NEWS

milabs NOA experiment. That project, to begin next year, will study neutrinos red 810 kilometers to a lower-tech surface detector in Ash River, Minnesota. (Fermilab also runs an experiment called MINOS that uses the same beamline to re neutrinos 735 kilometers to a detector in the Soudan mine in Minnesota.) At 10,000 tonnes, LBNE could resolve the mass hierarchy and detect evidence of CP violationalthough it couldnt make a def inite discovery. I would feel that anything less than 10,000 tonnes wouldnt be compelling, says Fermilabs Regina Rameika. But small doesnt mean cheap. The 5000-tonne detector would cost $132 million; the 10,000tonne model would run roughly $170 million.
INFLUENZA

ADRIAN CHO

One H5N1 Paper Finally Goes to Press; Second Greenlighted

They have been called the most famous papers that were never published. But now, one of two controversial studies that shows how to make H5N1 avian inuenza more transmissible in mammals is up on Natures Web site for all the world to scrutinizeincluding, some worry, would-be bioterrorists who might use the information to set off a pandemic. The other paper received a crucial go-ahead from the Dutch government last week and will likely be published by Science soon. In December, the U.S. National Science Advisory Board for Biosecurity (NSABB) recommended that the two studiesboth of which use ferrets, a popular model for human inuenzanot be published in full. But after an expert panel convened by the World Health Organization (WHO) disagreed with the decision, NSABB reviewed revised versions of the manuscripts and changed its position (Science, 6 April, p. 19). That cleared the way for Nature on 2 May to publish the rst of the two experiments, led by Yoshihiro Kawaoka of the University of Wisconsin, Madison, and the University of Tokyo. Kawaokas unusually long, 11-page article describes how his group stitched a mutated version of the hemagglutinin protein of the bird flu virusthe H5onto the H1N1 virus that caused a relatively mild pandemic in 2009. The team explains that introducing into H5 a mere four mutations, which are delicately balanced with each other, allowed this hybrid virus to bind more strongly to mammalian cells and copy itself at high enough levels to readily transmit via respiratory dropinitial recommendation, the Dutch government insisted that Ron Fouchier of Erasmus MC in Rotterdam apply for an export license before submitting his revised manuscript ( Science , 20 April, p. 285). He called the decision pure censorship, but on 24 April he led the application, still disputing his obligation to do so and stressing that he did not want to set a precedent. Fouchier sent the paper to Science soon after the Dutch government issued the permit on 27 April. Early this week, the paper was still under review and being edited. Both Fouchier and Kawaoka had hoped the two papers, whose fates had been closely linked for 6 months, would appear simultaneously, which Science Executive Editor Monica Bradford says would have been ideal as well. I regret that both papers will not appear online together, but our priority must be to serve our authors and readers, Nature Editor-in-Chief Philip Campbell said in a statement. You cant blame them, Fouchier says. Despite the massive debate about these two papers, the Kawaoka study adds only a piece to a puzzle that his and other groups have been putting together for years. Inuenza researchers have long attempted to understand the mutations and mechanisms that make a strain spread readily in humans. Kawaokas study is an important additional step along the way, says Malik Peiris, a u researcher at the University of Hong Kong, who co-wrote an article in Nature about the Kawaoka paper. Inuenza infection begins when hemag-

First to nish. Yoshihiro Kawaoka (above) had his paper published this week.

lets. Although the researchers dont know whether these mutations would support sustained human-to-human transmission, many virologists worry mightily about this scenario. To date, H5N1 has not spread easily between humans, but in 355 of 602 conrmed cases, the patient has died. The second paper has been held up in an extra bureaucratic tangle. After NSABBs
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Physicists may even have to give up on Homestake entirely. Some researchers want to reuse Fermilabs existing beamline, which is more powerful than neutrino beams in Europe or Japan, and build the LBNE detector at Soudan or Ash River. But others argue that the distance to either site in Minnesota is too short to ever fulll LBNEs complete scientic program. The two most likely options appear to be a 17,000-tonne detector on the surface at Soudan orif DOE is willing to spend just a bit morea 10,000-tonne detector on the surface at Homestake, said Charles Baltay, a steering committee member from Yale University. But his summary of the day-and-a-half-long workshop left some

physicists feeling rushed. I spent 3 months choosing my last car; were going to make a decision to go to Soudan in 3 weeks? asked Robert Svoboda of the University of California, Davis, who is co-spokesperson for the LBNE collaboration. But nothing will be gained by waiting, says Fermilab Director Pier Oddone. If you want to take a year to make a decision when everything is known, youre only adding a year to an already long process, he says. And the clock is ticking. LBNEs reconguration steering committee has promised to deliver a report to DOE on 1 July, in time for agency ofcials to digest it before submitting their 2014 budget request to the White House.

NEWS&ANALYSIS
glutinin binds to receptors Paulson, a co-author of the on the host cell. The proVirology paper with Cox who tein is shaped like a mushstudies inuenza binding at room, with a long stalk and the Scripps Research Instia globular head that contute in San Diego, California. tains the binding site. Three Keiji Fukuda, a u expert of the mutations Kawaokas at WHO, says the paper will group describes are in or near help guide surveillance for the binding site. They make viruses that may cause great the virus prefer receptors on harm in humans. Thats not human cells to avian ones. just because they highlight Several groups revealed specic mutations, Cox adds. similar binding site mutations What were really lookearlier. Indeed, on 5 Noveming for is generalizable patber 2011, while NSABB terns of changes that occur was debating the wisdom when viruses become more of publishing the Kawaoka transmissible in a mammaand Fouchier papers in full, lian model. You cant be a report appeared online in focused on a set of four speVirology that showed respicic mutations. ratory transmission in one Hot spots. Mutations near hemagNow, inuenza scientists of two ferrets with a lab- glutinins binding site (yellow) and are eagerly awaiting publicamade H5 virus that had two stalk increased transmissibility. tion of Fouchiers study, still of the binding-site mutations under wraps, which Kawaalso reported by Kawaokas group. But these oka recently said has striking similarities researchers stressed that respiratory transmis- with his own. Its unclear how these publicasion required additional mutations. tions will affect a self-imposed moratorium Nancy Cox, a flu researcher at the U.S. on studies that involve modifying the transCenters for Disease Control and Preven- missibility or lethality of H5N1. Announced tion in Atlanta who co-authored that study by researchers from the worlds most active which an internal biosecurity committee said could be publishedapplauds Kawaoka and his colleagues for their absolutely fantastic A R C H A E O LO G Y work and says their mutant denitely moved the transmission bar to the right towards being fully transmissible. But she notes that even the new mutant does not spread as readily as MEMPHIS, TENNESSEEBack in 2000, a nowcommon, seasonal u strains. famous scientic paper called The RevoluCox and others say the most novel nding tion That Wasnt argued that the then-conin the Kawaoka study involves a mutation in ventional wisdom that modern human behavthe stalk. This fourth mutation surfaced after ior had erupted in a creative explosion a series of experiments that coaxed out muta- about 50,000 years ago in Europe was wrong. tions to make the virus spread more easily in Rather, anthropologists Sally McBrearty and ferrets. The effort included screening 2 mil- Alison Brooks contended that modern behavlion randomly created mutants and infecting ior, including creativity, has deep and ancient ferrets to let strains further adapt to them. The roots, going back some 300,000 years ago in best transmitter spread from infected animals Africa (Science, 15 February 2002, p. 1219). to four of six healthy ferrets in neighboring At a meeting* here last month, researchcages. It did not kill any of the animals. ers heard new evidence that human evolution The role of the stalk mutation became took a gradual, rather than revolutionary, clear in a set of additional experiments. Hem- course during two other key junctures in preagluttinins second jobafter latching onto history. A study of ancient stone tools from the host receptoris to fuse viral and host South Africa concludes that hunters manucells membranes as the virus enters the cell. factured spears with stone pointsa sign The mutations at the binding site make it dif- of complex behavior200,000 years earcult for the protein to do that in the slightly lier than had previously been thought. And acidic environment of human mucosa, the new excavations at a 20,000-year-old settleresearchers say, but the mutation on the stalk ment in Jordan, laden with artifacts typical compensates by enabling the protein to operate in a more acidic environment. Its the *Paleoanthropology Society 2012 Annual Meeting. major discovery in the study, says James Memphis, Tennessee, 1718 April. H5N1 labs in January, the moratorium was extended indenitely at a February meeting organized by WHO. A related, vigorous debate continues about whether H5N1 modication studies should be conned to the most secure laboratories known in the United States as biosafety level 4 facilitiesor enhanced BSL-3 laboratories, where both Kawaoka and Fouchier performed their experiments. WHO will not take sides, nor will it advise on the moratorium, Fukuda says. Others say the moratorium should remain in force until the safety issues are resolved. We should not rush forward when the stakes are so high, Thomas Inglesby, director of the Center for Biosecurity at the University of Pittsburgh Medical Center in Pennsylvania, told a U.S. Senate committee at a hearing on 26 April. Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases, which funded the two studies, agrees. Before U.S. ofcials support lifting the ban, he said at last weeks hearing, they will have to feel comfortable that H5N1 labs understand how to evaluate the dual-use potential of their work and take steps to mitigate safety and security risks.
MARTIN ENSERINK AND JON COHEN
With reporting by David Malakoff.

of much later sites, suggest that the dramatic rise of farming villages in the Near East also had early and deep roots. The pair of talks provides still more reasons why we should be skeptical of revolutions in archaeology, says archaeologist Nicholas Conard of the University of Tbingen in Germany. Indeed, many archaeologists now think that apparent revolutions are due to gaps in the record or to behavioral shifts triggered by changing conditions, rather than sudden advances in cognition. What appear to be precociously sophisticated behaviors are really reections of what prehistoric humans were capable of all along, says archaeologist John Shea of Stony Brook University in New York state. Humans were getting smart about how to hunt wild animals much earlier than previously known, according to a talk by archaeologist Jayne Wilkins of the University of Toronto in Canada. Wilkins, Benjamin Schoville of Arizona State University (ASU), Tempe, and Kyle Brown of the University of Cape Town in South Africa analyzed stone

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New Light on Revolutions That Werent

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