The Extremes and In-Betweens of Synthetic Biology

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When a cartoon is in the early stages of production artists craft the storyline by creating a series of still images. Those images, referred to as “extremes”, depict characters in their most exaggerated positions and are often used in the final stories as visual hooks and punchlines for the audience: anvils are falling on heads; bodies are magically suspended miles above ground; tears are streaming from eyes. Chuck Jones, who famously created the Road Runner and Wile E. Coyote characters for the Looney Tunes series of animated shorts, was a master of extremes. In the example here, Wile E. Coyote has just suffered his first ever T.N.T. mishap at the hands of the Road Runner. In addition to hooking the audience, extremes can be thought of as caricatures of the characters and plot.

Of course the extremes might provide comical hooks, but they lack the detail required to bring the characters in any cartoon fully to life. That job falls to the “in-betweeners”, those individuals whose craft it is to link the extremes together with thousands of detailed drawings, each one a segment of the subtleties of life-like behaviour. The in-betweeners do a lot of heavy lifting. Without them a cartoon is merely a series of exaggerated postures.

I recently attended a colloquium on the state of Synthetic Biology (SynBio), hosted by the University of Ottawa’s Institute for Science, Society and Policy (ISSP). The colloquium was called Synthetic Biology at the Interface of Science and Policy. SynBio, roughly defined, is the technology (or set of technologies) that allows users to create in living organisms, new functions that have not previously existed. The colloquium brought together experts in the science of SynBio, policy, law, ethics and other academic fields, to foster a dialogue about SynBio’s many social implications. According to Marc Saner, the current Director of the ISSP, the colloquium was designed as an opportunity to begin moving away from the “extremes” of discourse surrounding SynBio, and into the in-betweens that allow for a fuller expression of the social dimensions of the technology.

The Extremes of SynBio

Both opponents and proponents often caricature new and controversial technologies. Those caricatures can take the form of blunt statements about why a technology is good or bad. In the early days of artificial insemination, for example, proponents characterized the technology as one that was giving the gift of life to couples who couldn’t get pregnant on their own, while opponents argued that the technology was dangerous, unproven and unnatural. These kinds of caricatures are typically drawn before the full impact(s) of a technology is understood by the various groups—users, developers, marketers, and so on—who find themselves engaging the technology first-hand. The result is that the caricatures are unhelpful to policy makers, because they lack the factual nuance that is required for good policy development.

These caricatures are also noticeable with biotechnologies such as SynBio, as was pointed out by keynote presenter, Michele Garfinkel, from the J. Craig Venter Institute. Opponents of biotechnologies argue that we shouldn’t be playing God, or that some unpredictable catastrophe will occur, such as the famous Grey Goo hypothetical, in which self-replicating machines devour the world as a process of their survival, leaving behind only grey goo. At the same time, proponents of new biotechnologies provide counterpoint caricatures by arguing how the technology could lead to a cure for diseases, or that SynBio is no different from what is already going on in nature.

None of these extremes properly characterizes SynBio, nor do they accurately capture the social implications of it. Caricatures might provide a starting point for a discussion on how to move forward on policy surrounding SynBio, but they must be jettisoned at some point in the process if the resulting discussion is going to be fruitful. As Garfinkel pointed out, the extremes must be recognized in order to help legitimize the outcomes of the policy discussion. But there is a lot of work to be done to sort out what to make of the extremes, that is how to interpret them, then in deciding how to use them to craft more nuanced understandings of the values that are at stake, including crafting meaningful policy recommendations.

Part of the problem with extremes is that they tend not to provide an accurate factual understanding of technologies like SynBio. Getting the facts right, understanding what SynBio is and what it is not, is important for getting past the extremes. I’ll offer a short synopsis of how SynBio was described during the colloquium in order to begin the shift away from the extremes, and toward the in-betweens of SynBio.

The State of SynBio

One of the most prominent themes at the colloquium was the use of engineering analogies when discussing the state of SynBio technologies. According to several of the speakers, including Mads Kaern, Canada Research Chair in Systems Biology at the University of Ottawa, SynBio has moved beyond the lab, where genes were sequenced and replicated with varying results and consistency, and into the production line, where genes are (relatively) easily sequenced, characterized, catalogued, replicated, and sold as standard parts on the Web.

Having standardized parts has played a big role in the development of modern technology, allowing virtually an unlimited number of people access to the bits and pieces needed to design and build things in the world. Think of the screw as an example. Prior to the standardization of screws, each person who wanted to screw things together had to design the screws himself in order to ensure some degree of consistency in the thread spacing, pitch, length, material being used, and the tool needed to screw it into place.

That changed once standard screws were designed, the kind you get from any hardware store today. Now you can order screws from anywhere and expect them to be interchangeable. Standard parts free up designers to focus on the bigger picture of the design, rather than toil away in the details of every part, and also speed up the design and manufacturing process considerably. Designers can communicate their designs easily to other experts by using standard parts in the description of the technology. That ease of communication and manufacturing also means that more people outside of the relatively small community of designers are able to build things.

SynBio has undoubtedly moved beyond the lab and into its own era of standardization. Online sites, such as the BioBricks Foundation and the Registry of Standard Biological Parts (http://partsregistry.org/Main_Page) are working towards cataloguing a collection of genetic parts—BioBricks—that are openly available for use in the reconfiguration of biological entities. BioBricks are “DNA sequences that encode a defined biological function and can be readily assembled with any other BioBrick part”. Put bluntly, it’s LEGO in a test tube.

BioBricks add a level of abstraction and speed to the design process. Researchers are encouraged to “mix and match” BioBricks to build “synthetic biology devices and systems”. Parts can be ordered online from companies like New England BioLabs (www.neb.com). The complete newbie can even order an assembly kit that includes “50 reactions” for $235 (http://www.neb.com/nebecomm/products/productE0546.asp). What’s a BioBrick assembly kit, you ask? According to the company’s Web site:

"The BioBrick™ Assembly Kit provides a streamlined method for assembly of BioBrick™ parts into multi-component genetic systems. BioBrick™ parts are DNA sequences that encode a defined biological function and can be readily assembled with any other BioBrick™ part. The process for assembling any two BioBrick™ parts is identical and results in a new composite BioBrick™ part."

BioBricks and the technology surrounding their use are relatively accessible. The annual International Genetically Engineered Machine competition (iGEM), features high-school students, university undergrads and grad students competing to see who can invent the coolest new organism. One of the example projects listed on the iGEM website (http://igem.org/IGEM/Learn_About) is “BactoBlood”:

"The UC Berkeley team worked to develop a cost-effective red blood cell substitute constructed from engineered E. coli bacteria. The system is designed to safely transport oxygen in the bloodstream without inducing sepsis, and to be stored for prolonged periods in a freeze-dried state."

SynBio could eventually be accessible to gardeners as well. Christina Agapakis, a research fellow at UCLA, described how BioBricks are being used in the Harvard iGarden (http://craftbot.tumblr.com/tagged/science):

"The Harvard iGarden is a venture into plant engineering. Our aim is to create a toolkit for the cultivation of a personalized garden containing features introduced through synthetic biology. In addition to a “genetic fence” designed to prevent the spread of introduced genetic material, we have developed three independent features to be included in this toolkit - inclusion of novel flavors, knockdown of plant allergens, and modification of petal color. All parts are BioBrick compatible and introduced into plants through agrobacterium-mediated transformation, using existing plant vectors modified with the BioBrick multiple cloning site. The Harvard iGarden, beyond being an application of the BioBrick system to plant engineering, is an effort to raise public awareness of synthetic biology, production of food, and how the two can intertwine. We envision the iGarden as a medium through which the non-scientist can see the power and potential of synthetic biology and apply it to everyday life."

A shift towards standardization and an engineering analogy raise important ethical questions for SynBio. The accessibility and speed of production that follows from standardization will mean that more and more people are able to turn to SynBio as a career choice, much like accessibility and standardization gave rise to careers in information technology (IT) through the latter half of the 20th century. Societal decisions will have to be made whether or not we want those individuals engaged in SynBio to meet certain ethical criteria. It would make sense to have the scientists doing the actual work as participants in that discussion.

The In-Betweens of SynBio

Based on the state of the underlying technology, an engineering analogy seems highly appropriate for describing SynBio. But if that’s the case, then we have good reason to ask whether or not SynBio ought to be subsumed under the same regulatory and ethical frameworks as other engineering disciplines. At the very least, we should ask whether or not it makes sense to demand certain formal education in ethics for SynBio designers.

What would that mean for SynBio? For a start, academic institutions might consider offering SynBio programs in partnership with already established Engineering faculties. A similar shift occurred throughout the 1990’s when many Computer Science departments became parts of newly formed Computer Engineering departments. In those moves much of the core of Computer Science curricula were maintained, the primary difference being that Computer Engineering students were required to complete the core Engineering courses, including the requisite ethics courses, that are integral to the practiced profession.

In addition to the ethics components embedded in the curriculum of an engineering program, all Canadian engineering graduates are required to swear an ethical oath as part of entry into the profession. This takes place during the “Iron Ring Ceremony”, and serves to remind graduates of the ethical responsibilities they bear as members of a community of practise. It also serves to remind graduates that they are bound by particular professional regulations. Members of other (non-Canadian) professional engineering organizations, such as the Association for Computing Machinery (ACM) or the IEEE require good standing in order to benefit from membership in those associations. Encouraging practicing professionals to remain in good standing with their respective associations reinforces the importance of adhering to those codes of conduct.

The benefits of training SynBio students under the auspices of professional engineering faculties and the professional ethics codes they imply, is that the language of ethics is embedded into the education process from the start, and into the profession in an ongoing manner. This can serve several purposes. First, it can help to develop good ethical traits in the individuals who will eventually practise SynBio. Second, it can establish expectations among SynBio professionals with respect to the boundaries of good practise. Third, a focus on ethics helps to frame an ongoing dialogue about the ethical implications of SynBio. Fourth, it ensures that SynBio designers will be able to participate fully in the discussions surrounding the ethical aspects of their practice.

A move to train SynBio designers in engineering faculties would be beneficial. However, it is a big move, and probably quite a ways off. In the meantime, it seems that it is incumbent on those departments that are currently teaching individuals how to build and use the technology, given the obvious social implications of SynBio, to teach them also how to evaluate the ethics of it.

Some sort of formal education in the ethics of SynBio in particular, and perhaps engineering ethics in general, would be a good start in developing in SynBio practitioners, at the very least, the vocabulary needed to discuss ethical issues surrounding SynBio with a degree of sophistication matching the sophistication of their technologies. The sense I got at the colloquium was that this is not yet happening. Take, for example, the student iGEM team I spoke with at the University of Ottawa. Though the rules of the competition require them to provide a “Human Practices” component in the report, which roughly tries to promote thinking through some of the social implications of SynBio, it was clear in discussing that aspect of the competition, that the students aren’t offered any formal introduction or education with regard to assessing the social implications of SynBio.

The lack of formal scientific education in the social implications of science and technology is not surprising, and I certainly don’t mean to seem as though I’m blaming students for not knowing what they don’t know. My own experience as a student in science and engineering faculties reminds me of the general disregard that exists there towards the humanities. But it is a disregard without warrant. The general outcome of a lack of formal ethics education is predictable enough: we are currently graduating scientists who are unable to engage in meaningful conversations about the ethics (social implications) of their very own work.

Am I proposing that science faculties ought to inject a pile of ethics courses into their already crowded curricula? No. But I am suggesting that science faculties ought to inject at least one course in ethics into their curricula. I’m also suggesting that science faculties will benefit from doing so. They will benefit by graduating scientists who have a capacity for responding to, and discussing, some of the concerns raised by the publics who support much of their work. They will benefit from the positive contributions that scientists will be able to make, not only in their technical fields, but also in the policy discussions surrounding them.

We can do better than to leave scientists in the dark when it comes to understanding and evaluating the social implications of their work. As SynBio develops further as an engineering-like discipline, but before it goes too far, it would be beneficial to the discipline to develop a more nuanced ethical vocabulary than it currently has. This can be accomplished through formal exposure to the rich ethics literature that exists on topics related to the sciences. A nuanced ethical vocabulary allows the discussion to move away from the extremes and towards the in-betweens of ethical issues. Other scientific disciplines, including engineering, nursing, and medicine, have all benefitted from similar moves. Is SynBio any different?