Lectures

Understated, not overlooked

A Simpler Life: Synthetic Biological Experiments

Talia Dan-Cohen

Cornell University Press, 2021. 174 pages.

First, take a self-consciously self-aggrandizing area of bioengineering, “synthetic biology,” which was said to aim at nothing less than “the design and construction of novel life-forms” (Dan-Cohen, p.12), an apparently clear claim made by those with a platform from which to make it, one that is in fact riddled with indeterminations. Then, take the fact that multiple modes and kinds of anthropological engagement with this domain of technoscience were undertaken, contemporaneously, in the decade between roughly 2006 and 2016. Two modes of such engagement can be named: one involved efforts at collaboration between those working in synthetic biology and those in the human sciences to think together about ethical questions pertaining to this practice and its effects, a mode of anthropological engagement that had critical (Aguiton 2018), and diagnostic variants (Rabinow and Bennett 2012), as well as variants that mixed first-order and second-order critical and diagnostic interventions (Balmer, Bulpin, and Molyneaux-Hodgson 2016). A second mode of anthropological engagement was focused on the rhetorical acts of synthetic biology, its claims about the future heralded from a supposedly emergent present, the study of which had both instrumental and diagnostic variants (cf. Ginsberg et al. 2014), as well as a version I have had the occasion to name as “kitsch” (Roosth 2017; Stavrianakis 2018).

Midst this cacophony of discourse enters A Simpler Life, Talia Dan-Cohen’s discerning study of two laboratories engaged in this crossover field, a field of practices located amongst and between engineering and biology. Drawing on a felicitous phrase from Steven Shapin, Dan-Cohen aims at “lowering the tone” (Shapin 2010, cited in Dan-Cohen, p.8). Hers is a mood of understatement, in a field of hyperbole; a mood that accompanies a descriptively rooted, and attentive, look at what is under those statements, which concern a set of activities that have been both, in a certain sense, under-observed and over-looked. 

The scene of inquiry is Princeton, which is both field site and setting of Dan-Cohen’s graduate pedagogy in anthropology, although the latter, despite Dan-Cohen’s own call (following Gusterson 2017) to make the university an object of anthropological attention, is kept well out of the frame: the first parameter of figuring out the genre of the book is that it is very much a kind of “anthropological realism” after “anthropological modernism”––if one takes up modernism in the sense of Rosalind Krauss’s explorations of the mutual interconnections of medium (in this case the medium of inquiry as fieldwork and writing), and technical supports (the norms, conventions and logic of inquiry cf. Rabinow and Stavrianakis 2019). It is “after” modernism to the degree that Dan-Cohen is explicit and reflective about the genre conventions she is following, and which she then brackets, closing off that modernist self-awareness in order to get at what the inquiry was really about, to wit: the ordinary life and work of making knowledge and making biological functions, through experiments, and perhaps even, although this is the hard part, making knowledge of those functions, and functions of that knowledge within a common experimental frame. 

Ordinary life and work, that is to say, within a developing discipline that considers itself out of the ordinary, on the verge of something else, a verge that Dan-Cohen captures by way of, what she calls, late in the book (Epilogue, p.118) a “pathos of vertiginous endings”: the pathos that is, of the inevitable and recurrent breakdowns of––and just as recurrent efforts to repair––The Big Idea, or The Vision of a Science (of life, and life of science) To Come. 

It is with this ringing last cord that I think we can go back to read the metaphorical key in which the book begins: against the pathos of the synthetic biology project, a pathos of the object of inquiry, on the observer side, with respect to the mode of observation of the object, Dan-Cohen refers to what Matei Candea has called the “calculated irony” of the “village study,” taking it as orientation, if not exactly a model, for what she calls her lab ethnography. Vertiginous pathos grasped through calculated irony. 

The term irony is ambiguous, however, not least what it could possibly mean to use such a trope without calculation. The reference to Candea (2007), and his consideration of the fact that the global, the network, and the multi-sited are just as much artifice as “the bounded field site,” is nevertheless the modernist gesture Dan-Cohen requires to then get back to her realist endeavor, an endeavor that despite the insistence on it being something like a village study of the close-at-hand, in my view could be read as something else; a proposal for how to use observations from fieldwork to disrupt how cartographic metaphors operate in anthropological frames of observation. 

Her use of irony, whatever else it may doing, insofar as it was “built in from the start,” is what allows Dan-Cohen to achieve a stable, even fixed, distance on her object of inquiry and to maintain a frame of observation on an object she locates “a little off to the side” of the major action in synthetic biology. Whether her spatial metaphor is ironic or not, I cannot say, but I do think that despite her insistence on the spatialized image of the periphery, and its sociological ranking, Princeton as located in “privileged isolation,” I see the effect of her use of distance (not the distance of the far away but a proximate distance), as disrupting recourse to any obvious spatial metaphor. Rather than her object being quaint or minor, the closeness between Dan-Cohen and the University site as field setting, the physical proximity to the two labs, regardless of their supposed symbolic distance from the institutional games of credit, reward and fame in synthetic biology, poses the question of what separates these two labs from each other, and what separates Dan-Cohen from the field of observation, and hence then also how to connect them, the two labs, and Dan-Cohen to them, with respect to the field of synthetic biology. The topological rather than topographical point is that sets of practices to be observed can be separated, within the open set that is defined by Dan-Cohen’s object of attention, namely, experimentation. 

In her deft hands, which I insist on, since the voice throughout is exegetical, the ironic mode and mood works to the degree that it is precisely built in to the constitution of the object of inquiry: it’s the expository alternative to a question that could also be, in turns, either naïve or bullying: “what are you doing?” (or, what are you doing??!!) It is the great merit of the work, and a pleasure for those who want to know something about synthetic biological experiments, that she found the register through which to ask the question. 

And this is the force of the work. In a very readable and cogent manner, the book provides a serious engagement with the question of what these two labs were doing. It provides an examination of the actuality of some instances of the scientific and engineering work that goes on under the banner of this endeavor, one that is supposed to be set (ready, set and go, still fifteen years later), to remediate the future of bioengineering. It is also, and moreover, a case in point of the broader question of why an anthropologist would be interested in a given area of technoscience, regardless whether or not that future comes about.

Failed pathos discerned through an unflinching adjacency, close to and knowingly separate from, an irony that is cool, not cruel (cf. Max Weber’s caustic mockery of those Big Children in University Chairs and Editorial Offices.)

Dan-Cohen’s concern is the specific relations between knowing, ignorance, experimental intervention, and experimental failure, which are a core set of terms that structure her account of the work of the two labs she observed: the Weiss lab, based at the time in the electrical engineering department, whose projects turned for the most part on programing different kinds of synthetic gene circuits to function in mammalian cells; and the Hecht lab in Princeton’s chemistry department, which worked mainly on de novo protein design. If the former is an exemplar of synthetic biology recruitment channels, an MIT-trained computer engineer who wanted to build biological circuits, the latter, a chemist, is crucial to the topology of the study, to the degree that insofar as the Hecht lab is something of an outlier, at the level of (cartographic) description, they are doing nevertheless what “synthetic biologists” are supposed to do, that is, make new biological functions. The Hecht lab couldn’t exactly be considered a “control” case, but the lab’s work functions as a difference that makes a difference to what the reader can consider as the synthetic biology endeavor, it provides the means of separation and distinction. It is also a key site for thinking about the more diffuse question of how experimental significance is judged. 

The core question of what knowledge does (rather than what it is) is parsed through two chapters “The virtues of the naïve point of view” (chapter two) and “looking for patterns” (chapter 3). The first of these takes up a central tenet of synthetic biology and addresses head on the key line of criticism that bioengineers face, usually when talking to molecular biologists, namely that biological functions are context-dependent and complex, and hence efforts to “black box” these characteristics are doomed to failure. Dan-Cohen takes a shrewd line on these discussions to the degree that a hallmark of social science is typically to side with complexity against any form of reductionism. As such, one might expect the anthropologist to engage in a critical reading of the synthetic biology endeavor precisely to the degree that as an endeavor it tries to reduce, to bracket, to make operative, regardless of context. Instead, Dan-Cohen asks what non-biologists’ ignorance (engineers and chemists) allows them to do. It is not a paean to not knowing, but it is a ruffling of the additive view of knowledge, as though synthetic biology could be reduced (so to speak) to the sum biology + engineering. 

We read instead of the kinds of questions that were posed and experiments tried when you don’t know already––can you transform stem-cells directly into beta-cells? Surveys in stem-cell biology say “no”; our synthetic biologists, who didn’t know better, say “yes!” –– and can prove it experimentally. Now, in point of fact, many synthetic biology experiments, we are then told, failed over longer periods of time precisely because of a lack of biological knowledge, and Dan-Cohen tells us that over the last few years, most practitioners have “conceded complexity.” The crucial point though is that complexity didn’t come for free: it had to be earned, and it was earned by those engineers who thought they could get around it, or didn’t know “better” than to start on the basis of it. 

Chapter three is then a case in point of the “negotiations” that occur between a stated design goal, a model, and the experiments, in which there is no obvious a priori or essential priority, or index. In the words of Weiss, the engineering lab director, “Ideally the model and the experiment produce the same results right off the bat,” (p.68) although this never happens, we are told. “The model and the experiment are therefore herded toward a point of convergence, and the choice of which one must be made to accommodate the other is itself not trivial.” Crucially, their convergence depends on the design goal. The example given is that of “Turing patterns” and the Weiss lab’s endeavor to create a designed biological pattern through a reaction-diffusion process in genetic circuits in e. coli (eight genes regulated by five promotors, secreting two artificial diffusible morphogens.) And there was a deterministic model to go with it that produced tidy patterns. The experiments we are told, in a beautiful example of Dan-Cohen’s penchant for litotes were “less than stellar.” Less than stellar, that is to say, in comparison to the model, which produced “neat shapes, evenly distributed.” In relation to the design goal, to make a Turing pattern, however, the question was then raised: what is a pattern? Weiss and colleagues had to rethink their model in relation to a re-imagined design goal, natural patterns aren’t neat and tidy, they had to rethink their orienting image. Dan-Cohen refers to Ingold and Hallam’s work on creativity (2007) to make a case for the (intellectual) work of design itself involving hands on making, and improvisation. Designs, and not only experiments are “underdetermined and flexible” requiring, at each moment a consideration of the purpose relative to which model and experiment are confronted with each other. 

The reader is then in position to think about the question of significance in relation to knowledge, ignorance, and biological function. Is it sufficient that a de novo biological design works? Is it important, or necessary, to know how it works for it to count as knowledge? And in the economy of science, the crucial question is whether it is necessary to know how it works for it to count as significant knowledge that should be published. 

The Hecht lab is the center of the fourth chapter, “To the Editor,” which focuses on a rebuttal written in response to a rejection of an article, at a major journal, a relatively rare genre of scientific writing, whose analysis allows Dan-Cohen to link the broad theme of trust and virtue in science, with the specific theme of ignorance and knowledge as it pertains to synthetic biology. 

Whether the Hecht lab are trustworthy scientists, and whether they know enough about how their proteins’ function, become two interlinked questions in the exchange of letters between the lab and the journal. The article that was submitted suggests that the lab’s synthetic genes that code for de novo proteins are rescuing cells that unable to synthesize a particular organic compound required for growth, “auxotrophs.” The reviewers agreed that if this were the case this would indeed be significant. All reviewers however seemed to share a similar concern: are the proteins themselves rescuing the cells, or is overexpression of the proteins changing something else in cell function, which is then responsible for the cells’ salvation? The reviewer says it is “disconcerting” that the Hecht lab did not test enzymatic activity of their purified proteins. The Hecht lab response is of note, not only because it give a glimpse into the ethos of this particular scientist (Hecht) and his lab, but also because of the hovering concern for synthetic biologists about what it means to know something on the basis of synthetic biological experiments. The Hecht lab response turns in part on discerning and determining that a synthetic biologist’s ethos is of a piece with the larger scientific endeavor. They wrote that it would be “foolish” or “arrogant” of them not to have tried exactly what the reviewer suggested. They have been doing just that: for three years. The difficulty of the task was unexpected, and certainly the reviewer cannot have known how difficult a task it is (purification of the enzyme). What the Hecht lab rebuttal aims at is to tackle head on the implicit claim that they were either too “lazy” or “careless” to bother doing the experiments or of thinking of them. Again, the question is not one of being for or against simplicity or complexity, but of the price to be paid to try to get around complexity. Hecht wanted the journal to know that they were paying that price. 

In that sense, Dan-Cohen’s own mode of work mirrors her object: she paid the descriptive price of endeavoring to describe parsimoniously, with nuance, the efforts to simplify the engineering of complex biological functions, and to observe, describe and analyze the underdetermined, overdetermined and indeterminate results of these experiments. 


Anthony Stavrianakis is an Assistant Research Professor in the CNRS, a member of the Laboratoire d’ethnologie et de sociologie comparative CNRS. His book, Leaving: A Narrative of Assisted Suicide, was published by University of California Press in 2020.


References

Aguiton, S. 2018. La démocratie des chimères. Gouverner la biologie synthétique, Lormont, Le Bord de l’eau, coll. « Objets d’histoire », 

Balmer, A., Bulpin, K., & Molyneux-Hodgson, S. (2016). Synthetic Biology: A sociology of changing practices. Springer.

Candea, M. (2007), Arbitrary locations: in defence of the bounded field-site. Journal of the Royal Anthropological Institute, 13: 167-184.

Ginsberg, A. D., Calvert, J., Schyfter, P., Endy, D., & Elfick, A. (2017). Synthetic aesthetics: investigating synthetic biology’s designs on nature. MIT press.

Gusterson, H. 2017. “Homework: Toward a critical ethnography of the university: AES presidential address, 2017.” American Ethnologist44(3), 435-450.

Hallam, E., & Ingold, T. (2007). “Creativity and Cultural Improvisation: An Introduction.” In Creativity and Cultural Improvisation, 1-24, edited by Elizabeth Hallam and Tim Ingold. Oxford: Berg.

Rabinow, P., & Bennett, G. 2012. Designing human practices: An experiment with synthetic biology. University of Chicago Press.

Rabinow, P., & Stavrianakis A. 2019. Inquiry after Modernism. Haven. Open access publication available at https://www.snafu.dog/publications-1 (last accessed May 2021). 

Roosth, S. (2017). Synthetic: How life got made. University of Chicago Press.

Stavrianakis, A. 2018. “Genre trouble.” BioSocieties 13, 657–663.


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