Wednesday, July 10, 2024

The origins of Covid

Wuhan Institute of Virology, image Wikimedia Commons.

 

This post was originally published in French here.

On June 3rd, an opinion piece was published in the New York Times with the title: “Why the Pandemic Probably Started in a Lab, in 5 Key Points. The author of the article, Alina Chan, is a postdoctoral researcher at MIT and Harvard. She also co-signed in 2021, with journalist Matt Ridley, a book promoting the thesis that the coronavirus pandemic resulted from an accident, a laboratory leak at the Wuhan Institute of Virology, in China (lab leak theory). This opinion piece received a lot of attention, and praise as well as condemnation.

The team of This Week in Virology (TWiV) has notably returned to this question in a special program dissecting the evidence and discussing the state of knowledge. Let's say it without nuance, the TWiV team gives no credit to Chan's theses.

Remember that there are essentially two theories to explain the origins of the pandemic: on the one hand, a zoonosis (the passage of the virus from an animal host to a human host), with a bat as the original animal host, taking place in the Huanan Seafood Wholesale Market, which also sold live wild animals. On the other hand, accidental contamination of researchers by the virus during their work, within the Wuhan Institute of Virology (WIV), contamination which would not have been contained and would have spread throughout the population. Let's put the cards on the table right away. At this time, the exact origin of the pandemic is not known, and it may never be known. Nevertheless, there is a preponderance of scientific evidence pointing to zoonosis, and so we must treat this as the most likely hypothesis, with the caveat that new information could change the situation.

Many articles (scientific or otherwise) have been published on this subject. I have found particularly useful, honest, and well-considered the summary of evidence written by American researchers James Alwine, Lynn Enquist, and three editors of scientific journals published by the American Microbiological Society: Arturo Casadevall (mBio), Felicia Goodrum (Journal of Virology) and Michael Imperiale (mSphere). This article, published at the end of March 2023, immediately warns us that a definitive determination of the origins of covid may remain impossible. One reason is that all the evidence is circumstantial (I provide a partial inventory a little further down).

Alwine et al. (2023): "The best existing scientific evidence supports a direct zoonotic origin. As new evidence continues to emerge from scientific studies or other investigations, our understanding of the origin of SARS-CoV-2 will continue to evolve. Nevertheless, it is possible that its origin may never be known with certainty."

But what could be the definitive evidence in favor of one or the other hypothesis? For the zoonotic origin, this would involve, for example, identifying an animal sold on the Huanan market that carries SARS-CoV-2. (After all, this was the case for the first SARS epidemic, in 2002-2003.) It is almost mission impossible, since the Huanan market was closed and the animals were exterminated (cremated or otherwise), shortly after the start of the epidemic, for obvious public health reasons. Concerning the laboratory leak, it would be a question of determining that the Wuhan Institute of Virology was studying SARS-CoV-2 before the pandemic, and that some of its researchers were the first people contaminated by covid. But as Alwine et al. explain, for this we would need proof from the archives of the institute of virology, but none exists, and the Chinese government has denied this possibility. Unfortunately, Chinese transparency has not been exemplary here, fueling doubts.

So, we will have to do with indirect evidence. Concerning the lab leak theory, there are in fact several sub-theories, some suggesting that SARS-CoV-2 was modified in the laboratory by genetic engineering, or even created from scratch. But as Alwine et al. note, there is no evidence to support this sub-theory, which is not even considered credible by U.S. intelligence. Genetic engineering leaves recognizable signatures in DNA, but no signatures are visible in the genome of SARS-CoV-2. Jointly, or shortly after the publication of the article by Alwine et al. in 2023, new elements have come to redistribute some cards.

The first element is the discovery in March 2023 of DNA sequences in samples from the Huanan market, sequences which support the origin by zoonosis. We owe this discovery to Florence Débarre, research director at CNRS, who came across the sequences by chance while browsing a virology database for her research. Until this date, in samples taken from the Huanan market no one had identified any co-occurrence of SARS-CoV-2 with non-human animal DNA. Thanks to Débarre's discovery, there is now evidence of the co-occurrence of covid with raccoon dogs and civets, animals sold on the market. Note that this is not definitive proof that these animals were infected with covid, but it is still a big step in that direction.

Strangely, immediately after this discovery, the Chinese researchers who had posted the sequences in the database requested their removal. It's not entirely clear why, but it doesn't help a tarnished image when it comes to transparent data sharing... But soon after, in early April 2023, Chinese researchers published the results including these new animal data. This publication was welcomed, but still left open questions regarding the analysis of this data. However, the existence of these sequences contributes to further weakening the lab leak thesis, in particular by showing that samples collected in areas of the market housing live animals had a greater chance of testing positive for the coronavirus.

The second element is the publication in June 2023 of an article published on their Substack ‘Public’ site by journalists Michael Schellenberger, Matt Taibbi and Alex Gutentag. The article claimed that sources within the US government had confirmed that the first Covid patients were researchers at the Wuhan Institute of Virology (if proven, this would, as explained above, be definitive evidence in favor of the laboratory leak). But the government sources cited remain anonymous... It must be said that these revelations do not seem so extravagant, when we know that certain official American bodies, such as a Senate committee or the Department of Energy, have publicly qualified the lab leak hypothesis as more likely than that of zoonosis, although with a low level of certainty.

The authors of the Public article had suggested that infections within the WIV would be confirmed in previously classified documents that were to be made public in June 2023 by US intelligence services. To the dismay of the journalists, the declassified documents do not confirm that, or even say the opposite: if certain WIV researchers were indeed ill at the end of 2019, covid was not diagnosed, and some of the symptoms listed are not compatible with covid.

Evidence in favor of zoonosis and against the laboratory leak, ranked in order of importance according to my own assessment:

1. All the historical examples of pandemics and epidemics that we know of have originated from a zoonosis, none from a laboratory leak. This is the case for SARS-CoV (the first), MERS, Ebola, coronaviruses causing colds, HIV, and many others.

2. Sequencing analysis of the first cases of covid in Wuhan showed that two genetically distinct lineages of SARS were involved very early in the pandemic. The existence of two distinct lineages is consistent with zoonosis but unlikely in a laboratory leak.

3. Analysis of the SARS-CoV-2 genome reveals no signature of laboratory passage or modifications by genetic engineering. The experience amassed by covid researchers shows that the virus, once cultivated in the laboratory, systematically undergoes characteristic changes. These changes are not present in SARS-CoV-2.

4. Epidemiological data showed that among the first documented cases of infection, half were associated with the Huanan market, supporting the idea that the market is the hotbed of the pandemic.

5. Covid DNA was identified in samples from the Huanan market which also contained DNA from non-human animals (raccoon dogs).

6. In the databases of the Wuhan Institute of Virology, no sequences corresponding to SARS-CoV-2 have been identified to date. Certainly the sequences could have been deliberately hidden, but it is difficult to imagine that no trace remained somewhere.

The facts therefore clearly speak in favor of zoonosis. And yet, I must admit, a slight doubt remains in my head. The reason ? The coincidence that the pandemic began in Wuhan, the city which is home to the virology institute known worldwide for its studies of coronaviruses. I have not yet heard this coincidence explained in a completely satisfactory manner, and unfortunately the article by Alwine et al. don't mention it. It was this extraordinary coincidence that for example journalist and talk show host Jon Stewart noted, which led to him being scolded. It is regrettable that the mere mention of the possibility of a laboratory leak arouses such outcry, because a priori it is not entirely far-fetched.

But perhaps this coincidence is less surprising if we take a closer look at it? This is what Brianne Barker does in the TWiV episode already mentioned (the discussion of the coincidence begins at 14'). Barker notes that it is not at all surprising that the pandemic emerged in a large city like Wuhan (7th largest city in the country with more than ten million inhabitants), because the first detections of a virus require good medical infrastructure and experts capable of realizing that this respiratory disease is not common and that it must be sequenced. Some commentators have also pointed out that the majority of major Chinese cities have a laboratory working on coronaviruses. These points are valid: Wuhan is a large city with the infrastructure necessary to detect a new viral outbreak. However, we risk overlooking the fact that there are many large cities in China (the twenty-three largest cities have at least five million inhabitants), and especially the fact that the WIV is not just one lab among many, but THE internationally recognized laboratory for the study of coronaviruses in China. The coincidence is therefore possible, and perhaps less surprising than it seems, but it remains, at least for me, a thorn in the side.