Home Bat Viruses, Gain-of-function Research, and National Security: Information from primary sources

 

Abbrevations: SARS: Severe Acute Respiratory Syndrome, SARS-CoV: the virus causing SARS, SARSr-CoV(s): SARS-related coronaviruses, SARS 2: Severe Acute Respiratory Syndrome 2; SARS-CoV-2: the virus causing SARS 2

Note: SARS 2 is officially referred to as COVID-19.

Disclaimer:  This is an attempt to get as many relevant facts as possible in order to understand this complex issue.  It will continue to be revised as more information is discovered.

INTRODUCTION

Although we might never know whether the second SARS virus escaped from from a Chinese lab or whether its crucial mutation was natural or created in such a lab, information regarding key choices of some American scientists involved is clearly set forth in some scientific publications. These publications cover their research aims and foreign collaboration choices, and their judgments about the dangers involved in inducing a certain type of mutation because of the risk of a pandemic should it escape into the community.  This article will attempt to trace the progress of this research as well as the attempts to resist it on the part of scientists who doubted its value and, in some cases, firmly believed that it should not take place because of these dangers.  These intentions, and their actions based on them, are enough to concern us.

The main issue here is gain-of-function research (GOF), which had been going on for years, and has generated a high level of controversy among scientists.  Selgelid (2016) defines GOF as science that "involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens".  The National Institutes of Health (NIH) says about this subject: "Certain gain-of-function (GOF) studies with the potential to enhance the pathogenicity or transmissibility of potential pandemic pathogens 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" (NIH: OSP, 2021), and the same source defines "Dual Use of Concern" as "life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security".  Its defenders justify it as a means of anticipating the causes of a possible pandemic and to provide insights into relevant vaccine development.  Of course, there are two possible causes of such a pandemic: 1) the natural transmission of a pathogen from animals to humans, and 2) the release of a novel pathogen from a lab, designed to be especially virulent and/or transmissable, whether by accident or design.  For reasons of natural security, it would make sense to confine this activity to the country that has chosen to engage in it and for it to proceed in secret.  But assumptions that only the former potential pandemic cause was worth considering have apparently paved the way for collaboration of American scientists with Chinese researchers, a step which is becoming increasingly difficult to defend.  That GOF has gone on at all, even within our borders, has generated controversy among scientists, so much so that then-President Obama initiated what turned out to be a three-year moratorium on such activity in 2014.

The focus of current interest is the Wuhan Institute of Virology, especially the CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, led by Zheng-Li Shi.  This is a Biosafety Level 4 (BSL4) lab. This institute has collaborated with a number of American scientists, most notably American scientists Peter Daszak of the EcoHealth Alliance and Ralph Baric of the University of North Carolina at Chapel Hill.  Related research also took place at two Japan universities (the University of Tokyo and Kobe University), at the University of Wisconsin at Madison, and at the University of North Carolina at Chapel Hill.

THE FACTS: MAINLY FROM SCIENTIFIC PUBLICATIONS

China had been carrying on research exploring the origins of the SARS virus, which had infected humans over a period from 2002 to 2004.  On April 26, 2004, Beijing's WHO official told a reporter that SARS struck China’s National Institute of Virology Laboratory (NIVL) in Beijing, part of China's Center for Disease Control, infecting two researchers two weeks apart, according to the Beijing WHO spokesperson; the lab was shut down and personnel quarantined, and a WHO inspection scheduled.  The two researchers, decribed as "postgraduate" and "postdoc", aged, respectively, 26 and 31, became ill on April 4 and 17.  A Hong Kong epidemiologist opined that this was most likely due to a lab accident, since the required Level Three guidelines were in place (Walgate, 2004).  In a May 19 update, the CDC reported that these two cases were part of a total of nine reported by the Chinese Ministry of Health, and another two were related to them: the mother of one of these two "graduate students" died of the disease, while a nurse treating the other infected the other five patients was the other fatality.  These cases were all reported by the Chinese authorities in the week of April 22-29, 2004; they reported no further cases since then, when they instituted surveillance measures "including health screening of travelers at ports of exit/entry".

EcoHealth Alliance (2018) reported that in 2005 its scientists "were among those invited by Chinese virologists and public health scientists to investigate the origins of the 2002-2003 SARS pandemic."  Then in 2007, the influenza A subtype H5N1 virus, killed 60% of the humans (fortunately few) who had contracted the disease from birds in several countries including China, causing great fear in the scientific community.  The next year, Ren et al. (2008) at the Wuhan Institute of Virology discovered that the SARS virus had a slight difference in the structure of the virus' spike protein, apparently a mutation.  As a result of analysis of the "structural fit" created by the mutation, they concluded that it accounted for the increase in the transmissability of the virus, causing it to infect humans.  This research did not appear to involve human-made changes to the virus molecule, although it might have been the inspiration for doing so by other people.

In June 2012, Imai et al., researchers mostly at the University of Wisconsin at Madison but also Kobe University and the University of Tokyo, published a study that described an "experimental adaptation" of an H5 haemaglutinin-possessing (H5HA) virus that made it more transmissable from a bat to a ferret via respiratory droplets.  This virus that was used as a backbone was similar in structure to the H5N1 virus, but much less virulent. 

Later that year, Anthony Fauci (Sep/Oct 2012), writing in the context of an earlier moratorium instituted in January of that year, acknowledged the ethical complexities associated with GOF research at length, but insisted that they should persist in developing measures that would not only assure the safety of this work, but ensure public acceptance of it.  He acknowledged the risk associated with GOF: "In an unlikely but conceivable turn of events, what if that scientist becomes infected with the virus, which leads to an outbreak and ultimately triggers a pandemic?".  Yet his point of view in favor of this type of research is clear: "Scientists working in this field might say—as indeed I have said—that the benefits of such experiments and the resulting knowledge outweigh the risks."  He went on to argue that the possibility of a pandemic caused by a virus would "occur in nature" provided a strong justification for GOF research.  He offered cautions about the necessity for getting the world informed and on board: "Public opinion (domestic and global) and the judgments of independent biosafety and biosecurity experts are also critical. If we want to continue this important work, we collectively need to do a better job of articulating the scientific rationale for such experiments well before they are performed and provide discussion about the potential risk to public health, however remote."  He concluded this publication with the statement that they should view the moratorium as "providing us the time and space we all need to work together and get this right, and it should be continued until we do so."  It is concerning that the last two of the five references given in this paper contain inactive links, titled 1) "United States Government policy for oversight of life sciences dual use research of concern", and 2) "The way forward in influenza research: a dialogue with the NIAID Director. Audio of presentation from the Sixth Annual Meeting of the Centers for Excellence for Influenza Research and Surveillance (CEIRS), New York, NY"; both were dated 2012, and the authors were, respectively, Fauci and the NIH.

Xu (2013), in a master's thesis cited by Rahalkar and Bahulikar (2020), reported that, in April and May 2012, Kunming Medical University, in Yunnan Province, treated six (in English translation) "workers in the same mine" for severe pneumonia and three of them died.  They had been exposed to bats and their feces in the mine; that university's zoology department determined that the bats in that mine were members of the Rhinolophus sinicus species, (in English translation) "from which was extracted SARS-like-CoV when Scientists in China were in the process of looking for SARS pathogen."  The abstract did not name the mine involved.  Xu, a student at Kunming Medical University, submitted this thesis in partial fulfillment of an (in English translation) "Emergency Medicine (Professional Degree)".

In 2015, Menachery et al., mostly affiliated with University of North Carolina at Chapel Hill, including Ralph Baric, but also including Zheng-Li Shi, of the Wuhan Institute of Virology, "generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone." They determined this both through in vitro and in vivo, i.e., in mice.  They also reported that "both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein."  They concluded that, because it was possible to create this resistant virus in the lab, existing viruses posed a great danger.  This article was prefaced with this text: "30 March 2020 Editors’ note, March 2020: We are aware that this article is being used as the basis for unverified theories that the novel coronavirus causing COVID-19 was engineered. There is no evidence that this is true; scientists believe that an animal is the most likely source of the coronavirus."

Ge et al. (2016), researchers mostly at the Wuhan Institute of Virology, but also at the Yunnan Provincial Key Laboratory for Zoonosis Control and Prevention, the Yunnan Institute of Endemic Diseases Control and Prevention, and the Mojiang Center for Diseases Control and Prevention  "conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013."  Yunnan Province is in the far southwest part of China, about 800 miles from Wuhan by plane. They detailed the different varieties of coronaviruses in the six species of bats represented, and concluded that "Coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens."  Two of these species were horseshoe bats (Rhinolophus genus), while two other genera (Hipposideros and Miniopterus) were also represented.  They did not cite or refer to the bat-associated disease discussed by Xu (2013).

In 2017, Hu et al. performed a detailed genomic analysis of the coronaviruses reported by Ge et al. (2016) in order to get some insights into the origins of the virus causing SARS ("SARS-CoV") by examining these "SARS-related corona viruses", abbreviated as "SARSr-CoVs".  They reported "the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China" in search of "the direct progenitor of SARS-CoV" after having disappointing results with bats in other caves.  This progenitor "may have originated after sequential recombination events between the precursors of these SARSr-CoVs".  They concluded: "This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases."

Wang et al. (2018) reported the discovery of antibodies in the serum of humans in the Wuhan area to coronaviruses detected in the entrance to the Tongguan mine in Jinning, Yunnan Province.  These serum samples were taken from "random blood donors".   These viruses consisted of 1) human coronaviruses, 2) Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and 3) Ebola 51 virus (EBOV).  EcoHealth Alliance (March 2, 2018) provided the link to this publication, reporting that "EcoHealth Alliance scientists, in partnership with Wuhan Institute of Virology and Duke-NUS, found SARSr-CoVs in bat caves near Jinning in Yunnan Province."  Five of the co-authors, Including Peter Daszak, were listed as being affiliated with the EcoHealth Alliance, and one with the "Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore".  Human testing revealed antibodies against "SARSr Co-V" in six people living nearby, though none recalled any symptoms related to SARS infection".  EcoHealth Alliance (2018) commented that this research "quite clearly show the value of continued biosurveillance in hotspot regions like Southeast Asia. If we know what viruses are out there in wildlife, and which people are getting infected, we have a chance to stop pandemics dead in their tracks."

REACTIONS AND DECISIONS

A U.S. Department of State document dated near the end of President Donald Trump's administration, i.e., January 15, 2021, warned of possible dangers posed by the Wuhan Institute of Virology, which it claimed demanded further scrutiny.  It stated, "We have not determined whether the outbreak began through contact with infected animals or was the result of an accident at a laboratory in Wuhan, China."   It reported that "The U.S. government has reason to believe that several researchers inside the WIV became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both COVID-19 and common seasonal illnesses."

There has been pushback against those asking for consideration of the possibility that the SARS-CoV-2 virus escaped from the Wuhan lab.  Now unnamed authors in The Lancet wrote in a February 19, 2020 letter, "The rapid, open, and transparent sharing of data on this outbreak is now being threatened by rumours and misinformation around its origins. We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin." 

Cyranoski (June 5, 2020) wrote that "SARS-CoV-2 came from an animal but finding which one will be tricky, as will laying to rest speculation of a lab escape."  He claimed that identifying the particular animal source would lay to rest "unsubstantiated theories — promoted by US President Donald Trump — that it escaped from a laboratory in China."   He added, "That the WIV, a laboratory highly regarded for its work on bat coronaviruses, is located in the city where the outbreak first emerged is probably just a coincidence. "

In an August 21, 2020 publication (Subbaraman, in Nature), "The NIH cancelled EcoHealth Alliance’s grant in April, days after US President Donald Trump told a reporter that the United States would stop funding work at the WIV"; the link in this quote is now dead. But it was reinstated in "early July", but with what Peter Daszak claimed were "absurd conditions" which were "politically motivated".  These requirements, mainly to obtain a sample for genomic sequencing and to arrange a second inspection of the relevant lab by U.S. federal officials, apparently generated Daszak's outrage because they were instituted to investigate the possibility that the virus escaped from that lab.  Subbaraman expressed support for this research by adding: "Scientific studies suggest that the SARS-CoV-2 coronavirus most likely originated in bats, and research on the topic could be crucial to identifying other viruses that might cause future pandemics."

On June 21, 2021, referring to the February 19, 2020 letter, an editorial in The Lancet stated, "In this letter, the authors declared no competing interests. Some readers have questioned the validity of this disclosure, particularly as it relates to one of the authors, Peter Daszak. "  It requested the authors to come forward with any previously unstated competing financial interests.  Daszak replied that his compensation came exclusively from EcoHelath Alliance and that "EcoHealth Alliance's work in China was previously funded by the US National Institutes of Health (NIH) and the United States Agency for International Development (USAID). Neither PD nor EcoHealth Alliance have received funding from the People's Republic of China."  He further stated that his work at the Wuhan Institute of Virology investigating SARS-CoV-2 origins was taken "undertaken as an independent expert in a private capacity, not as an EcoHealth Alliance staff member."  He also pointed out that the "NIH reviewed the planned recombinant virus work and deemed it does not meet the criteria that would warrant further specific review by its Potential Pandemic Pathogen Care and Oversight (P3CO) committee" and claimed that "EcoHealth Alliance's work in China is currently unfunded."  In general, he said that EcoHealth Alliance's work had been approved by "appropriate research ethics committees".

CONCLUSIONS THAT CAN BE DRAWN

1) Dr. Fauci favored the pursuit of gain-of-function research and pushed for the lifting of moratoriums on it, although he recognized its great potential political downside.

2) It makes sense that certain Chinese citizens were sent on suicide missions which involved close contact with sources of bat viruses; if they were virulent enough to endanger the lives of these individuals, these viruses were retrieved from them when they were hospital patients and sent to the Wuhan Institute of Virology, where experiments were conducted on them.  In view of this activity, it seems much less likely that uniquely dangerous bat viruses in the community were simply an inevitable Chinese idiosyncracy.

3) Some American scientists worked with Chinese scientists at the Wuhan Institute of Virology both in China and at several American universities performing experiments that involved mutating bat viruses.  Some were financed by an NIH subcontractor that claimed to have been given the green light by the NIH to continue with these studies. 

 

Copyright © 2021-2022 by Dorothy E. Pugh.  All rights reserved. 

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(Names of 27 authors withheld, untitled), February 19, 2020. Retrieved 31 Jul 2021 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30418-9/fulltext#%20

Editorial with reply from Peter Daszak, June 21, 2021. Retrieved 31 Jul 2021 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01377-5/fulltext

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