Is SARS-CoV-2 natural? Or did this virus – originally isolated from Nature – gain function in a laboratory and then escape?
Introduction
I feel passionately about this question. As a former research laboratory director involved in testing environmental samples and in protecting human health and safety, I want to know whether the SARS-CoV-2 virus that caused the first human cases of COVID-19 in Wuhan, China escaped from a laboratory.
I have toured a Biosafety Level 4 (BSL4) facility in Bethesda, MD prior to its opening, and I saw firsthand the many building design features and laboratory protocols that are put in place to insure lab workers are not exposed to highly infectious pathogens and that deadly microbes are not released into the environment. And yet, as a manager of several laboratories, I know firsthand that accidents happen and events occur that were not foreseen.
In this blog, I will focus on three compelling reasons why the SARS-CoV-2 virus that causes COVID-19 may have escaped from a research laboratory.
- No evidence of SARS-Cov-2 virus was circulating in wild or domesticated animals in China in the years prior to or in the months after the onset of the pandemic.
- Serious biosafety concerns that gain-of-function research on Corona viruses in human cell cultures and humanized mice could unleash a pandemic halted US funding of this type of research for several years.
- The strong implication that the virus did not leap directly from animals to humans because SARS-Cov-2 virus is extraordinarily well-suited to spread by human-to-human transmission. Studies show it is more adapted to infect humans, more so than other animals including bats.
No Evidence of Zoonosis – Infection from Animals to Humans
We do know that prior to the outbreak of the pandemic, many Corona viruses similar to SARS-CoV-2 were in circulation in bats in southern China. For example, during an interview on This Week in Virology recorded on December 9, 2019 at the Nipah Virus International Conference in Singapore hosted by Dr. Vincent Racaniello TWiV 615: Peter Daszak of EcoHealth Alliance, Dr. Peter Daszak, President of EcoHealth Alliance, said that his organization:
“did surveillance of bats across southern China and we’ve now found after, you know, six or seven years of doing this over 100 new SARS-related Corona viruses – very close to SARS.”
And yet, as reported in the journal Nature ‘Major stones unturned’: COVID origin search must continue after WHO report, say scientists despite extensive testing, scientists have been unable to identify bats or any other “kinds of animal that could have passed the virus to people. Ben Embarek said that Chinese researchers had tested many domestic, farmed and wild animals in the country but found no evidence that the virus was present or continued to circulate in these species.”
Gain-of-Function Research – Accidental Escape from Laboratory
Pause in Federal Funding for Gain-of-Function Research in 2014
As described on the NIH Office of Science Policy website (Gain of Function Research) “Certain gain-of-function studies with the potential to enhance the pathogenicity or transmissibility of potential pandemic pathogens (PPPs) have raised biosafety and biosecurity concerns, including the potential dual use risks associated with the misuse of the information or products resulting from such research.”
“On October 16, 2014, the White House Office of Science and Technology Policy announced the launch of the U.S. Government (USG) gain-of-function (GOF) deliberative process to re-evaluate the potential risks and benefits associated with certain GOF experiments. During this process the USG paused the release of federal funding for GOF studies anticipated to enhance the pathogenicity or transmissibility among mammals by respiratory droplets of influenza, MERS, or SARS viruses.”
“While this deliberative process was on-going, the U.S. government stopped the release of new funding for gain-of-function research projects that reasonably may be anticipated to confer attributes to influenza, Middle East Respiratory Syndrome (MERS), or Severe Acute Respiratory Syndrome (SARS).”
This pause ended in 2017 upon issuance of updated federal guidelines regarding the safe conduct of this research.
Risky Gain of Function Research Conducted in Laboratories
In 2015, Dr. Zhengli-Shi (Wuhan Institute of Virology), Professor Ralph Baric (UNC)*, and their co-authors expressed their concerns regarding the risks of their gain-of-function research in an article published in Nature A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence. Research in this manuscript was supported by grants from the National Institute of Allergy & Infectious Disease and the National Institute of Aging of the US National Institutes of Health (NIH).
“On the basis of these findings, scientific review panels may deem similar studies building chimeric viruses based on circulating strains too risky to pursue, as increased pathogenicity in mammalian models cannot be excluded. Coupled with restrictions on mouse-adapted strains and the development of monoclonal antibodies using escape mutants, research into CoV emergence and therapeutic efficacy may be severely limited moving forward. Together, these data and restrictions represent a crossroads of GOF research concerns; the potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens. In developing policies moving forward, it is important to consider the value of the data generated by these studies and whether these types of chimeric virus studies warrant further investigation versus the inherent risks involved.”
*[Note: Ralph Baric is the William R. Kenan Jr. Outstanding Professor in the Department of Epidemiology, and Professor in the Department of Microbiology and Immunology at The University of North Carolina at Chapel Hill].
Generation of Chimeric Viruses in Laboratories
Describing on-going research into the potential ability of the one hundred newly identified SARS-related Corona viruses to cause disease in humans, Dr. Daszak said in his above-mentioned interview with Vincent Racaniello “Some of them get into human cells in the lab, and some of them can cause SARS disease in humanized mouse models.” At the time of the interview, which occurred prior to the announcement by the Chinese government of the outbreak of disease caused by a novel Corona virus, Dr. Daszak characterized these newly identified SARS-related Corona viruses as “untreatable with therapeutic monoclonals and you can’t vaccinate them with the vaccine.”
In an effort to develop therapeutics and vaccines, Dr. Daszak went on to say “You can manipulate them in the lab pretty easily. The spike protein drives a lot of what happens with the Corona virus, with the zoonotic risk. So you can get the sequence, you can build the protein – and we work with Ralph Baric at UNC to do this – and insert it into the backbone of another virus and do some more work in the lab.”
This kind of research – genetically mixing different viruses together to create a new “chimeric” virus with enhanced virulence and transmissibility – poses just the kind of risk that prompted the NIH to pause funding in response to lab accidents and other biosecurity concerns in the US.
SARS-CoV-2 Appears Too Well Adapted to Have Come Directly from Animals
In May 2020, Sky News Australia interviewed Professor Nikolai Petrovsky of the College of Medicine and Public Health at Flinders University. Professor Petrovsky, who is also Chairman and Research Director of Vaxine Pty Ltd, found through his vaccine research that the virus that causes COVID-19 was extraordinarily well adapted for transmission to humans, far more than any other animal, including bats.
SARS-CoV-2 (the virus that causes COVID-19) enters human cells by using its spike protein to bind to the Angiotensin-Converting Enzyme 2 (ACE2) found on the surface of lung cells. By hitching a ride on ACE2, the virus passes through the otherwise impermeable cell membrane where it begins replicating inside the lung cell. Adaptation to human ACE2 (which differs from ACE2 found in other animals) could have arisen by a recombination event between viruses that occurred inadvertently or intentionally in a laboratory growing multiple corona viruses in human cell cultures or in humanized mice.
Speaking with investigative reporter Sharri Markson of Sky News Australia, Professor Petrovsky said “We found that the COVID-19 virus was particularly well-adapted to bind to human cells and that was far superior to its ability to bind to the cells of any other animal species which is quite unusual because typically when a virus is well-adapted to an animal and then it by chance crosses to a human, typically, you would expect it to have lower-binding to human cells than to the original host animal. We found the opposite so that was a big surprise,” he said.
“We just try to base our findings on facts rather than taking particular political positions but sometimes obviously the alternatives may have unintended consequences,” he said. “For instance, if it was to turn out that this virus may have come about because of an accidental lab release that would have implications for how we do viral research in laboratories all around the world which could make doing research much harder. “So I think the inclination of virus researchers would be to presume that it came from an animal until proven otherwise because that would have less ramifications for how we are able to do research in the future. The alternative obviously has quite major implications for science and science on viruses, not just obviously political ramifications which we’re all well aware of.”
Professor Petrovsky’s research was published in the open-access archive of moderated scholarly articles arXiv. His article was titled “In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus.”
Conclusions and Recommendations
Conclusions
- No animals (including bats) have been found carrying the SARS-CoV-2 virus, despite extensive and on-going testing in China, both in the years before and in the months after the outbreak of the COVID-19 pandemic.
- Risky gain-of-function research on SARS viruses was halted for several years in the US due to the dangers of accidental release of more transmissible and virulent pathogens, resulting in a worldwide pandemic; as well as the very real potential for the use of the products of this technology in biological warfare.
- At the time of the outbreak of COVID-19, gain-of-function research on SARS viruses in human cell cultures and humanized mice was on-going at laboratories in China (and elsewhere), funded in part by US tax dollars.
- From the inception of this pandemic, SARS-CoV-2 was extraordinarily well-adapted to infect the human body and to spread by human-to-human transmission. This behavior is highly unusual for a natural, wild-type virus and it strongly suggests that SARS-CoV-2 had been replicating in human cell cultures or in the cells of humanized mice for some time.
Recommendations
- We need more information. Contact your federal representatives and request greater transparency regarding “classified” information on the origins of SARS-CoV-2 currently in the possession of the US government.
- We need broader oversight. In a vibrant democracy, investigative and regulatory oversight of gain-of-function viral research should not be conducted only by those who have a vested interest in these technologies. We need the perspectives, the concerns, and the insights from a broad spectrum of society. The grave negative consequences to civilization – worldwide pandemics, biological warfare – are too great to delegate most of these responsibilities to an elite few of senior government administrators and experts who sit on medical and scientific review panels.
More to Come!
In the months ahead, we will continue investigating the origins of the SARS-CoV-2 virus and bring you updates here at the Floriescence Institute blog site.
We welcome your constructive comments and suggestions regarding how we as a society should deal with the very real risk of laboratory-initiated pandemics (even if it turns out in this case COVID-19 arose from the wild).