Origin of Covid-19: Should the hypothesis of the laboratory accident be studied from a scientific point of view?

On March 11, 2020, the WHO reclassified the Covid-19 epidemic as a pandemic. More than a year later, the SARS-CoV-2 coronavirus, responsible for the disease, continues to circulate actively, and its exact origin remains unknown.

We now know that the sequence of this virus is close from that of bat coronavirus. here is a few decades, its “ancestor” circulated in bat populations in southern Asia.

But many gray areas persist: it is still unclear how this virus arrived in Wuhan, how its sequence evolved to allow it to infect human beings, and under what conditions it infected the first people who crossed its path.

An additional point also remains to be clarified: for each of these stages, was there a human contribution (direct or indirect)?

Indeed, if the cases of "zoonotic" transmission, in other words of the passage of a pathogenic agent from animals to humans, are today largely documented - scientists even consider that it is a predominant mechanism for the emergence of new viruses - the fact that this epidemic started next to a large virology research center - the Wuhan Institute of Virology, also fueled another hypothesis: that of the laboratory accident. And this, especially since this institute specializes in the study of coronaviruses with epidemic potential in humans.

We also know that such accidents have already led to human infections, and even at the 1 H1N1977 influenza pandemic which claimed more than 700 victims.

The first argued texts considering a laboratory accident received little consideration, perhaps because they emanated from technocritical groups such as Parts and labor, neo-Luddite inspired collective, or the collective DRASTIC (acronym for "Decentralized Radical Autonomous Search Team Investigating Covid-19"). Composed of a thirty people (mostly anonymous, with the exception of a few scientists participating under their real identities), this group formed on Twitter in 2020 set out to explore the origins of SARS-CoV-2.

Yet their information and arguments deserved to be examined as such. They were then taken up and developed by a few virologists, of scientists and science popularizers.

In a text published Thursday, May 13 by the review Science, a new forum, co-signed by around twenty scientists, once again calls for this possibility to be examined. In addition, on the eve of this publication, three new documents (a thesis and two master's theses) were distributed via an anonymous Twitter account.

As the newspaper Le Monde reports, these documents (initially published in Chinese and anonymously translated into English) contain unpublished information which seem to call into question some of the information previously communicated by the WIV.

In the absence of definitive proof, and without promoting certain conspiracy theories, the debate on the origin of SARS-CoV-2 deserves to exist. What are currently the most scientifically sound arguments in favor of each of these two hypotheses, zoonosis or laboratory accident?

Read also :
Nothing proves that the coronavirus was created in the laboratory: the underside of the infodemic on Covid-19

A framed debate very early on

In the scientific community, the debate on the origin of SARS-CoV-2 was framed from the start of the epidemic by the publication of two articles.

Dated February 19, 2020, on premier was published in the medical scientific journal The Lancet. This forum, signed by 27 scientists, underlined the efforts of Chinese experts to "identify the pathogen at the origin of this epidemic [...] and share their results in a transparent manner". The authors deplored the "rumors and misinformation" about the origins of the virus, and said "strongly condemn conspiracy theories suggesting that Covid-19 does not have a natural origin".

They based their opinion on the first analyzes of the published sequence data, without however detailing the scientific arguments in favor of a natural origin.

Un second item published in March 2020 in Nature Medicine provided a series of scientific arguments in favor of a natural origin:

  • the natural hypothesis is plausible, because it is the usual mechanism of the emergence of coronaviruses
  • the sequence of SARS-CoV-2 is too distant from other known coronaviruses to consider the manufacture of a new virus from the available sequences
  • Its sequence does not show traces of genetic manipulation in the laboratory.

This last argument can be questioned, because methods allowing de change viral sequences without leaving traces exist. These are methods based on cutting the genome into jointable fragments, or more recently the ISAR method, thanks to which overlapping fragments naturally come together in cells by homologous recombination (phenomenon in which two DNA molecules exchange a fragment). Moreover, genetic manipulation is not the only scenario compatible with a laboratory accident.

The intense research carried out for more than a year to try to validate the zoonotic scenario has so far not been crowned with success: the 80 animal samples, from around thirty species tested, have all been been negative. These figures are taken from the joint WHO-China report. The samples came from farm animals and wild animals from different Chinese provinces. It is important to note that this large number of samples tested negative does not necessarily refute the zoonotic scenario.

The laboratory accident hypothesis

In August 2020 appeared for the first time in peer-reviewed scientific journals two people articles discussing the possibility of a laboratory accident. In November 2020, one of us (Étienne Decroly) also published a comment in the CNRS journal.

Several elements do indeed raise questions. In particular, it has been established that the Wuhan Institute of Virology manipulated of close viruses SARS-CoV-2 collected in southern China and in particular in Yunnan province.

Among these viruses, the closest cousin of SARS-CoV-2, called RaTG13, was collected in an abandoned mine in 2013. However in 2012, several workers who worked there had suffered from severe pneumonia resembling Covid-19, which caused the death of three of them. Although the causative agent of the infection has not been formally identified, a thesis revealed via Twitter indicates that "the samples revealed in these patients the presence of antibodies recognizing the coronaviruses".

If RaTG13 does not appear to be the direct progenitor of SARS-CoV-2 responsible for the Covid-19 pandemic, several questions still arise. Recently released documents indicate that the WIV sequenced several other coronaviruses related to SARS-CoV-2, collected from the mine where RaTG13 was found. Were there other viruses closer to SARS-CoV-2 among them? If this is not the case, could SARS-CoV-2 be the result of a gain-of-function experiment, followed by experiments on animal models during which accidental contamination could have occurred?

In addition to direct genetic manipulations, a laboratory accident could also have occurred following an infection during a collection in nature or during an experiment with a virus that we evolved in cells or mice in the laboratory (without necessarily directly manipulating its genome). This type of experiment, common in some virology laboratories, involves testing the ability of a virus to infect cells of various animal species. In doing so, they exert an artificial selection of mutations, favoring viruses carrying those that help them adapt to the new host, thereby mimicking natural species jumps.

To clarify things and study all possible scenarios of SARS-CoV-2 emergence, it is important that the sequences of these viruses be made available to the scientific community in order to trace the possible mechanisms of SARS-CoV emergence. -2. However, the WIV sequence databases were made inaccessible in September 2019.

How to be clear about it?

As a reminder, the joint China-WHO commission was unfortunately unable to identify the cause of the pandemic. The report she published concludes that the zoonotic origin of the epidemic is the most probable and indicates that the hypothesis of a laboratory accident is very unlikely. In a press release dated March 30, 2021, the WHO, however, recalled that all hypotheses remain open. Its director general, Tedros Adhanom Ghebreyesus, recalled that there were still questions which “will have to be dealt with in the framework of additional studies”.

To determine if SARS-CoV-2 has escaped from a laboratory, a thorough investigation and examine various elements. This requires, among other things, to have access to sequence databases as well as to the various resources used by Chinese researchers, which notably include laboratory notebooks, submitted projects, scientific manuscripts in preparation and submitted, viral sequences, the list of orders and the biological analyzes of the experimenters.

In the absence of direct evidence, alternative approaches could provide additional information. By analyzing in detail the available sequences of coronaviruses close to SARS-CoV-2, it is possible that the scientific community will reach a consensus based on strong clues, like what happened in the case other viruses escaped from laboratories, such as that of the H1N1 influenza of 1977.

We know that every time viruses infect cells, they make countless copies of themselves. In doing so, they make mistakes: these are mutations. All viruses continuously accumulate mutations, more or less quickly, and statistical tools make it possible to calculate their rate of evolution (the number of mutations that occur per unit of time). If a virus is stored for a long time (in a laboratory freezer for example), and therefore no longer reproduces, it no longer accumulates mutations. The mutations will resume when it is returned to culture.

Looking for such “freezing periods” could help determine whether the virus in question has come out of a laboratory. This is how the non-zoonotic origin of the 1 H1N1977 virus could be determined.

The need for biological “black boxes”

Even if it is not currently possible to determine whether the virus has a zoonotic origin linked to intensive farming or the destruction of natural habitats or if it has passed through a laboratory, the fact that the question arises reminds us that our lifestyles and the handling of viruses with pandemic potential entail significant risks. The risks of laboratory accidents associated with the handling of highly pathogenic viruses (during experiments called "gain of function") had moreover been very. discussed in the years 2012-2015.

Whatever the origin of SARS-CoV-2, it is necessary to question the consequences of our interactions with ecosystems and the industrialization of intensive farming, the safety / security conditions of collections and experiments on potentially pandemic viruses, the practice of gain-of-function experiments, and the proliferation of L3 and L4 security level laboratories, particularly near mega-cities. China notably announced the construction of 23 P4 and 88 P3.

In order to provide laboratories with security systems as demanding as in the nuclear field, consideration should be given to setting up "Organic black boxes", on the model of black boxes used in aeronautics. This would involve putting in place a series of measures to trace the history of a possible laboratory accident.

Access to laboratories P3 and P4 could, for example, be made subject to the detailed description of the experiments in electronic laboratory notebooks; sequencing data and those of synthesized DNAs could be systematically archived; laboratory air filters could be collected (and in case of suspicion of dissemination of pathogens, the genetic material present on their surface could then be sequenced), etc.

These new security measures should be implemented internationally in order to limit the risks of future pandemics linked to laboratory accidents. Regarding the current pandemic, it is important to trace the exact origins of SARS-CoV-2 to precisely understand the flaws that may have led to its spread, whatever they may be, and limit the risk of future emergencies.

Virginie Broker, Professor, evolutionary biology and genetics, University of Paris et Etienne Decroly, Research Director in Virology, Aix-Marseille University (AMU)

This article is republished from The Conversation under Creative Commons license. Read theoriginal article.

© Info Chrétienne - Short partial reproduction authorized followed by a link "Read more" to this page.


Info Chrétienne being an online press service recognized by the Ministry of Culture, your donation is tax deductible up to 66%.