How Close Are We To Learning COVID's Origin Story?

- MEDPAGE TODAY - JUNE 7, 2021 - Veronica Hackethal, MD, MSc, Enterprise & Investigative Writer -

— Experts discuss practical implications of a natural or accidental introduction for the virus


As interest grows in the hypothesis that SARS-CoV-2 may have escaped from the Wuhan Institute of Virology in China, more scientists are taking it seriously, in part because of the practical implications associated with it.


While many experts interviewed for this story were hesitant to speculate on the exact implications of a lab leak, they agreed that further research into the virus' origins is necessary, considering practical implications now may help forestall future pandemics.


"In the wake of the COVID-19 disaster -- the greatest disaster the world has faced since World War II -- an investigation of the causes of the disaster and policy changes to reduce the risk and impact of similar future disasters are urgently needed," said Richard Ebright, PhD, a molecular biologist and professor of chemistry and chemical biology at Rutgers University in New Jersey.


Implications of a Natural Origin


On May 26, President Biden called on the Intelligence Community to redouble past efforts to come to a "definitive conclusion" on the origins of SARS-CoV-2 within 90 days.


Vincent Racaniello, PhD, professor of microbiology and immunology at Columbia University, said that getting to the bottom of the issue is not likely to happen within Biden's deadline. Finding the ancestral virus of the first SARS virus in wildlife took 14 years, for instance.


For Racaniello, the renewed interest in this topic highlights an important problem: the need for better investigation of viral threats arising from wildlife.


"All human viruses begin in nature. There's an overwhelming preponderance of data that shows that, so it makes sense to look in nature when we're looking for the source of new viruses," Racaniello, who is also the host of the popular virology podcast "This Week in Virology," told MedPage Today.


As a result of human population growth, the need for food, and encroachment on wildlife habitats, more viruses are spilling over into humans from nature. Ebola, SARS-1, MERS, and bird and swine flu are prime examples. Because mammals are closest to humans evolutionarily, they are most concerning as sources of emerging human pathogens. Rodents and bats (which comprise about 20% of mammals), as well as various species of birds are good places to look. But right now, gaps exist in our surveillance of wildlife, so we have "very little" understanding of the viruses these types of animals harbor, and which ones could be threats to humans, Racaniello said.



"We need to do more wildlife sampling, to find out what's out there and what's potentially a threat," he said. "More investment in this could have prevented the trillions of dollars that we've spent to take care of this pandemic."


Implications of a Lab Leak


On the other hand, Ebright said the crux of the matter is in addressing the potential for future pandemics that could originate from lab accidents, a discussion that "needs to begin now."

"Irrespective of whether COVID-19 originated in a natural accident or a lab accident, the risk of a future pandemic originating in a lab accident is real," he told MedPage Today.


Ebright says that only voluntary biosafety guidelines, which pertain to protections against accidental release of pathogens, exist in the U.S. and abroad, and these are not enforceable by law. While the U.S. has legal regulations against several pathogens with high potential for use as biological weapons (called "select agents"), no biosecurity regulations exist for other pathogens. In most of the world, no biosecurity regulations exist for pathogens other than smallpox, not even voluntary ones, Ebright said.


The U.S. has had a bio-risk policy since 2017, which was drawn up by the NIH's National Science Advisory Board for Biosecuirty (NSABB) and requires a risk-benefit analysis before federal funding can be approved for high-risk research, such as gain of function research that could be used to increase a pathogen's transmissibility or pathogenicity, Ebright said.


Such research is sometimes conducted to better understand a pathogen, and how to control it. But in the wrong hands, this type of research has the potential for misuse, including bioterrorism.


The U.S. bio-risk policy has been "ignored, essentially completely, by federal funding agencies," Ebright said. In most of the world, no corresponding bio-risk policies exist for any pathogen except smallpox, he added.


"Discussion now, especially among policy makers and the public, needs to turn to the inadequacy of biosafety, biosecurity, and biorisk-assessment standards worldwide, and to the essentially complete absence of biosafety regulation worldwide," he said.


Why the Lab Question Re-Emerged


While much of the evidence is circumstantial, the basic idea is that a laboratory at the Wuhan Institute of Virology had been experimenting on a virus called RaTG13 (a coronavirus that is closely related to SARS-CoV-2 and infects horseshoe bats), and genetically manipulating other horseshoe bat viruses collected in rural areas of China. The thinking is that one of these laboratory viruses could have infected a staffer at the institute, who then transmitted it to the broader public, according to Ebright.


Reversing course and taking the lab leak hypothesis seriously occurred after the release of the WHO's March 30 report on its investigation into the origins of SARS-CoV-2. While that report labeled a laboratory origin "extremely unlikely," investigators acknowledged during a press briefing that their conclusion was based on the evidence available to them.


Even WHO Director-General Tedros Ghebreyesus, MBBS, PhD, said at the time that he did not believe the assessment of a laboratory origin was "extensive enough," that this hypothesis "requires further investigation," and that "this report is a very important beginning, but it is not the end."


"At this point in time, all scientific data related to the genome sequence of SARS-CoV-2 and the epidemiology of COVID-19 are equally consistent with a natural-accident origin or a laboratory-accident origin," Ebright said.


While the WHO report does not propose a follow-up study for laboratory origins, it acknowledges that both "follow-up of new evidence" and "regular administrative and internal review of high-level biosafety laboratories worldwide" is needed.


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