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Robust scientific review suggests: rivals US, China 'exposed' world to pandemic risks

By Bharat Dogra* 

It is a paradox that the point of research which became most controversial in the context of the COVID origin debate had a curious situation of a high-risk project in a Chinese lab being pursued with funds from the USA! This led to an even more curious situation in which powerful persons from both sides had an interest in covering up several inconvenient facts.
What is more, this is a reflection of the wider situation that both the rivals China and the USA, while by no means the only culprits, have been in a leading position in terms of exposing the world to pandemic risks. 
 The COVID origin debate has seen a division between those who emphasize environmental factors and those who emphasize lab-leaks. This deep divide in COVID origin debate should not obscure the wider reality that important global reforms are needed on both sides, yet not getting adequate attention. While the debate continues to rage, reforms relating to both possibilities should not be postponed till a final settlement of the controversy.
The natural transmission theory  draws attention to several aspects of increasing ecological degradation,  including indiscriminate deforestation,  possibilities of  risky contact between wild life and human beings, consumption of certain types of meat and animal products, unhealthy conditions in which some animals and birds are bred and slaughtered and in which some animals and their body parts are traded. There is obviously much need for reform in all these respects.
Reforms in all these areas, including restrictions and curbs accompanied by provision of alternative livelihoods for adversely affected people, are needed not just to reduce pandemic possibilities but also to check climate change and disasters, to protect biodiversity and animal welfare, to produce healthy food linked to sustainable, eco-friendly livelihoods. Linkage with pandemic increases the need for these reforms, but even if a linkage is not established with COVID-19, reform in these areas should still get strong support.
In this context the situation in some meat marketing areas of China and some other counties has been reported to be risky. At the same time the situation in some factory-farms where animals and poultry birds are kept in highly unsatisfactory conditions in the USA and western countries is also risky. 
The other possibility, gaining more acceptance at times, points to COVID-19 origin being linked to a lab-leak. Even earlier the scientific and safety basis of proliferation of work on very dangerous viruses, involving their lab-storage, transport and manipulation has been questioned from time to time, particularly as viruses are routinely being created in labs which are more dangerous than those that exist in nature. In this context while earlier some high risk labs in the USA had been more in the news, subsequently with the hasty setting up of some high-risk labs in China these too have attracted much controversy, particularly the one in Wuhan.
Is this work really so necessary as to be pursued on a large and increasing scale? Even if there are some potential benefits, are the risks and dangers still higher? Isn’t it true that earlier also bio-lab leaks have been excessive and often involved very dangerous possibilities? As such work has spread rapidly, and extrapolating from lab-leaks and related accidents taking place earlier, what is the mathematical probability of a very serious accidental release taking place once a decade, or even once in five years? 
Most of the recent increase in concern  is attributed to the  possibility that COVID-19 origin is related to the leak of a genetically engineered corona-virus from a virology lab in Wuhan, a virus which was in all probability engineered to be more harmful and infectious to human beings. This work was part of a project of gains-of-function research. Such research is inherently a risky venture, but has been justified by some experts on the ground that this will help in facing potential future pandemics and developing vaccines for them. This view of the benefits of such research has been widely contested.
Regardless of whether this is accepted as the most likely COVID-19 origin or not, the fact that this was a very high risk research cannot be denied. The worrying fact is that many such high risk projects, with military use linkages, are continuing unabated in several parts of world. Although several of these are called gains of function research, other scientists prefer to call some of this research as research relating to novel potential pandemic pathogens or PPPs.
Apart from raising bio-safety levels for all risk-prone research, a more basic issue is to find out what kind of research is inherently of very high risk category. Once such research areas and projects are identified, these should be given up.  Another reason for caution relates to the possibility of terrorists trying to misuse the knowledge emanating from such research, a possibility to which some senior scientists have also referred. 
A listing of avoidable types of research and experimentation has been made in a report titled Biotechnology Research in an Age of Terrorism, prepared by the National Academy of Sciences, Engineering and Medicine, USA:
  • demonstrating ways of making vaccines ineffective,
  • conferring resistance to antibiotics and anti-viral agents,
  • enhancing a pathogen’s virulence or making a non-virulent microbe virulent,
  • increasing the transmissibility of a pathogen,
  • altering the host range of a pathogen,
  • enabling a pathogen’s ability to evade diagnostic or detection modalities,
  • enabling the weaponisation of a biological agent or toxin .
Of course in practice these various possibilities may be mixed in a single project. Important narrow advantages relating to commercial, economic, career and military aspects are associated with this.
Clearly a time has come now to give long-overdue priority to safety concerns. When public concerns on this issue are high, now is just the right time to push for safety above all.
While the debate rages, reforms on both sides (natural transgression and lab-leaks) should go ahead, as all of these are urgently needed regardless of how the debate plays out.
The early stage of the spread of the COVID-19 pandemic was accompanied by serious concerns of the possibility of this being caused by a bio-lab leak in Wuhan, the place where the pandemic outbreak is believed to have occurred first. However it soon became more widely known that the project to which the alleged lab-leak was related was being funded by a leading USA government agency. 
The USA government agency sub-contracted it to a New York based organization which transferred the funds to the Wuhan based lab. Both at the level of contracting and sub-contracting very powerful US scientists and officials were involved. Previous warnings of safety risks in the context of such research had been received and were ignored by the funding agencies at both levels.
Hence to the extent that the lab-leak theory of COVID-19 origin was valid, the blame was to be shared by the USA and China. The controversial facts of the situation were known to many of the senior experts particularly virologists but they generally kept quiet about the funding aspect, although they were being increasingly approached by media-persons for more details on this issue.
On the other hand, several very influential scientists got together to prepare and issue statements which questioned and negated the entire lab-leak theory in strong terms. Although the scientific basis of these statements was in fact highly questionable, the fact that influential scientists had lent their names to these statements and that these had been published in journals of high credibility led to a rapid erosion of the theory of lab-leak in explaining COVID-19 origin. The initial phase of this theory was thus rather short-lived.  
Then emerged the big media story of the USA funding of controversial Wuhan research, which was presented as a somewhat bombshell kind of news, even though the main facts of this funding, which had continued for a fairly long time, were well-known to senior virologists and related experts.
When these facts came to the notice of many more people, of course there was much surprise and speculation, and some people in the west and the USA lost interest in pushing the lab-leak theory further.
The decline of the lab-leak theory was of course accompanied by the rise of the natural transmission theory, most likely in the form of transmission of bat corona viruses to human beings via an intermediary. This theory held ground for some time with growing strength. But soon some doubts started surfacing. A lot of time had passed and the intermediary involved had not been traced. Other expected confirmations were not occurring.
Then belated realization came that the statements which had debunked the lab-leak theory in the first place were organized to a significant extent by powerful scientists-officials themselves involved in the funding of the controversial Wuhan research. Even at a wider level, some of these very powerful virologists and related experts, who had gone around assuring the world that lab-leaks were not relevant in this context, were found to be themselves being big beneficiaries of huge funding for similar type of controversial, high-risk research concerning novel potential pandemic pathogens (PPPs).
This led to renewed interest again in the lab-leak theory, this time in a more balanced way. As numerous aspects including the details of the precise research being conducted in Wuhan were examined as also aspects of the COVID-19 pandemic, the possibility of a lab-leak was further strengthened.
Controversy regarding the research at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) again revived the concerns regarding continuation of certain types of high-risk biological research. As reported, a team of 14 scientists here developed a new strain of COVID-19 that killed 80% of the mice infected with the virus in a laboratory setting. NEIDL denied any serious hazards relating to this research but several critics raised serious issues.
Francis Boyle, Professor of International Law at the University of Illinois, a biosafety expert of repute who was also involved in framing laws relating to this, recalled how he and others were involved in a law suit to oppose the setting up of this high-risk lab facility but could not succeed in their effort. He said that such dangerous research should stop. Senator Roger Marshall, a doctor, stated that this research involved ‘lethal gain of function virus research’ that creates the ‘potential to kill more people than any single nuclear weapon.’
This research was partially funded by the National Institute of Allergy and Infectious Diseases (NIAID) which has come under pressure as it was involved earlier also in the financing of high-risk research. Dr. Emily Erbelding of NIAID has stated that the research team’s original grant application did not specify that the scientists wanted to do this precise work. The research group did not make it clear that it was doing experiments that might involve enhancing a pathogen of pandemic potential, this senior official from NIAID stated. 
The allegation that the researchers had held back critical information even from funders further raised speculations regarding their intentions, although NEIDL scientists firmly denied the risks for which their project has drawn much criticism. The wider question is that of bio-safety concerns, a hotly debated subject in recent times, which remains highly relevant even if the scientists involved in this particular context are able to offer a more convincing explanation regarding safety of their research. 
High level of concern has persisted among several senior scientists regarding unacceptably high risks relating to research which involves the creation of novel potential pandemic pathogens. These concerns were strong enough for the US government to impose a two to three year moratorium on some aspects of this research. This and some other related research is sometimes referred to as gains-of-function research. The US Government moratorium order defined such research as research that improves the ability of a pathogen to cause disease.
This order of the US government issued in October 2015 is titled ‘US Government Gain-of-Function Deliberative Process and Research Funding Pause on Selective Gain-of-Function Research Involving Influenza, MERS and SARS Viruses’. This order mentioned that such research has some benefits but also entails bio-safety and bio-security safety risks; hence the risks and benefits of gain-of-function research should be evaluated. Till a robust scientific review of this can be completed, a moratorium on US government funding of more risky aspects of such research was to be imposed. More specifically this much-discussed  order stated, “New US funding will not be released for gain-of-function research projects that may be reasonably anticipated to confer attributes to influenza, MERS or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.”
In addition this order said that the US government encourages others also (in the case of grants not funded by the US government) to join in adopting a voluntary pause on research that meets the stated definition.
A team of 14 Boston scientists developed a new strain of COVID-19 that killed 80% of mice in a laboratory setting
This order became a big discussion point among scientists. However the moratorium was not very complete as an escape clause had been left. This stated: An exemption from the research pause may be obtained if the head of the US funding agency determines that the research is urgently necessary to protect the public health or national security. This exemption was in fact used to continue to fund some research of the pause category even during the period of the moratorium. One such highly controversial project relating to altered corona viruses experimented on humanized mice was being implemented in the Wuhan Institute of Virology in China, a rare case of such research in China being financed by the USA. It will be very useful to know whether the exemption to continue this funding was made on grounds of public health or national security!
Those senior scientists who on the whole were pleased with the coming in of the moratorium were disappointed when the moratorium was lifted all too soon in December 2017 after the stated completion of the review process. 
Dr Mark Lipsitch, a senior epidemiologist, was  among those scientists who had welcomed the moratorium. He teamed up with Dr. Thomas V. Inglesby to write an important paper in mBio—Journal of American Society of Microbiology dated Nov-Dec. 2014 titled ‘ Moratarium on Research Intended to Create Novel Potential Pandemic Pathogens (PPPs)’. This paper while welcoming the moratorium stated that as some gain-of-function research can also be useful, it may be more relevant to talk of reducing the risk of novel PPPs. This paper stated that experiments which create the possibility of initiating a pandemic should be subjected to rigorous quantitative risk assessment and there should be search for safer alternatives. This paper regretted that despite the serious risks involved a rigorous and transparent risk assessment for this work has not yet been established. The authors emphasized that assessment should be completely unbiased and should be of a quantitative nature, not just qualitative. Any risk estimates should include estimates of the probabilities of accidental infection and extensive spread as well as estimates of the impacts of these events should they occur.
Further this paper went ahead of several other papers on this issue by specifically arguing that during the moratorium, progress should also be made in calculating the risks associated with potential deliberate misuse of PPP strains and with potential deliberate misuse of the information that is created and published following PPP experimental work. This calculation should take into account the possibility of deliberate theft and dissemination by either persons working within a lab or theft by those outside the lab. The paper pointed out that this possibility may be rare, but there have been precedents already of scientists using pathogens from their own labs to cause harm. Further the paper said that this assessment should take into account the possibility that some scientists may deliberately misuse the knowledge gained and published following the experiments by recreating the novel PPP strains in another laboratory using methods from published papers and then purposefully disseminate it.
Earlier a paper by Lynn C. Klotz Edward and J. Sylvester published in the Bulletin of Atomic Scientists had stated that SARS virus had already escaped from labs 3 times between 2003 and 2011. Even the security of the highest category BSL4 labs was not adequate as there had been 3 escapes from such highest safety labs between 1990 and 2011—one in Taiwan, one in England and one in the Soviet Union. This paper argued that assuming a rather low probability of accident, the possibility of accidental leak from the nearly 42 labs engaged then in live PPP research relating to three of the more dangerous viruses, escape of a dangerous virus from lab amounted to 80 per cent in at least one lab in 12.8 years, a very high probability indeed. 
Clearly there is a very serious threat from novel PPPs and efforts should be continued to restrict such research and reduce its inherent dangers in various ways. A worldwide moratorium should be considered, followed by an international commission of scientists and bioethicists, selected carefully to exclude those who derive personal gain from such research, to examine comprehensively, in an entirely unbiased way and with the precautionary principle as guide, all aspects of this controversial issue and to make recommendations based on this. The concerns raised following news regarding recent research at NEIDL should further alert the world to the urgency of important bio-safety reforms.
While the world may not reach common agreement on COVID-19 origin anytime soon, the chances of reaching an agreement on giving up such high-risk projects may be higher and should be pursued with the aim of avoiding any potential disasters. As is widely understood, although biological warfare and biological weapons are banned, some activity relating to these continues particularly at the level of the bigger powers. Research for this is required by them. As some research for defence from such weapons is permitted, this takes place in specifically military research establishments but in addition, for this to progress well, its linkages with several other research activities is needed or desired and therefore a lot of outwardly civilian research is actually promoted for its biological warfare linkages as well.
Anyway, important narrow advantages relating to commercial, economic, career and military aspects are associated and this is the reason why high-risk research has been promoted on a wide scale despite the dangers it creates for humanity and various other forms of life.
Clearly a time has come now to give the long-overdue priority to safety concerns in this context. At a time when public concerns on this issue are high, this may be most appropriate time to push for safety above all.
---
 *Honorary convener, Save the Earth Now Campaign. His recent books include “Planet in Peril”, “Protecting Earth for Children”, “Man over Machine” and “A Day in 2071” 

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