The Biotechnological Wild West: The Good, the Bad, and the Underknown of Synthetic Biology

Synthetic Biology ResearchBy Yong-Bee Lim

Amid the myriad panels and posters on Ebola and Zika, the 2017 American Society for Microbiology (ASM) Biothreats conference also featured a panel on emerging biotechnologies.  A panel of three distinguished scientists and policy-makers provided an overview of the current state of synthetic biology, its applications in the health and defense domains, and the policy conundrums that need to be addressed.

Synthetic Biology – The Good…

The majority of the presentations focused on the current state of synthetic biology and the most promising applications of the technology in the fields of health, life sciences research, and national security. Dr. Christopher Voigt of the Synthetic Biology Center at MIT described synthetic biology as the application of engineering principles to biological systems. The end goal of this bioengineering framework is to leverage ever-increasing computer capabilities to simplify the designing and writing of genomic sequences. Further simplification of this process would then allow for the creation of more complex systems.

Dr. Chris Hassell, Deputy Assistant Secretary of Defense for Chemical and Biological Defense, and Dr. Diane DiEuliis, Senior Research fellow at National Defense University respectively, noted that applications of synthetic biology can be beneficial to many sectors. In his presentation, Dr. Hassell noted how governments can use synthetic biology to address bio-related issues facing both the military and civilian populations. Synthetic biology can be leveraged to address chem/bio threats through both external (including environmental detection, individual protection, collective protection, and decontamination) and internal (pre-treatments, diagnostics, therapeutics, and vaccines) mechanisms.

Dr. DiEuliis focused on how synthetic biology is a tool that allows for three major activities: discovery, the manufacture of products, and the fundamental alteration of organisms. Discoveries in basic research from academia allow for greater programmability, manipulation, and scalability of synthetic biology. As a society, we have already been reaping the benefits of synthetically-produced products from private industry; examples include soybean hulls used for surfactant manufacturing, synthetic spider silk used for clothing, and synthetically-derived artemisinin to address raw plant material shortages for malaria treatment. In addition, the military has also leveraged synthetic biology to create biosensors, next-generation medical countermeasures (MCMs) and enhance force health protection through changing the characteristics (and thus, the functionality) of microbes.

Dr. Christopher Voigt of the Synthetic Biology Center at MIT described a promising new development that has the potential to accelerate the achievement of the benefits outlined by his fellow panelists. A promising application of this framework is the software known as Cello. Requiring over a decade of work, Cello utilizes engineering principles to allow academic researchers to customize functionality for living cells. Cello then takes the cellular requirements and provides a logical design template for a genomic sequence. This template can then be sent to a gene synthesis company such as Addgene to be synthesized. Once the researcher has received the synthesized genomic sequence, introduction of the sequence into a cell will provide researchers with a fully tailored cell. While current capabilities are limited to Escherichia coli, future projects include expanding so that genomic sequence circuits will work in other bacteria and yeast cells.

Synthetic Biology – The Bad…

While the benefits derived from synthetic biology are great, presenters noted that it suffers from the dual-use dilemma: the same information applied to beneficial uses could also be repurposed for nefarious purposes. Dr. Hassell noted that synthetic biology increases biologically-derived risks through three mechanisms. First, synthetic biology can be used to enhance existing microbial threats; synthetic biology allows actors to more easily manipulate the characteristics of microbes, including increasing environmental stability and introducing hypervirulence. Secondly, traditional methods of restricting access to biological select agents and toxins (BSATs) may be less effective in an age where synthetic biology can be used to construct microbes de novo. Finally, synthetic biology can be used to construct novel threats that are meant to subvert countermeasures.

Dr. DiEuliis noted that traditional threats may be revisited as synthetic biology allows actors to more easily engage in research that run contrary to the guidelines of the seminal 2004 Fink Report. However, DiEuliis also remarked that microbial manipulation and creation through synthetic biology may not only be used to inflict direct human casualties. The misuse of synthetic biology can be leveraged for strategic effect, such as economic damage due to industrial sabotage. Rather than the traditional paradigm of considering biological weapons as weapons of mass destruction, DiEuliis highlighted that synthetic biology may be leveraged as a weapon of mass disruption.

And the Underknown

All three presenters offered salient insights into the current state of synthetic biology from academic, private industry, and governmental perspectives. However, there was no mention of how actors from nontraditional backgrounds are changing the risk-benefit analysis of the life sciences. Specifically, the erosion of technological and knowledge barriers to life sciences engagement have enabled greater participation from the civilian population to engage in life science research in a way that had been limited to traditional institutions such as the government, academia, and private industry. These civilian actors, often referred to as being part of the Do-It-Yourself (DIY) Biology movement, are characterized by their wide range of professions (from artists and retirees to life sciences students and professionals), widely varying motivations for engaging in DIY Biology projects (from curiosity to a desire to create useful tools and commercial products), and differing objectives (from manipulating yeast to developing new types of biofuels and biosensors).

DIY Biology practitioners have been heralded as a paradigm-challenging source of innovation and a welcome demonstration of the public’s interest in the life sciences. They have also raised concerns for biosecurity experts and law enforcement officials as an underknown variable engaging in life sciences activities. As synthetic biology continues to be become more powerful and available to a broader audience of actors, it is important to note the impact that nontraditional actors such as DIY Biology practitioners will have on contributing to the promise and perils of synthetic biology. Therefore, future discussions on synthetic biology and emerging biotechnologies should place a greater emphasis on not only the characterization and implications of the introduction of this new actor outside the traditional life sciences, but should also engage the DIY Biology community in helping navigate the biotechnological wild west.

Yong-Bee Lim is a PhD biodefense candidate at George Mason University, focusing on the implementation of an ethnographic study of the do-it-yourself biology (DIYBio) community to see how this group fits into the ever-changing landscape of risks and benefits in areas of biosecurity, biosafety, etc. He is currently a Predoc at Lawrence Livermore National Laboratory, where he works on topics ranging from leveraging high-performance computer model and strategic forecasting of biotechnology to reconceptualize models of risk for emerging and democratized technologies.

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