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Wednesday, April 27, 2022

OPINION:

As we mark the two-year anniversary of COVID-19 lockdowns and the pandemic that claimed almost a million American lives, it is time to assess how this began and how to prevent a future, perhaps worse, pandemic.

We should admit we probably have all the evidence we will ever have. The Chinese government and its scientists, the World Health Organization, and Western virologists have collected a substantial quantity of evidence. Unfortunately, this mountain of evidence includes evidence of data having been destroyed, manipulated or withheld. There has never been even a rudimentary forensic investigation of Wuhan laboratories. And there is no clear mechanism to repair the record or recover lost evidence without the cooperation of the Chinese government, which to date has been withheld.


We have also learned, not from the parties themselves but through FOIA requests, that the early narrative of the pandemic arising in a seafood market in Wuhan and not through genetic manipulation in a laboratory was crafted and not totally evidence-driven. The parties creating the story were NIH leadership in conjunction with prominent Western virologists. Many of these virologists have seen a significant increase in taxpayer-funded research following this origin public relations campaign. Finally, a largely unchallenging Fourth Estate, at the time tying the lab leak to former President Donald Trump and the 2020 presidential election, completed the trifecta that kept a robust, public scientific debate from occurring.

So where are we? In a nutshell, a preponderance of evidence supports a lab origin, with no direct evidence of a natural spillover.

For example, no animal has been found in nature infected with SARS-CoV-2 or even a close cousin. No animals from the market, the market supply chain, the farms supplying the market, or any wild animals around Wuhan or in all of China have evidence of the virus or a previous infection. The bat viruses closest to SARS-CoV-2 come from caves and mines in southern China and Laos, over 800 miles from Wuhan. There is no evidence of an animal supply chain from those places to markets in Wuhan.

There is a research supply chain to Wuhan, however. Between 2013 and 2018, bat virus samples from these very same caves or mines were sent to the Wuhan Institute of Virology for study. To develop SARS-CoV-2 in a lab, these bat viruses would be a perfect backbone to begin with. This part of the origin analysis is stuck until the Chinese release a database of over 22,000 virus sequences they stopped sharing with the world in September 2019.

With respect to the timing of the outbreak, analyzing 83,688 virus genomes collected over 18 months indicates human infection began in Wuhan in late summer 2019. Analyzing less than 200 clinical cases, Western virologists suggest it began in December 2019 at that market in Wuhan. But there is evidence that some of this clinical data from December might not be reliable. And the Chinese CDC has said their own data from the market indicates the pandemic did not begin there. With respect to the timing, the much more abundant and unbiased genome sequencing data showing it began months before the market cases obviate any need to even discuss further an origin in that particular market.

The SARS-CoV-2 genome has other clues that support a lab origin. 

We have learned the original virus is remarkably unstable outside of a highly controlled laboratory environment. Because of this instability, by early January 2020 SARS-CoV-2 had acquired a stabilizing mutation known as D614G. Two years later, over 99% of the 9.8 million genomes sequenced have this stabilizing change. One imaginative origin hypothesis was that the virus arrived in China on the outside of frozen food from processing centers abroad. This “Popsicle Pandemic” hypothesis can be dismissed because the original virus is inactivated under frozen shipping conditions.

Laboratory experiments also demonstrate the original virus is too unstable to spread sustainably among susceptible animals. Only the more stable D614G virus can be passed from animal to animal. The seafood market contained only the unstable version of SARS-CoV-2. The instability of the first viruses infecting humans makes it hard to imagine how this virus could circulate in nature and not have acquired the D614G stabilizing change before the first human case. But it is easy to imagine a virus growing in the protected environment of a laboratory, where the D614G stabilization is not necessary, and then accidentally infecting a worker. Such a laboratory infection of SARS-CoV-2 in late 2021 was well documented by the Taiwan CDC. With admirable transparency, they used cellphone GPS signals to trace the subway trains, metro buses, retail stores and restaurants the infected lab scientist visited in the three weeks between exposure and diagnosis.

We have also learned the key to infectivity, the furin cleavage site, is not found anywhere in nature in a SARS-CoV-2-related virus. But in 2018, U.S. scientists together with the WIV wrote a research plan to purposely insert a furin cleavage site into bat viruses to see what it would do. The Department of Defense failed to fund the research proposal, but we don’t know if the Chinese went ahead with the research anyway.

Where do we go from here?

As physicians, if a patient dies and we don’t know why we perform an autopsy. Here we have a million U.S. deaths and a million reasons to get to the bottom of what happened. To accomplish that, one of us (Sen. Roger Marshall) has co-sponsored a bill, that recently passed the U.S. Senate Committee on Health, Education, Labor and Pensions, to create a bipartisan 9/11-style COVID-19 task force.

The task force will have a broad charter to investigate all aspects of the COVID-19 pandemic, including its origin and public health policies related to the response. Most importantly, the benefits and risks of continued gain-of-function research on potential pathogens will be determined. No one wants a more lethal virus lab leak to be the next infectious disease crisis.

• Roger Marshall, MD, is a physician and a Republican U.S. senator from Kansas and Steven Quay, MD, PhD, is a physician-scientist and CEO of Atossa Therapeutics, Inc.


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