[Among the thousands of pages of Dr. Anthony S. Fauci’s emails released recently by BuzzFeed News, a short note from Kristian Andersen, a virologist at the Scripps Research Institute in La Jolla, Calif., has garnered a lot of attention.

Over the past year, Dr. 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 email to Dr. Fauci in January 2020, Dr. Andersen hadn’t yet come to that conclusion. He told Dr. 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 analyzing 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. Dr. Andersen has reiterated this point of view in interviews and on Twitter over the past year, putting him at the center of the continuing controversy over whether the virus could have leaked from a Chinese lab.

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

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James Gorman and Carl Zimmer (GZ): Much has been made of your email to Dr. 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?

Dr. Kristian Andersen: 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.

GZ: You also said you found the virus’s genome to be “inconsistent with expectations from evolutionary theory.”

KA: 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 email 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.

GZ: 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?

KA: 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 favor of a competing hypothesis after more data become available and analyses are completed.

GZ: Some people, including virologist David Baltimore, say the presence of the furin cleavage site 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?

KA: 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.

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

KA: 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.

GZ: Some people have pointed to your email to Dr. Fauci, suggesting that it raises questions about whether scientists and government officials gave more credence to the lab-leak theory than they let on to the public. And some recent reports have suggested that certain government officials didn’t want to talk about the lab-leak theory because it would draw attention to the government’s support of so-called gain-of-function research. What is your response to these suggestions? Were you worried in the spring of 2020 about the public latching on to a lab-leak theory?

KA: My primary concern last spring, which is true to this day, is to perform research to discern exactly how SARS-CoV-2 emerged in the human population.

I won’t speak to what government officials and other scientists did or didn’t say or think. My comments and conclusions are strictly driven by scientific inquiry, and I strongly believe that careful, well-supported public messaging around complex topics is paramount.

GZ: Many scientists have now expressed an openness to the possibility that a lab leak occurred. Looking back over the past year, do you have any regrets about the way you or the broader scientific community have communicated with the public about the lab-leak idea?

KA: First, it is important to say that the scientific community has made tremendous inroads in understanding Covid-19 in a remarkably short amount of time. Vigorous debate is integral to science and that’s what we have seen regarding the origins of SARS-CoV-2.

It can be difficult at times for the public, I think, to observe the debate and discern the likelihood of the various hypotheses. That is particularly true where science becomes politicized, and the current vilification of scientists and subject matter experts sets a dangerous precedent. We saw that with the climate change debate and now we’re seeing it with the debate around various facets of the Covid-19 pandemic.

Throughout this pandemic, I have made my best efforts to help explain what the scientific evidence is and suggests, and I have no regrets about that.

GZ: Do you support President Biden’s call for U.S. intelligence agencies to further investigate these various possibilities? Could they find anything that would change your mind?

KA: I have always supported further inquiries into the origin of SARS-CoV-2, including President Biden’s recent call, as it is important that we more fully understand how the virus emerged.

As is true for any scientific process, there are several things that would lend credence to the lab-leak hypothesis that would make me change my mind. For example, any credible evidence of SARS-CoV-2 having been at the Wuhan Institute of Virology prior to the pandemic — whether in a freezer, in tissue culture or in animals, or epidemiological evidence of very early confirmed Covid-19 cases associated with the institute.

Other evidence, were it to emerge, could lend further weight to the natural origin hypothesis. That includes the identification of an intermediate [animal] host (if one exists). Also, now that we know that live animals were sold at markets across Wuhan, further understanding of the flow of animals and connected supply lines could lend additional credence to natural emergence.

GZ: It seems that you’ve shut down your Twitter account. Why? Will you come back?

KA: I have always seen Twitter as a way to interact with other scientists and the general public to encourage open and transparent dialogue about science.

Increasingly, however, I found that information and comments I posted were being taken out of context or misrepresented to push false narratives, in particular about the origins of SARS-CoV-2. Daily attacks against scientists and the scientific method have also become common, and much of the conversation has steered far away from the science.

For those reasons, I felt that at present, I could no longer productively contribute to the platform, and I decided it would be more productive for me to invest more of my time into our infectious disease research, including that on Covid-19.

(James Gorman is a science writer at large and the author of books on hypochondria, penguins, dinosaurs and the ocean around Antarctica. He writes about animals, viruses, archaeology and the evolution of dogs. Carl Zimmer writes the “Matter” column. He is the author of fourteen books, including “Life’s Edge: The Search For What It Means To Be Alive.” Courtesy: New York Times.)