GENEWATCH
 
DREAMING OF LES JARDINS CHIMIQUES
By Andrew D. Thibedeau
 

1.

It is the ambition of synthetic biology to unlock the secrets of life by creating it anew. This is, of course, the ambition of all biology — to discover hitherto unknown facts about how life works. To say that something is synthetic, however, is to say that it is artificial, "fake, false . . . man-made, manufactured, fabricated." [1] In the realm of biology, these terms carry a host of negative implications. It is the artifactuality of biotechnology itself that gives rise to many central issues in bioethics. What is more, modern culture has erected an entire iconography of fear around the notion of man-made life. As the title of one book on the subject suggests, to create synthetic life is to walk in "Frankenstein's footsteps." [2] But is the field of synthetic biology akin to Dr. Frankenstein's laboratory? I argue that it is not. Rather, the label synthetic has afflicted synthetic biolo- gy with many negative associations that are at least prima facie underserved.

Synthetic biology is the ongoing effort to "develop[] artificial systems using engineering design tools . . . to explore new functions by modifying existing organisms." It aspires to make both cellular and non-cellular biological structures that function in ways not found in the natural environment. It is in this sense unnatural. The creation of "artificial systems" is not an end in itself, but rather a means "to improve the understanding of various biological mechanisms." In other words, synthetic biology is a method. [3]

Method can be described as "the proper arrangement of our mental processes in the discovery and proof of truth." There are two primary methods: analysis and synthesis. Analysis proceeds "from the concrete to the abstract, from the complex to the simple . . . from the phenomena to the underlying general law, from the effect to the cause." Synthesis is the converse of analysis. It passes "from the simple to the complex, from the general to the special . . . from cause to effect." [4] My focus is the latter. My argument is that a consideration of the meaning of synthesis as a scientific methodology suggests that synthetic biology can be viewed as instrumentally valuable, which is to say: valuable as a means to an end.

2.

In the first decade of the 20th Century, French scientist Stéphane Leduc "showed that a spectacular plant-like growth occurs when crystals of metal salts . . . are dropped into an aqueous solution of sodium silicate." [5] His experiments produced multicolored plant-like filaments that appeared to grow from crystal surfaces, which he called "les jardins chimiques" — chemical gardens. To microscope and naked eye alike, Leduc's chemical gardens were highly biomimetic. Long green stalks grew from turquoise beds of crystal; osmotic action produced cell- like structures that seemed indistinguishable from simple prokaryotes. Based on these experiments, in 1912 Leduc published La Biologie Synthétique, in which he postulated using chemical synthesis "as a means to understand the basic biology of organic growth and morphology." [6] He believed his work held the key to "les lois générales de la vie" — general laws of life. [7] These laws, Leduc believed, could "illuminate the nature and origin of life by bridging the gap between the living and the nonliving, offering a new version of the 'missing link' between inorganic and organic." [8]

Although Leduc's findings proved unrelated to life — they were instead the results of oxide precipitation and osmotic growth, two chemical processes now well-understood — they nevertheless demonstrated the heuristic value of what Leduc called "la méthode synthétique." [9] Leduc himself observed in La Biologie Synthétique that "[a] general theory, containing even a great element of error, promotes progress more than no theory at all." [10] Leduc posits that "synthetic biology represents a new, legitimate scientific method [that tries] to reproduce outside of living beings, each of the phenomena of life." [11] Leduc's work was explicitly modeled "par l'imitation de la vie" — by the imitation of life. His method was synthetic and his approach analogical: "the relevance of these phenomena is in their analogy with what we observe in living beings." [12] In his experiments he believed that he observed "la reproduction des cellules artificielles, des structures, des tissus, des formes générales, des fonctions, de la circulation centripète et centrifuge." [13] Instead, he was observing far simpler chemical processes. Although Leduc's les jardins chimiques never bore fruit, his method was nevertheless a significant step forward for modern biology.

In one sense, Leduc's work was important because it argued against the concept of vitalism. Vitalism is "the doctrine that the phenomena of biology are due to a vital principle distinct from physicochemical forces, and cannot be explained by the laws of physics and chemistry alone." Positing that life is the result of some "nonnatural, perhaps unknowable, properties of living systems," vitalism still held sway among many biologists when Leduc wrote La Biologie Synthétique. The notion dates to the Greek philosophers, who believed that the cause of an event happening in the physical world is the so-called Aristotelian efficient cause, which by definition is external to the thing acted upon. In other words, the Aristotelian theory of causality at the heart of vitalist theories of life holds "that there is a basic discontinuity between that which acts and that which is acted upon." This discontinuity introduces the "unknowable" element to vitalism that threatened to delimit an endpoint to biology itself. Through the work of many notable scientists including Leduc, however, by 1966 Francis Crick assigned vitalism to the "lunatic fringe."

 

3.

Despite les jardins chimiques ultimate failing to relate to the processes of life, Leduc's work nevertheless stands with that of Darwin and Pasteur because of his method. [14] In this sense, his experiments are a testament to the synthetic: not as something "artificial" or "man-made," but as a methodological approach to biology. As Leduc wrote in The Mechanism of Life:

Each branch of science at its com- mencement employs only the simpler methods of observation. It is purely descriptive. The next step is to sepa- rate the different parts of the object studied—to dissect and to analyze. The science has now become analytical. The final stage is to reproduce the substances, the forms, and the phenomena which had been the subject of investigation. The science has at last become synthetical.[15]

Following Leduc, synthesis as a scientific methodology has certain inherent advantages over analysis. To approach a problem analytically is to arrive at a generalization grounded in observations of individual phenomena. It is the work of science to build up these generalizations into theories that aim to explain the phenomena. Galileo's study of planetary motion, for example, led to his refinement of Copernicus' heliocentric theory of astronomy. But analysis can be a tricky business. Although observing the same planets as Copernicus and Galileo, for millennia astronomers held to Ptolemy's inaccurate geocentric cosmology.

Put simply, Ptolemaic doctrine stated that all heavenly bodies moved in perfect circles and placed the earth at the center of a vast "celestial sphere," upon which rotated all the stars and planets. For reasons now obvious, Ptolemy's theory failed to account for retrograde planetary motion: when the planets observed from earth appear to move backward in their orbits. Rather than devise a new conceptual system, early astronomers invented "epicycles" — smaller circular orbits whose center moved along the circumference of the celestial sphere (see figure at right). As conflicting observational data accumulated, astronomers produced ad hoc increasingly complex systems of compound circular movement to account for them. Nevertheless, despite remaining the dominant planetary theory for more than a millennium, "[n]o version of [Ptolomy's geocentric] system ever quite withstood the test of additional refined observations."

As Thomas Kuhn describes in The Structure of Scientific Revolutions, when confronted with observations that contradict a prevailing theory, scientists "will do what we have already seen scientists doing when confronted by anomaly . . . [t]hey will devise numerous articulations and ad hoc modifications of their theory in order to eliminate any apparent conflict." [16] Scientists, after all, are only human. And it is only human to see a desired pattern where there is none, or ignore an unwanted anomaly. In this way, Kuhn argues, all analytic science produces its own version of epicycles.

To approach a problem synthetically is another thing entirely: it is to produce individual phenomena based on theory — for instance, to construct a clock based on Galileo's law of pendulum motion. In the end, the clock will either tell the correct time or it will not; if Galileo's law is wrong, no amount of tinkering could set the clock right. In this way, a synthetic methodology poses a check to the human tendency to interpret away inconsistency that Kuhn describes. [17] This is not to say that analysis has no part to play in science. It is rather to highlight the limitations of a scientific method rooted solely in analysis — and to suggest that scientific progress is best achieved when the two methodologies work in concert.

For biology today, the value of Leduc's methodological concept — a synthetic biology in this classical sense — lies in its potential to reveal unknown features of life. In micropaleontology, for example, "morphology is still one of the main parameters to decide whether microfossils could be considered as traces of life rather than just mineral forms." [18] Although more sophisticated models of crystalline growth now delimit the boundary between the living and the nonliving, Leduc's methodology retains its heuristic value — as a means of producing useful knowledge. Another important discovery attributable to synthetic biology is the development of the branched DNA diagnostic assay — a medical tool that "helps to manage the care of approximately 400,000 patients infected with HIV and hepatitis viruses each year." [19] Only by working to engineer synthetic genetic systems did researchers come to understand the biology behind this important technology. Thus, to the extent that its outcomes remain consistent with ends such as these, the negative implication of synthetic ought not obscure the utility of synthetic biology.

It should be remembered that the creature created by Dr. Frankenstein had both emotion and a moral conscience. "I do know that for the sympathy of one living being," the creature implored, "I would make peace with all." In the end, he takes his own life, but not before expressing remorse at the death of his creator. The creature, in other words, was an ethical being, valuable unto himself — rather than as the end of a particular project of research. In a very true sense, the monstrosity of the story belonged to Dr. Frankenstein, who created a being by nature so disjointed that he could not survive in the human world. Unlike Dr. Frankenstein's doomed creation, the work of Leduc and modern synthetic biology does not aspire to create beings capable of either pain or pleasure. It does not aspire to create per se, but to know through the act of creation. On this view, there is a strong prima facie reason to defend synthetic biology against its negative linguistic associations: the value of the knowledge gained by its pursuit.


Andrew Thibedeau ,J.D.,is a fellow with the Council for Responsible Genetics.

 
 
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