Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 28;97(2):e0008923.
doi: 10.1128/jvi.00089-23. Epub 2023 Jan 26.

Virology under the Microscope-a Call for Rational Discourse

Felicia Goodrum  1 Anice C Lowen  2 Seema Lakdawala  2 James Alwine  1   3 Arturo Casadevall  4 Michael J Imperiale  5 Walter Atwood  6 Daphne Avgousti  7 Joel Baines  8 Bruce Banfield  9 Lawrence Banks  10 Sumita Bhaduri-McIntosh  11 Deepta Bhattacharya  12 Daniel Blanco-Melo  7 David Bloom  11 Adrianus Boon  13 Steeve Boulant  11 Curtis Brandt  14 Andrew Broadbent  15 Christopher Brooke  13 Craig Cameron  16 Samuel Campos  12 Patrizia Caposio  17 Gary Chan  18 Anna Cliffe  19 John Coffin  20 Kathleen Collins  21 Blossom Damania  16 Matthew Daugherty  22 Kari Debbink  23 James DeCaprio  24 Terence Dermody  25 Jimmy Dikeakos  26 Daniel DiMaio  27 Rhoel Dinglasan  11 W Paul Duprex  25 Rebecca Dutch  28 Nels Elde  29 Michael Emerman  7 Lynn Enquist  30 Bentley Fane  12 Ana Fernandez-Sesma  31 Michelle Flenniken  32 Lori Frappier  33 Matthew Frieman  15 Klaus Frueh  17 Michaela Gack  34 Marta Gaglia  14 Tom Gallagher  35 Denise Galloway  7 Adolfo García-Sastre  31 Adam Geballe  7 Britt Glaunsinger  36 Stephen Goff  37 Alexander Greninger  38 Meaghan Hancock  17 Eva Harris  36 Nicholas Heaton  39 Mark Heise  16 Ekaterina Heldwein  20 Brenda Hogue  40 Stacy Horner  39 Edward Hutchinson  41 Joseph Hyser  42 William Jackson  40 Robert Kalejta  39 Jeremy Kamil  43 Stephanie Karst  11 Frank Kirchhoff  44 David Knipe  24 Timothy Kowalik  45 Michael Lagunoff  38 Laimonis Laimins  46 Ryan Langlois  47 Adam Lauring  21 Benhur Lee  31 David Leib  48 Shan-Lu Liu  49 Richard Longnecker  46 Carolina Lopez  50 Micah Luftig  39 Jennifer Lund  7 Balaji Manicassamy  51 Grant McFadden  40 Michael McIntosh  11 Andrew Mehle  14 W Allen Miller  52 Ian Mohr  53 Cary Moody  16 Nathaniel Moorman  16 Anne Moscona  37 Bryan Mounce  35 Joshua Munger  54 Karl Münger  20 Eain Murphy  18 Mojgan Naghavi  46 Jay Nelson  17 Christopher Neufeldt  55 Janko Nikolich  12 Christine O'Connor  56 Akira Ono  21 Walter Orenstein  55 David Ornelles  57 Jing-Hsiung Ou  58 John Parker  8 Colin Parrish  8 Andrew Pekosz  23 Philip Pellett  59 Julie Pfeiffer  60 Richard Plemper  61 Stephen Polyak  38 John Purdy  12 Dohun Pyeon  62 Miguel Quinones-Mateu  26 Rolf Renne  11 Charles Rice  63 John Schoggins  60 Richard Roller  51 Charles Russell  64 Rozanne Sandri-Goldin  65 Martin Sapp  43 Luis Schang  8 Scott Schmid  66 Stacey Schultz-Cherry  64 Bert Semler  65 Thomas Shenk  30 Guido Silvestri  28 Viviana Simon  31 Gregory Smith  46 Jason Smith  38 Katherine Spindler  47 Megan Stanifer  11 Kanta Subbarao  67 Wesley Sundquist  29 Mehul Suthar  55 Troy Sutton  68 Andrew Tai  21 Vera Tarakanova  69 Benjamin tenOever  53 Scott Tibbetts  11 Stephen Tompkins  70 Zsolt Toth  11 Koenraad van Doorslaer  12 Marco Vignuzzi  71 Nicholas Wallace  72 Derek Walsh  46 Michael Weekes  73 Jason Weinberg  21 Matthew Weitzman  74 Sandra Weller  75 Sean Whelan  50 Elizabeth White  74 Bryan Williams  76 Christiane Wobus  21 Scott Wong  17 Andrew Yurochko  43
Affiliations

Virology under the Microscope-a Call for Rational Discourse

Felicia Goodrum et al. J Virol. .

Abstract

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Keywords: COVID-19; Coronavirus; DURC; Gain of function; SARS-CoV-2; biosafety; influenza; pandemic; vaccines; zoonosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare a conflict of interest. Sana Biotechnology has licensed intellectual property of D.B. and Washington University in St. Louis. Gilead Sciences has licensed intellectual property of D.B. and Stanford University. D.B. is a co-founder of Clade Therapeutics. D.B. previously served on an advisory panel for GlaxoSmithKline. D.B. and The University of Arizona hold a patent on SARS-CoV-2 serological assays. K.C. is a special government employee and a member of the Office of AIDS Research Advisory Committee. T.S.D.: Board of Directors, Burroughs Wellcome Fund; Editor, Annual Review of Virology. D.D. is on the scientific advisory board of Theriva. W.P.D. receives support from Moderna. M. F. receives funding from National Institute of Allergy and Infectious Diseases (NIAID), Biomedical Advanced Research and Development Authority (BARDA), Defense Advanced Research Projects Agency (DARPA), Gates Foundation, Aikido Pharma, Emergent, Astrazeneca, Novavax, Regeneron, and the CDC, outside the submitted work. M. F. received royalties/licenses from Aikido Pharma for antiviral drug patent licensing, consulting fees from Aikido Pharma, Observatory Group, for consulting for COVID-19, and participation on Scientific Advisory Board for Aikido Pharma, outside the submitted work. K.F. has substantial financial interest in Vir Biotechnology, Inc., and is a co-founder of the company. K.F. is co-inventor of patents licensed to Vir and receives compensation for consulting for Vir. The potential conflicts of interest have been reviewed and managed by OHSU. D.G. is on the HPV Global Advisory Board for Merck. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen and Pfizer. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. B.A.G. is on the scientific advisory board for IMUNON. A.L.G. reports central testing contracts from Pfizer, Janssen, Novavax, Sanofi, Abbott, Hologic, Cepheid, and Quidel, and research support from Gilead. E.E.H. is co-founder of Thyreos Inc. E.C.H. has carried out research work in collaboration with AstraZeneca and received honoraria for consultancy work for the Center for Open Science and Seqirus. M.J.I. consults for Gilead Sciences and Via Nova Therapeutics. D.M.K. is a consultant, Replay Bio. T.K. receives funding from Moderna related to CMV. A.S.L. is a paid member of steering committee for clinical trial of baloxavir (Roche). A.C.L. is an inventor on the patent Influenza Vaccines and Uses Thereof, owned by the Icahn School of Medicine at Mount Sinai. G.M. is co-founder of a biotech company devoted to oncolytic virotherapy. W.A.M. is co-inventor of a pending patent application on improved mRNA vaccines. A. Moscona is scientific founder of Thylacine Biotherapeutics, a startup company for antiviral therapeutics. J.A.N., Vir Biotechnology. W.A.O., uncompensated member, Moderna Scientific Advisory Board. D.A.O., Defense Threat Reduction Agency. L.M.S. is a virologist performing research on potential antivirals. L.M.S. is the president-elect of the International Society for Antiviral Research, the membership of which includes people working in companies working on antivirals. L.M.S. has performed paid and non-paid consultantships with private companies developing antivirals or virucidals. L.M.S. is a founder member of a start-up company that had an interest in antivirals. L.M.S. has received funding to work on antivirals. S.S. is Contract Consultant for Curevo Vaccines. J.W.S. consults for the Federal Trade Commission on matters related to COVID-19. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays which list V.S. as co-inventor. G.A.S. is President of Thyreos, Inc. M.S.S. serves an advisory role with Moderna and Ocugen. S.K.W. is co-founder of startup Quercus Molecular Design. C.M.R.: Founder, Apath LLC; Advisor, SAB, and Research Support, Vir Biotechnology; Research support, GSK; SAB Invisishield; SAB Arbutus. C.R.B. is consultant for Ocular Services On Demand (OSOD) located in Madison, WI, and a collaborator with Amebagone a small biotech company in Madison, Wisconsin. C.R.B. has no financial interest in Amebagone and is not owner or part owner of OSOD. All other authors report no conflicts of interest.

Figures

FIG 1
FIG 1
Federal and institutional regulations. A brief breakdown of current U.S. Department of Health and Human Services regulations on microbiology research and the implementation of federal requirements by individual institutions, through various committees and processes. Important additional oversight that is not shown includes that provided by occupational health services to ensure safety of research personnel, and federal and institutional regulation of research involving vertebrate animals or human subjects, which are overseen by Institutional Animal Care and Use Committees (IACUC; animal research) and Institutional Review Boards (IRB; human subjects research).
FIG 2
FIG 2
Current regulations surrounding funding, monitoring and approval of gain-of-function research of concern. A flow chart describing the steps a principal investigator must follow prior to receiving funding or initiating research considered dual-use-research-of-concern (DURC) on pathogens of pandemic potential (P3). The blue shaded box corresponds to the general practices that all investigators carry out at the institutional level described in Fig. 1. Research with the potential to enhance the properties of pathogen is referred for additional oversight. Asterisks (*) indicate an iterative process typically involving 1–3 reviews and revisions.
FIG 3
FIG 3
Publishing process for articles involving gain-of-function research-of-concern or with pathogens of pandemic potential at ASM journals. Articles in the GOF/DURC/P3 category are flagged by multiple layers at the screening stage. This process will initiate discussion among the scientific editor in chief and other subject matter experts and lead to a publication decision after careful consideration of risks and benefits.

Comment in

  • Statement in Support of: "Virology under the Microscope-a Call for Rational Discourse".
    Speck P, Mackenzie J, Bull RA, Slobedman B, Drummer H, Fraser J, Herrero L, Helbig K, Londrigan S, Moseley G, Prow N, Hansman G, Edwards R, Ahlenstiel C, Abendroth A, Tscharke D, Hobson-Peters J, Kriiger-Loterio R, Parry R, Marsh G, Harding E, Jacques DA, Gartner MJ, Lee WS, McAuley J, Vaz P, Sainsbury F, Tate MD, Sinclair J, Imrie A, Rawlinson S, Harman A, Carr JM, Monson EA, Hibma M, Mahony TJ, Tu T, Center RJ, Shrestha LB, Hall R, Warner M, Ward V, Anderson DE, Eyre NS, Netzler NE, Peel AJ, Revill P, Beard M, Legione AR, Spencer AJ, Idris A, Forwood J, Sarker S, Purcell DFJ, Bartlett N, Deerain JM, Brew BJ, Asgari S, Farrell H, Khromykh A, Enosi Tuipulotu D, Anderson D, Mese S, Tayyar Y, Edenborough K, Uddin JM, Hussain A, Daymond CJI, Agius J, Johnson KN, Shirmast P, Abedinzadeshahri M, MacDiarmid R, Ashley CL, Laws J, Furfaro LL, Burton TD, Johnson SMR, Telikani Z, Petrone M, Roby JA, Samer C, Suhrbier A, Van Der Kamp A, Cunningham A, Donato C, Mahar J, Black WD, Vasudevan S, Lenchine R, Spann K, Rawle DJ, Rudd P, Neil J, Kingston R, Newsome TP, Kim KW, Mak J, Lowry K, Bryant N, Meers J, Roberts JA, McMillan N, Labzin LI, Slonchak A, Hugo LE, Henzeler B, Newton ND, David CT, … See abstract for full author list ➔ Speck P, et al. J Virol. 2023 May 31;97(5):e0045123. doi: 10.1128/jvi.00451-23. Epub 2023 Apr 25. J Virol. 2023. PMID: 37097023 Free PMC article. No abstract available.
  • Statement in Support of: "Virology under the Microscope-a Call for Rational Discourse".
    Speck P, Mackenzie J, Bull RA, Slobedman B, Drummer H, Fraser J, Herrero L, Helbig K, Londrigan S, Moseley G, Prow N, Hansman G, Edwards R, Ahlenstiel C, Abendroth A, Tscharke D, Hobson-Peters J, Kriiger-Loterio R, Parry R, Marsh G, Harding E, Jacques DA, Gartner MJ, Lee WS, McAuley J, Vaz P, Sainsbury F, Tate MD, Sinclair J, Imrie A, Rawlinson S, Harman A, Carr JM, Monson EA, Hibma M, Mahony TJ, Tu T, Center RJ, Shrestha LB, Hall R, Warner M, Ward V, Anderson DE, Eyre NS, Netzler NE, Peel AJ, Revill P, Beard M, Legione AR, Spencer AJ, Idris A, Forwood J, Sarker S, Purcell DFJ, Bartlett N, Deerain JM, Brew BJ, Asgari S, Farrell H, Khromykh A, Enosi Tuipulotu D, Anderson D, Mese S, Tayyar Y, Edenborough K, Uddin JM, Hussain A, Daymond CJI, Agius J, Johnson KN, Shirmast P, Abedinzadeshahri M, MacDiarmid R, Ashley CL, Laws J, Furfaro LL, Burton TD, Johnson SMR, Telikani Z, Petrone M, Roby JA, Samer C, Suhrbier A, Van Der Kamp A, Cunningham A, Donato C, Mahar J, Black WD, Vasudevan S, Lenchine R, Spann K, Rawle DJ, Rudd P, Neil J, Kingston R, Newsome TP, Kim KW, Mak J, Lowry K, Bryant N, Meers J, Roberts JA, McMillan N, Labzin LI, Slonchak A, Hugo LE, Henzeler B, Newton ND, David CT, … See abstract for full author list ➔ Speck P, et al. mBio. 2023 Jun 27;14(3):e0081523. doi: 10.1128/mbio.00815-23. Epub 2023 Apr 25. mBio. 2023. PMID: 37097032 Free PMC article. No abstract available.

References

    1. Cohen J. 2022. Studies bolster pandemic origin in Wuhan animal market. Science 375:946–947. 10.1126/science.adb1760. - DOI - PubMed
    1. Maxmen A. 2022. Wuhan market was epicentre of pandemic's start, studies suggest. Nature 603:15–16. 10.1038/d41586-022-00584-8. - DOI - PubMed
    1. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. 2020. The proximal origin of SARS- CoV-2. Nat Med 26:450–452. 10.1038/s41591-020-0820-9. - DOI - PMC - PubMed
    1. Casadevall A, Weiss SR, Imperiale MJ. 2021. Can Science Help Resolve the Controversy on the Origins of the SARS-CoV-2 Pandemic? mBio 12:e0194821. 10.1128/mBio.01948-21. - DOI - PMC - PubMed
    1. Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE, Goldstein SA, Rasmussen AL, Kraemer MUG, Newman C, Koopmans MPG, Suchard MA, Wertheim JO, Lemey P, Robertson DL, Garry RF, Holmes EC, Rambaut A, Andersen KG. 2022. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science 377:951–959. 10.1126/science.abp8715. - DOI - PMC - PubMed

Publication types