Signal and noise

The largest of the telescopes in the hunt— the Low Frequency Array, or LOFAR—bristles in the middle of a peat bog in the north- ern Netherlands. One of its creators, co– principal investigator (PI) Michiel Brentjens of ASTRON, the Netherlands Institute for Radio Astronomy, in Dwingeloo, calls it “the most unimpressive radio telescope in the world.” He’s right: It’s just a thicket of hundreds of white plastic poles about the height of a person, braced by guy ropes. The guys are the antennas, no different in prin- ciple from a rooftop TV antenna. Large low boxes under tarpaulin covers contain more, smaller antennas. A few scattered electrical cabinets hum ominously.
LOFAR is an interferometer, a device that combines signals from widely spaced detec- tors to extract information from the differ- ences between them. The core of the array

But the location of LOFAR is far from ideal. The Dutch government provided €53 million to build the array so long as its core was sited in the north of the country to help build up high-tech infrastructure there. Besides the boggy terrain, LOFAR has to contend with interference from nearby radio sources, including the 88-to-108 megahertz band of FM broadcasts, which are slap in the middle of the frequencies LOFAR is trying to detect. “The signals from all the radio and TV transmitters in [the FM] band are just phenomenal,” says LOFAR PI Ger de Bruyn of ASTRON. “They’re a million times brighter [than the EoR signal], so you can’t observe there.” Fortunately, the team found that the main hunting ground for EoR signals, about 150 MHz, “seemed to be very quiet,” he says.
The other main arrays are sensibly situ- ated in remote radio-quiet areas. The Precision Array for Probing the Epoch of Reionization (PAPER)—Backer’s brainchild— is in the semidesert Karoo region of South Africa. Its garden chair–like antennas have been growing in number since 2009 and have now reached 128. The third instru- ment, MWA, sits on the semiarid plains of Western Australia, a few hundred kilo- meters north of Perth. MWA was instigated by a group of U.S. institutions that were originally part of the LOFAR project. They parted company with the Dutch over the is- sue of building LOFAR in the noisy environ- ment of the Netherlands and set out to build their own array, teaming up with research- ers in Australia, New Zealand, and India. The resulting telescope has 2048 spider- like antennas arranged in 128 four-by-four tiles. “It’s in good shape and running well,” Bowman says.

But building the arrays is, in a sense, the easy part. The antennas are “old tech- nology,” says theorist Saleem Zaroubi of the University of Groningen in the Neth- erlands, a co-PI on LOFAR. They have no moving parts and so cannot focus on a particular spot—they simply pick up every- thing coming from the sky. It falls to dis- tant supercomputers to make sense of the signals, processing them to calibrate the instrument, focus on a part of the sky, and separate the signal from the noise. Such “software telescopes” offer the advantage of becoming more powerful as computers do, even without changes to the antennas on the ground.

The biggest challenge the arrays face is picking out the extremely feeble EoR sig- nal from all the other radio sources at the same frequency. In our Milky Way galaxy, radio waves at those frequencies come from sources including supernova rem- nants, charged particles accelerated by the galaxy’s own magnetic field, and radiation from electrons colliding with ions inside hydrogen clouds. Outside the Milky Way, countless radio galaxies and galaxy clusters also broadcast their own signals. Models of the EoR signal suggest that these other ra- dio sources are between 1000 and 100,000 times brighter—which means astronomers 

Genetics may foster bugs that keep you thin

Twin study shows genes influence gut micro biome

Gut microbes are soldiers in the battle
of the bulge, researchers have learned in the past few years, with some or- ganisms seeming to promote thin- ness and others triggering weight gain. The makeup of such microbes

is known to be influenced by a person’s diet and environment. Now, a study of twins shows that genetics can also provide an edge in the microbial battle. Researchers identi- fied a microbe that appears to keep waist- lines trim—and found that genes influence its abundance. “It’s the first really strong evidence that human gut microbiology is genetically controlled,” says geneticist Oluf Pedersen of the University of Copenhagen, who wasn’t involved in the study.
The work, published in the 6 November issue of Cell, raises hopes for microbial treat- ments for obesity. But microbial ecologist Ruth Ley of Cornell University and her col- leagues originally wanted to answer a more basic question: Do genes affect the makeup of the gut microbiome? Like many research- ers trying to distinguish environmental from inherited influences, they turned to twins. Working with colleagues running a large-scale project called TwinsUK, the team collected more than 1000 stool sam- ples from 171 identical and 245 fraternal pairs of twins, as well as 173 samples from unrelated individuals. Among these people,322 were overweight and 183 were obese. Previous twin studies had failed to identify a genetic connection to microbiome diver- sity and abundance, but those studies looked at the microbiome as a whole. The new study instead takes a species-by-species approach. By sequencing and analyzing DNA from the fecal samples, Cornell graduate student Julia Goodrich and her colleagues found more than 9600 genetically distinct micro- bial “species.” Most microbes varied accord- ing to environmental factors, but some were apparently influenced by genetics, because they were more similar in identical twins than in fraternal twins. The genetic makeup of these twins may affect gut physiology or biochemistry in a way that favors the growth of some microbes over others, the researchers suggest.

The microbes most strongly affected by genes belong to a recently discovered, rather obscure family of bacteria called Christensenellaceae. To the researchers’ surprise, this family was most abundant in lean twins and rare in obese ones. To see how the microbes might influence weight, Ley and her team transferred fecal material from lean and obese twins into germ-free mice. The weight gain in the mice mirrored that of the humans donating the feces. And when Goodrich supplemented feces from obese twins with one of the microbes, Christensenella minuta, and gave them to mice, the mice stayed lean. The microbe “has some aspect of being able to influence weight,” says Cornell geneticist and co-author Andrew Clark.
“We want to see if [the microbe] can be developed as a probiotic for helping people maintain their weight once they’ve lost it,” Ley says. But she and her colleagues first need to figure out how C. minuta exerts its effects and whether such a treatment would work only in people genetically dis- posed to supporting it. At this point, says Nita Salzman, a pathologist at the Medi- cal College of Wisconsin in Milwaukee, to think about a probiotic “is almost certainly an oversimplification.” ■ 

An Internet research project draws conservative ire

Truthy project at Indiana University analyzes Twitter traffic to understand patterns of political discourse 

The truth about Truthy has become a
scarce commodity.
Truthy is a 4-year-old academic study of how information spreads on Twitter. The work, by researchers at Indiana University (IU), Bloomington, has been cited favorably in mainstream media reports about the broader phenom- enon of online memes—messages about ideas, issues, and events—and the role they can play in ev- erything from shaping protest movements to signaling out- breaks of disease. But recently the Indiana project fell afoul of another Internet phenom- enon—how some messages can spread even if they are not correct.
In the past few months, Truthy has become the target of wither- ing attacks from conservative bloggers and politicians. In particular, they have char- acterized a 4-year, $920,000 grant the sci- entists received in 2011 from the National Science Foundation (NSF) as an attempt by the U.S. government to monitor and restrict free speech. The attacks are “not simply a misunderstanding of our research,” says  computer scientist Filippo Menczer, the principal investigator on the NSF grant. They are “a deliberate attempt to distort what we have done.”

Menczer’s work, which is also supported by the military’s Defense Advanced Research Projects Agency and by the private James S. McDonnell Foundation, is rooted in the growing field of complex, nonlinear feed- back systems. “It has become a very hot topic of research,” notes Menczer, who is the director of IU’s Center for Complex Networks and Systems Research. The field includes studies of natural systems such as planetary orbits and climate—and also social ones, such as the spread of information on Twitter. Twit- ter itself has begun awarding grants to aca- demics who want to study its daily torrent of more than half a billion tweets.
Under the NSF grant, Menczer and his colleagues have studied Twitter messages to shed light on the nature of social dis- course. Some of their early work on U.S. po- litical debate, for example, found evidence of a growing polarization, in which people communicate mostly with those who hold similar views on any particular issue rather than trying to engage those who disagree with them. More recently, the researchers’ examination of the 2013 protests against the Turkish government found that the movement became more democratic over time, with a growing number of people shaping the direction of the protest. The re- searchers also hope to learn how to differ- entiate memes spread by real people from those broadcast by automated software, a technique used by some businesses and advocacy groups to create the illusion of a groundswell of public interest in an issue.

This summer, Truthy itself fell under scrutiny, starting with a 25 August piece in The Washington Free Beacon, a con- servative online news website. Its head- line proclaimed that the U.S. government is “Creating [a] Database to Track ‘Hate Speech’ on Twitter.” Within days, several conservative commentators jumped on the anti-Truthy bandwagon. “So some bureau- crat decides whether you are being hateful or misinforming people—what could pos- sibly go wrong?” a reporter for Fox News asked sarcastically.
Elizabeth Harrington, who wrote the Free Beacon story, says she was just doing her job. “One of the areas that I cover is how government is spending taxpayers’ money, and I found this grant interesting,” she ex- plains. “The whole premise of the project struck me as questionable, and I hadn’t seen any other coverage of this aspect of the research.” Many of the critical stories quote selectively from a Truthy grant abstract on NSF’s website to argue that the research is an example of the Obama adminis- tration’s targeting of conserva- tives. The Free Beacon story, for example, says NSF “is financing the creation of a web service that will monitor ‘suspicious memes’and what it considers ‘false and misleading ideas,’ with a major focus on political activ- ity online.” But those phrases actually apply to an online platform that the researchers created to give the public a chance to com- ment on anything being tweeted. The sci- entists weren’t deciding which tweets were “suspicious,” nor targeting any particular ideological position.

 “The headlines are saying something that is completely false and fabricated,” Menczer told the Columbia Journalism Re- view, which covered the flap in September. “We are not defining hate speech. We are not tracking people. We don’t have a database.” New findings are posted regularly on the project’s website and written up in regular academic journals, he explained, and noth- ing is being secretly funneled to a govern- ment agency for some nefarious purpose.

Even so, conservative commenters have continued to pillory the work. A 17 October op-ed in The Washington Post by Ajit Pai, one of two Republicans on the five-member Fed- eral Communications Commission, called the project an attempt “to squint for and squelch” political comments. “The federal government has no business spending your hard-earned money on a project to monitor political speech on Twitter,” Pai asserted.
Senior Republican lawmakers are also suspicious of Truthy. Representative Lamar Smith (R–TX), the chair of the science com- mittee in the U.S. House of Representa- tives, said he’s adding the grant to his list of questionable research projects that NSF has funded over the years (Science, 10 Octo- ber, p. 152). “[T]his one appears to be worse than a simple misuse of public funds,” Smith said in a 21 October press release.
Truthy takes its name from “truthiness,” a word satirist Stephen Colbert invented for his television show, The Colbert Report. In a 2006 interview, Colbert explained why he coined the word. “It used to be, everyone was entitled to their own opinion, but not their own facts,” Colbert noted. “But that’s not the case anymore. Facts matter not at all. Perception is everything. It’s certainty [that counts].”
Ironically, the NSF solicitation for the program that is funding Menczer’s team notes that the growth of social media may aggravate social conflict because it offers a common platform to “parties who may not know or trust each other.” Those conflicts can easily snowball online, the program so- licitation noted.
NSF officials warned Menczer that at- tempting to defend himself could backfire, he notes. “They said, ‘Be very careful. You don’t want to talk about politics. That’s not what you do.’ ” Even so, the Truthy research- ers have posted a running rebuttal on their website, including what the project is and isn’t, and Menczer says he’s willing to speak with those he views as “bona fide reporters who want to know about my work.”

The team’s current NSF grant ends next summer, and Menczer isn’t sure if he’ll sub- mit a new proposal to the agency. But if he does, he predicts that “we will probably stay away from anything to do with politics.” ■ 

Delays hinder Ebola genomics

For months, no sequences from the virus have been released

as the Ebola epidemic sweeps through
West Africa, scientists lack key ge- netic data to answer a question that has provoked much worried specu- lation: Is the virus becoming more transmissible or more deadly, or ac-
quiring changes that would let it evade diag- nostic tests or vaccines? Thousands of blood samples from Ebola patients have been sit- ting in refrigerators in Africa and Europe, untouched. And, as Science went to press, the few groups that have new sequence data have not made them public.
Researchers are eager for a close-up look at how the virus may be evolving. Besides answering questions about its virulence, genomic data could reveal details about the epidemic, including hotspots of trans- mission and how often the virus has escaped from its animal reservoir to humans, says Andrew Rambaut, an evolutionary biologist who studies infectious diseases at the Uni- versity of Edinburgh in the United Kingdom. “If it can be done on a timely basis, you can really get insight into what is going on.” But faced with the all-consuming public health response to the epidemic, bureaucratic obstacles, and chaotic record keeping, scien- tists have had to wait.

In August, the world got its closest mo- lecular look at the virus so far, when re- searchers published 99 genomes of viruses from 78 patients who were infected in or around Kenema, Sierra Leone, from late May to mid-June. That analysis, published online on 28 August in Science, included more than half of the known cases in Sierra Leone at the time.
The sequence data, which the researchers deposited in public databases as soon as they were generated, showed how the virus changed as it passed from person to person at the start of the Si- erra Leone outbreak, with one variant dis- appearing as another gained  rominence among later cases. Since then, the outbreak has exploded into an epidemic—it has now sickened more than 13,000 and killed 5000—but the team, led by Pardis Sabeti and Stephen Gire at the Broad Institute in Cam- bridge, Massachusetts, has been unable to import any new samples from Sierra Leone. 

Other groups have been similarly stymied. Several researchers say that getting export approval from beleaguered health ministries has been tough. “I can only assume that the system is so overwhelmed that processing samples beyond simple diagnostic tests is not high priority,” says Rambaut, who was a co-author on the August sequence paper. Stephan Günther, a virologist at the Ber- nhard Nocht Institute for Tropical Medicine (BNI) in Hamburg, Germany, and coordi- nator of the European Mobile Laboratory (EMLab) consortium, says they have been unable to export samples from Nigeria or Liberia. But BNI has been receiving samples from the EMLab mis- sion in Guinea since March and now has close to 3000, he says. (BNI is storing them in its high-security lab on behalf of the Guinean government, which

still owns them.) Günther and his col-
leagues have not yet sequenced any of the samples, because consortium staff members have been busy supporting diagnostic cen- ters in affected countries. “We are all busy with fieldwork,” Günther says. “Personnel is a bit of a problem.” That should ease, he says, with a new €1.7 million ($2.1 million) award from the European Union to EMLab for Ebola research.
In France, the Institut Pasteur, where early samples from Guinea were first iden- tified as Ebola, also experienced delays exporting samples from West Africa but plans to start sequencing new viral ge- nomes soon. The institute’s lab in Dakar recently received samples from Guinea, says Felix Rey, who is coordinating the institute’s Ebola task force in Paris. The Dakar lab will extract RNA and send it to Paris for high-throughput sequencing. “We hope to have sequenced viruses from
a couple of hundred samples in the next month or so,” Rey says.

Sabeti and her colleagues should soon get their Sierra Leone samples, which finally were cleared for export and arrived in the United States last week, says Robert Garry of Tu- lane University in New Orleans, Louisiana, who collaborates with Sabeti. But to speed the research, she and her colleagues are try- ing to secure funding to send se- quencing machines to West Africa. “If we can’t get the samples here, we will get the sequencers there,” she says. The effort will build on the researchers’ ongoing work with the African Centre of Excellence for Genomics of Infectious Diseases, a consortium of universities and research institutes in the United States, Nigeria, Sierra Leone, and Senegal, which for several years has been training African researchers in the use of genomics tools.

Blood samples alone aren’t enough for genomic studies. Investigators need to know at least where each patient was from; ideally they will also have clinical information such as whether he or she survived. “Only when you have those pieces of information can you come up with useful information from the sequences,” Günther says—and because of spotty record keeping, that information is often missing. He and his colleagues are working with Doctors Without Borders and the World Health Organization to match samples with relevant information, but set- ting up a database is time- and labor-inten- sive, he says.
Meanwhile, the few Ebola virus sequences that have been generated since that ini- tial batch from Sierra Leone have not been made public. The U.S. Centers for Disease Control and Prevention (CDC) announced in August that it had sequenced Ebola virus samples from patients treated in the United States. But the data have not been placed in any public sequence repositories. That’s un- fortunate, Rambaut says. “As the U.S. cases are from Liberia and we have zero sequences from there so far, even one genome would be interesting and potentially useful,” he says. Duncan MacCannell, a bioinformat- ics specialist at CDC in Atlanta, told Science that the sequences had been “actively shared and discussed with the public health com- munity.” He says CDC is working to submit the sequences to a public database.
New sequences probably won’t show that the virus is finding new ways to attack or spread, Rambaut says. Instead, the prize is a clearer picture of the outbreak. A cluster of closely related viruses might point to a hotspot of transmission, he says, while un- expectedly diverse sequences would suggest that many cases were going undetected. Sequence data could also help researchers tell whether there has been more than one animal-to-human introduction.

Earlier sequence data did suggest that the virus was undergoing rapid changes, but that is not necessarily a sign that it is becoming more dangerous, Rambaut says. “Most RNA viruses mutate quickly, but ad- aptation and functional change is a much slower process.” Measles mutates nearly as quickly as Ebola virus, but it has never evolved to escape the lifelong immunity of previously infected or vaccinated individu- als. Even in an outbreak this big, Rambaut says, “I see no reason to suspect the virus will radically change its life cycle or its mode of transmission.” ■