On 30 December 2019, the Program for Monitoring Emerging Diseases notified the world about a pneumonia of unknown cause in Wuhan, China. Since then, scientists have made remarkable progress in understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogenesis, and mitigation by vaccines, therapeutics, and non-pharmaceutical interventions. Yet more investigation is still needed to determine the origin of the pandemic. Theories of accidental release from a lab and zoonotic spillover both remain viable. Knowing how COVID-19 emerged is critical for informing global strategies to mitigate the risk of future outbreaks

Baric, R.S.

Bjorkman, P.J.

Bloom, J.D.

Chan, Y.A.

Cobey, S.

Deverman, B.E.

Fisman, D.N.

Gupta, R.

Iwasaki, A.

Lipsitch, M.

Medzhitov, R.

Neher, R.A.

Nielsen, R.

Patterson, N.

Relman, D.A.

Stearns, T.

van Nimwegen, E.

Worobey, M.

English

PubMed

Carolina Digital Repository

Investigate the origins of COVID-19On 30 December 2019, the Program for Monitoring Emerging Diseases notified the world  about a pneumonia of unknown cause in Wuhan, China (1). Since then, scientists have made remarkable progress in understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogene-sis, and mitigation by vaccines, therapeutics, and non-pharmaceutical interventions. Yet more investigation is still needed to deter-mine the origin of the pandemic. Theories of accidental release from a lab and zoonotic spillover both remain viable. Knowing how COVID-19 emerged is critical for inform-ing global strategies to mitigate the risk of future outbreaks. In May 2020, the World Health Assembly requested that the World Health Organization (WHO) director-general work closely with partners to determine the origins of SARS-CoV-2 (2). In November, the Terms of Reference for a China–WHO joint study were released (3). The informa-tion, data, and samples for the study’s first phase were collected and summarized by the Chinese half of the team; the rest of the team built on this analysis. Although there were no findings in clear support of either a natural spillover or a lab accident, the team assessed a zoonotic spillover from an intermediate host as “likely to very likely,” and a laboratory incident as “extremely unlikely” [(4), p. 9]. Furthermore, the two theories were not given balanced consider-ation. Only 4 of the 313 pages of the report and its annexes addressed the possibility of a laboratory accident (4). Notably, WHO Director-General Tedros Ghebreyesus com-mented that the report’s consideration of evidence supporting a laboratory accident was insufficient and offered to provide additional resources to fully evaluate the possibility (5).As scientists with relevant expertise, we agree with the WHO director-general (5), the United States and 13 other countries (6), and the European Union (7) that greater clarity about the origins of this pandemic is necessary and feasible to achieve. We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data. A proper investigation should be transparent, objective, data-driven, Edited by Jennifer Sills4. WHO, “WHO-convened global study of origins of SARS-CoV-2: China part” (2021); www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part.5. WHO, “WHO director-general’s remarks at the Member State Briefing on the report of the international team studying the origins of SARS-CoV-2” (2021); www.who.int/director-general/speeches/detail/who-director-general-s-remarks-at-the-member-state-briefing-on-the-report-of-the-international-team-studying-the-origins-of-sars-cov-2.6. US Department of State, “Joint statement on the WHO-Convened COVID-19 origins study” (2021); www.state.gov/joint-statement-on-the-who-convened-covid-19-origins-study/.7. Delegation of the European Union to the UN and other International Organizations in Geneva “EU statement onthe WHO-led COVID-19 origins study” (2021); https://eeas.europa.eu/delegations/un-geneva/95960/eu-statement-who-led-covid-19-origins-study_en.8. J. Hollingsworth, Y. Xiong, “The truthtellers: China createda story of the pandemic. These people revealed details Beijing left out,” CNN (2021). 9. A. Green, L. Wenliang, Lancet 395, 682 (2020).10.1126/science.abj0016inclusive of broad expertise, subject to independent oversight, and responsibly managed to minimize the impact of conflicts of interest. Public health agencies and research laboratories alike need to open their records to the public. Investigators should document the veracity and provenance of data from which analyses are conducted and conclusions drawn, so that analyses are reproducible by independent experts. Finally, in this time of unfortunate anti-Asian sentiment in some countries, we note that at the beginning of the pandemic, it was Chinese doctors, scientists, journalists, and citizens who shared with the world crucial information about the spread of the virus—often at great personal cost (8, 9). We should show the same determination in promoting a dispassionate science-based discourse on this difficult but important issue.Jesse D. Bloom1,2, Yujia Alina Chan3, Ralph S. Baric4, Pamela J. Bjorkman5, Sarah Cobey6, Benjamin E. Deverman3, David N. Fisman7, Ravindra Gupta8, Akiko Iwasaki9,2, Marc Lipsitch10, Ruslan Medzhitov9,2, Richard A. Neher11, Rasmus Nielsen12, Nick Patterson13, Tim Stearns14, Erik van Nimwegen11, Michael Worobey15, David A. Relman16,17*1Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. 2Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. 3Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA. 4Department of Epidemiology and Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. 5Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. 6Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637, USA. 7Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A8, Canada. 8Cambridge Institute of Therapeutic Immunology & Infectious Disease, Cambridge, UK. 9Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA. 10Department of Immunology and Infectious Diseases and Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA. 11Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Basel, Switzerland. 12Department of Integrative Biology and Department of Statistics, University of California, Berkeley, CA 94720, USA. 13Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA. 14Department of Biology and Department of Genetics, Stanford University, Stanford, CA 94305, USA. 15Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. 16Department of Medicine and Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. 17Center for International Security and Cooperation, Stanford University, Stanford, CA 94305, USA.*Corresponding author. Email: relman@stanford.eduREFERENCES AND NOTES1. “Undiagnosed pneumonia—China (Hubei): Request for information,” ProMED post (2019); https://promedmail.org/promed-post/?id=6864153.2.  World Health Assembly Resolution 73.1: COVID-19 response (2020); https://apps.who.int/gb/ebwha/pdf_files/WHA73/A73_R1-en.pdf. 3.  WHO, “WHO-convened global study of the origins of SARS-CoV-2” (2020); www.who.int/publications/m/item/who-convened-global-study-of-the-origins-of-sars-cov-2.

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