by Dr. David C. Hassell, U.S. Department of Health and Human Services, Assistant Secretary for Preparedness and Response & Dr. Christopher R. Houchens, U.S. Department of Health and Human Services, Assistant Secretary for Preparedness and Response (ASPR), Biomedical Advanced Research and Development Authority (BARDA), Washington DC, USA
For those of us focused on combatting threats from infectious diseases, the last five years have brought a real-world test of preparedness in the form of the worldwide COVID-19 pandemic, creative thinking about biodefense, and useful new tools from synthetic biology. Although many in government have been focused on COVID-19 since March 2020, we should not begin anew with our thinking as we consider preparedness going forward. Of course, we must consider lessons from the pandemic, but we also have pre-existing plans, reports, and science that will still serve us well moving forward.
Two documents were published in the US in 2018 that are still very relevant today. The National Academy of Sciences, Engineering and Medicine (NASEM) issued the report Biodefense in the Age of Synthetic Biology, and the U.S. Government (USG) published the National Biodefense Strategy (NBS). The NASEM Report emphasized the need to be better prepared for unknown biological pathogens, and that efforts need to go beyond lists of threat pathogens; it also promoted the idea that synthetic biology and other advanced biotechnologies are themselves effective defenses against nefarious use of synthetic biology. The NBS emphasized the need to assess, prevent, protect against, respond to, and recover from biological threats— whether naturally-occurring, accidental or intentional— and to consolidate efforts across institutional boundaries.
More recently, the SARS-CoV-2 virus has demonstrated the devastating impact a single pathogen can have on individuals, broader society, and the world economy. Government departments across the U.S. (including federal, state, local tribal and territorial) have worked together with the private sector to confront COVID-19 and to rapidly develop, distribute and administer effective vaccines, therapeutic drugs, and diagnostics. The science behind these medical countermeasures (MCMs) has employed many aspects of advanced biotechnology, thus demonstrating one key aspect of the NASEM Report. Likewise, the response effort has involved U.S. federal departments working together with private sector partners, which was a tenet of the NBS.
Early in the COVID-19 pandemic, the USG established Operation Warp Speed (OWS) to rapidly develop effective MCMs in historically unprecedented timeframes. OWS leveraged earlier investments in biotechnology research and brought together the strengths of respective departments, including the scientific and medical expertise of the U.S. Department of Health and Human Services, and the logistics and acquisition capabilities of the U.S. Department of Defense. The success of OWS, which delivered FDA-authorized vaccines and therapeutics in less than one year, relied heavily on three major elements:
- First was the use of proven platform technologies in which the USG had previously invested for the discovery, development, and manufacturing of mRNA-based vaccines and monoclonal antibody-based therapeutics. The ability to rapidly pivot existing, proven technologies to new threats will surely become the paradigm to expedite availability of MCMs during future responses.
- ·The second key aspect was the decision to invest in a portfolio of MCMs being developed using different platform technologies to reduce the risk that any specific technology would fail to deliver a safe and effective product. For vaccines, the result was a portfolio of two candidates each of mRNA, viral vector and adjuvanted protein vaccines, each of which has proven to be safe and effective.
- The last critical element that accelerated the delivery of effective MCMs was leveraging pre-existing relationships with industry partners. Long before SARS-CoV-2 emerged, the USG developed strong, collegial, and collaborative working relationships with various industry partners so that when the pandemic arrived, we already had willing and able partners eager to quickly work together to address the threat.
The lessons and experiences from OWS are now being more permanently established so that we can both continue to maintain readiness for SARS-CoV-2 variants, while remaining vigilant and prepared for unknown or emerging pathogens.
In September 2021, the White House Office of Science and Technology Policy published the American Pandemic Preparedness Plan: Transforming Our Capabilities (APPP), capturing many lessons learned from COVID-19. It includes goals to:
- Transform our medical defenses, including dramatically improving and expanding our arsenal of vaccines, therapeutics and diagnostics
- Ensure situational awareness about infectious-disease threats, for both early warning and real-time monitoring
- Strengthen public health systems, both in the U.S. and internationally, to respond to emergencies, with a particular focus on reducing inequities and protecting the most vulnerable communities
- Build core capabilities, including personal protective equipment, stockpiles and supply chains, biosafety and biosecurity, and regulatory improvement
- Manage the mission, with seriousness of purpose, commitment, and accountability
Although COVID-19 is the driver for this plan, these same goals would apply to intentional biological threat scenarios. Again, if the U.S. were to fall victim to another unexpected pandemic pathogen, regardless of the source, these constructs will be essential and will rely on many examples of advanced biotechnology and related converging technologies.
One area of current focus to transform medical defenses is the development of threat-agnostic MCMs. The traditional approach to developing pathogen-specific solutions limits our ability to develop MCMs against newly emerging yet previously unknown threats. Products that “treat the injury” rather than the pathogen directly, in contrast, have the potential to improve morbidity and mortality caused by a wide range of pathogens. This approach aligns with the NASEM Report recommendation to move beyond pathogen lists alone. It has also been embraced by the APPP, which emphasized the importance of broad-acting antivirals capable of targeting multiple species within a family of viruses, and highlighted the value of products that treat the symptoms of infection, particularly those associated with dysregulated immune responses. Such an approach includes developing antiviral drug classes, such as nucleoside analogs, with efficacy against multiple viruses; it also includes host-directed therapeutics that treat common syndromes or disease states associated with viral infection, thereby slowing, or stopping the course of the infection and disease. Developing broad-acting antivirals in conjunction with injury-directed countermeasures provides the greatest insurance against new or emerging viral pathogens. This approach also provides better options to confront previously unknown pathogens that might be developed by adversaries.
Communications and public education are challenges with any response to a biological incident, whether a bioweapon attack or a naturally occurring disease; COVID-19 has vividly shown this for the latter, with challenges due to vaccine hesitancy and the proliferation of conspiracy theories. These challenges are further exacerbated by the fearmongering that is sometimes associated with synthetic biology, especially the “biohacker” movement, as well as with such converging technologies as nanotechnology, advanced data science, and automation. Therefore, as many of us focus on technology solutions, we must also address with equal vigor complementary behavioral sciences, effective public communications, and education. Our efforts must also address equity so that all members of society are informed and protected, including the most vulnerable and underserved. Finally, all the above must be considered on a global scale.
Synthetic biology and other advanced biotechnologies hold tremendous promise to provide innovative and economically advantageous solutions for health care, energy, advanced materials, nutrition, and more. These technologies also pose certain risks; indeed, biological warfare in the era of SynBio may present many new challenges. However, the promise of these same technologies is a significant counter to any potential peril. The three documents highlighted herein could be summarized collectively in an admonition to be better prepared for unknowns (NASEM Report), work together for solutions (NBS) and learn and act on the lessons from COVID-19 (APPP). Responsible development of advanced biotechnology holds the promise to deliver on that broad admonition.
References
1. nap.nationalacademies.org/catalog/24890/biodefense-in-the-age-of-synthetic-biology
2. www.phe.gov/Preparedness/biodefense-strategy
3. https://www.whitehouse.gov/wp-content/uploads/2021/09/American-Pandemic-Preparedness-Transforming-Our-Capabilities-Final-For-Web.pdf; www.whitehouse.gov/briefing-room/statements-releases/2021/09/03/fact-sheet-biden-administration-to-transform-capabilities-for-pandemic-preparedness/
Authors: Bio
Dr. Christopher Houchens, PhD, is the Director of the Division of Chemical, Biological, Radiological and Nuclear Countermeasures within the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services.
His primary role is building and managing a diverse product portfolio focused on the advanced research, development and procurement of novel vaccines, prophylactics, therapeutics, diagnostics and devices as medical countermeasures against chemical, biological, radiological and nuclear threats. In this role, Dr. Houchens conducts outreach with industry to identify new partnership opportunities and participates on numerous interagency working groups across the US government with the goal of strengthening the ability and capacity of the United States to rapidly respond to naturally occurring and intentionally engineered threats to public health.
Dr. David Christian “Chris” Hassell serves as the Acting Principal Deputy Assistant Secretary and Senior Science Advisor to the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services. He most recently served as the Deputy Assistant Secretary of Defense for Chemical and Biological Defense, where he led research, development, testing, and acquisition of technical solutions to counter chemical and biological threats.
Prior to joining the Department of Defense, Dr. Hassell was an Assistant Director of the Federal Bureau of Investigation (FBI), where he served as Director of the FBI Laboratory and Executive Champion for LGBT concerns. He previously held research and leadership positions at Los Alamos National Laboratory and DuPont.
Dr. Hassell is an analytical chemist and a Fellow of the Society for Applied Spectroscopy. He is a recipient of the Defense Medal for Exceptional Civilian Service (US) and the Médaille de la Défense Nationale (France).
