Gain-of-function research

{{see also|CRISPR}}In early 2011, two groups were investigating how flu viruses specific to birds could possibly cross over and create pandemics in humans: one led by Yoshihiro Kawaoka at the University of Wisconsin–Madison in Madison, Wisconsin, and another led by Ron Fouchier at Erasmus University Medical Center in the Netherlands.{{cite journal |doi=10.1038/nature10831 |title=Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets |year=2012 |last1=Imai |first1=Masaki |last2=Watanabe |first2=Tokiko |last3=Hatta |first3=Masato |last4=Das |first4=Subash C. |last5=Ozawa |first5=Makoto |last6=Shinya |first6=Kyoko |last7=Zhong |first7=Gongxun |last8=Hanson |first8=Anthony |last9=Katsura |first9=Hiroaki |last10=Watanabe |first10=Shinji |last11=Li |first11=Chengjun |last12=Kawakami |first12=Eiryo |last13=Yamada |first13=Shinya |last14=Kiso |first14=Maki |last15=Suzuki |first15=Yasuo |last16=Maher |first16=Eileen A. |last17=Neumann |first17=Gabriele |last18=Kawaoka|first18=Yoshihiro |journal=Nature |volume=486 |issue=7403 |pages=420–428 |pmid=22722205 |pmc=3388103 |bibcode=2012Natur.486..420I}}{{cite journal |last1=Schrauwen |first1=Eefje J. A. |last2=Herfst |first2=Sander |last3=Leijten |first3=Lonneke M. |last4=van Run |first4=Peter |last5=Bestebroer |first5=Theo M. |last6=Linster |first6=Martin |last7=Bodewes |first7=Rogier |last8=Kreijtz |first8=Joost H. C. M. |last9=Rimmelzwaan |first9=Guus F. |last10=Osterhaus |first10=Albert D. M. E. |last11=Fouchier |first11=Ron A. M. |last12=Kuiken |first12=Thijs |last13=van Riel |first13=Debby |title=The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets |journal=Journal of Virology |date=April 2012 |volume=86 |issue=7 |pages=3975–3984 |doi=10.1128/JVI.06828-11 |pmid=22278228 |pmc=3302532 |issn=1098-5514}} Both groups had serially passaged the H5N1 avian influenza in ferrets, manually taking the virus from one ferret to another, until it was capable of spreading via respiratory droplets. The normally bird-specific virus, through replication over time in the ferrets' lungs, had adopted several amino acid changes that enabled it to replicate in the mammalian lungs, which are notably colder than those found in birds.{{cite journal |last1=Connor |first1=R. J. |last2=Kawaoka |first2=Y. |last3=Webster |first3=R. G. |last4=Paulson |first4=J. C. |title=Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates |journal=Virology |date=1994-11-15 |volume=205 |issue=1 |pages=17–23 |doi=10.1006/viro.1994.1615 |pmid=7975212 |issn=0042-6822}}{{cite journal |last1=Dance |first1=Amber |title=The shifting sands of 'gain-of-function' research |journal=Nature |date=28 October 2021 |volume=598 |issue=7882 |pages=554–557 |doi=10.1038/d41586-021-02903-x |pmid=34707307 |bibcode=2021Natur.598..554D |s2cid=240071919|doi-access=free }} This small change also allowed the virus to transmit via droplets in the air made when the ferrets coughed or sneezed.

Proponents of the Kawaoka and Fouchier experiments cited several benefits: these answered the question of how a virus like H5N1 could possibly become airborne in humans, allowed other researchers to develop vaccines and therapeutics which specifically targeted these amino acid changes,{{cite journal |last1=Belser |first1=Jessica A. |last2=Tumpey |first2=Terrence M. |title=H5N1 pathogenesis studies in mammalian models |journal=Virus Research |date=2013-12-05 |volume=178 |issue=1 |pages=168–185 |doi=10.1016/j.virusres.2013.02.003 |pmid=23458998 |pmc=5858902 |issn=1872-7492}}{{cite journal |last1=Holzer |first1=Barbara |last2=Morgan |first2=Sophie B. |last3=Matsuoka |first3=Yumi |last4=Edmans |first4=Matthew |last5=Salguero |first5=Francisco J. |last6=Everett |first6=Helen |last7=Brookes |first7=Sharon M. |last8=Porter |first8=Emily |last9=MacLoughlin |first9=Ronan |last10=Charleston |first10=Bryan |last11=Subbarao |first11=Kanta |last12=Townsend |first12=Alain |last13=Tchilian |first13=Elma |title=Comparison of Heterosubtypic Protection in Ferrets and Pigs Induced by a Single-Cycle Influenza Vaccine |journal=The Journal of Immunology |date=2018-06-15 |volume=200 |issue=12 |pages=4068–4077 |doi=10.4049/jimmunol.1800142 |pmid=29703861 |pmc=5985365 |url=https://www.jimmunol.org/content/200/12/4068 |access-date=29 May 2021 |language=en |issn=0022-1767 |archive-date=2022-10-24 |archive-url=https://web.archive.org/web/20221024225752/http://www.jimmunol.org/content/200/12/4068 |url-status=live }}{{cite journal |last1=Belser |first1=Jessica A. |last2=Katz |first2=Jacqueline M. |last3=Tumpey |first3=Terrence M. |title=The ferret as a model organism to study influenza A virus infection |journal=Disease Models & Mechanisms |date=2011-09-01 |volume=4 |issue=5 |pages=575–579 |doi=10.1242/dmm.007823 |pmid=21810904 |pmc=3180220 |issn=1754-8403 }} and also demonstrated that there was a linkage in avian viruses between transmissibility and lethality: while the virus had become more transmissible, it had also become significantly less deadly.{{cite journal |last1=Resnik |first1=David B. |title=H5N1 Avian Flu Research and the Ethics of Knowledgg |journal=The Hastings Center Report |date=2013 |volume=43 |issue=2 |pages=22–33 |doi=10.1002/hast.143 |pmid=23390001 |pmc=3953619 |issn=0093-0334}}{{cite journal |last1=Herfst |first1=Sander |last2=Schrauwen |first2=Eefje J. A. |last3=Linster |first3=Martin |last4=Chutinimitkul |first4=Salin |last5=de Wit |first5=Emmie |last6=Munster |first6=Vincent J. |last7=Sorrell |first7=Erin M. |last8=Bestebroer |first8=Theo M. |last9=Burke |first9=David F. |last10=Smith |first10=Derek J. |last11=Rimmelzwaan |first11=Guus F. |last12=Osterhaus |first12=Albert D. M. E. |last13=Fouchier |first13=Ron A. M. |title=Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets |journal=Science |date=2012-06-22 |volume=336 |issue=6088 |pages=1534–1541 |doi=10.1126/science.1213362 |pmid=22723413 |pmc=4810786 |bibcode=2012Sci...336.1534H |issn=0036-8075}} Various critics of the research (including members of Congress) responded to the publications with alarm. Others called the experiments an "engineered doomsday".{{cite news |title=Opinion An Engineered Doomsday |url=https://www.nytimes.com/2012/01/08/opinion/sunday/an-engineered-doomsday.html |work=The New York Times |date=2012-01-07 |archive-date=2023-03-26 |access-date=2021-05-29 |archive-url=https://web.archive.org/web/20230326085331/https://www.nytimes.com/2012/01/08/opinion/sunday/an-engineered-doomsday.html |url-status=live }} Questions were raised by other scientists including Marc Lipsitch of the T. H. Chan School of Public Health at Harvard University about the relative risks and benefits of this research.{{cite book |last1=Lipsitch |first1=Marc |title=Influenza Virus |chapter=Why Do Exceptionally Dangerous Gain-of-Function Experiments in Influenza? |series=Methods in Molecular Biology |date=2018 |volume=1836 |pages=589–608 |doi=10.1007/978-1-4939-8678-1_29 |pmid=30151594 |pmc=7119956 |isbn=978-1-4939-8677-4 |issn=1940-6029}}

At an international technical consultation convened by the WHO, it was concluded that this work was an important contribution to public health surveillance of H5N1 viruses and to a better understanding of the properties of these viruses, but that broader global discussions were needed.{{Cite web |date=February 2012 |title=Report on technical consultation on H5N1 research issues |url=https://www.who.int/publications/m/item/report-on-technical-consultation-on-h5n1-research-issues |access-date= |website=World Health Organization |language=en}} The European Academies of Science Advisory Council (EASAC) concluded that all required laws, rules, regulations, and codes of conduct are in place in several EU countries to continue this type of work responsibly.{{Cite web |date=2015-10-16 |title=Gain of Function: experimental applications relating to potentially pandemic pathogens |url=https://easac.eu/publications/details/gain-of-function-experimental-applications-relating-to-potentially-pandemic-pathogens |access-date= |website=easac.eu |language=en}} In the US, where regulations were previously less strict than in the EU, a new governmental policy and review mechanism was launched for "Potential Pandemic Pathogen Care and Oversight" (P3CO).

In May 2013, a group led by Hualan Chen, director of China's National Avian Influenza Reference Laboratory, published several experiments they had conducted at the BSL3+ laboratory of the Harbin Veterinary Research Institute, investigating what would happen if a 2009 H1N1 circulating in humans infected the same cell as an avian influenza H5N1.{{cite journal |doi=10.1126/science.1229455 |title=H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet |year=2013 |last1=Zhang |first1=Y. |last2=Zhang |first2=Q. |last3=Kong |first3=H. |last4=Jiang |first4=Y. |last5=Gao |first5=Y. |last6=Deng |first6=G. |last7=Shi |first7=J. |last8=Tian |first8=G. |last9=Liu |first9=L. |last10=Liu |first10=J. |last11=Guan |first11=Y. |last12=Bu |first12=Z. |last13=Chen |first13=H. |journal=Science |volume=340 |issue=6139 |pages=1459–1463 |pmid=23641061 |bibcode=2013Sci...340.1459Z |s2cid=206544849|doi-access=free }} Importantly, the experiments had been conducted before a research pause on H5N1 experiments had been agreed upon by the broader virologist community.{{cite news |last1=Yong |first1=Ed |title=Scientists create hybrid flu that can go airborne |url=https://www.nature.com/news/scientists-create-hybrid-flu-that-can-go-airborne-1.12925 |access-date=29 May 2021 |work=Nature News |year=2013 |language=en |doi=10.1038/nature.2013.12925 |archive-date=21 February 2023 |archive-url=https://web.archive.org/web/20230221212233/https://www.nature.com/news/scientists-create-hybrid-flu-that-can-go-airborne-1.12925 |url-status=live }}{{cite journal |last1=Fouchter |first1=Ron A. M. |last2=García-Sastre |first2=Adolfo |last3=Kawaoka |first3=Yoshihiro |last4=Barclay |first4=Wendy S. |last5=Bouvier |first5=Nicole M. |last6=Brown |first6=Ian H. |last7=Capua |first7=Ilaria |last8=Chen |first8=Hualan |last9=Compans |first9=Richard W. |last10=Couch |first10=Robert B. |last11=Cox |first11=Nancy J. |last12=Doherty |first12=Peter C. |last13=Donis |first13=Ruben O. |last14=Feldmann |first14=Heinz |last15=Guan |first15=Yi |last16=Katz |first16=Jacqueline M. |last17=Kiselev |first17=Oleg I. |last18=Klenk |first18=H. D. |last19=Kobinger |first19=Gary |author19-link=Gary Kobinger|last20=Liu |first20=Jinhua |last21=Liu |first21=Xiufan |last22=Lowen |first22=Anice |last23=Mettenletter |first23=Thomas C. |last24=Osterhaus |first24=Albert D. M. E. |last25=Palese |first25=Peter |last26=Petris |first26=J. S. Malik |last27=Perez |first27=Daniel R. |last28=Richt |first28=Jürgen A. |last29=Schultz-Cherry |first29=Stacey |last30=STteel |first30=John |last31=Subbarao |first31=Kanta |last32=Swayne |first32=David E. |last33=Takimoto |first33=Toru |last34=Tashiro |first34=Masato |last35=Taubenberger |first35=Jeffrey K. |last36=Thomas |first36=Paul G. |last37=Tripp |first37=Ralph A. |last38=Tumpey |first38=Terrence M. |last39=Webby |first39=Richard J. |last40=Webster |first40=Robert G |title=Transmission Studies Resume For Avian Flu |journal=Science |date=2013-02-01 |volume=339 |issue=6119 |pages=520–521 |doi=10.1126/science.1235140 |pmid=23345603 |pmc=3838856 |bibcode=2013Sci...339..520F |issn=0036-8075}} They used these experiments to determine that certain genes, if reassorted in such a dual-infection scenario in the wild, would allow transmission of the H5N1 virus more easily in mammals (notably guinea pigs as a model organism for rodent species), proving that certain agricultural scenarios carry the risk of allowing H5N1 to cross over into mammals. As in the Fouchier and Kawaoka experiments above, the viruses in this study were also significantly less lethal after the modification.{{cite journal |last1=Hvistendahl |first1=Mara |title=Veterinarian-in-Chief |journal=Science |date=2013-07-12 |volume=341 |issue=6142 |pages=122–125 |doi=10.1126/science.341.6142.122 |pmid=23846887 |bibcode=2013Sci...341..122H |url=https://www.science.org/doi/abs/10.1126/science.341.6142.122 |access-date=29 May 2021 |language=en |issn=0036-8075 |archive-date=2021-09-23 |archive-url=https://web.archive.org/web/20210923073712/https://www.science.org/doi/abs/10.1126/science.341.6142.122 |url-status=live |url-access=subscription }}

Critics of the 2013 Chen group study (including Simon Wain-Hobson of the Pasteur Institute and former Royal Society President Robert May) decried this as an unsafe experiment that was unnecessary to prove the intended conclusions, calling Chen's work "appallingly irresponsible" and also raising concerns about the biosafety of the laboratory itself. Others (including the director of the WHO Collaborating Centre on Influenza in Tokyo, Masato Tashiro) praised Chen's laboratory as "state of the art". Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, described the work as "remarkable" and said that it demonstrated the "very real threat" that "continued circulation of H5N1 strains in Asia and Egypt" posed.

A preprint by Boston University researchers, published on 14 October 2022, described their experiments splicing the SARS-CoV-2 BA.1 Omicron's spike protein into an ancestral SARS-CoV-2 variant isolated in the early days of the pandemic, creating a new chimeric version of the virus. All of the six mice exposed to the ancestral variant died; eight of the ten mice exposed to the chimeric variant died; and none of the ten mice exposed to Omicron died. This suggests that "mutations outside of spike are major determinants of the attenuated pathogenicity of Omicron in K18-hACE2 mice". According to the preprint, the work was supported by grants from various branches of the NIH, but the NIH later denied funding the experiments and the researchers stated the NIH did not fund the experiments directly.{{cite journal |last1=Callaway |first1=Ewen |last2=Kozlov |first2=Max |title=Which COVID studies pose a biohazard? Lack of clarity hampers research |journal=Nature |date=21 October 2022 |volume=611 |issue=7934 |pages=17–18 |doi=10.1038/d41586-022-03344-w |pmid=36271042 |bibcode=2022Natur.611...17C |s2cid=253063691 |language=en|doi-access=free }}{{cite journal |last1=Chen |first1=Da-Yuan |last2=Kenney |first2=Devin |last3=Chin |first3=Chue Vin |last4=Tavares |first4=Alexander H. |last5=Khan |first5=Nazimuddin |last6=Conway |first6=Hasahn L. |last7=Liu |first7=GuanQun |last8=Choudhary |first8=Manish C. |last9=Gertje |first9=Hans P. |last10=O'Connell |first10=Aoife K. |last11=Kotton |first11=Darrell N. |last12=Herrmann |first12=Alexandra |last13=Ensser |first13=Armin |last14=Connor |first14=John H. |last15=Bosmann |first15=Markus |last16=Li |first16=Jonathan Z. |last17=Gack |first17=Michaela U. |last18=Baker |first18=Susan C. |last19=Kirchdoerfer |first19=Robert N. |last20=Kataria |first20=Yachana |last21=Crossland |first21=Nicholas A. |last22=Douam |first22=Florian |last23=Saeed |first23=Mohsan |title=Role of spike in the pathogenic and antigenic behavior of SARS-CoV-2 BA.1 Omicron |date=14 October 2022 |journal=bioRxiv |doi=10.1101/2022.10.13.512134|pmid=36263066 |pmc=9580375 }} On 17 October, the Daily Mail ran the headline "Boston University CREATES a new COVID strain that has an 80% kill rate—echoing dangerous experiments feared to have started the pandemic". The headline was later flagged "as part of Facebook's efforts to combat false news and misinformation". PolitiFact noted the "lab leak" theory was unproven, and also stated "citing the 80% figure alone leaves out key context, including that the resulting strain was less fatal than the original, which killed 100% of mice. Experts say this kind of research is not unusual and the experiment was conducted in accordance with accepted safety procedures."{{cite web |website=PolitiFact |title=Instagram posts: 'Boston University CREATES a new COVID strain that has an 80% kill rate.' |url=https://www.politifact.com/factchecks/2022/oct/20/instagram-posts/claim-boston-university-created-covid-19-strain-80/ |access-date=24 October 2022 |archive-date=24 October 2022 |archive-url=https://web.archive.org/web/20221024030211/https://www.politifact.com/factchecks/2022/oct/20/instagram-posts/claim-boston-university-created-covid-19-strain-80/ |url-status=live }} All research funded by the NIH that can make COVID more virulent or transmissible must undergo an extra gain-of-function review. Critics charged that, because the chimera could have combined Omicron's high transmissibility with the ancestral strain's lethality, the experiment should have undergone the extra review. The researchers denied that the experiment qualified as gain-of-function in the first place.{{cite news |last1=Piper |first1=Kelsey |title=Why do labs keep making dangerous viruses? |url=https://www.vox.com/future-perfect/2022/10/19/23412562/covid-omircron-gain-of-function-research-engineered-pandemic-biosafety |access-date=24 October 2022 |work=Vox |date=19 October 2022 |language=en}}

Significant debate has taken place in the scientific community on how to assess the risks and benefits of gain-of-function research, and how to engage the public in deliberations for policymaking. These concerns encompass biosafety, relating to the accidental release of a pathogen into the population, biosecurity relating to the intentional release of a pathogen into the population, and bioethics, the principles of biorisk management and research review procedures.

In December 2014, the National Research Council and the Institute of Medicine organized a two-day symposium to discuss the potential risks and benefits of gain-of-function research. The event was attended by scientists from around the world, including George Gao, Gabriel Leung and Michael Selgelid, Baruch Fischhoff, Alta Charo, Harvey Fineberg, Jonathan Moreno, Ralph Cicerone, Margaret Hamburg, Jo Handelsman, Samuel Stanley, Kenneth Berns, Ralph Baric, Robert Lamb, Silja Vöneky, Keiji Fukuda, David Relman, and Marc Lipsitch.{{cite web|url=https://www.nationalacademies.org/our-work/gain-of-function-research-a-symposium|title=Gain-of-Function Research: A Symposium|website=National Academies|access-date=2021-02-05|archive-date=2021-02-10|archive-url=https://web.archive.org/web/20210210002255/https://www.nationalacademies.org/our-work/gain-of-function-research-a-symposium|url-status=live}} Shortly thereafter, the US government granted exceptions to the GoFR moratorium to 7 out of 18 research projects that had been affected.{{cite news |date=12 December 2014 |title=Summary Report – Dual Use Research on Microbes: Biosafety, Biosecurity, Responsibility |publisher=Volkswagen Foundation |url=https://www.volkswagenstiftung.de/sites/default/files/downloads/Summary_Report_HS_Dual_Use_Research_on_Microbes.pdf |archive-date=8 February 2021 |access-date=5 February 2021 |archive-url=https://web.archive.org/web/20210208233621/https://www.volkswagenstiftung.de/sites/default/files/downloads/Summary_Report_HS_Dual_Use_Research_on_Microbes.pdf |url-status=live }}

On March 10–11, 2016, the National Academies of Sciences, Engineering, and Medicine held its second public symposium to discuss potential U.S. government policies for the oversight of gain-of-function research. The symposium was held at the request of the U.S. government to provide a mechanism to engage the life sciences community and the broader public and solicit feedback on optimal approaches to ensure effective federal oversight of GoFR as part of a broader U.S. government deliberative process.{{Cite book |author1= Board On Life Sciences |author2= Division on Earth and Life Studies |author3= ((Board on Health Sciences Policy)) |author4= Health And Medicine Division |author5= ((Committee on Science, Technology, and Law)) |author6= ((Policy And Global Affairs)) |author7= ((National Academies of Sciences, Engineering, and Medicine)) |editor-first1= Piers|editor-first2= Jo|editor-first3= Frances|editor-first4= Audrey|editor-last1= Millett|editor-last2= Husbands|editor-last3= Sharples|editor-last4= Thevenon|url=https://easac.eu/fileadmin/PDF_s/reports_statements/GOF_symposium_summary_March_2016.pdf |title=Gain-of-Function Research: Summary of the Second Symposium |date=March 2016 |isbn=978-0-309-44077-6 |doi=10.17226/23484 |pmid=27403489 |access-date=January 29, 2021 |archive-url=https://web.archive.org/web/20201229174145/https://easac.eu/fileadmin/PDF_s/reports_statements/GOF_symposium_summary_March_2016.pdf |archive-date=December 29, 2020 |url-status=live}}

The Cambridge Working Group was formed by Harvard epidemiologist Marc Lipsitch with fellow scientists at a meeting held in Cambridge, Massachusetts, following a "trifecta" of biosecurity incidents involving the CDC, including the accidental exposure of viable anthrax to personnel at CDC's Roybal Campus,{{cite news |title=CDC Director Releases After-Action Report on Recent Anthrax Incident; Highlights Steps to Improve Laboratory Quality and Safety |url=https://www.cdc.gov/media/releases/2014/p0711-lab-safety.html |access-date=29 May 2021 |work=CDC |date=2016-01-01 |language=en-us |archive-date=2021-05-26 |archive-url=https://web.archive.org/web/20210526162443/https://www.cdc.gov/media/releases/2014/p0711-lab-safety.html |url-status=live }}{{cite news |title=Report on the Potential Exposure to Anthrax |work=CDC |url=https://www.cdc.gov/labs/pdf/Final_Anthrax_Report.pdf |access-date=29 May 2021 |date=11 July 2014 |archive-date=16 June 2021 |archive-url=https://web.archive.org/web/20210616183544/https://www.cdc.gov/labs/pdf/Final_Anthrax_Report.pdf |url-status=live }} the discovery of six vials containing viable smallpox from the 1950s, labeled as Variola but in a box with other samples poorly labeled, at the FDA's White Oak campus,{{cite journal |last1=Kaiser |first1=Jocelyn |title=Six vials of smallpox discovered in U.S. lab |url=https://www.science.org/content/article/six-vials-smallpox-discovered-us-lab |access-date=29 May 2021 |journal=Science |date=8 July 2014 |language=en}} and the accidental shipping of H9N2 vials contaminated with H5N1 from the CDC lab to a USDA lab.{{Cite journal |date=July 15, 2014 |title=Scientists call for limit on creating dangerous pathogens |url=https://www.science.org/content/article/scientists-call-limit-creating-dangerous-pathogens |journal=Science |archive-date=June 29, 2022 |access-date=June 30, 2022 |archive-url=https://web.archive.org/web/20220629072325/https://www.science.org/content/article/scientists-call-limit-creating-dangerous-pathogens |url-status=live }}

On July 14, 2014, the group published a Consensus Statement authored by 18 founding members, including Amir Attaran, Barry Bloom, Arturo Casadevall, Richard H. Ebright, Alison Galvani, Edward Hammond, Thomas Inglesby, Michael Osterholm, David Relman, Richard Roberts, Marcel Salathé and Silja Vöneky. Since its initial publication, over 300 scientists, academics, and physicians have added their signature.{{cite journal |last1=Husbands |first1=Jo L. |title=The challenge of framing for efforts to mitigate the risks of "dual use" research in the life sciences |journal=Futures |date=September 2018 |volume=102 |pages=104–113 |doi=10.1016/j.futures.2018.03.007 |pmid=32226095 |pmc=7094442 |issn=0016-3287}}{{cite web |title=The Cambridge Working Group |url=http://www.cambridgeworkinggroup.org/ |website=Cambridgeworkinggroup.org |access-date=29 May 2021 |archive-date=26 May 2021 |archive-url=https://web.archive.org/web/20210526174822/http://www.cambridgeworkinggroup.org/ |url-status=live }}

The statement advocates for all work involving potential pandemic pathogens to be halted until a quantitative and objective assessment of the risks has been undertaken. It then argues that alternative approaches that do not involve such risks should be used instead.{{cite journal |last1=Burki |first1=Talha |title=Ban on gain-of-function studies ends |journal=The Lancet Infectious Diseases |date=2018-02-01 |volume=18 |issue=2 |pages=148–149 |doi=10.1016/S1473-3099(18)30006-9 |pmid=29412966 |pmc=7128689 |language=English |issn=1473-3099}}{{cite journal |last1=Lipsitch |first1=Marc |last2=Esvelt |first2=Kevin |last3=Inglesby |first3=Thomas |title=Calls for Caution in Genome Engineering Should Be a Model for Similar Dialogue on Pandemic Pathogen Research |journal=Annals of Internal Medicine |date=2015-09-08 |volume=163 |issue=10 |pages=790–791 |doi=10.7326/M15-1048 |pmid=26344802 |s2cid=37616990 |url=https://www.acpjournals.org/doi/abs/10.7326/M15-1048 |access-date=29 May 2021 |issn=0003-4819 |archive-date=2022-09-17 |archive-url=https://web.archive.org/web/20220917061309/https://www.acpjournals.org/doi/abs/10.7326/M15-1048 |url-status=live |url-access=subscription }}

The group engaged in public advocacy, influencing the US government's decision in December 2014 to suspend funding of research that would create certain types of novel potential pandemic pathogens.{{Cite journal |last1=Lipsitch |first1=Marc |last2=Inglesby |first2=Thomas V. |date=December 12, 2014 |title=Moratorium on Research Intended To Create Novel Potential Pandemic Pathogens |journal=mBio |volume=5 |issue=6 |doi=10.1128/mBio.02366-14 |pmc=4271556 |pmid=25505122}}

Shortly after the Cambridge Working Group released its position statement, Scientists for Science was formed by 37 signatories taking an alternative position, that "biomedical research on potentially dangerous pathogens can be performed safely and is essential for a comprehensive understanding of microbial disease pathogenesis, prevention and treatment."{{Cite journal |last1=Edelmann |first1=Achim |last2=Moody |first2=James |last3=Light |first3=Ryan |date=2017-05-24 |title=Disparate foundations of scientists' policy positions on contentious biomedical research |journal=Proceedings of the National Academy of Sciences |language=en |volume=114 |issue=24 |pages=6262–6267 |doi=10.1073/pnas.1613580114 |issn=0027-8424 |pmid=28559310 |pmc=5474814 |bibcode=2017PNAS..114.6262E |doi-access=free}} Since its publication, the SfS statement has received 200+ signatures from working scientists, academics, and biosafety professionals.{{cite web |title=Scientists for Science |url=http://www.scientistsforscience.org/ |website=www.scientistsforscience.org |access-date=29 May 2021 |archive-date=17 May 2021 |archive-url=https://web.archive.org/web/20210517135348/http://www.scientistsforscience.org/ |url-status=live }}

One of the group's founding members, University of Pittsburgh virologist W. Paul Duprex, has argued ({{circa|2014}}) that the then-recent few events were exceptions to an overall good record of lab safety, and that these exceptions should not have been a reason for shutting down experiments that may have been of tangible benefit to public health.{{Cite web |title=Biologists Choose Sides In Safety Debate Over Lab-Made Pathogens |url=https://www.npr.org/sections/health-shots/2014/08/13/339854400/biologists-choose-sides-in-safety-debate-over-lab-made-pathogens |access-date=2021-05-07 |website=NPR |language=en |quote="There are multiple events that have come together in a rather unusual convergence," says Paul Duprex, a microbiologist at Boston University. He sees the recent reports of lab mistakes as exceptions — they don't mean you should shut down basic science that's essential to protecting public health, he says."These viruses are out there. They cause disease; they have killed many, many people in the past," Duprex says. "We bring them to the laboratory to work with them." |archive-date=2021-05-07 |archive-url=https://web.archive.org/web/20210507024722/https://www.npr.org/sections/health-shots/2014/08/13/339854400/biologists-choose-sides-in-safety-debate-over-lab-made-pathogens |url-status=live }} He and other SfS signatories have argued that these pathogens are already subject to extensive regulations and that it would be more advantageous and effective to focus on improving lab safety and oversight, ensuring that experiments are conducted in the public interest.{{cite web |title=Scientists for Science |url=http://www.scientistsforscience.org/ |website=www.scientistsforscience.org |access-date=29 May 2021 |quote="In recognition of this need, significant resources have been invested globally to build and operate BSL-3 and BSL-4 facilities, and to mitigate risk in a variety of ways, involving regulatory requirements, facility engineering, and training. Ensuring that these facilities operate safely and are staffed effectively so that risk is minimized is our most important line of defense, as opposed to limiting the types of experiments that are done." |archive-date=17 May 2021 |archive-url=https://web.archive.org/web/20210517135348/http://www.scientistsforscience.org/ |url-status=live }}{{cite journal |last1=Duprex |first1=W. Paul |last2=Fouchier |first2=Ron A. M. |last3=Imperiale |first3=Michael J. |last4=Lipsitch |first4=Marc |last5=Relman |first5=David A. |title=Gain-of-function experiments: time for a real debate |journal=Nature Reviews Microbiology |year=2015 | issue=January 2015 |publication-date=2014-12-08 |volume=13 |pages=58–64 |doi=10.1038/nrmicro3405 |pmid=25482289 |pmc=7097416 |language=en |issn=1740-1534}}

Notable signatories are Constance Cepko, Dickson Despommier, Erica Ollmann Saphire, Geoffrey Smith, Karla Kirkegaard, Sean Whelan, Vincent Racaniello and Yoshihiro Kawaoka. Columbia University virologist Ian Lipkin, who signed both statements, said "there has to be a coming together of what should be done".{{Cite web |title=Science Magazine - 05 September 2014 - page20 |url=https://www.sciencemagazinedigital.org/sciencemagazine/05_september_2014?pg=20 |access-date=2021-05-07 |website=www.sciencemagazinedigital.org |language=en |archive-date=2021-08-02 |archive-url=https://web.archive.org/web/20210802100247/https://www.sciencemagazinedigital.org/sciencemagazine/05_september_2014?pg=20 |url-status=live }}

Founders of both groups published a series of letters detailing their discussions and viewpoints. All authors, however, agreed that more education of the public and open discussion of the risks and benefits was necessary. Several also wrote that sensationalized headlines and framings of the ongoing process as a "debate" with "opposing sides" had negatively affected the process, while the reality is much more collegial.

International outlook and engagement on gain-of-function research policy and regulation vary by country and region. Due to the potential effect on the global community at large, the ethical acceptability of such experiments depends on the extent to which it is accepted internationally.{{Cite journal|pmc=4996883 |year=2016 |last1=Selgelid |first1=M. J. |title=Gain-of-Function Research: Ethical Analysis |journal=Science and Engineering Ethics |volume=22 |issue=4 |pages=923–964 |doi=10.1007/s11948-016-9810-1 |pmid=27502512}} In 2010, the World Health Organization developed a non-binding guidance document for DURC, summarizing the positions of many different nations as "self-governing" and others as strictly following oversight based on the International Health Regulations, the Biological and Toxin Weapons Convention (BTWC), and the Center for International Security Studies' Biological Research Security System. The document also recommended the aforementioned as potential resources for countries to develop their own policies and procedures for DURC.{{cite news |title=Dual Use Research of Concern (DURC) |url=https://www.who.int/csr/durc/en/ |archive-url=https://web.archive.org/web/20131029002508/http://www.who.int/csr/durc/en/ |archive-date=October 29, 2013 |access-date=4 February 2021 |publisher=World Health Organization}}{{Cite web |url=https://www.who.int/csr/resources/publications/HSE_GAR_BDP_2010_2/en/ |archive-url=https://web.archive.org/web/20141020125107/http://www.who.int/csr/resources/publications/HSE_GAR_BDP_2010_2/en/|archive-date=October 20, 2014 |title=WHO | Responsible life sciences research for global health security |website=World Health Organization}}{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK458498/ |title=The Current Policy Environment |date=14 September 2017 |publisher=National Academies Press (US) |archive-date=13 March 2023 |access-date=16 May 2021 |archive-url=https://web.archive.org/web/20230313100312/https://www.ncbi.nlm.nih.gov/books/NBK458498/ |url-status=live }}

The European Academies Science Advisory Council has formed a working group to examine the issues raised by gain-of-function research and to make recommendations for the management of such research and its outputs. The possibility for developing common approaches between the United States and Europe has been explored.{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK373318/ |title=International Policy |date=20 June 2016 |publisher=National Academies Press (US) |archive-date=8 November 2022 |access-date=16 May 2021 |archive-url=https://web.archive.org/web/20221108222853/https://www.ncbi.nlm.nih.gov/books/NBK373318/ |url-status=live }}

In May 2014, the German National Ethics Council presented a report to the Bundestag on proposed guidance for governance of GoFR.{{cite journal |title=Regulating dual-use research: Lessons from Israel and the United States |journal=Journal of Biosafety and Biosecurity |date=2019-09-01 |volume=1 |issue=2 |pages=80–85 |doi=10.1016/j.jobb.2019.06.001 |language=en |issn=2588-9338|last1=Lev |first1=Ori |doi-access=free }} The report called for national legislation on DURC. As of May 2021, the German government has not passed the endorsed legislation.{{cite book |last1=Harris |first1=Elisa D. |last2=Acton |first2=James M. |last3=Lin |first3=Herbert |title=Governance of Dual-Use Technologies: Theory and Practice American Academy of Arts and Sciences |date=April 2016 |publisher=American Academy of Arts and Sciences |url=https://www.amacad.org/publication/governance-dual-use-technologies-theory-and-practice/section/5 |access-date=29 May 2021 |archive-date=2 June 2021 |archive-url=https://web.archive.org/web/20210602212659/https://www.amacad.org/publication/governance-dual-use-technologies-theory-and-practice/section/5 |url-status=live }} The NEC also proposed a national code-of-conduct for researchers to consent, endorsing which experiments qualify as misconduct and which do not, based on founding principles of public benefit.{{cite web |title=Biosecurity – freedom and responsibility of research |url=http://www.ethikrat.org/files/opinion-biosecurity.pdf |publisher=German Ethics Council |access-date=29 May 2021 |archive-date=16 April 2015 |archive-url=https://web.archive.org/web/20150416112719/http://www.ethikrat.org/files/opinion-biosecurity.pdf |url-status=dead }} The German Research Foundation and German National Academy of Sciences made a joint suggestion to expand the role of existing research ethics committees to also evaluate proposals of DURC.{{cite journal |last1=Salloch |first1=Sabine |title=The dual use of research ethics committees: why professional self-governance falls short in preserving biosecurity |journal=BMC Medical Ethics |date=2018-06-05 |volume=19 |issue=1 |page=53 |doi=10.1186/s12910-018-0295-0 |pmid=29871633 |pmc=5989368 |issn=1472-6939 |doi-access=free }}

From 2014 to 2017, the White House Office of Science and Technology Policy and the Department of Health and Human Services instituted a gain-of-function research moratorium and funding pause on any dual-use research into specific pandemic-potential pathogens (influenza, MERS, and SARS) while the regulatory environment and review process were reconsidered and overhauled. Under the moratorium, any laboratory who conducted such research would put their future funding (for any project, not just the indicated pathogens) in jeopardy.{{cite news |title=U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses |url=http://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf |agency=Office of the Assistant Secretary for Preparedness and Response |publisher=U.S. Department of Health & Human Services |date=17 October 2014}}{{cite news |last1=McNeil |first1=Donald G. Jr. |title=White House to Cut Funding for Risky Biological Study |url=https://www.nytimes.com/2014/10/18/us/white-house-to-cut-funding-for-risky-biological-study.html |newspaper=The New York Times |date=17 October 2014 |archive-date=7 February 2021 |access-date=5 February 2021 |archive-url=https://web.archive.org/web/20210207185506/https://www.nytimes.com/2014/10/18/us/white-house-to-cut-funding-for-risky-biological-study.html |url-status=live }}{{cite journal |last1=Kaiser |first1=Jocelyn |last2=Malakoff |first2=David |title=U.S. halts funding for new risky virus studies, calls for voluntary moratorium |url=https://www.science.org/content/article/us-halts-funding-new-risky-virus-studies-calls-voluntary-moratorium |access-date=28 July 2016 |journal=Science |date=17 October 2014 |volume=346 |issue=6208 |page=404 |doi=10.1126/science.346.6208.404 |pmid=25342775 |doi-access=free |archive-date=22 October 2021 |archive-url=https://web.archive.org/web/20211022033249/https://www.science.org/content/article/us-halts-funding-new-risky-virus-studies-calls-voluntary-moratorium |url-status=live }}{{cite journal|url= |doi=10.1128/mSphere.00069-16 |title=Zika Virus Focuses the Gain-of-Function Debate |year=2016 |last1=Imperiale |first1=Michael J. |last2=Casadevall |first2=Arturo |journal=mSphere |volume=1 |issue=2 |pmid=27303723 |pmc=4894681}} The NIH has said 18 studies were affected by the moratorium.{{cite journal |last1=Kaiser |first1=Jocelyn |title=NIH lifts 3-year ban on funding risky virus studies |journal=Science |date=19 December 2017 |doi=10.1126/science.aar8074 |url=https://www.science.org/content/article/nih-lifts-3-year-ban-funding-risky-virus-studies |access-date=31 May 2021 |language=en |archive-date=25 September 2021 |archive-url=https://web.archive.org/web/20210925033840/https://www.science.org/content/article/nih-lifts-3-year-ban-funding-risky-virus-studies |url-status=live |url-access=subscription }}

The moratorium was a response to laboratory biosecurity incidents that occurred in 2014, including not properly inactivating anthrax samples,{{Cite news |last=Sun |first=Lena H. |date=2014-06-19 |title=CDC says about 75 scientists may have been exposed to anthrax |language=en-US |newspaper=The Washington Post |url=https://www.washingtonpost.com/national/health-science/cdc-says-about-75-scientists-may-have-been-exposed-to-anthrax-and-receiving-antibiotics/2014/06/19/4b96467e-f7ea-11e3-8aa9-dad2ec039789_story.html |access-date=2021-07-19 |issn=0190-8286 |archive-date=2021-10-07 |archive-url=https://web.archive.org/web/20211007015846/https://www.washingtonpost.com/national/health-science/cdc-says-about-75-scientists-may-have-been-exposed-to-anthrax-and-receiving-antibiotics/2014/06/19/4b96467e-f7ea-11e3-8aa9-dad2ec039789_story.html |url-status=live }} the discovery of unlogged smallpox samples,{{Cite web |last1=Kaiser |first1=Jocelyn |date=2014-07-08 |title=Six vials of smallpox discovered in U.S. lab |url=https://www.science.org/content/article/six-vials-smallpox-discovered-us-lab |access-date=2021-07-19 |website=Science {{!}} AAAS |language=en |archive-date=2021-11-06 |archive-url=https://web.archive.org/web/20211106172135/https://www.science.org/content/article/six-vials-smallpox-discovered-us-lab |url-status=live }} and injecting a chicken with the wrong strain of influenza.{{Cite web |last1=Kaiser |first1=Jocelyn |date=2014-08-15 |title=CDC explains mix-up with deadly H5N1 avian flu |url=https://www.science.org/content/article/cdc-explains-mix-deadly-h5n1-avian-flu |access-date=2021-07-19 |website=Science {{!}} AAAS |language=en |archive-date=2021-11-07 |archive-url=https://web.archive.org/web/20211107180233/https://www.science.org/content/article/cdc-explains-mix-deadly-h5n1-avian-flu |url-status=live }} These incidents were not related to gain-of-function research. One of the goals of the moratorium was to reduce the handling of dangerous pathogens by all laboratories until safety procedures were evaluated and improved.

Subsequently, symposia and expert panels were convened by the National Science Advisory Board for Biosecurity (NSABB) and National Research Council (NRC).{{cite news |last1=Akst |first1=Jef |date=21 October 2014 |title=Moratorium on Gain-of-Function Research |publisher=The Scientist |url=https://www.the-scientist.com/the-nutshell/moratorium-on-gain-of-function-research-36564 |archive-date=27 January 2021 |access-date=5 February 2021 |archive-url=https://web.archive.org/web/20210127224457/https://www.the-scientist.com/the-nutshell/moratorium-on-gain-of-function-research-36564 |url-status=live }} In May 2016, the NSABB published "Recommendations for the Evaluation and Oversight of Proposed Gain-of-Function Research".{{cite news |title=RECOMMENDATIONS FOR THE EVALUATION AND OVERSIGHT OF PROPOSED GAIN-OF-FUNCTION RESEARCH |url=https://osp.od.nih.gov/sites/default/files/resources/NSABB_Final_Report_Recommendations_Evaluation_Oversight_Proposed_Gain_of_Function_Research.pdf |agency=National Science Advisory Board for Biosecurity |publisher=United States Department of Health and Human Services |date=May 2016 |archive-url=https://web.archive.org/web/20170107112313/https://osp.od.nih.gov/sites/default/files/resources/NSABB_Final_Report_Recommendations_Evaluation_Oversight_Proposed_Gain_of_Function_Research.pdf |archive-date=7 January 2017}} On 9 January 2017, the HHS published the "Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight" (P3CO).{{cite news |title=Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight (P3CO) |url=https://www.phe.gov/s3/dualuse/Documents/P3CO-FinalGuidanceStatement.pdf |date=9 January 2017 |publisher=Department of Health and Human Services |agency=Office of the Assistant Secretary for Preparedness and Response |archive-date=30 March 2023 |access-date=5 February 2021 |archive-url=https://web.archive.org/web/20230330202448/https://www.phe.gov/s3/dualuse/Documents/P3CO-FinalGuidanceStatement.pdf |url-status=live }} This report sets out how "pandemic potential pathogens" should be regulated, funded, stored, and researched to minimize threats to public health and safety.

On 19 December 2017, the NIH lifted the moratorium because gain-of-function research was deemed "important in helping us identify, understand, and develop strategies and effective countermeasures against rapidly evolving pathogens that pose a threat to public health."{{cite news |last1=Collins |first1=Francis S. |title=NIH Lifts Funding Pause on Gain-of-Function Research |url=https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-lifts-funding-pause-gain-function-research |publisher=Director, National Institutes of Health |date=19 December 2017 |archive-date=17 April 2020 |access-date=5 February 2021 |archive-url=https://web.archive.org/web/20200417075339/https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-lifts-funding-pause-gain-function-research |url-status=live }}

{{See also|COVID-19 lab leak hypothesis|COVID-19 misinformation#Wuhan lab origin}}

During the COVID-19 pandemic a number of conspiracy theories emerged about the origin of the SARS-CoV-2 virus and links to gain-of-function research.{{cite journal |last1=Frutos |first1=Roger |last2=Gavotte |first2=Laurent |last3=Devaux |first3=Christian A. |title=Understanding the origin of COVID-19 requires to change the paradigm on zoonotic emergence from the spillover to the circulation model |journal=Infection, Genetics and Evolution |date=March 2021 |volume=95 |page=104812 |doi=10.1016/j.meegid.2021.104812 |pmid=33744401 |language=en |pmc=7969828|bibcode=2021InfGE..9504812F }}{{cite news |date=12 May 2020 |first=Mary |last=Van Beusekom |title=Scientists: 'Exactly zero' evidence COVID-19 came from a lab |url=https://www.cidrap.umn.edu/news-perspective/2020/05/scientists-exactly-zero-evidence-covid-19-came-lab |access-date=10 June 2021 |work=CIDRAP |language=en |archive-date=1 February 2021 |archive-url=https://web.archive.org/web/20210201091101/https://www.cidrap.umn.edu/news-perspective/2020/05/scientists-exactly-zero-evidence-covid-19-came-lab |url-status=live }}{{cite journal |last1=Hakim |first1=Mohamad S. |title=SARS-CoV-2, Covid-19, and the debunking of conspiracy theories |journal=Reviews in Medical Virology |date=2021-02-14 |volume=31 |issue=6 |pages=e2222 |doi=10.1002/rmv.2222 |pmid=33586302 |pmc=7995093 |issn=1052-9276 |quote=Believers in conspiracy theories promote misinformation that the virus is not contagious, is the result of laboratory manipulation or is created to gain profit by distributing new vaccines...The believers of conspiracy will continuously search for 'scientific evidence' to defend their claims that SARS‐CoV‐2 is a human‐made virus, such as the case with an HIV‐1 bioRxiv paper that has been retracted.}}{{cite journal |last1=Evans |first1=Nicholas G. |title=Human Infection Challenge Studies: a Test for the Social Value Criterion of Research Ethics |journal=mSphere |date=26 August 2020 |volume=5 |issue=4 |pages=e00669-20 |doi=10.1128/mSphere.00669-20|pmid=32669462 |pmc=7364225}} In January 2021, University of Saskatchewan virologist Angela Rasmussen wrote that one version of the information invoked previous gain-of-function work on coronaviruses to promulgate the idea that the virus was of laboratory origin. Rasmussen stated that this was unlikely, due to the intense scrutiny and government oversight to which GoFR is subject, and it is improbable that research on hard-to-obtain coronaviruses could occur under the radar.{{cite journal |journal=Nature Medicine |vauthors=Rasmussen A |author-link=Angela Rasmussen |title=On the origins of SARS-CoV-2 |year=2021 |pmid=33442004 |volume=27 |issue=9 |page=9 |doi=10.1038/s41591-020-01205-5 |s2cid=231606580 |doi-access=free}}

In a congressional hearing on May 11, 2021, about Anthony Fauci's role as the Chief Medical Advisor to the United States Office of the President, senator Rand Paul stated that "the U.S. has been collaborating with Shi Zhengli of the Wuhan Virology Institute, sharing discoveries about how to create super viruses. This gain-of-function research has been funded by the NIH." Fauci responded "with all due respect, you are entirely and completely incorrect...the NIH has not ever and does not now fund gain-of-function research [conducted at] the Wuhan Institute of Virology."{{cite news |title=Analysis - Fact-checking the Paul-Fauci flap over Wuhan lab funding |url=https://www.washingtonpost.com/politics/2021/05/18/fact-checking-senator-paul-dr-fauci-flap-over-wuhan-lab-funding/ |access-date=13 July 2021 |newspaper=The Washington Post |archive-date=6 July 2021 |archive-url=https://web.archive.org/web/20210706065130/https://www.washingtonpost.com/politics/2021/05/18/fact-checking-senator-paul-dr-fauci-flap-over-wuhan-lab-funding/ |url-status=live }} The Washington Post fact-checking team later rated Paul's statements as containing "significant omissions and/or exaggerations".{{cite news |last1=Kessler |first1=Glenn |title=About The Fact Checker |url=http://www.washingtonpost.com/blogs/fact-checker/about-the-fact-checker/ |newspaper=The Washington Post |access-date=13 July 2021 |archive-date=19 October 2015 |archive-url=https://web.archive.org/web/20151019202538/https://www.washingtonpost.com/blogs/fact-checker/about-the-fact-checker/ |url-status=live }} NIH funding to the EcoHealth Alliance and later sub-contracted to the Wuhan Institute of Virology was not to support gain-of-function experiments, but instead to enable the collection of bat samples in the wild.{{cite news |last1=Basu |first1=Zachary |title=Fauci and Rand Paul clash over NIH funding for Wuhan Institute of Virology |url=https://www.axios.com/fauci-rand-paul-wuhan-lab-coronavirus-eff1bb08-f6c7-4d63-b170-c49e87c2e3dd.html |access-date=13 July 2021 |work=Axios |language=en |archive-date=12 July 2021 |archive-url=https://web.archive.org/web/20210712190912/https://www.axios.com/fauci-rand-paul-wuhan-lab-coronavirus-eff1bb08-f6c7-4d63-b170-c49e87c2e3dd.html |url-status=live }} EcoHealth Alliance spokesperson Robert Kessler has also categorically denied the accusation.

The Washington Post also quoted Rutgers University biosecurity expert Richard Ebright's dissenting opinion about Fauci's testimony, demonstrating that there is disagreement about what qualifies as "gain of function" research. Ebright asserted that experiments conducted under the EcoHealth grant "met the definition for gain-of-function research of concern under the 2014 Pause." MIT molecular biologist Alina Chan has argued that these experiments would not have been affected by the 2014 moratorium, because the experiments involved "naturally-occurring viruses" adding that the moratorium had "no teeth".{{cite news |last1=Robertson |first1=Lori |title=The Wuhan Lab and the Gain-of-Function Disagreement |url=https://www.factcheck.org/2021/05/the-wuhan-lab-and-the-gain-of-function-disagreement/ |access-date=14 July 2021 |work=FactCheck.org |date=21 May 2021 |archive-date=8 June 2021 |archive-url=https://web.archive.org/web/20210608123024/https://www.factcheck.org/2021/05/the-wuhan-lab-and-the-gain-of-function-disagreement/ |url-status=live }}

Several scientists have criticized the US government's GoFR regulations as having serious shortcomings (especially with regard to the NIH's funding of the EcoHealth Alliance grant proposal). Ebright has remarked that the process is not applied to all the experiments covered by the government's policies, while virologists David Relman and Angela Rasmussen have cited a worrying lack of transparency from oversight panels.{{cite news |last1=Zimmer |first1=Carl |last2=Gorman |first2=James |title=Fight Over Covid's Origins Renews Debate on Risks of Lab Work |url=https://www.nytimes.com/2021/06/20/science/covid-lab-leak-wuhan.html |access-date=14 July 2021 |work=The New York Times |date=20 June 2021 |archive-date=28 October 2021 |archive-url=https://web.archive.org/web/20211028001750/https://www.nytimes.com/2021/06/20/science/covid-lab-leak-wuhan.html |url-status=live }}

• Biotechnology risk
• Directed evolution
• Dual-use technology
• Global Virome Project

{{Reflist}}

• European Academies' Science Advisory Council: Gain of function: experimental applications relating to potentially pandemic pathogens ([https://www.leopoldina.org/uploads/tx_leopublication/2015_EASAC_GOF_Report_complete.pdf Report])
• {{cite news |last1=Lowen |first1=Anice |last2=Lakdawala |first2=Seema |title=Gain-of-function research is more than just tweaking risky viruses – it's a routine and essential tool in all biology research |url=https://theconversation.com/gain-of-function-research-is-more-than-just-tweaking-risky-viruses-its-a-routine-and-essential-tool-in-all-biology-research-202084 |work=The Conversation |date=8 May 2023}}

Category:Virology

Category:Zoonoses