By Tsang Kwong-hoi and Wan Sui-Lun
Ever since the onset of the pandemic disease (COVID-19), caused by a new SARS-like coronavirus (SARS-CoV-2), questions such as whether the virus is from animals in nature, or whether it is from artificial recombinants of genome sections, carefully selected and copied from two or more species of coronaviruses, using bio-synthetic technology such as polymerase chain reaction (PCR) and DNA cloning to synthesize, and/or whether it is from laboratory leakage or directly from wild animal traders, are amongst some of the key questions which are still pending for answers.
According to official figures of newly confirmed cases released by Beijing, China seems to have gone through the most critical moment of the pandemic. But the danger of an unexpected next wave outbreak due to the reappearance of the old or appearance of a new coronavirus or both cannot be ruled out. Though legislation has been made to prohibit the trading of wild animals, but such legislation alone is grossly insufficient. For without investigating into the laboratories in Wuhan City, in particular the Wuhan Institute of Virology, all policy measures are deemed to be incomplete. People are still under threat.
As Wuhan Institute of Virology (WIV) is the single institute in the world that publishes the richest pool of research papers on coronavirus and has probably kept a large collection of viral species and considerable number of viral strains of coronavirus in their stock, it is important for the Government to launch investigations into this institute, checking the past work of its researchers, its safety control measures, the coronavirus samples they have kept, and the way they handle the tested animals. To facilitate such investigation, this article analyzes the work its key researchers have done in the last 14 years. A list of journal papers with key points highlighted is presented in a table as Appendix. This article aims at providing readers a more comprehensive picture of the potential bio-threats they are facing. (These journal papers can all be accessed through the respective links given in the Appendix.)
This article is an extension of two previous papers we have published in this Hong Kong Citizen News this March. These are: (1) "Wuhan outbreak the result of engineered virus in laboratories - Research papers in China point to this direction?" in both Chinese and English; and (2) "China's successful containment of SARS pandemics leakage in 2004 and its future implications" . In this article we will present our analysis under three sub-headings: (1) the bio-threat of WIV's research; (2) a historical account of how WIV's researchers acquired their knowledge on coronavirus; (3) the failure of their justification of vaccine and antivirals development?
Bio-threat of WIV's Research
Shi Zheng Li, the Director of the Centre for Emergence of Infectious Disease under WIV, and her colleagues have conducted several controversial experiments related with coronavirus. Examples are:
(1) In 2012, Shi's colleague has extracted 27 isolates of SARS-like CoVs from 117 samples of bats anal swab and faeces that they collected from a Yunnan bat cave. They divided them into seven groups. Each group of strains belongs to one species. Of these seven groups, one type of strains can directly infect human without going through any animal host, which they registered in a Gene Bank as WIV1 ( Wuhan Institute of Virology #1); and two types have a similarity of 95% to SARS-CoV, as compared with most other SARS-like CoVs which have similarities in the range of 76-92% in full genome comparison. They registered them as Rs3367 and SHC014. Later they used the SHC014 to create an artificial coronavirus (SHC014-MA15) which has high pathogenicity on human.
(2) In 2015, Shi joined with an American researcher, Ralph Baric of University of North Carolina, to generate an artificial coronavirus (a chimera), SHC014-MA15, by recombining a SARS coronavirus extracted from an infected mouse as backbone and a section of genome representing the Spike-protein of the SARS-like coronavirus, SHC014, which Shi's colleague found in 2012. This chimera were tested in vitro (test tube) and in vivo (live animals) and showed that it was capable of viral replication and could cause "robust refection to human airway culture and mice, particularly aggressive to aged mice". This chimera showed resistance to antiviral drugs, antibodies and vaccines which were effective in neutralizing the infectivity of MER-CoV and SARS-CoV. These vaccines and drugs were not only ineffective to this chimera but turned even more toxic toward aged mice.
The authors mentioned that further adaption of the full genome chimera has to be improved to make it more capable to replicate in live animal and human airway. However, it is restricted to continue with such type of experiments in US due to new restrictions from US Government fearing of the potential danger of such experiment to public health. The authors felt it disappointed because they believed continuing with enhancing the virulence of the chimera will help development of vaccines and antivirals ready to counter any future outbreaks. However, no one knows if further experiment to enhance the pathogenicity of the virus have been continued in China by WIV or not. In any case, the findings of this experiment remind us of the horrible effect of the Wuhan Coronavirus SARS-CoV-2 on aged people, its high infectivity, pathogenicity, drug resistance, and asymptomatic characteristic.
A historical account of how WIV's researchers acquired their knowledge on coronavirus
Researchers from WIV have involved in the research in coronavirus starting as early as 2006. A list of the work and research papers they have jointly involved and written with other scientists in China and abroad are listed in the Appendix. We can see that they have gradually increased their knowledge on coronavirus through the following experiments and findings (For details of the following, readers can refer to the Table in the Appendix of this article, Links to the original journal papers are given there) :
1) In 2008, it showed that they could already synthetically produced the S-protein from SARS and SARS-like coronaviruses and have tested this protein can infect human.
2) Between 2008 to 2012, Shi and her colleague have made several studies to identify the key functional areas of the coronavirus that are important to mutate to infect human through human cells. These functional areas are the S-protein and the receptor binding domain (RBD) on the envelop of the coronavirus. Today, the coronavirus attacking the whole world is one that can mutate very fast. This fast mutation is due to this RBD which is the most unstable region of the virus. Hence, this virus is difficult to deal with.
3) In 2011-12, they spent a year in a Yunnan cave and collected a rich pool of coronaviruses from bats' anal swabs and faecal samples. The whole pool of SARS-like viruses up to 27 different types of viral strains have been isolated from 117 pieces of these samples which enriched their coronavirus collection for their future use. From this collection, they discovered three new SARS-CoVs and four old ones. One of three new ones can directly enter into human cells to cause infection. They named it "Wuhan Institute Virus #1" (WIV1), the other two are less infectious but highly similar to the old SARS-
CoVs which they named as SHC014 and Rs3367. (See discussion in above sub-section (1)).
4) In 2015, they joined with R. Baric from America to create an artificial coronavirus, SHC014-MA15 by combining the S-gene of the SARS-like coronavirus (SHC014), with a SARS coronavirus extracted from an infected mouse as backbone (SARS-MA15). This new virion is capable to replicate itself efficiently and tested to be contagious. (See discussion in above sub-section (2)).
5) Their partners in US has warned them of the danger of this kind of GoF (Gain-of-Function) research in as early as 2015 and reiterated the warning in 2016.
6) Their partner Baric and others have experience to generate full genomes of the SARS- coronavirus in as early as 2003, which Shi ZL and her colleague failed to generate in their research in 2010. It showed that this use of synthetics technology to generate fatal coronavirus has long been practiced in US laboratories and their Chinese partners have acquired such technique from their US partners.
7) In 2017, they published a paper analyzed a family of rich pool of coronavirus they have discovered in the past years. They reviewed their previous over 13 years adventurous work in Yunnan locating bats habitats. They mentioned that they final identify a cave in Yunnan full of bat coronavirus varieties. They then spent 5 years in one cave there and have found a rich pool of coronavirus species. It is uncertain if their long years exposure to bat habitats and trips between Yunnan and Wuhan will cause them any infection or leaking of infected animals or virus samples to the public or inside the Institute?
8) In 2018, they reported that they have found that the mutation of DNA sensor in bats can help increase their unique capacity to serve as coronavirus reservoir.
9) In 2019, they wrote a review paper on their accumulated knowledge of CoVs and predicted that the next coronavirus outbreak will likely be in China. They suggested that early detection of outbreak and further investigation of CoVs have become urgent issues.
10) In 2020, they suddenly disclosed in their journal paper a SARS-like virus RaTG13 which they have registered in a Gene Bank in 2013, but have never discussed in their past papers. The importance of this viral strain is that it is phylogenetically closest to the new coronavirus SARS-CoV-2 that causes the present outbreak. Their similarity is 96.2%. It is high when compared with the next closest one, the SAR-like coronavirus SL-CoVZC45, which is only 89.1%. It is uncertain if they have still kept some other SARS-like viral species which are capable to infect human but not yet registered in the public Gene Bank.
Failure of their justification of vaccine and antivirals development?
From early on, the researchers of WIV stressed that their aim of research on coronavirus is to find vaccines and antivirus drugs to deal with possible future outbreak due to new attack of coronaviruses on human. But it seems that this has just been talking and justification giving in the last 14 years. In the last 14 years, they have published a rich pool of papers on the study of coronavirus and making collection of viruses from bats in their habitat. However, we have so far not seeing the department under Shi has published any research paper on vaccines and antiviral drugs countering the coronaviruses they have collected from nature and laboratory synthesized. This give us a big question mark as to what they have preached and what they have acted. We have seen warning of the danger of these experiment and virus collection and hear justification for vaccines and antiviral drugs development for 14 years. But the danger remains there, not getting lower but higher. Shi and her teammate's warning of the potential outbreak of disease caused by a new coronavirus with high infectivity and pathogenicity become real. But vaccines and drugs they promised are not being delivered.
Conclusion: High-level standing committee to study the cause without pre-set Restricted Zone
To conclude, for the investigation into the outbreak and to draw lesson for the formulation of preventive, response, and preparedness measures, one should not eliminate the possibility of laboratory leaking and/or inadequate laboratory management control standards and compliance. If we focus our investigation of the disease’s origin and the path of its spreading only on animals and ignore human factors, we will be misled and fooled by the animals.
Authors of this article
Bachelor Degree in Engineering, the University of Hong Kong, Master Degrees in Law and in Public Policy, the Australia National University.
Bachelor's degree in social sciences of the University of Hong Kong, Master's degree of Sophia University, Japan, previously stationed in Tokyo for an inter-government organization, Director of Greater China for an international accounting firm, member of the former Commission on Strategic Development of Hong Kong SAR Government.