Thesis Final ORE Version

The Role of Normal Development in Experimental Embryology Submitted by James William Edward Lowe, to the University of Exeter as a thesis for the degree of Doctor of Philosophy in Philosophy, May 2015. This thesis is available for Library use on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. I certify that all material in this thesis which is not my own work has been identified and that no material has previously been submitted and approved for the award of a degree by this or any other University. (Signature) ……………………………………………………………………………… 2 Abstract This thesis presents an examination of the notion of ‘normal development’ and its role in biological research. It centres on a detailed historical analysis of the experimental embryological work of the American biologist Edmund Beecher Wilson in the early-1890s. Normal development is a fundamental concept in biology, which underpins and facilitates experimental work investigating the processes of organismal development. Concepts of the normal and normality in biology (and medicine) have been fruitfully examined by philosophers. Yet, despite being constantly used and invoked by developmental biologists, the concept of normal development has not been subject to substantial philosophical attention. In this thesis I analyse how the concept of normal development is produced and used in experimental systems, and use this analysis to probe its theoretical and methodological significance. I focus on normal development as a technical condition in experimental practice. In doing so I highlight the work that is required to create and sustain both it and the work that it enables. Variation between embryos can cause problems for scientists trying to produce valid and comparable results. In my study of Wilson’s work, I examine how the practices associated with normal development deal with the variation between embryos. In the 1890s, Wilson became increasingly interested in which causes were responsible for the processes of differentiation (the production of different cells and organs) and determination in the process of embryonic development. He performed a series of experiments on the marine invertebrate Amphioxus , which exhibits considerable variability in early development (Wilson, 1893a). Wilson carefully observed his samples and outlined a normal development based on them, which included a considerable range of variation. How Wilson treated variation was reflected in the different way in which he conceived of the process of development compared to other prominent embryologists, such as Hans Driesch and Wilhelm Roux. 3 Having introduced and assessed normal development, I use two analytical approaches to make further sense of it. Furthermore, these approaches identify why appreciating the role of normal development enables us to understand important aspects of scientific practice, such as experimental methodology and making causal attributions based on the results of experimental manipulations. The two main analytical approaches I use are James Woodward’s manipulationist theory of causation (Woodward, 2003 and 2010), and Hans- Jörg Rheinberger’s experimental systems approach (Rheinberger, 1997). The former assesses the factors involved in assessing proposed causal factors, rather than simply demarcating between causes and non-causes. The latter focuses on the way experimental set-ups are configured by scientists in ongoing series of experiments to frame phenomena of interest: “epistemic objects”. My analysis establishes the centrality of the concept of normal development to the way experimental systems are produced and reproduced, and to how attributions of causality which arise from experimental work are made. 4 Contents Abstract ........................................................................................................................................ 3 List of figures ............................................................................................................................. 12 Introduction ................................................................................................................................ 14 Methodology .......................................................................................................................... 20 Plan of the thesis .................................................................................................................. 25 Chapter 1 – Framework of analysis ....................................................................................... 31 1.1. Introduction ........................................................................................................................ 31 1.2. The experimental systems approach ............................................................................. 32 1.3. Assessment of causal factors in development ............................................................. 37 1.4. Conclusion ......................................................................................................................... 42 Chapter 2 – The role of embryology in nineteenth-century biology .................................. 44 2.1. Introduction ........................................................................................................................ 44 2.2. Morphology and embryology in the nineteenth-century .............................................. 45 5 2.2.1. Defining homology ..................................................................................................... 51 2.2.2. The impact of Darwinism .......................................................................................... 60 2.2.3. Methodological changes ........................................................................................... 68 2.3. The nature and challenges of embryological research ............................................... 71 2.4. Conclusion ......................................................................................................................... 81 Chapter 3 – From germ-layers to cell-lineage: morphology and the problems of development .............................................................................................................................. 83 3.1. Introduction ........................................................................................................................ 83 3.2. Evolutionary morphology and Wilson ............................................................................ 86 3.3. Wilson’s training and early research .............................................................................. 89 3.4. Wilson from the late-1880s .............................................................................................. 94 3.5. The shift from ‘traditional’ morphology to cell-lineage work ....................................... 99 3.5.1. Before cell-lineage – working with Lumbricus ..................................................... 101 3.5.2. Wilson’s cell-lineage research ............................................................................... 113 3.6. Conclusion ....................................................................................................................... 128 6 Chapter 4 – Establishing ‘normal development’ as an embryological research strategy ................................................................................................................................................... 132 4.1. Introduction ...................................................................................................................... 132 4.2. Background to the Amphioxus experiment ................................................................. 134 4.2.1. Amphioxus ................................................................................................................ 139 4.3. The Amphioxus experiment – methods ....................................................................... 141 4.3.1. The paper ................................................................................................................. 142 4.3.2. Collection and handling of Amphioxus ................................................................. 143 4.3.3. Manipulating Amphioxus ........................................................................................ 145 4.3.4. Comparing and calibrating – the structure of Wilson’s experimental set-up .. 146 4.3.5. Observing and representing Amphioxus .............................................................. 150 4.3.6. The Amphioxus experiment – comparisons with Roux and Driesch ............... 156 4.4. The Amphioxus experiment – results .......................................................................... 158 4.4.1. ‘Normal Development’ ............................................................................................ 159 4.4.2. ‘Induced’ embryos and assumptions about normality ........................................ 162 7 4.5. Conclusion – ‘Normal development’ as an input and output of experimental work ................................................................................................................................................... 164 Chapter 5 – Variation and conceptualisations of development ....................................... 168 5.1. Introduction ...................................................................................................................... 168

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