Building a Virtual Lifeform Maps, Model Organisms and Collaboration in Digital Biology Tommas Måløy Masteroppgave ved senter for Teknologi, Innovasjon og Kultur UNIVERSITETET I OSLO 30.05.2016 II III © Tommas Måløy 2016 Building a Virtual Lifeform: Maps, Model Organisms and Collaboration in Digital Biology Tommas Måløy http://www.duo.uio.no/ Trykk: CopyCat IV Abstract Collaborative modelling of neural networks is a growing field in neuro science. The recent years has seen an upscale in number and size of projects who utilize digital simulation to explore the brain. In 2011 a team of computer scientists and neurobiologists announced that they had started a project to create a complete in silico model of the nematode worm Caenorhabditis Elegans. It is a millimeter long, transparent free living worm, consisting of about 1000 cells. The C. elegans has been much studied, as its nervous system is small, consisting of only 302 neurons, and many human pathologies have proto equivalents in the worm. Research on the worm has been awarded 3 Nobel prices. It was the first creature to have its complete cell lineage mapped, the first creature to have is nervous system mapped, and the first creature to have its entire genome sequenced. Now it is poised to become the first create that has a complete digital model of itself as well. This thesis is a case study on the process to create the in silico model. I have used a framework from Actor Network Theory to follow the worm through a chain of translations: from the petri dish to the digital model, to its implementation in a Lego Mindstorms Robot. In this thesis, the process of creating the model is analyzed in terms of research animals, maps, and collaboration in science. The aim of my thesis is provide an answer to the question “what is a virtual organism. To provide an answer I employ the notions of inscription, experimental system and biological exchange from Actor Network Theory. I try to explore how virtual life is constructed, and how life is enacted in a digital substrate. V VI Preface I would like to thank the people who have enabled me in writing this thesis. I have had a great deal of support from many people. I would like to extend my gratitude to my first supervisor, Tone Druglitrø. If it hadn’t been for your good advices, guidance and counseling early in the process, this thesis would never had been written. I would also like to Hilde Reinertsen who took over as my supervisor when Tone left for maternity leave. Your help has also been invaluable. I would also give thanks to my good friend Audun Sørheim for IT support and corrections. I am also grateful to Ida Støa for enduring me through the process of writing this thesis. Your support has been of great importance throughout this process. VII VIII Innholdsfortegnelse 1 Introduction ........................................................................................................................ 1 1.1 Research Questions...................................................................................................... 2 1.2 Structure....................................................................................................................... 3 1.3 OpenWorm .................................................................................................................. 6 2 Theory, Method and Material ............................................................................................. 9 2.1 Introduction ................................................................................................................. 9 2.2 Animals in Biomedisine .............................................................................................. 9 2.3 Models, Maps and Collaboration ............................................................................... 14 2.3.1 Model organisms ................................................................................................ 14 2.3.2 Collaboration ...................................................................................................... 17 2.3.3 Codifying Collaboration in Open Science ......................................................... 19 2.3.4 Maps ................................................................................................................... 23 2.3.5 Summary ............................................................................................................ 26 2.4 Material and Analytical resources ............................................................................. 27 2.4.1 The Material ....................................................................................................... 28 2.4.2 Analytical resources ........................................................................................... 31 2.4.3 Experimental systems, epistemic things and technical objects .......................... 32 2.4.4 Differential reproduction .................................................................................... 35 2.4.5 Spaces of representation ..................................................................................... 36 2.4.6 Summary ............................................................................................................ 40 3 Empirical Matter and Analysis ......................................................................................... 43 3.1 Introduction ............................................................................................................... 43 3.2 The Petri Dish ............................................................................................................ 45 3.3 The Digital ................................................................................................................. 51 3.3.1 The digital connectome ...................................................................................... 52 3.3.2 Muscle - Neuron Interaction .............................................................................. 58 3.3.3 The Toolchain .................................................................................................... 65 3.3.4 Movement Validation ......................................................................................... 68 3.3.5 Tuning the Connectome with Genetic Algorithms ............................................ 72 3.3.6 Bionet ................................................................................................................. 75 3.4 The Connectome Engine ........................................................................................... 79 IX 3.5 Summary:................................................................................................................... 86 4 Conclusion ........................................................................................................................ 90 Literature .................................................................................................................................. 94 Empirical matter ....................................................................................................................... 96 No table of figures entries found. X 1 Introduction This thesis is about the development of the first digital model of a complex organism. It is a case study on the OpenWorm project, an international collaboration with the long term goal to create a fully digital model of the nematode worm Caenorhabditis Elegans. It addresses the coming together of the digital and the biological, in what is intended to be a digital model organism. My first encounter with the project was in a video I saw in social media. It was a Lego Robot scuttling about by itself presented as a worm. I found this immensely fascinating. A series of questions came to mind; In what sense was the robot a worm? Was it meant figuratively or literally? How was it made? How did it work? After a quick search I found the project’s main page, where one could read that it is an international open source collaboration, with the purpose of creating the world’s first virtual organism. By means of bottoms up modeling the behavior of the worm was to emerge from the model1. This further spiked my interest. This thesis reflects that process of finding out how a Lego robot came to represent a living creature. There are several organisms that is currently being modeled digitally. There is, of course C. elegans, but also the fruit fly, Drosophila Melanogaster, is being emulated in a digital model, in the neurokernel2 project. And the Human Brain Project3, is making a digital model of a part of the mouse brain. Not incidentally, these organisms are well used model organisms. Many of these projects are dedicated to open science as well. In an article on collaborative modeling in neuro science A.P Davidson gives an overview of the field. The detailed modeling studies of individual neurons and networks of neurons, has until recently, been the work of individual researchers. This is now changing. There is now several projects who employ a large scale, industrial approach to neural modeling. The first was the Blue Brain Project. Similar projects are undertaken by the Allen Institute of Brain Sciences, and the Human Brain Project (Davidson 2012, 158). They address a need for collaboration, as neuron models are running into increasing complexity barriers. The open source movement is part of 1 http://www.openworm.org/getting_started.html Accessed 12.04.16 2 www.github.com https://neurokernel.github.io/ Accessed 27.4.16 3 http://ieet.org/index.php/IEET/more/sim20150301