Playing With Fire: A Lab-Made Frankenstein COVID-19 Virus by Boston University

The creation of a new recombinant COVID-19 virus at Boston University, viewed as a “Frankenstein virus” by many, has raised a public uproar. This is not merely a risky gain-of-function experiment on “enhanced potential pandemic pathogens (ePPPs)”, it is a creation of an enhanced pandemic pathogen.  NO “potential” here.  

What is the rationale for this statement? What is the chimeric virus that we talk about here? 

A team of researchers at Boston University’s National Emerging Infectious Diseases Laboratories posted a paper on October 14, 2022, on BioRxiv, a preprint server for biology, revealing that they had created a lab-made COVID-19 chimeric virus with reverse genetics technology. 

Specifically, they’ve swapped the S gene of the spike protein in the original SARS-CoV-2 Wuhan strain with the corresponding S gene from the Omicron variant.  So, the lab-made Chimeric virus (Wuhan-Omi-S chimeric virus) has all the genes from the Wuhan strain, which is much more pathogenic than the Omicron strain, except the S gene, which is from the highly transmissible yet relatively mildly pathogenic Omicron strain. 

According to the preprint paper, the Omicron spike-bearing virus is able to effectively and robustly escape vaccine-induced humoral immunity just like the Omicron variant. In addition, unlike the naturally occurring Omicron variant, the Wuhan-Omi-S chimeric virus efficiently replicates in cell lines and primary-like distal lung cells. 

Furthermore, it has killed at least 80 percent of infected K18-hACE2 mice (a type of transgenic mice expressing human ACE2 receptors), whereas the mortality rate of the Omicron variant was zero while the Wuhan strain caused 100 percent death in two weeks in control experiments in the same transgenic mice. This 80 percent mortality in the mice model by the Wuhan-Omi-S chimeric virus was observed in a two-week period.  The paper did not provide any further observations on whether the surviving 20 percent of mice eventually died faster than the control mice group infected with Omicron variants.  

The defenders for this risky study stated that the chimeric virus product showed reduced pathogenicity (100 versus 80 percent mortality) when compared to Wuhan strains, so it is not a gain-of-function study.  However, this is an unjustifiably optimistic statement. The study did not provide any detailed or comprehensive pathology exam of different organs in the transgenic mice infected with the Wuhan-Omi-S virus. For example, do we know that this chimeric virus has the same neuropathogenesis as the Omicron or Wuhan viruses?  This study did not provide any data on that. 

In addition, although this experiment was presented as a swap of the S gene on the backbone of the Wuhan strain, it could also be viewed as swapping other viral genes on the backbone of the Omicron strain, considering the overall high genome homology among different variants of SARS-CoV-2 viruses. Rather than study individual gene motifs that might have influenced the Omicron variant’s pathogenicity,  researchers at Boston University instead swapped all the pathogenicity-related viral gene motifs/sites from the Wuhan strain into the Omicron strain.

Then, this study is a bonafide proven gain-of-function study: it makes the Omicron virus obtain more virulent factors, enhancing its infectivity and pathogenicity in in vitro and in vivo experiments.  And this publication did not reveal any study to test the transmissibility of the chimeric lab-made virus in animal models. Is the Wuhan-Omi-S virus more or less transmissible in animal models?  Can any of the researchers in this study 100 percent guarantee that this new chimeric virus is not more transmissible in different animal models, e.g. golden hamsters, ferrets, and primates?  

This study presented the main conclusion: “while the vaccine escape of Omicron is defined by 53 mutations in S, major determinants of viral pathogenicity reside outside of S.” However, it is a known fact that other genes outside S are involved in viral-host interactions at different steps of the viral life cycle and many genes outside S are relevant to viral pathogenicity in different tissues, organs, and animal hosts. So, by combining the pathogenicity-related components of the ancestral Wuhan strain and Omicron’s spike protein, the researchers would surely expect to create a virus that’s both highly deadly and highly transmissible. Even though it might be lucky that the final chimeric virus strains are less deadly and/or less transmissible than the Wuhan and/or Omicron strains, there is no guarantee that the degree of the risks or threats cannot be precisely controlled or assessed. The researchers at Boston University are intentionally playing with fire with clear knowledge of the risks involved. 

So, in essence, Boston University researchers created a lab-made Omicron variant with enhanced pathogenicity. As Omicron is a clear pandemic pathogen, taking over Delta and other COVID-19 virus variants, this study has created an enhanced pandemic pathogen. Not an “enhanced pandemic potential pathogen.”  

It is true that we don’t know whether this lab-made chimeric virus can out-compete natural omicron variants when co-circulating in human society. And defenders of this gain-of-function study also argued that similar recombinant variants existed early this year, the Deltacron, which contains a Delta variant backbone with an Omicron S gene. They argued that the Deltacron did not generate a pandemic wave and was quickly replaced with Omicron variants, and therefore, this experiment at Boston University did not generate additional risk. So, are these defenders arguing that humankind was simply too lucky and we need to create additional risks ourselves?  

This study is absolutely playing with fire and should be totally forbidden. It is unbelievable that Boston University allowed this research to be carried out. It is an ultimate failure of the bioethics committee that evaluates biomedical research projects at Boston University. 

Furthermore, this gain-of-function research project is partially funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID), which has denied its knowledge of these experiments. As the related grant documents and the communication between Boston University and NIAID are not currently released to the public, it is surely unverifiable whether NIAID was aware of these experiments during the whole process. Nevertheless, it suggests that the oversight mechanism to review grants related to “enhanced potential pandemic pathogens (ePPPs)”, set up by NIAID after the 2014 pause of all gain-of-function studies, did not work at all in this incidence. 

In December 2017, NIH lifted the funding pause and invited new gain-of-function (GOF) proposals. And by 2019, risky experiments with influenza viruses proposed by Dr. Yoshihiro Kawaoka of the University of Wisconsin in Madison and Dr. Ron Fouchier in the Netherlands were awarded NIAID funding to be continued. And Dr. Fouchier’s proposed experiments included identifying molecular changes that make flu viruses more virulent and mutations that emerge when H5N1 is passaged through ferrets. So, it appears that NIAID is okay with creating a more virulent H5N1 virus strain now. 

It appears that even if NIAID had set up a related oversight mechanism to review grant proposals related to ePPPs, the system would be completely futile when the grant reviewers or health agencies have a tendency to support gain-of-function studies in the name of pursuing a better understanding of viral-host interactions or pandemic controls. If the green light was granted for creating a more dangerous highly pathogenic H5N1 influenza virus, it is just a step forward to grant permission to create more virulent pandemic-ready SARS-CoV-2 omicron strains. 

So, can the public trust the government agencies such as NIAID to play a more effective regulatory role regarding such dangerous gain-of-function research projects? NIAID and Boston University should treat this incident seriously and immediately halt the operation in related laboratories. As the related researchers have mastered the reverse genetics technology, theoretically speaking, they can easily conduct more gain-of-function studies, including the creation of new viral strains. NIAID and Boston University cannot hide behind risk-mitigating protocols. Public oversight and transparency are essential to avoid repeatedly putting ourselves at great risk.  

If there are no competing virus strains, e.g. after the natural COVID-19 pandemic is over, this lab-made Wuhan-Omi-S chimeric virus will generate a new wave of the pandemic if it were to leak outside. In the last two to three years, the world was concerned that the COVID-19 pandemic originated from a disastrous gain-of-function lab-leaked incident at the Wuhan Institute of Virology. Are we trying to prove the lab-leak theory by doing it for real in the United States? Weren’t the lessons from the COVID-19 pandemic serious enough? 

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Dr. Xiaoxu Sean Lin is an assistant professor in Biomedical Science Department at Feitian College – Middletown NY. Dr. Lin is also a frequent analyst and commentator for Epoch Media Group, VOA, and RFA. Dr. Lin is a veteran who served as a U.S. Army microbiologist. Dr. Lin is also a member of Committee of Present Danger: China.