University:
Boston University
Course:
GMS AN 704 | Experimental Design and Statistical Methods
Academic year:

2023
Views:

83

Pages:

12
Author:

GalacticGuru

Uncomfortable resting point? ¨ “This is an uncomfortable resting point. Longino has argued for the continuing importance of multiple, incommensurable approaches, and yet urges greater interaction among those same approaches. Incommensurability suggests inability for one approach to speak to another, and on the other hand, interaction among approaches suggests the integration that Longino dismisses.” Potochnik, NDPR Pluralism + Integration ? ¨ ¨ ¨ ¨ What is it to be a “pluralist”? When/why ought we to embrace pluralism about scientific taxonomy, methods, or theories? Can we consistently embrace a pluralist view, and see (at least part) of scientific progress as involving greater interaction, or “integration”? What is productive interaction? When are integrations “successful”? When and how do they fail? Pluralism ¨ “… inquiry may sustain a multiplicity of viable approaches, each generating some knowledge. The question becomes not which one is best or better, but what each contributes – both in terms of our positive results, and in terms of critical perspectives on the others – to our overall understanding of the phenomenon. This openness to plurality of approaches constitutes philosophical pluralism.” (Longino, 2013, p. 2) Pluralisms ¨ ¨ ¨ Methodological: a variety of methods or disciplinary approaches, at least initially, may be worth pursuing independently. Epistemic: “natural phenomena cannot be fully explained by a single theory or fully investigated using a single approach…. multiple approaches are required for the explanation and investigation of such phenomena.” (Kellert, et. al. 2006) Metaphysical: the world is “dappled” (Cartwright 1999). ¤ ¤ (1) Laws of limited scope form a loose patchwork rather than reducing to a compact, unified set of fundamental laws. (2) Alternatively, “promiscuous realism”: diversity of possible classifications of kinds. (Dupré, 1993) My view: ¨ ¨ ¨ Methodological: unproblematic. Epistemic: Different aspects of the same phenomenon may require different explanations. Success is piecemeal and multifaceted, in part due to diverse predictive and explanatory goals. General theories can explain large classes of phenomena, but explanatory scope is often at the cost of precision. “Integrative” approaches vary. Metaphysical: There is one world, but legitimate cross-cutting classifications. Theoretical Model or mathematical integration Mechanistic inter-level integration Dimensions of Integration Methodological Systems approaches: e.g., functional molecular networks Data integration: analysis & coordination of clinical/ histological/genetic information across platforms Data A “unified” explanation ¨ ¨ Tomasetti & Vogelstein, (2014) “only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells.” (Assumes somewhat artificial partitioning of causes.) The argument ¤ ¤ ¤ ¤ ¤ ¤ Cells divide. Mutations happen. Some tissues have more stem cell divisions than others. Cells that divide more often have more mutations. Tissues with more stem cell divisions & more mutations are more frequently subject to cancers. QED (VERY) Local mechanistic integration ¨ Typical pattern of (80%?) of molecular genetic research on cancer: X gene is found commonly mutated in cancer Y. ¤ X gene is associated with function F. ¤ Function f is associated with pathway P. ¤ Pathway P affects downstream expression of genes A, B, and C, and/or epigenetics of gene expression, etc.. ¤ Genes A, B, and C, when mutated or differentially expressed, can cause one of the typical hallmarks of cancer cells: chromosomal duplication, dedifferentiation, cell cycle disruption, can desensitize the cell to apoptotic signaling, etc. ¤ X gene is found to be differentially expressed in mice, yielding distinctive pathology. ¤ “In conclusion, we have identified a novel tumor-promoting mechanism…” ¤ Mechanistic explanations in context ¨ ¨ ¨ Diagrams of cell regulatory pathways bear a striking resemblance to circuit diagrams. Nodes in these pathways play functional roles akin to those in a circuit. Some nodes “interrupt” the flow of information; these are analogous to switches that are “open” in that they “block” or “inhibit” activity, or the continued production of a signal. Other nodes serve as “resistors”; they “do work” with the information – usually by directing the signal to activate another pathway, which may in turn either induce transcription of a gene, or “upregulate” a protein. A series circuit 99 The Apoptotic Circuit Board Core .=iii=-=-=-� � �------- :�• : FJOiR ...-+-=;--:,::::__::-:..•.. ---lloundttalt ··.---·. ---·: о ::-�lllolt :-ima8lall IIIOawt..., .... .... ---·· : ................................................ ..........................:o ..... :• ,_ -=�•WI • :t - ••w.;plu• The full array of oomponents governing apoptosis i s not known_ An initial attempt at modeli ng the system is shown. djll:II Cell signaling pathway ≠? circuit ¨ ¨ ¨ ¨ ¨ Activated by “floating intervenors”: external signals with more or less specificity (e.g., “IGF-1,” “cyclins,” “ligands,” “mitogens,” “DNA damage,” or “Cellular stress”) No “closed” circuits in the cell. Multiple “inputs,” and “endpoints.” That is, the same elements may play a variety of functional roles in distinct regulatory pathways. Same pathway may be deployed to different ends, drawing in different elements at different stages in development or the life cycle of a cell. Many pathways are often operating simultaneously and co-regulate one another.