Like many influenza virologists, John Steel of Emory University in Atlanta often uses a feeble lab strain of influenza in his studies of how seasonal flu spreads. “It’s a nasty virus if you’re a mouse” but doesn’t sicken humans, Steel says of this 80-year-old lab strain, known as PR8. But last month, under orders from the National Institutes of Health (NIH), Steel told his two staff members working with PR8 to put their experiments on hold and find other things to do while NIH decides whether the work falls under a temporary ban on risky virus experiments.“Our feeling is that the likelihood [of harm from studies with the PR8 strain] is exceedingly slim,” says Walter Orenstein, who oversees Emory’s NIH-funded influenza research center. “But it’s something for the NIH to decide.”Last month in an unusual step, the U.S. government announced a “pause” in federal funding for virology studies that involve tweaking influenza, MERS, and SARS viruses in ways that could make them more transmissible or pathogenic in mammals. The government encouraged everyone conducting such gain-of-function (GOF) projects to voluntarily pause while experts spend a year hashing out the risks and benefits of the studies and developing a policy for when to allow them.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)The United States’s move came amid long-running concerns about GOF studies involving highly pathogenic avian flu strains such as H5N1. But the funding pause covers much more. Through a Freedom of Information Act request, ScienceInsider obtained copies of the 18 letters from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) telling 14 institutions to halt projects that may be covered by the pause. They suggest a scramble at NIAID to sort out exactly which projects must stop in the wake of the new order, which came from the White House Office of Science and Technology Policy and the Department of Health and Human Services.The instructions vary according to whether the work is done under contract or grant. The “Notice of Partial Stop Work Order” letters sent on 21 October to the seven institutions with government-funded contracts are blunt: They state that specific projects “must stop effective immediately” if they fall under the pause policy and give investigators 14 days to submit a list of halted experiments. But NIAID soon stepped back with a 30 October letter explaining that scientists should work with contracting officers to decide whether their experiments fall under the new policy.The 11 letters to institutions with grants state the pause is voluntary because the studies are already funded, but that once that funding runs out the work must stop. Investigators have 90 days to tell NIAID which experiments are stopping and to propose different directions for their research. (ScienceInsider compiled this list of the halted grants.)Many investigators are in the midst of negotiating with NIAID about whether some truly fit the policy’s GOF definition or, even if they do, are important enough to public health that they should be allowed to continue. (The NIH director can approve exemptions for research urgently needed to protect public health.) Among the halted projects:MERS and SARS: The pause includes three grants and two contracts that are attempting to develop a strain of the MERS coronavirus that sickens mice so that researchers will have an animal model for testing MERS drugs and vaccines. Matthew Frieman of the University of Maryland and NIAID intramural researcher Kanta Subbarao, whose planned MERS mouse project is also on hold, argued at a recent meeting of the National Science Advisory Board for Biosecurity (NSABB) that their work should be exempted because of the current MERS outbreak in the Middle East. Two projects on SARS, another coronavirus, have also been stopped.Influenza: Besides stopping grants for controversial GOF studies of H5N1 in the lab of University of Wisconsin, Madison, virologist Yoshihiro Kawaoka, the pause covers contracts for NIAID’s five Centers of Excellence for Influenza Research and Surveillance (CEIRS). The long-running program conducts surveillance for potential pandemic flu strains in the wild and studies the factors that allow influenza viruses to spread.One center is at St. Jude Children’s Research Hospital in Memphis, whose investigator Stacey Schultz-Cherry warned NSABB last month that the pause had halted important flu surveillance studies. The letter states that the pause potentially applies to six projects that range from studying the ecology of avian flu in live bird markets in Colombia to looking at drug-resistance mutations in seasonal influenza strains. St. Jude told ScienceInsider in a statement that after an internal review, investigators have halted all GOF studies but that “routine surveillance work will not be impacted.”At Emory, the pause has halted not only the CEIRS project with the lab-attenuated PR8 strain, but also a research grant project headed by Anice Lowen that is looking at how the cell types targeted by two different influenza viruses affect their propensity to exchange genes. Lowen, who has told NIAID she thinks the study does not fall under the pause definition, says the uncertainty is affecting her ability to recruit new graduate students because she can’t say for sure which projects they might work on.An investigator at the CEIRS center at Johns Hopkins University in Baltimore, Maryland, virologist Andrew Pekosz, says he has halted two projects listed in his stop work letter. But he has told NIAID that his studies introducing changes to seasonal influenza to understand how it circulates year to year are not done with the intention of increasing pathogenicity or transmissibility. “I don’t think they qualify as gain-of-function,” he says.Harvard University epidemiologist Marc Lipsitch, who has pushed for a moratorium on GOF studies on potential pandemic pathogens, told ScienceInsider he could not comment on the paused studies without seeing details. He points out that NIH funds at least 220 influenza research grants, so the pause has stopped only a small fraction. Still, “Flu and coronavirus research is extremely important as an overall NIH activity, and it will be crucial to separate the activities that meet the definition of the pause from those that don’t,” he says. At last month’s NSABB meeting, the board discussed plans to write U.S. officials to express concerns about the reach of the pause. The board is holding a teleconference on 25 November to finalize its draft statement.