National Science Advisory Board For Biosecurity Research Articles

Stakeholder Engagement Workshop on the Implementation of the United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern: Workshop Report

This report documents the discussions of the 2017 Stakeholder Engagement Workshop on the Implementation of the United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern. It is not an official record of the Stakeholder Engagement Workshop. It was compiled to assist the research and policy communities as they consider updating U.S. Government policies on Dual Use Research of Concern (DURC). Neither the National Institutes of Health nor the National Science Advisory Board for Biosecurity (NSABB) produced a report out of the workshop, and it is hoped that this summary of the discussion, based on analysis of the videos of the workshop, will be useful for those interested in the development of the United States Policies on dual use research of concern.

Is regulation preventing the development of therapeutics that may prevent future coronavirus pandemics?

Is regulation preventing the development of therapeutics that may prevent future coronavirus pandemics?

Gain-of-Function Research: Ethical Analysis.

Gain-of-function (GOF) research involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens. Such research, when conducted by responsible scientists, usually aims to improve understanding of disease causing agents, their interaction with human hosts, and/or their potential to cause pandemics. The ultimate objective of such research is to better inform public health and preparedness efforts and/or development of medical countermeasures. Despite these important potential benefits, GOF research (GOFR) can pose risks regarding biosecurity and biosafety. In 2014 the administration of US President Barack Obama called for a “pause” on funding (and relevant research with existing US Government funding) of GOF experiments involving influenza, SARS, and MERS viruses in particular. With announcement of this pause, the US Government launched a “deliberative process” regarding risks and benefits of GOFR to inform future funding decisions—and the US National Science Advisory Board for Biosecurity (NSABB) was tasked with making recommendations to the US Government on this matter. As part of this deliberative process the National Institutes of Health commissioned this Ethical Analysis White Paper, requesting that it provide (1) review and summary of ethical literature on GOFR, (2) identification and analysis of existing ethical and decision-making frameworks relevant to (i) the evaluation of risks and benefits of GOFR, (ii) decision-making about the conduct of GOF studies, and (iii) the development of US policy regarding GOFR (especially with respect to funding of GOFR), and (3) development of an ethical and decision-making framework that may be considered by NSABB when analyzing information provided by GOFR risk-benefit assessment, and when crafting its final recommendations (especially regarding policy decisions about funding of GOFR in particular). The ethical and decision-making framework ultimately developed is based on the idea that there are numerous ethically relevant dimensions upon which any given case of GOFR can fare better or worse (as opposed to there being necessary conditions that are either satisfied or not satisfied, where all must be satisfied in order for a given case of GOFR to be considered ethically acceptable): research imperative, proportionality, minimization of risks, manageability of risks, justice, good governance (i.e., democracy), evidence, and international outlook and engagement. Rather than drawing a sharp bright line between GOFR studies that are ethically acceptable and those that are ethically unacceptable, this framework is designed to indicate where any given study would fall on an ethical spectrum—where imaginable cases of GOFR might range from those that are most ethically acceptable (perhaps even ethically praiseworthy or ethically obligatory), at one end of the spectrum, to those that are most ethically problematic or unacceptable (and thus should not be funded, or conducted), at the other. The aim should be that any GOFR pursued (and/or funded) should be as far as possible towards the former end of the spectrum.

US Policy Proposals for Gain-of-Function Research Raise Global Questions

Officials seem poised to accept the updated broad framework for assessing gain-of function (GoF) research proposals that the National Science Advisory Board for Biosecurity (NSABB) developed last year, making it the basis for federal policy. As part of a painstaking vetting of those proposals, NSABB members presented their draft guidance publicly under the auspices of the National Academy of Sciences (NAS) in Washington, D.C., in March, asking for feedback from scientific and science policy experts.

Zika Virus Focuses the Gain-of-Function Debate.

This year, the National Science Advisory Board for Biosecurity (NSABB) will be making recommendations to the U.S. Government regarding the ongoing saga of gain-of-function (GOF) experiments with highly infectious respiratory pathogens, such as influenza virus, severe acute respiratory syndrome (SARS) coronavirus, and Middle East respiratory syndrome (MERS) coronavirus.

DUAL USE RESEARCH OF CONCERN: DERIVATIVES OF 3-QUINUCLIDINYL BENZILATE (BZ)

Summary Dual Use Research of Concern (DURC) deals with the unintended consequences of and development and is particularly acute in the area of drug development. The United States National Science Advisory Board for Biosecurity (NSABB) has defined DURC as research that, based on current understanding, can be reasonably anticipated to provide knowledge, products, or technologies that could be directly misapplied by others to pose a threat to public health, agriculture, plants, animals, the environment, or materiel” (1). One particular receptor antagonist and glycolate anticholinergic compound (BZ, QNB or 3 -quinuclidinyl benzilate) was stockpiled by the United States as a non-lethal chemical weapon that incapacitates and severely degrades the capability of exposed individuals (2). Given time and medical treatment, combatants and non-combatants exposed to such incapacitating agents could recover without any long-term effects. The purpose of this review is to identify potential new and more potent incapacitating agents based on the structures of BZ or atropine using peer reviewed publications of new pharmaceutical agents. A number of peer reviewed studies have reported on compounds with effects observed at lower concentrations than or comparable to BZ suggesting that these compounds could also be developed as potential chemical incapacitating chemical warfare agents and represent good examples of the principal of Dual Use Research of Concern.

Will Heat of Debate Thaw Latest Freeze on Gain-of-Function Viral Research?

Last October, the White House imposed a “pause” on gain-of-function (GoF) research involving the influenza and two coronaviruses, SARS and MERS, pending a two-part review of safety and security concerns that is aimed at developing a new policy for dealing with such research. One part of that review continues within the federal National Science Advisory Board for Biosecurity (NSABB), while the second part took place more publicly last December during the symposium “Potential Risks and Benefits of Gain-of-Function Research,” convened by the National Academy of Sciences in Washington, D.C. This latter phase apparently helped persuade officials late in December to exempt some MERS projects from the pause, which otherwise remains in effect.

Rules of engagement.

The recent discussion about how to handle the results of security‐relevant “dual‐use” research has generated substantial polarization among stakeholders. In essence, there are two major options to prevent the abuse or misuse of research data: to restrict research itself so as to prohibit certain experiments, or to restrict the publication of research that could be abused by the military, terrorists or criminals. The case in question was the gain‐of‐function experiments by a research group in the Netherlands that created a strain of the H5N1 virus with increased transmissibility among mammals. The initial recommendation by the US National Science Advisory Board for Biosecurity (NSABB) was to allow only limited access to crucial data in the publications, which raised the ire of the scientific community who were concerned that their freedom of research could be curtailed in the name of security. When a Dutch district court eventually ruled in favour of the publication of H5N1 gain‐of‐function research—but upheld the requirement to apply for export licences [1]—it was obvious that the final judgment over restricting the publication of security‐sensitive research data will rest on the judicial system and neither on individual or collective self‐governance by the research community, nor advisory boards such as the NSABB. Indeed, a key problem in finding common ground between those who are concerned about security and those who defend the freedom of research is the unresolved issue over who will have to make such decisions and which procedural principles to manage the risks of publication should be applied. This paper addresses this issue by looking into the pros and cons of different risk management concepts that have been suggested to resolve the dilemma, such as risk–benefit assessment, the Precautionary Principle or the Proportionality Principle. Notwithstanding who will eventually have to make decisions about information security—scientists, regulators …

Consensus is needed at a global level concerning dual‐use research

Consensus is needed at a global level concerning dual‐use research

The H5N1 Moratorium Controversy and Debate

The pause in gain-of-function experiments involving highly pathogenic avian influenza virus to dissect mechanisms of mammalian transmission and virulence is a historic moment for science. The scientific community and the greater society that it serves are currently engaged in a vigorous debate on whether and how to carry out experiments that could provide essential information for preparedness against a pandemic of avian influenza. To foster discussion and to provide a venue to record the arguments for or against this moratorium, mBio has commissioned a series of views from experts in the field. In addition to these views, we note a need for a clear scientific rationale for gain-of-function studies and suggest that many of the current concerns involving such experiments can be circumvented by efforts to generate safer systems that could provide comparable information with much-reduced risk. In the winter of 2012, a group of influenza virus investigators announced in a joint letter a “voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals” (1). The pause came at a time of great controversy in science, which was caused by the recommendation of the National Science Advisory Board for Biosecurity (NSABB) to redact details from two manuscripts that provided molecular information on mutations which allowed H5N1 to become transmissible in mammals (2). Although the self-imposed moratorium was originally meant for 60 days, experimental work has presumably not resumed. In the summer of 2012, the U.S. Government proposed an indefinite continuation of the moratorium on gain-of-function studies with H5N1 viruses that could affect mammalian virulence and transmissibility until a consensus emerges on what type of experiments should be done and the level of containment that should be imposed. In this fluid environment, …

The "H5N1 publication case" and its conclusions.

The request of the National Science Advisory Board for Biosecurity (NSABB) to the editors of the scientific journals SCIENCE and NATURE not to publish details on the modified H5N1-virus has surprisingly not caused a discussion on censorship within the scientific community (NSABB, 2012a, P.1). This may show that science generally acknowledges the necessity to cut out sensitive data from research results in publications that may serve as a manual for weapons of mass destruction. In this article the policy of the NSABB and the reaction of the scientific community is discussed, as well as the meaning of censorship in dual use research and how an appropriate organisation of future surveillance in sensitive science fields could be organised: To guarantee future undisturbed work in sensitive science fields, the establishment of an internationally organised frame for scientists dealing with dual-use-research is suggested.

H5N1 infects the biosecurity debate

The generation of mutant H5N1 flu virus raised fundamental questions about the assessment and management of the risks of dual‐use biological research. Governments might well increase oversight and regulation to rectify the current shortcomings.

H5N1 research unleashed, almost

On Feb 10, we reported the tale of two research articles in which the authors had generated viruses based on highly pathogenic avian influenza H5N1 that were transmissible in mammals. The publication of these papers was put on hold at the request of the US National Science Advisory Board for Biosecurity (NSABB) on the basis of concerns about biosafety and bioterrorism. The board advised that redacted research papers reporting only the aims and conclusions without details of the methods and results be published, with more technical details being supplied to only a select group of influenza researchers. Avian influenza and the dual-use research debateSince the first human cases of infection with avian influenza H5N1 were reported 15 years ago, the disease has caused 344 deaths among 583 known cases—a case fatality of nearly 60%. Despite the highly lethal nature of this virus, it is very rarely transmitted from birds to people, and even less frequently, if ever, transmitted from person to person. Nonetheless, the possibility of the virus mutating or recombining with another to develop pandemic potential is a bleak prospect for public health. So it is not surprising that the news that two groups of researchers have purposefully generated H5N1 strains that are transmitted easily in aerosols among ferrets, a widely used model of human influenza transmission, has generated a fierce debate about the conduct and dissemination of dual-use research, as reported in this month's Newsdesk. Full-Text PDF H5N1 research put on holdIn December last year, the publication of two papers submitted to Nature and Science was put on hold after an unprecedented recommendation from the US National Science Advisory Board for Biosecurity (NSABB) that details of the methods and results be removed before the articles were released. The two articles contain details of experiments in which researchers had generated influenza A H5N1 viruses that could be transmitted from mammal to mammal—something natural mutations have failed to achieve. Full-Text PDF

Government Acts On Biosecurity

A long-awaited federal policy on oversight of dual-use research in the life sciences was issued on March 29 on a somewhat obscure government website (oba.od.nih.gov). The policy comes in the midst of controversy over the conduct and publication of two recent H5N1 avian flu experiments. The policy document was quickly followed by a statement from the National Science Advisory Board for Biosecurity (NSABB) citing that same policy for its new recommendation to publish—in a revised form—H5N1 avian flu research that involved key mutations of the virus. Previously, the federal biosecurity advisory board recommended that only heavily redacted forms of the research be published, citing dual-use and biosecurity concerns because the work adapted the virus to mammals and rendered it aerosol-transmissible ( C&EN, Feb. 6, page 6). “The data described in the revised manuscripts do not appear to provide information that would immediately enable misuse of the research in ways that ...

Creating a Mammalian-Transmissible A/H5N1 Influenza Virus: Social Contracts, Prudence, and Alternative Perspectives

Much has been written about 2 unpublished manuscripts submitted to Science and Nature that describe research studies in which mutant derivative strains of highly-pathogenic influenza A/H5N1 virus were created that can be transmitted by respiratory droplets or aerosols between mammals (specifically, ferrets) [1–23]. These manuscripts were referred by the US government to the National Science Advisory Board for Biosecurity (NSABB) for assessment of the dual-use research implications of this work and to make recommendations regarding the responsible communication of the work. The results of the NSABB risk-benefit review process and the subsequent recommendation that neither manuscript be fully communicated in an open forum are well-known to the international life sciences community. We propose to address this critical issue from both a historical perspective, the view through the rearview mirror, and from a future perspective, the view forward through the windshield. From the rearview mirror perspective, we review critical guidance from the life sciences community that predates the formation of the NSABB but clearly provides a relevant framework for our deliberations regarding the recent A/H5N1 virus research. We also consider existing work that the NSABB had completed prior to this recent research. From the windshield perspective, we consider 3 issues involving social and ethical principles that these 2 studies and any other future research efforts must address. We do not cover issues related to the A/H5N1 case-fatality rates or the potential benefits in sharing the entire research record of these studies for purposes of improving A/H5N1infection surveillance or countermeasure production. We posit that the case-fatality rates associated with A/H5N1 virus infection are worrisome and that the potential benefits at present are limited, but we suggest that other important matters deserve treatment here [8,19]. The concept of dual-use research of

International Debate Erupts Over Research on Potentially Dangerous Bird Flu Strains

TWO TEAMS OF SCIENTISTS HAVE identified genetic mutations that enable the H5N1 avian influenza virus to spread more easily among ferrets, which are often used as a model to determine whether an influenza virus might be transmissible among humans. Concerns about the potential for such findings to aid terrorists and the possibility of accidental release of the virus into the wild touched off a worldwide debate, delayed publication of the results, and prompted a temporary moratorium on such research. The controversial studies were both scheduled for publication in December. Findings from a team of researchers led by Ron Fouchier, PhD, of the Erasmus Medical Center in the Netherlands, were slated to appear in Science, and those from a team led by Yoshihiro Kawaoka, PhD, DVM, of the University of Wisconsin in Madison and the University of Tokyo, were to be published in Nature. However, concerns about potential biosecurity risks led the journals and authors to postpone publication. At that time, the National Science Advisory Board for Biosecurity (NSABB), which advises the National Institutes of Health on research that, while useful, might also pose biosecurity risks, took the unprecedented step of recommending that the researchers and journals omit some details from the papers to prevent individuals with ill intent from replicating the results. The publications were subsequently delayed. Both the research itself and the NSABB’s recommendations sparked a firestorm of debate about whether the merits of such research outweigh the risks and when sensitive information should be withheld.

Mammalian-Transmissible H5N1 Virus: Containment Level and Case Fatality Ratio

Dr. Casadevall serves on the NSABB, and the views expressed in this Editorial do not represent official policy or those of the NSABB. In addition, the views expressed in this Editorial do not necessarily reflect the views of the journal or of ASM . The life sciences, and the field of microbiology in particular, are in the midst of an unprecedented debate regarding the risks posed by the publication of two studies that report the generation of mammalian-transmissible H5N1 virus in the laboratory. The controversy was precipitated when the National Science Advisory Board for Biosecurity (NSABB) advised the U.S. government that the best course of action was to seek a redaction of the manuscripts to delete important details that could be used for nefarious purposes (1, 2). In a recent issue, mBio published pro- and anti-NSABB decision commentaries (3–6) with the goal of informing the debate and the hope that airing these views would lead to the best decisions. At the time of this writing the issue remains unsettled, and a fierce debate is raging in government and academic circles on the best course of action. Even with the question of how to publish these studies unsettled, two …

H5N1 research put on hold

In December last year, the publication of two papers submitted to Nature and Science was put on hold after an unprecedented recommendation from the US National Science Advisory Board for Biosecurity (NSABB) that details of the methods and results be removed before the articles were released. The two articles contain details of experiments in which researchers had generated influenza A H5N1 viruses that could be transmitted from mammal to mammal—something natural mutations have failed to achieve. Avian influenza and the dual-use research debateSince the first human cases of infection with avian influenza H5N1 were reported 15 years ago, the disease has caused 344 deaths among 583 known cases—a case fatality of nearly 60%. Despite the highly lethal nature of this virus, it is very rarely transmitted from birds to people, and even less frequently, if ever, transmitted from person to person. Nonetheless, the possibility of the virus mutating or recombining with another to develop pandemic potential is a bleak prospect for public health. So it is not surprising that the news that two groups of researchers have purposefully generated H5N1 strains that are transmitted easily in aerosols among ferrets, a widely used model of human influenza transmission, has generated a fierce debate about the conduct and dissemination of dual-use research, as reported in this month's Newsdesk. Full-Text PDF

Censoring Research Results

The methods and results should be redacted from two research papers describing controversial experiments on the H5N1 avian flu virus, concludes a federal biosecurity advisory board (Science, DOI: 10.1126/science.1217994). To support its conclusion, the National Science Advisory Board for Biosecurity (NSABB) cites the “dual use” nature of the research—meaning that it can be used for good or ill purposes—and the resulting threat to global human health, in the event that more dangerous forms of the virus somehow escape research laboratories or fall into the hands of evildoers. The two papers describe pathbreaking work on H5N1 by two independent groups, one in Wisconsin and the other in the Netherlands, and they have been accepted for publication in Science and Nature. Both journals, however, agreed to withhold publication because of widespread biosecurity concerns over the experiments to direct mutations of the H5N1 virus. These experiments resulted in airborne transmission between mammals and, ...

The H5N1 Manuscript Redaction Controversy

Scientists are an argumentative bunch, and science is no stranger to controversy. Since the beginning of the scientific revolution, science has witnessed and engaged in great controversies, including heliocentrism, the theory of evolution, the N-ray affair, and most recently the debate over climate warming. Prior controversies were settled with additional scientific study, which provided convincing data for one faction or the other. Today scientists are engaged in a new type of controversy involving the benefits, debits, appropriateness, and wisdom of redacting experimental data from scientific manuscripts on the grounds that the information could be used for nefarious purposes. This controversy was triggered when a government advisory committee known as the National Science Advisory Board for Biosecurity (NSABB) examined two manuscripts describing genetic changes that enabled bird flu virus (H5N1) to become transmissible in mammals. The NSABB then advised the U.S. Department of Health and Human Services that …