Stephan Guttinger at the Biological Interest Group – Monday, 27th November, 2-3pm, Byrne House

The fifth meeting of BIG saw the presentation of a draft-paper by Stephan Guttinger. His paper, entitled ‘From Practice to Process’, examines how several practices in molecular protein biology have encouraged a view of the nature of proteins that misleadingly reconceives them, changing them from the process-like entities that are encountered in practice and experiment, into thing-like entities when posited in theoretical models. For instance, the author observes that to consider protein microstructure as thing-like is at a discord with the experimental practices from which such assertions are derived, e.g. maintaining protein microstructure is technically difficult, since it is highly dynamic and fragile to sustain in vivo (cf. ‘protonation states’).

The molecular level of biology is often seen as a significant challenge for process ontologists. More specifically, the sequence-structure-function paradigm (SFF) of protein nature and behaviour could be seen supporting the idea that proteins exist substantially as things (and not processually). As the author explains, the SFF paradigm consists of two key claims: (1) the protein exists as its three dimensional structure (or “fold”) and this fold causes the protein’s function; (2) the fold exists as the amino acid sequence and this sequence, often called the ‘primary structure’ or ‘microstructure’, causes the structure of the fold to form (for a review, see Keskin et al., 2008). For example, for a protein to interact with another protein, such an action depends on the presence of corresponding acidic or hydrophobic patches on the surface of the corresponding protein – this is often referred to as “the hand-and-glove model” (Koshland, 1958), which is itself a play on Fischer’s famous lock-and-key analogy (1894). In a similar way, enzymes are acknowledged as displaying a structure, within a region designated as the “active site”, which corresponds with the structure of their substrate.

However, as the author indicated, an understanding of proteins based on the SFF paradigm has been threatened by cases of Intrinsically disordered proteins (Dunker et al., 2001; Dyson & Wright, 2005; Uversky & Dunker, 2010). The author asks whether this change in understanding necessitates a transformation in the underlying ontological assumptions also, and thereby undermining one of the last bastions of a substance ontology in biology. IDPs are explicated as having no fixed three-dimensional structure in their native state, and that this can be true of a part of a polypeptide chain or it can be true of its whole length. The author characterised the disorder of IDPs along three dimensions: (1) the intensity of the disorder (i.e. at one end of the scale the IDP exhibits complete disorder, allowing its amino acids the maximum freedom of movement that its covalent bonds allow for, but at the other end the IDP exhibits ‘molten-globule-like’ disorder, which represents a hybrid state between a fully ordered state and a random-coil); (2) the extent of the disorder (i.e. whether it is localised to a short stretch, a single domain, or the whole length of a protein); and (3) the relation between the disordered state and the functional state of the protein.

The group discussed the giddiness of extrinsic and intrinsic relations in the context of grounding the two ontologies, and we attempted to provide some analytical distinctions of the important concepts in play. It would seem typical to a substance ontology that an existing substance is grounded in its essential characteristics. In some sense it might be said that the essence is intrinsic to its substance. It might then seem to follow from this that the relations between substances are accidental upon that which determines a substances existence; in other words, the existence of a substance is somewhat independent of its extrinsic relations. Contrarily, if a process (and not a substantial entity) is all that can be said to exist, what was once ascribed as its essences becomes an effluence, undergoing indefinite changes. For a process ontology then, relations are constitutive of their existence; a process’ relations are essential to its existence.

The author situates his discussion within two philosophical projects, whose concerns converge in the case he examines. With regards to the first project, proponents wish to provide the intellectual resources that brings our thinking towards a naturalistic metaphysics, specifically the author examines the dispute between a substance ontology and a process ontology; in the second project, proponents bring renewed attention towards scientific practices as something which is as important for scientific understanding as theory building. Specifically the author examines how the practices of some cases of protein science inform discussions concerning metaphysical assumptions. In effect, the author argues, what some scientists model as the (theoretical) nature of proteins is antagonistically opposed to how they are treated practically and experimentally. Moreover, the author argues that it is because the substance ontology is deeply embedded in the received thinking of the sciences that this juxtaposition and contradiction between the theory and practice of protein science has endured; but, as the author believes, this problem is overcome when the practices of these scientists are sufficiently exposed.

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Dunker, A.K., J.D Lawson, C.J. Brown, R.M. Williams, P. Romero, J.S. Oh, C.J. Oldfield, A.M. Campen, C.M. Ratliff, K.W. Hipps, & J. Ausio, ‘Intrinsically disordered protein’, Journal of Molecular Graphics and Modelling, 19:1 (2001) 26-59

Dyson, H.J., & P.E. Wright, ‘Intrinsically unstructured proteins and their functions’, Nature Reviews Molecular Cell Biology, 6:3 (2005) 197-208

Fischer, E., ‘Einfluss der Configuration auf die Wirkung der Enzyme’, Berichte der deutschen chemischen Gesellschaft, 27:3 (1894) 2985-2993

Keskin, O., A. Gursoy, B. Ma, & R. Nussinov, ‘Principles of protein-protein interactions: what are the preferred ways for proteins to interact?’, Chemical reviews, 108:4 (2008) 1225-1244

Koshland, D.E., ‘Application of a theory of enzyme specificity to protein synthesis’, Proceedings of the National  Academy of Sciences, 44:2 (1958) 98-104

Uversky, V.N. & A.K. Dunker, ‘Understanding protein non-folding’, Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics, 1804:6 (2010) 1231-1264

 

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Giovanna Colombetti and Eder Zavala at the Biological Interest Group – Monday, 20th November 2017, 2-3pm, Byrne House

The fourth meeting of BIG saw the presentation of a paper by Professor Giovanna Colombetti and Eder Zavala, from the Living Systems Institute at Exeter University. Their paper, entitled ‘Moving beyond “brain-based” accounts of affectivity’, critically evaluates what some neuroscientists call the ‘the neural basis’ or ‘the brain basis’ of affective states in humans and other mammals (e.g. LeDoux, 1996, p. 18; Lindquist et al., 2012). ‘Affective states’ refer primarily to emotions (e.g. anger, happiness & shame), but include moods (e.g. irritability, elations, nervousness, stress) and mood disorders as well (e.g. depression, anxiety & mania).

The authors admit that far too much on this topic is left implicit and vague as to what affective neuroscientists mean by ‘the neural-basis of affective states’; the authors formulate two possible interpretations of the view. One formulation (the brain constitution thesis) specifies the brain as a physical realiser of mammalian individual’s affective states – a physical realiser of affective states is some condition that is metaphysically sufficient for the awareness of the presence of those states in the object attributed with the physical realiser (cf. Wilson, 2004, pp. 101-105). In other words, the brain is the ‘vehicle’ of the affective states as they are entirely constituted by brain processes; the basis for affective states is “brain-bound” (see Clark, 2008). The authors note that this view entails a position of explanatory internalism: that for one to explain the presence of affective states in an individual, one need only look inside it and at its brain activity, recording how brain states change as affective states change. A second possible formulation (the brain causal thesis), which, generally, attributes the brain a particularly significant causal role for the manifestation of affective states – to describe the relation as one where the brain is said to “make”, “generate”, “produce”, or “construct” affective states is to posit the former as efficient cause of the latter. More specifically, one version of this view will posit particular neurochemical processes occurring in the brain as the cause of a cascade of effected changes in the body (e.g. in the autonomic nervous system, vocal and facial expressions, behaviour etc.); these changes are considered to be constitutive of particular affective states (e.g. a particular neurochemical change in the brain causes an accelerated heart rate, and this is constitutive of the affective state of fear).

The authors argue that both formulations of brain-based affectivity become problematic when compared with more recent empirical findings. In particular, neuroendocrine research on mood and cognitive disorders have found that in order to better understand hormonal functions, it is essential to understand the “cross-talk” (sequences of causal influences and feedback loops) between the brain and several endocrine organs. The authors noted that “cross-talk” interactions are typical to endocrine axes, such as the Hypothalamic-Pituitary-Adrenal (HPA) axis, the HP-Gonadal (HPG) axis, and the HPA-metabolic axis. Hormone secretion depends on the nature of the interactions in these axes, and the levels of hormones secreted play a significant causal role in bodily affects. This understanding (of a neuroendocrine basis for affectivity) is certainly opposed to the first formula of the neural basis for affectivity (the brain constitution thesis). However this understanding also raises concerns for the second formula (the brain causal thesis), since the presence of feedback mechanisms require a more holistic and systemic understanding of affectivity. Put more simply, perhaps one could say that given the cross-talk of many endocrine axis, which are essential for an understanding of the basis of affectivity, one can no longer state that the brain (and only the brain) is causally responsible for an affect. The authors illustrate this with a clear case where certain affects cannot occur without endocrine organs: the stress response (cf. Lupien et al., 2007). The stress response involves rapid changes in magnitudes of glucocorticord hormones (e.g. corticosterone in rodents, cortisol in humans), which circulate in the organism. The HPA axis regulates these changes through a highly dynamic mechanism. Although the glucocorticoids are synthesised in the adrenal glands, the highly dynamic mechanism of the HPA axis involves feedback loops between the adrenal glands, the pituitary gland, and the hypothalamus (Spiga et al., 2015).

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I was unable to make this session and join in with the discussion, but the draft of this paper was a fascinating read.

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Clark, A., Supersizing the Mind: Embodiment, Action and Cognitive Extension, (Oxford University Press, 2008)

LeDoux, J.E., The Emotional Brain, (Simon and Schuster, 1996)

Lindquist, K., T. Wager, H. Kober, E. Bliss-Moreau, L.F. Barrett, ‘The brain basis of emotion: A meta-analytic review’, Behavioral and Brain Sciences, 35:3 (2012) 121–143.

Lupien, S.J., F. Maheu, M. Tu, A. Fiocco, & T.E. Schramek, ‘The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition’, Brain Cognition, 65 (2007) 209-237.

Spiga, F., J.J. Walker, R. Gupta, J.R. Terry, & S.L. Lightman, ‘60 Years of Neuroendocrinology: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies’, Journal of Endocrinology, 226 (2015) T55-66.

Wilson, R.A., Boundaries of the Mind: The Individual in the Fragile Sciences: Cognition, (Cambridge University Press, 2004)

 

Katharine Tyler at the Biological Interest Group – Monday, 13th November, 2-3pm, Byrne House

The third meeting of BIG was on the role of genetic ancestry testing in shaping and supporting the entrenchment of attitudes of nationalism and racism. In her paper, entitled ‘Blogging Descent: Genetic Ancestry Testing, Whiteness and the Limits of Anti-racism’, Dr. Katharine Tyler examined the expression of these attitudes, which were found to be published in an anonymous internet-based comments section and blog. This generated some fascinating discussion over a broad range of complex issues.

The author builds on the work of M’Charek, who examined how potential differences, based on race, begin to materialise and actualise only when certain social relations serve to enact them (M’Charek, 2010). The author sought, amongst the published web-based content, to categorise the attitudes found, into one of two narrative discourses: one discourse uses scientific findings to support an image of British identity, which is entwined with images of white Nordic European origins; the second discourse, advocating an apparently opposing image, uses scientific findings to support a discourse on the common descent of humanity from African origin. The author showed how those adhering to the first discourse evoked scripts, icons and images, which conform to some aspects of the media’s dissemination of Walter Bodmer’s work – Bodmer is a population geneticist who has had a leading role in the public dissemination of both the science and the technology of genetic ancestry testing (e.g. see Fortier (2012) and Nash (2015) on Face of Britain [Channel 4, 2007]). The author also explores how those adhering to the second discourse, reflect some of the guiding beliefs underpinning The Genographic Project, which succeeded the Human Genome Diversity Project. For example, Reardon and Tallbear write that such a project is motivated by the “common belief among human population geneticists and biological anthropologists [that] if you undercut race as a biological category, you also undercut racism” (Reardon & Tallbear, 2012, p. 243). However, the author contends that both discourses shape and support attitudes of nationalism and racism. Despite the explicitly anti-racist ethos embedded in the second discourse, it nonetheless reproduces (albeit unintentionally) hierarchies of racial, ethnic and national differences, which reflect asymmetrical relations of values and inequalities (e.g., see: Cross, 2001; Reardon & Tallbear, 2012).

Since it was apparent that some agencies had used some scientific findings to suit agendas other than the dissemination of information, a few participants raised a question of responsibility concerning some agencies (e.g. the marketing and advertising of genetic ancestry testing and some media broadcasts and productions), which were responsible for enacting the narrative discourses that the paper discusses. In addition, since science does not, all at once, speak with one voice or as one agency, the group discussed the divergent research cultures that comprise it. Moreover, it was felt that some criticism could be levied at the service industry for their role in promoting genetic ancestry. This is especially acute, since a change in industries (i.e. from the science to service) could mean a change in aims: where the intentional action could change from making a problem comprehensible to making some product or service marketable.

We discussed some of the peculiar methodological concerns, which would face the researcher who would use the blogs and comments sections of websites as a resource for social research. In particular, what sort of voices do these publications represent? How would a blog that was curated effect the sort of voice telling a narrative? One could imagine that curated blogs might require each blogger to set up an account with some amount of contact information; but how would this differ to a website where authors could be completely anonymous? What sort of voice would be represented there? An interesting feature the group discussed was the capacity and ease of an author to revise a position after publication.

If you’d be interested in joining the group and discussing, with Katharine, her research, please contact us here.

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Cross, K., ‘Framing whiteness: the human genome diversity project (as seen on TV)’, Science as Culture, 10:3 (2001) 411-438

Fortier, A., ‘Genetic indigenisation in ‘The People of the British Isles’, Science as Culture, 21:2 (2012) 153-175

M’Charek, A., ‘Fragile differences, relational effects: stories about the materiality of race and sex’, European Journal of Women’s Studies, 17:4 (2010) 307-322

Nash, C., Genetic Geographies: the Trouble with Ancestry, (University of Minnesota Press, 2015)

Reardon, J., & K. Tallbear, ‘“Your DNA is our history”, genomics, anthropology, and the construction of whiteness as property’, Current Anthropology, 53:5 (2012) 233-245.