Team:Evry/Policy and Practices/Philosophy

From 2014.igem.org

Revision as of 16:45, 11 October 2014 by Sophie Gontier (Talk | contribs)

IGEM Evry 2014

Policy and Practices - Philosophy

Design in Synthetic Biology: rationality versus kludge



Though scientists have many different definition for what is synthetic biology, a recurrent element of these definitions is the analogy with engineering. This comparison is supported by the idea that synthetic biology allows to build standardized parts of living systems, whose functions and properties are know ; and that those parts can be assembled together in any system thanks to a rational and transposable protocol. Synthetic biologists should also be able to make a model of the constructed organism and to predict its behavior. Eventually, building new living systems should become as easy for synthetic biologists as assembling non-biological parts in a machine is easy to engineers.


“Synthetic biology is the engineering of biology”

High-level Expert Group European Commission

However, living organisms are exceedingly complex, and at first sight it looks impossible to fully understand them ; and if we don't, how could we possibly have enough control over them to force them to behave like mechanical, predictable machines? This question is important, because it is precisely what we are trying to do in iGEM: to design and build a "Genetically Engineered Machine". We are, like most synthetic biologists, assuming (or at least hoping) that living systems can be designed to act in a calculated and useful way, like the machines of engineers do. However, in truth it is obviously not so. Everyday during our iGEM experience, we discovered how unpredictable living systems can be - and even though we sometimes managed to have the result we expected, the protocols to achieve such a result were hardly as rational as engineers protocols. In biology, we never fully understand the living systems we are working on, and as a consequence, the design process of our genetically engineered machine is more often a trial-and-error process than a fail-proof one.

This observation has led us to wonder about the importance of kludging and tinkering in synthetic biology. The word "kludge" stands for "klumsy, lame, ugly, dumb but good enough", and seems to describe quite accurately what we are actually doing in synthetic biology, when we use inelegant but successful solutions to solve a problem when the rational design doesn't bear the expected results. In fact, we were led to notice that this not-always rational, but very efficient way of doing research is common in many scientific fields; but we thought that it was even more significant in synthetic biology, because the researchers of this field are precisely claiming that their design is rational and systematic. The contrast between what synthetic biology want to do and what they are actually doing is, as a result, even more apparent.

Kludge : "klumsy, lame, ugly, dumb, but good enough"
Inelegant but successful solution to a problem.

Thus, as we are synthetic biologists ourselves and are confronted everyday to the actual practice of the field in the lab, we thought that it was very important to take a step back and have an objective and reflexive look at design in synthetic biology. The questions we want to address in the following reflexion are the following:

  • How can synthetic biology pretend to achieve rational and predictable design of living systems?
  • Is design in synthetic biology rational, of is it the result of kludging?
  • Is one way better than the other?



How can synthetic biology pretend to achieve rational and predictable design of living systems?


In 2005, a European Commission that gathered many experts in synthetic biology offered the following definition of the new field:

“Synthetic biology is the engineering of biology: the synthesis of complex, biologically based (or inspired) systems which display functions that do not exist in nature. This engineering perspective may be applied at all levels of the hierarchy of biological structures – from individual molecules to whole cells, tissues and organisms. In essence, synthetic biology will enable the design of ‘biological systems’ in a rational and systematic way.”

High-level Expert Group European Commission

We can notice here that synthetic biologists are confident that such designs can be rational and systematic, which means that like the machines or the computer programs of the engineers, the designed synthetic systems must be composed of parts that are fully understood and characterized. Thus the researchers should be able to assemble those parts and obtain the expected result.

Let's take a quick look at the history of synthetic biology to better understand how such an ambition could arise in a field working on living systems, which are intrinsically complex and unpredictable. With the development of systemic biology in the last decades, it has been observed that there is an organized hierarchy in cellular networks, between functional modules. And from there, the idea appeared that some mechanisms in living organisms could be reduced to simple mechanisms such as those built by engineers in machines ; which meant that with the proper tools, we could modify and design cells in a rational way to obtain a predefined result. Then in 2004, the first international conference on synthetic biology, SB 1.0, organized by the MIT, brought together researchers specialized in fields as varied as biology, chemistry, physics, engineering and informatics. It is probably during this interdisciplinary meeting that the ambition to use the engineers' rational bottom-up approach in molecular biology and genetics took shape.

In order to achieve a rational design of living systems, the priority was first given to the characterization of their functional parts, which is the main goal of the iGEM competition. These researchers had the intuition that it would then become possible to assemble these parts in different ways, that don't necessarily exist in nature, using rational and systematic protocols ; and to construct biological devices that would act exactly as they were intended to.

"As envisioned by SynBERC, synthetic biology is perhaps best defined by some of its hallmark characteristics: predictable, off-the-shelf parts and devices with standard connections, robust biological chassis (such as yeast and E. coli) that readily accept those parts and devices, standards for assembling components into increasingly sophisticated and functional systems and open-source availability and development of parts, devices, and chassis.”

SynBERC