The symposium focused on identifying the principles and key issues that the assessments of potential risks and benefits would need to address (see Appendix A for a list of points made by individuals or during group discussions taken from the relevant chapters). In addition, policy implications were discussed at many points in the symposium, which Alta Charo, University of Wisconsin (UW)-Madison summarized in Session 9. She commented that in some cases the policy implications that one might draw from the discussions at the meeting are very specific to Gain-of-Function (GoF) research, while in other cases the implications are common to policy problems regardless of the substantive area.
Charo stated that to reduce risk with regard to biosafety requires a systems approach, which is very complex and requires representation and contributions from a very wide range of stakeholders, including people not ordinarily considered. For example, the presentation by Rebecca Moritz (UW), referenced the need to train the fire department to let the building burn. The discussion of the UW’s very complex and thorough system illustrates that. There are also other things not really focused on during the meeting, such as the need to be attentive to protecting nonhuman animals, the flora and fauna in the environment, and so on. This very complicated process is also expensive and resource intensive if the research continues while trying to optimize the mitigation of risks.
One question that falls out of that is, in light of the range and intensity of the necessary investments, do we really want to spend limited resources that way? Charo noted that some commenters spoke about how
it might be better to spend the money on more conventional public health interventions because the goal at the end of the day is to improve public health by preventing disease. In that vein participants heard that perhaps we should be looking at budgetary trade-offs. How much is being spent on this research and the protections it requires in comparison to how much it would cost to move that money into public health?
She stated that in this particular discussion (i.e., of GoF research) there is “lots of room for being a little bit more nuanced in trying to see how trade-offs would or could be made.” She also reminded the audience that the benefits and risks are not distributed in the same way. The risks of this research, to the extent it involves potential pandemics, will affect everybody, and yet the benefits will disproportionately go to people who are either personally better off or in wealthier countries because that is often where the healthcare system or economic access to healthcare is better. We need to pay more attention to making sure that the benefits are justly distributed and the science is beneficial for everybody. This is not something scientists can do by themselves, but it is something that is important to keep in mind to maintain public support. The “entire” public has to feel as though it has a stake in both the risks and the benefits.
Charo said that she was struck by the way in which the discussion would shift unpredictably between looking at the value of GoF research overall versus looking at its net benefit or its marginal increase in value when viewed as an addition to all the other types of research or public health efforts that are being done to address the same problem. For example, this appears in the discussions around whether GoF research would help make new vaccines versus GoF research as helpful—in addition to everything done in terms of monitoring—in making more precise predictions of which influenza strain should be worked on next year. The same applies to the discussion of risks. Pandemic potential is not something that is exclusive to GoF research, so the risks that are raised, such as Laboratory Acquired Infections (LAIs), are present for research with many other pathogens. Understanding the policy trade-offs might be helped if one could be clear about whether the discussion is about potential GoF-specific risks and benefits or marginal possible benefits as opposed to marginal increase in risks.
Charo noted that the policy options being discussed were basically in two camps: prohibition, with the fundamental question of which research should be banned, or regulation, with the fundamental question of how to regulate and whether control should be strict or light. The choice between the options will be heavily influenced by the presumptions one brings to the problem. Given that many of the experiments will inevitably fall in a “grey zone,” where there can be disagreements about whether their
potential benefits outweigh their potential risks, the chosen default position will determine whether they go forward. If the presumption is that one must prove that an experiment is needed, then anything in the grey zone is going to be prohibited. If the presumption is that research is free to proceed until the government or some other authoritative body has determined that it is unacceptable for some reason, then everything in the grey zone will proceed because the burden of proof will be on the government. Whoever has the burden of proof of making the case will have the more difficult task, and that is a fundamental issue for any policy.
In his opening remarks to the symposium, Dr. Harvey Fineberg had also addressed the burden of proof issue. When the original debate about publication of GoF research to make H5N1 transmissible between ferrets occurred in 2011, the burden of proof was clearly on the National Science Advisory Board for Biosecurity to limit or restrict or modify publication of those findings. With the new U.S. government pause, he thought the burden had shifted more emphatically than in the 2012 policy guidance toward those who would proceed with research to demonstrate that the safety and the potential benefits are such that the research is worthwhile.
Given the importance of the default for policy choices, it is not surprising that so much attention is being given to terminology and finding precise ways to describe what should clearly be prohibited or allowed. Charo stated that ambiguity in policy might very well yield a chilling effect, for example on the pipeline of young researchers entering a field if there is doubt about whether certain lines of work will be permitted. This is not an unfamiliar problem, but it is one to which one should always be attentive.
Charo set out three approaches she heard from the discussions during the symposium about how a policy for GoF research might operate. One possibility would be to create a threshold beyond which experiments are either prohibited or given special attention. Depending on one’s point of view, this approach can raise concerns about categories that are either too inclusive or not inclusive enough. Another would be a pure case-by-case approach, probably at the funding stage, with each of the factors considered important to making the choice of whether to allow the experiment to proceed reviewed independently, and then the overall project assessed holistically. The third approach would be “risk-based” regulation that reflects experience with a particular type of research, agent, or setting. The U.S. Select Agent program reflects this sort of approach.
Charo commented that the continuing diffusion and decentralization of science noted by Dr. David Relman and others posed challenges for the choice of approach. Most of the policy options that had been discussed were what she called a “point source” approach, such as that found in environmental law. For example, a factory might send pollutants
into a river. This is the point source of the pollution, and environmental laws will regulate the factory. It is a very detailed, hands-on regulatory approach, which is possible because there are a limited number of sites releasing a limited number of pollutants. “Non-point source” effluent has its own entirely different regulatory and policy challenges. The pollution of rivers and lakes from fertilizer runoff is an example of non-point source pollution. Many individual settings each add only a small amount of damage that collectively creates the pollution, and it is much more difficult to devise policies to regulate such problems.
Charo suggested that it will be essential for GoF research policy to figure out how much the challenge of decentralization is a realistic current problem. This is relevant for GoF research because there are continuing arguments about how readily someone could use the results to carry out bioterrorism or create biological weapons. As Relman’s talk and the discussions in Session 7 illustrated, this in turn depends on judgments about the security implications of greater dissemination of scientific information, such as through increasing international research collaboration and the growth of do-it-yourself biology and amateur science versus the barriers posed by the need for tacit knowledge and specialized equipment on the other.
Charo concluded her remarks with a series of special challenges posed by the global nature of GoF research.
- National cultures—to what extent is there agreement about the general balance between risk avoidance and innovation/research support?
- Governmental powers—which powers are traditionally used to regulate or prohibit research? Is it accomplished by placing conditions on receipt of funds, directly regulating personal activity, licensing institutions, etc.? Or is it done primarily through rules with force of law or by advice and voluntary actions?
- Relative resources—given that protective measures can be resource intensive (both equipment and personnel), and countries vary in their capacity, how much should be spent in order to achieve a minimum level of safety? Optimal level of safety?
- International governance—how should regulation or prohibition be managed in cases of research collaborations that cross borders?
In the discussions following various sessions and at the end of the symposium, additional points were made. Laurie Garrett, Council on Foreign Relations, commented that the symposium’s purpose of providing information for the NSABB made it difficult to consider the international context of the GoF issue, but it should not be ignored. In some less developed countries, there is general suspicion of certain types of research
carried out in Europe, the United States, and other developed countries. The World Health Organization is the only body that has the capacity to bring all the players together in a neutral format that recognizes the various perspectives of all cultures. But Garrett stated that it was her view that the Ebola epidemic has undermined the credibility of the WHO, so any governance effort for GoF research may require increased U.S. government attention to try to assist WHO.
A participant commented on the experience that had already accumulated through the first, voluntary moratorium by influenza researchers in early 2012 and beyond that through the debates and discussions of GoF research. One should take into account what has already been considered and tried as part of the policy process.
One person from the webcast reminded the meeting participants that regardless of what the United States ultimately decides to do or not do, it is important to be mindful that not all research is a global enterprise in other countries, some of which may be less well positioned than the United States and European countries in terms of sophisticated science and adequate investment to be able to carry out this research. Two other viewers raised questions about the roles of scientists and nonscientists, not only in the deliberative discussions that have been described as an important part of public engagement, but also ultimately among the panel or others who will be given the responsibility to make decisions. They questioned whether the scientific community alone is actually in a position to render the necessary judgments to create public confidence without participation from nonscientists.
Dr. Mark Denison commented on the importance of considering the regulatory burden that universities are already carrying when discussing options for GoF research policy. He stressed the need for alternatives to regulation. If there is agreement that pandemic pathogens or potential ones are in and of themselves significant and will continue to appear, then there is a need to think about resources within the laboratories and to supplement those resources to enable them to develop and share best practices within and across institutions that perform research. He also called for policies and resources to facilitate and encourage the development of scientists who are transdisciplinary in their understanding of pathogens, pathogenesis, social sciences, risk analysis, and biosafety.
Dr. Christophe Fraser echoed Denison’s comment about the importance of avoiding an increased regulatory burden or hindering the development of good animal models for SARS and MERS. At the same time he acknowledged what he considered a widely shared concern about a very small number of experiments that develop pathogens that are highly transmissible and highly pathogenic and where empirical evidence suggests there are issues related to containment measures.
In his final remarks Fineberg stated that he was very impressed with the thoughtfulness and respectful dialogue exhibited during the symposium in contrast to many of the other “so-called discussions” about GoF research. “I think there has been a lot of talking to rather than talking past in the course of this last day and a half … even more importantly, a great deal of listening to.” This met one of the hopes he articulated in his opening comments, to get beyond how some of the scientists who have been involved felt: as though they were treading water, a little bit like the movie Groundhog Day, where every day they had to wake up and relive, rehearse, and revisit the same arguments and discussions and debates, sometimes with the same people and sometimes with a slightly wider audience. He said that one of the key lessons is that it will be incumbent to develop a schema that identifies the research that is of particular concern and that an important contribution will be one that identifies and structures the nature of the considerations that should enter the problem.
If there is any area of commonality, said Fineberg, then it is around the acceptance of the legitimacy of the concerns that have been raised on all sides of this issue. What is much less clear is how to inform, evaluate, quantify, and weigh those various elements. Where are the points of contention, and where are the pivot points—those particular elements of estimation, understanding, projection, and possibility that, when entered into the final assessment, are really the ones that will make the most difference? That is where one has to then concentrate all of the ability one can to mobilize and manage the information that will inform and develop those particular aspects. As noted before, quantifying an assessment does not mean that a decision is reached because the whole idea of risk/benefit analysis is not tantamount to a decision. It is one piece in a balance of information that can inform decision-making. What comes out of it, if well done, will identify those points that really make the most difference in the final decisions and that will enable a set of activities to go forward in a way that gives confidence to the public as well as to the policy makers.
Fineberg closed the meeting by noting that the reality is that the virology community brings a special understanding and depth of experience to these particular problems, while the larger scientific community brings a perspective of understanding what is at stake for science. However, those who are part of the security community have a perspective of understanding of what it takes to live securely, what is at stake internationally, and what it may take globally to establish a higher degree of harmony in the conduct of the global research enterprise.