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Covid-19 origins: Why the search for the source is vital

<i>CDC</i><br/>Transmission electron microscopic image of an isolate from the first U.S. case of Covid-19
Transmission electron microscopic image of an isolate from the first U.S. case of Covid-19

By A. Chris Gajilan, CNN

No clear culprit.

No smoking gun.

While Covid-19’s origin story is currently defined by a lack of hard evidence and data, scientists around the world continue their search for answers to how the pandemic began. CNN Chief Medical Correspondent Dr. Sanjay Gupta speaks to leading virologists, epidemiologists and coronavirus researchers in “The Origins of Covid-19: Searching for the Source,” premiering at 8 p.m. ET Sunday.

As the world approaches the two-year mark since this novel coronavirus was first detected, there have been many twists and turns in the investigation into the origins of SARS-CoV-2, the virus that caused the pandemic. Some clues have lead to dead ends, while others have spurred even more questions.

To date, there are two prevailing theories.

The zoonotic hypothesis hinges on the idea that the virus spilled over from animals to humans, either directly through a bat, or through some other intermediary animal. Most scientists say that this is the likely origin, given that 75% of all emerging diseases have jumped from animals into humans. Previous coronavirus outbreaks include the first SARS in 2003, which started in bats, then spread to civet cats and into humans; and the 2012 MERS outbreak, which spilled over from bats to camels, and ultimately to people.

But there also remains the possibility that the virus leaked from a lab. Through much of 2021, the lab leak theory gained momentum. In March of this year, Dr. Robert Redfield, the former director of the US Centers for Disease Control and Prevention and a career virologist, told Gupta that he thinks Covid-19 originated in a lab in Wuhan, China.

The controversial World Health Organization report

Days after Redfield’s comments aired on CNN, the highly anticipated World Health Organization’s report into the origins of SARS-CoV-2 was released, on March 30, 2021. The report found that a direct spillover from animals to humans was a “possible-to-likely pathway,” and a jump from another intermediate host animal was “likely to very likely.” The virus coming in through frozen food was a “possible pathway,” and a laboratory incident was deemed “extremely unlikely.”

Swiftly, criticism of the report came from far and wide. More than a dozen countries issued a joint statement about the independence and credibility of the findings. WHO Director-General Tedros Adhanom Ghebreyesus was also critical of the findings and soon called the report’s dismissal of the lab leak theory “premature.”

“We learned from the report that … if you look at the trends in influenza-like illness, in excess mortality, it’s clear that there was circulation of this virus earlier, that there was likely widespread circulation in December. That’s really, really important,” says Maria Van Kerkhove, and infectious disease epidemiologist and WHO’s Covid-19 Technical Lead. “The area of work in the report that wasn’t covered in detail was the lab, and the lab audit, and the lab hypothesis,” she told Gupta.

“It was clear to me, and I think to many, that they had looked reasonably hard at one plausible hypothesis (zoonotic spillover), but really had ignored or brushed aside the other: the laboratory-associated hypothesis. … I just think that they were not fair and objective,” said Dr. David Relman, an infectious disease expert and microbiologist at Stanford University.

Relman tallied up the WHO report’s number of pages dedicated to the lab leak theory. “The total: annex and main report, for the laboratory (hypothesis) was about four pages out of 313 … and in those four pages the title of the section was, ‘Conspiracy Theories.’ “

Critics say that the WHO study was flawed even before the WHO team landed in Wuhan in January 2021. From the outset, the Chinese government had to agree to the terms of the WHO’s study, including which scientists were selected to go to China, which locations would be visited, and what primary data could be accessed. Alina Chan, a molecular biologist at the Broad Institute of MIT and Harvard points out, “All of the original analyses had been done by Chinese scientists before the WHO came in.”

“The United States submitted three US researchers for selection. … All three of them were rejected by China, which did ultimately have final say, since the WHO was coming into their country. … The only American who was permitted on the team was Peter Daszak,” according to CNN’s Katie Bo Williams, who reports on intelligence and national security.

“It’s official title is a ‘joint study,’ which is very important … because if it’s a joint study, it’s a collaborative study between the WHO and the member state China. The public looked at this as an investigation from the start, and I think that was a mistake,” said Daszak, the only American to serve on the WHO team on the ground in Wuhan. Daszak, a renowned virus hunter and president of EcoHealth Alliance, would become the most controversial member of the WHO team. Critics say that he had a clear conflict of interest because of his ties to the Wuhan Institute of Virology, including funding bat coronavirus research at the institute through subgrants from the US National Institutes of Health.

“It’s caused by bat coronavirus, something that we’ve been working on for over 20 years in China. So, I do have some level of expertise that is going to be valuable to that team,” Daszak told Gupta. Daszak and EcoHealth Alliance’s work was key to unlocking the origins of the first SARS outbreak in 2003.

“We didn’t have people on the mission team who were experts in biosafety, biosecurity. So, it wasn’t really their mandate to do,” Van Kerkhove acknowledged.

“I think WHO should have spoken out more forcefully and said we are not going to do a forensic investigation of a lab in China as part of this work,” Daszak told Gupta.

WHO’s Van Kerkhove explained to Gupta why Tedros was so critical of the WHO report. “If you look at the way that they reported on that (lab leak theory), they classified it as ‘extremely unlikely.’ For us to be able to take that off the table, it needs to be studied properly. It needs to be studied thoroughly.”

Less than two months after the WHO report was released, the lab leak theory gained more momentum when a group of 18 scientists, including Relman and Chan, published a letter in the journal Science calling for an investigation into all possible origins.

Evolutionary biology

To be sure, SARS-CoV-2 is a new pathogen that can be hard to visualize and even harder to investigate — especially as it evolves and more variants emerge. Visual Science created this highly detailed scientific 3D animation to illustrate the complexity of the SARS-CoV-2 virus particle. Those infamous spike proteins are shown on an unprecedented macro level in their rendering.

Scientists around the world continue to delve deeper into the unique features of the virus.

Kristian Andersen, an evolutionary biologist at the Scripps Research Institute, is the lead author on the most influential paper in support of the natural origins theory to date.

But when Andersen first learned of a novel coronavirus sweeping across China and beyond in early 2020, he was focused on this question: Why is SARS-CoV-2 spreading so easily? In those earliest weeks, he wondered about any possible connection between the Wuhan Institute of Virology and its work on bat coronaviruses and its location situated in the very city where human cases were first detected. “Initially in January, knowing the type of work that was going on at the Wuhan Institute of Virology, we started thinking like, ‘Look, we need to consider the possibility that this is maybe not a natural virus.’ “

In late January 2020, Andersen raised that red flag to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. In an email which that was later released, Andersen writes that he and other scientists “find the genome inconsistent with expectations from evolutionary theory.”

Shortly after that email, some of the world’s top scientists gathered on a call to discuss what they saw in the genome. That group included Andersen, Fauci and NIH Director Dr. Francis Collins among others. “There were concerns … because this was not a familiar sequence. Is there something here that looks like it might be the signature of human manipulation?” Collins said.

But this idea was quickly dismissed. Even though researchers thought this novel virus initially showed traits of bioengineering, they subsequently found evidence of similar traits in other known viruses.

“The engineering aspect of this … very quickly we realized that we just don’t have the evidence to support that. … If we can find any evidence of this virus previously having been sequenced, or worked on, maybe there’s fragments of the virus, which have used previously in experiments, would be, quote-unquote, ‘a smoking gun.’ And we didn’t find anything at all, and that’s why the whole idea about engineering was sort of like, ‘Look, this is completely unsupported by any evidence,’ ” Andersen told Gupta.

“We debated … up one side and down the other and ultimately decided: no. Actually, if you were a human trying to design a really dangerous coronavirus, you would not design this one. Its spike protein had some unusual features but not ones that anybody would have guessed would make it so effective in binding to the ACE2 receptor and getting into human cells,” Collins told Gupta. It’s a view held by many genetic epidemiologists, virologists and coronavirus researchers.

“There was nothing that could have been brought into the lab and manipulated to make it look like this. It’s a unique virus like every other virus that’s circulating in the wild is unique,” said Joel Wertheim, a molecular epidemiologist at UC San Diego who recently co-authored an updated critical review of SARS-CoV-2’s origins with Andersen and 19 other prominent scientists.

But the questions remain: If the virus did not come out of a lab, where did it come from? When did it start circulating? And is there any chance of finding the animal or animals that might have been the carriers?

Was it a wild animal bred for sale in one of China’s wet markets, where exotic meat, pelts and live animals are on display?

Was an animal carrying the virus imported from elsewhere in Southeast Asia?

Was a researcher studying bats accidentally infected and perhaps started spreading the virus unknowingly?

Does China have banked blood samples that could pinpoint when the virus first started infecting people — and show what it looked like at the moment it jumped from animal to human? And if so, how could the always secretive and now defensive Chinese government be persuaded to share what’s there?

While many questions linger about the Wuhan lab, Danielle Anderson, the last and only foreign scientist to work at the Wuhan Institute of Virology Biosafety Level 4 lab, spoke to Gupta about her experience working there. While Anderson attests to the high standards of the institute’s BSL-4 lab to handle deadly pathogens, other scientists have raised concerns about bat coronavirus research conducted at Wuhan’s lower level BSL-2 labs.

Ralph Baric, a top coronavirus researcher at UNC Chapel Hill who has collaborated with the Wuhan Institute of Virology, points to specific evidence needed to further the understanding of the virus’ origins. “Early cases, serology in China done on the right populations; not many of the populations that were in the WHO report. Systematic surveys of that information, analysis of idiopathic respiratory cases that appeared at hospitals, not only in Wuhan, but in the surrounding communities … those answers are all in China,” Baric said.

The Chinese government vehemently denies the possibility of any Wuhan lab leak and has rejected any further WHO origins studies in their country.

“I’m still hopeful that, if not the Chinese government, the Chinese scientists, friends of Chinese scientists and others with whom they have worked will all come forward and get organized in these various ways, shapes and forms,” Relman said.

“Pandemics are rare, and this is a really devastating one. … It’s frustrating and we want answers,” Andersen told Gupta. “We want to know what led to this, so we can hopefully try and prevent something similar from happening in the future.”

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