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1. 2021-05-11 15:48 Robert F. Garry open
   Competing hypotheses have been put forward to explain the emergence of SARS-CoV-2. Natural spillover directly from a bat or via an intermediate animal host could have occurred via several different scenarios (Fig. 1). Likewise,several variations of the Lab Leak hypothesis have been proposed (Fig. 2). A dispassionate science-based discourse on the topic of the origin of SARS-CoV-2 must account for this new data revealed by the WHO study showing: 1. multiple markets were linked to the early cases, and 2. divergence of SARS-CoV-2into lineages A and Bwas an early occurrence. These facts are represented by yellow boxes in each figure.``` Figure 1. Natural scenarios of SARS-CoV-2 origin. Natural spillover directly from a bat or via an intermediate host may have involved trade in wildlife susceptible toSARS-CoV-2, either trapping and hunting of wildlife in nature or farming of "wildlife species." There is now clear evidence that SARS-CoV-2 is capable of effective spread, not only in humans, but to a diverse group of mammals (Garry, 2020). The multi-market aspect of the early outbreak can be explained by distribution of SARS-CoV-2 infected animals to more than one market (Fig. 1). In Natural scenarios diversification of SARS-CoV-2 to lineages Aand B could have occurred prior to the distribution, either at a wildlife farm or during transport of the animals to the markets. It is possible that humans involved in the wildlife trade were also infected and involved in this pathway. Figure 2. Lab Leak scenarios of SARS-CoV-2 origin. ```Proponents of Lab Leak theories speculate that SARS-CoV-2 or a close progenitor was present in the Wuhan Institute of Virology or another Wuhan virology lab before the start of the COVID-19 pandemic and the appearanceof the first cases in Wuhan (Fig. 2). It has been proposed that SARS-CoV-2 was released either via an infected laboratory worker, an escaped lab animal or via waste disposal (Relman 2020; Butler et al., 2021). Pangolins carry and appear to be naturally infected with at least two lineages of sarbecoviruses (Liu et al., 2019; Lam et al., 2020).The Guangdong strain of pangolin coronavirus carries a receptor binding domain (RBD) that is highly similar to the RBD of SARS-CoV-2 (Lam et al., 2020, Andersen et al., 2020). Some proponents of the Lab Leak theory have speculated the RBD of GD pangolin was recombined via genetic engineering with the backbone of an undisclosed sarbecovirus to produce SARS-CoV-2. Alternatively, it has been suggested that an undisclosed close progenitor ofSARS-CoV-2 was passaged on human cells or experimental animals (such a humanized mice) in gain-of-function type experiments to adapt for human replication (Relman, 2020, Segreto and Deigin, 2020; Sirotkin and Sirotkin,2020). The direct role of the Chinese military in conducting classified research on sarbecoviruses at the WIV has also been proposed (United States, 2021). In Lab Leak scenarios diversification of SARS-CoV-2 to its two separate early lineages A and B would have had to occur in the laboratory setting. Lab Leak scenarios must also account for the fact that the majority of early cases were associated with different wildlife markets in Wuhan.``` ```
2. 2021-05-11 15:48 Robert F. Garry
   *Discussion* Lab Leak scenarios are inconsistent with several established facts regarding the origin of SARS-CoV-2. The majorityof early cases were linked to different markets that sold wildlife or wildlife products in Wuhan. All theories of the origin of SARS-CoV-2 must account for the linkage to different market engaged in wildlife trade. Theories onSARS-CoV-2 must also account for the fact that two distinct lineages of SARS-CoV-2 were distributed at different Wuhan wildlife markets. Scenarios where an infected laboratory worker, an escaped lab animal or faulty wastedisposal spread not one but two lineages of SARS-CoV-2 specifically to different wildlife markets are difficult torationalize.The original SARS-CoV outbreaks in 2002-2004 were linked to the wildlife trade (Guan et al., 2003). In contrast toLab Leak theories, linkage of the origin of SARS-CoV-2 to wildlife or the wildlife trade provides several plausible scenarios for the appearance of SARS-CoV-2 at different wildlife markets. It fully accounts for the fact that the majority of early Wuhan COVID-19 cases were linked to different wildlife markets in a straightforward manner. It also provides simple explanations for the fact that two different lineages of SARS-CoV-2 were linked to markets. In one possible scenario divergence of SARS-CoV-2 to lineages A and B occurred prior to the transport of infected animalsto Wuhan and the infected animals were subsequently distributed to different wildlife markets. Proponents of the Lab Leak theory will point out that none of the animals sold at the Huanan Market tested positive for SARS-CoV-2 (WHO, 2021). Although mentioned in the WHO Report, but not discussed in detail, several independent sources indicate that wildlife species susceptible to SARS-CoV-2, including civets and raccoon dogs, were sold at the Huanan market (Stout, 2020; Yee, 2020; Zhang and Holmes, 2020). Similar species were likely tohave been available to purchase at other wildlife markets in Wuhan. Certain species of animals may have been removed after the appearance of the first COVID-19 cases and the linkage of COVID-19 cases to the market, but prior to the closure of the Market on January 1, 2020. It should also be noted that environmental samples that did test positive were associated with the portion of the market where wildlife or wildlife products were sold. A temporalanalysis of the early human cases at the Huanan market confirms the pattern of spread from the areas of the market where wildlife products were sold to other parts of the market. (WHO, 2021).A hybrid of natural and Lab Leak scenarios suggests that SARS-CoV-2 is a natural virus that infected a scientist while doing field work or other personnel after being brought back to a laboratory where it was stored or propagatedand then released unknowingly (Relman, 2020; Baker, 2020). Compared to the millions of worldwide encounters ofhumans with wildlife, including the trapping of bats for food, the number of exposures of scientists doing field work isminiscule. Thus, this hybrid scenario is of very low probability. It also fails to explain how two lineages ofSARS-CoV-2 came to be distributed at the different wildlife markets. Conclusions New data compiled by the WHO team regarding the presence of distinct lineages of SARS-CoV-2 in different Wuhan wildlife markets are inconsistent with a laboratory-based origin of SARS-CoV-2.
3. 2021-05-11 16:02 Edward C. Holmes open
   You're on fire Bob! I'll take a look when I get a chance.

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