Human Practices 1 Overview 2 Metaphors We Build Life By 3 Outreach 4 Cooperation and Collaboration 5 Does intellectual property work as intended for synthetic biology? 5.1 Introduction 5.2 The Problem 5.3 Alternatives 5.3.1 Status Quo 5.3.2 Abolition of Gene Patents 5.3.3 Sui Generis Framework 5.4 References

Human Practices

Overview

When reflecting on human practices over the course of our iGEM project, several major themes emerged. We considered major policy issues (intellectual property policy, biosecurity, licensing), the extent and nature of public opposition to synthetic biology, research and bioethics, outreach, collaboration, and decision-making in conditions of uncertainty.

Metaphors We Build Life By

Synthetic biology is a creative human activity, and although quantitative engineering frameworks can increasingly be employed for formalized analysis, prediction, and optimization of biological systems, the influence of human cognitive quirks, limitations, and uniquenesses on synbio design remains inherently substantial. Especially when considering challenges in synthetic biology that might be called “wicked problems,” (and it may be the case that all problems are wicked, only becoming tractable when artificially defined tamely - http://www.sciencedirect.com/science/article/pii/S0142694X04000626), the metaphors and symbolic systems we use crucially determine our problem-defining and solution-exploring activity. Many of these metaphors are verbal (“BioBrick,” “circuit,” etc.), and have drawn some reflection and investigation, but the primary emphasis of discussions of metaphor in synthetic biology representation has so far seemed to have been on metaphors being taken literally or framing public discourse.

We propose incorporating insights from cognitive science into the intentional design of representations in synthetic biology for the purpose of fostering clearer, more innovative, and more reflective synthetic biology practice. Many dimensions of synthetic biology radically diverge from the normal objects of established ways of considering design, risk, and ethics using conventions of natural language, intuitive models of causality, and narrative structures. This branch of human practices research and intentional reflection would develop a vocabulary of concepts, visual metaphors, and relational phrases with researchers in mind.

Although a stereotypical “synthetic biology thought process” is not obviously easily characterized--synthetic biologists include people from a dizzying array of backgrounds, institutional affiliations, age groups, and (inter-)disciplines, working in an emerging field without a stable definition itself--there are also many aspects of the composite elements of synthetic biology practice that may be limiting.

Our language and physical actions and surroundings are not irrelevant to our design choices. A core lesson we’ve learned about cognition over the past few decades is that it is fundamentally embodied. Physical environments and actions are profoundly intertwined with higher-order mental processes scaffolded onto them (http://www.yale.edu/acmelab/articles/Scaffolded_Mind_EJSP.pdf). Seemingly irrelevant aspects of physicality influence behavior and cognition related to concepts connected by mere metaphor to the stimulus, such as room or coffee temperature impacting description of others as having “warmer” or “colder” personalities (height of ceilings, visibilities of certain colors, etc. also have strong effects - http://blogs.plos.org/neuroanthropology/2012/01/10/brainy-trees-metaphorical-forests-on-neuroscience-embodiment-and-architecture/, particularly on engineering creativity http://www.newyorker.com/reporting/2012/01/30/120130fa_fact_lehrer), and similarly, physical metaphors in language frame how we think about problems. In the context of synthetic biology, metaphors like “BioBrick,” “circuit,” etc., as well as the structure of diagrammatic representations (such as block diagrams, genome annotations, smiley faces on E. coli) don’t just reflect but influence how we think about constraining our imaginable possibility-ome.

To make the forward-engineering of biological systems manageable, synthetic biology has largely relied on porting electrical engineering and chemical engineering language into a biological context. Although this kind of systematization enables the analysis, prediction, and engineering of otherwise impossibly complex systems, it also risks hampering innovation if it prematurely determines a single function-object pairing when many are conceivable, a cognitive bias called functional fixedness.

Our project specifically involved overcoming functional fixedness on a number of levels: the use of bacteriophages for diagnostics conventionally involves phage display reliant on a marker on the phage particle rather than the expression of a reporter gene, and pregnancy tests are usually used to determine pregnancy. We open-endedly describe potential uses for our parts in the Registry.

Accompanying rapid advancements in graphic-computational power, a number of visualization and animation projects have aimed to capture in increasing depth the bewildering world of the cell (cf. Maya molecular movies http://www.molecularmovies.com/learning/, Cornell’s 2011 iGEM Team’s animation project https://2011.igem.org/Team:Cornell/Video). The language used to describe such projects often entails some variant of “draw pictures to dumb things down for the general public” (e.g. Cornell iGEM: “Bringing up "Synthetic Biology" in a conversation with anyone outside the field will elicit question marks. Anything muttered after those words will be forever lost to the public. … We seek to communicate our ideas with the public via effective animation … designed to entice our audience, draw them in, and enable them to attach our explanations to physical phenomena.”). It's not just the public who needs careful representations, though. In the face of bewildering biological complexity, likely unmanageable uncertainty, simultaneous conflicting value frameworks, overlapping imaginaries of fantastic promise and doomsday scenarios, and especially as synthetic biology’s de-skilling agenda results in increased diffusion to lower-expertise practitioners, visceral mental models of how biology works and can be rebuilt will be increasingly influential in determining the products of synbio design.

In the sphere of ethical reflection, using inorganic metaphors (information, computer, machine) may lead to different normative conclusions about objects of genetic engineering than more conventional language used to describe life. Given that everything we know about life supports an exclusively mechanistic understanding of its biochemical/biophysical underpinnings, such metaphors are likely more precise descriptions of reality, but they can also clash with and provoke strong opposition from those who are operating in incompatible frames. Additionally, ethical thinking about emerging technologies is strongly conditioned by culturally embedded arch-narratives despite unprecedented and counter-intuitive technical realities (http://www.springerlink.com/content/c910r5n055614585/). Further, ideologically-laden vocabularies are used by opposition groups to frame debates, and conversely public proponents of synthetic biology may espouse optimistic unbalanced vocabularies in describing the future.

Careful conceptual vocabulary design can also be an important strategy as synthetic biology seeks distributed mechanisms for promoting biosafety. Ensuring safe practices among increasingly diffuse practitioners of synthetic biology is a complex challenge that is not feasibly amenable to conventional models of centralized regulatory oversight, and self-enforcing models are increasingly being pursued. Interestingly enough in at least some contexts, priming subjects with a moral code can completely eliminate of a particular form of dishonest behavior, likely a byproduct of self-concept maintenance (http://duke.edu/~dandan/Papers/PI/Dishonest_JMR.pdf). Although the results observed in the context of test-taking behavior can hardly be transferred directly to the challenge of synthetic biology self-governance, they imply that an agenda of promoting mindfulness of principles of safety by embedding them into the synbio culture in conjunction with some shared self-concept that prioritizes safety. Since self-concept is strongly influenced by media representations, the continued portrayal of technologists in promethean/frankensteinian/autistic stereotypes might make this an uphill battle.

Conclusions and Recommendations

Talking about and practices synthetic biology necessarily involves active human involvement in presentation, which profoundly impacts present and follow-on design cognition. The generation of explanatory concepts, visual representations, and language-based models in most fields happens fluidly, but in synthetic biology, many established or familiar ways of thinking about problems are conceptually inadequate to handle the technical reality, especially when situated in unmanageably complex global ecologies. To facilitate thoughtful synthetic biology design in the public good, synthetic biologists should drawn on cognitive science to develop habits of mind, representations, and metaphors amenable to more realistic design intuition and effective engagement.

Criteria for designing synbio representations
Designability
- Conceptual precision - Does the representation realistically portray its referent?
- Quantifiability - Is the representation compatible with related quantitative analysis?
- Imaginability - To what concrete, mentally manipulable images is the representation linked?
- Functional fixedness - Does the representation exclusively determine a particular function?

Public engagement and policy
- Clarity - Is the representation foreseeably misunderstood, especially, if taken literally?
- Framing - Does the representation prematurely imply a particular problem definition or solution strategy?
- Sensationalism - Does the representation imply unrealistically optimistic or pessimistic views?

Properties to incorporate in synbio metaphors
- Evolution
- Self-organization
- Self-replication
- Complexity
- Multiplicity
- Parallelism
- Emergence
- Situation within global microbial ecologies
- Situation within global socioeconomic ecologies
- Uncertainty

Metaphors worth critically re-visiting
- Biology as machine
- Biology as information
- Human as “engineer”

Outreach

- We dramatically increased awareness and visibility of iGEM and synthetic biology on UVA Grounds as part of recruitment over the past year, attending as a group or running informational tables at events related to bioethics, engineering, and synthetic biology.
- We organized and helped lead a Flash Seminar on Ethical Issues in Synthetic Biology with a member of the Presidential Bioethics Commission. Flash Seminars are one-time student-organized “learning flash mobs” open to undergraduate and graduate students, community members, and faculty, during which people from diverse backgrounds can meet and discuss topics of interest (http://www.washingtonpost.com/wp-dyn/content/article/2011/02/20/AR2011022002666.html).

Ethical Issues in Synthetic Biology
Led by Bioethics, Philosophy, and Public Health Professor John Arras
Two years ago, the J. Craig Venter Institute announced that it had created the world's first self-replicating synthetic genome in a bacterial cell of a different species. The discovery prompted many people to consider the benefits and drawbacks of the emerging field of synthetic biology. While new innovations present opportunities for progress in clean energy products, pollution control, affordable food, vaccines and other medicines, they also introduce harmful risks to humans and communities. This seminar will focus on the safety and security issues posed by the new technology and discuss some of the future-oriented concerns involved with human enhancement.

Cooperation and Collaboration

- Solicited and offered skills using NTMU’s Matchmaker: https://2012.igem.org/Team:NTNU_Trondheim/Matchmaker
- Our advisor was able to help Team Groningen: https://2012.igem.org/Team:Groningen/international_cooperation
- Provided feedback to Team Grenoble on their design for a BioBrick Safety Sheet: https://2012.igem.org/Team:NTNU_Trondheim/Matchmaker
- Responded to UBC’s survey on intellectual property: https://2012.igem.org/Team:British_Columbia/Human_Practices/IP_FAQ

Does intellectual property work as intended for synthetic biology?

Introduction

The emerging field of synthetic biology generally aims to make biology easier to engineer by adapting engineering methodologies to biological systems (Endy, 2005). It promises to produce fundamental advancements in fields ranging from biomedicine to energy, but is also rife with concerns regarding ethics, safety, and governance.

Synthetic biology also spotlights issues of intellectual property, sharing, and innovation (Oye & Wellhausen, 2010). Ideally, intellectual property would provide incentives that effectively promote innovation, align those incentives with social utility, and promote socially equitable cost burden and distribution of the products of innovation. in the form of patents

The Problem

Patent protection is unlikely to harness the potential of synthetic biology. When intellectual property was constitutionally established in the United States as a method for “promoting the progress of the useful arts,” the nature of foreseeable innovation was very different from today’s innovative landscape. Whereas inventions were almost exclusively macro-scale mechanical contraptions, the range of contemporary technologies that have been shoehorned into the patent framework now includes innovations ranging from business strategies to software to self-replicating biomolecular machines. Software code, for example, which can be thought of as a machine made of language, is extremely difficult to justify as either copyrightable or patentable and ends up protected under both systems, an outcome scholars widely regard as harmful to innovative outcomes (Rai & Boyle, 2007). Biotechnology is another field whose nature has defied the conceptual limits of legal constructs formulated. It has been noted that synthetic biology represents a “perfect storm” of characteristics of software and biotechnology that will render existing intellectual property frameworks harmfully obsolete (Rai and Boyle, 2007). Some have gone as far as to claim that status quo patenting practices may snuff out synthetic biology altogether (“How to kill synthetic biology,” 2006).

Patent-driven innovative outcomes synthetic biology can expect can be observed in other contexts. When tested empirically over the past 150 years, stronger patent protection was actually associated with lower rates of patenting (Lerner, 2002, cited in Torrance, 2010). When tested using interactive computer simulations, not only is a patent system significantly worse at promoting innovation than a pure commons in terms of innovation rate, productivity, and social utility, but a commons coexisting with a patent system is statistically no better than a pure patent system (Torrance & Tomlinson, 2009). Psychological insights into the process of innovation are also becoming increasingly messy, indicating that many seemingly irrelevant factors ranging from the height of the ceiling to environmental stimuli influencing dream incubation have strong effects on innovative output (e.g. Kraft, 2005; Anthes, 2009). Biomedical and biological sciences may be particularly susceptible to the so-called “tragedy of the anticommons:” excessive fragmentation of knowledge too far upstream by intellectual property enclosure strongly inhibits follow-on research (Heller and Eisenberg, 1998). An especially strong ethos of open innovation exists within a large segment of the synthetic biology research community in part due to a justified fear of the effects of excessive patenting in the field (Torrance, 2010).

The application of synthetic biology to biomedicine in particular deserves special attention, as it represents an extremely active field of synthetic biology research, many theoretical successes, and astounding promise for the near future (Weber & Fussenegger, 2012).

Although often heralded as the single resounding success of patent policy, pharmaceutical research more broadly is dramatically skewed toward low-importance, high- profit drugs at excessive consumer cost (Love & Hubbard, 2007). Overall, roughly $50 billion per year in private medical R&D spending is incentivized by the social cost of $400-480 billion per year in additional royalty costs due to patent monopoly pricing (Love & Hubbard, 2007) . Status quo legal configurations can be expected to produce similar outcomes in medical applications of synthetic biology.

Alternatives

Alternative policy futures for intellectual property in synthetic biology are diverse and unpredictable, but include the status quo, abolishing gene patents, and the formulation of a sui generis legal framework for synthetic biology innovation. Criteria for evaluation include political feasibility, effectiveness of increasing innovation rate, alignment between incentives and social utility, and distributive justice measured in terms of consumer cost and fairness in distribution.

Status Quo

The existing policy configuration remains the subject of intense criticism from a variety of perspectives. Gene patents are opposed on principle by a variety of groups that view them as commodifying life (Andrews & Paradise, 2005), scientists and researchers believe that the current patent landscape harms openness of research (“Who owns science?” 2009), and the courts have recently challenged prevailing notions of gene-patentability . Since these and other principled concerns are highly unlikely to dissipate in the foreseeable future, we can anticipate a continuing degree of legal uncertainty about the largely court-defined patentability of synthetic biology gene products. As explained above, the status quo will likely inhibit research, skew research toward highly profitable domains that do not necessarily represent social need, and dramatically inflate consumer costs. Although patents also provide an unambiguous method of leveraging “copyleft” licenses, as demonstrated by the BioBricks Foundation (Rai & Boyle, 2007), there is reason to conclude that coexistence of such a commons with the rest of the patent system will not produce substantially better innovation outcomes (Torrance & Tomlinson, 2009).

Abolition of Gene Patents

Recent polls indicate abolishing gene patents is probably the most generally popular alternative, representing a near-majority of the public and about twice the number in favor of keeping the current system as it is (Genetic Engineering and Biotechnology News, 2012). Industry intensely claims, however, that patents are necessary to their innovation. Although it might appease opposition groups, making gene sequences unpatentable subject matter without also providing an alternative system would likely promote a spillover from patents to other forms of intellectual property protection, since genetic material in synthetic biology is formally susceptible not only to patent enclosure, but also to copyright and trademark (Torrance, 2010). Especially in biomedical applications, some form of financial incentive is necessary to overcome the extremely expensive process of clinical trials and regulatory approval, which complicates simplistic analogy to innovation patterns in open source software development (Rai & Boyle, 2007).

Sui Generis Framework

Drafting sui generis (custom, one-of-a-kind) legislation for synthetic biology or biotechnology more broadly may thus be justified. A strong argument can be made that patents simply are conceptually inadequate structures for genetic information (Calvert, 2008), and that this is a key internal link to effectively promoting socially useful research without exorbitant. The BioBricks Foundation constitution, which emphasizes standardization, openness, and social responsibility, provides a model on which to build such a framework (Torrance, 2010). A framework based on this model would ideally provide tailor-made solutions to synthetic biology’s unique challenges of potentially costly regulatory hurdles to translation, ecological risk, and interactional complexity while acknowledging its unique research requirements. However, the process of drafting such legislation is likely to be long, difficult, and uncertain (Rai & Boyle, 2007).

References

Andrews, L. B., & Paradise, J. (2005). Gene patents: The need for bioethics scrutiny and legal change. Yale Journal of Health Policy and Ethics. 5, 403-412.

Anthes, E. (2009). Building around the mind: Brain research can help us craft spaces that relax, inspire, awaken, comfort and heal. Scientific American Mind. 20, 52-59. Retrieved from http://www.nature.com/scientificamericanmind/journal/v20/n2/full/scientificamericanmind0409-52.html.

Calvert, J. (2008). The commodification of emergence: Systems biology, synthetic biology and intellectual property. Biosocieties. 3(4), 383-398. Retrieved from http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=2872712

Endy, D. (2005). Foundations for engineering biology. Nature. 438(7067), 449-453. Retrieved from http://www.nature.com/nature/journal/v438/n7067/full/nature04342.html.

Genetic Engineering and Biotechnology News. (2012). Recent poll results highlight how divisive gene patenting is. Retrieved from http://www.genengnews.com/gen-news-highlights/ recent-poll-results-highlight-how-divisive-gene-patenting-is/81246482/.

Heller, M. A., & Eisenberg, R. S. (1998). Can patents deter innovation? The anticommons in biomedical research. Science. 280(5364), 698-701. Retrieved from https://www.cornellcollege.edu/dimensions/workshops/reading-group-resources/science-280.pdf.

How to kill synthetic biology. (2006). Scientific American, Retrieved from http://www.scientificamerican.com/article.cfm?id=how-to-kill-synthetic-bio.

Kraft, U. (2005). Unleashing creativity. Scientific American Mind. 16, 16-23. Retrieved from http://www.nature.com/scientificamericanmind/journal/v16/n1/full/scientificamericanmind0405-16.html.

Love, J., & Hubbard, T. (2007). The big idea: Prizes to stimulate R&D for new medicines. Chicago-Kent Law Journal. 82(3), 1519-1556.

Oye, K. A., & Wellhausen, R. (2010). The intellectual commons and property in synthetic biology. Synthetic Biology. 121–140.

Rai, A., & Boyle, J. (2007). Synthetic biology: Caught between property rights, the public domain, and the commons. PLoS Biology. Retrieved from http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0050058.

Torrance, A. W. (2010). Synthesizing law for synthetic biology. Minnesota Journal of Law, Science & Technology. 11(2), 629-665.

Torrance, A. W., & Tomlinson, B. (2009). Patents and the regress of the useful arts. Columbia Science and Technology Law Review. 10.

Weber, W., & Fussenegger, M. (2012). Emerging biomedical applications of synthetic biology. Nature Reviews Genetics. 13, 21-35. Retrieved from http://www.nature.com/nrg/journal/v13/n1/full/nrg3094.html.

Who owns science? The Manchester Manifesto. (2009). Retrieved from www.isei.manchester.ac.uk/TheManchesterManifesto.pdf.