Tomorrow's Biology?

Synthetic biology is a decade-old research initiative that seeks to merge biology with engineering and experimental research with manufacture. While the most visible proponents of synthetic biology insist that the field is global, the vast majority of synthetic biology research occurs in Western Europe and the United States. Of that work, much is concentrated in California and New England, and in Cambridge, Massachusetts, in particular. By 2009, when I wrapped up fieldwork conducted primarily in laboratories in MIT's Department of Bioengineering and Computer Science and Artificial Intelligence Laboratory (CSAIL), the synthetic biology research market had swelled to 600 million dollars, and an estimated 95 American universities were doing some kind of synthetic biology research (Bernauer Reference Bernauer2005). This research was funded primarily by the National Institutes of Health, the Defense Advanced Research Projects Agency (DARPA), the Department of Energy, and the National Science Foundation, as well as by private organizations, universities, and venture capital (Bhutkar Reference Bhutkar2005).

Such organizations, which fund the lion's share of professional synthetic biology research, are interested in the field primarily for its potential commercial applications, such as clean energy, bioweapons, and cheap drug synthesis (Andrianantoandro et al. Reference Andrianantoandro, Basu, Karig and Weiss2006; Church Reference Church2005; Forster and Church Reference Forster and Church2007; Purnick and Weiss Reference Purnick and Weiss2009). The most prominent – and mediagenic – example of recent synthetic biology work is Berkeley Professor Jay Keasling's development of a synthetic microbial pathway to synthesize inexpensive artemisinin, an anti-malarial compound, for distribution in developing countries (Ro et al. Reference Ro2006). Another notable synthetic biology project is the work of the J. Craig Venter Institute (JCVI) to synthesize a “minimal” organism (Gibson and Benders et al. Reference Gibson and Benders2008), a single-celled, independently living entity that maintains, JCVI researchers posit, the minimum amount of genetic information necessary to sustain life. In 2010, the Venter Institute announced that it had synthesized and assembled a synthetic version of the M. mycoides genome, inserting it into M. capricolum cells. Venter exulted that his team had made “the first self-replicating species we've had on the planet whose parent is a computer” (Wade Reference Wade2010).Footnote ⁵ If synthetic biologists now define life through its material construction, then the minimal organism becomes a receding horizon: it is not the simplest, smallest, and most genetically austere organism found on earth, but the most genetically minimal viable organism that can be built.

The Synthetic Biology Working Group comprised two laboratories at MIT that were, while I was doing my fieldwork between 2005 and 2009, at the forefront of the burgeoning synthetic biology movement. The first lab was headed by Drew Endy, who, in addition to running his lab at MIT and a DNA synthesis company called “Codon Devices,” also co-founded and directed the BioBricks Foundation, which promoted the Open-Sourcing of standardized biological parts. Over the course of my time in his MIT lab, I watched as Endy's star rose, and both his doctoral students and synthetic biology skeptics described him to me as a charismatic and “larger than life” “religious figure” whose name grew indissociable from the new research initiative he was working to popularize. The principal investigator of the second laboratory at MIT was Tom Knight, a CSAIL research scientist. When I first met Knight, who is affiliated with Science Commons and other Open Source groups, he had already been at MIT for over forty years. He arrived in the early 1960s at the age of fourteen and never left.

One of the central projects of this group was outlining a series of community-approved standards that would set guidelines for the composition and assembly of genetic sequences, objects they term “BioBricks.” The MIT-based Registry of Standard Biological Parts catalogs all such standardized genetic sequences; it currently comprises around 5,100 genetic parts. Practitioners store BioBricks both digitally in an online catalog and physically in freezers at MIT's Registry of Standard Biological Parts. The parts cataloged in the Registry must meet community-approved standards, including the insertion of genetic prefixes and suffixes and the use of approved plasmids and anti-bacterial resistance genes. These standards are meant to make the parts interchangeable between synthetic biologists working on different projects. They are freely licensed in hopes that the strains will be shared openly among researchers, who in turn are expected to share either sequence data or actual DNA with each other. As the slogan of the BioBricks Foundation, which was plastered on t-shirts, bumper stickers, and the signature lines of synthetic biologists’ emails, repeatedly enjoined me: “Share your parts!”

Synthetic biologists hope that a library of standardized biological parts will be a foundational technology that could transform bioengineering from a mode of artisanal production to molecular Taylorism. That is, while the design and assembly of synthetic biological systems is not standardized, synthetic biologists’ aim is that standardized components will allow researchers to use the same BioBrick on multiple projects, rather than testing by trial and error whether functional genetic components will work together each time they begin a new engineering project. They imagine parts or whole systems may soon be ordered from “biofabs” or “foundries,” DNA synthesis companies that fabricate made-to-order genetic sequences. The manufacture and distribution of these BioBricks among synthetic biologists constitutes a “moral economy” of researchers dedicated to building, modifying, and exchanging these parts (Kohler Reference Kohler1994; Shapin Reference Shapin1988; Thompson Reference Thompson1971). BioBricks are built by synthetic biologists, and are almost exclusively used by synthetic biologists rather than “traditional” life scientists. Over seventy academic laboratories are currently enrolled Registry users. Synthetic biologists’ dedication to Open Source approaches to bioengineering is underwritten by BioBricks’ putative modularity, as practitioners value collaboration and sharing and posit that standardizing genetic sequences will engender “openness.” The standardization of BioBrick parts, they hope, will standardize the ethos of openness among current and future synthetic biologists. These built biotic artifacts are at once technical objects and social tools that orient and organize the synthetic biology community.

In his history of drosophila geneticists from 1910 to 1940, Robert Kohler demonstrated that the exchange of fruit flies among researchers engendered the standardization of model organisms. In the case of synthetic biology, this order is reversed. Synthetic biologists build standardization into the system from the get-go in the interest of cultivating free exchange. Their approach is radically different from much of the current bioengineering terrain, which seeks to commercialize and capitalize on new biotechnologies. Synthetic biologists align themselves with an intellectual property doctrine closer to that of Free Software and Open Source adherents than that of most other biotechnologists today. When I once asked Drew Endy why he was so passionate about Open Sourcing biology, he responded, “I don't want wheat fields in 2010 to operate like Windows 95.” On this view, one shared by many researchers with whom I spoke, openness allows for an iterative process that will engender “better” biology, as researchers work together to tweak, debug, and improve upon a system. According to this logic, standardization breeds openness, openness furthers standardization, and the combination leads to “better” biology.Footnote ⁶ Synthetic biologists work to embed the technical and practical norms they want to ground their movement in the objects that they make. Through the work of making and assembling standardized biological parts that are freely shared within the synthetic biology community, synthetic biologists also forward-engineer themselves as a community dedicated to Open Source approaches to biological manufacture. That is, the people and the parts are mutually composed, as the parts condition the sociality synthetic biologists hope to realize.

Paul Rabinow has characterized synthetic biology as “a return of the organism . . . as an object of reformation” or “remediation” (Rabinow Reference Rabinow2006). Perhaps this is so. But the organism that is the object of synthetic biology is now beside the point, because the locus of the engineering impulse is being directed elsewhere.Footnote ⁷ If the various genome projects of the 1990s – for humans, mice, dogs, fruit flies, yeast, tomatoes, flu virus, grapes – sedimented the genome as the signature of a particular species, then synthetic biologists are building a heteroclite taxonomy of parts and devices that genetically draw together diverse species and socially draw together a community of practitioners devoted to and defined by BioBricks’ propagation. An example clarifies this point. In 2006, I watched a group of MIT undergraduates, repulsed by the malodor of bacterial cultures, build bacteria that smelled like banana and wintergreen. This biological system constituted genetic parts from three biological kingdoms: eubacteria (E. coli, P. aeruginosa), fungi (S. cerevisiae), and plants (Petunia x hybrida). Though they adhere to composition standards, the living things synthetic biologists freely exchange are composed of trans-species genetic exchanges.

That is, BioBricks do not simply designate physical objects, but relations between biological and social kin and kinds – including the normative relations between synthetic biologists who publish BioBricks online and store them in the Registry's freezer in Cambridge. Transgenic critters, such as strawberries bearing fish genes, have been troubling categories of relatedness – species, lineage, and consanguinity – for some time, as scholars such as Sarah Franklin (Reference Franklin2007) and Donna Haraway (Reference Haraway1997) have noted. They “fit into well-established taxonomic and evolutionary discourses and also blast widely understood senses of natural limit. What was distant and unrelated becomes intimate” (Haraway Reference Haraway1997, 56).

Indeed, clicking through the online Registry of Standard Biological Parts is like touring a very strange menagerie. Each BioBrick part is classified according to its source, but the logics under which those sources are cataloged vary radically – think of Borges's Chinese Encyclopedia. Parts from yeast, petunias, snapdragons, bioluminescent marine bacteria, Arabidopsis, and fairy fan flowers appear under their Linnaean nomenclature. However, parts assembled by de novo synthesis might list the name of the company that synthesized or sold them (e.g., Sigma Aldrich) or the published sequence from which they were synthesized (e.g., GenBank, Codon Devices). To further complicate things, parts borrowed from another researcher are sourced to the names of the researchers that gifted these parts, delineating a kind of lab pedigree. For example, one such pedigree reads: “We thank Natalia . . ., Department of Horticulture and Landscape Architecture, Purdue University for the gift of the expression vector with the petunia BSMT1 coding sequence.”Footnote ⁸ Biotic and social modes of circulation and relatedness, and natural and artificial origins and exchanges, here hybridize.

The resulting living artifacts, in which species boundaries deliquesce in transgenic exchanges of yeast and petunias, reflect and underwrite social exchanges of biomaterials. These BioBrick parts are multiply about relations among things: they denote potential interspecies minglings, such that DNA from snapdragons may be ported into bacteria, they reference the social conventions by which standards are agreed upon, and through their free circulation, they coordinate practices among synthetic biologists who exchange and contribute ever more parts. In an essay on new biotechnologies, Freeman Dyson compared such genetic minglings to free software movements:

Dyson's comparison of genetic exchanges, couplings of petunias and E. coli, to the circulation of intellectual property and material artifacts echoes Haraway's reminder that species not only marks stories of relatedness and exclusion, but is also about “filthy lucre, specie, gold, shit, filth, wealth” (Haraway Reference Haraway2003, 16). BioBricks, in their putative unmooring from species, betwixt and between source species and the organisms into which they will be inserted, promise other kinds of circulation, unbound from intellectual property regimes. Or at least, so the synthetic biological imagination claims. Synthetic biologists draw together not only diverse species, but also knit together the researchers who are arguing about, assembling, modifying, and sharing their parts. Genetic and social sorts of circulation and relatedness remake and reflect one another in the fabricated artifacts of twenty-first century bioengineering.

Alain Pottage has argued, in language that calls to mind Foucault's formulation of “life itself,” that “were the ambitions of synthetic biology to be realized,” it would “open up a kind of ‘life’ or ‘biology’ that is quite unlike ‘life’ as it is construed by existing biotechnologies.” Whereas biotechnology, simply put, has sought to functionalize and instrumentalize existing living things and biological processes, synthetic biology would both sort living things according to digital organization strategies and synthesize new genetic components not found in nature (Pottage Reference Pottage2006, 144–146). Whether synthetic biologists’ ambitions are “realized” or not, their project would not be tenable if “life” were not already a troubled and troubling epistemological category. Synthetic biologists treat life as a coherent and stable entity despite the fact that the very thing on the table is its material reconstruction.

A Fragile Monster

What could such a high-stakes, highly funded field as synthetic biology have in common with a collaborative, grassroots, handicraft project? Over three thousand crafters have helped fabricate The Hyperbolic Crochet Coral Reef, with the aim of raising awareness of how fragile marine ecosystems are imperiled by anthropogenic climate change. The Reef currently has two incarnations – the first is the wooly one, described by the Wertheims as “an on-going evolutionary experiment” in which crafters rear “an ever-evolving crochet ‘tree of life’.”Footnote ⁹ The second, plastic reef is an invocation of the Great Pacific Garbage Patch, a swirling mass of plastic detritus that waxes as silicon-based coral reefs wane. The Wertheim twins describe it as an “evil twin to yarn-based reefs; a malevolent synthetic analog to the delicate fiber-forms.”Footnote ¹⁰ As one reef looks back to living systems imperiled and at risk, the second, like synthetic biology, prognosticates synthetic futures. If “synthetic,” for synthetic biologists, means something assembled, as in “synthetic chemistry,” the Great Pacific Garbage Patch is synthetic in the senses of artificial, human-made, and unnatural.

Crochet is a traditional handicraft that uses a single hook to thread loops through other loops. Cornell mathematician Daina Taimina discovered in 1997 that by adding stitches at a constant rate, one could crochet a three-dimensional model of hyperbolic geometry. Hyperbolic geometry, which is a non-Euclidean geometric manifold that defies Euclid's parallel postulate, has a constant negative curvature. It had long proven extremely difficult to understand, let alone physically model, even though filter-feeding marine animals, not to mention frilly plant leaves and fungi gills, approximate hyperbolic morphologies, which maximize the permeable and absorptive surface of an organism while minimizing the body's interior. Margaret Wertheim emphasizes coral reefs’ imminent endangerment while also referencing the deep time of coralline evolution. In a public lecture, she showed her audience photographs of nudibranchs and flatworms, pronouncing: “Here are two creatures who have never heard of Euclid's parallel postulate, didn't know that [it] was impossible to violate, and they're simply getting on with it. They've been doing it for hundreds of millions of years.”Footnote ¹¹

The Reef now makes itself at home in art-science ecotones: it broods in the Ocean Hall of the Smithsonian's National Museum of Natural History and in the Hayward Gallery in London; it runs riot on the pages of both Science and Crochet Fantasy. The original crocheted reef has bred multiple satellite reefs, which flourish in craft circles and workshops around the world – Capetown, Sydney, Riga, Dublin, Chicago, New York. The fifty crafters who have contributed most to the Reef include artists and professional craftspeople, as well as a math teacher, several computer programmers, a librarian, a retired geneticist, and a sheep farmer.

The Hyperbolic Crochet Coral Reef first took shape in 2005 when Margaret Wertheim, a science writer and native of Queensland, and her sister Christine Wertheim read about Taimina's fibrous geometric models. They began crocheting their own hyperbolic geometries. For months, they followed Taimina's simple algorithm, until Christine Wertheim, growing restless, began to drift from mathematical exactitude, increasing stitches at whim. To her sister, “The effect was electrifying. Suddenly the models came to life – they began to look like natural organisms instead of Platonic ideals.”Footnote ¹² When the Wertheims noticed that the hyperbolic forms they had crocheted evoked the organisms of the Great Barrier Reef, they solicited contributions on their website, asking that, like the cumulative work of coral polyps, crafters join them in spawning a crocheted coral reef. The models, made of yarn and plastic, are certainly not “alive” in any biotic sense. To what kind of fabricated “life,” then, does Margaret Wertheim here refer, and how might it compare to the “life” synthetic biologists manufacture?

Throughout the twentieth century, theoretical biology has been marked by a penchant for using mathematical and geometric formalisms as either descriptions of or explanations for the ways in which living bodies grow and evolve in interaction with their surrounding environments. Scholars such as D'Arcy Thompson, C.H. Waddington, Brian Goodwin, J.B.S. Haldane, Stuart Kauffman, and Humberto Maturana each articulated theories of biological growth, form, and formalism mathematically. Twentieth-century biology is littered with examples of such mathematical thinking, ranging from cellular automata (Varela, Maturana and Uribe Reference Varela, Maturana and Uribe1974) to L-systems (Kelty and Landecker Reference Kelty and Landecker2004) to biocybernetics (Asaro Reference Asaro, Müller and Müller2007; Keller Reference Keller2008; Pickering Reference Pickering2010). However, while the Reef originated in non-Euclidean geometry, it did not, for its crafters, “come to life” until they deviated from mathematical principles. On their view, the spark of life resides in creative, accidental, or fortuitous swerves away from mathematical formalism.

Reef crafters explicitly treat the process of crocheting hyperbolic geometries as an analog for biological evolution. This analogy traffics both ways: Reef crafters describe Darwinian and neo-Darwinian evolution – the manner in which organisms are slowly shaped by or attuned to their environment via the accumulation of genetic alterations – as akin to craft. Further, they understand craft as a practice analogous to evolution in its slowness and gradual modification. Margaret Wertheim explains that Reef makers

Anita Bruce, a British crafter with degrees in both zoology and textile arts, describes the process by which she “evolves” plankton forms she knits out of scientific wire:

Other contributors have similarly begun articulating their craftwork using evolutionary terminology. Margaret Wertheim describes Reef makers’ innovations as engendering “whole genera of crochet reef organisms,”Footnote ¹⁵ “creating several major branches on the crochet tree of life,”Footnote ¹⁶ rendering “wooly mutants seemingly coughed up from the stomach of some bilious leviathan,”Footnote ¹⁷ and “invent[ing] an entire taxonomy of ‘radiolarians.’”Footnote ¹⁸ She claims that multiple contributors will simultaneously stumble across the same crochet innovation while working in isolation, a process she likens to convergent evolution, the biological process by which distinct lineages share analogous structures or functions (such as wings in bats, birds, and insects). Retired geneticist and HCCR crafter Helle Jorgensen speculates as to what forms her crochet might take if she were “crocheting in another world with non-carbon based life and different physical laws,” and describes the forms that recur in her crocheted artifacts, writing, “We have learnt the meaning of organic shapes, textures and colours occurring in Nature, for survival. Evolution?”Footnote ¹⁹ More grandiloquently, an anonymous Reef crafter enigmatically named “Dr. Axt” proclaims, “If hyperbolic figures represent the rhythm of life then I am the center of the Universe.”Footnote ²⁰

In both synthetic biology and the Hyperbolic Crochet Coral Reef, practitioners regard the techniques they use as intrinsic to biology, identifying their own tactics, whether of streamlining, engineering, standardizing, or crocheting, as fundamental features of biology that precede their interventions. If synthetic biologists build standardized, rational, or minimal biological objects in order to persuade themselves that life might be standardizable, partible, or even Open-Sourceable, the people crocheting the Reef also identify their techniques with biology by figuring evolution as akin to craft practice. Evolution and craftwork, according to this thinking, are both protracted affairs, by definition unpredictable, improvisatory, transformative, entangled, and materials-based. In the mid-twentieth century, cybernetics and information theory snuck teleological stories about evolution into biology. Synthetic biologists who fantasize about “optimizing” biological design recognize post-genomic complexity while remaining committed to the ambitions of a mathematically inflected formalized biology. Reef contributors reject such notions altogether, instead mimicking evolutionary complexity through their manufacture of new coralline forms.

For the thousands of women who have fabricated the Reef, fabrication is a mode of improvisational, materially exploratory craftwork, a grappling with biological things apprehended by their manufacture. Simulating oceanic morphologies renders biology something whose evolutionary unfoldings crafters not only mimic, but also analogically generate, through an ad hoc crafting of new crochet forms. The result is a composite, materially-instantiated evolutionary theory – that is, the Reef itself demonstrates how error, adaptation, and interspecies relations drive changes in living form and function while calling attention to how anthropogenic climate change imperils the health of marine ecologies. Reef makers’ repetitive gestures recapitulate the protracted piecemeal depositions of polyps and their improvisations offer a tangible understanding of morphogenesis. Their wooly corals are hybrid and freeform crafted objects. So too are their evolutionary yarns.

Projects such as the Reef indicate a new sort of engagement with biological things, one whose characteristics, I posit, are not limited to the two examples discussed here, but can increasingly be found in professional laboratories and research centers. This approach is about apprehending biology not only materially, but also in and through its collaborative making. Both synthetic biologists and Reef crafters construe biology as a process – specifically, an evolutionary one – that, like crafting, tends to be changeable, error-prone, messy, and risky. As Drew Endy often reminded his students, the contingencies of four billion years of evolution have developed living systems that are not easy to understand. The task of synthetic biology, he believes, is to optimize and streamline evolved organisms. Whereas synthetic biologists aim to rationalize evolution, Reef makers instead simulate evolutionary unpredictability. The project is, in the Wertheims’ words, “a collective experiment in textile-based evolution.”Footnote ²¹ In both cases, practitioners advance their understandings of biology by manufacturing biological forms, whether out of DNA or yarn. In the age of biological fabrication, life is best understood by making it.

Importantly, in both cases, the products are cultural artifacts that embed notions of how biology works, as well as claims about how biology should work. This fact suggests that all biotechnical and bioengineered entities in the age of biological fabrication – including, perhaps especially, those currently being manufactured in high-powered laboratories such as those at MIT, the Lawrence Berkeley Laboratory, or the J. Craig Venter Institute, are material instantiations of sums of biological theories. In the last two decades, researchers have taken the biological knowledge accumulated over the last two centuries and installed it into newly manufactured biological artifacts. These objects do not represent biological theories; they literally incorporate them – form them into bodies. Life scientists and their allies may build new biological things to learn more about biology, but they also try to install their theories, apprehensions, faiths, and preconceptions in the objects they manufacture.

Biological Facts and Artifacts

Making new biological things is, for synthetic biologists and Reef crafters alike, “the royal route to an understanding of” biology (Keller Reference Keller2009). Their approach is “post-organismic,” in that researchers do not think about biology at the level of whole organisms, but rather in terms of the experimental and manufacturing techniques they use. That is, they identify their particular manufacturing methods as inherent in biology prior to their own interventions. The “postvital” turn in twentieth-century molecular biology, as it is periodized by Richard Doyle, meant the collapse of the body onto “a transparent sequence that has nothing behind or beyond it” (Doyle Reference Doyle1997, 13). But this is the postvital in the post-genomic moment. Here, the post-organismic means that the biological features researchers fasten on are determined by their own experimental tactics, which they then identify with the thing itself.

Making and modeling life, whether in eminent laboratories or humbler locales, entails a rhetorical transaction in which practitioners posit that biology has always been amenable to their constructive impulses. They go so far as to say that biology exhibits those interventions they themselves perform: biology, for synthetic biologists, operates like an engineer. For Reef crafters, it proceeds in a kind of knitting. In making such claims, they destabilize life as an object of investigation. Life becomes dispersed into technique, as practitioners identify their own methods as qualities essential to “life itself.”

At the tail of the twentieth century and the twenty-first's head, life's investigation became progressively amenable to constructive approaches. Remember synthetic biologists’ pronouncement that “life is what we make it.”Footnote ²² Lorraine Daston and Peter Galison speculate that science recently has transitioned from an age of scientific representation to one of presentation, in which the acts of “making and seeing are indistinguishable” (Daston and Galison Reference Daston and Galison2007, 46). Extending their claim into biology, I suggest that biological knowing and biological making, paired under the twin signs of the biologically factual and the biologically artifactual, are now mutually constitutive. More than pointing to an absence of any coherent referent for “life,” this trend demonstrates that not only is “life itself” something richly constructed, but so is biological substance. Now is certainly not the first time biological things are being made: prominent earlier examples include the pigeon fanciers of Darwin's day, hybrid corn in the 1930s and 40s, and laboratory model organisms from tobacco mosaic virus to drosophila. However, for synthetic biologists and Reef crafters, making new living things is not a means to an epistemic end, but the end in itself. Making here operates in a dialectical relationship with the epistemic work of investigation, examination, and analysis. Simply put, people now build biotic things in order to understand the things that they themselves are making. As “life itself” deliquesces and recrystallizes, reforms and deforms, in the hands of contemporary life scientists, the relations between making and knowing are also reconfigured, with serious consequences for the stories we tell about nature and artifice, analysis and synthesis.