In this short contribution we explore the historical roots of recent synthetic approaches in biology and try to assess their real potential, as well as identify future hurdles or the reasons behind some of the main difficulties they currently face. We suggest that part of these difficulties might not be just the result of our present lack of adequate technical skills or understanding, but could spring directly from the nature of the biological phenomenon itself. In particular, if life is conceived (...) as autonomy in open-ended evolution, which would help to explain the highly complex and dynamic organization of the simplest known organisms (i.e., genetically-instructed cellular metabolisms), external synthetic implementations of such systems, or interventions on them, are bound to interfere with some of their characteristic transformation processes, both at the ontogenetic and phylogenetic scales. In any case, this will prove very revealing and productive, technologically and scientifically speaking, since the knowledge gathered from those implementations/interventions will be extremely valuable in establishing our capacities and limitations to fully comprehend, utilize, and expand the living domain as we know it today. (shrink)

The comparison between natural evolution and the action of a tinkerer has become highly popular since its reintroduction by François Jacob at the end of the 1970s. It has been used as a weapon against the existence of an “intelligent design” as well as a way for synthetic biologists to promote their ambitious projects. I will describe the complex history of this metaphor, and examine its pertinence. Whereas Darwin considered it as a way to describe how evolution proceeded, Jacob linked (...) it with a description of the imperfections of organisms, while Stephen Jay Gould and Richard Lewontin criticized what they called the “Panglossian” vision of most evolutionary biologists. The distinction between the work of engineers and that of tinkerers is not obvious. There are limits to the process of evolution, but their alleged description so far reflects the limits of knowledge on the part of evolutionary biologists more than the existence of true barriers to the evolutionary process. And, in their work, synthetic biologists crucially need the optimizing action of natural selection. To give a definition of synthetic biology is no easy task; the false distinction drawn between the work of synthetic biologists and the action of evolution is of no help. (shrink)

Probably the most distinctive feature of synthetic biology is its being “synthetic” in some sense or another. For some, synthesis plays a unique role in the production of knowledge that is most distinct from that played by analysis: it is claimed to deliver knowledge that would otherwise not be attained. In this contribution, my aim is to explore how synthetic biology delivers knowledge via synthesis, and to assess the extent to which this knowledge is distinctly synthetic. On the basis of (...) distinctions between knowledge-how and knowledge-why, and between syntheses that succeed and syntheses that fail, I argue that the contribution of synthesis to knowledge is best understood when syntheses are construed as experimental interventions that aim at probing causal relationships between properties of the entities that are combined through these syntheses and properties of their target products. The distinctiveness of synthetic biology in its quest for knowledge through synthesis stems from its ability to sample at will a space of empirical possibilities that is not only huge but also that has been so scarcely sampled by nature. (shrink)

The term “synthetic biology” is a popular label of an emerging biotechnological field with strong claims to robustness, modularity, and controlled construction, finally enabling the creation of new organisms. Although the research community is heterogeneous, it advocates a common denominator that seems to define this field: the principles of rational engineering. However, it still remains unclear to what extent rational engineering—rather than “tinkering” or the usage of random based or non-rational processes—actually constitutes the basis for the techniques of synthetic biology. (...) In this article, we present the results of a quantitative bibliometric analysis of the realized extent of rational engineering in synthetic biology. In our analysis, we examine three issues: (1) We evaluate whether work at three levels of synthetic biology (parts, devices, and systems) is consistent with the principles of rational engineering. (2) We estimate the extent of rational engineering in synthetic biology laboratory practice by an evaluation of publications in synthetic biology. (3) We examine the methodological specialization in rational engineering of authors in synthetic biology. Our analysis demonstrates that rational engineering is prevalent in about half of the articles related to synthetic biology. Interestingly, in recent years the relative number of respective publications has decreased. Despite its prominent role among the claims of synthetic biology, rational engineering has not yet entirely replaced biotechnological methods based on “tinkering” and non-rational principles. (shrink)

The goal of synthetic biology is to create artificial organisms. To achieve this it is essential to understand what life is. Metabolism-replacement systems, or (M, R)-systems, constitute a theory of life developed by Robert Rosen, characterized in the statement that organisms are closed to efficient causation, which means that they must themselves produce all the catalysts they need. This theory overlaps in part with other current theories, including autopoiesis, the chemoton, and autocatalytic sets, all of them invoking some idea of (...) closure. A simple model of an (M, R)-system has been implemented in the computer, and behaves in ways that may shed light on the requirements for a prebiotic self-organizing system. In addition to a trivial steady state in which nothing happens, it can establish a non-trivial steady state in which all intermediates have finite concentrations, with their rates of degradation balanced by their rates of synthesis. The system can be regenerated from the set of food components plus a single intermediate, and maintain itself in that state indefinitely, despite continuous degradation. At the very low compartment volumes that may have existed in prebiotic conditions, for example in cavities in minerals, or in micelles formed by simple amphiphiles, statistical fluctuations in the numbers of molecules need to be taken into account. With the stochastic approach there is no non-trivial steady state in strict mathematical terms, because the system will always collapse to the trivial state after sufficient time. However, the average time before collapse is so long for volumes greater than $10^{-19}\;{\textsc{l}}$ (much smaller than the volume of the order of $10^{-15}\;{\textsc{l}}$ for a typical bacterial cell) that for practical purposes the self-maintaining state of non-null concentrations becomes significant, recalling the situation of bistability that is observed in deterministic analysis. In turn, there exists a minimum size below which the self-organizing system cannot maintain itself on chemically relevant time scales. The value of the critical volume depends on the particular concentrations and rate constants assumed, but the principle could apply generally. (shrink)

Synthetic biology is a new biotechnology that is developing at an impressive pace and attracting a considerable amount of attention from outside the scientific community as well. In this article, two main philosophically and ethically relevant characteristics of this field of research will be laid bare, namely its reliance on mechanistic metaphors to denominate simple forms of life and its appeal to the semantic field of creativity. It is argued that given these characteristics synthetic biology can be understood as a (...) prime example of a kind of human interference with reality that German philosopher Hannah Arendt called “fabrication.” This kind of self-world-relation contrasts to “action,” a relation that introduces, among other things, the idea of an inherent value of the object acted upon. Taking up this latter perspective, one scientific and two ethical challenges to synthetic biology’s take on the realm of life are identified. (shrink)

A science is an intellectual activity defined by its mechanisms that prevent its scientists from always reaching the conclusions that they set out to reach. Such mechanisms are needed because, if scientists are given full control over what hypotheses they select, what data they discard, and what results they publish, they can communicate any conclusion that they desire. Synthesis, by setting a grand challenge, forces scientists across uncharted territory where they encounter and solve unscripted problems. When theory is inadequate, the (...) synthesis fails, and fails in a way that cannot be ignored. Therefore, synthesis drives discovery and paradigm change in ways that simple hypothesis testing cannot. Here, we describe the discoveries that emerged when synthetic biologists were challenged to create an alternative genetic system that has different molecular structures than DNA and RNA. In pursuit of this particular “grand challenge,” synthesis forced the recognition that the community did not know as much about the double helix as it had constructively assumed. In general, a field of science having access to synthesis as a research strategy can create knowledge even if its practitioners do not fit the ideal of a dispassionate, advocacy-free scientist. (shrink)

Top-down synthetic biology makes partly synthetic cells by redesigning simple natural forms of life, and bottom-up synthetic biology aims to make fully synthetic cells using only entirely nonliving components. Within synthetic biology the notions of complexity and emergence are quite controversial, but the imprecision of key notions makes the discussion inconclusive. I employ a precise notion of weak emergent property, which is a robust characteristic of the behavior of complex bottom-up causal webs, where a complex causal web is one that (...) is incompressible and its behavior cannot be derived except by crawling through all of the gory details of the interactions in the web. The central thesis of this article is that synthetic biology centrally is the activity of engineering the desired weak emergent properties of synthetic cells. Synthetic biology has many different ways to engineer desired weak emergent properties of synthetic cells, including Edisonian trial and error, standardized parts, refactoring, and reprogramming synthetic genomes. The article ends by noting two philosophical consequences of engineering weak emergence. One is epistemological: synthesis is crucial for discovering weak emergent properties. The other is metaphysical: simple life forms are nothing but complex chemical mechanisms. (shrink)

The sociological dimension of science is studied using the discovery of the Wasserman reaction and its accidental application as a test for syphilis as a basis, ...

A range of views on the morality of synthetic biology and its place in public policy and political discourse.