Proceedings of a Workshop

Making the Living World Engineerable: Science, Practice, and Policy

Proceedings of a Workshop—in Brief

INTRODUCTION

On November 16, 2016, the Forum on Synthetic Biology of the National Academies of Sciences, Engineering, and Medicine’s Committee on Science, Technology, and Law (CSTL) hosted a workshop titled Making the Living World Engineerable: Science, Practice, and Policy. The workshop was organized by an ad hoc planning committee to discuss current trends in synthetic biology, including international scientific and technical developments in synthetic biology; possible risks and benefits related to these developments; and legal, regulatory, and policy concerns. Funding for the workshop was provided by Agilent Technologies, the Federal Bureau of Investigation (FBI), and the U.S. Department of Homeland Security (DHS).

During opening remarks, planning committee chair Jef D. Boeke (New York University Langone Medical Center) noted the sponsors’ interest in facilitating a discussion that considers scientific and technical progress made to date, how the current policy landscape is affecting the science and practice of synthetic biology, and what the current state of affairs means for federal policy.

As a point of context, Boeke referred to a recent report by the Secretary of Energy Advisory Board that recognized the crucial implications of progress in the biomedical sciences for the nation’s health, security, and competitiveness.¹ That report recommended that researchers at the U.S. Department of Energy (DOE) and the National Institutes of Health (NIH) work together to develop an integrated capability for moving directly from sequencing genomes to high throughput imaging, metabolomics, and biochemistry at molecular to cellular scales and then to recapitulate metabolism and cellular systems via the synthesis of genes, pathways, and genomes. The report also noted that—unlike the United States—China, the European Union, and the United Kingdom have standing bodies and roadmapping exercises to direct the advancement of DNA synthesis technologies and suggested that past U.S. government efforts to ensure domestic leadership in computing and networking technologies be revisited as potential models for strategic framing and program development.

In structuring the workshop, Boeke said, the planning committee sought to stimulate discussions to advance understanding of the opportunities and challenges in synthetic biology and illuminate a path forward for practitioners and policy makers.

The workshop agenda consisted of two individual addresses and four panel discussions. The complete agenda is available at: http://sites.nationalacademies.org/cs/groups/pgasite/documents/webpage/pga_174790.pdf.

___________________

¹ U.S. Department of Energy. Secretary of Energy Advisory Board Report of the Task Force on Biomedical Sciences. September 22, 2016, available at: http://www.energy.gov/sites/prod/files/2016/10/f33/9-22-16_Report%20of%20the%20SEAB%20TF%20on%20Biomedical%20Sciences%20with%20transmittal.pdf.

A FEDERAL STRATEGY IN SUPPORT OF AN EMERGING FIELD—LESSONS FROM HISTORY

The workshop began with a keynote address from Robert E. Kahn (Corporation for National Research Initiatives) reflecting on the development of the Internet at the Defense Advanced Research Projects Agency (DARPA) and how lessons learned from that transformational technology might be translated into a strategy to assist in the development and advancement of synthetic biology. Kahn observed that synthetic biology, like many new technologies, offers great hope for the future and carries a promise to change the world, but he cautioned that major successes would come in the long run.

Kahn identified the challenges encountered during the development of the Internet as paralleling the challenges now facing synthetic biology. He articulated potential goals for the synthetic biology community, emphasizing the necessity of sharing tools so that they do not need to be invented de novo by each researcher; defining standards to enable meaningful sharing; and supporting the timely, efficient, cost-effective implementation of key ideas and constructs. Kahn proposed digital libraries as an infrastructural requirement to preserve works in a form more easily shared.

Kahn described DARPA’s decision to invest in infrastructure and then noted the importance of having a champion in the government. He suggested that an individual company or a consortium of companies could support the creation of a shared infrastructure, but that industry’s desire to retain a strategic advantage might preclude such an investment. If a champion in the government does not exist, Kahn said, then the synthetic biology community may need to identify a person or a small set of people who could play that role.

Kahn observed that, in the evolution of the Internet, the social structures that enabled people to work collaboratively in organized forums were every bit as important as the technology. Kahn said that with careful planning, competent researchers, and helpful infrastructure to support their needs the synthetic biology community could greatly amplify its chances of success.

DISCUSSION

Participants asked about the common tools and processes needed to enable synthetic biology to move quickly to applications. Kahn observed that university researchers, sometimes joining with industry, can produce what the community needs, but this usually requires government funding. Participants also raised questions about security concerns. Kahn said he believes there is an unresolvable tension between the needs of the private sector and the needs of the government in both law enforcement and national security. Public perceptions and distrust of new technologies were discussed. Kahn remarked that, initially, only a handful of researchers thought the Internet was a good idea.

DRIVERS OF INNOVATION: BENEFITS AND APPLICATIONS

Session moderator Drew Endy (Stanford University) introduced the session by stating that its purpose was to hear from individuals who are working to address global food challenges, medical needs, and concerns about environmental degradation.

The first speaker, Patrick Brown (Impossible Foods), began his presentation by describing the environmental impact of using animals as a food source. He identified greenhouse gas emissions and the competition for water and land associated with animal agriculture¹ as the single greatest threat to global security. Brown said that animal agriculture is also the biggest driver of what he considers an ongoing wildlife holocaust.² Extrapolating to 2050, Brown estimated that a 60 percent increase in land devoted to animal agriculture will be needed if animal-derived food is to sustain the global population.

Brown suggested that a sustainable approach is needed to transform plants into foods that are comparable to foods currently derived from animals. He described how Impossible Foods identified heme, an iron-containing molecule in blood that carries oxygen, as central to the unique flavor and aroma of meat and how, by using the biosynthetic capacity of yeast to produce vast quantities of heme and combining heme with the most abundant plant protein on Earth (rubisco), Impossible Foods was able to create a hamburger substitute that, “can run head-to-head

___________________

¹ As examples, Brown presented findings from the Food and Agriculture Organization of the United Nations in 2013 showing animal farming was responsible for more net greenhouse gas emissions than the entire transportation sector and consumes more of the world’s supply of fresh water than any other industry. He also cited the 2011 International Livestock Research Institute and the 2014 U.S. Department of Agriculture reports showing land areas used for animal agriculture, specifically 49 percent of the land area of the continental United States.

² In support of this statement Brown cited a report from the World Wildlife Fund showing that across all species the total number of wild animals living on Earth in 2014 was less than half what it was 40 years ago attributable mostly to habitat destruction and degradation due to the expansion of animal agriculture.

against the best burger from a cow.” The production process, Brown said, produces “one-eighth of the greenhouse gas emissions, one-quarter of the water, and uses one-twentieth of the land” involved “in producing the same thing in the United States using a cow.”

Scott Fahrenkrug (Recombinetics) began his presentation by stating that he believes that the biggest global challenge will be feeding 3 billion additional people expected to inhabit Earth by 2050. He said that Recombinetics is using gene editing to provide solutions for both food production and human health. He suggested that gene editing technologies can solve some of the biggest problems of animal agriculture. A video presented by Fahrenkrug³ showed how gene editing enabled researchers to produce hornless cows that obviate the need for dehorning and cattle with increased muscle mass that produce 7-30 percent more meat, produce more milk, and thrive in hot climates. The video also showed work to edit the genome of pigs to aid the development of faster, less expensive ways to develop drugs and medical devices for the treatment of diseases like cancer, cardiovascular disease, and Alzheimer’s disease. Fahrenkrug sees a future where gene-edited pigs could provide human patients with tissues and organs and anticipates that Recombinetics could start clinical trials on animal to human transplants within 6 years.

Elizabeth Sattely (Stanford University) described plants as molecular factories and noted that plants provide “the food we eat, all the air we breathe, all the biomass we consider [using] for renewable energy sources” and “also a number of molecules that are important for human health.” Sattely described her research to engineer a more efficient and reliable method of producing valuable plant molecules and to optimize compounds in order to make better drugs. By isolating the genes responsible for producing particular molecules, Sattely’s team can design manufacturing platforms to create compounds in the lab that would otherwise only be available by isolation from medicinal plants. Sattely also discussed engineering plants to provide essential nutrients, e.g., the production of vitamin A in rice. She described her lab’s current focus on engineering the production of particular molecules specific to the Brassica family of plants into plants that lack these molecules so as to improve both their nutritional value and fitness.

Kevin Esvelt (Massachusetts Institute of Technology) described his research on gene drives, a technique that promotes the inheritance of a particular gene to increase its prevalence in a population. He discussed research to engineer mice that are resistant to tick-borne Lyme disease. Esvelt described potential field trials where the engineered mice would be released on islands to study the effect of their presence on the number of disease-infected ticks and to determine whether there are unexpected ecological effects. Esvelt believes that it is best to introduce genetic changes into a population by creating a daisy chain of serially dependent genetic elements. Such “daisy drives” enable researchers to introduce changes into a population “that are local, reversible, efficient, and above all small scale.” According to Esvelt, such gene drives can be used to alter local populations of wild organisms for the purposes of eliminating diseases and parasites and also to aid conservation efforts. With such technology, organisms would not suffer as they would if traditional pesticides were used to control the spread of pathogens.

Esvelt said that the response of communities on islands where field tests were proposed was enthusiastic. He attributed the enthusiasm to having approached the communities beforehand and involving them in key decisions about possible technical solutions. Esvelt believes that transparency and dialogue are critical in order to ensure that science is responsive to public interests.

Boeke described work to synthesize a single yeast chromosome designed from scratch. He said this effort has grown to a worldwide collaboration, called Sc2.0 for Saccharomyces cerevisiae CI 2.0. The effort, which seeks to design a fully synthetic genome for yeast, involves 16 laboratories from Australia, China, Singapore, the United Kingdom, and the United States. Boeke attributed the success of Sc2.0 to support from the U.S. National Science Foundation and a statement of principles signed by all collaborators to share DNA molecules and yeast strains without restriction.

Boeke also discussed a potential project, modeled on Sc2.0, to synthesize a human genome in cells.⁴ After noting that work on human genomes should be accompanied by responsible discussion, Boeke said that his motivations in joining the human genome effort included gaining new knowledge about genome fundamentals, technology development with spinoffs for applications to global problems, and biomedical somatic applications. Boeke described studies where 100,000 base pair segments of human DNA were assembled and studies that resulted in the development of a haploid human cell line. He also described research to understand regions of the human genome that contribute to disease but are not fully understood and research that seeks to build an ultra-safe human cell line that could be used in biotechnology and could be useful in stem cell therapies.

___________________

³ The video is available at: http://kstp.com/news/gene-editing-food-supply-medical-research-recombinetics/4315545/.

⁴ Boeke referred to http://engineeringbiologycenter.org, where information about this project can be found.

DISCUSSION

Participants raised questions about consumer acceptance of new technologies in pharmaceuticals versus in foods and about heterogeneity in engineered crops and livestock. It was pointed out that gene editing could increase diversity and redress the undesirable effects of inbreeding. It was suggested that greater public openness about research and building in biosecurity early in design were best practices. There was acknowledgment that promises of the grand benefits of synthetic biology are not necessarily being met. Panelists discussed their attempts at public engagement, efforts to obtain societal input early, and interactions with regulatory bodies around the world. When asked to comment on the difficulty of collaboration in academia given the competitive funding situation, panelists described a need for discretionary funds to support pilot projects when government support is not available.

CHANGES IN TECHNOLOGY AND PRACTICE

Session moderator Lalitha Sundaram (Arsenic Biosensor Collaboration) introduced the session by stating that its purpose was to uncover “the nuts and bolts” of engineering biology from multiple perspectives.

The first speaker, Todd Peterson (Synthetic Genomics, Inc. [SGI]), observed that conventional vaccine production takes 35 days, a time period within which many cases of influenza infection and deaths occur. Peterson stated that SGI can produce a vaccine seed in five days by synthesizing flu-specific genes based on sequences obtained from the Internet, dropping the genes into a scaffold for transforming tissue culture cells, and regenerating RNA viral genomes.⁵ Peterson also described an approach to develop a synthetic vaccine against a large double-stranded DNA virus using sequence information from two different strains. With this approach, the best properties with respect to the vaccine potential of one strain are mixed with the scalability and manufacturing properties of the other. Finally, he described two messenger RNA-based systems—one based on the “gold standard” alphavirus with a series of rational changes to achieve high expression levels and another based on a natural virus—engineered so a single RNA can express multiple proteins in a tunable and multi-genic manner.

Ben Shen (The Scripps Research Institute) described research focused on understanding the structure of natural products with anti-cancer or anti-infective properties. He stated that 75 percent of the $1 trillion pharmaceutical market involves small molecules, of which 50 percent are based on molecules harvested from natural sources. Shen suggested that synthetic biology can change the landscape for natural product discovery because it enables the production of naturally based products in much larger quantities with less environmental impact.

In Shen’s view, the most powerful potential for synthetic biology is to explore alternative producers, structural analogs, or novel scaffolds. He noted that Merck discovered platencin by a random screening of 83,000 strains, whereas his group screened 2,000 strains for gene markers and identified 6 high-producing strains, enabling them to increase production of platencin from 1 mg/liter to 1.5 g/liter. Shen observed, however, that there is a knowledge gap in how to translate genomic information into a final product.

Bill Efcavitch (Molecular Assemblies) spoke of his company’s efforts in next-generation DNA synthesis. Efcavitch observed the chemistry of DNA synthesis has changed little since it was invented in 1981, that synthesis remains limited to DNA strands of up to 150 nucleotides, suffers from reliability issues, and involves the use of toxic chemicals. Efcavitch described Molecular Assemblies’ enzymatic approach for de novo DNA synthesis using terminal deoxy transferase (TdT). He said that this process is much more efficient than traditional DNA synthesis, enables the recycling of reactants, is capable of making homopolymers tens of thousands of nucleotides long, and accepts modified nucleotides. Efcavitch identified DNA as the industrial polymer of the 21st century with applications in agriculture, biofuel, chemical production, DNA nanotechnology and electronics, DNA vaccines, health care, and information storage.

Rob Carlson (Bioeconomy Capital) traced the growth of genetically modified “stuff” from products resulting from single genes placed in single cells (e.g., human growth hormone) to complex pathways consisting of 12 genes from 4 organisms expressed in yeast. He presented data showing biotechnology is growing rapidly, comprising 2-3 percent of the U.S. economy.⁶ Carlson observed that DARPA’s 1,000 Molecules Program has started delivering results, featuring a company that developed a 10-enzyme pathway to make fluoropolymers. Carlson believes the shift to biology will eliminate societal costs associated with chemical synthesis, citing GlaxoSmithKline’s (GSK’s) decision to

___________________

⁵ As a case in point, Peterson described the 2013 H7N9 outbreak, where SGI was able to produce a vaccine seed within one week, before the U.S. Centers for Disease Control and Prevention even received the virus from China.

⁶ See Carlson, R. 2016. Estimating the biotech sector’s contribution to the U.S. economy. Nature Biotechnology 34:247-255; Solomon, U.S. Senate Briefing, November 5, 2013.

manufacture amoxicillin using biology as a positive example.⁷ He described beer micro-brewing as proof that distributed biological manufacturing can compete with centralized manufacturing. Carlson noted, however, that there are genuine challenges to scaling up biomanufacturing. Amyris, he said, incurred $1.4 billion in costs over 12 years with revenues of only $100 million per year. Carlson concluded his remarks by noting the efficiency of cows as biomanufacturing platforms. It will cost $170 billion, he said, to build biorefineries capable of producing enough biofuel to meet renewable fuel standards, but it costs only $28 billion to produce an equivalent volume of milk using cows.

DISCUSSION

Peterson suggested that if DNA was to be broadly used as an information storage device, the potential scale of the amount of information stored could significantly reduce the cost of DNA synthesis. Shen pointed to two national initiatives⁸ where molecules are key to solving emerging challenges. Other panelists observed that there is great demand for DNA in industries beyond synthetic biology and underscored the difficulties associated with understanding future applications of synthetic DNA. Ed You (FBI) asked about the national security and foreign policy implications of shifting from a petroleum-based to a biology-based economy. Carlson predicted that energy needs in 20 years would be met by solar, wind, and nuclear power and that the bioeconomy would replace 15 percent of oil consumption and result in a more sustainable, resilient production infrastructure with fewer points of failure and vulnerability.

FROM SCIENCE AND TECHNOLOGY TO EFFECTIVE POLICY

In introducing speaker Stephen Hilgartner (Cornell University), workshop planning committee chair Boeke stated that Hilgartner was tasked with transitioning the discussion from science and technology to policy.

In his remarks, Hilgartner described two ways of thinking about moving to effective policy in synthetic biology—an innovation-policy perspective and a politics-of-technology perspective. Noting that policy questions connected to synthetic biology touch on many domains (funding, intellectual property, risks, ethics, etc.), Hilgartner discussed intellectual property (IP) as illustrative.

Hilgartner first described the policy discourse⁹ for IP from an innovation-policy perspective, which casts innovation as a social good: the innovator is the hero and “the free rider is the villain.” He observed that this storyline gets translated into the language of patent law. He said that the debate typically assumes that the level of innovation is the key measure of success and supports people who want stronger intellectual property rights. From a politics-of-technology perspective, technological systems are viewed as an inextricable part of the social fabric and emerging technologies occupy a sphere where political power is formed and adjudicated and fought over.

Hilgartner pointed out that the innovation-policy discourse views science and technology as a rising tide that lifts all boats (more is better), whereas the politics-of-technology discourse sees science and technology as embedded in social contexts that require an assessment of how innovation causes harm and benefit. He observed that patents allocate voice and choice in the negotiation process. He suggested that sharing or openness in science must also be situated in the specific structure of the regimes in which they are operating because there are always rules for what gets shared with whom and under what conditions and terms.

Hilgartner observed that the innovation-policy discourse focuses on innovators. The public shows up late as the recipient of benefits or as a consumer expressing choice or a citizen irrationally rejecting things on offer. The politics-of-technology discourse focuses on the citizen and is more concerned with making legitimate decisions in democratic societies.

Hilgartner concluded his remarks by emphasizing the importance of giving space to the politics-of-technology perspective in synthetic biology policymaking. The biggest challenges, he suggested, do not involve how to stimulate innovation but rather are about how to govern increasingly technological democratic societies in ways that are neither authoritarian nor “incapable of settling disputes and figuring out ways to muddle through and move ahead.”

___________________

⁷ Carlson said that GSK, in collaboration with Codexis, is replacing chemical synthesis of amoxicillin in its Singapore plant with biological production using enzymes, which removes almost 80 percent of the chemical waste, reduces the amoxicillin value chain carbon footprint by up to 12 percent, and improves industry leading product quality standards.

⁸ The two initiatives noted by Shen were the National Microbiome Project and the National Action Plan for Combatting Antibiotic Resistant Bacteria.

⁹ By policy discourse, Hilgartner was referring to a set of concepts, categories, and narratives that people use to formulate their perspectives and give structure to an area of policymaking.

DISCUSSION

Participants raised questions about the influence of governance mechanisms on technologies with transformational impact. Hilgartner said that policy levers exist in broadly distributed locations rather than in a single location. He suggested that decisions could be made in a political space where there are multiple points for individual intervention. Consensus, he said, is not easy to achieve. Decisions are contentious because they bring into play different visions about what kind of society we want to live in and the kind of future we desire.

IMPLICATIONS OF SCIENTIFIC ADVANCES AND CHALLENGES AND CHANGES IN TECHNOLOGY AND PRACTICE (CHALLENGES/OPPORTUNITIES)

Session moderator Hank Greeley (Stanford University) introduced the panel by stating that the purpose of the session was to examine the ethical and social implications of synthetic biology.

The first speaker, Laurie Zoloth (Northwestern University), described the 1975 Asilomar Conference on Recombinant DNA as a meeting where scientists wrote out safety rules for the regulation of recombinant DNA technologies.¹⁰ She observed that this meeting led to the formation of a Recombinant DNA Advisory Committee (RAC) and the idea that ethical issues should be part of discussions about recombinant DNA research.

Zoloth described public objections related to research on DNA or the engineering of DNA. She observed that in 1999, a working group of the American Association for the Advancement of Science (AAAS) met with ethical and religious leaders and scientific leaders in genetics to consider concerns related to human inheritable genetic modifications. According to Zoloth, the working group concluded that objections to such modifications were largely theological in nature, could not be agreed on, and were values driven. She said that AAAS subsequently published a consensus statement on inheritable genetic modification with what she described as four reasonable questions to consider with any technology.¹¹

Zoloth reflected on what makes the current moment different from the time of the Asilomar Conference: the entrance and new role of the marketplace in science; the growth of patient advocacy coupled with Internet connectivity, a deep sense of uncertainty in biological science; cognizance of the potential for environmental catastrophe; and the reality of terrorism.

Emma Frow (Arizona State University) described the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules as the key framework for oversight in the United States. She noted that synthetic biology research is moving into places not covered by existing oversight mechanisms. Frow observed that the NIH Guidelines formally extend to researchers funded by NIH or other federal funding agencies but are voluntary for groups using private funding. She also noted that the current self-governance system grew from concern about managing safety and does not address broader concerns such as biosecurity, ethics, economics, and social implications.

Frow observed that design aspects of synthetic biology require a high level of training but that building and testing engineered circuits and organisms can be performed by (and are falling to) less skilled individuals. She suggested that employment prospects for future synthetic biologists should be thought about carefully. Frow also reflected on developments in automated platforms and investments in genome foundries and suggested that the field be attentive to tradeoffs involved in implementing automated workflows and to keeping open the possibility of alternative designs and the emergence of different priorities.

Jeantine Lunshof (University Medical Center Groningen) said that research should be openly available and guided by the ethical principles of reciprocity, mutuality, and veracity.¹² Citing calls for the sharing of data from publicly funded research,¹³ Lunshof identified the following key questions: “How can claims for openness be met in cases of technologies that next to the benefits have clear inherent risk?” and “Will public availability of information add to

___________________

¹⁰ Zoloth said that the group could only agree on three safety rules: don’t insert pathogens into E. coli, don’t insert cancer, and don’t insert genes for drug resistance.

¹¹ The four questions are: 1. Are there reasons in principle why performing the basic research should be impermissible? 2. What contextual factors should be taken into account and do any of these prevent development and use of the research? 3. What purposes, techniques, or applications would be permissible and under what circumstances? 4. What procedures, structures, and involving what policies should be used to decide on appropriate techniques and uses?

¹² Lunshof referred to Knoppers, B.M., and R. Chadwick. 2005. Human genetic research: Emerging trends in ethics. Nature Reviews Genetics 6:75-79.

¹³ Lunshof cited the 1985 National Security Decision Directive Number 189 and National Research Council. 2007. 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, available at: https://www.nap.edu/catalog/12013.

that risk or will it allow for better risk management?” Lunshof suggested that Esvelt’s daisy drive approach has two important strengths: first, it potentially reduces biological, ecological, biosafety, and biosecurity problems; and second, it puts an ethics model into practice that meets the criteria for true reciprocity in research.

Kathleen Vogel (North Carolina State University) reflected that after almost 15 years of worrying about the biosecurity threats related to synthetic biology, there still is no good framework or body of data to inform thinking. Vogel recalled looking at biosecurity issues in the early 2000s when Eckard Wimmer created a synthetic polio virus and observed that, because Wimmer published in a scientific journal, the media and certain policy makers identified his work as a blueprint for bioterrorism. She said that the expertise to conduct Wimmer’s experiments was specialized and limited to a small subset of polio virology labs. Vogel argued that it is important to understand why this type of protocol has not diffused in the intervening years. It is also important to look at what is actually happening in laboratories in order to understand how people are trained and how knowledge is transferred. Vogel believes that a lack of empirical research in the security realm is not specific to synthetic biology and argued that detailed case studies are needed to create a refined spectrum of understanding about which kinds of threats and what particular technologies are most concerning from a security perspective.

DISCUSSION

Greely asked the panelists what worried them most about synthetic biology. Vogel observed she did not know what to be afraid of due to the lack of data. Lunshof remarked she was not particularly afraid, though she thought the unpredictability and fast pace of developments were problematic. Zoloth said she believed good things can happen but worried that fear might prevent beneficial projects from happening. Frow worried that framing conversations in a way that views the public as an obstacle to technological progress may lead to polarization.

Participants raised questions about barriers to misuse and whether mechanisms for regulating technologies have actually made the world safer. Esvelt asked how those concerned about a potential development can make decisions about whether it should be allowed to proceed or how information about the development should be shared. You asked what happens if the United States is no longer first to develop or maintain foundational technology and capability.

There was discussion about the relationship between safety and risk, safety being a circumstance where a certain amount of risk is tolerated. Zoloth suggested the synthetic biology community could do more to support organizational forums with the normative power to create some degree of accountability for conduct.

POLICY LEVERS: A STRATEGY FOR MOVING FORWARD (REGULATIONS AND OTHER APPROACHES)

Session moderator Shobita Parthasarathy (University of Michigan) introduced the panel by stating that the purpose of the session was to hear different policy perspectives so as to place American policy into broader context, both historically and comparatively.

The first speaker, Lionel Clarke (Synthetic Biology Leadership Council in the United Kingdom), shared his reflections on developing a UK roadmap for synthetic biology. He said that creating the roadmap was akin to creating a hiking map for unfamiliar territory. Clarke recounted the history of the development of the roadmap, beginning with recognition at the government level by then Minister of State for Universities and Science David Willetts and public dialogue in 2011 and followed by convening a Roadmap Coordination Group and Leadership Council to oversee progress and update and re-steer as needed. Clarke observed that the UK government included synthetic biology as one of the “Eight Great Technologies” in 2012 and fully supported recommendations from the roadmap.

Clarke described six Synthetic Biology Research Centers, each with its own self-defined area of interest and expertise. He observed that technology is progressing quickly. Furthermore, the roadmap is about global challenges and needs. Clarke said that the United States and the United Kingdom have engaged in joint activities (Six Party Dialogues, LEAP, Synberc, International Genetically Engineered Machines [iGEM]) that he considers valuable to all.

Robbie Barbero (White House Office of Science and Technology Policy [OSTP]) offered a view of how the Obama administration has thought about biotechnology and the bio-economy and the role that synthetic biology played there.¹⁴ He described how he and others at OSTP dedicated a year to clarifying the roles and responsibilities of the U.S. Environmental Protection Agency, the U.S. Food and Drug Administration, and the U.S. Department

___________________

¹⁴ Barbero referred to the OSTP’s top 100 science and technology accomplishments of the Obama administration, which are available at: https://www.whitehouse.gov/the-press-office/2016/06/21/impact-report-100-examples-president-obamas-leadership-science.

of Agriculture with respect to the products of biotechnology and wrote a strategy for how the three agencies will prepare for future products of biotechnology.¹⁵ Barbero observed that a Pew Study found that more than two-thirds of respondents were concerned that biotechnologies would exacerbate inequality that already exists. He stated that it is important to think about how to make sure solutions are available to everyone in a fair and open way.

Luis Campos (University of New Mexico) described the history of roadmapping. He observed that it was only recently that roadmaps became a central feature of science policy. Campos questioned why roadmaps have become so pervasive and observed that there is “a recurring tension between those ... who need to operationalize analytical insights as levers for policy on the one hand ... and those on the other hand ... who specialize in questioning, problematizing, interrogating ... such operationalizing.” He concluded that recurring “tensions” and “uncomfortable frictions” in communicating about topics such as synthetic biology are “not to be gotten rid of” but rather are part of the process and practice of engaging the public in policy discussions about complicated issues. As we “muddle” through, Campos suggested, we just might be figuring it out.

Jane Calvert (University of Edinburgh) began by describing how she was drawn to the field of synthetic biology because it embodied an explicit attempt to rethink relationships among science, technology, and society. She described the UK roadmap as open ended and without defined technological deliverables, partially because it was about an emerging technology. She discussed uncertainty, ambiguity, and transformative potential and noted that emerging biotechnologies are susceptible to being framed in certain ways and risk being locked into directions that may not be the most beneficial.¹⁶

Calvert believes that different ways of imagining the future are very important. She said that one of her concerns about the UK roadmap is that it created pressure for applications of synthetic biology in the short term. A robust roadmap, she said, may require the inclusion of a broader range of people, including nongovernmental organizations, citizen-scientists, speculative designers, and people who think a lot about the future. Calvert suggested some kind of “tree map” might be useful. She described a tree map as a roadmap with multiple possible trajectories, some of which would not depend on quick commercial returns and some of which would nurture the features of synthetic biology that captured her and others’ attention.

Jason Delborne (North Carolina State University) cited several reasons for pursuing public engagement; local knowledge, principles of justice, opportunities for mutual learning, and building trust. He presented a framework for public engagement in which information flows in both directions and both parties are vulnerable to being moved.¹⁷ He observed that deliberative engagement offers a different kind of insight about what other people think about issues and that these kinds of exercises are necessary for accessing public values in making decisions about synthetic biology.

DISCUSSION

Parthasarathy asked the panel to comment on how distrust and frustration about the establishment (as reflected in Brexit and the results of the 2016 U.S. presidential election) might change the way we think about policy, politics, and the policy process. Clarke described his efforts to create mechanisms within the United Kingdom whereby anyone can communicate directly and suggested that the discussion needs to shift to particular applications. Calvert suggested better public dialogue might orient the discussion toward a particular application where synthetic biology is part of a diverse range of solutions.

Participants raised questions about the role of education to increase ethical science and responsible innovation. It was noted that the iGEM competition influences students by integrating a human practices component. There was also discussion about how funders shape the structure of public engagement and the questions asked and, ultimately, the policy decisions made about synthetic biology.

___________________

¹⁵ See Emerging Technologies Interagency Policy Coordination Committee. National Strategy for Modernizing the Regulatory System for Biotechnology Products. Washington, DC, September 2016, available at: https://www.whitehouse.gov/sites/default/files/microsites/ostp/biotech_national_strategy_final.pdf.

¹⁶ In reflecting on emerging technologies, Calvert drew from the report published by the Nuffield Council on Bioethics in the United Kingdom. See Nuffield Council on Bioethics. Emerging Biotechnologies: Technology, Choice and the Public Good. London, December 2012, available at: http://nuffieldbioethics.org/wp-content/uploads/2014/07/Emerging_biotechnologies_full_report_web_0.pdf.

¹⁷ For this framework, Delborne cited Rowe, G., and L.J. Frewer. 2005. A typology of public engagement mechanisms. Science, Technology, & Human Values 30(2):251-290.

FINAL REMARKS

The workshop ended with an open discussion. Carlson observed that the differences in strategy and culture between China and the United States are being played out in the use of genetic technologies. He pointed out that the United States has no strategic plan for biology. You observed that, while the United States has a national bioeconomy blueprint, it does not have a roadmap for synthetic biology.

Participants raised questions about whether it is the most productive to examine the social and organizational questions coupled to technology development within a security framework. You remarked that, without an overarching roadmap or strategy for addressing innovation as well as security, entities like DHS and the FBI are “at wit’s end” because they are left with existing legal frameworks. He pointed out existing frameworks for biosecurity are focused on a Cold War–era definition of threats and that, while we can envision where innovation is leading (e.g., a growing bio-economy and systems biology data), current security measures are inadequate for dealing with the innovations we are witnessing.

DISCLAIMER: This Proceedings of a Workshop—in Brief was prepared by Anne-Marie Mazza and Steven Kendall as a factual summary of what occurred at the meeting. Linda Kahl provided technical assistance. The statements made are those of the rapporteurs or individual meeting participants and do not necessarily represent the views of all meeting participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine.

PLANNING COMMITTEE ON CURRENT TRENDS IN SYNTHETIC BIOLOGY: A WORKSHOP: Jef D. Boeke (Chair), New York University Langone Medical Center; Drew Endy, Stanford University and The BioBricks Foundation; Henry T. Greely, Stanford University; Shobita Parthasarathy, University of Michigan; Darlene Solomon, Agilent Technologies. National Academies of Sciences, Engineering, and Medicine Staff: Anne-Marie Mazza, Senior Director, Committee on Science, Technology, and Law; Steven Kendall, Program Officer, Committee on Science, Technology, and Law; Karolina Konarzewska, Program Coordinator, Committee on Science, Technology, and Law.

To ensure that it meets institutional standards for quality and objectivity, this Proceedings of a Workshop—in Brief was reviewed in draft form by Gerald Epstein, White House Office of Science and Technology Policy; Barbara Evans, University of Houston; Karmella Haynes, Arizona State University; and Richard Murray, California Institute of Technology. The review comments and draft manuscript remain confidential to protect the integrity of the process.

SPONSORS: This workshop was supported by Agilent Technologies, the Federal Bureau of Investigation, and the U.S. Department of Homeland Security.

For additional information regarding this meeting, visit: http://sites.nationalacademies.org/PGA/stl/SynBio_Forum/index.htm.

Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2016. Making the Living World Engineerable: Science, Practice, and Policy: Proceedings of a Workshop—in Brief. Washington, DC: The National Academies Press. doi: 10.17226/24656.

Committee on Science, Technology, and Law
Policy and Global Affairs

Copyright 2016 by the National Academy of Sciences. All rights reserved.