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From 2012.igem.org

Would you be my chassis?

Introducing Xenopus tropicalis as a new chassis in the iGEM contest requires a few epistemological investigation. The term “chassis” refers to a specific kind of model organisms which are bound to the specific ways of experimenting developed in synthetic biology. Examples through history have shown that the organisms used for conducting the experimentation often influence deeply the theories and projects inferred. As the term “chassis” is at the center of our study, it is important to remind why Xenopus tropicalis is an interesting model organism, and to what extent the term chassis is epistemologically relevant when referring to vertebrates.

Xenope as a model organism

In experimental biology the choice of the right organism is a crucial beginning of research, this has been widely repeated, so was saying Claude Bernard, father of experimental medicine, and confirmed on the matter by many historian and philosophers of biology, such as Lederman and Burian . Though the choice the organism studied is often a matter of contingent circumstances (and it was indeed the case for our research), it often has an undeniable impact on the development of a research. As R. Burian explains, “most biologists realize that the choice of an organism can greatly affect the outcome of well-defined experiments and can thus have a major impact on the valuation of biological theory” , thus some model organisms, like Drosophila melanogaster and Escherichia coli accomplished their role with great success, while others, like “Hieracium, Oenothera and Ascaris […] led investigators astray” . The history of Drosophila melanogaster is quite interesting in that matter, as the fly studied by Thomas H. Morgan had a huge impact on the practices and problems of genetics , the simplicity of its genome favoring the theory of the central dogma, on gene, one protein, one feature, and the projects of mapping genomes. As genetic modifications had huge impacts on Drosophila melanogaster’s phenotype, we put in the genome an explanatory power that neglected important aspects of the complexity of genetic regulation and organisms’ environment. However it was a fertile way to limit this ungraspable complexity in a first time.

Synthetic biology brought a new word when referring to model organism: the term “chassis”. Though this term may surprise when first heard (one spontaneously thinks of mechanics rather than biology) it is quite coherent with the project of synthetic biology: making biology easier to engineer. The epistemology of synthetic biology is not a descriptive one but a pragmatic or a technological one. We have to produce knowledge by building and standardizing our construction, to make it possible to work in a large scale. As synthetic biology introduces new terms, it is important to analyze them in order to get clearly what they mean, and try to establish whether they are necessary or not. Recalling the Occam’s Rathor, maybe it is no use and sometimes misguiding to multiply entities when there is no need. We will first remind what is understood by the term model organism, and justify why Xenopus tropicalis is a very interesting model organism. We will analyze the term chassis in order to emphasize the epistemological differences that can be made between a chassis and a model organism, and therefore wonder if Xenope matches those characteristics.

R. Burian suggested four characteristics defining what a good model organism is: a) the organism should be useful to realize a certain objective of research, b) easy to manipulate regarding the topic of the research, c) there should exist a large amount of experimental resources coming with the organism such as genomic data, and d) the organism should represent a class of organism with a specific interest. Though the practical usefulness of a model organism is mainly the large amount of data gathered around it, it is important for biology to have many different model organisms, representing different nods in the phylogenetic tree and remembering us that contrary to what François Jacob once said, what is true for Escherichia coli isn’t necessary true for the elephant. As seen with the foreword, frogs have been by the past a quite useful organism for biology, for reasons different from those invoked before and on which we will develop in another part of our reflection. The old martyr of experimental physiology has been progressively replaced by the now favorites model organisms of molecular biology and experimental medicine, which are the fly Drosophila melanogaster, the bacteria Escherichia coli, the plant Arabidopsis thaliana and the mouse Mus musculus (these are the most popular).

However batrachians in the name of Xenopus tropicalis are still widely use and might come back in the limelight. In 2010 Xenopus tropicalis’ genome has been fully sequenced and the toad enters in the realm of postgenomic model organisms. The toad slowly replaces its counterpart Xenopus laevis presenting interesting features for various kinds of research. Xenopus laevis was widely used as a model organism in developmental biology, cell biology, toxicology and neurology since the 1950s, being a particularly attractive model because of its manipulability and the size of its embryo, visible by naked eye. Without being a mammal, this vertebrate is evolutionary close enough with human to give us expandable results . However, Xenopus laevis is a tetraploid and has a quite slow rate of reproduction, reaching its sexual maturity around one or two years, whereas Xenopus tropicalis is a diploid reproducing twice as fast which makes it a more practical model, especially for genetics and for an iGEM project. Though the size of the egg is a bit smaller (< 1mm), it still is visible by naked eye and quite practical to microinject.

Xenope as a chassis?

Thus Xenopus tropicalis clearly fits the characteristics defining a good model organism. A large amount of data exists on it as its genome has been sequenced, a large variety of studies are already done on Xenopus tropicalis and it is known to be easy to manipulate (characteristics b), c) and d)). If we keep an eye on Burian’s criteria, being a chassis is a specific mode of the first one: being useful to realize a specific objective of research. As a chassis is a specific kind of a model organism, directed toward a specific use, we have to investigate more closely what it is expected from a chassis to get the interest of bringing Xenopus in the realm of engineering.

Synthetic biology introduced the term “chassis” as a new way to refer to an organism. The metaphor is quite suggestive, in French the term appeared in the end of XVIIth century in joinery and is today more specifically known when talking about cars: the chassis is the rigid structure on which the various elements constituting the vehicle are fixed. This definition of a chassis can be kept and slightly developed when talking about living things: in synthetic biology, the term chassis primarily concerned bacteria, and specifically Escherichia coli. A chassis is meant to receive designed devices composed of standardized parts realizing specific functions.

Thus a chassis is meant to become a living tool, such as a biosensor (giving us reliable results concerning the state of an environment), a biological factory (producing materials of values, like drugs or fuel) and a cleaning machine doing bioremediation. Even when used for more fundamental purposes (exchanging information, counting), the interest of chassis is to be the container of any application that we can imagine being possibly implemented in it. As the parts implemented in the chassis aimed to be standardized and as the chassis is aimed to be inserted in an industrial system of production, the chassis as to fit some criteria of technological artifacts, as safety, efficiency, reliability and profitability . These are, according to M. Bunge, the epistemological principles of technology.

These principles of technology applied to biology