Event Summary: Building Capacities for Addressing Future Biological Threats

Defining Convergence

By Geoffrey Mattoon, Biodefense MS Student

On Tuesday, 20 September, the Council on Strategic Risks (CSR) hosted the “Building Capacities for Addressing Future Biological Threats” webinar, which included keynote speaker Dr. David Christian (Chris) Hassell, Deputy Assistant Secretary for Preparedness and Response at ASPR, speakers Dr. Pardis Sabeti, Professor at the Center for Systems Biology at Harvard University, and Dr. Akhila Kosaraju, CEO and President of Phare Bio, and was moderated by Dr. Yong-Bee Lim, Deputy Director of the Janne E. Nolan Center on Strategic Weapons and George Mason Biodefense Program alumni. Together they discussed the evolving biological threats landscape and the means that exist to improve preparedness and response. This event follows the previous webinar “The American Pandemic Preparedness Plan: One Year of Progress & The Path Forward,” also hosted by CSR on 8 September, and focused heavily on the need for greater cooperation, collaboration, and innovation to prepare for the next pandemic.

             Dr. Hassell began the event by highlighting the misconceptions associated with the terms “convergence” and “bioconvergence” within the field. His concern was that these terms have become buzzwords within biodefense and their use implies that the different fields and disciplines necessary for biodefense are converging or cooperating organically. Such a misconception leads those within and outside of the field to assume that unity of effort is common and effortless, which is not the case. Barriers to convergence are prevalent and numerous, both in government and private sectors. Dr. Hassell provided an example from his previous experience in the Department of Defense developing chemical detectors, comparing a lack of higher-level convergence to the lack of standardized interfaces on different detectors preventing operators from gaining competency on all systems after mastering any single system. Such stove-piping of systems and efforts prevents convergence and is common across biodefense. The solution is a greater degree of crosstalk between disciplines working towards a unified solution or goal. Providing another example of this failure of convergence, Dr. Hassell highlighted the recent Pentagon appropriations for biodefense failing to account for the need for cyber funding to be successful against future threats as that discipline becomes more critical.

            Dr. Hassell also indicated that biological threats, in addition to the biodefense, are converging. As biotechnology and other life sciences continue to advance, the line between chemical and biological threats blurs. Previous research has demonstrated this growing convergence, from opioid-producing yeast conducted by Galanie et al. published in Nature to chemical synthesis of toxins conducted by Matinkhoo et al. in the Journal of the American Chemical Society. He urges a greater convergence of chemical and biodefense disciplines to effectively overcome these threats in the future. Such efforts would come at a substantial cost and require the reorganization of numerous government agencies, but it may be necessary to respond to the evolving threat landscape and enable more efficient use of future funding to unify efforts.

            Dr. Hassell then commented on the need for greater inclusion of data sciences, data technologies, and nanotechnologies in future biodefense efforts. The necessity of greater convergence between chemical and biodefense and the inclusion of these disciplines is a key requirement identified in Biodefense in the Age of Synthetic Biology, a report prepared by the National Academies for the Department of Defense in 2018. The addition of these technology-based disciplines is indicative of a greater requirement for technology convergence in chemical and biodefense efforts to combat the rising technology integration in the threat landscape. Modern biotechnology has created significant risk of dual use to create ever greater biological threats. Dr. Hassell pointed to the recent “Dual Use of Artificial-Intelligence-Powered Drug Discovery,” published by Urbina et al. in Nature Machine Learning, that indicated how easy it may be for a machine learning system designed with the best of intentions to identify new therapeutic disease inhibitors to be reprogrammed to instead identify novel toxin molecules. In that report, the MegaSyn system was able to generate 40,000 novel VX molecules in less than 6 hours. Dr. Sonia Ben Ouagrham-Gormley, Associate Professor at George Mason University and author of Barriers to Bioweapons, indicated such results do not directly equate to actionable threats on the Radiolab episode 40,000 Recipes for Murder that covered this journal article, but they still are indicative of the evolving chemical and biological threat landscape. Dr. Hassell also indicated the convergence of other disciplines critical to future biological threats, including climate change, which is enabling greater zoonotic spillover events, generating new and often novel biological threats.

            Dr. Pardis Sabeti underscored deadly infectious diseases as an existential threat to humanity during her remarks. She agreed with Dr. Hassell’s call for greater convergence and stated we must aspire to use technology to outpace the evolution of diseases so that we can be more anticipatory and less reactionary in the face of future outbreaks. She emphasized that COVID-19, though a recent a traumatic pandemic, is not the biggest threat we have faced or could face in the future. She argued we are on the precipice of cataclysm if we do not relentlessly pursue these efforts of convergence to enhance biodefense. Infectious disease is an existential threat that we can address because the tools necessary for biodefense are not bespoke or esoteric. Effective current and future biodefense tools, she argued, must be broad spectrum, offer daily value, contain transferrable benefits and knowledge, and be embraced at a cultural level to be effective. In line with the previous CSR webinar on COVID-19, Dr. Sabeti called for a greater commitment to community engagement as a key effort to combat future biological threats.

            Dr. Akhila Kosaraju then emphasized the need to take novel technologies required for biodefense out of the lab and into the field. She also supported the need for greater convergence, stating such efforts must be intentional to be successful. Her company, Phare Bio, exemplifies such efforts, employing AI and deep learning to enable rapid antibiotic discovery to overcome rising drug resistances. This approach provides Phare Bio a strategy to overcome the drug development “valley of death” where most current pharmaceutical development fails and presents an opportunity for other organizations like it across biodefense.  Modern biodefense efforts must emphasize biotechnology, relying on computational biologists, bioengineers, and other technical experts to maximize advances in the field.  She also indicated a need for organizations like The Audacious Project, a backer of Phare Bio, to effectively unify disciplines to solve intractable problems like drug resistance. The Audacious Project is a “collaborative funding initiative catalyzing social impact on a grand scale” across a broad range of disciplines that seeks to de-risk and encourage innovation. Injection of philanthropic, grant, or even government funding sources to adequately de-risk the “valley of death” and other obstacles is essential to future preventative and treatment therapeutics. Additionally, biodefense must strive to recognize small players in the field that often offer bespoke technologies and solutions that can accelerate efforts beyond that of the usual bigger players, as demonstrated throughout the COVID-19 pandemic. Efforts like Operation Warp Speed serve as foundational examples to the benefits such efforts can provide to the future of biodefense.  

Finding Its Niche in Biodefense: Bioprinting

By Alena M. James

Three-Dimensional printing has become a major controversial topic in the new age technology sector for the past few years now. Earlier this month, Yoshitomo Imura was arrested in Kawaski, Japan after using his 3-D printer to build five guns; two of which held the capability to fire bullets. This is an example of the potential dangers of 3-D printing. In April, a private company working in Shanghai used 3-D printers to print 10 full-sized houses in approximately 24 hours. This demonstrates the technology’s potential utility in building development. The benefits and risks of 3-D printing continue to be illustrated via innovators, but there has not yet been a clear consensus on the accepted utility of this advancing technology.

However, on the medical front these machines have proved incredibly advantageous. 3-D printers have advanced the medical field by allowing the creation of artificial limbs for patients, skin grafs for burn victims, and even noses for patients requiring facial reconstruction.  Despite the ambiguity of whether or not 3-D printing induces more harm than good or more good than harm for society, the Defense Threat Reduction Agency (DTRA) has found a significant utility for this rising technology in the biodefense world.

Last week, DTRA announced the new role for 3-D printers in biodefense research. According to DTRA, using 3-D printers in countermeasures research against chemical and biological weapons would allow for scientists to rapidly produce human tissue on which treatments against chemical and biological agents can be tested.

The technique is known as bioprinting—the use of 3-D printers to develop human tissues and organs.  In bioprinting, a specialized 3-D printer is designed to disseminate viable cells that can strategically lay the framework to biofabricate organoids—smaller version of organs. Ears and skin have been the two most common organs that have been developed via this technology.

Studies at Harvard University have helped to pique DTRA’s interest in bioprinting. So far, the Harvard Scientists have successfully developed 3-D organoids that can survive for at least eight days. The length of viability is significant, because it allows more time for testing to be performed on sensitive organisms like bacteria.

If DTRA scientists can test the effectiveness of treatments against biological or chemical weapons on bioprinted human tissue, they maintain the capacity to evaluate these treatments in more accurate human models without harming actual patients. Using biofrabricated systems will also enable DTRA scientists to determine the best countermeasures against these types of weapons without solely relying on animal modeling systems. These types of studies are traditionally condemned due to ethical concerns for the animals and are limited in producing side effects that are associated within the human model.  By using human tissue fabricated from 3-D printers, scientists reduce animal testing trials and gain a more accurate understanding of the effectiveness of the treatments being investigated. The fabrication of organoids may also allow drug testing to occur at a faster pace saving time and money in the research field.

One of the leading companies of this technology is Organovo. The company focuses on developing structurally and functionally accurate human tissue models used in medical research. The process of bioprinting requires several steps to produce the intended tissue or organ type. First, a design of the target tissue must be created. Second, the key architectural and compositional elements of the tissue must be identified. Third, the software must be used to develop a printing protocol.  Fourth, a bioprocess is required to develop the bio-ink for the project. Bio-ink comes from cells involved in the development of the tissue copy. Fifth, the ink gets dispensed from the bioprinter layer-by-layer building the tissue in 3-D.

Although the process outlined above appears simple, bioprinting still requires more investigative studies to truly evaluate its advantages and disadvantages.  However, it is quite exciting to know that the technique is finding a significant role in to the Biodefense realm.


(Image Credit. Image Caption: The scaffolding for two replacement ears printed is shown above. Prior to bioprinting replacement ears were developed from rib cartilage.)