News this Week

Science  23 Aug 2013:
Vol. 341, Issue 6148, pp. 826
  1. Around the World

    1 - Emmeloord, the Netherlands
    Tiger Mosquito Moves North in Europe
    2 - Page, Arizona
    Drought Forces Cutbacks on the Colorado River
    3 - Yasuni National Park, Ecuador
    Opponents Vow to Block Amazon Drilling

    Emmeloord, the Netherlands

    Tiger Mosquito Moves North in Europe

    CREDIT: JAMES GATHANY/CDC

    A series of outbreaks in the Netherlands of the Asian tiger mosquito (Aedes albopictus), which can transmit viral diseases such as dengue and chikungunya, has raised the possibility that the mosquito could be establishing its northernmost beachhead in Europe.

    The mosquito often hitches a ride in second hand tires (Science, 16 May 2008, p. 864), and this summer it has turned up near seven tire-importing companies in the Netherlands. In each case, the Food and Consumer Product Safety Authority has moved in quickly with insecticides. Tire companies have also agreed to store tires from tropical countries in dry places, depriving mosquito eggs of the water they need to hatch. Yet without more aggressive measures, the tropical insect will soon become a fixture in the Netherlands, predicts Bart Knols of In2Care, a company focusing on mosquito control. One study by the European Centre for Disease Prevention and Control has suggested that the mosquito could survive as far north as Scandinavia.

    Page, Arizona

    Drought Forces Cutbacks on the Colorado River

    In an ominous precedent, operators of the Glen Canyon Dam on the Colorado River will reduce the water released over next year from the Lake Powell reservoir by 9%, the U.S. Bureau of Reclamation announced last week. Millions of farms and homes depend on the river for their water supply. "I view this as another serious warning to users of the Colorado River that we're headed for big trouble," says Peter Gleick of the Pacific Institute in Oakland, California.

    Low water.

    Lake Powell at the Glen Canyon Dam.

    CREDIT: T. ROSS REEVE

    Thanks to a 14-year drought, less water has been flowing into the upper Colorado River. Flows in July were just 13% of normal. According to a 2007 agreement between seven Western states, the bureau must keep a certain amount of water in the reservoirs. For now, a gigantic downstream reservoir, Lake Mead, will remain full enough for the same amount of water to be released from the Hoover Dam as this year. So the supply to homeowners and farmers will not be reduced, but the decision highlights the likelihood of future shortages as early as 2015. http://scim.ag/Colowater

    Yasuni National Park, Ecuador

    Flash point.

    Cobalt-winged parakeets in Yasuni National Park, site of a controversial drilling plan.

    CREDIT: PRISMA BILDAGENTUR AG/ALAMY

    Opponents Vow to Block Amazon Drilling

    Ecuador will move ahead with controversial plans to drill for oil in a renowned Amazon park, President Rafael Correa announced on 15 August. But opponents are hoping to block the move in a national vote.

    Yasuni National Park is a biological hot spot and home to the Waorani people, including two clans who live in voluntary isolation. The park also holds lots of oil. In 2010, Correa promised to forgo drilling if the international community donated $3.6 billion—one-half of the oil's value—to a special fund. But lackluster fundraising forced the government to act, Correa said. "The world has failed us."

    Polls suggest that a majority of Ecuadorians oppose drilling, and opponents are pushing for a referendum. Meanwhile, they are encouraged by antidrilling demonstrations in Guayaquil, a bellwether city. "This is now not just about a handful of environmentalists," says Kevin Koenig of Amazon Watch in Quito. "It has become a point of pride." http://scim.ag/Yasunidrill

  2. Random Sample

    The Science of a Falling Building

    CREDITS: (BOTTOM LEFT TO RIGHT) JENNIFER WILLIAMS/FIRE HORSE LEO/WIKIMEDIA COMMONS; DAN HONDA/BAY AREA NEWS GROUP/AP PHOTO

    What do an imploding tower and an earthquake have in common? Seismic energy. Before Warren Hall, a 13-story building overlooking California's San Francisco Bay, toppled to the ground on 17 August, U.S. Geological Survey (USGS) scientists planted nearly 600 seismometers in a 2.5-kilometer-radius ring around the building to record the resulting seismic signals. By studying these signals, the scientists hope to better map the complicated fault lines of the Hayward fault zone, which runs east of the bay, through Oakland, San Jose, and Berkeley.

    The last major earthquake (magnitude 6.8) on the Hayward fault was in 1868. But in 2009, USGS declared that a major earthquake on the fault is "increasingly likely"—and that there's a 27% chance that the Hayward fault will rupture before 2032. Such a temblor could devastate the Bay Area, but forewarned is forearmed: By mapping out the fault zone's traces and the ground's response to shaking, scientists hope to better understand the potential hazard.

    They Said It

    "1996-2012. The world has become safer."

    —A plaque at "Plutonium Mountain," a Soviet-era nuclear test site in eastern Kazakhstan, commemorating a secret 17-year collaboration between Russian and U.S. scientists to remove nuclear materials to keep them out of terrorist hands. The Harvard Kennedy School published a report on the collaboration on 15 August.

    Out of Oil? Just Add Fungi

    CREDIT: GARY STROBEL

    The long-held view of the origin of shale oil—a buried leaf cooking for 70 million years under pressure from mud and sand—might leave out a vital component of the process: fungi. A new experiment suggests that endophytic fungi—fungi living symbiotically inside plants—can generate hydrocarbons as they eat away at their decaying hosts. Gary Strobel, a plant microbiologist at Montana State University in Bozeman, says that fungi could have speeded up oil production by tens of millions of years.

    Strobel calls his experiment the Paleobiosphere (pictured), a kitchensink–sized contraption designed to simulate a Cretaceous-era rainforest floor. Strobel mixed leaves from maple, sycamore, and aspen trees with a fungus that grows inside semitropical Key lime trees, then sandwiched the concoction between two layers of bentonite shale and flooded the whole thing with water a few times. A mere 3 weeks later, the growing fungi had digested the leaf matter's sugars, starches, and cellulose, converting them into a variety of hydrocarbons that seeped into the shale layers—closely resembling the oil-rich Montana shale around Strobel's lab. "Not all of the hundreds of compounds found in diesel are present in this simple experiment, but representative molecules in each of the major classes of hydrocarbons are there," he explains.

    Entrepreneur Bryan Blatt hopes to use Strobel's hydrocarbon-producing fungi to churn out new biofuels. His company, Endophytics LLC, will announce its first patent on a promising organism this month. "We just don't have to sit here and assume that at some point there's an end to the oil," he says.

  3. The CRISPR Craze

    1. Elizabeth Pennisi

    A bacterial immune system yields a potentially revolutionary genome-editing technique.

    Fighting invasion.

    When viruses (green) attack bacteria, the bacteria respond with DNA-targeting defenses that biologists have learned to exploit for genetic engineering.

    CREDIT: EYE OF SCIENCE/SCIENCE SOURCE

    Bacteria may not elicit much sympathy from us eukaryotes, but they, too, can get sick. That's potentially a big problem for the dairy industry, which often depends on bacteria such as Streptococcus thermophilus to make yogurts and cheeses. S. thermophilus breaks down the milk sugar lactose into tangy lactic acid. But certain viruses—bacteriophages, or simply phages—can debilitate the bacterium, wreaking havoc on the quality or quantity of the food it helps produce.

    In 2007, scientists from Danisco, a Copenhagen-based food ingredient company now owned by DuPont, found a way to boost the phage defenses of this workhouse microbe. They exposed the bacterium to a phage and showed that this essentially vaccinated it against that virus (Science, 23 March 2007, p. 1650). The trick has enabled DuPont to create heartier bacterial strains for food production. It also revealed something fundamental: Bacteria have a kind of adaptive immune system, which enables them to fight off repeated attacks by specific phages.

    Precise cuts.

    In just 8 months, CRISPR modifications of DNA resulted in dumpier nematodes (top, bottom), zebrafish embryos with an excess of ventral tissue (middle, bottom), and fruit flies with dark eyes (bottom, right), demonstrating its broad utility for editing genes in animals.

    CREDITS (TOP TO BOTTOM): FRIEDLAND ET AL., NATURE METHODS 10 (JUNE 2013); ANDREW GONZALES/JOANNA YEH; SCOTT GRATZ/UNIVERSITY OF WISCONSIN, MADISON

    That immune system has suddenly become important for more than food scientists and microbiologists, because of a valuable feature: It takes aim at specific DNA sequences. In January, four research teams reported harnessing the system, called CRISPR for peculiar features in the DNA of bacteria that deploy it, to target the destruction of specific genes in human cells. And in the following 8 months, various groups have used it to delete, add, activate, or suppress targeted genes in human cells, mice, rats, zebrafish, bacteria, fruit flies, yeast, nematodes, and crops, demonstrating broad utility for the technique. Biologists had recently developed several new ways to precisely manipulate genes, but CRISPR's "efficiency and ease of use trumps just about anything," says George Church of Harvard University, whose lab was among the first to show that the technique worked in human cells.

    With CRISPR, scientists can create mouse models of human diseases much more quickly than before, study individual genes much faster, and easily change multiple genes in cells at once to study their interactions. This year's CRISPR craze may yet slow down as limitations of the method emerge, but Church and other CRISPR pioneers are already forming companies to harness the technology for treating genetic diseases. "I don't think there's any example of any field moving this fast," says Blake Wiedenheft, a biochemist at Montana State University in Bozeman.

    Humble beginnings

    DNA surgeon.

    With just a guide RNA and a protein called Cas9, researchers first showed that the CRISPR system can home in on and cut specific DNA, knocking out a gene or enabling part of it to be replaced by substitute DNA. More recently, Cas9 modifications have made possible the repression (lower left) or activation (lower right) of specific genes.

    CREDIT: K. SUTLIFF/SCIENCE

    The first inkling of this hot new genetic engineering tool came in 1987, when a research team observed an oddly repetitive sequence at one end of a bacterial gene. Few others took much notice. A decade later, though, biologists deciphering microbial genomes often found similar puzzling patterns, in which a sequence of DNA would be followed by nearly the same sequence in reverse, then 30 or so seemingly random bases of "spacer DNA," and then a repeat of the same palindromic sequence, followed by a different spacer DNA. A single microbe could have several such stretches, each with different repeat and intervening sequences. This pattern appears in more than 40% of bacteria and fully 90% of microbes in a different domain, the archaea, and gives CRISPR its name. (It stands for clustered regularly interspaced short palindromic repeats.)

    Many researchers assumed that these odd sequences were junk, but in 2005, three bioinformatics groups reported that spacer DNA often matched the sequences of phages, indicating a possible role for CRISPR in microbial immunity. "That was a very key clue," says biochemist Jennifer Doudna of the University of California (UC), Berkeley. It led Eugene Koonin from the National Center for Biotechnology Information in Bethesda, Maryland, and his colleagues to propose that bacteria and archaea take up phage DNA, then preserve it as a template for molecules of RNA that can stop matching foreign DNA in its tracks, much the way eukaryotic cells use a system called RNA interference (RNAi) to destroy RNA.

    Enter the Danisco team. In 2007, Rodolphe Barrangou, Philippe Horvath, and others with the company showed that they could alter the resistance of S. thermophilus to phage attack by adding or deleting spacer DNA that matched the phage's. At the time, Barrangou, who is now at North Carolina State University in Raleigh, didn't see CRISPR's full potential. "We had no idea that those elements could be readily exploitable for something as attractive as genome editing," he says.

    Doudna and Emmanuelle Charpentier, currently of the Helmholtz Centre for Infection Research and Hannover Medical School in Germany, took the next step. They had independently been teasing out the roles of various CRISPR-associated proteins to learn how bacteria deploy the DNA spacers in their immune defenses. But the duo soon joined forces to focus on a CRISPR system that relies on a protein called Cas9, as it was simpler than other CRISPR systems.

    When CRISPR goes into action in response to an invading phage, bacteria transcribe the spacers and the palindromic DNA into a long RNA molecule that the cell then cuts into short spacer-derived RNAs called crRNAs. An additional stretch of RNA, called tracrRNA, works with Cas9 to produce the crRNA, Charpentier's group reported in Nature in 2011. The group proposed that together, Cas9, tracrRNA, and crRNA somehow attack foreign DNA that matches the crRNA.

    The two teams found that the Cas9 protein is a nuclease, an enzyme specialized for cutting DNA, with two active cutting sites, one site for each strand of the DNA's double helix. And in a discovery that foreshadowed CRISPR's broad potential for genome engineering, the team demonstrated that they could disable one or both cutting sites without interfering with the ability of the complex to home in on its target DNA. "The possibility of using a single enzyme by just changing the RNA seemed very simple," Doudna recalls.

    Before CRISPR could be put to use, however, Doudna's and Charpentier's teams had to show that they could control where Cas9 went to do its cutting. First, Doudna's postdoc, Martin Jinek, figured out how to combine tracrRNA and spacer RNA into a "single-guide RNA" molecule; then, as a proof of principle, the team last year made several guide RNAs, mixed them with Cas9, and showed in a test tube that the synthetic complexes could find and cut their DNA targets (Science, 17 August 2012, p. 816). "That was a milestone paper," Barrangou says.

    This precision targeting drives the growing interest in CRISPR. Genetic engineers have long been able to add and delete genes in a number of organisms. But they couldn't dictate where those genes would insert into the genome or control where gene deletions occurred. Then, a decade ago, researchers developed zinc finger nucleases, synthetic proteins that have DNA-binding domains that enable them to home in and break DNA at specific spots. A welcome addition to the genetic engineering toolbox, zinc fingers even spawned a company that is testing a zinc finger to treat people infected with HIV (Science, 23 December 2005, p. 1894). More recently, synthetic nucleases called TALENs have proved an easier way to target specific DNA and were predicted to surpass zinc fingers (Science, 14 December 2012, p. 1408).

    Now, CRISPR systems have stormed onto the scene, promising to even outcompete TALENs. Unlike the CRISPR system, which uses RNA as its DNA-homing mechanism, zinc finger and TALEN technologies both depend on custom-making new proteins for each DNA target. The CRISPR system's "guide RNAs" are much easier to make than proteins, Barrangou says. "Within a couple weeks you can generate very tangible results that using alternative methods would take months."

    Harnessing CRISPR

    CRISPRed rice.

    Earlier this month, researchers showed CRISPR works in plants, such as rice, where the knocked-out gene resulted in dwarf albino individuals (right).

    CREDIT: GAO CAIXIA LABORATORY

    Speed is not its only advantage. Church's group had been pushing the use of TALENs in human cells, but when he learned of Doudna and Charpentier's results, he and his colleagues made guide RNA against genes they had already targeted with TALENs. In three human cell types, the CRISPR system was more efficient than TALENs at cutting the DNA target, and it worked on more genes than TALENs did (Science, 15 February, p. 823). To demonstrate the ease of the CRISPR system, Church's team synthesized a library of tens of thousands of guide RNA sequences, capable of targeting 90% of human genes. "You can pepper the genome with every imaginable CRISPR," he says.

    That makes it possible to alter virtually any gene with Cas9, exploiting its DNA-cutting ability to either disable the gene or cut it apart, allowing substitute DNA to be inserted. In an independent paper that appeared at the same time as Church's, Feng Zhang, a synthetic biologist at the Broad Institute in Cambridge, Massachusetts, and his colleagues showed that CRISPR can target and cut two genes at once in human cells (Science, 15 February, p. 819). And working with developmental biologist Rudolf Jaenisch at the Whitehead Institute for Biomedical Research in Cambridge, Zhang has since disrupted five genes at once in mouse embryonic stem (ES) cells.

    Such work lays the foundation for generating mutant mice, a key tool for biomedical research. One approach would be to add the altered mouse ES cells to a developing embryo and breed the resulting animals. But Zhang has demonstrated a faster option. His team found it could simply inject fertilized mouse eggs, or zygotes, with Cas9 messenger RNA and two guide RNAs and, with 80% efficiency, knock out two genes. They could also perform more delicate genomic surgery on the embryos by shackling Cas9, so that it nicks target DNA instead of cutting it. In this way, they could introduce a new part of a gene through a process called homology-directed repair, they reported in the 2 May issue of Cell.

    Developing a new mouse model for a disease now entails careful breeding of multiple generations and can take a year; with Zhang's CRISPR technique, a new mouse model could be ready for testing in a matter of weeks. And Zhang thinks the approach is not limited to mice. "As long as you can manipulate the embryo and then reimplant it, then you will be able to do it" in larger animals, perhaps even primates.

    Doudna's group and a Korean team reported using CRISPR to cut DNA in human cells 3 weeks after Zhang's and Church's papers went online, and, at the same time, another group revealed they had used CRISPR to make mutant zebrafish. This cascade of papers has had a synergistic effect, commanding the attention of a broad swath of the biology community. "If a single paper comes out, it gets some attention, but when six papers come out all together, that's when people say, 'I have to do this,'" says Charles Gersbach, a biomedical engineer at Duke University in Durham, North Carolina.

    Once she saw Doudna and Charpentier's paper a year ago, Gao Caixia became one of the early converts. Her group at the Chinese Academy of Sciences' Institute of Genetics and Developmental Biology in Beijing had been using zinc finger and TALENs technology on rice and wheat. Using CRISPR, they have now disabled four rice genes, suggesting that the technique could be used to engineer this crucial food crop. In wheat, they knocked out a gene that, when disabled, may lead to plants resistant to powdery mildew. In a measure of the excitement that CRISPR has generated, the team's report in the August issue of Nature Biotechnology was accompanied by four other papers describing CRISPR successes in plants and in rats.

    The cost of admission is low: Free software exists to design guide RNA to target any desired gene, and a repository called Addgene, based in Cambridge, offers academics the DNA to make their own CRISPR system for $65. Since the beginning of the year, Addgene—to which 11 teams have contributed CRISPR-enabling DNA sequences—has distributed 5000 CRISPR constructs, and in a single July week the repository received 100 orders for a new construct. "They are kind of crazy hot," says Joanne Kamens, Addgene's executive director.

    Fine-tuning gene activity

    The initial CRISPR genome-editing papers all relied on DNA cutting, but other applications quickly appeared. Working with Doudna, Lei S. Qi from UC San Francisco and his colleagues introduced "CRISPRi," which, like RNAi, turns off genes in a reversible fashion and should be useful for studies of gene function. They modified Cas9 so it and the associated guide RNA would still home in on a target but would not cut DNA once there. In bacteria, the presence of Cas9 alone is enough to block transcription, but for mammalian applications, Qi and colleagues add to it a section of protein that represses gene activity. Its guide RNA is designed to home in on regulatory DNA, called promoters, which immediately precede the gene target.

    Last month, that team and three other groups used a Cas9 to ferry a synthetic transcription factor—a protein fragment that turns on genes—enabling them to activate specific human genes. Just using one CRISPR construct had a weak effect, but all four teams found a way to amplify it. By targeting multiple CRISPR constructs to slightly different spots on the gene's promoter, says Gersbach, one of the team leaders, "we saw a huge synergistic effect."

    In the 25 July issue of Nature Methods, he reported activating genes tied to human diseases, including those involved in muscle differentiation, controlling cancer and inflammation, and producing fetal hemoglobin. Two other teams also targeted biomedically important genes. CRISPR control of such genes could treat diseases ranging from sickle cell anemia to arthritis, Gersbach suggests.

    CRISPR technology may yet have limitations. It's unclear, for example, how specific the guide RNAs are for just the genes they are supposed to target. "Our initial data suggest that there can be significant off-target effects," says J. Keith Joung from the Massachusetts General Hospital in Boston, who back in January demonstrated that CRISPR would alter genes in zebrafish embryos and has used CRISPR to turn on genes. His work shows that nontarget DNA resembling the guide RNA can become cut, activated, or deactivated.

    Joung's group showed that a guide RNA can target DNA that differs from the intended target sequence in up to five of its bases. Zhang has gotten more reassuring results but says that "the specificity is still something we have to work on," especially as more people begin to think about delivering CRISPR systems as treatments for human diseases. "To really make the technology safe, we really have to make sure it goes where we want it to go to and nowhere else."

    Researchers must also get the CRISPR components to the right place. "Delivery is an enormous challenge and will be cell type and organism specific," Joung notes. With zebrafish, his team injects guide RNA and messenger RNA for Cas9 directly into embryos; with mammalian cells, they use DNA constructs. How CRISPR might be delivered into adult animals, or to treat disease in people, is just now being considered.

    Ultimately, CRISPR may take a place beside zinc fingers and TALENs, with the choice of editing tool depending on the particular application. But for now, researchers are dazzled by the ease by which they can make and test different CRISPR variants and by the technology's unexplored potential. Charpentier and others are looking at the versions of Cas9 in other bacteria that might work better than the one now being used. Microbiologists have harnessed the CRISPR system to vaccinate bacteria against the spread of antibiotic resistance genes. Church, Doudna, Charpentier, and others are forming CRISPR-related companies to begin exploring human therapeutic applications, including gene therapy.

    And there's more that can be done, Barrangou says. "The only limitation today is people's ability to think of creative ways to harness [CRISPR]."

    Not bad for a system that started with sickly bacteria.

  4. Planetary Science

    The Save-the-World Foundation

    1. Robert Irion*

    Convinced that NASA will not finish the job, a private foundation intends to raise $450 million for a space mission to find asteroids that may threaten Earth.

    Dodge the bullets.

    NASA has identified just 1% of the 1 million sizable asteroids thought to swirl close to Earth's realm. This plot shows the orbits of the known Near-Earth Objects more than 140 meters across—those most dangerous should they collide with our planet.

    CREDIT: NASA/JPL-CALTECH

    MENLO PARK, CALIFORNIA—In Antoine de Saint-Exupéry's beloved novella, The Little Prince, a pilot stranded in the Sahara Desert encounters a being from an asteroid called B-612. "There are also hundreds of others," Saint-Exupéry wrote, "some of which are so small that one has a hard time seeing them through the telescope."

    That figure was far too conservative. There may be a million asteroids with masses far greater than ocean liners in Earth-approaching orbits, nearly all of which telescopes have yet to see. Far from being benign abodes like the Little Prince's domain, some of those Near-Earth Objects (NEOs) are potential killers.

    Those at least 40 meters across could wipe out a metropolis; a kilometer-wide asteroid could devastate part of a continent and shroud the planet in soot. NASA-sponsored searches, mostly from the ground, have found most of the kilometer-size, civilization-threatening asteroids, but only a fraction—perhaps 1%—of the smaller, but still menacing, objects. Two former astronauts with a soft spot for Saint-Exupéry and a drive to safeguard fellow citizens have set out to find the rest.

    Protectors.

    Former NASA astronauts Ed Lu (top) and Rusty Schweickart spearhead the B612 Foundation.

    CREDITS (TOP TO BOTTOM): NASA; COURTESY OF THE B612 FOUNDATION

    Planetary scientists agree that a full inventory of NEOs will require a dedicated space observatory—at least a half-billion-dollar proposition. That's a stretch for NASA, in a thin budgetary era when new planetary missions without "Mars" in the title are rare. Even the agency's current assignment, a 2005 mandate from Congress to identify 90% of NEOs at least 140 meters wide, is behind schedule. More than halfway toward the target date of 2020, NASA has found just 10% of them.

    "I believe the agency has ducked its responsibility a little bit," says Lindley Johnson, NASA's program executive for NEO Observations. "I never dreamed it would take as long as it has to develop a robust capacity." Although it now seems feasible to deflect an incoming asteroid, scientists would need many years of advance warning to do so—an unlikely cushion at current rates of discovery.

    Into this breach have stepped the astronauts and their B612 Foundation. The foundation has set its sights on launching a $450 million mission by July 2018. The infrared telescope, called Sentinel, would spy a half-million NEOs from a vantage point near Venus. B612 has a star-studded team of planetary science veterans and a fixed-price contract with Ball Aerospace & Technologies to build and operate the satellite.

    In the new economy of commercial ventures into Earth's orbit, the B612 Foundation is aiming for much farther—into deep space—propelled by nothing but philanthropic dollars. Although the team's mission design has sparked some dissent and the fundraising goal is steep, all agree that Sentinel's dynamic cartography of the swarm of objects in Earth's milieu would transform planetary science. Says physicist Mark Boslough, an impact specialist at Sandia National Laboratories in Albuquerque, New Mexico: "If we're going to take the impact threat seriously, we have to do something like this."

    The Mercury 7 mystique

    Space surprise.

    A 17-meter-wide asteroid that no one saw coming exploded in February near Chelyabinsk, Russia, but even space surveys will strain to find objects that small.

    CREDIT: © JIANG KEHONG/XINHUA PRESS/CORBIS

    The public faces of B612 are astronauts from two generations: CEO Edward ("Ed") Lu, 50, and Russell ("Rusty") Schweickart, 77, chair emeritus of the board of directors. Their passions and cultural cachet have lifted B612's profile. "The Mercury 7 mystique of 'the best of the best' still exists," says Sentinel program architect Scott Hubbard of Stanford University in Palo Alto, California, and former Mars program director for NASA. "They have a special place in society."

    Lu, an astrophysicist and solar scientist, flew on two space shuttle missions before spending 6 months on the International Space Station in 2003, in the wake of the Columbia shuttle disaster. He and Russian cosmonaut Yuri Malenchenko maintained the station and ran experiments, but Lu also had time for photography, playing a compact electric piano (his renditions of Beethoven's Moonlight Sonata and Linus and Lucy by Vince Guaraldi are both on YouTube), and Earth-gazing. "You see shooting stars below you," he says. "You know where the impact craters are. It's a constant reminder." After leaving NASA in 2007, Lu worked as program manager for advanced projects at Google—but protecting Earth had become an irresistible pull.

    That transition took longer for Schweickart, a U.S. Air Force fighter pilot chosen for NASA's third class of astronauts in 1963. He flew on Apollo 9 in March 1969, the first test of the lunar module in orbit—a critical step in the sequence leading to the moon landing. During a spacewalk, Schweickart had the rare luxury of simply watching Earth pass under him for 5 minutes as one of his crewmates fixed a jammed camera. Not until 1974, during a remarkable unscripted speech to the Lindisfarne Association—a group dedicated to issues of spirituality and consciousness—did he express how that serendipity had changed him. "You know very well at that moment … that you're the sensing element for man," he said. "You're a piece of this total life. You have to bring that back somehow. And that becomes a special responsibility."

    Schweickart took a step toward fulfilling those words in 1995 by founding the Association of Space Explorers, a cadre of former astronauts devoted to public education and planetary stewardship. Then in 1998, he saw Stanford University geophysicist Norman Sleep speak about Earth's impact history. "The incredible energies blew my mind," he says.

    Lu and Schweickart soon began discussing how to prevent such blasts from happening again. They founded the B612 Foundation in 2002 with astrophysicist Piet Hut of the Institute for Advanced Study in Princeton and planetary scientist Clark Chapman of the Southwest Research Institute in Boulder. For a decade, they and colleagues examined ways to nudge an NEO off a collision course given at least 10 years of warning. Lu and fellow astronaut Stanley Love devised the "gravity tractor," a spacecraft hovering near an NEO to alter its orbit a touch. Another leading concept, ramming a projectile into an asteroid, would also do the trick if done far enough in advance, studies showed.

    "We were four guys and a website and tens of dollars," says Lu, who talks about planetary cataclysms with next-door-neighbor informality. "We came to the conclusion that deflection was doable. Finding the other 99% [of NEOs] is the entire problem."

    All along, the team pushed NASA to ramp up the search for hazardous asteroids—often in harsh terms from the characteristically blunt Schweickart. But when Lu spoke at Google and lamented that the government seemed incapable of putting money down, an engineer approached him and said, "Why don't you just do it?" Lu called Schweickart, and B612's new purpose was clear to both of them.

    "We put together a list of the 10 best people in the world, and we hired them all," Lu says. "That took about 2 weeks." In addition to Hubbard, they recruited veteran mission director Harold Reitsema, retired from Ball Aerospace; program manager John Troeltzsch, also of Ball Aerospace, who also manages the Kepler planet-hunting telescope; and mission scientist Marc Buie of the Southwest Research Institute, an asteroid authority. B612 also convened a review team that Troeltzsch calls "a Who's Who of every deep-space mission flown in the last 45 years."

    To Venus, and beyond

    Sentinel (artist's concept) CREDIT: B612 FOUNDATION/BALL AEROSPACE

    Troeltzsch describes Sentinel as a "pinnacle mission" for its heritage of proven systems from other space probes—notably Kepler, the infrared Spitzer Space Telescope, and the comet-colliding Deep Impact. Ball Aerospace played a central role in each one.

    The contract between Ball and B612 lays out a cost of about $250 million for Sentinel; launch, operations, and staffing will take about $200 million more. In his talks, Lu specifies a launch date of 20 July 2018, the anniversary of Neil Armstrong's famous step. Plans call for a 6.5-year mission, the time needed to find 90% of the NEOs larger than 140 meters in diameter and perhaps half of the ones down to 40 meters across. Extending the mission to 10 years would sweep up many others.

    Sentinel's half-meter-wide telescope will spot NEOs with new infrared detectors sensitive to 10 microns—a long wavelength at which asteroids warmed by the sun pop out against the cold backdrop of space. But the most notable aspect of Sentinel's design is its planned orbit in a path similar to that of Venus. This perch, Buie says, will allow Sentinel a view of fully illuminated asteroids as it looks out toward Earth's orbit, away from the sun. Ball engineers first made a pitch for a Venus-like orbit in 2002, Buie recalls: "I said, 'You guys have got the answer.' I could see it in an instant."

    But the choice forces compromises. For instance, Sentinel's remote position means that it will not detect as many smaller NEOs in the 40-meter range as it might from a closer vantage, says Tim Spahr, director of the Minor Planet Center at the Smithsonian Astrophysical Observatory in Cambridge, Massachusetts. That's the suspected size of the object that blew up in 1908 over Tunguska, Siberia, flattening 2000 square kilometers of forest. B612's website leads off with the bold slogan "Sentinel: Prevent the Next Tunguska." But as Spahr points out, "If you want that as your goal, you must stay near the Earth."

    In another tradeoff, Sentinel's distance from Earth—between roughly 40 million kilometers to 250 million kilometers—limits the amount of data it can beam back. B612 signed an agreement with NASA to use its Deep Space Network of radio antennae to download data, but to limit the burden an onboard computer will allow Sentinel to transmit only image frames in which an object appears to have moved within 1 hour. "The vast majority of the sky will not have changed," Reitsema says. That step, he projects, will trim data rates by a factor of 1000.

    Spahr frets about that purge, as does astronomer Amy Mainzer of NASA's Jet Propulsion Laboratory (JPL) in Pasadena, California, who has proposed that NASA fund an alternative NEO-hunting satellite, called NEOCam, to be stationed closer to Earth. "Most of what you'll find that's new is at the faintest limit of detection," she says. "You have to have all of the data [to find them]. If you don't, you might as well cut the telescope aperture in half." As a case in point, Mainzer notes that a deeper analysis of the full data set from a recent extension of NASA's Wide-field Infrared Survey Explorer (WISE) mission, called NEOWISE, should yield NEOs beyond the 134 new ones her team announced in 2011.

    Reitsema says that the B612 team parsed its orbital options thoroughly and knows Sentinel won't catch everything. But he says the goal driving the design—notwithstanding the Tunguska banner on the website—is finding 90% of the 140-meter-size asteroids and above, as Congress dictated. For that, Reitsema states, "We're quite confident Venus is the preferred orbit."

    If the satellite spies an NEO that could make a very close pass by Earth, large radar antennae on the ground will bounce signals off the asteroid to zero in on its trajectory. A precise orbit usually rules out an impact, but Lu pegs the odds that Sentinel will find an NEO requiring deflection sometime in the next century at 3-in-10. If one looms, nations will confront the tangled geopolitics of deflection. Altering an orbit, Schweickart points out, may shift the likeliest impact spot from one country to another until the projected path misses Earth. Years of debate about asteroids in U.N. committees, he says, haven't led to a set of "mission rules" about what to do. "In some ways this will be the first global decision on survival," he says. "Will we recognize our commonality well enough to overcome our differences?"

    Museum wings and observatories

    The overall reaction to B612's plans has been positive. "I think they're doing everything right," says Donald Yeomans, manager of NASA's NEO program office at JPL. But he worries that the philanthropic goals are too ambitious.

    The foundation's immediate goal is $20 million in donations by the new year, followed by at least $40 million each year for a decade. To oversee the effort, Lu hired Karen Putnam, a veteran of East Coast museum fundraising and former CEO of the Central Park Conservancy in New York. Lu compares Sentinel's costs to the wing of a major art museum—a "midsize project," he says, "with the added benefit that you can help save the world." Putnam declined to state the amount raised to date, noting only that "we have the $20 million in various stages in the pipeline."

    A recent study by economist Alexander Mac-Donald, program executive for NASA's emerging space office, suggests that B612's financial goals are no more ambitious than those of classic astronomy ventures. MacDonald examined the costs of major observatories built before World War II, almost entirely with private money. When he scaled those expenses to 2008 dollars as comparable fractions of the U.S. gross domestic product, he found that Mount Wilson Observatory in California and Yerkes Observatory in Wisconsin would have cost $408 million and $441 million, respectively. Others were even more lavish.

    If B612 falls short, might NASA carry the project? "We'd be happy to talk about a deeper public-private partnership, sure," Lu says. "Our goal isn't us building the telescope; our goal is completing the telescope." Johnson at NASA headquarters says the climate in Washington, D.C., for asteroid detection is "the best that it has been." At a House of Representatives science committee hearing in March, 1 month after the surprising airburst of a 17-meter-wide asteroid near Chelyabinsk, Russia, receptive legislators heard the B612 Foundation called out seven times by NASA Administrator Charles Bolden and Office of Science and Technology Policy Director John Holdren. Lu has testified twice on Capitol Hill as well.

    Some in the field regret that it took Chelyabinsk to trigger this rush of concern. "It's unlikely any space survey would find such [small] objects, and they should not be sold that way," says planetary scientist Edward Beshore of the University of Arizona in Tucson, former director of the Catalina Sky Survey—the world leader in numbers of NEOs found to date.

    Distinctions among asteroid sizes may elude the public, but B612 team members report they've never encountered such rapt reactions in classrooms, public forums, and elevators when they describe their goals. And if Sentinel flies, the new NEO catalog will yield rich insights into our solar system's flotsam and jetsam—and how best to stay out of its way. "I've always thought that asteroids were solvable," Spahr says.

    That's just how two problem-solving astronauts see it.

    • * Robert Irion directs the Science Communication Program at the University of California, Santa Cruz.

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