On March 10-11, 2016, the National Academies of Sciences, Engineering, and Medicine held a public symposium on potential U.S. government policies for the oversight of gain-of-function (GOF) research.1 This was the Academies’ second meeting held at the request of the U.S. government to provide a mechanism to engage the life sciences community and the broader public and solicit feedback on optimal approaches to ensure effective federal oversight of GOF research as part of a broader U.S. government deliberative process. Approximately 125 people attended the event in person, while more than 200 others watched the webcast.2
The first symposium, held in December 2014, examined the underlying scientific and technical questions surrounding the potential risks and
1 As described in the Draft Working Paper of the National Science Advisory Board for Biosecurity, “the phrase ‘gain-of-function research’ has become synonymous with certain studies that enhance the ability of pathogens to cause disease. However, gain-of-function studies, as well as loss-of-function studies, are common in molecular and microbiology and form the foundation of microbial genetics. Changes to the genome of an organism, whether naturally occurring or directed through experimental manipulations in the laboratory, can manifest as altered phenotypes as biological functions are lost or gained. Such loss- and gain-of-function experiments allow investigators to understand the complex nature of host-pathogen interactions that underlie transmission, infection, and pathogenesis and can help attribute biological function to genes and proteins. The term ‘gain-of-function’ is generally used to refer to changes resulting in the enhancement or acquisition of new biological functions or phenotypes” (NSABB, 2015a: 7).
2 The archived webcast, the presentation slides, and a complete transcript of the symposium are available on the project website at http://dels.nas.edu/Upcoming-Event/Gain-Function-Research-Second/AUTO-9-61-70-Q?bname=bls.
The second symposium focused on discussion of the draft recommendations regarding GOF research of the National Science Advisory Board for Biosecurity’s (NSABB’s) Working Group (WG). The recommendations are contained in a draft paper, which was released in December 2015 and discussed at an NSABB meeting on January 7-8, 2016 (NSABB, 2015a).4 It also included discussion of a formal risk and benefit assessment (RBA) commissioned to inform the NSABB’s work (Gryphon Scientific, 2015) and sessions devoted to current U.S. policy and the international developments that provide essential context for U.S. decisions. The public symposium did not attempt to develop consensus recommendations, but rather sought individual perspectives and robust discussion to inform the development of the NSABB’s final recommendations. The Statement of Task for the symposium may be found in Box 1-1.
This report has been prepared by the rapporteurs as a factual summary of what occurred during the symposium. The planning committee’s role was limited to organizing and convening the workshop. The views contained in the report are those of individual workshop participants and do not necessarily represent the views of all workshop participants, the planning committee, or the Academies. The report offers a summary of the key issues and ideas identified during the symposium, but it offers no consensus conclusions or recommendations and is intended to reflect the discussions during the meeting. In order to be as responsive to the charge as possible, it is organized thematically rather than chronologically so that ideas raised at various points in the symposium are grouped together. A complete transcript that provides additional information about the contents of the presentations and discussions is available on the project website.5
The symposium was opened by Ralph J. Cicerone, president of the National Academy of Sciences (NAS). His remarks reflected on the long
3 In addition to the summary report of the meeting, the archived webcast and the presentation slides may be found at http://dels.nas.edu/Workshop-Summary/Potential-Risks-Benefits-Gain/21666?bname=bls.
4 The NSABB WG’s paper, along with the commissioned papers, the archived webcast, and all the presentations at the January meeting, are available on the NSABB website at http://osp.od.nih.gov/office-biotechnology-activities/event/2016-01-07-130000-2016-01-08-220000/national-science-advisory-board-biosecurity-nsabb-meeting.
5 The transcript may be found at http://dels.nas.edu/Upcoming-Event/Gain-Function-Research-Second/AUTO-9-61-70-Q?bname=bls.
history of the NAS’s engagement with the complexities of balancing the risks and benefits of science and technology. Providing a neutral forum in which to discuss the scientific underpinnings of complex and controversial topics is one of the major missions of the Academies, and he urged participants to engage fully in the discussions over the two days of the symposium.
Margaret Hamburg, Foreign Secretary of the National Academy of Medicine, then discussed the evolution of oversight of so-called dual use research in the life sciences, from the 2004 report on Biotechnology Research in an Age of Terrorism to the current GOF discussions (NRC, 2004).6 Dr. Hamburg highlighted the role of the Academies in providing science advice to government. She indicated the importance of the GOF debate and the international nature of the issues and diseases involved. Dr. Hamburg noted that while the discussions at the symposium were focused on advice for the U.S. government, they would have implications for the global research enterprise. She underscored the importance of the symposium and its role in building on a wide range of earlier discussions on policy frameworks and approaches to addressing GOF research. This meeting, according to Dr. Hamburg, was an opportunity to look at those frameworks and approaches and identify desirable next steps. She identified a need to develop a strategic approach to support scientific progress while addressing the impacts for our societies.
Jo Handelsman from the White House Office of Science and Technology Policy believed this to be a landmark meeting, one that could direct future policy in important ways. She noted that the White House has focused on issues around GOF research for 18 months and recognizes the need to keep life sciences vibrant but also to protect safety and security across the globe. Officials had become engaged because of concerns around the creation of new pathogens, especially those with pandemic potential. The White House has also worked to address safety incidents at laboratories that raised public concerns over work with such pathogens (Holdren and Monaco, 2014). In response to these concerns, in October 2014 the White House announced a deliberative process and, along with it, a pause on federal funding for certain types of GOF research (White House, 2014a). Dr. Handelsman highlighted the importance of key exceptions to the funding pause to enable necessary emergency research to continue.
The NSABB was asked to draft recommendations for a conceptual approach for dealing with GOF research that would then be made available for public comment. As mentioned above, the Academies were asked
to convene two public meetings to facilitate a broad discussion of all the relevant issues: one to review technical developments, and a second to discuss the draft recommendations prepared by the NSABB as well as policy options for GOF. Dr Handelsman noted that the NSABB’s draft recommendations would be revised in light of the discussions at this symposium and in line with the public input they have received. Following this, an interagency process led by the Office of Science and Technology Policy will produce a policy that will provide federal oversight for GOF research and replace the funding pause.
Carrie Wolinetz from the National Institutes of Health began her remarks by stating that a robust life sciences research endeavor is critical to promoting public health and well-being in light of evolving threats posed by microbial pathogens. This endeavor will entail a certain amount of risk, she noted, requiring a thoughtful approach to reducing risk while taking advantage of the broad range of benefits. She commented that GOF research was a fundamental scientific tool to:
- Help define the nature of host–pathogen interactions;
- Enable assessment of the pandemic potential of emerging infectious agents;
- Inform public health and preparedness efforts; and
- Further medical countermeasure development.
Dr. Wolinetz stated that some GOF experiments had raised safety and security concerns about whether they could result in engineered pathogens capable of causing a pandemic if accidentally or deliberately released. There was also concern that information describing their development could be used by those with malign intent to cause harm through a deliberate release.
Dr. Wolinetz described the GOF deliberative process (see Figure 1-1). She recalled that the deliberative process included a pause in funding for GOF research involving influenza viruses and Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV).7 She highlighted the role that had been
7 “New USG [U.S. government] 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. The research funding pause would not apply to characterization or testing of naturally occurring influenza, MERS, and SARS viruses, unless the tests are reasonably anticipated to increase transmissibility and/or pathogenicity. In parallel, we will encourage the currently-funded USG and non-USG funded research community to join in adopting a voluntary pause on research that meets the stated definition” (White House, 2014a: 2).
played by the NSABB and recalled that it had been charged to advise on the design, development, and conduct of a risk–benefit assessment of GOF studies as well as to provide formal recommendations to the U.S. government on the conceptual approach to the evaluation of proposed GOF studies. During the process, the NSABB had also acted as a convening body. Dr. Wolinetz noted that the NSABB had received many valuable inputs to assist it in its work, including the report from the first Academies GOF symposium (NRC, 2015), the risk and benefit assessment conducted by Gryphon Scientific (Gryphon Scientific, 2015), and the ethics report commissioned from Michael Selgelid (Selgelid, 2015). Dr. Wolinetz concluded by noting that more input was being sought, for example, through the discussions at this symposium.
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