Table Of Content

SYSTEMATIC For my family, my teachers, and the original Broadway cast of Hamilton Contents Author’s Note Preface: The Big Idea PART I: THE BASICS Chapter 1: Seeing the Systems in Biology: Technological Advances Are Letting Scientists Understand Living Things in a New Way Chapter 2: Déjà Vu All Over Again: The Common Patterns and Principles of Natural Systems Chapter 3: America’s Next Top Mathematical Model: Understanding Complex Systems Sometimes Requires Math Chapter 4: Ignoring the Devil in the Details: Robustness, Prediction, Noise, and the General Properties of Systems PART II: CELLS, ORGANISMS, AND ECOSYSTEMS Chapter 5: Beyond Tom Hanks’s Nose: Sequencing Technology Is Enabling Scientists to Study All of a Cell’s Genes at Once Chapter 6: The Smells of the Father: RNA, DNA Margin Notes, and the Other Missing Parts of the Cellular System Chapter 7: Growing Pains: How Cells and Tissues Coordinate Development, from Egg to Adulthood Chapter 8: No Organism Is an Island: The Interactions between Individuals and Species that Shape Ecosystems PART III: APPLICATIONS Chapter 9: Build Me a Buttercup: Using Synthetic Biology to Make Diesel Fuel, Programmable Cells, and Malaria Medicine Chapter 10: More Than Just 86 Billion Neurons: The Science of the Brain, and How Connections among Neurons Make It Work Chapter 11: Death and Taxes: Aging Is Governed by an Organism-Wide System that We Might Be Able to Manipulate Chapter 12: Your Microbiome and You: The Body Is Host to Trillions of Microbes that Affect Human Health Chapter 13: This Is Your System on Drugs: Tweaking Biological Systems to Produce Better Medical Treatments Epilogue Acknowledgments Notes Index A Note on the Author Author’s Note In introducing general readers to systems biology, I am including interesting research that is guided by the systems idea rather than pretending to provide a comprehensive or even fully representative overview of the field. The challenge to responsibly communicate new ideas that may be revised or even discarded with future research is one I take very seriously. The reader should keep in mind that this book covers many areas of research that are rapidly changing. In some of these cases, the work is still very preliminary. I have attempted to present our best current understanding of what’s happening, and I hope readers will pair enthusiasm for the progress scientists have made so far with a realization that there is still much more work to be done. I encourage the reader to check this book’s website at www.systematicbook.com for updates on the topics discussed herein. Preface: The Big Idea Neurons are the cells that do most of the heavy lifting in your brain, but the most exciting thing a single neuron can do is fire an electrical pulse. Big deal. So can my toaster. But 86 billion neurons connected together in just the right way form your brain, which enables you to think, feel, imagine, and wonder. That’s pretty impressive for a three-pound hunk of cells. The difference between one neuron and your brain is more than a matter of scale. Those 86 billion neurons must be connected together, and then something fundamental changes. This book is about the magic that happens when many proteins, cells, or other biological pieces are connected into a system. In biology, connected systems underlie many complex behaviors that have historically been hard to understand. Microbes in your gut, for instance, interact closely with your body, and some evidence suggests this system might affect your weight, alter your risk of developing cancer, or even influence your mood. Bacteria can use simple systems of proteins, DNA, and other biological material to anticipate sunrise, to decide what to eat, and even to predict what kind of food they are likely to encounter next. Systems in other living things affect aging, development, and overall health. And thinking in terms of systems can help explain interactions between organisms, such as the spread of plague through gerbil populations in the deserts of Kazakhstan. Unfortunately for the impatient scientist, the systems found in biology are enormous and complex. Each person has about 40 trillion cells,1 and each cell is made of billions of tiny components.2 If you bought a gumball for every cell in your body, you could fill Fenway Park in Boston about 1,000 times over,3 and those gumballs would cost you the entire GDP of Russia if you ordered them from Amazon.com at current bulk rates.4 When this many parts are connected together in one big biological system, astoundingly complex behavior results. Even simple systems of just three or four components can produce sophisticated behaviors, and it is precisely these webs of interacting components that make life possible. Systems biology—the study of connected groups of biological parts that all work together—is relatively new. For example, the Harvard Systems Biology Ph.D. Program matriculated its first class in 2005. There is even still some disagreement about what it means to be a systems biologist. Some think it’s all about bringing the math back to biology research; others say it’s about working with huge amounts of data. But at its core, systems biology is simply the recognition that life is complex because it’s connected. Systems biologists want to understand how systems make life—and all of its weirdness—possible. This is a book about how understanding natural systems is helping us unravel some of the biggest mysteries in science. We will explore biological systems that range in size from microscopic proteins to entire ecosystems. Despite superficial differences, these systems can be studied with similar approaches, and all of them have implications for our understanding of life or our ability to treat diseases.