139200
  • Log in
The Daily Sceptic
No Result
View All Result
  • Articles
  • About
  • Archive
    • ARCHIVE
    • NEWS ROUND-UPS
  • Forum
  • Donate
  • Newsletter
The Daily Sceptic
No Result
View All Result

COVID-19 Virus Has a Telltale “Fingerprint” That Makes it Highly Likely to Have Come From a Lab, Study Finds

by Will Jones
21 October 2022 7:00 AM

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.

Pre-print:

Endonuclease fingerprint indicates a synthetic origin of SARS-CoV-2

A collaborative product by @VBruttel, @tony_vandongen, and myself.

Here's what we found:https://t.co/GR0f0vGFyE

1/ pic.twitter.com/n4q7elUbHm

— Alex Washburne (@WashburneAlex) October 20, 2022

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’.

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.

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.

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.

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.

Digesting CoVs with only type IIS enzymes that could be used for assembly, SARS-CoV-2 is an even greater outlier. It’s in the bottom 1% max-fragment-length for all restriction enzymes. It’s the single largest outlier (<0.07%) of 1,491 type IIS digestions.

We then tested the lab-assembly hypothesis. If SARS2 has a synthetic origin via golden gate assembly, several other criteria must be met. For example: all sticky ends must be unique, non-palindromic and contain at least one A/T. SARS2 passed this test (60% chance of this).

The mutations separating SARS-CoV-2 BsaI/BsmBI sites from its close relatives must all be silent mutations. All 14 mutations in BsaI/BsmBI sites are silent. 84% of mutations in SARS2 and close relatives are silent, so 9% chance all 14 distinct mutations will be silent.

There’s a significantly higher concentration of silent mutations per nucleotide within BsaI/BsmBI recognition sequences than in the rest of the genome. P=0.004 for BANAL52-SARS2 P=9e-8 for RaTG13-SARS2.

Such an idealised reverse genetic system is unlikely to evolve by chance from the close relatives of SARS-CoV-2. There’s a 1% chance of random RaTG13 mutants having as great or greater z-score and 0.1% chance for BANAL52.

Testing this from multiple angles, we could not reject the hypothesis that SARS-CoV-2 has a synthetic origin. Each test also decreased the odds of SARS-CoV-2 having a natural origin. The BsaI/BsmBI fingerprint of SARS-CoV-2 indicates synthetic origin of SARS-CoV-2.

Please read our manuscript for our careful language and limitations. These are important. For example, our results are independent of the Furin Cleavage Site (FCS). While the RBD is docked in fragment 5, we shine no light on the origin of the FCS.

Our research does not identify the lab. We hypothesise this restriction map would enable construction of chimeric viruses, much like the recent controversial work done in Boston (but with a different method for in vitro assembly).

Our theory of a synthetic origin of SARS-CoV-2 can and should be tested. Further tests may reject our theory. We welcome these tests. Our code is available on GitHub and we point to future research that can reject our hypothesis or refine our understanding of this issue.

Making chimeric viruses in vitro carries risks. We encourage transparency from researchers studying CoVs in Wuhan. We strongly encourage global coordination on biosafety.

We encourage open, civil and compassionate discourse on this important topic. This pre-print was not rushed. It was reviewed by many colleagues, truly world experts. We thank them all immensely for their feedback. This has been an incredible project. Yet, for obvious reasons, this is the saddest paper I’ve ever written.

Stop Press: The paper has been heavily criticised by multiple specialists on Twitter, who have highlighted what they deem to be fatal flaws in it. Prof. Balloux has unexpectedly deleted his Twitter account, apparently in light of the criticisms of the paper, though he has not confirmed this. Dr. John Ross has (somewhat snidely) tweeted: “In case you missed it, U.K. Covid minimiser Francois Balloux has deleted his account after amplifying a spectacularly wrong preprint claiming to have proven that SARS-CoV-2 was synthetic (refuted below).”

In case you missed it, UK COVID minimizer Francois Balloux has deleted his account after amplifying a spectacularly wrong preprint claiming to have proven that SARS-CoV-2 was synthetic (refuted below) https://t.co/MjCGVRzFwv

— John Ross (@JohnRossMD) October 21, 2022

Dr. Ross’s Twitter thread and the replies to it provide links to a number of criticisms of the paper.

Dr. Washburne has responded here and here defending his paper.

Hey folks,

We're grateful for many thoughtful comments and smart discussions on this topic.

There's one point of discussion I'd like to weigh in on, after which I'll be back at my day-job before drinking from the firehose again this evening.

Multiple comparisons:

1/ https://t.co/g9MneNlcpP

— Alex Washburne (@WashburneAlex) October 21, 2022

Matt Ridley has praised the response for being reasoned and without invective: “This thread is a good response to a reasonable criticism. Not an insult in sight. Science as it should be done.”

This thread is a good response to a reasonable criticism.

Not an insult in sight.

Science as it should be done. https://t.co/kTTEyGnx7s

— Matt Ridley (@mattwridley) October 21, 2022
Tags: covid originsCOVID-19Endonuclease fingerprintFurin cleavage siteLab leak

Donate

We depend on your donations to keep this site going. Please give what you can.

Donate Today

Comment on this Article

You’ll need to set up an account to comment if you don’t already have one. We ask for a minimum donation of £5 if you'd like to make a comment or post in our Forums.

Sign Up
Previous Post

News Round-Up

Next Post

Time for Doctors and Politicians to Stop Ignoring the Devastating Data on the Vaccines and Change Course

Subscribe
Login
Notify of
Please log in to comment

Profanity and abuse will be removed and may lead to a permanent ban.

23 Comments
Oldest
Newest Most Voted
Inline Feedbacks
View all comments

NEWSLETTER

View today’s newsletter

To receive our latest news in the form of a daily email, enter your details here:

DONATE

PODCAST

Nick Dixon and Toby Young Talk About Toby’s Appearance on the 77th Brigade’s Watch List, the Scrubbing of the Internet After the Pfizer Sting and the Trans Insanity Unfolding in Scotland

by Will Jones
31 January 2023
0

LISTED ARTICLES

  • Most Read
  • Most Commented
  • Editors Picks

MIT Expert on Drug Safety Calls for Immediate Withdrawal of mRNA Vaccines: “Clearly the Most Failing Medical Product in History, Causing Unprecedented Harm”

30 January 2023
by Will Jones

News Round-Up

31 January 2023
by Will Jones

Scientists Struggle to Understand Why Antarctica Hasn’t Warmed for Over 70 Years Despite Rise in CO2

29 January 2023
by Chris Morrison

The Ministry of Truth

31 January 2023
by Dr Carl Heneghan and Dr Tom Jefferson

Elderly Vaccination Saved Lives in East Asia

31 January 2023
by Noah Carl

News Round-Up

48

Elderly Vaccination Saved Lives in East Asia

39

The JCVI is Right to Withdraw Boosters for Under-50s, But It’s Still Spinning the Stats

34
Mandatory Credit: Photo by JUSTIN LANE/EPA-EFE/Shutterstock (10421665ds)
Sixteen-year-old climate activist Greta Thunberg addresses world leaders at the start of the 2019 Climate Action Summit which is being held in advance of the General Debate of the General Assembly of the United Nations at United Nations Headquarters in New York, New York, USA, 23 September 2019. World Leaders have been invited to speak at the event, which was organized by the United Nations Secretary-General Antonio Guterres, for the purpose of proposing plans for addressing global climate change. The General Debate of the 74th session of the UN General Assembly begins on 24 September.
United Nations 2019 Climate Action Summit, New York, USA - 23 Sep 2019

Elite Billionaire Foundations Fund Wave of Green Climate Propaganda Flooding into British Schools

18

The Ministry of Truth

14

Elderly Vaccination Saved Lives in East Asia

31 January 2023
by Noah Carl
Mandatory Credit: Photo by JUSTIN LANE/EPA-EFE/Shutterstock (10421665ds)
Sixteen-year-old climate activist Greta Thunberg addresses world leaders at the start of the 2019 Climate Action Summit which is being held in advance of the General Debate of the General Assembly of the United Nations at United Nations Headquarters in New York, New York, USA, 23 September 2019. World Leaders have been invited to speak at the event, which was organized by the United Nations Secretary-General Antonio Guterres, for the purpose of proposing plans for addressing global climate change. The General Debate of the 74th session of the UN General Assembly begins on 24 September.
United Nations 2019 Climate Action Summit, New York, USA - 23 Sep 2019

Elite Billionaire Foundations Fund Wave of Green Climate Propaganda Flooding into British Schools

31 January 2023
by Chris Morrison

The JCVI is Right to Withdraw Boosters for Under-50s, But It’s Still Spinning the Stats

31 January 2023
by Amanuensis

MIT Expert on Drug Safety Calls for Immediate Withdrawal of mRNA Vaccines: “Clearly the Most Failing Medical Product in History, Causing Unprecedented Harm”

30 January 2023
by Will Jones

In Praise of Boris Johnson’s Stance on Ukraine

28 January 2023
by Noah Carl

POSTS BY DATE

October 2022
M T W T F S S
 12
3456789
10111213141516
17181920212223
24252627282930
31  
« Sep   Nov »

SOCIAL LINKS

Free Speech Union
  • Home
  • About us
  • Donate
  • Privacy Policy

Facebook

Twitter

Instagram

RSS

Subscribe to our newsletter

© Skeptics Ltd.

No Result
View All Result
  • Articles
  • About
  • Archive
    • ARCHIVE
    • NEWS ROUND-UPS
  • Forum
  • Donate
  • Newsletter

© Skeptics Ltd.

Welcome Back!

Login to your account below

Forgotten Password?

Create New Account!

Please note: To be able to comment on our articles you'll need to be a registered donor

Already have an account?
Please click here to login Log In

Retrieve your password

Please enter your username or email address to reset your password.

Log In
wpDiscuz
You are going to send email to

Move Comment