But the research on the bat viruses in Wuhan showed that infecting live animals with altered viruses can have unpredictable consequences. A report to NIH on the project’s progress in the year ending in May 2018 described scientists creating new coronaviruses by changing parts of WIV1 and exposing genetically engineered mice to the new chimeric viruses. Research published in 2017 in the journal PLOS Pathogen showed that, in cells in a laboratory, similar chimeric viruses reproduced less effectively than the original. NIH cited that research as one of the reasons the moratorium on gain-of-function research of concern didn’t apply to this experiment. “It was a loss of function, not a gain of function,” the email from NIH explained. (NIH also pointed out that the changes to the chimeric viruses “would not be anticipated to increase virulence or transmissibility in humans.”)

Inside the lungs of the humanized mice, however, the novel viruses appear to have reproduced far more quickly than the original virus that was used to create them, according to a bar graph shown in the documents. The viral load in the lung tissue of the mice was, at certain points, up to 10,000 times higher in the mice infected with the altered viruses than in those infected with WIV1. According to Deatrick, the NIH spokesperson, the difference in the rates of viral reproduction — which were particularly pronounced two and four days after the mice were infected with the virus — didn’t amount to gain of function because, by the end of the experiment, the amount of virus produced by the parent and chimeric strains evened out. “Viral titers were equivalent by the end of the experimental time-course,” Deatrick wrote. The email also said, “NIH supports this type of research to better understand the characteristics of animal viruses that have the potential to spill over to humans and cause widespread disease.”

Scientists The Intercept consulted expressed differing views on whether the increase in viral load could be translated to an increase in transmissibility, which relies on the virus’s ability to replicate. To some, the jump in viral load indicated that the modified RNA virus could replicate far more rapidly than the original in the lungs of the mice, likely leading to increased pathogenicity and spread. Rasmussen, of the Vaccine and Infectious Disease Organization, pointed out that viral load is not identical to reproduction rate, noting: “This shows the chimeric viruses replicated a little faster, but that tells us exactly nothing about transmissibility. Furthermore, WIV1 caught up by the end of the experiment. We see differences in the rate of viral replication all the time, but it is often not directly correlated with pathogenicity.”

Another figure in the documents suggests that at least one of the altered viruses not only enhanced viral reproduction, but also caused the humanized mice to lose more weight than those exposed to the original virus — a measure of the severity of illness.

https://theintercept.com/2021/09/09/covid-origins-gain-of-function-research/

The real question is still, "Why did you immediately jump to personal attacks, infodumping irrelevant studies, and why are you vehemently defending this lab as if you're the one who caused the leak?

[–] justdoit@lemm.ee 12 points 1 year ago* (last edited 1 year ago) (1 children)

Oh boy, so this is where you stumbled. I should have known it would be The Intercept article.

The documents are ancillary, huh? You cited the exact same grant proposal I sent you. So is it ancillary or not?

Here are some really critical points I’m willing to bet you misunderstood:

“We will construct chimeric SARSr-CoVs using WIV1 backbone and the S genes of selected SARSr-CoV strains and assess capacity to infect hACE2, bACE2, and cACE2 Vero cells…”

The WIV1 backbone is NOT the backbone found in SARS-CoV-2. It’s from a completely different human-infectious coronavirus strain. Furthermore, the spike proteins they’re studying would be gathered from bat coronaviruses found in the wild. So, this method is NOT considered GoF research by the NIH nor is it even potentially possible it resulted in the pandemic. They proposed assessing transmissibility by using an already known infectious backbone and an uncharacterized spike protein, not engineering a more deadly virus. WIV1 is already infectious in humans. The spike proteins gathered are the exact same sequences as those already present in the wild. You may still have reservations about this approach, but I’d argue it’s actually safer for studying viruses in this way because you use what’s known as a Bacterial Artificial Chromosome (BAC) to infect the cells rather than live virus. Meaning, no storage, handling, or serial passaging of viral samples is required past the initial isolation and the plaque assessments.

You may argue that any viral research which can result in genetic change should be classified unilaterally as GoF, and is too dangerous to be performed, much less at labs we don’t directly regulate. I would disagree on those points, but you’d join a rich debate on the subject which The Intercept article actually points out as well. But the fact remains that none of the above studies were designed to engineer more deadly pathogens for humans, and is ultimately a red herring for the SARS-CoV-2 debate. We know the backbone sequences and they do not match, so you and The Intercept article are barking up the wrong tree.

The same is true for the PLOS study you cited. Same viral backbone, same process. It’s there to assess transmissibility of a naturally occurring virus and try to predict future pandemic potential (of the original SARS-CoV, in their case), not to engineer more effective viruses. Same misunderstanding on its classification as GoF research, too. Even in the Intercept article you cite it talks about the results of other studies as technically “loss of function” in relation to some strains, which is true. But again, all of this is a red herring. SARS-CoV-2 did NOT use the backbone referenced here, and thus this study did not result in a genetically engineered virus that caused the pandemic.

As for citations, I’d point you to this snippet from a review article in Cell:

A near identical nucleotide sequence is found in the spike gene of the bat coro- navirus HKU9-1 (Gallaher, 2020), and both SARS-CoV-2 and HKU9-1 contain short palindromic sequences immediately up- stream of this sequence that are indicative of natural recombina- tion break-points via template switching (Gallaher, 2020). Hence, simple evolutionary mechanisms can readily explain the evolu- tion of an out-of-frame insertion of a furin cleavage site in SARS-CoV-2 (Figure 2).

You keep insisting that I think a lab leak is impossible, when I’ve made it very clear that a lab leak is still a possibility. There were safety concerns at Wuhan long before this whole thing. But a “lab leak” of a stored sample is completely different than “Fauci paid incompetent Chinese labs to engineer deadly pathogens”, and I’ve never seen evidence for the latter. Yet you’ve stated that sentiment here in the comment section, so somehow that unsubstantiated belief lives on. Until our pool of evidence changes, the most likely scenario is a zoonosis from a natural reservoir, or a lab leak from a gathered or cultured sample.

I’m curious why you seem so insistent that the evidence is being hidden and that everyone is silencing you. You come in here with unsubstantiated accusations, and then get angry when people call you out for it. Had you started with sources for your claims, I would have been happy to engage with you on that level. Acting like an ass in any forum isn’t going to get you far. Stop playing the victim.