Dr. Anthony Berglas – A laboratory origin of COVID-19 in 500 words

Background

June 19, 2023 – The following letter was submitted to the Journal of Virology. The letter summarizes the key arguments for a laboratory origin of COVID-19 in 500 words. It covers:

• The lack of evidence for any natural zoonosis.
• The distance of Wuhan from the relevant bats.
• The sudden adaption of SARS-CoV-2 to humans.
• The genetic engineering work performed at the Wuhan Institute of Virology.
• The unlikely natural source of the critical furin cleavage site.
• The lack of regulation of potentially dangerous virology.

This letter was written in response to a letter titled “Statement in Support of: “Virology under the Microscope—a Call for Rational Discourse” published on 25 April 2023 by members of the Australasian Virology Association asserting without justification that:

• “the zoonosis hypothesis has the strongest supporting evidence…” and
• “an extensive history of gain-of-function research safely and effectively contributing to the development of vaccines and antivirals” concluding
• “We do not believe virology research needs additional legislative controls.”

These statements are manifestly false. First, available evidence indicate the origin of SARS-CoV-2 is a research-related spillover, not zoonosis. Second, there is no evidence that gain of function research on potential pandemic pathogens has been useful. Third, there is no effective oversight on gain of function research on potential pandemic pathogens.

The letter was edited by David Bahry prior to submission.

July 25, 2023 – The letter was rejected because reviewers felt:

• it repeats arguments previously made in an article by David Bahry titled “Rational Discourse on Virology and Pandemics” published in MBio
• the description of the furin cleavage site is incomplete, and
• a comment about absence of evidence being evidence of absence

While the letter does repeat some of the arguments made by Bahry, it did so because it was produced in response to a letter that, itself, repeats arguments previously made against regulation of virology that the letter by Bahry was a response to. Thus, ASM does not appear to apply the same standard to this letter and the letter from members of the Australasian Virology Association.

Letter - A laboratory origin of COVID-19 in 500 words

Speck at al., writing as members of the Australasian Virology Society (AVS), have recently cross-published a letter claiming that i) natural zoonosis has the strongest supporting evidence as the proximal origin of SARS-2; ii) gain of function research is safe and necessary; and iii) virology is already sufficiently regulated (1–3). The AVS letter is a “statement in support” of an editorial by Goodrum et al. (4–6), which has previously been criticized by Bahry (7).

There is no “dispositive” evidence for the market zoonosis hypothesis (8, 25). Natural zoonoses and laboratory accidents have both occurred repeatedly in the past (8–10, 28). Although some early COVID-19 cases were linked to the Huanan Seafood Market (HSM), there were market-unlinked cases preceding these (11, 12). The initial discovery of the HSM-linked cluster led to a high degree of ascertainment bias, rendering fallacious any argument based on apparent geographic association between most early cases and HSM or between positive environmental samples and wildlife stalls within HSM (7).

Unlike the case of SARS, where infected palm civets were quickly found (13), no ancestral SARS-CoV-2-infected animal has been reported anywhere (8), despite sampling of thousands of animals (23) including hedgehogs and hares at the HSM (14). Speck et al. cite speculations about raccoon dogs as the intermediate host (15), but such speculations are baseless: in fact raccoon dog and SARS-CoV-2 genetic material were negatively correlated among HSM stalls (16).

SARS-CoV-2 emerged in Wuhan, central China, over 1,000 kilometers from the presumptive bat reservoir.  Wuhan has even been used as a negative control for seropositivity of bat-coronavirus antibodies (17). Yet Wuhan is also home to the world’s leading bat coronavirus research institute, the Wuhan Institute of Virology (WIV) which had assembled a very large collection of coronavirus samples (27). The DEFUSE grant proposal (rejected by DARPA) is evidence that the WIV was part of a collaboration interested in inserting furin cleavage sites into sarbecoviruses (SARS-CoV-2-like coronaviruses) (18).   SARS-CoV-2 has a furin cleavage site, unlike any of the hundreds of other known sarbecoviruses (19), and it is at the S1/S2 junction.  Unlike SARS and MERS, SARS-CoV-2 emerged suddenly (24) and bound more tightly to the receptor for SARS viruses (ACE-2) from humans than to ACE-2 from other animals (22). This unusual characteristic would be consistent with genetic engineering for binding to human ACE-2, or serial passage in human cells or humanized mice (8).  WIV has withheld data and not permitted an external review.  It has previously been criticized for virus research at the grossly inadequate BSL-2 biosafety level (20).

Gain of function research of concern (GoFRoC), which creates or enhances potential pandemic pathogens,  has not contributed to the development of vaccines or antivirals. Other research which does not increase virulence or infectiousness is not under debate (7).

Existing virology regulation is grossly inadequate. In the USA, the HHS P3CO Review Group has only reviewed three research proposals since its inception in 2017 (21, 26).

COVID-19 has killed millions of people. The enormity of this disaster demands the strongest measures to ensure that it does not happen again.

Anthony Berglas, Ph.D., University of Queensland

 

References

  1. Speck, P. et al. (2023). Statement in support of: “Virology under the microscope—a call for rational discourse.” J Virology [ahead of print]. https://doi.org/10.1128/jvi.00451-23
  2. Speck, P. et al. (2023). Statement in support of: “Virology under the microscope—a call for rational discourse.” mBio [ahead of print]. https://doi.org/10.1128/mbio.00815-23
  3. Speck, P. et al. (2023). Statement in support of: “Virology under the microscope—a call for rational discourse.” mSphere [ahead of print]. https://doi.org/10.1128/msphere.00165-23
  4. Goodrum, F. et al. (2023). Virology under the microscope—a call for rational discourse. J Virology 97: e00089-23. https://doi.org/10.1128/jvi.00089-23
  5. Goodrum, F. et al. (2023). Virology under the microscope—a call for rational discourse. mBio 14: e00188-23. https://doi.org/10.1128/mbio.00188-23
  6. Goodrum, F. et al. (2023). Virology under the microscope—a call for rational discourse. mSphere 8: e00034-23. https://doi.org/10.1128/msphere.00034-23
  7. Bahry, D. (2023). Rational discourse on virology and pandemics. mBio [ahead of print]. https://doi.org/10.1128/mbio.00313-23
  8. Chan, A. & Ridley, Matt. (2022). Viral: The Search for the Origin of COVID-19 [paperback ed.]. Harper Perennial.
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  10. Young, A. (2023). Pandora’s Gamble: Lab Leaks, Pandemics, and a World at Risk. Center Street.
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  13. Wang, L.-F. et al. (2006). Review of bats and SARS. Emerg Infect Dis 12: 1834–1840. https://doi.org/10.3201/eid1212.060401
  14. Liu, W. J. et al. (2023). Surveillance of SARS-CoV-2 at the Huanan Seafood Market. Nature [accelerated article preview]. https://doi.org/10.1038/s41586-023-06043-2
  15. Crits-Christoph, A. et al. (2023). Genetic evidence of susceptible wildlife in SARS-CoV-2 positive samples at the Huanan Wholesale Seafood Market, Wuhan: Analysis and interpretation of data released by the Chinese Center for Disease Control. Zenodo [preprint server]. https://zenodo.org/record/7754299
  16. Bloom, J. D. (2023). Association between SARS-CoV-2 and metagenomic content of samples from the Huanan Seafood Market. bioRxiv [preprint server]. https://doi.org/10.1101/2023.04.25.538336
  17. Wang, N. et al. (2018). Serological evidence of bat SARS-related coronavirus infection in humans, China. Sin. 33: 104–107. https://doi.org/10.1007/s12250-018-0012-7
  18. Lerner, S. & Hibett, M. (Sep 23, 2021). Leaked grant proposal details high-risk coronavirus research. The Intercept. https://theintercept.com/2021/09/23/coronavirus-research-grant-darpa/ [accessed May 16, 2023].
  19. Chan, Y. A. & Zhan, S. H. (2022). The emergence of the spike furin cleavage site in SARS-CoV-2. Mol Biol Evol 39: msab327. https://doi.org/10.1093/molbev/msab327
  20. Suryanarayanan, S. (Dec 27, 2021). Wuhan’s lower biosafety level labs posed greater risk for coronavirus lab leak, experts said. S. Right to Know. https://usrtk.org/risky-research/wuhans-lower-biosafety-level-labs-posed-greater-risk-for-coronavirus-lab-leak/ [accessed May 16, 2023].
  21. S. Department of Health and Human Services. Research Review Under the HHS P3CO Framework. https://www.phe.gov/s3/dualuse/Pages/ResearchReview-PPP.aspx [accessed May 16, 2023].
  22. Sakshi Piplani (2021), Singh, Winkler, Petrovsky. In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin Nature 2021 https://www.nature.com/articles/s41598-021-92388-5
  23. World Health Organization (2022) WHO-convened global study of origins of SARS-CoV-2: China Part. https://www.who.int/publications/i/item/who-convened-global-study-of-origins-of-sars-cov-2-china-part
  24. Shing Hei Zhan (2020), Deverman, Chan SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence? https://www.biorxiv.org/content/10.1101/2020.05.01.073262v1
  25. WHO Director-General’s opening remarks at the media briefing – 17 March 2023 https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing—17-march-2023
  26. Rick Scott and Colleagues to HHS Secretary Becerra: Americans Deserve Full Accountability of COVID Research
    https://www.rickscott.senate.gov/2022/9/sen-rick-scott-and-colleagues-to-hhs-secretary-becerra-americans-deserve-full-accountability-of-covid-research
  27. Hu S, Zeng, …, Shi Z. (2017). Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. In PLoS Pathog. 2017 Nov. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708621/
  28. Furmanski M. (2014) Threatened pandemics and laboratory escapes: Self-fulfilling prophecies https://thebulletin.org/2014/03/threatened-pandemics-and-laboratory-escapes-self-fulfilling-prophecies/

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