US expert explains his early e-mails to Fauci on virus origins

NEW YORK • Over the past year, virus expert Kristian Andersen from the Scripps Research Institute in La Jolla, California, has been one of the most outspoken proponents of the theory that the coronavirus originated from a natural spillover from an animal to humans outside of a lab.

But in the e-mail messages to United States top infectious disease expert Anthony Fauci in January last year, Professor Andersen said some of the virus' features made him wonder if it had been engineered. He also said he and his colleagues were planning to investigate further by analysing the virus' genome.

The researchers published those results in a paper in the scientific journal Nature Medicine in March last year, concluding that a lab origin was very unlikely.

Prof Andersen answered written queries from The New York Times about the e-mail. Here's the Q&A, edited for length.

Q When you said one has to "look really closely at all the sequences to see that some of the features (potentially) look engineered". Can you explain what you meant? A At the time, based on limited data and preliminary analyses, we observed features that appeared to be potentially unique to Sars-CoV-2. We had not yet seen these features in other related viruses from natural sources, and thus were exploring whether they had been engineered into the virus.

Those features included a structure known as the furin cleavage site that let the Sars-CoV-2 spike protein be cleaved by furin, an enzyme found in human cells, and another structure, known as the receptor binding domain, that allowed the virus to anchor to the outside of human cells via a cell-surface protein known as ACE2. Q You and other scientists published the Nature Medicine paper saying "we do not believe that any type of laboratory-based scenario is plausible". Can you explain how the research changed your view? A The features in Sars-CoV-2 that initially suggested possible engineering were identified in related coronaviruses, meaning that features that initially looked unusual to us weren't. Many of these analyses were completed in a matter of days, while we worked around the clock, which allowed us to reject our preliminary hypothesis that Sars-CoV-2 might have been engineered, while other "lab"-based scenarios were still on the table.

More extensive analyses, significant additional data and thorough investigations to compare genomic diversity more broadly across coronaviruses led to the peer-reviewed study published in Nature Medicine. For example, we looked at data from coronaviruses found in other species, such as bats and pangolins, which showed the features that first appeared unique to Sars-CoV-2 were in fact found in other related viruses. Q Do you still believe all lab scenarios are implausible? If not an engineered virus, what about an accidental leak from the Wuhan lab? A As we stated in our paper, it is currently impossible to prove or disprove specific hypotheses of Sars-CoV-2 origin. But while both lab and natural scenarios are possible, they are not equally likely. Precedence, data and other evidence strongly favour natural emergence as a highly likely scientific theory for the emergence of Sars-CoV-2, while the lab leak remains a speculative hypothesis based on conjecture.

Based on detailed analyses of the virus conducted to date by researchers around the world, it is extremely unlikely that the virus was engineered. The scenario in which the virus was found in nature, brought to the lab and then accidentally released is similarly unlikely, based on current evidence.

In contrast, the scientific theory about the natural emergence of Sars-CoV-2 presents a far simpler and more likely scenario. The emergence of Sars-CoV-2 is very similar to that of Sars-CoV-1, including its seasonal timing, location and association with the human food chain.

NYTIMES