Study Finds Covid-19 Has Fingerprint Suggesting It May Have Come From Lab

The Covid-19 coronavirus SARS-CoV-2 has a telltale “fingerprint” that means it is highly likely to have been made in a lab, new research has found.

Mathematical biologist Dr. Alex Washburne and colleagues Valentin Brutte and Antonius VanDongen have published their research in a preprint that found “a high likelihood that SARS-CoV-2 may have originated as an infectious clone assembled in vitro”.

They explain that this evidence, which they term an “endonuclease fingerprint”, is independent of the evidence relating to the Furin Cleavage Site, which others have suggested is a ‘smoking gun’ for a lab origin.

Dr. Washburne stresses that he is not alleging malign intent or even gain-of-function work in this paper. He writes:

“We find no evidence of SARS-CoV-2 being a bioweapon (on the contrary, this looks like an accident) or any gain of function work. We find evidence suggesting SARS-CoV-2 may have been synthesised in the lab with known methods, probably for normal pre-Covid research purposes.”

Professor Francois Balloux has given the study his imprimatur on Twitter, writing:

“This is an important piece of work. To me, it looks solid both conceptually and methodologically. I was given advance warning and was able to replicate the key findings. To the best of my knowledge, I confirm the reported patterns are genuine.”

To accompany the study Dr. Washburne has published a Substack and a Twitter thread. The Twitter thread is reproduced in full below – it can be a bit technical in places, but the message it’s conveying should come through clearly enough.

Study Finds Covid-19 Has Fingerprint Suggesting It May Have Come From Lab

The origin of SARS-CoV-2 is unknown. Some hypothesised two spillover events at the wet market, but methodological flaws make that work inconclusive. We need to know the true origin of SARS-CoV-2 to prevent pandemics.

We examined whether SARS-CoV-2 was synthesised in a lab. We studied a common method for synthesising coronaviruses (CoVs) in the lab. This method was thought to not leave a fingerprint. We found the fingerprint. That fingerprint is in the SARS-CoV-2 genome.

Here’s how you make a CoV in the lab. To make a 30,000 base (30kb) RNA virus in the lab, you need a 30kb DNA clone. To assemble a 30kb DNA clone, scientists glue together several smaller fragments.

A popular method for DNA assembly is ‘golden gate assembly’.

Study Finds Covid-19 Has Fingerprint Suggesting It May Have Come From Lab

Golden gate assembly requires the DNA sequence have special ‘cutting’ sites (type IIS restriction sites). Cutting sites create three to four nucleotide (nt) ‘sticky ends’. Sticky ends help you ‘paste’ DNA segments together, ensuring faithful assembly of your 30kb DNA copy of a viral genome.

RNA viruses like CoVs are not under selection specifically for this kind of cutting and pasting. So, wild viruses tend to have cutting and pasting sites randomly scattered in their genome. Researchers building viruses in a lab will often add or remove cutting sites.

We collected examples of CoV infectious clones assembled with these type IIS cutting and pasting systems from 2000-2019. We found a clear pattern in how researchers tended to add or remove cutting and pasting sites.

Researchers tend to turn randomly-spaced restriction maps into regularly-spaced ones (A-B). Regular spacing comes from desiring fewer fragments (typically five to eight) while keeping the longest fragment lengths low.

Study Finds Covid-19 Has Fingerprint Suggesting It May Have Come From Lab

Digesting 70 CoVs with 200-plus restriction enzymes yields a ‘wild type distribution’, a null model for how long the longest fragment may be as a function of the number of fragments [when the virus is wild]. The red box is the ideal range for reverse genetic systems used to make infectious clones.

Study Finds Covid-19 Has Fingerprint Suggesting It May Have Come From Lab

CoVs engineered to be infectious clones will move from having restriction maps falling within the wild type distribution to being outliers under the wild-type distribution, falling within the lab-ideal range of fragment number and low longest-fragment-length.

Study Finds Covid-19 Has Fingerprint Suggesting It May Have Come From Lab

Having found this fingerprint, we examine specific cutting and pasting sites in the SARS-CoV-2 genome (BsaI/BsmBI).

BsaI and BsmBI are very popular enzymes for this kind of in vitro assembly They also have many conserved sites in CoVs. Very useful for making chimeras.

The SARS-CoV-2 BsaI/BsmBI restriction map falls neatly within the ideal range for a reverse genetic system. It is an anomaly (bottom 1%) amongst wild type CoVs. It is a midpoint amongst engineered CoVs…

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