BioBuilder

Preface

This book began with a relatively modest mission, namely to support the growing BioBuilder community, the teachers and students around the country and the world who are learning to engineer biology. BioBuilding is a challenging endeavor, and we heard over and over that a book like this would help. So here it is. We hope it’s helpful. We hope you like it.

We’ve written for a non-scientist, non-engineer reader. Importantly, though, the questions that motivate the content are the very hard questions that synthetic biologists wrestle with daily. How can cells be engineered in a rational way? Is it possible to ensure reliable behaviors? What can we learn as we approach life science with an engineer’s toolkit?

Who Should Read This Book

We hope a wide range of readers will find this book useful. Our writing began with teachers in mind, since these are the individuals we’ve come to know through the BioBuilder program. They have been enthusiastically bringing this content into their biology and biotechnology classrooms around the country and throughout the world. Early feedback we got on the book made us realize that teachers wanted to share the book directly with their students, and so the teacher’s manual we’d originally envisioned soon morphed into a resource that students and teachers can use together.

We think our book now meets the needs of many curious readers and all kinds of learners. Our intended audience includes high school and college instructors, students active in biodesign clubs, adults engaged in community laboratories, and artists working in design studios. We hope there is something in this book for everyone who wants to know more about the theoretical and practical aspects of synthetic biology.

Why We Wrote This Book

BioBuilder bridges the gap between the way we do science and the way we teach it. The ideas presented here and the labs that spring from them are based on current research in the field. The authenticity sparks student interest, and we’ve seen how it can excite and empower learners at all levels. But it’s hard to be working on the edge of what’s known, so we wrote this book to support the teachers and students who want to use unknowns as their point of departure for learning.

We also wrote this book because we love synthetic biology’s mixture of science and engineering, and we wanted to show how it’s working in practice. Our foundational chapters emphasize how synthetic biology brings some successful tools from more mature engineering disciplines to the life sciences. Our laboratory-focused chapters start with an authentic research question and then provide protocols to approach it from an engineering perspective.

With its mixture of foundational content, lab investigations, and biodesign activities, this book is our best effort to engender curiosity and enthusiasm for the field. We take an approach to synthetic biology and education more generally that resembles what Antoine de Saint Exupéry encouraged for ship-building in The Little Prince, namely “If you want to build a ship, don’t drum up people to collect wood and don’t assign them tasks and work, but rather teach them to long for the endless immensity of the sea.”

A Word on Synthetic Biology Today

The goal of synthetic biology is to engineer robust, synthetic, living systems in scalable and reliable ways. Some who are working in the field are applying synthetic biology to address our planet’s need for sustainable food and fuel production. Others are developing biotechnologies such as medical diagnostics or treatments. A smaller but vital subset of people view synthetic biology as a design challenge that they can apply to art, architecture or community innovations. No matter what the application space, though, you’ll see we’ve got a lot to learn and long way to go before the work is easy to do.

Even in its early days, synthetic biology has a lot to teach us. New scientific understanding, improved engineering approaches and novel technologies are all “naturally” derived from this “synthetic” approach. Building biology tests our current understanding of the world and so serves as a powerful force to discover new science. It also motivates the development of new tools and processes that speed the engineer’s design/build/test cycle. As a genuinely interdisciplinary endeavor, the field brings coherence to STEM education in a way that seems unique to us. So while the field may be immature, we think it is already an outstanding approach to teaching and learning. Because it is based on synthetic biology’s real unsolved questions, BioBuilder’s curriculum applies knowledge, and so moves classroom and laboratory education away from rote memorization and cookbook technical steps. It features synthetic biology as a series of investigations that integrate scientific understanding with engineering approaches to develop solutions that meet real-world challenges.

Navigating This Book

This book is intentionally modular and can be reordered to suit your needs. In its digital form, the chapters can easily be rebundled and shared through our creative commons license. The book’s printed form required a sequence for the chapters, and so we have organized things as follows.

Chapters 1–4 introduce some of the approaches fundamental to synthetic biology:

• Chapter 1, Fundamentals of Synthetic Biology, provides a basic introduction to the field, emphasizing synthetic biology’s interdisciplinary nature and some of its foundational tools from engineering and molecular biology.
• Chapter 2, Fundamentals of Biodesign, provides a framework for biodesign, including an abstraction hierarchy for managing complexity and some examples that unpack living systems into the devices and parts that encode them.
• Chapter 3, Fundamentals of DNA Engineering, discusses the role of standardization in engineering and dives into a few examples of standardized DNA assembly techniques.
• Chapter 4, Fundamentals of Bioethics, introduces questions about what constitutes “good” work, using modern and historic examples to illustrate the challenges and then provides a framework for teaching with these examples.

Chapters 5 through 10 detail BioBuilder’s laboratory investigations. Each starts with a description of a current challenge or developing idea in the field, offering some organizing principle or question that the experiments can then probe. Each lab chapter also includes an abbreviated protocol for carrying out a relevant investigation and helpful illustrated guides. Posters and quick guides can be downloaded from a GitHub repository for this book:

• Chapter 5, Introduction to the BioBuilder Labs, is an overview of the labs, defining distinct entry points in the design/build/test cycle for engineering.
• Chapter 6, Eau That Smell, models the biodesign framework detailed in Chapter 2 to ultimately ask the question: which genetic design will more effectively enable exponentially growing bacterial cells to generate a banana-scent?
• Chapter 7, iTune Device, focuses on principles of measurement and the role measurement plays in the predictable design. The laboratory portion of the chapter compares predicted and measured outcomes using combinations of genetic parts that regulate enzyme production.
• Chapter 8, Picture This, applies modeling techniques to understand and characterize the “bacterial photography system” in which bacteria serve as pixels in a living photograph.
• Chapter 9, What a Colorful World, considers the role of chassis in biological engineering first with a few complementary frameworks for chassis design and then by comparing the function of identical genetic programs in different strains of E. coli.
• Chapter 10, Golden Bread, examines the unreliable performance of a synthetic living system, namely a yeast that can produce the precursor to vitamin A. Scientific and engineering experiments explore redundancy as a way to understand and improve the behavior of the cells.

The book ends with abbreviated instructions for the preparation of common laboratory reagents, followed by a glossary of terms used throughout the book.

Online Resources

The material in this book only scratches the surface of what you’ll find on the BioBuilder website, so if you like what you find here, then we encourage you to navigate to biobuilder.org.

The site is fully open-access and provides the following:

• Animations that explain a few of the foundational concepts presented in this book
• Downloadable slides for teaching the laboratory and classroom materials in Chapters 5–10
• Screen capture videos from our teacher professional development workshops
• Practical tips for running the experiments, including quick guides and posters for printing
• A portal for sharing and comparing data collected in these experiments with the data collected by others
• Assessment ideas and rubrics
• Newsletters to keep up with ongoing development of the BioBuilder content and community

If you’d like to get directly involved, the website also has the following:

• Links to order kits for carrying out the experiments themselves
• Links to sign up for BioBuilder workshops
• A companion “Biobuilder for Teachers” resource site with classroom-tested extensions of the BioBuilder content
• Information on BioBuilder’s BioDesign Club, an afterschool extracurricular option for bringing the content to students

The curriculum and teacher training from BioBuilder are developed and supported through a non-profit organization. More information about The BioBuilder Educational Foundation, a 501c(3), is available at biobuilder.org.

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Acknowledgments

As we wrote this book we asked many of our friends and colleagues for guidance and feedback. They’ve responded with incredible generosity, and we’ve relied on things they’ve taught us. We thank them all, and offer special acknowledgement of Michael Loukides and Brian MacDonald at O’Reilly, who made this book possible with their vision and encouragement. We also thank SynBERC for their generous early support of this endeavor, and Prof. Susan Marqusee and Mr. Daniel Grushkin for introducing several of us to each other. Many colleagues read chapters in their earliest stages, including Prof. Kristala Prather from MIT and Dr. Reshma Shetty from Ginkgo Bioworks. Their insights were critically important as we got off the ground, and Reshma also made our initial introduction to the team at O’Reilly, so we extend great thanks to her for that as well. Dr. Megan Palmer framed our thinking and our explanation of what it means to do good work, material you’ll see in our chapter on Bioethics. Along the way we’ve also asked more targeted questions of some experts. Dr. Jason Kelly and Mr. Bill Burns helped on the trans-Atlantic cable history, Dr. Barry Canton framed our discussion on chassis design, Ms. Sarah Tyndall answered our measurement questions, and Mr. Chris Brown answered our questions about the use of models in architecture.

The BioBuilder content itself has been developed in collaboration with teachers in secondary and post-secondary classrooms all over the country. It grew out of some teaching in the Department of Biological Engineering at MIT that started in 2004, including some project and laboratory classes co-taught with Prof. Drew Endy. The initial extension of this teaching curriculum to the high school setting was launched in collaboration with Mr. Jim Dixon. Since this book was written to be useful for teachers, we got lots of input on the drafts. In particular we thank: Dr. Veronica Zepeda, Dr. Ellen Jorgensen, and Dr. Oliver Medvick for their review of the content from start to finish. We also thank Ms. Sherry Annee, Dr. Melissa Wu, Dr. Rebekah Ravgiala, Mr. George Cachianes, Mr. Aaron Mathieu, Prof. Stephanie Stockwell, Dr. David Mangus, Dr. Sarah Bissonnette, Dr. Eddy Kim, Prof. Sarah Moore, Ms. Tammy Due Fay, Dr. Steven Nagle, Ms. Samia Saleem, Dr. Justin Pahara, Mr. Wythe Marschall, and Mr. Kevin McCormick.

In addition to our wonderful families, friends and colleagues, we four of us are grateful for each other. This book has been a team effort and, without each other, there would be nothing like it.