On the first page, three silhouettes of soldiers sit next to those of a dozen bats in full flight, against the backdrop of a pale cave opening. The presentation file of the DEFUSE project sets the tone. Led by the non-governmental organization EcoHealth Alliance against emerging infectious diseases, chaired by British biologist Peter Daszak, DEFUSE aimed to " defuse ("defuse" in English) the threat of bat coronaviruses » in collaboration with the virology laboratories of the Wuhan Institute of Virology (WIV). It planned to modify an existing bat coronavirus to make it more contagious in humans by adding characteristics similar to those found in the Covid-19 virus, which emerged a year after the project was submitted for funding. For most scientists, authorities and investigative groups around the world, the revelation of this project by the self-proclaimed Drastic collective of investigators is a strong argument supporting the emergence of the Covid-19 virus from the WIV following a laboratory error, but remains far from disqualifying a potential emergence via animals (zoonosis).
Read alsoEPISODE 1. ORIGINS OF COVID-19: ANATOMY OF THE VIRUS, THOSE STRANGE ELEMENTS THAT SOW DOUBT
Coronavirus modified to make it more infectious in humans
“ The DEFUSE project is overwhelming", estimates the phylogeneticist (specialist in genetic links between species) at the Sorbonne Alexandre Hassanin. If it was never funded, the very existence of the DEFUSE project is enough to support the hypothesis of a laboratory leak. " All the elements are there, the skills and the ingredients, to do it by the end of 2018.", summarizes the epidemiologist at Pitié-Salpêtrière Renaud Piarroux, author of "Sapiens and Microbes - Epidemics of the Past" (CNRS Editions). Especially since most of the research team leaders interviewed by Science and Future agree that in the laboratory, it is common to start unfunded projects in parallel with those that are funded.
The “identical portrait” of the Covid-19 virus
In order to build this virus, the project leaders had initially specified – then deleted from the final version – wanted to divide the viral genome into six equal parts and then join them together, a standard technique for synthesizing large genomes. These six blocks must be separated by short identical sequences that are recognized by the assembly enzymes and called "restriction sites." When we look at the genetic profile of SARS-CoV-2*, we find the restriction sites as proposed in the DEFUSE project", says virologist Etienne Decroly, research director at the CNRS and author of "Experiments in Virology - Benefits and Risks" (Editions Quæ). Their presence is not, however, proof of human manipulation: coronaviruses naturally possess around ten of these sites, to the point that having only five would require removing some of them. For this, a simple mutation is enough. However, SARS-CoV-2 mutates rapidly. " Finding these sites identical to those described in the DEFUSE project is a disturbing coincidence but in no way proof." concludes Etienne Decroly.
The project also mentioned the addition, if necessary, of a cleavage site by a protease such as furin, one of the most dangerous and surprising characteristics that the SARS-CoV-2 virus possesses in terms of its transmission efficiency in humans, and which no other known virus of the same family possesses. Should we think that it is purely by coincidence that this virus, which is the composite of the one from the DEFUSE project released in 2018, emerged in Wuhan in 2019? points out epidemiologist Renaud Piarroux.
The laboratory accident hypothesis holds even without DEFUSE
Whether DEFUSE was carried out or not, the very existence of this project underscores that WIV scientists had the skills and short-term ambition to work on bat coronaviruses to identify those that would be dangerous to humans, a year before the pandemic broke out in their city. Moreover, accidental contamination while carrying out the DEFUSE project is only one of the hypotheses of the researchers who consider the Wuhan laboratory as a plausible origin of Covid-19. LThe risks associated with research work are multiple and occur at different experimental stages." explains Etienne Decroly. " This could be an accident during sampling, viral culture, or even during serial passage experiments on humanized transgenic mice.", that is, modified to express human genes or possessing human tissues
Serial passages consist of controlled laboratory infections that mimic, in fast motion, the evolution of the virus as it spreads. In humanized mice, the virus could theoretically have adapted quickly to the ACE2 receptor, the virus's gateway to mammalian cells, in a way that is difficult to distinguish from "natural" evolution in a host animal. However, this hypothesis is unlikely because studies have shown that the site of furin cleavage does not appear during serial passage experiments.
What they say about it. “ Unfortunately, (the DEFUSE project) was rejected, it became an outstanding grant in the archive system and the work was never done." , testifies Peter Daszak in November 2023, questioned by the US Congress. To the question " To your knowledge, UNC Laboratories (University of North Carolina at Chapel Hill, American laboratory also a partner in the DEFUSE project, editor's note) or did the WIV ever carry out any aspect of the project?", he replies " You'll have to ask them. I don't know. I doubt it."As for the director of the WIV, Shi Zhengli, she told the magazine Science in July 2020 that »To date, no pathogen leaks or personnel infection accidents have occurred" She also added that the analysis of blood serums " of all the staff and students of the laboratory » confirmed that « no one is infected with SARSr-CoV or SARS-CoV-2 (SARSr as “SARS related”, a coronavirus linked to SARS, editor’s note)”.
An unknown viral medium: the pro-zoonosis argument
The existence of the DEFUSE project, however, remains a purely contextual element of the investigation, which cannot be scientifically analyzed or refuted. It was also ignored by the World Health Organization's (WHO) investigation group on the origins of the coronavirus, which issued conclusions full of questions and calls for additional information. June 27, 2025. In this context where solid elements are lacking, their absence also has weight. Thus, the genome of an existing, close and known virus is necessary to serve as a basis for genetic modifications. No virus known to date could have supported such an insertion and given rise to the creation of SARS-CoV-2 in the laboratory.", written on The Conversation the research director at the CNRS, a fervent supporter of zoonosis, Florence Débarre. For the hypothesis of an artificial insertion of the cleavage site by furin to hold (the hypothesis that the virus was modified in the laboratory, editor's note), we must assume that Wuhan researchers are lying to us and hiding viruses. »
Of course, in a context where no one would want to be held responsible for the 20 million deaths attributed to the Covid-19 pandemic, the laboratory could indeed have lied. But even without going that far, the scientific process itself regularly leads researchers to publish sequences several years after their discovery. This is also the case for RaTG13, the bat coronavirus closest to SARS-CoV-2 and discovered in 2013, but whose partial sequence was published in 2016 and the complete sequence in 2021. It would therefore not be surprising if the WIV had a much more extensive viral genome bank than what is publicly known.
“ They have unpublished viruses, that's for sure.", says Alexandre Hassanin. " In 6 months to 1 year, we ourselves collected 40 sarbecoviruses (the family of coronaviruses to which SARS-CoV-2 belongs, editor's note). In 20 years, do the math, they have at least 400 or even 1000.. » The researcher spotted very early on, in 2020, that the sequence of a pangolin coronavirus very similar to SARS-CoV-2 had been published in 2019 by a collaborating laboratory at the WIV. In particular, he observed that its host cell binding domain (RBM) is identical to that of the Covid-19 virus. For him, the most likely hypothesis is that, having learned of the existence of the pangolin coronavirus, thus capable of playing the role of secondary host between bats and humans, the WIV scientists searched for and found a bat coronavirus in this database possessing the same RBM. They would then have used it as a support for their genetic experiments. It is the ideal candidate, capable of infecting several different host species, and therefore potentially humans.“, points out Alexandre Hassanin.
None of these hypotheses can be verified, however, without documents attesting to the WIV's activities in 2019 or evidence of early cases of Covid-19 among its employees. But despite the WHO's express request, as reflected in its report, China continues to refuse to provide information. “staff medical records, biosafety and biosecurity information from the Wuhan Institute of Virology and the Wuhan CDC Laboratory.”
Read episode 3 soon : Wild animals or Mahjong hall, where could the virus have emerged at the Huanan market in Wuhan?
* The acronym SARS is the French version of the English SARS and is used here to refer to severe acute respiratory syndrome. The English version of the acronym is retained in the name of the Covid-19 virus by scientific convention.
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