The Illusion of Biosafety During SARS-CoV-2 Research: Multiple Apparent Occult Lab-Acquired Infections Are Identified Under BSL-3 Conditions at a Premier US-based Coronavirus Laboratory

ABSTRACT

An active debate exists over the use of synthetic biology and other advanced research tools on dangerous pathogens. Virologists doing gain-of-function and related research on dangerous pathogens, including creating synthetic chimeric infectious clones, believe their work is essential to preventing the next pandemic. Many scientists in related fields do not believe the benefit of the research outweighs the risk of a laboratory-acquired infection, leading to community spread. They also believe that current regulations and guidelines for the funding, conduct, and biosafety reporting of research accidents, that is, infections of laboratory personnel, is inadequate.

The consensus of the virologists’ position is that, if creating synthetic pathogens is conducted under appropriate Biological Safety Laboratory (BSL) standards, the work can be performed safely. However, abundant evidence indicates that laboratory-acquired infections (LAI) still do occur, even under the highest BSL-3 and even BSL-4 standards.

Here we develop methods and criteria to identify occult LAIs and distinguish them from community-acquired infections. We then apply these tools to a test case.

Using these methods, we identify seven apparent LAI SARS-CoV-2 infections from June 2020 to January 2021, sequenced at the Clinical Molecular Microbiology Laboratory, University of North Carolina (UNC) Hospital, Chapel Hill, NC. While the laboratory from which they were acquired cannot be known with certainty, using the criteria herein, including the response to our inquiry and genome sequence comparison, all of the LAIs have a high probability of being SARS-CoV-2 variants being actively studied at premier coronavirus laboratories on the University of North Carolina Campus (UNC), ostensibly under BSL-3 conditions. We could find no public records of reported LAIs from the UNC during this period and conclude it is likely these LAIs were unknown to the laboratory itself.

The finding of seven likely occult LAIs in an eight-month period of time from what many consider the premier coronavirus synthetic biology laboratory in the US, or even the world, combined with the apparent failure to identify and report these LAIs by the laboratory or university at large, underscores a failure of current LAI regulations. Although current regulations have mandatory reporting, they do not have a process for finding and reporting occult infections.

Laboratory constructed synthetic viruses from UNC were watermarked with SNV T15102C/A and it was established by examining all GISAID sequence entries from North Carolina for the period of January 1, 2020, to January 31, 2021, a total of 1958 cases, that no sequenced human case had that SNV. This demonstrates the usefulness of such watermarks in synthetic coronavirus biology in determining the attribution, or lack thereof, for a community outbreak in the vicinity of the laboratory. We suggest such a process be considered as a mandatory step for all research involving significant human pathogens.

Given the high probability that the COVID-19 pandemic began with one or more scientists at the Wuhan Institute of Virology who became infected during synthetic virus engineering, and this report of undetected laboratory-acquired infections from synthetic clones and laboratory variants at the premier US coronavirus laboratories, it behooves us to pause all such research and develop robust biosafety standards, protocols, and regulations that can meet the heightened infectivity that synthetic viruses can achieve before resuming such research.

Before uploading the first version of this pre-print, the authors contacted the UNC sequencing lab personnel who submitted the suspected LAI cases to GISAID but received no response. Shortly after, the authors were contacted by GISAID's Washington DC office, relaying complaints from unnamed officials at the CDC and UNC about the preprint. GISAID threatened to revoke the authors' access unless metadata and sequence files were removed.

This pressure campaign to suppress inquiry, coupled with a lack of transparency from institutional actors, supports the hypothesis that these infections were potentially acquired in a laboratory setting.

Finally, this work highlights a regulatory conundrum: identifying occult laboratory-acquired infections that arise from laboratories conducting dangerous research requires the willingness for self-governance of the institutions in which the research is being conducted. As such, it is not amenable to an easy third-party or governmental oversight if the closed loop of accountability cannot be pierced.