a result, the latest Dmanisi skull, which even includes the fragile midface bones, has given early Homo a new visage.

    If it, too, is a member of H. erectus, as the researchers think, that species had more diversity in brain size and facial traits than previously believed. New dating of the skull and its four companions also suggests that H. erectus left Africa soon after it appeared there 1.9 million years ago.

    But some paleoanthropologists suggest the skull could belong to Homo habilis, a more distant earlier human ancestor that lived in Africa about 2.3 million to 1.4 million years ago. Or it could belong to a new species. Regardless of the skull's precise identity, its remarkable preservation will make it an icon for the face of early Homo for decades, if not centuries, to come.

    Vertebrate of the Year: The Rat That Ages Beautifully

    CREDIT: ROMAN KLEMENTSCHITZ, WIEN (OWN WORK) [GFDL (HTTP://WWW.GNU.ORG/COPYLEFT/FDL.HTML) OR CC-BY-SA-3.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0/)], VIA WIKIMEDIA COMMONS

    They will never win a beauty contest, but naked mole rats (Heterocephalus glaber) may hold a lesson or two for humans. Two studies this year, for instance, found clues to why these rodents can live 30 years, cancer-free. One secret may be a ribosome that excels at producing error-free proteins; misformed proteins can clog up the body's systems and accelerate aging. Another could be a supersized version of a complex sugar that seems to protect against cancer. Naked mole rats don't break this compound down as fast as other animals, so it builds up in the spaces between cells and may keep the cells from clumping together and forming tumors.

    Invertebrate of the Year: Top-Gear Planthopper

    Turns out humans weren't the first organism to gear up to gain a powerful mechanical advantage. In September, high-speed videos revealed that immature Issus coleoptratus planthoppers are such great leapers because of toothy interacting gears on their rear legs. By meshing together, the gears cock and coordinate the legs prior to and during each explosive hop.

    CREDIT: BURROWS ET AL., SCIENCE 341 (13 SEPTEMBER 2013)

    Breakout of the Year: Voyager Is Really Out There, Somewhere

    Thirty-six years out from Earth, its power dwindling and several instruments dead, the Voyager 1 spacecraft has left the invisible cocoon spun by the sun and entered interstellar space. So concluded Voyager team leaders and most space physicists in September. But it had taken them a year to realize Voyager had broken out of the heliosphere—the bubble inflated by the sun's wind of charged particles. That is a testament to just how weird the outer "edge" of the solar system proved to be.

    Going, gone.

    Voyager 1 (top) has exited the heliosphere in this artist's conception, while Voyager 2 (bottom) is getting close.

    CREDIT: NASA/JPL-CALTECH

    Team members had a checklist of indicators that would confirm that Voyager 1 had crossed into interstellar space. The density of plasma—the soup of low-energy charged and neutral particles pervading space—should jump, cosmic rays produced within the heliosphere should drop while those of interstellar space should increase sharply, and the direction of the magnetic field that pervades all space should switch. Voyager couldn't detect any change in plasma density, because its plasma instrument failed shortly after passing by Saturn. It did measure the expected changes in cosmic rays, in August 2012. But it never saw the magnetic field switch. So the official team line had Voyager in a "depletion region" still within the heliosphere.

    There, Voyager would have remained if not for a little help from the sun. Twice it sent a solar blast out Voyager's way, setting off oscillations in the plasma that the spacecraft's plasma wave instrument could detect, giving team members a proxy for plasma density. Extrapolating back, they could see that the plasma density had shifted in August 2012, just when cosmic rays had switched. Team leaders concluded that Voyager 1 had actually entered interstellar space at that time, even though the magnetic field did not shift.

    That interpretation will be tested as Voyager 2, a few years behind its sibling, brings its operating plasma instrument to bear on the same region.

    Politico of the Year: Chairman Smith Versus the Scientists

    U.S. Representative Lamar Smith (R–TX) likes to recall how a "D" in a freshman physics class at Yale University taught by a former presidential science adviser, D. Allan Bromley, caused him to switch his major to American studies—and started him on the road to a career in politics. Now, the tables have turned: This year, Smith gave a failing grade to the National Science Foundation (NSF) as part of a controversial attempt to reshape U.S. science policy that has scientists talking.

    CREDIT: NASA

    As the new chair of the House of Representatives science committee, Smith has drafted legislation that would alter how NSF manages peer review. He says the proposed changes would make the system more transparent and ensure that tax dollars are being spent wisely. But science leaders view the bill as a threat to a system that has fueled 60 years of innovation—and that other nations are trying to copy.

    In a bid to preempt the draft legislation, this month NSF announced plans to sharpen its descriptions of funded grants to emphasize their relevance to important societal goals. Will it be enough?

    Breakup of the Year: Siberian Meteor Blast Delivers a Warning Shot

    February's window-shattering explosion over Chelyabinsk, Russia, terrified thousands and caused hundreds of injuries, mostly minor. It also provided a windfall for scientists and a public relations bonanza for asteroid hunters.

    CREDIT: RIA NOVOSTI/SCIENCE PHOTO LIBRARY

    For scientists, the midair self-destruction of a 19-meter-diameter rock provided a key benchmark for reevaluating the threat from such relatively small visitors from the asteroid belt. Researchers had plenty of observations to work with. Data came from 400 public and private video cameras, seismographs, ground-based sensors that record ultra-low-frequency sound, and satellites intended to catch clandestine nuclear tests.

    The Chelyabinsk blast had an energy equivalent of about 500 kilotons of TNT, researchers estimate, or about 23 times the energy of the nuclear bomb dropped on Nagasaki. Initially, that output appeared to make the airburst a rarity, far larger than expected by astronomers who use telescopic surveys to gauge asteroid hazards. But after researchers compared the sound and brightness of Chelyabinsk with other meteor airbursts over a 20-year period, they found that big airbursts are at least three times—and perhaps 10 times—more frequent than astronomers thought.

    The incident energized those eager to find other small asteroids, whether heading for Earth or passing nearby. NASA is cranking up its search effort because it wants to find an asteroid smaller than 10 meters for an astronaut rendezvous. The nonprofit B612 Foundation wants to fly a spacecraft-borne telescope to help with that mission and search for hazardous asteroids, if someone will provide the funding.

    Ruling of the Year: U.S. High Court Bars Human Gene Patents

    In June, the U.S. Supreme Court reversed three decades of policy—and rattled the biotech world—when it ruled that human genes cannot be patented. The case, Association for Molecular Pathology v. Myriad Genetics, pitted a Utah company that owns patents on the human breast cancer genes BRCA1 and BRCA2 against doctors and researchers who argued that the patents were invalid and stifling research. The court agreed unanimously, finding that human genes are a "product of nature" and so not patentable.

    CREDIT: CQ ROLL CALL/NEWSCOM

    It will take years for the full consequences of this revolution in legal thinking to become clear. But the decision is already making waves. It spurred several companies to offer breast cancer diagnostic tests that competed with Myriad's—sparking a contentious new legal battle. And in October, federal Judge Susan Illston in San Francisco cited the Supreme Court's reasoning in striking down another DNA patent, involving a Down syndrome test developed by Sequenom of San Diego, California. Sequenom plans to appeal, and it is likely that many companies will be asking judges to clarify exactly how the law defines a product of nature.

    Breakdowns of the Year

    CREDIT: NASA

    In May, for the first time in recorded history, atmospheric concentrations of carbon dioxide rose above 400 parts per million, dramatizing the failure of governments to limit greenhouse gas emissions. • The same month, a second reaction wheel failed on the Kepler planet-hunting spacecraft, dooming its ability to point accurately and collect precise data. • In October, congressional gridlock on spending issues forced the U.S. government to partially shut down for 16 days, paralyzing science funding agencies, disrupting research projects, and canceling many Antarctic field studies. • More than one-half of 304 free open-access journals accepted a bogus paper submitted by Science journalist John Bohannon, who sparked fierce debate over the quality of peer review when he reported his sting. • By year's end, disgraced Dutch social psychologist Diederik Stapel had retracted at least 54 papers based on made-up data, but was giving a TED talk about his misconduct.

    Genomes of the Year

    CREDIT: COURTESY OF BORIS MICHEL

    Notable sequences of 2013: The oldest human mitochondrial DNA, which comes from a 400,000-year-old Neandertal ancestor found in Spain but mysteriously resembles that of a different extinct human • The oldest organismal genome, from a 700,000-year-old frozen horse hoof • Other complete genomes came from the comb jelly, changing views of the animal tree of life • Minke whale, revealing how marine mammals cope with deep dives • Amborella, sister to all flowering plants, explaining the early days of angiosperms • Tiger, lion, and snow leopard, capturing the genomic essence of big cats • The scorpion Mesobuthus martensii (at right), which has 10,000 more genes than humans do • Norway spruce (Picea abies), white spruce (Picea glauca), and, soon, loblolly pine (Pinus taeda), each with genomes about seven times the size of a human's—a sequencing tour de force • The invaluable HeLa cancer research cell line, requiring permission from the family of Henrietta Lacks • King cobra and Burmese python, telling an evolutionary tale of extreme adaptations • Four bats which, when compared to dolphins, highlight a common core of echolocation genes • Pigeon, revealing the gene for crests • Irish famine potato blight, showing that this historic strain is extinct.

    Also Noted: Ribosome Robot

    CREDIT: BY JÁ (OWN WORK) [GFDL (HTTP://WWW.GNU.ORG/COPYLEFT/FDL.HTML) OR CC-BY-SA-3.0-2.5-2.0-1.0 (HTTP://CREATIVECOMMONS.ORG/LICENSES/BY-SA/3.0)], VIA WIKIMEDIA COMMONS

    In January, one of the world's first nanofactories made its debut. Researchers built a molecular machine that mimics the cell's protein-building factory, the ribosome, but is one-tenth the size. This ribosome robot includes a molecular axle track with a ring around it. When heated, the ring's sulfur-containing amino acid sequentially grabs each of three amino acids from the track to build a short peptide chain. The machine has been hailed as ingenious, but it won't replace ribosomes anytime soon. It takes days to do what the real ribosome can do in tenths of a second.

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