Understanding the origins of SARS-CoV-2

Hutch evolutionary biologist calls for more research on how COVID-19 pandemic started
Photo of Dr. Jesse Bloom
Dr. Jesse Bloom has begun focusing on understanding how the pandemic began. Photo by Robert Hood / Fred Hutch News Service

Over a year after the start of the COVID-19 pandemic, it’s still unclear exactly how it began. Dr. Jesse Bloom, an evolutionary biologist at Fred Hutchinson Cancer Research Center, has become one of the leading scientific voices calling for a more thorough investigation of SARS-CoV-2’s origins. Knowing how this pandemic began can help with thinking about how science can best mitigate the risk of future pandemics.

Before SARS-CoV-2, Bloom and his team in the Basic Sciences Division at Fred Hutch were focused on the evolution of flu viruses. But as SARS-CoV-2 became a worldwide threat last year, they switched gears to study how it was evolving and what that evolution could mean for applied questions about antibodies and vaccines used to treat and prevent infection with the virus.

As the pandemic increasingly comes under control in the U.S., Bloom and other scientists have begun focusing on understanding how the pandemic began. This spring, Bloom teamed up with other experts in his field to speak out publicly in support for a more thorough investigation. In a letter published in Science, Bloom and 17 other scientists argued that “greater clarity about the origins of this pandemic is necessary and feasible to achieve. We must take hypotheses about both natural and laboratory spillovers seriously until we have sufficient data."

What breakthroughs are coming next?

Recovered sequences offer clues

On June 22, Bloom reported his discovery of SARS-CoV-2 sequences from early in the Wuhan outbreak that had been deleted from a National Institutes of Health database. In his non-peer-reviewed preprint and a complementary Twitter thread, he explained how he found and reconstructed 13 of these sequences and what he learned from his analysis of them.

He wrote that the sequences support other lines of evidence that SARS-CoV-2 was circulating in Wuhan before the December 2019 outbreak in a seafood market. They do not provide evidence either for or against either a natural animal origin for the virus or an accidental lab leak. More early sequences are probably out there, he wrote, and scientists should focus on identifying them and analyzing all available data to determine the origins of the pandemic.

In a Q&A, we asked Bloom to explain the significance of understanding pandemic origins in the context of understanding viruses and preventing future outbreaks.

Why is it important to figure out how the COVID-19 pandemic started?

Bloom: By understanding the origins of SARS-CoV-2, we can be informed about how to best use the power of science to mitigate the risk of possible future viral outbreaks.

Currently, there is a lack of clear evidence about how the SARS-CoV-2 virus emerged. The deep ancestors of SARS-CoV-2 are coronaviruses from bats, but so far no bat virus has been identified that is closely enough related to SARS-CoV-2 to be the immediate ancestor. There are two major theories about how the bat ancestor viruses could have led to the emergence of the pandemic in Wuhan. One theory is that there was a natural zoonosis, with the virus jumping directly from a bat to a human, or passing from a bat to an intermediate animal host and then to a human. The other theory is that there was some sort of accident in one of the labs in Wuhan that was working with bat coronaviruses.
Both theories are plausible given the currently available evidence. I also believe as a scientist it’s important to clearly convey that there is scientific uncertainty — especially because this is a hot-button topic. The job of scientists like myself is to take a more objective and dispassionate approach, and be sure that the discussion is framed in terms of scientific facts, rather than the many strong opinions that some people have about this topic. And unfortunately, at this point, the facts are limited.

What do you think happened? Was it an accidental lab leak or natural emergence?

Bloom: Natural zoonosis is plausible because most pandemics start that way. For instance, four of the last five influenza pandemics started from natural zoonoses, while one (the 1977 influenza pandemic) was due to human error: either a misguided vaccine trial or a lab accident. In the case of coronaviruses, we know that in the past there have been other animal coronaviruses that have caused outbreaks in humans due to direct animal-to-human jumps. These include the original SARS-CoV-1 and MERS-CoV. My first assumption when I heard about SARS-CoV-2 back in January of 2020 was that it most likely had jumped from a bat.

But there have also been lab accidents. For instance, in 2004 a number of people in Beijing were infected with SARS-CoV-1 due to a lab accident. The reason that a lab accident is a plausible explanation for the origins of SARS-CoV-2 is that one of the leading labs studying SARS-like coronaviruses is located in Wuhan, and researchers there are known to have collected many coronaviruses, although at this point there is no evidence that they had collected any virus sufficiently similar to SARS-CoV-2 to be its direct ancestor.

That’s why I joined other scientists in an open letter published in Science calling for more investigation. We’re not taking an advocacy position on one scenario being more likely than another. We’re just pointing out that the existing scientific evidence is insufficient to know what happened. We need more investigation of this topic if we ever hope to get a clear answer.

Why was publishing an open letter in Science important and how did it come together?

Bloom: I am among 18 scientists who wrote and signed the letter that appeared May 13 in the journal Science.

We wanted a letter published in a scientific journal. Our goal in writing a letter by practicing scientists and publishing it in a scientific journal was to remind people that how the pandemic started is ultimately a scientific question, not a political one.

A few of us started drafting the letter to support calls from the World Health Organization and U.S. government to further investigate the origins of the virus. We reached out to other scientists with relevant expertise who were currently studying SARS-CoV-2 and virus evolution — and most other scientists we contacted agreed to sign the letter.

What has been the response to the letter?

Bloom: I’m still getting a lot of emails. Many from other scientists who are supportive of the need for more investigation, others saying that further investigation is a distraction. Almost everyone concurs that the science is unclear, but people differ in their assessments of the relative likelihoods of a lab accident versus a natural zoonosis. As a scientist, I’m used to the idea of dealing with uncertainty, but I’m not accustomed to dealing with uncertain topics where so many people want one or the other possibility to be true even if the evidence remains unclear.

However, I’m encouraged by the growing consensus on the need for further investigation. Many basic facts about the earliest SARS-CoV-2 cases remain unclear, so of course scientists and experts have different guesses on the relative likelihoods of a lab accident versus a natural zoonosis. But there is a shared view that further careful scientific investigation is needed.

What would you want from another investigation? And how likely is that considering so much will have to happen in China?

Bloom: It’s clear further study is needed to determine the origins of the virus.

Ideally, we can get more access to underlying data about the sequences of the coronaviruses that were being studied in Wuhan labs and more insight on the earliest human cases of COVID-19.

There are complex and political dimensions, but that’s beyond the scope of what I can control. My job as a scientist is to focus on trying to get at the truth.

Some dismissed the lab leak idea as a conspiracy theory and others have wondered if it was intentional. What’s your view?

Bloom: We don’t have enough scientific evidence to rule anything out. In my view, an investigation should include study of both a possible natural zoonosis and a possible lab accident.

I do not think that intentional release is a plausible theory: There is no motive, and all indications are that the outbreak was a surprise to China just like the rest of the world, which would not be the case for an intentional release.

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