The next pandemic is right around the corner. Let’s keep it there.
We need a UN International Agency to regulate and control research on pathogens with pandemic potential.
By Andre M. Goffinet, Helen E. Mundler, Sebastien Viret, and Roland Wiesendanger
It is our collective responsibility to ensure that technology is applied for the common good. To cite the most celebrated case, research in nuclear physics led to the discovery of nuclear fission and the development of nuclear reactors, but also to nuclear weapons. Nuclear technology is burdened with deep and obvious moral and ethical issues that led the United Nations to create the International Atomic Energy Agency.
The hugely disruptive Covid19 pandemic should trigger an analogous response addressing the risks inherent to research on enhanced pathogens with pandemic potential—hereinafter ePPP.
We propose the creation by the UN of an International Pandemic Pathogen Agency, the IPPA, defined thus:
The world’s central intergovernmental forum for scientific and societal cooperation in the ePPP Framework. IPPA will work for safe, secure and peaceful uses of ePPP Research, contributing to international health, safety and security, and the UN Sustainable Development Goals.
Arguably, there are enough international Agencies. Why do we need yet another one? Let us briefly present the context and arguments for creating such an agency.
Like other biomedical sciences and technologies, virology has made phenomenal progress in recent decades. This raises disturbing ethical questions, particularly concerning the creation of novel viruses and the manipulation of existing ones.
We are working scientists, bioethicists, and concerned citizens who are extremely concerned about the type of virological research activities known to specialists by three designations: “Gain of Function Research of Concern” (GOFROC), Dual Use Research of Concern” (DURC), and “enhanced Potential Pandemic Pathogens” (ePPP) research. These definitions lead to endless debate, which we propose to forestall by selecting the term ePPP, which seems increasingly favored, particularly in the US.
Research into ePPP strives to understand the way viruses pass from one species to another, adapt to become more transmissible and lethal, and interact with the hosts’ immune systems. Researchers seek to identify, classify and characterize all the viruses in the biosphere so better to predict which are the most likely to infect humans and generate pandemics.
Those are legitimate questions, the ultimate goal of which is to predict and prevent the transfer of viruses from wildlife to humans, that is to say zoonoses. The One Health concept—a transdisciplinary approach in which humans are considered as a component of the biosphere, the global network of all species and microorganisms, and their environment—promotes ePPP research.
The One Health concept makes sense. It is easy to explain, easy to understand, and easy to sell to media. However, like all research, ePPP work has potentially deleterious consequences, and these are too rarely discussed.
A typical ePPP project begins by collecting samples that may contain viruses from wildlife: mostly mammals and birds, sometimes other vertebrates and even invertebrates, more rarely microorganisms (fungi, bacteria, etc.) In principle, sampling is performed by specifically trained personnel, using appropriate methods for personal protection and handling animals. Plasma and other body fluids are processed or frozen for analysis in laboratories. Among the most important analyses are DNA/RNA extraction and sequencing, along with virus isolation, identification, and study by inoculation of different types of cells in culture.
Samples are studied in laboratories with four increasing levels of security: BioSafety Levels 1 to 4 (BSL-1-4), also called Pathogen levels 1-4 (P1-P4). For example, processing for DNA/RNA extraction inactivates viruses, and samples can then be studied at BSL-2 (sometimes even BSL-1) level, which is standard. Samples potentially containing active pathogens such as SARS-CoV-2 are studied in BSL-3/P3 conditions. When highly pathogenic viruses such as filoviruses (Ebola, Marburg) are suspected, work is carried out in a BSL-4/P4 laboratory.
As we write (autumn 2022), there are an estimated sixty to seventy P4 laboratories in the world. Some are not reported, or in construction, but it is reasonable to assume that they number less than one hundred. The precise number of BSL-3 laboratories is unknown, but estimates suggest some 1,500 worldwide, and they probably do not exceed twice that number.
There is a commensurate need for highly qualified personnel to operate those laboratories, an issue that is often overlooked. If ePPP programs are carried out as planned, many more P3 and P4 laboratories and competent personnel will be required to carry out the required experiments.
Past experience shows that accidents do occur even in the best operated facilities. For example, the SARS-CoV virus, which caused the 2002-2003 SARS epidemic in Asia, later leaked at least four times, leading to loss of life, but fortunately, only to limited and local spread. A SARS-CoV-2 leak was well documented in a Taiwan laboratory in 2021.
Recent revelations and publications show that highly risky ePPP experiments are being carried out right now, in P3 and P4 laboratories all over the world, some of which are near densely populated urban centers. The risk of accidental release associated with each individual experiment is low and will decrease with improved facilities, better operational practice, and experience. But the global risk will increase considerably with the proliferation of experiments and facilities.
A group of US experts recently outlined the risks posed by such pandemics not only to human health, but to our societies and economies. As Covid19 demonstrated, a virus like SARS-CoV-2—which is not overly virulent, with a lethality (Infection Fatality Rate, IFR) of around 1 percent, but which is highly transmissible—can hugely disturb the workings of our societies. During lockdown, Covid19 brought our society almost to a halt. Imagine if it had been only three times more lethal. Food and basic supplies would have become scarce, solidarity would have reached its limits, and dramatic societal troubles would have ensued.
Our modern civilization is extremely fragile. We must consider not only the damage a pandemic does to human health and the related shortages of medical personnel, hospital beds and medical supplies. It is imperative to factor into the equation the risks to societies and economies. One way to approximate this is to estimate the risk of a pandemic virus not just in terms of its danger to human life, but also in terms of its transmissibility. A relatively mild virus becomes high risk when it is highly transmissible, like SARS-CoV-2. This awareness is key to prevention and handling of future pandemics, and therefore to any evaluation of ePPP research programs.
Finally, modern international travel contributed to the ultrafast spreading of SARS-CoV-2. Any incident that occurs at any given location on Earth poses an almost immediate risk all over the world. Prediction and prevention are an international, not solely a national affair.
So, what can be done?
The US attempted to regulate risky ePPP experiments in 2012 following controversial experiments with bird flu viruses carried out in the United States and in the Netherlands. The Cambridge Working Group of scientists argued against such research, whereas another group supported it. Discussions within the Obama Administration led to a moratorium in 2014, which was applied laxly by NIH, NIAID and other grant agencies, and finally lifted in 2017.
The moratorium was replaced with the elaborate “Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens,” abbreviated as P3CO (Potential Pandemic Pathogens Care and Oversight). P3CO procedures have not been implemented zealously and are mandatory only in agencies that depend on funding from the Health and Human Services Department, such as the NIH, but not those conducted under the auspices of the Department of Defense or private NGOs. Nevertheless, it is worth emphasizing that the P3CO framework is extremely useful and can serve as model for future action. Other countries have proved less eager to control ePPP research than the US.
Intriguingly, apart from isolated attempts and alerts, there has been almost zero debate on risks and control of ePPP programs. Discussion is rare in the US and even more infrequent in the EU, UK, Japan, China, India and other countries, even in those with a sound scientific tradition.
The public’s alarm, and protests, have shaped nuclear arms and climate change policy. Thanks to many discussions about Covid19, even citizens with a limited scientific background now know enough to realize that there is indeed something to worry about. Yet ePPP research remains under the control of direct stakeholders, who have an unavoidable conflict of interest. The public must demand a more rational approach.
Professional scientists such as virologists, epidemiologists, and public health experts are the key stakeholders in this enterprise. But the debate must not be left solely in their hands, because the question concerns everyone. To paraphrase Georges Clémenceau: “Regulation of ePPP work is too serious a matter to be left to virologists alone.” The wider public and politicians must take a more active part.
A future IPPA must have international authority to inspect, monitor and regulate activities in virology and epidemiology laboratories in each member country. Its aim would not be to slow the pace of biomedical research or restrict academic freedom, but to foster cooperation that benefits everyone.
The IPPA would not be designed to interfere with activities in each individual country, a task best left to local governments and institutions, but to set guidelines with the force of law, ensure laws and rules are followed, report problems, and ultimately, if need be, recommend sanctions. The IPPA must be under UN jurisdiction if it is to act with legitimacy in all member countries. Ideally, it should avoid redundant bureaucracy.
The WHO might be suited to regulate ePPP, as proposed by the Lancet COVID-19 Commission. But the WHO lost credibility by yielding to political pressure during the Covid pandemic. Restoring confidence in its independence and competence would require significant reforms and a revised charter. A new UN Agency would be preferable.
Until the IPPA is operational, we need a temporary moratorium on this research, implemented as widely as possible, while responsible nations review the experimental alternatives, risk-mitigation measures, and the criteria for risk-benefit calculations.
The next pandemic is right around the corner. Let’s keep it there. Let’s urgently request a moratorium and the creation of the IPPA to control and regulate ePPP research.
It is a matter of life and death.
Dr. Andre M. Goffinet, Prof. em. Univ. Louvain, Belgium
Dr. Helen E. Mundler, Maître de conférences HDR (11e section), Université Paris-Est Créteil
Dr. Sebastien Viret, Chargé de recherche, CNRS, France
Prof. Dr. Roland Wiesendanger, Dr. h.c., University of Hamburg, Germany
This is an interesting proposal, but as always, the devil is in the details. The proposal that these investigators make would have been even better if they would have addressed the elephants in the room up front. The following issues occur to me as being particularly important:
1) Most of the work with dangerous pathogens is being conducted in China, the United States, the UK and to a lesser extent continental Europe. Much of it is funded by the NIH, DOD, the Chinese Government and the MRC and the Wellcome Trust in the UK. China has already proven during the COVID-19 crisis that it has no interest in transparency. Why should we think that China will be any more transparent with this new agency than it has been with the WHO or other governmental and non-governmental agencies trying to unravel the origins of SARS-CoV-2?
The United States hasn’t been particularly transparent either. Documents requested under the Freedom of Information Act have been redacted to within an inch of their lives. How does a new agency address this problem?
2) How is the issue of regulatory capture addressed? In the United States, at the inception of the crisis, Drs. Fauci (NIAID) and Collins (NIH) worked feverishly to squelch any suggestions of a lab origin for COVID and to this day, Fauci claims NIAID never funded gain of function research. Can we trust government officials like these to serve on the expert panel of the new organization? One of the leading experts in the world on bat viruses is the Bat Lady of Wuhan. Should she be a leader in the new organization? How about an excellent scientist behaving like a crude politician like Kristian Anderson? Should Professor Daszak be allowed to serve?
3) The WHO has not exactly distinguished itself during the COVID crisis but rather than creating a whole new bureaucracy shouldn’t we consider adding this portfolio to the WHO’s remit?
4) And speaking of bureaucracy, is it realistic to expect the United States, China or other nations to surrender any autonomy to this new organization? The authors suggest that rules issued would be mandatory and legally binding. Realistically speaking, is there any chance that the United States, China and the UK would surrender sovereignty to a new organization with substantial or even ample representation from European investigators when the majority of the research in question and most of the funding that supports it comes from outside of Europe. Respectfully, many Americans (including me) can’t help but notice that European intellectuals often fall in love with bureaucratic notions that lead to gridlock and sclerosis and end up doing as much harm as good (consider the EU itself to see what I mean).
The authors are to be commended for proposing something to address what is sure to be a growing problem. More regulation is desperately needed. I just wish that they had fleshed out their ideas a bit more.
Thank you, Doctors! That is an interesting proposal.