Andrew Tuntable, Ph.D.
20 Dec 2021
Updated March 2022
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.
(Permission to use the above cartoon is granted with attribution.)
- The Lab Leak Hypothesis
- Evidence for the Laboratory Leak
- Rebuttal of the Lab Leak Hypothesis
- Reactions to the Lab Leak Hypothesis
- Gain of Function Research
There is now substantial evidence that the Covid-19 pandemic was caused by the leak of the virus from a laboratory in Wuhan. This has led leading virologists including Ralph Baric to call for a full investigation.
See https://originofcovid.org/summary-of-evidence/ for a TLDR summary.
The cumulative weight of this evidence proves the lab leak hypothesis 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. For example, a recent (2022) experiment by Boston University created a chimera (mixture) of SARS-2 viruses that was much more virulent than the natural strains [Kaiser22].
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.
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.
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].
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 the 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.
The NIH has recently funded further searching of unknown viruses of pandemic potential, and bringing them into laboratories. This is looking for trouble [Saltzburg22]. It appears nothing has been learned from Covid-19.
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.
Evidence for the Laboratory Leak
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, Wuhan has a very low risk of bat crossover [Sanchez22]. 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 [Goa22] and WIV chief scientist Shi Zhengli [Shi20] have stated that the “wet markets” that sell exotic animals were not the source of the virus. (There are a few bats in near Wuhan, but none tested positive for SARS-COV-2 or its progenitor [Wang22].)
A natural virus takes some time to adapt to a new host, as SARS-1 and MERS did [Guo-ping07]. But SARS-COV-2 arose suddenly, fully formed and functional [Senate22]. 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.) Surprisingly, the very earliest samples of SARS-CoV2 bound better to human ACE2 receptors than any other species [Piplani21].
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 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. SARS also leaked from the National Institute of Virology in Beijing [WHO04].
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.
Furin Cleavage Site
The diagram above shows part of the genome of SARS-CoV-2 (labelled Wuhan-Hu-1) and other known closely related viruses. Each letter refers to an amino acid in the critical spike protein. These viruses are very similar but have occasional differences.
Then at at 1121 there is a novel insertion of not one but four amino acids, PRRA. Combined with the following acids, this forms a Furin Cleavage Site (FCS) RRAR’SVAS. This causes a human Furin enzime to cleave (cut) the protein at 1125 as marked with the red arrow. Inserting an FCS has been known to make other Coronaviruses much more infectious.
The FCS required just the correct amino acids to be inserted in just the correct location. Other, more distantly related coronaviruses also have a FCS, so FCSs can evolve in nature. However, the viruses close to SARS-CoV-2 do not have one. This means that SARS-CoV-2 would have to have evolved just the FCS again without substantial changes elsewhere. Viruses do not sexually reproduce, so it is difficult for them gain just a small sequence from a virus that is not a direct ancestor.
There are several different sequences of RNA base pairs that can produce a FCS, and the one in SARS-CoV-2 happens to be exactly the same as human the ENaC FCS. This is well studied and known to be very effective in lung epithelial cells, which is important for a respiratory virus.
While anything can theoretically happen in nature, this FCS is extremely unusual and has been considered to be “inconsistent with evolutionary theory” [Andersen20a]. Further, the Wuhan Institute of Virology stated that they intended to do this very thing in their DEFUSE proposal [Drastic21].
Modern technology makes it relatively easy to manipulate RNA in the laboratory and modern “no-see-um” techniques can leave no obvious trace that the genome has been manipulated. There is no doubt that the WIV was genetically engineering coronaviruses because they proudly published their excellent results. Shi in 2007 and Baric in 2008 created chimeric viruses based on the SARS-1 virus, with the most influential paper being [Menachery15]. A 2017 WIV paper reported eight chimeric viruses [Hu17].
The FCS is what makes SARS-CoV-2 highly infections, and experiments that remove it show that the virus becomes much less infections. SARS-1 did not have an FCS and was not nearly as infectious.
Convenient Restriction Sites
It is not technically feasible to artificially construct large viruses such as SARS-2 as one piece. Instead, smaller pieces are synthesized, and then glued together to form the complete virus. Further, when working with viruses, it is convenient to be able to cut out an individual piece and replace it with a variant, rather than needing to reconstruct the entire virus for each experiment. These cuts happen at special base pair sequences known as “restriction sites”.
[Bruttel22] showed that the pattern of restriction sites in SARS-2 were very conveniently placed for this purpose. They further show that this even pattern would be unlikely to arise naturally. Specifically, from the nearest known virus BANAL-20-247 4 sites need to be removed, and 1 added, and 4 kept, which is very unlikely. This is similar to what was proposed in the DEFUSE application. There is no natural selection pressure for the existence of these restriction sites.
This evidence is independent of the furin cleavage site.
SARS-COV-2 contains ORF-8, a special protein that suppresses the immune system by interfering with Interferon, which in turn makes the the disease often asymptomatic. Master’s thesis were discovered from the WIV analyzing the effectiveness of ORF-8. [Quay22].
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.
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 at batvirus.whiov.ac.cn. However, on 12 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.
The US government stated there was some 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].
Yanling Huang was a researcher that worked at the WIV since 2012, and was shown in the staff profiles of 2018. However, her entry was removed without explanation. Like most research institutions, the WIV generally continues to show profiles after researchers have left the institution. Yanling has not been located, and there is speculation that she might have died from the virus. [laowhy86-21]
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.
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.
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 [CCDC20] [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
Wuhan Seafood (“Wet”) Market
On 26 February 2022 the prestigious New York Times confidently announced that “New Research Points to Wuhan Market as Pandemic Origin” [NYTimes22], which was then confidently echoed around the world’s press. This was based on a then unpublished preprint [Worobey22] that confidently argued that many early cases were clustered around the market provided “Dispositive” (irrefutable) evidence that the market must have been the source of pandemic.
However, a brief look of their mapping data shows that the unrelated cases were, on average, much closer to the market [Yong22], and that the map had been overly smoothed, the flaw of averages. But more importantly, early cases were identified because they were association with the market, so naturally the early data is biased towards cases associated with the market [Who21a]. The first known case in early December was Mr Chen who lived some 30 km away from the market and never went there.
Worobey also asserts that cases within the market are closely associated with wildlife vendors. But a more thorough analysis shows that they were actually associated with nearby toilets [Zhang22].
The Chinese CDC also did a more extensive analysis [Goa22] and concluded that “no significant differences were observed between different vendors” being of wildlife, animals, or vegetables. No samples from animals were positive. They concluded that by 1 January 2020 the virus had been circulating in the market for some time and that “the market might have acted as an amplifier due to the high number of visitors every day”. Shi Zhengli herself confirms no animals were found to be infected, despite an extensive search [Shi20, Question (5)]. [Courtier22] also performed a detailed analysis of the early cases and found no correlation with animals. None of these well known papers were cited by [Worobey22].
All but one of the samples found at the market were Lineage B, which is thought to have evolved after Lineage A. This led to the bizarre argument about their being two spillovers which is discussed below.
Professor Andersen, who was an author of the Worobey paper, accused Alina Chan of scientific misconduct for daring to issue her accurate rebuttal [Chan22a] [Chan22b]. That is a serious threat to a junior researcher.
Lineage 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] [Pekar22]. 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, 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.
Further, [Massey22] shows that there are in fact intermediate cases with just one of the mutations. They had been excluded from earlier analysis for invalid reasons.
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, the WIV had collected hundreds of viruses, and RaTG13 is probably not the “backbone” used to make SARS-CoV-2.
The significance of RaTG13 is to show that the virus is a chimera, and that it may have arisen 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].) Virologists routinely “3D print” viruses from just their genome, and other techniques such as averaging the genome of several different viruses can produce a large number of changes in the laboratory.
BANAL-52 is another virus that had been recently found in Laos and is slightly more similar to SARS-CoV-2 than RaTG13 in the important spike protein area, although like RaTG13 it lacks a furin cleavage site [Temmam21].
The intermediate virus may also 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 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.
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.
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.
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.
Australian researcher Danielle Andersen worked closely with 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 US NIH. Andersen was also named with Eco Health Alliance on the DEFUSE application.
Chinese Bio-weapons Program
It has been suggested that China was developing bio-weapons 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.
That said, there is genomic evidence that the WIV also worked on the far more deadly Nipah virus [Quay21a].
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.
EVALI is a disease caused by vaping that has similar symptoms to Covid-19. It has been suggested that some of the early cases might actually have been Covid-19, although no direct evidence has been found. [Segreto22]
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
Proximal Origins 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 was not based on a known “backbone”, i.e. the virus that may have been modified to create SARS-2. However, it was the stated goal of the WIV to study novel viruses to assess their pandemic potential, not to study existing backbones. They have removed their database so we do not know what viruses they had.
Finally, Andersen argues that the virus could not have been produced by passaging 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.
Shortly before drafting the paper Andersen had said he thought the virus was in fact engineered [Andersen20a]. However, a meeting with Anthony Fauci that provides funding seemed to change Andersen’s mind [Kopp22c]
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 conflicting 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.
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.
The report was severely criticized by several countries, and head of the WHO, Tedros Adhanom Ghebreyesus, that the investigation was “not extensive enough” and it should examine the laboratory leak hypothesis [Tedros21].
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 [OSNI21]. 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. There has been no followup as of August 2022.
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.
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 Ralf 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.
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 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].
Concerns about the dangers of genetically engineering novel viruses have been raised before the Covid-19 pandemic. Of major concern was a 2011 paper making deadly Avian Influenza transmissible among ferrets [Kaiser19].
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. [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.
There is no mathematical proof, but there is certainly strong evidence for an accidental laboratory leak. The lack of any proper investigation is of major concern.
But regardless of whether there was a leak, there most certainly could have been, from the Wuhan Institute of Virology any other laboratory around the world engaged in Gain of Function research.
Covid-19 has proved to be the disease of a century. Much stronger controls are required to ensure that no other disease is ever produced.