SARS-COV-2 Laboratory Leak Hypothesis

Guest Post by Andrew Tuntable, Ph. D. Email: atuntable@gmail.com Twitter: @atuntable

  1. SARS-COV-2 Laboratory Leak Hypothesis
    1. The Lab Leak Hypothesis
      1. The Importance of the Hypothesis
      2. Beyond Reasonable Doubt
    2. Summary of the Evidence
      1. Geography
      2. Natural precursors
      3. Laboratory Leaks
      4. Chimera
      5. Furin Cleavage Site
      6. 2013 Sick Bat Guano Miners
      7. Database Removal and Obfuscation
      8. Sick WIV Workers
      9. Eco Health Alliance and NIH Research Grants
      10. Early Contact Tracing
      11. Chinese Reaction
    3. Rebuttal of the Lab Leak Hypothesis
      1. Linage A and B
      2. RaTG13 is Too Different
      3. The Furin Cleavage Site Encoding
      4. Engineering SARS-COV-2 is Beyond Current Technology
      5. The WIV Cannot Disprove a Leak
      6. Researchers Became Infected Inside the Caves
      7. Danielle Andersen
      8. Chinese Bioweapons Program
      9. Wuhan World Military Games
    4. Reactions to the Lab Leak Hypothesis
      1. Andersen Paper
      2. Daszak Letter
      3. WHO Investigation
      4. Biden Investigation
      5. Ralph Baric Letter
    5. Political Environment
      1. Trump Administration
      2. Anthony Fauci and Gain of Function
      3. The Virology Community
    6. Gain of Function Research
    7. Conclusion
    8. Annotated Biography

The Lab Leak Hypothesis

Virologists study dangerous viruses.  They collect them from the wild, they study them in labs, and they genetically engineer them.  One goal of their research is to help prevent future pandemics.

However, viruses have escaped from laboratories around the world on several occasions.  New techniques for bioengineering can enable dangerous viruses to be created in research laboratories. 

Previous pandemics such as SARS and MERS have arisen naturally as viruses jump from species to species and evolve through natural selection.  The lab leak hypothesis proposes that the SARS-COV-2 virus responsible for Covid-19 did not arise naturally but escaped from a virology laboratory, the Wuhan Institute of Virology (WIV) [Segreto20] [Deigin21].

The Importance of the Hypothesis

If SARS-COV-2 did result from a lab leak then such research needs to be much more carefully controlled in order to prevent any future outbreak of an even more potent virus.

There is no suggestion that the leak was deliberate.  The Wuhan Institute of Virology published their impressive results and collaborated openly with other virologists around the world.  For example, their chief scientist Shi Zhengli collaborated closely with Ralph Baric of the University of North Carolina.  The Wuhan Institute of Virology is a well respected member of the international community of virologists.

Until recently, any suggestion of a laboratory leak was discounted as an unsubstantiated far right conspiracy theory.  However, as more and more evidence has accumulated many leading scientists now consider the theory plausible if not proven.

This paper should not be viewed as an attack on China.  But rather, it provides a strong motivation to review the practice of virology internationally.

Beyond Reasonable Doubt

There will never be a mathematical proof that SARS-COV-2 is the result of a laboratory leak. 

However there is now a large body of evidence to support a leak hypothesis.  Taken collectively we believe that it proves the hypothesis well beyond any reasonable doubt.  But the reader is encouraged to review the evidence and draw their own conclusions.

There is no absolute proof.  But there is most certainly plenty of evidence.

Summary of the Evidence

Geography

The outbreak of a bat coronavirus occurred in the city which hosted the world’s leading bat coronavirus laboratory.  This does not prove anything, but it certainly warrants investigation.

Moreover, the relevant horseshoe bats live 1500 kilometers from the laboratory.  No explanation has been offered as to how the virus traveled to Wuhan.  The Chinese CDC and WIV chief scientist Shi Zhengli have stated that the “wet markets” that sell exotic animals were not the source of the virus.

Natural precursors

A natural virus takes some time to adapt to a new host, as SARS-1 and MERS did.  But SARS-COV-2 arose suddenly, fully formed and functional.   Early genomes showed minimal variation, and it took many months and billions of infections in order for it to substantially improve upon the first variant (with the Beta and then Delta strains).

The virus is not particularly infectious to bats.  So any natural evolution would require some other unknown intermediate host animal.  (The coronavirus’s critical spike protein is very host species dependent.) 

The WHO report stated that none of the hospitals in Hubei Province (in which Wuhan is located) reported any SARS-like viruses in the months before December 2019, so it is unlikely to have matured in humans.  No other natural precursor has been found, despite an extensive search.  (The direct precursors to SARS-1 and MERS were identified within several months of their outbreaks.)

The only currently known potential intermediate host is laboratory cell cultures and genetically engineered “humanized” mice which are commonly used for research into coronaviruses.

Laboratory Leaks

Laboratory leaks have occurred many times around the world.  Examples include leaks of SARS-1 from Singapore and Taiwan in 2003 and Beijing in 2004, Foot and Mouth from the USA in 2004, Ebola from Germany in 2009, and Brucellosis from China in 2016.

A review of the WIV in 2017 by the US embassy had concerns about the institute’s biosecurity protocols.  To their credit, the WIV had asked for help in improving their biosecurity.[Rogin21][Pompeo21][Liu20]

SARS-COV viruses were not considered particularly dangerous before 2020, and published papers indicate that much of the research both at the WIV and the University of North Carolina was conducted at Biosecurity Levels 2 and 3 (BSL-2, BSL-3).  The WIV’s new high security BSL-4 facility was used for more dangerous viruses such as Ebola.

Chimera

The virus appears to be 96.1% similar to a genome RaTG13 which was released by the WIV in January 2020, after the outbreak.

The genome suggests that SARS-COV-2 was a chimera, a mixture between two or more viruses.   This is because the “body” of the SARS-COV-2 is 98% similar to RaTG13 while the “head” of the virus (the tip of the spike protein) is significantly different. 

Such chimeras do occur naturally.  However, the two viruses need to infect the same cells in the same animal.  No host has been found or proposed.  (Evidence that pangolins were involved is now discounted.)

Modern technology makes it relatively easy to create such chimera’s in the laboratory, and this is often performed.  They leave no obvious trace that the genome has been manipulated.  There is no doubt that the WIV was engineering many such chimeras because they proudly published their results.  Shi in 2007 and Baric in 2008 created chimeric viruses based on the SARS virus, with the most influential paper being [Menachery15].  A 2017 WIV paper reported eight chimeric viruses [Hu17].

Furin Cleavage Site

SARS-COV-2 has a “S1/S2 furin cleavage site” that had been known to greatly increase the potency of coronaviruses.  This is not found naturally in other beta coronaviruses like SARS-COV-2 yet it is essential for SARS-COV-2 to be able to infect humans.  Further, the actual genome that represents the cleavage site is unusual for a coronavirus, but is commonly used in the laboratory.

SARS-1 did not have a furin cleavage site.

Both the very effective spike protein and the furin cleavage site might possibly have arisen naturally.  However, it seems extremely unlikely that both would have arisen together without any intermediate virus being discovered.  The virus would need to win the genetic lottery twice while being restricted to a small, unknown population.  Perhaps this is why it is the most infectious coronavirus in 100 years (much more infectious than SARS or MERS).

2013 Sick Bat Guano Miners

In 2013 six bat guano miners in Mojiang, Yunnan province became very ill with a SARS-like virus, and three died.  This was well documented in a recently discovered master’s thesis published at the time by Li Xu [Latham20].

Samples of the virus were sent to the WIV, as they should have been, and some 293 other coronaviruses were then sampled around the cave.  It seems likely that one of these formed the basis of SARS-COV-2 and is related to RaTG13.

Chief scientist Shi Zhengli had stated that the miners had died from a fungal infection [Qui20].  However, the subsequent discovery of Li’s thesis makes it clear that it was not a fungal infection.  And SARS-1 was never prevalent in Yunnan.

Database Removal and Obfuscation

The WIV had published an important database of virus genetic sequences.  However, in September 2019 they removed this database with the excuse that it was subject to cypher attacks, and they have not made it available to any researchers [Bostickson21]. This makes it impossible to determine the exact path of the development of SARS-COV-2. 

In 2018 the WIV published the partial genome of BtCoV/4991 from the Mojiang caves.  When RaTG13 was subsequently published in 2020, it was discovered to be an exact match.  This shows that RaTG13 is the same as BtCoV/4991 and that the WIV had been studying the virus since at least 2018.

Sick WIV Workers

The US government stated there was evidence that several workers at the WIV had become ill enough to require hospitalization in December 2019 [State21].  It is possible that they were infected with SARS-COV-2. 

Shi said she was unaware of any sick workers at that time which would be untrue if the US government source is correct.  She also said that serum samples were taken from workers around March 2020 and all proved negative for any SARS virus, but no verifiable details have been released.  Given the general prevalence of Covid-19 in Wuhan by then that seems most unlikely even if the WIV is not the source of SARS-COV-2 [Quay21].

Eco Health Alliance and NIH Research Grants

The WIV was partially funded from the US Government via the Eco Health Alliance (EHA). EHA’s CEO Peter Daszak explained that it was relatively easy to add a different spike protein to a coronavirus, which was a useful way to study their potential for pandemics [Daszak19]. 

In 2018 the EHA applied for a DARPA grant to develop novel chimeras and specifically to add furin cleavage sites [Drastic21].  That grant was declined due to Gain of Function concerns.  They subsequently received smaller grants from the USA National Institute of Health.

Early Contact Tracing

The WHO report described searches of hospital records and other sources and determined the beginning of the outbreak to be early December 2019 [WHO20].  However, there does not appear to have been any follow up on the earliest cases to test those people’s close contacts for SARS antibodies.  This contact tracing has been very effective in containing outbreaks in Australia and elsewhere, and should be able to push the source back to a small number of initial cases. 

Director of WIV biosafety, Yuan Zhiming, said that zero staff tested positive for antibodies, which would actually be surprising given that the virus was so prevalent in Wuhan [Global21].  ON 3 January 2019, the head of the CDC Robert Redfield offered to send a US team to help identify the origins of SARS-COV-2, but this was declined. 

One explanation for these observations is that the Chinese government already knew the source, namely the WIV.  Not proof, but yet more evidence.

Chinese Reaction

The Chinese government has reacted angrily to any suggestion of a laboratory leak and has obstructed any investigation.  They have prevented laboratory workers from being interviewed, or their laboratory notes being reviewed by external parties.

Further, the Chinese government has forbidden other Chinese researchers from publishing any papers relating to the origins SARS-COV-2 [Kirchgaessner21].

The Chinese government has conducted their own investigation which includes the sampling of some 80,000 animals.   They would certainly refute the lab leak hypothesis if they could.

Rebuttal of the Lab Leak Hypothesis

Linage A and B

An unusual feature of SARS-COV-2 is that all samples appear to be a direct descendant of a single case, a 39 year old man seen at a Wuhan PLA Hospital.

But Nature published an article claiming that there were in fact two distinct lineages A and B of SARS-COV-2 prior to 28 February 2019 [Mallapaty21]. They assert that this could only happen if there were not one but two different laboratory leaks, and so “puts a dagger through the heart” of the laboratory leak hypothesis.  Strong words indeed.

However, this article is based on an unreviewed preprint on a discussion board.  The difference in the lineages is based on just two nucleotides C8782 and T28144, which could have easily evolved naturally after a lab leak in October or November.  Indeed, [WHO21] estimates that the most recent common ancestor was 11 December 2019, well after the beginning of the outbreak in late November.

RaTG13 is Too Different

RaTG13 has over 1000 different bases than SARS-COV-2 and it has been argued that there are too many scattered differences to be the result of genetic engineering.  However, most of the differences are concentrated in the spike protein “head” area, and not the “body” of the virus which suggests a chimera, whether man made or natural.

The intermediate virus may then have had many generations in cell cultures and humanized mice which would have introduced random changes throughout the virus.  Such changes are known to happen at a faster rate than in natural evolution.

The significance of RaTG13 is to show that the virus is a chimera, and that it arose in the Mojiang caves which the WIV had studied.  But the actual source may actually be some other closely related virus known only to the WIV.  The DARPA grant application says that they had “>180 SARSr-CoV strains sequenced”, most unpublished.

RaTG13 is just a series of letters in a text file that was published after the outbreak.  It might not even be the exact genome of any virus and it has not been independently verified. [Deigin21a] (Steven Carl presents evidence that RaTG13 was indeed fabricated [Carl21], [Zhang20], [Rahalkar20].)

The Furin Cleavage Site Encoding

The unusual CGG encoding within the furin cleavage site does occur naturally in about 5% of the arginine’s amino acid codons.  There are two of them, so that is 0.25% likely, and certainly not impossible.  It is only evidence, not proof.

The Furin cleavage site was also inserted out of frame, meaning that it was inserted in the middle of an existing three nucleotide codon.  That excludes certain natural processes, but could have been manipulated.  Regardless, it evidently works very well.

What is certain is that having both the furin site and the effective spike protein is very unusual.

Engineering SARS-COV-2 is Beyond Current Technology

It is now relatively easy to engineer a virus to produce any desired protein, but it is extremely difficult to engineer a protein that will have a particular function.  In particular, to design a spike protein from first principals that fits snugly into the human ACE2 receptor is beyond current technology.  So it is argued that it could not have been engineered.

In 2007 Shi’s group  determined that a relatively short part of the spike protein is responsible for binding to different species [Segreto20].   New models to predict human ACE2 affinity have been developed.  Subsequent reproduction in cell cultures or humanized mice could refine that sequence to produce SARS-COV-2.

What is certain is that laboratories regularly create chimeras that would be unlikely to occur naturally.

The WIV Cannot Disprove a Leak

Shi Zhengli has complained that it is unreasonable to expect the lab to prove that something did not happen.  To prove the non-existence of an event. 

However, a lab leak is likely if and only if the WIV was working on or had created a virus that was very similar to the initial SARS-COV-2.  Evidence of that would be in their lab notes.  Indeed, Shi had earlier said that she had carefully reviewed all lab notes and said “none of the sequences matched those of the viruses her team had sampled from bat caves” (emphasis added).  Note that she did not say that there were no engineered sequences that matched SARS-COV-2.  An independent review of those same notes would help resolve the issue.

Shi had made misleading statements about the miner’s disease being fungal as well as the source of RaTG13.  Peter Daszak had also stated that no bats were kept at the institute, even though there were published videos showing such bats.

Researchers Became Infected Inside the Caves

It has been speculated that researchers may have become infected while collecting viruses, just as the six miners had been.  The researchers could then have spread it to others in Wuhan.  However, that does not explain why the virus was so infectious to humans, unlike the miner’s virus.  No evidence of such an infection has been presented, nor do we know of any recent trips to the caves.

Danielle Andersen

Australian researcher Danielle Andersen visited the WIV leaving in November 2019.  She stated that they were friendly and that she saw nothing untoward.  However, the WIV is a large institute with many labs, and she left at about the time of the leak.  It is not surprising she would have been unaware of any issues.  Anderson’s Duke University of Singapore also received partial funding from the NIH.

Chinese Bioweapons Program

It has been suggested that China was developing bioweapons at the WIV.  This could explain their secrecy, rather than their concealing a lab leak.  However, there were many visitors to the WIV prior to December 2019, including Ralph Baric and Danielle Andersen, who reported that they were friendly and open.

Wuhan World Military Games

In October 2019 a major sporting event was held in Wuhan.  There are confused reports that many athletes became ill with a SARS-like disease that might have been flu [Squitieri20].   However, if several athletes from around the world had been infected with SARS-COV-2 in October 2019 then there should have been many subsequent cases around the world in November, yet the first confirmed external case is 31 December 2019 in France.

Chinese government officials have accused the USA of creating the virus in Fort Detrick laboratories and deliberately seeding it in the games to discredit China [Panda20].  However, there is no evidence for such an outrageous claim.

Reactions to the Lab Leak Hypothesis

Andersen Paper

In this influential paper Kristian Andersen et. al. wrote that the virus could not have been genetically engineered because their computer analysis suggested that there was a better way to engineer it [Andersen20].  But there are, of course, many approaches that can be taken, and the WIV’s research goal may have been to simply investigate the chimera rather than producing a super virus.  Andersen then argues that the virus could not have been produced in cell cultures or humanized mice because the development of both the chimera and the furin cleavage site at the same time would require genetic engineering.  A more technical rebuttal can be found at [Segreto20].

They then concluded “Our analysis clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.”  To present their arguments in not unreasonable, but this is an outrageously strong conclusion to draw from such weak arguments.  Surprisingly, this paper was accepted for publication in Nature and cited over 400 times.

Daszak Letter

Charles Calisher and 27 others state they “strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin” without justification.  They declare no competing interests [Calisher20].  The letter was drafted by one of the signatories, Peter Daszak, who oversaw the US funding of the WIV and thus had a huge conflict of interest.  This was published in the Lancet, March 2020.

WHO Investigation

A committee of the World Health Organization (WHO) released a report stating that a lab escape was “extremely unlikely” [WHO21] .  However, they did not interview workers at the WIV and the 120 page report only devoted 2 pages to the lab leak hypothesis.  The only American member of the committee was Peter Daszak, whose obvious conflict of interest was considered to be acceptable.

The report argues that there is no record of a closely related virus at the WIV, but they fail to mention that genetic records from the WIV had been removed.   They note that other more distantly related SARS viruses have furin cleavage sites or bind to humans, but without any explanation as to how that could be relevant.

They also note that there is no evidence of anyone infected with SARS-COV-2 before December 2019.  (That would be expected if that was the date of the lab leak.)

The report also cites the dubious Andersen paper as evidence.

Biden Investigation

An intelligence community assessment prepared for President Biden in August 2021 stated that it was not possible to know the source of the virus because the Chinese government would not cooperate in any investigation.  We would argue that withholding evidence is not normally a reason to presume innocence.  The assessment does not address any of the specific points made in this paper.

The Biden administration wishes to heal rifts with China created by President Trump.  More specifically, it wants China to continue to cooperate on health related matters.  An overt accusation that Covid-19 was probably the result of a laboratory leak could cause China to terminate such cooperation.  We suspect that such cooperation has already been terminated in practice.

Ralph Baric Letter

In May 2021 Jesse Bloom and 19 other prominent researchers published a letter in Science magazine stating that the virus might have been engineered and calling for a full investigation [Bloom21].  Signatories included Ralph Baric who had worked closely with Shi Zhengli on coronavirus research. 

The lab leak hypothesis can no longer be discounted as a radical conspiracy theory.

Political Environment

Trump Administration

In April 2020 President Trump started calling Covid-19 “the China virus” in order to deflect attention from his handling of the pandemic.  Secretary of State Pompeo made similar accusation without providing any evidence.  Republican senator Tom Cotton then asserted that China was building a bioweapon.

This led many to believe that any discussion of a lab leak was just right wing fake news.

Anthony Fauci and Gain of Function

Fauci approved a grant of $600,000 to the WIV for bat coronavirus research.  Fauci has sworn to congress that this was not for “Gain of Function” research.  Fauci was relying on a very narrow definition of the term, in which the purpose of the research was to produce more potent viruses.

There is no doubt that the type of genetic engineering conducted at the WIV and other research institutions could have produced potent viruses, even if its purpose was simply to examine the effects of such manipulation.  Fauci and others involved in the grant such as Peter Daszak have a clear interest in the virus not to have been produced as a result of this research.

The Virology Community

The international community of virologists has a natural disinclination to believe that this terrible pandemic was created by one of their own.  But more importantly, they do not want to suffer the increased bureaucratic controls on their research that would follow should this be shown to be a laboratory leak.  Thus they all have an inherent conflict of interest.

An important result of this is the difficulty until very recently of having any papers presenting evidence of the lab leak hypothesis from being accepted in any academic journals.  They were all relegated to preprint sites despite providing obviously important insights such as the fact that RaTG13 was the same as the earlier reported BtCoV/4991 and so was found in the Mojiang mine.  This is a very serious issue [Thacker21].

Gain of Function Research

Concerns about the dangers of genetically engineering novel viruses have been raised before the Covid-19 pandemic.  It had been argued that it has been impossible to predict the course of epidemics [Wain-Hobson21] and so the small contribution of such research to deal with pandemics is greatly outweighed by the danger that such research presents if a virus was to leak.   Virologist Simon Wan-Hobson said “If such a virus escaped, nobody could predict its trajectory.”   Richard Ebright, a molecular biologist, said “The only impact of this work is the creation, in a lab, of a new, non-natural risk”. [Butler15]

In 2014 the Obama administration imposed some restrictions on the funding of Gain of Function (GoF) research.  But there were many caveats, and the restriction was only on federal funding, not upon the research being conducted.  The ban was then lifted in 2017.

The Cambridge Working Group produced a statement calling for such research to be curtailed, and has been signed by over 300 scientists [Cambridge21].

Until recently, only the most advanced research laboratories had the ability to perform genetic engineering.  However, powerful equipment that is relatively easy to use can now be purchased off-the-shelf at relatively modest cost.  Many Ph.D. students are learning how to manipulate viral genomes.  This has greatly increased the number of laboratories around the world that can conduct these experiments.

Conclusion

There is no mathematical proof, but there is certainly evidence for an accidental laboratory leak:-

  1. The bat coronavirus outbreak occurred in Wuhan, home to the Wuhan Institute of Virology (WIV), the world’s leading bat coronaviruses laboratory.   (Not proof, but certainly of interest.)
  2. Wuhan is over 1000 km from the relevant bats.  The bats were not traded in the Wuhan wet markets. 
  3. The virus arose suddenly, fully functional, with no known human or animal precursors.  This is unlike SARS-1 and MERS.
  4. The virus is a chimera (a mixture) of two different viruses.  Chimera’s can arise naturally, but are also often engineered in laboratories.
  5. The virus also contains two different powerful adaptations at the same time, an effective spike protein and a furin cleavage site.  This is why it is the most infectious coronavirus in 100 years.
  6. The WIV and the Eco Health Alliance proudly published their earlier results on genetically engineering chimeras based on coronaviruses.  They have also submitted grant proposals to add furin cleavage sites to coronaviruses.
  7. It was discovered that in 2013 six bat guano miners became ill with a SARS-like virus, samples of which were sent to the WIV.  This could have been the precursor to SARS-COV-2.  The WIV had said the miners had a fungal infection. 
  8. The WIV conducted coronavirus research at biosecurity levels 2 and 3, not high security BSL-4.  A US government report had raised concerns about their biosecurity practices in 2017.
  9. Lab leaks are not uncommon and have happened in many laboratories around the world.
  10. There is some evidence that workers at the WIV became ill in late 2019.
  11. More importantly, the Chinese government has removed data and has angrily thwarted any proper investigation.  They refuse to disclose whether the WIV was studying a SARS-COV-2 like virus. 
  12. There does not appear to have been any attempt to trace the contacts of the earliest cases by looking for long lived antibodies.
  13. The Chinese government has still not found any natural precursor after an extensive search testing over 80,000 samples.
  14. There are no credible rebuttals.

We believe that the weight of this evidence proves that the virus escaped from the WIV beyond reasonable doubt.

This is important because this technology has become much more accessible to laboratories around the world, often with minimal oversight.  Advances in technology could enable future genetically engineered viruses to be far more infectious and virulent than SARS-COV-2.

(Permission to use this cartoon is granted with attribution to Andrew Turntable)

This is what must not be allowed to happen.  Students from existing laboratories setting up their own laboratories around the world and conducting dangerous Gain of Function research with inadequate safety precautions.

The next engineered virus could be even more infectious, have a longer incubation period, a higher mortality rate and, like HIV, attack the immune system.  It could be far more dangerous than SARS-COV-2.

Annotated Biography

[Segreto20] Rossana Segreto, Yuri Deigin November 2020
The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744920/
This is a detailed description of the evidence presented in this paper, including many references.  Discusses the Pangolin MP789 spike protein.

[Deigin21b] Yuri Deigin, Rossana Segreto July 2021 The genetic structure of SARS-CoV-2 is consistent with both natural or laboratory origin: Response to Tyshkovskiy and Panchin
https://onlinelibrary.wiley.com/doi/full/10.1002/bies.202100137
Refutation of cricisism of [Segreto20]

[Deigin21a] Yuri Deigin, Rossana Segreto May 2021 SARS-CoV-2′s claimed natural origin is undermined by issues with genome sequences of its relative strains
https://onlinelibrary.wiley.com/doi/full/10.1002/bies.202100015
Issues with genomes of RaTG13, MP 789 (from pangolins) and RmYN02.

[Deigin20] Yuri Deigin April 2020.  Lab-Made? SARS-CoV-2 Genealogy Through the Lens of Gain-of-Function Research
https://yurideigin.medium.com/lab-made-cov2-genealogy-through-the-lens-of-gain-of-function-research-f96dd7413748
An excellent, detailed technical analysis of the virus and of gain of function research.

[Daszak19] Peter Daszak on This week in Virology.  Recorded 9 December 2019
https://www.youtube.com/watch?v=IdYDL_RK–w
Reference to manipulating Coronaviruses is at 28:00.  This was recorded just before the outbreak became known.

[Menachery15] Vineet Menachery, Yount, …, Shi Zhengli, Ralph Bric November 2015.  A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797993/
Paper detailing the creation of a dangerous chimera of the spike SHC014 in a mouse-adapted SARS-CoV backbone/

[Hu17] B. Hu, Zeng, … Z. Shi.  Discovery of a rich gene pool of bat SARS‐related coronaviruses provides new insights into the origin of SARS coronavirus.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708621/
Reports creating eight SARS chimeras using the W1V1 backbone and differentbat SARS-like spike protein genes.

[Drastic21] The DARPA DEFUSE Project
https://drasticresearch.org/2021/09/20/1583/
Analysis of leaked DARPA grant application for Gain of Function research at the WIV.

[Carl21] Steven Carl, January 2021.  A Bayesian analysis concludes beyond a reasonable doubt that SARS-CoV-2 is not a natural zoonosis but instead is laboratory derived
https://zenodo.org/record/4477081#.YWNyfn0RUd4
Long paper that analyzes much of the evidence.

[Latham20] Jonathan Latham, Allison Wilson.  A Proposed Origin for SARS-CoV-2 and the COVID-19 Pandemic.
https://www.independentsciencenews.org/commentaries/a-proposed-origin-for-sars-cov-2-and-the-covid-19-pandemic/
Discovery and analysis of Li’s masters thesis on the sick guano miners.

[Qiu20] Jane Qiu June 2020 How China’s ‘Bat Woman’ Hunted Down Viruses from SARS to the New Coronavirus
https://www.scientificamerican.com/article/how-chinas-bat-woman-hunted-down-viruses-from-sars-to-the-new-coronavirus1/
Includes disproved claim miners died from fungal infection.

[State21] January 2021 Fact Sheet: Activity at the Wuhan Institute of Virology
https://2017-2021.state.gov/fact-sheet-activity-at-the-wuhan-institute-of-virology/index.html
Reason to believe WIV researchers became sick.  The WIV performed Gain of Function research.

[Quay21] Steven Quay May 2021 An analysis of the results of routine employee testing for SARS-like infections within the WIV and other Wuhan labs raises serious issues about their validity
https://www.researchgate.net/publication/351711216_An_analysis_of_the_results_of_routine_employee_testing_for_SARS-like_infections_within_the_WIV_and_other_Wuhan_labs_raises_serious_issues_about_their_validity
The title says it all.

[Global21] Global Times June 2021 Scientists close to the Wuhan virologist lab break silence, push away latest conspiracies
https://www.globaltimes.cn/page/202106/1226242.shtml
Zero workers tested positive for SARS antibodies.  (Global Times is a Chinese Communist Party publication.)

[Bostickson21] Billy Bostickson, Gilles Demaneuf, January 2021. An investigation into the WIV databases that were taken offline
https://www.researchgate.net/publication/349073738_An_investigation_into_the_WIV_databases_that_were_taken_offline
Detailed analysis of what was in the database, when it was removed, and (dubious) reasons given for the removal.

[Kirchgaessner21] Stephanie Kirchgaessner et. al. April 2020 China clamping down on coronavirus research, deleted pages suggest
https://www.theguardian.com/world/2020/apr/11/china-clamping-down-on-coronavirus-research-deleted-pages-suggest
Publications of documents about the source of SARS-COV-2 have been removed from university web sites.

[Thacker21] Paul Thacker 2021 The covid-19 lab leak hypothesis: did the media fall victim to a misinformation campaign?
https://www.bmj.com/content/374/bmj.n1656
Overview of the way the scientific media rejected any mention of the lab leak.

[Squitieri20] Tom Squitieri June 2020 Did the Military World Games Spread COVID-19?
https://prospect.org/coronavirus/did-the-military-world-games-spread-covid-19/
Dubious claim that the virus actually spread from the October 2019 Wuhan world military games.

[Panda20] Ankit Panda March 2020, Chinese Foreign Ministry Spokesperson Implies US Military Brought Coronavirus to Wuhan
https://thediplomat.com/2020/03/chinese-foreign-ministry-spokesperson-implies-us-military-brought-coronavirus-to-wuhan/

[Andersen20] Kristian Andersen March 2020.  The proximal origin of SARS-CoV-2 Nature Medicine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095063/
Paper asserting that SARS-COV-2 could not have been a laboratory construct.

[Calisher20] Charles Calisher et. al. February 2020 Statement in support of the scientists, public health professionals, and medical professionals of China combating COVID-19 The Lancet
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30418-9/fulltext
Paper calling the lab leak “rumors and misinformation” but without argument.

[WHO21] WHO March 2021 Origins of the SARS-CoV-2 virus
https://www.who.int/health-topics/coronavirus/origins-of-the-virus
The World Health Organization report

[Bloom21] Jesse Bloom et. all. May 2021 Investigate the origins of Covid-19 Science Magazine
https://www.science.org/doi/10.1126/science.abj0016
Letter by many promenant scientists including Ralph Baric calling for an investigation into the lab leak hypothesis.

[Wain-Hobson21] Simon Wain-Hobson. New Analysis of DEFUSE Proposal
https://drasticresearch.org/2021/10/06/new-analysis-of-defuse-proposal/
Casts doubt on the potential usefulness of such gain of function research.

[Butler15] Declan Butler November 2015 Engineered bat virus stirs debate over risky research Nature
https://www.nature.com/articles/nature.2015.18787
Pre-Covid-19 discussions of the risk of gain of function research.

[Cambridge21] Cambridge Working Group Consensus Statement on the Creation of Potential Pandemic Pathogens (PPPs)
http://www.cambridgeworkinggroup.org/
Over three hundred scientists raising concerns.

[McDonald21] Jessica McDonald 2021 The Facts – and Gaps – on the Origin of the Coronavirus
https://www.factcheck.org/2021/06/scicheck-the-facts-and-gaps-on-the-origin-of-the-coronavirus/
Good paper on the evidence, both for and against a lab leak.

[Robertson21] Lori Robertson 2021 The Wuhan Lab and the Gain-of-Function Disagreement
https://www.factcheck.org/2021/05/the-wuhan-lab-and-the-gain-of-function-disagreement/

[Rogin21] Josh Rogin 2021, In 2018, Diplomats Warned of Risky Coronavirus Experiments in a Wuhan Lab. No One Listened.
https://www.politico.com/news/magazine/2021/03/08/josh-rogin-chaos-under-heaven-wuhan-lab-book-excerpt-474322

[Pompeo21] Michael Pompeo January 2021 Ensuring a Transparent, Thorough Investigation of COVID-19’s Origin
https://web.archive.org/web/20210116020513/https:/www.state.gov/ensuring-a-transparent-thorough-investigation-of-covid-19s-origin/
Describes sick workers at the WIV, Gain of Function, links to military, call for Chinese transparency.

[Liu20] Liu Caiyu, Leng Shumei, February 2020 Biosafety guideline issued to fix chronic management loopholes at virus labs
https://www.globaltimes.cn/content/1179747.shtml
Global times (Chinese government paper) talks of improved lab security shortly after the Covid-19 pandemic started.

https://www.globaltimes.cn/content/1179747.shtml
[Wade21] Nicholas Wade May 2021 The origin of COVID: Did people or nature open Pandora’s box at Wuhan?
https://thebulletin.org/2021/05/the-origin-of-covid-did-people-or-nature-open-pandoras-box-at-wuhan/
Widely read article proposing a lab leak theory

[Malone21] David Malone 2021 Did Covid Leak from a Lab in China Channel 4
https://www.youtube.com/watch?v=S2sg_cwu6LY
Not a bad summary for TV.

[Zhang20] Daoyu Zhang August 2020, Anomalies in BatCoV/RaTG13 sequencing and provenance
https://zenodo.org/record/5018435#.YUFz5H0RUd7
Zhang argues that RaTG13 was created in cell cultures.

[Rahalkar20] Monali Rahalkar, Rahul Bahulikar, August 2020, The Abnormal Nature of the Fecal Swab Sample used for NGS Analysis of RaTG13 Genome Sequence Imposes a Question on the Correctness of the RaTG13 Sequence
https://www.researchgate.net/publication/343582083_The_Abnormal_Nature_of_the_Fecal_Swab_Sample_used_for_NGS_Analysis_of_RaTG13_Genome_Sequence_Imposes_a_Question_on_the_Correctness_of_the_RaTG13_Sequence

[Maxmen21] Amy Maxmen, Smriti Mallapay June 2021 The COVID lab-leak hypothesis: what scientists do and don’t know
https://www.nature.com/articles/d41586-021-01529-3
Not a lab leak because we do not know exactly how it was made.  Evidence not discussed.  No mention of sick miners.

[Mallapaty21] Smriti Mallapaty September 2021 Did the coronavirus jump from animals to people twice?
https://www.nature.com/articles/d41586-021-02519-1
Proposes that Lineage A and Lineage B “puts a dagger through the heart” of the lab origin thesis.

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