Discovering Cell Mechanisms: The Creation of

Between 1940 and 1970, pioneers in the new field of cell biology discovered the operative parts of cells and their contributions to cell life. Cell biology was a revolutionary science in its own right, 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. William Bechtel emphasizes how mechanisms were discovered by cell biologists.

Preface

xi

1. Introduction: Cell Mechanisms and Cell Biology

1

(18)

1. A Different Kind of Science

1

(4)

2. The Organization of Science into Disciplines

5

(8)

3. The New Discipline of Cell Biology

13

(6)

2. Explaining Cellular Phenomena through Mechanisms

19

(45)

1. Historical Conceptions of Mechanism

20

(4)

2. Twentieth-Century Conceptions of Mechanism

24

(2)

3. Current Conceptions of Mechanism

26

(7)

Mechanisms Explain Phenomena

27

(3)

Component Parts and Component Operations

30

(2)

Organization and Orchestration

32

(1)

4. Representing and Reasoning about Mechanisms

33

(7)

5. Levels of Organization and Reduction

40

(4)

6. Organization: From Cartesian to Biological Mechanisms

44

(10)

7. Discovering and Testing Models of Mechanisms

54

(8)

Identifying Working Parts

55

(2)

Identifying Component Operations

57

(3)

Localizing Operations in Parts

60

(1)

Testing Models of Mechanisms

61

(1)

8. Conclusion

62

(2)

3. The Locus of Cell Mechanisms: Terra Incognita between Cytology and Biochemistry

64

(54)

1. Cytological Contributions to Discovering Cell Mechanisms up to 1940

65

(24)

Cytology in the Nineteenth Century

68

(9)

Cell Membranes (1825-1935)

77

(3)

Mitochondria (1890-1925)

80

(3)

Ergastoplasm or Basophilia (1900-1930)

83

(1)

The Golgi Apparatus (1900-1940)

84

(4)

The State of Cytology circa 1940

88

(1)

2. Biochemical Contributions to Discovering Cell Mechanisms up to 1940

89

(28)

Foundations for Biochemistry in the Nineteenth Century

89

(5)

The Emergence of Biochemistry in the Twentieth Century

94

(3)

Alcoholic and Lactic Acid Fermentation (1895-1940)

97

(8)

Aerobic Cellular Respiration (1910-1940)

105

(11)

The State of Biochemistry circa 1940

116

(1)

3. The Need to Enter the Terra Incognita between Cytology and Biochemistry

117

(1)

4. Creating New Instruments and Research Techniques for Discovering Cell Mechanisms

118

(44)

1. The Epistemology of Evidence: Judging Artifacts

121

(7)

2. The Ultracentrifuge and Cell Fractionation

128

(12)

Breaking Cell Membranes

131

(2)

Choice of Media

133

(2)

Centrifugation Regimes

135

(2)

Interpreting Fractionation Results

137

(3)

3. The Electron Microscope and Electron Microsopy

140

(17)

Obtaining Sufficiently Thin Specimens

143

(6)

Altering the Specimen to Survive Microscopy and Generate an Image

149

(8)

4. A Case Study of an Artifact Charge

157

(3)

5. Equipped with New Instruments and Techniques to Enter Terra Incognita

160

(2)

5. Entering the Terra Incognita between Biochemistry and Cytology: Putting New Research Tools to Work in the 1940's

162

(28)

1. First Steps toward Cell Biology at the Rockefeller Institute: Claude's Introduction of Cell Fractionation

163

(3)

2. Robert Bensley: An Alternative Approach to Fractionation

166

(2)

3. Competing Interpretations of Fractions from Normal Cells

168

(3)

4. Linking Claude's Microsomes to Protein Synthesis

171

(6)

Brachet: Selective Staining of RNA and Correlation with Protein Synthesis

171

(2)

Caspersson: Spectrographic Analysis, RNA, and Protein Synthesis

173

(4)

5. Adding a Biochemical Perspective to the Rockefeller Laboratory

177

(5)

6. Adding Electron Microscopy as a Tool

182

(6)

7. The State of Cell Studies at the End of the 1940's

188

(2)

6. New Knowledge: The Mechanisms of the Cytoplasm

190

(68)

1. The Mitochondrion 192 Biochemists Confront Particulate Structure: Mitochondrial Enzyme Systems

192

(30)

More Structure: The Discovery of the Cristae of the Mitochondrion

199

(2)

A Competing Perspective on Mitochondrial Morphology

201

(8)

Biochemists Further Fractionate Mitochondria

209

(6)

One More Piece of Structure and a Proposal as to Its Function

215

(4)

Radical Reconceptualization of Oxidative Metabolism

219

(3)

2. Microsomes, the Endoplasmic Reticulum, and Ribosomes

222

(21)

From Lace—like Reticulum to Endoplasmic Reticulum

222

(6)

Dissenting Voices

228

(3)

Securing the Connection to Protein Synthesis

231

(2)

Integrating Morphology and Biochemistry

233

(3)

Naming the Ribosome

236

(1)

Going to a Lower Level: Decomposing the RNA Machinery

237

(6)

Transporting Newly Sequenced Polypeptides

243

(1)

3. Two Additional Organelles

243

(14)

The Golgi Apparatus

244

(6)

The Lysosome

250

(7)

4. Conclusion

257

(1)

7. Giving Cell Biology an Institutional Identity

258

(21)

1. Creation of the Journal of Biophysical and Biochemical Cytology

260

(8)

2. Creation of the American Society for Cell Biology

268

(8)

3. Conclusion

276

(3)

Afterword

279

(2)

References

281

(32)

Index

313

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Discovering Cell Mechanisms: The Creation of Modern Cell Biology

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