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UNIVERSITY of CALIFORNIA, SAN DIEGO Biochemical Kinds And UNIVERSITY OF CALIFORNIA, SAN DIEGO Biochemical Kinds and Selective Naturalism A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Philosophy (Science Studies) by Joyce Catherine Havstad Committee in charge: Professor William Bechtel, Chair Professor Craig Callender Professor Nancy Cartwright Professor Cathy Gere Professor James Griesemer 2014 © Joyce Catherine Havstad, 2014 All rights reserved. The Dissertation of Joyce Catherine Havstad is approved, and it is acceptable in quality and form for publication on microfilm and electronically: __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ __________________________________________________________________ Chair University of California, San Diego 2014 iii DEDICATION for my parents iv TABLE OF CONTENTS Signature Page…………………………………………………………………….. iii Dedication…………………………………………………………………………. iv Table of Contents………………………………………………………………….. v List of Figures……………………………………………………………………... viii Vita………………………………………………………………………………… x Abstract of the Dissertation………………………………………………………... xi Introduction………………………………………………………………………... 1 References……………………………………………………………………... 7 Chapter 1: Messy Chemical Kinds………………………………………………… 8 Section 1: Introduction………………………………………………………… 8 Section 2: Microstructuralism about Chemical Kinds…………………………. 11 Sub-Section 2.1: Neither Strictly…………………………………………... 16 Sub-Section 2.2: Nor Solely……………………………………………….. 18 Sub-Section 2.3: Hendry on Elements……………………………………... 21 Sub-Section 2.4: Hendry on Compounds………………………………….. 25 Section 3: A Different Kind of Chemical Kind………………………………... 29 Sub-Section 3.1: Basic Protein Science……………………………………. 32 Sub-Section 3.2: Individuating Proteins…………………………………… 34 Sub-Section 3.3: Proteins, Microstructuralism, and Unification…………... 40 Sub-Section 3.4: Slater, Tobin, and Goodwin……………………………... 45 Section 4: The Argument from Iso-Ism………………………………………... 53 Section 5: Conclusion………………………………………………………….. 55 References……………………………………………………………………… 58 Chapter 2: Protein Taxa……………………………………………………………. 60 Section 1: Introduction………………………………………………………… 60 Section 2: A Primer on Proteins……………………………………………….. 65 Section 3: The Classification of Proteins……………………………………… 71 Sub-Section 3.1: Superstructural Considerations………………………….. 73 Sub-Section 3.2: Functional Considerations………………………………. 75 Sub-Section 3.3: Evolutionary Considerations……………………………. 77 Section 4: Classificatory Complications………………………………………. 80 Sub-Section 4.1: Nuclear Receptors………………………………………. 83 Sub-Section 4.2: A Brief Note about Reference…………………………... 86 Sub-Section 4.3: Phylogenies of the NHRSF……………………………... 87 Sub-Section 4.4: Types of NRs……………………………………………. 89 v Sub-Section 4.5: The NHRSF by Expression Pattern……………………… 91 Sub-Section 4.6: Implications……………………………………………… 93 Section 5: Conclusion………………………………………………………….. 99 References……………………………………………………………………… 102 Chapter 3: Complex Objects………………………………………………………. 104 Section 1: Introduction………………………………………………………… 104 Section 2: Complexity…………………………………………………………. 112 Section 3: Extending Mitchell’s View………………………………………… 117 Section 4: Proteins as Complex Objects………………………………………. 122 Section 5: Conclusion…………………………………………………………. 136 References……………………………………………………………………... 138 Chapter 4: Classification as a Tool for Discovery………………………………… 140 Section 1: Introduction………………………………………………………… 140 Section 2: Complications……………………………………………………… 142 Section 3: Constraints…………………………………………………………. 145 Sub-Section 3.1: Inaccessibility…………………………………………… 145 Sub-Section 3.2: Information Overload…………………………………… 146 Sub-Section 3.3: Diffuse Effects…………………………………………... 148 Sub-Section 3.4: Strain on Resources……………………………………... 149 Section 4: Classification as a Tool for Discovery……………………………... 150 Sub-Section 4.1: Origins…………………………………………………... 151 Sub-Section 4.2: Application……………………………………………… 153 Sub-Section 4.3: Evidence………………………………………………… 155 Section 5: Demonstrating the Concept………………………………………... 158 Section 6: Conclusion…………………………………………………………. 164 References……………………………………………………………………... 166 Conclusion………………………………………………………………………… 167 References……………………………………………………………………... 172 Appendix A………………………………………………………………………... 173 Section 1: Introduction………………………………………………………… 173 Section 2: Protein Science……………………………………………………... 174 Section 3: Molecular Biology………………………………………………….. 178 Section 4: Endocrinology……………………………………………………… 181 Section 5: The Nuclear Hormone Receptor Superfamily……………………… 185 Section 6: Conclusion………………………………………………………….. 191 References……………………………………………………………………… 194 Appendix B………………………………………………………………………… 197 Section 1: Introduction………………………………………………………… 197 Section 2: GEL-X……………………………………………………………… 203 Section 3: Applying the Ideas of Laboratory Life to GEL-X………………….. 213 vi Sub-Section 3.1: The Daily Activity of Science…………………………... 214 Sub-Section 3.2: Literary Inscription and Origin Stories…………………. 220 Sub-Section 3.3: Statement Types and Cycles of Credit………………….. 225 Sub-Section 3.4: The (Social) Construction of Scientific Facts…………… 233 Sub-Section 3.5: The Creation of Order out of Disorder………………….. 235 Section 4: Conclusion………………………………………………………….. 236 References……………………………………………………………………… 239 vii LIST OF FIGURES Figure 2.1: Four levels of proteins structure………………………………………. 68 Figure 2.2: A helpful pair of diagrams from Lehninger’s Principles of Biochemistry. On the left is a depiction of the tetravalent nature of carbon; on the right is a schematic of the basic structure of amino acids……………………… 68 Figure 2.3: Diagram of a (zinc finger) protein with both alpha helixes and beta sheets. The curly-cues or telephone-cord shapes represent the alpha helixes; the arrows represent the beta sheets……………………………………………………. 74 Figure 2.4: The DNA-binding helix-turn-helix motif……………………………… 74 Figure 2.5: A snapshot that shows the superfamilies, families, subfamilies, and entries identified by the Atlas project by 1983, as well as the criteria of establishment for each division…………………………………………………….. 79 Figure 2.6: On the left, the taxa of standard biological classification, progressing up the hierarchy from least to most inclusive. On the right, a prospective taxonomy for protein classification, similarly structured from least to most inclusive categories………………………………………………………………… 82 Figure 2.7: A phylogeny of the nuclear hormone receptor superfamily…………… 87 Figure 2.8: The five domains of a nuclear receptor………………………………... 89 Figure 2.9: A physiologic nuclear hormone receptor superfamily………………… 92 Figure 2.10: The PBD graphic of RARα…………………………………………… 94 Figure 2.11: From left to right, the taxonomic structures of the nuclear hormone receptor superfamily by phylogeny, typing, and expression pattern……………….. 95 Figure 3.1: Diagram of an alpha helix……………………………………………… 126 Figure 3.2: Structure of the estrogen receptor (ER) ligand-binding domain………. 127 Figure 3.3: On the left, a protein with a triple zinc finger motif in complex with DNA. On the right, a repressor with a helix-turn-helix motif DNA-binding domain, also in complex…………………………………………………………… 129 Figure 3.4: Three distinct classifications of the nuclear hormone receptor superfamily, one from each of the different classification systems………………... 131 Figure 4.1: Step 1 – Indicate the different types of nuclear receptor with different shapes in a mechanistic nuclear hormone receptor superfamily…………. 159 viii Figure 4.2: Step 2 – Associate a different color with each cluster of nuclear receptors in the physiologic nuclear hormone receptor superfamily, while also importing the type-indicating shapes from the mechanistic superfamily………….. 160 Figure 4.3: Step 3 – Place an appropriately colored and shaped indicator next to each nuclear receptor in a phylogenetic nuclear hormone receptor superfamily….. 161 Figure B.1: On the left, the Salk Courtyard, facing the Pacific Ocean; on the right, a view of the North Building from the lawn………………………………… 204 Figure B.2: Diagram of the interior of Guillemin’s laboratory……………………. 207 Figure B.3: Diagram of the interior of the GEL-X laboratory…………………….. 208 Figure B.4: A comparison of laboratory hierarchies………………………………. 211 ix VITA 2001–2007 Research Assistant, The Salk Institute for Biological Studies 2004 Bachelor of Arts, University of California, San Diego 2007 Master of Arts, San Diego State University 2008–2010 Editorial Assistant, Philosophical Psychology 2014 Doctor of Philosophy, University of California, San Diego PUBLICATIONS “Problems for Mechanism and Natural Selection” in Philosophy of Science 78(3): 512– 523. July 2011. “Human Reproductive Cloning: A Conflict of Liberties” in Bioethics 24(2): 71–77, February 2010. “Biological Individuality and the Unit of Selection”— Unpublished Master’s Thesis, San Diego State University, May 2007. “The Price of Dignity: Kantian Accounts of Moral Responsibility to Non-Human Entities” in Dialogue 49(2–3): 99–107, April 2007. FIELDS OF STUDY Major Fields: Philosophy and Science Studies Studies in Philosophy of Science Professors Craig Callender and Nancy Cartwright Studies in Philosophy of Biology Professors William Bechtel and James Griesemer Studies in Science and Technology Studies Professors Cathy Gere and Robert Westman x ABSTRACT OF THE DISSERTATION Biochemical Kinds and Selective Naturalism by Joyce Catherine Havstad Doctor of Philosophy in Philosophy
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