Thread by @Ayjchan

I was recently asked what I would like to see come out of SARS-CoV-2/covid origins investigations.

I would like to know that, the next time a pandemic like this occurs, the world is better prepared, better informed as to how to determine its origins and prevent future outbreaks.

I'm going to break down 3 key publications that I think relate to covid origins. What were the questions they asked to determine whether SARS-CoV-2 came from nature vs from a lab?

Are these approaches sufficient to prepare us for the next mysterious pandemic?

The 1st is the widely-read Proximal Origins article - a correspondence published in @NatureMedicine on March 17, 2020. How did the authors determine that "SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus"?
nature.com/articles/s4159…

The authors essentially asked: Is this how someone would’ve designed or selected for a pathogen based on published sequences and computational tools? And could this have possibly evolved naturally?

Happy to be corrected if I'm mistaken @K_G_Andersen

The major caveat of this approach is over-reliance on the public literature. Many scientists know that an overwhelming % of our work is not published in a timely manner.

The article also does not ask: could someone have engineered this pathogen based on unpublished sequences?

I understand that this could be perceived as wandering deep into "conspiracy land" but imo is a very practical question. We know numerous virus sequences are not shared publicly, we know of years of virus sampling, manipulation, infectivity assays performed at the WIV...

That's why I don't understand why the Proximal Origins authors said “generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described”

There is a clear track record of the WIV performing SARS virus infection assays in cell culture and mice with human ACE2. FCS has also been inserted into SARS1 in the lab by other groups since 2006.

https://twitter.com/Ayjchan/status/1306419491300167680https://twitter.com/Ayjchan/status/1266805310313967617

Furthermore, the Proximal Origins approach cannot distinguish natural viruses, isolated from animals or even humans, that were brought back to a bustling city and cultured in the lab, or sequenced and synthesized in the lab.

The 2nd publication is today's Biosecurity Perspectives (Dec 8, 2020) in @NatureComms which doesn't even mention covid or the SARS2 pandemic. So I'm going out on a limb guessing that this article was at least partially inspired by current global events. nature.com/articles/s4146…

Key questions in this approach: Where did the outbreak occur? Was it in a conflict zone or near a lab working on similar pathogens? What does intelligence say? Can existing technology tell whether this was definitely engineered (and who dunnit)?

The Perspectives focuses on the last question in particular: Is here a distinct signature left by the genetic engineering? Is there a way of “tracing these design choices back to the likely designer”?

Again major caveats of such an approach: over-reliance on what is in the public domain. Inability to detect pathogens that were not engineered but emerged from other lab activities. Bad actors who copy signatures by other labs to confuse origins investigations.

I get into the limitations of this approach a bit more and why it cannot help us in the investigation for SARS-CoV-2's origins in this thread from this morning:

https://twitter.com/Ayjchan/status/1336363523862048768

You're probably asking if I'm bashing all experts. I saved the one I approved of for last: "A Guide to Investigating Outbreak Origins: Nature versus the Laboratory" @JamesMartinCNS Oct 28, 2020 by Rich Pilch @MilesPomper Jill Luster @FilippaLentzos
nonproliferation.org/op-49-a-guide-…

Twitter concatenated my urls:

https://twitter.com/Ayjchan/status/1306419491300167680

https://twitter.com/Ayjchan/status/1266805310313967617

The CNS article directly addresses the COVID pandemic and their approach starts with: What are the evidence supporting each hypothesis?

And imo they gave each hypothesis a fair evaluation.

I almost want to screenshot everything, but key questions include: is this outbreak usual based on location, time of year, index cases (e.g., occupations), typical exposure of this human pop to such pathogens/reservoirs, genetic features that could suggest manipulation, lab risk.

The CNS article does a deep dive into factors to consider in the context of risky lab activities and recommends that lab and sample logs "provided on a need-to-know basis to an approved international investigative body under IHR 2.0"...

This approach acknowledges that public domain knowledge is the more practical way to determine whether related pathogens exist in labs, "however, the laboratory’s scientists must be permitted to publish openly in order for such information to be available."

In the context of covid, I'm fairly confident, based on 2020 events, that these unrestricted access to lab logs and databases, and open, honest communications with scientists at the heart of this controversy, free from intimidation, are going to be near impossible.

The world is sitting on a precedent-setting decision right now. It is unclear if Sars2 is 100% natural or emerged due to lab/research activities.

If we walk away from this, demonstrating that we cannot effectively investigate its origins, it will pave the way for future covids.

Contrary to what Proximal Origins and Biosecurity Pers. suggest, there is no need to get fancy with computational models+machine learning.

Scientists just have to continue doing what we're already doing: Not being transparent or accountable with our research in a timely manner.