NEW YORK (NYTIMES) - Among the thousands of pages of Dr Anthony Fauci's e-mails obtained recently by The Washington Post and BuzzFeed News, a short note from Kristian Andersen, a virus expert at the Scripps Research Institute in La Jolla, California, has garnered a lot of attention.

Over the past year, Andersen 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 to Fauci in January 2020, Andersen hadn't yet come to that conclusion. He told Fauci, the government's top infectious disease expert, that some features of the virus made him wonder whether it had been engineered, and noted that he and his colleagues were planning to investigate further by analysing the virus's genome.

The researchers published those results in a paper in the scientific journal Nature Medicine on March 17, 2020, concluding that a laboratory origin was very unlikely. Andersen has reiterated this point of view in interviews and on Twitter over the past year, putting him at the centre of the continuing controversy over whether the virus could have leaked from a Chinese lab.

When his early e-mail to Fauci was released, the media storm around Andersen intensified, and he deactivated his Twitter account. He answered written questions from The New York Times about the e-mail and the fracas. The exchange has been lightly edited for length.

Q: Much has been made of your e-mail to Fauci in late January 2020, shortly after the coronavirus genome was first sequenced. You said, "The unusual features of the virus make up a really small part of the genome (0.1%) so 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 potentially be 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 allows the SARS-CoV-2 spike protein to 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 also said you found the virus's genome to be "inconsistent with expectations from evolutionary theory."

A: This was a reference to the features of SARS-CoV-2 that we identified based on early analyses that didn't appear to have an obvious immediate evolutionary precursor. We hadn't yet performed more in-depth analyses to reach a conclusion, rather were sharing our preliminary observations.

I cautioned in that same e-mail that we would need to look at the question much more closely and that our opinions could change within a few days based on new data and analyses - which they did.

Q: In March, you and other scientists published the Nature Medicine paper saying that "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.

Yet 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 demonstrated that the features that first appeared unique to SARS-CoV-2 were in fact found in other, related viruses.

Overall, this is a textbook example of the scientific method where a preliminary hypothesis is rejected in favour of a competing hypothesis after more data become available and analyses are completed.

Q: As you know, there has been a lot of speculation and hype over the past few weeks about a particular protein in the coronavirus: the furin cleavage site. Some people, including virus expert David Baltimore, say the presence of this protein could be a sign of human manipulation of the virus, whereas you and other virologists have said it naturally evolved. Can you explain for readers why you don't think it is proof of an engineered virus?

A: Furin cleavage sites are found all across the coronavirus family, including in the betacoronavirus genus that SARS-CoV-2 belongs to. There has been much speculation that patterns found in the virus's RNA that are responsible for certain portions of the furin cleavage site represent evidence of engineering.

Specifically, people are pointing to two "CGG" sequences that code for the amino acid arginine in the furin cleavage site as strong evidence that the virus was made in the lab. Such statements are factually incorrect.

While it's true that CGG is less common than other patterns that code for arginine, the CGG codon is found elsewhere in the SARS-CoV-2 genome and the genetic sequence(s) that include the CGG codon found in SARS-CoV-2 are also found in other coronaviruses. These findings, together with many other technical features of the site, strongly suggest that it evolved naturally and there is very little chance somebody engineered it.

Q: Do you still believe that all laboratory scenarios are implausible? If not an engineered virus, what about an accidental leak from the Wuhan lab?

A: As we stated in our article last March, it is currently impossible to prove or disprove specific hypotheses of SARS-CoV-2 origin. However, while both lab and natural scenarios are possible, they are not equally likely - precedence, data and other evidence strongly favor 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 release(d) 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.