“Designer Biology” and the Need for Biosecurity-by-Design

By Dr. Diane DiEuliis, National Defense University and Dr. James Giordano, Departments of Neurology and Biochemistry and Cyber-SMART Center, Georgetown University

Homo faber suæ quisque fortunæ

(humanity creates its own destiny)

Appius Claudius Caecus

Synthetic biology has a number of definitions. Most recently, the National Academies of Sciences (NAS), in an effort to develop further understanding of risks associated with synthetic biology capabilities, defined the field as “concepts, approaches, and tools that enable the modification or creation of biological organisms.” The NAS notes that, ‘While the goals of synthetic biology are beneficial, these capabilities also could be used to cause harm.”² We concur; to be sure, synthetic biology can – and we believe rightly should – be regarded as dual-use technology, with risks that extend beyond the purview of current biosecurity controls. As originally conceived, biosecurity measures tend to be focused upon controlling access to pathogens that bad actors could use for harm; given the emphasis on physical security, such protocols were considered as policies of “gates, guns, and guards”. However, synthetic biology now affords capabilities to modify or create dangerous microorganisms, including viruses, as evidenced by synthetic development of polio,³ influenza viruses (and notably the 1918 strain),⁴ and horsepox, among others. While somewhat more technically difficult, engineering harmful bacteria also poses a dual use threat. While such syntheses are typically undertaken in controlled, secure laboratory environments by experienced research personnel, these endeavors are exemplary of the expanding capabilities – and power – of synthetic biology, which could be misused. Of particular concern in this regard is the growing number of synthetic DNA providers that have made molecular tools and substrates available to users worldwide. Recently, there has been vigorous debate regarding the possible origins of the novel coronavirus (viz -, that it could have been created or modified in a research laboratory, and then accidentally disseminated into either the wild and/or human populations). While this remains conjecture, it nonetheless represents a viable scenario; as the synthetic creation of SARS-CoV-2 was readily accomplished at the start of the pandemic for research purposes, thereby emphasizing the rapidity with which certain goals and products of synthetic biology creation can be achieved and produced. Equally important is that tools and methods of synthetic biology are increasingly available to an expanding group of users (e.g.- public scientists accessing direct-to-consumer resources and services, and the do-it-yourself [DIY] community) that is outside of the regulatory provenance of academic and/or governmental research institutions.

The increasing use of synthetic biology is influential to international bioeconomic activity.⁵ We have previously described how biological data, (“biodata”) are primary drivers of discovery and innovation in the life sciences.⁶ With the iterative convergence of biotechnology and digital technology, synthetic biology offers capabilities to engineer living organisms and cell-free systems for the production of high value chemicals, materials, foods, and/or other commodities (i.e.- “designer-biology”, or synthetic “biodesign” abilities). Synthetic biodesign may leverage natural pathways in a variety of microbes, algae and fungi, and/or enable transplantation of genetic pathways into different organisms, which can then be utilized for industrial scaling (irrespective of whether such industries are engaged for dual-use means and ends). This expansion of synthetic biology capacities generates security risks. For example, in silico biodesigns can be hacked in acts of corporate and political espionage; and automated, digital manufacturing systems can be accessed, manipulated, and disrupted to incur economic or social damage. As revealed by attempts at purloining many countries’ vaccine platforms during the COVID19 pandemic,^{7, 8} purposive manipulation of synthetic biology processes can pose public health and national – if not global – security concerns.

Obviously, the aforementioned risks provide ample reasons to expand traditional biosecurity configurations; yet, we also opine that there are special concerns that must be addressed regarding the both the use(s) of human biological data, and synthetic biological products and tools in humans.⁹ We argue that such concerns are real and present, given the use of synthetic biology (and force-multiplying efforts in big data and machine learning technologies) in the rapid development of COVID vaccines, gene editing, and other novel interventions.¹⁰ Our concerns certainly relate to issues of relative uncertainty of near- and far-term effects, inequities of distributive justice, and the requirements – and vulnerabilities – of massive and diverse data.¹¹ But we assert that further consideration, concern, and preparedness is warranted in light of the very real possibility, if not probability, that synthetic biological techniques and technologies can and will be employed in kinetic and/or non-kinetic disruptive engagements, and other exercises of national (or non-state actors’) power.¹²

In sum, it is evident that synthetic biology is rapidly advancing, and in ways that we believe to be well beyond the oversight and controls of traditional biosecurity models.^{13, 14} Therefore, we advocate flexibility to adapt current practices – and develop others anew – to remain apace with the capabilities, concerns, risks and threats of ongoing developments in both synthetic biology and its possible uses on the global stage. A first step is to employ “biosecurity by design”: to establish strategic biosecurity protocols and methods within the scope, tenor and trajectories of synthetic biology research programs at their inception, and iteratively so as to adapt to changing conditions and competences (of both synthetic biology and security domains). Risk assessments should be conducted “early and often“ to determine risks to human, animal and/or plant health, or the environment at-large. Such assessments must focus upon the risks of bioengineering a variety of organisms, not merely pathogens. It is not the aim to impede progress, however, and we have called for the need of a “homo faber” approach (see also, above) as espoused by the philosophers Hannah Arendt¹⁵ and Max Scheler¹⁶ in which insight, reflection, projection, scrutiny and prudence are inherent to and accompany each and every effort of enterprise.¹⁷ Because risk assessments have long focused upon pathogens and pathogen controls, we believe that risk assessment frameworks must broaden so as to go beyond evaluating select agent programs, and should be extended to encompass academic, industrial/commercial and governmental pursuits.¹⁸ Given the fairly rapid development and engagement of novel manufacturing platforms in and for the commercial space, we believe that perhaps the more pressing need is assessment of risk – and threats – within the synthetic biology industry. Biosecurity experts can and should be constituent to liability and risk assessment programs that employ biosecurity-by-design to evaluate commercial activities. As a culture of biosecurity-by-design becomes more widespread, shared forums for best practices, and partnerships of biotechnology and biosecurity endeavors established to create and maintain a posture of preparedness and readiness should become the norm (as opposed to reactive efforts in the aftermath of a biothreat or public health events). Adapting and employing biosecurity paradigms to multi- and international settings and contingencies will be challenging, and we are encouraged by groundwork activity at recent Biological Toxin and Weapons Convention (BTWC) meetings directed toward review and analysis of extant risk assessment models.¹⁹ Biosecurity management can become more relevant through the adoption of best practices, that are sensitive and responsive to international enterprises and standards. An example of such biosecurity best practices exists within the International Gene Synthesis Consortium of companies, which has created and shares a commitment to security screenings of orders and customers for indications of using products and services for nefarious intent,²⁰ and the World Economic Forum has provided suggestions for biosecurity screening models that could be utilized in multinational settings.²¹ While these efforts are indeed promising, and could be leveraged as templates for future success, an unresolved issue is what ethical norms, standards, and guidelines should be used to guide the ways that potential risks and threats can and should be addressed and mitigated.^22,23 The differing histories, cultures, politics, needs and values of nations engaged in synthetic biology pursuits generates challenges – and opportunities for a synthetic, multi-perspectival, multi-ideological (i.e.-syncretic) cosmopolitan approach – in international ethical discourse, debate deliberations, and direction.^{24, 25}

In conclusion, it is evident that synthetic biology will influence and be influenced by the near- and future-term constructs and conduct of the global bioeconomy. Acknowledging the multi-dimensional hegemonies that synthetic biology capabilities render is important to recognizing and identifying biosecurity risks and threats that arise in and from the field, its practices, and its uses. Recognizing such risks and threats obligates a preparedness approach to enabling benefits, while concomitantly and proactively addressing, meeting, mitigating and/or preventing risk, threat and possible harms. We argue that such dedication is essential to efforts to manifest and sustain a positively valent destiny in an ever more biotechnologically shaped future.

Acknowledgement: The views and opinions presented in this article are those of the authors and do notnecessarily reflect those of the US Department of Defense, National Defense University, and/or the institutions and organizations that support the authors’ work. JG is supported by federal funds from Award UL1TR001409 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through the Clinical and Translational Science Awards Program (CTSA), a trademark of the Department of Health and Human Services, part of the Roadmap Initiative, “Re-Engineering the Clinical Research Enterprise”; National Sciences Foundation Award 2113811 – Amendment ID 001; and funding from the Henry Jackson Foundation for Military Medicine; Aesklepios Biosciences; and Leadership Initiatives.

Article End Notes

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About the Authors

James Giordano, Ph.D., is Professor in the Departments of Neurology and Biochemistry; Chief of the Neuroethics Studies Program; Director of the Program in Biotechnology, Biosecurity and Ethics of the Cyber-SMART Center; and Chair of the Sub-program in Military Medical Ethics at Georgetown University. He is Senior Fellow in Biosecurity, Technology, and Ethics at the US Naval War College, Newport, RI; Bioethicist-in-Residence of the US Defense Medical Ethics Center; and Senior Science Advisory Fellow of the SMA Branch, Joint Staff, Pentagon. Prof. Giordano is the author of over 300 peer-reviewed publications, 7 books and 35 governmental reports on bioscience and technology, biosecurity, and ethics, and is an elected member of the European Academy of Science and Arts, and a Fellow of the Royal Society of Medicine (UK). A former US Naval officer, holding designations as an aerospace physiologist, research physiologist, and research psychologist, he served with the US Navy and Marine Corps.

Dr. Diane DiEuliis is a Senior Research fellow at National Defense University.  Her research areas focus on emerging biological technologies, biodefense, and preparedness for biothreats.  Specific topic areas under this broad research portfolio include synthetic biology, the US bioeconomy, dual use life sciences research, disaster recovery, and behavioral, cognitive, and social science as it relates to important aspects of deterrence and preparedness. Dr. DiEuliis teaches a biotechnology course, and guest lectures in a variety of foundational professional military education courses. Prior to joining NDU, Dr. DiEuliis was the Deputy Director for Policy, and served as Acting Deputy Assistant Secretary for Policy and Planning, in the Office of the Assistant Secretary for Preparedness and Response (ASPR), U.S. Department of Health and Human Services. While there, she coordinated policy in support of domestic and international health emergency preparedness and response activities, including implementation of the Pandemic All-Hazards Preparedness Act, the National Health Security Strategy, and the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE). From to 2007 to 2011, Dr. DiEuliis was the Assistant Director for Life Sciences and Behavioral and Social Sciences in the Office of Science and Technology Policy (OSTP) in the Executive Office of the President.  During her tenure at the White House, she was responsible for developing policy in areas such as biosecurity, synthetic biology, biotechnology, social and behavioral science, scientific collections, human subjects’ research, and STEM education.  Dr. DiEuliis also worked to help coordinate the interagency response to public health issues such as the H1N1 flu pandemic. Prior to working at OSTP, Dr. DiEuliis was a program director at the National Institutes of Health (NIH), where she managed a diverse portfolio of neuroscience research in neurodegenerative diseases.  She completed a fellowship at the University of Pennsylvania in the Center for Neurodegenerative Disease Research, and completed her postdoctoral research in the NIH Intramural research program, where she focused on cellular and molecular neuroscience. Dr. DiEuliis has a Ph.D. in biology from the University of Delaware, in Newark, Delaware.