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Molecular-biological machines: a defense

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Abstract

I offer a defense, albeit a qualified one, of machine analogies in biology, focusing on molecular contexts. The defense is rooted in my prior work (Levy in Philosopher’s Imprint 14(6), 2014), which construes the machine machine-likeness of a system as a matter of the extent to which it exhibits an internal division of labor. A concrete aim is to shore up the notion of molecular biological machines, paying special attention to processive molecular motors, such as Kinesin. But I will also try to show how the division of labor account gives us guidance more broadly, both about where and why machine analogies can be expected to prove helpful and about their limitations.

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Notes

  1. Besides ‘division of labor’, in Levy (2014) I also used the phrase ‘causal order’. I’ve found that this terminology carries unintended connotations, especially in connection with the statistical mechanical concept of order. So I avoid it here.

  2. Some of the cases I discuss in this paper may, strictly speaking, be instances of metaphor or simile, rather than analogy. But I will not worry too much about distinctions within figurative devices.

  3. This condition doesn’t appear in Levy (2014). It is closely related to Skillings’ “isolatability” (2015, 1149–1150).

  4. Daniel Nicholson says that “confronted with a machine, one is justified in inferring the existence of an external creator responsible for producing it in accordance with a preconceived plan or design” (2013, 671). Nicholson’s argument rests on a distinction between intrinsic and extrinsic purposiveness, which I do not fully understand. But the key point I would make is that what is relevant to arguments of the sort Nicholson has in mind is not the apparent machine-likeness of the system in question but its adapted character—they appear designed in the sense that they are fit for some purpose. Even though humans tend not to, one can design a system in this sense without producing a system that divides labor.

  5. A more consistent term would be head-over-head, but I follow standard usage in the field.

  6. There are different concrete versions of the BR idea. The figure illustrates one version, known as a flashing ratchet model. Note that the figure depicts an energy landscape, not the physical structure of the molecule.

  7. Indeed, Nicholson (2019, 117) goes so far as to suggest that advocates of PS models operate under severe misunderstandings of the physics of molecular processes. I think this accusation is an exaggeration, to put it mildly. A range of precise, biophysically sound PS models exist in the literature (Howard 2001).

  8. For more on early work on Kinesin, on how its hand-over-hand motion was characterized and verified, and on the evolution of work in this area see Bechtel and Bollhagen (2021) and Bollhagen (2021).

  9. Another motility assay, used primarily in work by Steven Block and associates, involves attaching a glass bead to the Kinesin itself, which can then be captured (with force applied) by optical tweezers. One of the first papers using this method is Block et al. (1990), although it is still being further developed and put to new uses (e.g. Howard and Hancock 2020).

  10. As of the time of writing, and to the best of my knowledge, the clearest evidence on these questions is contained in Wolff et al. (2023). It suggests that ATP is hydrolyzed in the one-head-bound state and that while a full cycle involves the protein moving 16 nanometers, step size varies and can be either 6 nm, 8 or 10 nm.

  11. This is so both on PS and on BR model (Wagoner and Dill 2016) contra Nicholson’s suggestion (2020, 58).

  12. It is possible, of course, that some audiences, such as students in relevant areas or the general public, are liable to misunderstanding and errors. But, first, this is not my target in this paper—pedagogy and/or science communication cannot be easily read off from discussions of internal, research-focused questions. And, second, communicating the subtleties of machine analogies to non-specialists, even to lay audiences, is perfectly possible. See, for instance Hoffman (2012).

  13. This is a simplification in several respects, perhaps most importantly because it is well-known that a protein with the same tertiary structure can perform different roles depending on the cellular context, i.e. on cell type, developmental phase, which other cellular constituents are present etc.

  14. For this reason they are often described as self-organizing. But this term is overused and has multiple, sometimes ill-defined, meanings and so I avoid it.

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Acknowledgements

For comments on previous versions of this paper I thank Kelli Barr, Daniel Burnston, Laura Gradowski, Eleanor Knox, Ehud Lamm, Edouard Machery, John Mathewson, Dana Matthiessen, Sandra Mitchell, Meghan Page and Eörs Szathmáry. I am especially indebted to work by Daniel Nicholson, who has been a trenchant critic of machine analogies in biology. While disagreeing with Nicholson on some central points, working through his arguments has sharpened and focused my thinking.

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  1. Department of Philosophy, The Hebrew University of Jerusalem, Jerusalem, Israel

    Arnon Levy

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Levy, A. Molecular-biological machines: a defense. Biol Philos 38, 36 (2023). https://doi.org/10.1007/s10539-023-09915-z

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