Discovering Cell Mechanisms
The Creation of Modern Cell Biology

William Bechtel
University of California, San Diego

Cambridge University Press, 2006
ISBN-13 978-0-521-81247-4 hardback

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Between 1940 and 1970 pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. They offered mechanistic accounts that explained cellular phenomena by identifying the relevant parts of cells, the biochemical operations they performed, and the way in which these parts and operations were organized to accomplish important functions. Cell biology was a revolutionary science but in this book it also provides fuel for yet another revolution, one that focuses on the very conception of science itself. Laws have traditionally been regarded as the primary vehicle of explanation, but in the emerging philosophy of science it is mechanisms that do the explanatory work. Bechtel emphasizes how mechanisms were discovered, focusing especially on the way in which new instruments made these inquiries possible. He also describes how new journals and societies provided institutional structure to this new enterprise.

This book:

• Develops an account of mechanistic explanation as it figures in the biological sciences

• Advances a revolutionary approach to philosophy of science in which mechanistic explanation is emphasized rather than laws

 • Analyzes the history of discovery of cell mechanisms and of the research techniques and instruments involved


Preface page xi
1.   Introduction: Cell Mechanisms and Cell Biology 1
    1. A Different Kind of Science 1
    2. The Organization of Science into Disciplines 5
    3. The New Discipline of Cell Biology 13
2.   Explaining Cellular Phenomena through Mechanisms 19
    1. Historical Conceptions of Mechanism 20
    2. Twentieth-Century Conceptions of Mechanism 24
    3. Current Conceptions of Mechanism 26
      Mechanisms Explain Phenomena 27
      Component Parts and Component Operations 30
      Organization and Orchestration 32
    4. Representing and Reasoning about Mechanisms 33
    5. Levels of Organization and Reduction 40
    6. Organization: From Cartesian to Biological Mechanisms 44
    7. Discovering and Testing Models of Mechanisms 54
      Identifying Working Parts 55
      Identifying Component Operations 57
      Localizing Operations in Parts 60
      Testing Models of Mechanisms 61
    8. Conclusion 62
3.   The Locus of Cell Mechanisms: Terra Incognita between Cytology and Biochemistry 64
    1. Cytological Contributions to Discovering Cell Mechanisms up to 1940 65
      Cytology in the Nineteenth Century 68
      Cell Membranes (1825–1935) 77
      Mitochondria (1890–1925) 80
      Ergastoplasm or Basophilia (1900–1930) 83
      The Golgi Apparatus (1900–1940) 84
      The State of Cytology circa 1940 88
    2. Biochemical Contributions to Discovering Cell Mechanisms up to 1940 89
      Foundations for Biochemistry in the Nineteenth Century 89
      The Emergence of Biochemistry in the Twentieth Century 94
      Alcoholic and Lactic Acid Fermentation (1895–1940) 97
      Aerobic Cellular Respiration (1910–1940) 105
      The State of Biochemistry circa 1940 116
    3. The Need to Enter the Terra Incognita between Cytology and Biochemistry 117
4.   Creating New Instruments and Research Techniques for Discovering Cell Mechanisms 118
    1. The Epistemology of Evidence: Judging Artifacts 121
    2. The Ultracentrifuge and Cell Fractionation 128
      Breaking Cell Membranes 131
      Choice of Media 133
      Centrifugation Regimes 135
      Interpreting Fractionation Results 137
    3. The Electron Microscope and Electron Microsopy 140
      Obtaining Sufficiently Thin Specimens 143
      Altering the Specimen to Survive Microscopy and Generate an Image 149
    4. A Case Study of an Artifact Charge 157
    5. Equipped with New Instruments and Techniques to Enter Terra Incognita 160
5.   Entering the Terra Incognita between Biochemistry and Cytology: Putting New Research Tools to Work in the 1940s 162
    1. First Steps toward Cell Biology at the Rockefeller Institute: Claude’s Introduction of Cell Fractionation 163
    2. Robert Bensley: An Alternative Approach to Fractionation 166
    3. Competing Interpretations of Fractions from Normal Cells 168
    4. Linking Claude’s Microsomes to Protein Synthesis 171
      Brachet: Selective Staining of RNA and Correlation with Protein Synthesis 171
      Caspersson: Spectrographic Analysis, RNA, and Protein Synthesis 173
    5. Adding a Biochemical Perspective to the Rockefeller Laboratory 177
    6. Adding Electron Microscopy as a Tool 182
    7. The State of Cell Studies at the End of the 1940s 188
6.   New Knowledge: The Mechanisms of the Cytoplasm 190
    1. The Mitochondrion 192
      Biochemists Confront Particulate Structure: Mitochondrial Enzyme Systems 192
      More Structure: The Discovery of the Cristae of the Mitochondrion 199
      A Competing Perspective on Mitochondrial Morphology 201
      Biochemists Further Fractionate Mitochondria 209
      One More Piece of Structure and a Proposal as to Its Function 215
      Radical Reconceptualization of Oxidative Metabolism 219
    2. Microsomes, the Endoplasmic Reticulum, and Ribosomes 222
      From Lace–like Reticulum to Endoplasmic Reticulum 222
      Dissenting Voices 228
      Securing the Connection to Protein Synthesis 231
      Integrating Morphology and Biochemistry 233
      Naming the Ribosome 236
      Going to a Lower Level: Decomposing the RNA Machinery 237
      Transporting Newly Sequenced Polypeptides 243
    3. Two Additional Organelles 243
      The Golgi Apparatus 244
      The Lysosome 250
    4. Conclusion 257
7.   Giving Cell Biology an Institutional Identity 258
    1. Creation of the Journal of Biophysical and Biochemical Cytology 260
    2. Creation of the American Society for Cell Biology 268
    3. Conclusion 276
Afterword 279
References 281
Index 313