And the well adapted to humans furin site is just plain luck? Its not like this has not happen before, SARS like virus's have crossed species within modern history that we have detected, and they all flame out eventually. I'm no virologist, but I believe its typically because of selection pressure and the mutations needed to start to adapt to humans don't come easily once a jump occurs, it usually takes a few jumps to get it right. This one came out already well adapted to humans and has a furin site not seen in other bat corona viruses, plus 4 additional amino acid chains that give it even more ability to infect cells. This is why Elon Musk got egg on his face for making the prediction that it would be over within a few months, that was based on past outbreaks.
Bret is very clear that yes, this can happen naturally, but the chances are very slim that such a alignment of events occurred in proximity to a lab that was performing gain of function research which does this very thing of combining aspects of multiple viruses and rapidly adapting them in either other animal hosts or petri dishes of cells, including human cells.
Furin cleavage sites naturally occur in coronaviruses [1]
> The spike protein is a focused target of COVID-19, a pandemic caused by SARS-CoV-2. A 12-nt insertion at S1/S2 in the spike coding sequence yields a furin cleavage site, which raised controversy views on origin of the virus. Here we analyzed the phylogenetic relationships of coronavirus spike proteins and mapped furin recognition motif on the tree. Furin cleavage sites occurred independently for multiple times in the evolution of the coronavirus family, supporting the natural occurring hypothesis of SARS-CoV-2.
Not "just plain luck" but a relatively rare recombination event that can occur in nature with co-infection. I have no problem with the lab hypothesis but I expect to see clear signs of a recent lineage recombination in the full SARS-CoV-2 genome. The lab theory requires not only a lab leak but the active suppression of the sequence(s) of the viral isolate(s) used in the hypothetical gain-of-function experiment.
Wuhan is no more unlikely than the mainland near Hong Kong where SARS-1 emerged. Any major city center in China that is accessible from Kunming, Yunnan [2] is a likely outbreak hotspot.
You have to quantify "relatively rare". Its closest relatives of high genetic match do not have this furin site, as they admit in the paper you linked to, only the sister clade does:
"Moreover, SARS-CoV-2 is the only virus in subgenus Sarbecovirus having this feature, while even its closest relatives, bat coronavirus RaTG13 (sequence identity 97.7%) and pangolin coronaviruses (92.9%–90.7%), do not have furin site. However, in Hibecovirus, the sister clade of Sarbecovirus, a Hipposideros bat coronavirus collected in 2013 at Zhejiang Province in China has furin site at S1/S2. Interestingly, the other member in Hibecovirus lacks such site, similar to the situation of SARS-CoV-2 and its close relatives. Interestingly, the other member in Hibecovirus lacks such site, similar to the situation of SARS-CoV-2 and its close relatives. "
Notice they don't publish the genetic match of the sister clade. Howe exactly does it jump clade when its closest relatives don't have the site?
This is what they point out in the podcast. Can it occur naturally, yes, but what are the chances if its closest relatives do not have it at all and none in the same clade? What exactly is the mechanism that this can occure? Its not just the furin site, they also discuss 4 other amino acid chains present that expanded its infectiousness. If this was a relatively chance combination of bat and pangolin incubated mutation that someone also gained the furin site and 4 other amino chains, why has it not flamed out like past jumps such as MERS which had the same? Pretty fortunate for a new mutation.
>>The lab theory requires not only a lab leak but the active suppression of the sequence(s) of the viral isolate(s) used in the hypothetical gain-of-function experiment.
Agreed, and although I don't necessarily think highly of the sources (Daily Mail), there does appear to be suppression of evidence even recently:
I believe Bret's podcast also talks about a database that was also taken down shortly after the outbreak from the Wuhan lab that may contain the sequence of the virus SARS Cov 2, which is standard practice for engineered viruses for study. I've also heard that there were samples destroyed in China during the early outbreak. If they were truly transparent they would release all records and backups of their databases going back a year or 2 before the outbreak to prove no such sequencing took place. So far I have not seen that. Keep in mind that all these level 4 labs globally are at risk of being shut down if any of this gets proved. They become political hot potatoes. If the public became fully aware (as in the laymen on the street knew) that multiple companies exist that can print any virus DNA sequence for $30,000 USD, and one of them escaped, they would likely be horrified.
I do agree that this can arise naturally, but the confluence of rare events arising a couple blocks from a level 4 lab studying exactly this gives me pause.
Bret is very clear that yes, this can happen naturally, but the chances are very slim that such a alignment of events occurred in proximity to a lab that was performing gain of function research which does this very thing of combining aspects of multiple viruses and rapidly adapting them in either other animal hosts or petri dishes of cells, including human cells.