Abstract
Recent developments in cellular microscopy provide an interesting example of the role played by what William Wimsatt calls “robustness analysis” in the establishment of experimental results. According to a commonly accepted biochemical model, clathrin-mediated endocytosis (that is, one of the main processes by which external material is internalized by the cell via the plasma membrane) takes place only if the size of the entering object does not exceed 120–150 nm. However recent studies provide evidence that invasive bacteria whose diameter is far larger than 150 nm can enter host cells in a clathrin-dependent manner. In particular, images obtained by fluorescence microscopy indicate the presence of clathrin molecules and their active role in such processes. Yet, due to the well-known risk that artifacts introduced during the preparation of the sample may influence the results obtained with this technique, the scientific community still does not deem the currently available evidence sufficient to revise the well-established and so far unchallenged model of clathrin-mediated endocytosis. The aim of ongoing research is thus to crosscheck the results of fluorescence microscopy by means of techniques involving transmission electron microscopy. The focus of this chapter will be on the methodologies adopted in a type of “correlative microscopy” combining (cryo-) fluorescence microscopy and (cryo-) electron tomography. It will be argued that real cases of robustness analysis offer, in general, a complicated pattern in which, a multiplicity of derivations are indeed combined, but their independence comes in degree and the results they yield stand with one another in a relation of partial overlap rather than identity. It will thus appear that the situation portrayed by Wimsatt’s robustness scheme is often to be regarded as an aim to be pursued through a long and stepwise process or even as a regulative ideal directing the researchers’ efforts, rather than as a readily available option in their methodological tool-box.
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Notes
- 1.
- 2.
Nickles (1989).
- 3.
A classical argument of this type is to be found in Hacking (1985). Although this article will focus on the notion of theoretical independence only, it is worth mentioning that a careful historical analysis may in principle reveal that a convergence between two or more theoretical techniques has been at least partly due to a mutual adjustment between them perhaps taking place at the level of their implementation or of the interpretation of their results. Whenever this is the case, the techniques in question would still be theoretically independent while not being genetically independent (see Chapter 1, Section 1.8), and this would render problematic the chancy character of their convergence.
- 4.
For the different interpretations of which see Chapter 9.
- 5.
Nederbragt (2003).
- 6.
Keen (1987, p. 1997).
- 7.
Conner and Schmid (2003, p. 40).
- 8.
But see Kelly (1997) for doubts about this hypothesis.
- 9.
Veiga and Cossart (2005).
- 10.
Ibid., p. 503.
- 11.
- 12.
For an analysis of the intrinsic solidity of a single derivation and its impact on the overall resulting robustness, see Chapter 10.
- 13.
Nederbragt (2003).
- 14.
In the following chapter of this volume, Nederbragt will further develop his taxonomy by adding a fourth level (triangulation), which I won’t discuss here (See Chapter 5, Section 5.2.3).
- 15.
Ibid., p. 609.
- 16.
According to Nederbragt, the hypothesis of the mesosome (a supposed cytoplasmatic organelle of bacteria, whose existence seemed to be proved by observations carried out with electron microscopy) was abandoned because it failed to pass tests at level 2 and 3.
- 17.
Nederbragt (2003, p. 609).
- 18.
Ibid., p. 606.
- 19.
The idealized situation of an experiment being repeated several times exactly in the same way could be seen as a limiting unrealistic case showing independence with respect to space, time and perhaps to the experimenters.
- 20.
I will not consider here cases in which images can be seen themselves as final results of an experiment. For an analysis of this interesting situation, see Chapter 7.
- 21.
Clathrin coated vesicles have been imaged with EM for many years.
- 22.
See, for instance, Betzig et al. (2006).
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Acknowledgements
Writing this chapter would have been impossible without the keen help of Dr. Anna Sartori Rupp of the Institut Pasteur (Paris), who has patiently introduced me to the current state of the research on endocytosis and whose suggestions have constantly guided my work. I wish also to thank Léna Soler and Hubertus Nederbragt for helping me to improve this article.
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Trizio, E. (2012). Achieving Robustness to Confirm Controversial Hypotheses: A Case Study in Cell Biology. In: Soler, L., Trizio, E., Nickles, T., Wimsatt, W. (eds) Characterizing the Robustness of Science. Boston Studies in the Philosophy of Science, vol 292. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2759-5_4
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