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Introduction

The potential misuse of advances in life sciences research are raising concerns about national security threats. The current report examines the U.S. strategy for reducing biosecurity risks in life sciences research and considers mechanisms that would allow researchers to manage the dissemination of the results of research while mitigating the potential for harm to national security.¹ We begin this report by tracing the development of ideas about the dissemination of scientific information, broadly defined, in the United States.

There is a growing tension between a scientific culture based on transparency and the need for secrecy to protect national security. While “most scientists would argue that the openness that characterizes much of the scientific research enterprise is the source of the extraordinary gains in scientific knowledge that have enriched us materially and intellectually,”² the ideal of a scientific culture based on principles of openness and transparency faces continuing challenges. One challenge relates to a concern that adversaries might take advantage of advances in science and technology for malicious purposes. This is particularly challenging in the biological sciences given recent dramatic advances, especially in the genetic engineering of pathogenic or potentially pathogenic micro-organisms, and fears that these advances could be exploited by non-state actors or terrorists. There is a recognition among some leaders in the scientific community of an informal social contract wherein “scientists as individuals and the international scientific community have a shared respon-

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¹ Numerous proposals for handling the dissemination of sensitive dual-use information have been suggested. See, e.g., R. A. Zilinskas and J. B. Tucker, “Limiting the Contribution of the Open Scientific Literature to the Biological Weapons Threat,” Journal of Homeland Security, December 2002 and National Research Council, Science and Security in a Post 9/11 World: A Report Based on Regional Discussions Between the Science and Security Communities (Washington, DC: The National Academies Press, 2007), doi:https://doi.org/10.17226/12013.

² National Research Council, Biotechnology Research in an Age of Terrorism (Washington, DC: The National Academies Press, 2004), doi:https://doi.org/10.17226/10827, pp. 99-100.

sibility, together with other members of society, to do their utmost to assure that scientific discoveries are used solely to promote the common good.”³ This premise is not, however, accepted by all scientific practitioners.

In today’s world of rapidly advancing science, where tools and technologies are more widely available than ever before and where the dissemination of scientific findings occurs through multiple channels and at multiple levels, developing policies for managing the dissemination of knowledge, tools, and techniques produced by scientific research has become ever more difficult.

The balance between minimizing the risks and maximizing the benefits of research requires consistent attention, as do the mechanisms for the oversight of such research. Any discussion of risk necessitates a consideration of uncertainty.⁴ In this context, it is important to consider whether, among the broader scientific community, there is appropriate awareness of the issues and policies related to life sciences research with the potential for dual use and whether limits placed on research and dissemination are reasonable and serve both scientific and security interests.

BIOSAFETY AND BIOSECURITY

Risks from biological research can result from lapses in biosafety and biosecurity. Biosafety policies focus on ensuring that research practices prevent laboratory accidents from creating risks of exposure to infectious pathogens for researchers, laboratory workers, and the general public. Biosecurity is related to the procedures that are intended to keep information or materials from individuals or groups seeking to use such information or materials for malicious purposes. While concerns about security risks arising from communication about scientific research fall within the realm of biosecurity, strong biosafety practices promote responsible research practices that provide a foundation for many elements of effective biosecurity. Moreover, research that raises significant biosafety issues may also prompt concerns about potential biosecurity risks.⁵

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³ International Council for Science (ICSU), Freedom, Responsibility, and Universality of Science (Paris: International Council for Science, 2014), p. 5. Available at http://www.icsu.org/publications/cfrs/freedom-responsibility-and-universality-of-science-booklet-2014/CFRS-brochure-2014.pdf.

⁴ Risk is the probability or threat of a negative occurrence: when conducting an assessment of risk, it is possible to accurately calculate the odds of a probable outcome. Uncertainty occurs where possible outcomes are known but probabilities cannot be attached to them. With any given problem (e.g., should a particular paper be published without redaction?), there is a sense of the outcome (or outcomes) to be avoided (e.g., an individual with nefarious intent using information about a particular pathogen to cause harm “to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security”). What isn’t known is the probability of a particular outcome.

⁵ The controversy over the publication of papers describing the means to increase transmissibility of the H5N1 influenza virus that led to the creation of several key U.S. policies to oversee DURC is

In general, the United States’ record with regard to the safe conduct of biological research appears solid, but data are incomplete. There are cases where laboratory workers have died,⁶ but the number of documented biosafety incidents that resulted in serious harm to human health has been very small. Similarly, only one serious biosecurity incident—the mailings of anthrax to members of Congress and the media in October 2001—has occurred in the United States. Nevertheless, given the size of the biological research enterprise, the diversity of research and research institutions, and the lack of a uniform reporting system, it is difficult to determine the full extent of lapses in biosafety.

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the most recent example of these connections. The National Science Advisory Board on Biosecurity (NSABB) recommended against publication of the two gain-of-function (GOF) papers because they presented a threat to biosecurity and “argued that ‘publishing these experiments in detail would provide information to some person, organization or government that would help them to develop similar mammal-adapted influenza A/H5N1 viruses for harmful purposes.’” However, “many national-security experts and scientists objected to the work simply because they believed it was not safe.” See G. Kwik Gronvall, H5N1: A Case Study for Dual-Use Research (New York: Council on Foreign Relations, July 2013). By the time of the White House announcement in October 2014 of a pause in funding for certain GOF experiments, biosafety and biosecurity concerns were receiving equal weight: “Gain-of-function studies may entail biosafety and biosecurity risks; therefore, the risks and benefits of gain-of-function research must be evaluated, both in the context of recent U.S. biosafety incidents and to keep pace with new technological developments, in order to determine which types of studies should go forward and under what conditions [White House, U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses, (Washington, DC, 2014a). Available at: http://www.phe.gov/s3/dualuse/Documents/gain-of-function.pdf].

⁶ The introduction to the 5th edition of Biosafety in Microbiological and Biomedical Laboratories (BMBL) [U.S. Department of Health and Human Services, Biosafety in Microbiological and Biomedical Laboratories, 5th ed. (Washington, DC, 2009)] includes a discussion of the data available about laboratory acquired infections (LAIs) and provides the information available at the time of publication (2009) about fatalities. For example, the BMBL cites studies by Pike and Sulkin [see S. E. Sulkin and R. M. Pike, “Survey of Laboratory-acquired Infections,” American Journal of Publich Health, 1951: Vol. 41, pp. 769-781; R. M. Pike, S. E. Sulkin, and M. L. Schulz “Continuing Importance of Laboratory-acquired Infections,” American Journal of Public Health, 1965, Vol. 55, pp. 190-199; R. M. Pike, “Laboratory-associated Infections: Summary and Analysis of 3921 Cases, Health Laboratory Science, 1976, Vol. 13, pp. 105-114; R. M. Pike, “Past and Present Hazards of Working with Infectious Agents,” Archives of Pathology and Laboratory Medicine, 1978, Vol. 102, pp. 333-336; and R. M. Pike, “Laboratory-Associated Infections: Incidence, Fatalities, Causes, and Prevention, Annual Review of Microbiology, 1979, Vol. 33, pp. 41-66] that identified 4,079 LAIs between 1930 and 1978 that resulted in 168 deaths. “During the 20 years following the Pike and Sulkin publications, a worldwide literature search by Harding and Byers [see A. L. Harding and K. B. Byers, “Epidemiology of Laboratory-associated Infections,” in D. O. Fleming and D. L. Hunt, eds., Biological Safety: Principles and Practices, 3rd ed. (Washington, DC: ASM Press, 2000), pp. 35-54] revealed 1,267 overt infections with 22 deaths” (see BMBL, p. 2).

“DUAL USE” RESEARCH

In the United States, policies related to security concerns about scientific research have traditionally focused on research results that have both civilian and military applications. Such research has come to be known as “dual use” research.⁷ Initially, emphasis was placed on certain kinds of research in the physical sciences and engineering, with nuclear physics as the classic example. During the Cold War, the United States and its NATO allies constructed national and international frameworks, including coordinated export control regimes, to prevent advances in Western science and technology from reaching the Soviet Union and its allies.

By the late 1990s, incidents such as the bombing at the World Trade Center and the Aum Shinrikyo attacks on the Tokyo subway raised the specter of “mass casualty terrorism,” including through the use of biological agents.⁸ The anthrax mailings in the wake of the September 11, 2001, attacks in New York City and Washington, DC, thrust bioterrorism into public awareness.

Earlier in 2001, concerns about biological research had been raised when researchers in Australia published the results of a study that led to the creation of a highly virulent strain of mousepox that was lethal even to mice that had been vaccinated for naturally occurring mousepox.⁹ This publication was followed by a paper that investigated the basis for the difference between the virulence factors in variola major virus, which causes smallpox, and vaccinia virus, which is used as a vaccine against the disease.¹⁰ While, to some, the research provided valuable information for those seeking to understand and treat infectious disease, to others these papers represented a type of open publication that could provide a “roadmap” for terrorists seeking to weaponize biological agents.¹¹

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⁷ In this case, dual use also could have positive connotations, where investments in military research and development could lead to valuable civilian “spin-offs.”

⁸ J. C. Gannon, “Viewing Mass Destruction Through a Microscope,” New York Times, Section E, p. 10, October 11, 2001, and D. Hearst, “Smart Bio-Weapons Are Now Possible,” The Guardian. May 20, 2001, available at http://www.guardian.co.uk/uk_news/story/0,3604,959473,00.html. It should be noted that the international community was also concerned about the discovery in Iraq, after the Persian Gulf War, of efforts by Iraq to develop biological weapons and the discovery, after the fall of the Soviet Union, that the Soviets had continued their offensive biological weapons programs after joining the Biological Weapons Convention in the early 1970s.

⁹ R. J. Jackson et al., “Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox,” Journal of Virology, February 2001, Vol. 75, pp. 1205-1210.

¹⁰ A. M. Rosengard et al., “Variola Virus Immune Evasion Design: Expression of a Highly Efficient Inhibitor of Human Complement,” Proceedings of the National Academy of Sciences of the United States of America, June 25, 2002, Vol. 99, No. 13, pp. 8808-8813.

¹¹ G. L. Epstein “Controlling Biological Warfare Threats: Resolving Potential Tensions Among the Research Community, Industry, and the National Security Community,” Critical Reviews in Microbiology, January 1, 2001, Vol. 27, No. 4, pp. 321-354.

In 2004, editors of major life sciences journals published a joint “Statement on Scientific Publication and Security.” The editors affirmed that “there is information that, though we cannot capture it with lists or definitions, presents enough risk of use by terrorists that it should not be published.” They continued by saying, “how and by what processes it might be identified will continue to challenge us, because . . . it is also true that open publication brings benefits not only to public health but also in efforts to combat terrorism.” The journal editors: (1) affirmed peer-reviewed journals’ responsibility to publish high-quality research in enough detail to permit reproduction of the experiments; (2) affirmed their commitment to dealing responsibly with safety and security issues that arise; (3) urged scientists and journals to develop processes to deal with papers that may pose security risks; and (4) affirmed that “on occasion an editor may conclude that the potential harm of publication outweighs the potential societal benefits” and that in these cases “the paper should be modified or not published.”¹² This challenge remains unresolved as there are no agreed-upon guidelines for determining when a paper should be modified or when it should not be published.

Around the same time, a National Research Council (NRC) report helped frame the debate about open scientific communication in the life sciences. Biotechnology Research in an Age of Terrorism, which became known as the Fink Report after study committee chair Gerald Fink, highlighted a concept of dual use research through its identification of the “dual use dilemma in which the same technologies can be used legitimately for human betterment and misused for bioterrorism.” The concept of applying the results of research undertaken for one purpose to other, sometimes controversial, ends was not new. But life scientists were much less familiar with addressing security concerns than their colleagues in the physical sciences and engineering.¹³ The Fink Report argued for preparedness and made a series of recommendations on the oversight of research that raised potential security concerns. The recommendations drew on existing regulations, provided guidelines, and leveraged the traditions of self-governance in the life sciences. The report stressed the need to grapple with potential dual use risks early in the research process:

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¹² Journal Editors and Authors Group, “Statement on Scientific Publication and Security,” Science Online, February 21, 2003, Vol. 299, No. 5610, p. 1149.

¹³ This is a result, in part, of the implementation of the Biological Weapons Convention and the ban on the development of biological weapons. The resulting cessation of acknowledged state biological weapons programs made these weapons appear less relevant to life sciences researchers.

With regard to publication, the report endorsed self-governance by the scientific community.¹⁵ It also endorsed the principles laid out in a national security decision document issued during the Reagan era [National Security Decision Directive 189 (NSDD-189)] which provided that, unless the work is classified, open release consistent with statutory requirements was the appropriate course.¹⁶ The report also noted that, to be effective,

In 2005, in response to recommendations made in the Fink Report, the U.S. government established the National Science Advisory Board for Biosecurity (NSABB) to assist the federal government in assessing the potential risks of life sciences research and to offer advice to policymakers, research institutions, and researchers about the conduct, oversight, and communication of sensitive research.¹⁸ As almost all research in the life sciences could potentially be considered “dual use” and to underscore that only a small set of experiments raise significant issues, the NSABB created a new category of research it described as “dual use research of concern” (DURC):

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¹⁴Biotechnology Research in an Age of Terrorism, pp. 116-117.

¹⁵ “Publication of research results provides the vehicle for the widest dissemination, including to those who would misuse them. The Committee believes strongly that this part of the system should be based on the voluntary self-governance of the scientific community rather than formal regulation by government.” See Biotechology Research in the Age of Terrorism,” p. 8.

¹⁶ NSDD-189 is discussed further herein.

¹⁷Biotechnology Research in an Age of Terrorism, p. 117.

¹⁸ Information about the National Science Advisory Board for Biosecurity (NSABB) may be found at http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/nsabb.

¹⁹Biotechnology Research in an Age of Terrorism, p. 17.

CONTINUING CONTROVERSIES OVER DISSEMINATION

Since its inception, the NSABB has been asked by a few federal agencies to review several manuscripts of concern (see Table 1-1). The manuscripts included a 2005 paper that described research conducted to reconstruct the influenza virus responsible for the 1918 Spanish Flu epidemic that claimed 40 to 50 million lives across the globe. When the manuscript was undergoing peer review for publication in Science, it was “recognized that the work might raise questions about the propriety of publication” and the authors were urged to consult experts at the Centers for Disease Control and Prevention, the U.S. National Institute of Allergy and Infectious Diseases, and the Office of Biotechnology Activities at the National Institutes of Health. Concerns were subsequently raised by the Office of the Secretary of the U.S. Department of Health and Human Services. This prompted a request for the members of the NSABB to review the paper.²⁰ The NSABB approved the paper for publication but suggested changes (see Table 1-1). The paper²¹ was then published with an accompanying editorial in Science, but without the textual changes recommended by the NSABB.²²

Another controversial 2005 paper provided a mathematical model of a potential bioterror attack on the food supply through the introduction of botulinum toxin into the milk supply.²³ The paper was approved for publication in the Proceedings of the National Academy of Sciences (PNAS) and the authors’ uncorrected proof was provided under embargo to reporters, but publication was delayed, and the embargo extended, in response to a letter from the Assistant Secretary for Public Health Emergency Preparedness of the U.S. Department of Health and Human Services. PNAS and National Academy of Sciences representatives met with government representatives to discuss their specific concerns about the paper. Following this meeting, the Council

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²⁰ See D. Kennedy, “Better Never Than Late,” Science, October 14, 2005, Vol. 310, No. 5746, doi:10.1126/science.310.5746.195, p. 195.

²¹ T. M. Tumpey et al., “Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus,” Science, October 7, 2005, Vol. 310, No. 5745, pp. 77-80.

²² In a subsequent issue of Science, Editor-in-Chief Donald Kennedy wrote an editorial about the government’s authority to restrict publication and the role of the NSABB specifically. “Government officials can advise,” he wrote, “and should be listened to thoughtfully. But they can’t order the nonpublication of a paper just because they consider the findings ‘sensitive.’ No such category short of classification exists, as the Reagan-era Executive Order National Security Decision Directive 189, still in force, makes clear. If a paper should not be published because of biosecurity risks, then it should be classified. Second, the NSABB should regard this first exercise as a helpful one-off and turn to its mandate of developing principles rather than making decisions on individual papers.” See D. Kennedy, “Better Never Than Late,” Science, October 14, 2005, Vol. 310, No. 5746, doi 10.1126/science.310.5746.195, p. 195.

²³ L. M. Wein and Y. Liu, “Analyzing a Bioterror Attack on the Food Supply: The Case of Botulinum Toxin in Milk,” Proceedings of the National Academy of Sciences of the United States of America, July 12, 2005, Vol. 102, No. 28, pp. 9984-9989.

TABLE 1-1 Manuscripts Reviewed by the National Science Advisory Board for Biosecurity (NSABB)

of the National Academy of Sciences elected to publish the article as originally accepted with a commentary by Bruce Alberts, President of the National Academy of Sciences. Alberts suggested that the paper should “be used by the NSABB as a case study to help guide both the government and the scientific community in further matters of this kind.”²⁴

Subsequently, in 2011, the NSABB reviewed two papers submitted for publication in Science and Nature, respectively, by U.S. government-funded research teams in the United States and the Netherlands.²⁵ The papers identified genetic mutations that conferred aerosol-based mammalian transmissibility to H5N1 avian influenza, a highly pathogenic strain. The papers were particularly controversial due to broader concerns about pandemic influenza. They became the focus of international attention and put a spotlight on DURC research and the NSABB’s role (see Chapter 2).

In all, the NSABB has reviewed six manuscripts of dual use concern between 2005 and 2012. While, to some, this suggests that there is not a significant problem, to others this suggests that problematic research is not being identified.²⁶ It is difficult to make an assessment either way as data on the number of papers rejected for publication (or modified prior to publication) on the basis of dual use concerns are not collected across journals.²⁷ Moreover, given the vital role that publishing plays in defining the success of a research career, there is a strong disincentive to impose restrictions at the time of publication. As such, leaving such decisions to the final stages of a research project is not ideal.

More recently, in 2013, researchers at the California Department of Health announced the discovery of a new strain of Clostridium botulinum. Botulinum

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²⁴ B. Alberts, “Modeling Attacks on the Food Supply,” Proceedings of the National Academy of Sciences of the United States of America, July 12, 2005, Vol. 102, No. 28, pp. 9737-9738.

²⁵ This particular case is particularly illustrative of the complicated nature of global research and publishing. One team was Japanese-American working in the United States with U.S. government funding. The other team was funded by the U.S. government but working in the Netherlands. The team based in the United States was seeking to publish in an American journal (Science). The team in the Netherlands was seeking to publish in a British journal (Nature).

²⁶ The reviews highlight the challenge in taking actions that might prevent the publication of beneficial research that contributes to the scientific literature or to public health and safety.

²⁷ See, e.g., D. Patrone, D. Resknik, and L. Chin, “Biosecurity and the Review and Publication of Dual-Use Research of Concern,” Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, 2012, Vol. 10, No. 3.

The American Society for Microbiology (ASM), publisher of multiple journals that seek to “advance the microbiological sciences” (see https://www.asm.org/index.php/journals), reports that of the manuscripts submitted to the ASM journals Antimicrobial Agents and Chemotherapy; Applied and Environmental Microbiology; Clinical and Vaccine Immunology; Infection and Immunity; Journal of Bacteriology; Journal of Clinical Microbiology; Journal of Virology; mBio; and Molecular and Cellular Biology, those that mention DURC agents are 0.04% annually. Of the manuscripts submitted to these journals annually, “the total number of manuscripts rejected solely for DURC is 0%.” Amy L. Kullas, Ph.D., Publishing Ethics Manager, Journals Department, American Society for Microbiology, communication with committee staff, March 15, 2017.

toxins are among those most dangerous to humans, and the researchers voluntarily opted not to release genetic information about the strain, as at that time, there was no known antidote for the newly discovered toxin.²⁸ Only later was it determined that the virulence of the strain could be blocked by available antitoxins.^29,30

In view of ongoing concerns about the communication of biological research results that might convey significant risks and in the wake of incidents (such as the 2001 anthrax mailings)³¹ in which biological materials were used for nefarious purposes, the United States has given significant attention to policies and practices that can enhance biosafety and biosecurity. A small but knowledgeable group of biological and social scientists, policy and security experts, and lawyers in the United States and overseas has become expert in various policy options to address biosecurity. However, most of the biological research community is not aware of these discussions and has not been actively engaged in them.³²

CHARGE TO THE COMMITTEE

Our committee was charged with reviewing DURC policy and the management of DURC. Its objective was to review possible mechanisms for managing dissemination of research findings that strike an appropriate balance between the value of openness in scientific research and the needs of national security. As such, this encompasses the roles and responsibilities of students, researchers, institutions, publishers, and the federal government in the conduct of research. While one might think of dissemination in terms of publication, the committee, with encouragement from the project’s sponsors, considered the management

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²⁸ A commentary on the decision not to publish the information was included in the journal along with the article (see D. A. Relman, “‘Inconvenient Truths’ in the Pursuit of Scientific Knowledge and Public Health,” Journal of Infectious Diseases Advance Access, October 7, 2013, Vol. 209, No. 2. Available at https://www.researchgate.net/publication/257535481_Inconvenient_Truths_in_the_Pursuit_of_Scientific_Knowledge_and_Public_Health.

²⁹ See H. Branswell “Researchers Keep Mum on the Botulinum Discovery,” Scientific American, October 22, 2013. See also http://www.cidrap.umn.edu/news-perspective/2015/06/study-novel-botulinum-toxin-less-dangerous-thought.

³⁰ Unlike previous examples, this particular case is an example of basic research that generated new knowledge that raised concerns about dual use.

³¹ Two sources of information about biosecurity incidents since 1900 are W. S. Carus, Bioterrorism and Biocrimes: The Illicit Use of Biological Agents Since 1900 (Washington, DC: Center for Counterproliferation Research, National Defense University, 2001) and K. Berger et al., “Biosecurity Risk Assessment of Acts Targeting a Laboratory” in Gryphon Scientific, Risk and Benefit Analysis of Gain of Function Research: Final Report—April 2016 (Takoma Park: Gryphon Scientific, 2016). Available at http://www.gryphonscientific.com/wp-content/uploads/2016/04/Risk-and-Benefit-Analysis-of-Gain-of-Function-Research-Final-Report.pdf.

³² Individuals working with select agents and toxins or in particular fields, e.g., influenza research, would doubtless have knowledge of such discussions.

of dissemination as occurring along a spectrum from idea generation to the formal publication of research results in journals.³³ The committee hopes that the current report and its findings will provide policymakers with baseline information for further deliberation. Consequently, it does not provide recommendations for further action.

The committee gathered information both at a public information gathering meeting on July 11-12, 2016, and at a public workshop on January 4, 2017. To assist in its deliberations, the committee commissioned papers on a range of topics including biosafety and biosecurity, international approaches to biosecurity, ethics, export controls, and current government policies on information control. These papers are available at https://www.nap.edu/catalog/24761 under the Resources tab. Authors were asked explicitly to consider the implications of restrictions on the dissemination of scientific information, and it was expected that contrasting viewpoints would be expressed during the course of interaction between the committee, the audience, and session moderators. In Chapter 2, the committee provides a review of current U.S. policy and the broader international environment. Chapter 3 examines challenges and opportunities identified during the committee’s meetings and in the commissioned papers. Chapter 4 offers findings to guide any reconsideration of DURC policy.

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³³ Points along the spectrum include, for example, the point where research is funded, the period when research is being conducted, the transmission of information about research through informal communications among researchers, presentations at meetings and conferences, training and teaching, and the circulation of draft manuscripts and pre-prints or other self-published papers through traditional or electronic means.