A Critical Analysis of the Evidence for the SARS-CoV-2 Origin Hypotheses.

When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.

A Critical Analysis of the Evidence for the SARS-CoV-2 Origin Hypotheses.

When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.

A Critical Analysis of the Evidence for the SARS-CoV-2 Origin Hypotheses.

When humans experience a new, devastating viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), significant challenges arise. How should individuals as well as societies respond to the situation? One of the primary questions concerns the origin of the SARS-CoV-2 virus that infected and was transmitted efficiently among humans, resulting in a pandemic. At first glance, the question appears straightforward to answer. However, the origin of SARS-CoV-2 has been the topic of substantial debate primarily because we do not have access to some relevant data. At least two major hypotheses have been suggested: a natural origin through zoonosis followed by sustained human-to-human spread or the introduction of a natural virus into humans from a laboratory source. Here, we summarize the scientific evidence that informs this debate to provide our fellow scientists and the public with the tools to join the discussion in a constructive and informed manner. Our goal is to dissect the evidence to make it more accessible to those interested in this important problem. The engagement of a broad representation of scientists is critical to ensure that the public and policy-makers can draw on relevant expertise in navigating this controversy.

Virology under the Microscope-a Call for Rational Discourse.

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.

Virology under the Microscope-a Call for Rational Discourse.

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.

Virology under the Microscope-a Call for Rational Discourse.

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.

2021 Acknowledgment of mSphere Ad Hoc Reviewers

Yet, we accomplished it, in no small part due to years of fundamental research on how the immune system recognizes and responds to pathogens, how mRNAs are synthesized and translated, and how to effectively deliver macromolecules into cells. Much of this progress was anchored in the microbial sciences: studies of viral immunology, landmark work on mRNA metabolism in bacteria and virally infected cells, understanding how pathogens bind to and enter cells, development of techniques that were originally used to introduce viral oncogenes into mammalian cells in culture, and the use of viral vectors for gene therapy all set the stage for the COVID-19 vaccines. [...]we list below the many individuals who served as ad hoc reviewers in 2021. Kjersti Aagaard Mohamed M. H. Abdelbary Sabrina Absalon Michael C. Abt Mark D. Adams Josephine Azikuru Afema Kayode Olayinka Afolabi Surya D. Aggarwal Hector Aguilar-Carreno Christian Paul Ahearn Brian M. M. Ahmer Mustafa Akkoyunlu Md. Tauqeer Alam Ashraf Al Ashhab M. John Albert Anoop Alex Caroline Alfieri Holly M. Scott Algood Jonathan Allen Emma Allen-Vercoe Juan C. Alonso Francis Alonzo Christopher Alteri John Alverdy Christopher S. Anderson Matthew Zack Anderson David R. Andes Laura Maria Andrade De Oliveira Marco Andreolli Diego O. Andrey Alberto Antonelli Yoshiteru Aoi Cristian Apetrei Chelsie Elizabeth Armbruster Sandra K. Armstrong Jennifer M. Auchtung Tatjana Avšič-Županc Domenico Azarnia Tehran Sophie Bachellier-Bassi Michael A. Bachman Steffen Backert Matthew Baideme Camden R. Bair Jonathon L. Baker Katherine H. Baker Scott Baliban Jimmy D. Ballard Guilia Bandini Fernando Baquero Noa Barak-Gavish Joseph T. Barbieri Brianne Barker Jason C. Bartz Martine Bassilana Christine Marie Bassis Tilman Baumstark Marco Becherelli Sara Beier Daniel P. Beiting Georgios N. Belibasakis Aeriel D. Belk Samantha L. Bell Jessica A. Belser Jorge L. Benach Jose A. Bengoechea Peter Bergholz Teresa M. Bergholz Tanja Berić David Bernstein Stefan Bertilsson Ralph Bertram Sanchita Bhadra Dipankar Bhattacharyya Bijit Bhowmik Fadil A. Bidmos Claire H. Birkenheuer Jacob P. Bitoun Daniel Blanco-Melo Jon S. Blevins Joseph M. Bliss Patricia Pringle Bloom Antje Blumenthal Kasun H. Bodawatta Pierre Bogaerts Gregory Bonito Sébastien Bontemps-Gallo Angela Bordin Jens Bosse Anna Both Travis Bourret Kate Bowerman Eric Boyd Ethna Fidelma Boyd Todd Bradley Rita Branco Kyndall Braumuller Linda Breeden Mathieu Brochet Nichole A. Broderick Christopher B. Brooke Grayson Brown Jeremy S. Brown Kevin M. Brown Michael G. Brown Harry Brumer Donald A. Bryant Alison Buchan Lori L. Burrows Karen Bush Andrea Cabibbe Laty A. Cahoon Yi Cai Eloiza Helena Campana Edgar I. Campos-Madueno Eric Caragata Alessandra Carattoli Franck Gael Carbonero Miguel Carda Diéguez Jeffrey Carey Ryan B. Carnegie Jaime Carrasco Vern B. Carruthers Leslie S. Casey Irene Castano Santiago Castillo-Ramírez Clayton C. Caswell Rodrigo Cayô Daniel Cazares Brandi N. Celia Nuno Cerca Miguel Angel Cevallos Dipshikha Chakravortty Douglas L. Chalker Thomas M. Chambers Josephine R. Chandler Michael Chandler Robert L. Charlebois Sujata S. Chaudhari Neeraj Chauhan Damien Chaussabel Michael S. Chaussee Francisco P. Chavez Liang Chen Chiuping Cheng Rachel A. Cheng Laurent Roberto Chiarelli Alex W. H. Chin Michaelle Chojnacki Stephen A. Clark Erika C. Claud David W. Cleary Sara Clohisey Shira Milo Cochavi Darrell Cockburn Ashley Cohen Sean Conlan Laura Cook Gretchen Cooley Brendan Cormack Pierre Cornelis Caitlin Cossaboom Siobhan C. Cowley Robert A. Cramer Max Cravener Alison K. Criss Karissa L. Cross Robert W. Cross Liwang Cui Paul J. Cullen Natacha Cuoto Cameron R. Currie Todd Andrew Cutts Dennis G. Cvitkovitch F. Heath Damron Ajai A. Dandekar Stephen Daniels Biswadip Das Bryan W. Davies Charles R. Dean Jean-Winoc Decousser Elizabeth N. De Gaspari Miranda De Graaf Kirk W. Deitsch Harry P. De Koning Frank R. DeLeo Thomas G. Denes David W. Denning Rajendar Deora Cynthia Ann Derdeyn Steven C. Derrick Jigar V. Desai Lalitagauri Deshpande Sanjay Kumar Dey Vijaykrishn Dhanasekaran Rishu Dheer Robert P. Dickson Diego G. Diel Beatriz Diez Moreno Stephen P. Diggle Joseph P. Dillard Siyuan Ding Marc S. Dionne Alan Angelo Dispirito Dirk P. Dittmer Eunsoo Do Carlota Dobaño Lazaro Yohei Doi Janet Donaldson Caihong Dong Matthew J. Dorman Laurent Dortet Benoît Doublet Charles M. Dozois Jan Felix Drexler Yuchun Du Elves Duarte Edward G. Dudley Breck A. Duerkop Anne K. Dunn Sanjucta Dutta Kathryn Eaton Leo Eberl Kathryn M. Edenborough Tom Edlind Elizabeth A. Edwards Maren Eggers Sabine Ehrt Patrick Eichenberger Waldir P. Elias Jeremy R. Ellermeier Roland Elling Najib M. El-Sayed Mostafa S. Elshahed Joanne B. Emerson Virve Irene Enne Eeva Liisa Eronen-Rasimus Alice L. Erwin Javier Antonio Escobar-Perez Matthe J. Evans Franziska Faber Robert Fagan Christina S. Faherty Linda Falgenhauer Séamus Fanning Mauricio J. Farfan Matthew L. Faron Amy K. Feehan Mario F. Feldman Jinrong Feng J. Christopher Fenno David J. Ferguson Isabel Fernández Escapa Astrid Ferrer Richard L. Ferrero Kenneth A. Fields Joshua Fierer Sergio R. Filipe Maria F. Fillat Scott G. Filler Douglas K. Fischer Carlos Flores Stephanie Flowers Fabrizio Foieni Steven L. Foley Laura Ford Jarrod R. Fortwendel Michael T. France Kristi L. Frank Natalia Freund Georg Fritz Inga Fröding Takasuke Fukuhara Marta M. Gaglia Hannah Gaimster Raj Gaji James E. Galen Markus Ganter Michael G. Ganzle Erin C. Garcia Sarahi L. Garcia Amy Shirley Gargis Kathleen Gärtner Caroline Attardo Genco Noel Gerald Carmen Gherasim Lorenzo Giacani Heather L. Glasgow Oleg Glebov Erin S. Gloag Marek Gniadkowski Richard V. Goering Gustavo H. Goldman Jonathan Louis Golob Benjamin Golomb Laura Gómez-Consarnau Angela Gomez-Simmonds Yanhai Gong Jesus Gonzalo-Asensio Steven D. Goodman Tobias Goris Morgan Gorris Ria Goswami Matthias Gotte Revathi Govind Manish Goyal Andreas Grabrucker Lisa Gralinski Luke R. Green Alexander L. Greninger Finn Grey Elizabeth Grice Dennis Grogan Elisabeth Grohmann Trudy H. Grossman Cassandra Guarino Marc-Jan Gubbels Eric Guédon Pascale S. Guiton Arda Gulay Ravindra Kumar Gupta Gabriel Gutkind David Hackstadt Andrea Hahn Anders P. Hakansson Riley Hale Vanessa L. Hale Robert Hall Roy A. Hall Ruth M. Hall Brian K. Hammer Tobin Hammer Abdul N. Hamood Axel Georg Hamprecht Ken-Ichi Hanaki Lynn E. Hancock Blake M. Hanson Mingju Hao Md. Manjurul Haque Sohei Harada Clare Harding Lee H. Harrison Oliver Harschnitz Erica M. Hartmann Eric T. Harvill Asma Hatoum-Aslan Ben M. Hause Margo G. Haygood Cynthia Y. He Susu He Aoife T. Heaslip Nicholas S. Heaton Nagendra R. Hegde Christine Heilmann Henry S. Heine David E. Heinrichs Peera Hemarajata Tory A. Hendry Cristina Herencias Ana Hernandez Cordero Robert L. Hettich Andrés Hidalgo Steven Higgins Penelope Higgs Takahiro Hiono Itaru Hirai Theresa D. Ho Thomas Hoenen Nicole A. Hoff Deborah A. Hogan Peiying Hong Lauren Michelle Hook Thomas Hooven Alexander M. Horspool Paul A. Hoskisson Daniel K. Howe Gongzheng Hu Ke Hu Linden T. Hu Stephen S. H. Huang Eili Huhtamo Lewis Hun Jason F. Huntley Jillian H. Hurst Bonnie L. Hurwitz Wilhelmina Huston Justin Hutchison Albina Ibrayeva Melissa Ingala Thomas J. Inzana William W. Ja Mary Ann Jabra-Rizk Cody B. Jackson Anna C. Jacobs William R. Jacobs Guilhem Janbon Ingmar Janse Michael A. Jarvis Vicki Jeffers Niuniu Ji Dong-Yan Jin William Johnson Susan Joseph Lok R. Joshi Yuan Jun Barbara C. Kahl Maria Kalamvoki Suzanne R. Kalb Jeremy Phillip Kamil Manabu Kanno Fathi Karouia Anbu Kumar Karuppannan Fatah Kashanchi Joseph Keane Daniel B. Kearns Scott P. Keely Eliisa Kekäläinen Brendan Kelly Volkhard A. J. Kempf Arnaud Kengmo Tchoupa Nemat O. Keyhani Shabaana A. Khader Arifa

Can Science Help Resolve the Controversy on the Origins of the SARS-CoV-2 Pandemic?

The origins of the calamitous SARS-CoV-2 pandemic are now the subject of vigorous discussion and debate between two competing hypotheses for how it entered the human population: (i) direct infection from a feral source, likely a bat and possibly with an intermediate mammalian host, and (ii) a lab accident whereby bat isolates infected a researcher, who then passed it to others. Here, we ask whether the tools of science can help resolve the origins question and conclude that while such studies can provide important information, these are unlikely to provide a definitive answer. Currently available data combined with historical precedent from other outbreaks and viewed through the prism of Occam's razor favor the feral source hypothesis, but science can provide only probabilities, not certainty.

Rethinking Gain-of-Function Experiments in the Context of the COVID-19 Pandemic.

Proponents of the use of gain-of-function (GOF) experiments with pathogens with pandemic potential (PPP) have argued that such experiments are necessary because they reveal important facets of pathogenesis and can be performed safely. Opponents of GOF experiments with PPP have argued that the risks outweigh the knowledge gained. The COVID-19 pandemic demonstrates the vulnerability of human societies to a new PPP, while also validating some arguments of both camps, questioning others, and suggesting the need to rethink how we approach this class of experiments.