February 20, 2016

NSABB and NAS Advance Toward Formalizing Policies on Gain-of-Function Pathogen Research

In 2016, the National Science Advisory Board for Biosecurity (NSABB) has returned to reconsider the issues regarding the approval, funding and oversight of experiments on pathogens that are engineered to contain mutations conferring elevated transmissibility in mammals and/or enhanced pathogenicity (virulence). This line of research has been called gain-of-function research (GOF). Such pathogens are studied to determine which genetic changes in a virus or bacterium confer attributes which create a more dangerous pathogen. Knowledge that a specific genetic mutation could confer a higher risk profile could theoretically allow more precise and knowledgeable public health surveillance of naturally occurring mutations. In addition, therapeutic countermeasures could be developed in advance of an actual strain appearing in the population. Nonetheless, these experiments could produce what have been called potentially pandemic pathogens (PPP) and are therefore controversial because of the possible release of a dangerous microbe, either by accident (biosafety) or design (biosecurity). The NSABB is charged with advising the federal government on bioterrorism-related scientific matters, the panel being created post-9/11. In the wake of controversial experiments published in 2011 and 2012 describing the creation of GOF H5N1 influenza viruses with enhanced transmissibility in humans, the NSABB has been working on formalizing a risk-benefit framework for determining whether certain experiments should be restricted or their funding limited. In 2014, a federal moratorium on the funding of GOF studies was imposed following a series of biosafety incidents at federal laboratories (some GOF studies have been allowed to resume, involving Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza). The NSABB is now conducting public meetings as the next stage in the deliberative process it outlined in 2015. The NSABB commissioned a formal risk and benefit assessment (RBA) from an outside contractor to provide the board with qualitative and quantitative information about the risks and benefits of conducting certain scientific studies. The NSABB also commissioned a formal study of the ethical frameworks that could be relevant to the formulation of official policy. In addition, a working group of the NSABB has published their review of the current issues. Their findings are as follows: 
Key Finding 1: There are many types of GOF studies and not all of them have the same level  of risks. Only a small subset of GOF studies - GOF studies of concern - entail risks that are  potentially significant enough to warrant additional oversight. 
Key Finding 2. The U.S. government has effective policy frameworks in place for managing  risks associated with life sciences research. There are several points throughout the research  life cycle where, if the policies are implemented effectively, risks can be managed  and oversight of GOF studies could be applied.
Key Finding 3. Oversight policies vary in scope and applicability, therefore, current oversight  is not sufficient for all GOF studies that raise concern. 
Key Finding 4. There are life sciences research studies that should not be conducted on ethical or public health grounds if the potential risks associated with the study are not  justified by the potential benefits. Decisions about whether GOF studies of concern should  be permitted will entail an assessment of the potential risks and anticipated benefits  associated with the individual experiment in question. The scientific merit of a study is a central consideration during the review of proposed studies but other considerations and  values are also important.  
Key Finding 5. The biosafety and biosecurity issues associated with GOF studies are similar to those issues associated with all high containment research, but a small subset of GOF studies have the potential to generate strains with high and potentially unknown risks (emphasis added). Managing risks associated with all high containment research requires Federal-level oversight, institutional awareness and compliance, and a commitment by all stakeholders to safety and  security. Biosafety and biosecurity are international issues requiring global engagement.   
Last month, the NSABB held an public committee meeting to review all of these recently commissioned reports, with the purpose of making progress in developing a formal roadmap for the federal government to use in deciding whether and/or how to support GOF experiments. The NSABB also invited public comments on the studies cited above. Criticism from other scientists include critiques of the GOF definition itself, objections to the comparatives used in the RBA assessment (e.g., 1918 pandemic influenza virus), a call for more clinician involvement in the process, as well as general objections to a lack of avenues for more public participation in the debate. As this deliberative process plays out over the next several months, the fate of the government-imposed moratorium will also be a consequence of the NSABB conclusions. The deliberative process continues: the second public National Academies of Sciences Symposium on GOF research will be held on March 10 & 11, 2016 and will include a discussion of the RBA study as well as NSABB’s preliminary findings and draft recommendations (the first symposium was held in 2014, see here). There will be an opportunity for the public to participate in the event as well as to submit questions online.

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