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  REGENESIS

  REGENESIS

  How Synthetic Biology Will

  Reinvent Nature and Ourselves

  BASIC BOOKS

  A Member of the Perseus Books Group

  NEW YORK

  Copyright © 2012 by George Church and Ed Regis

  Published by Basic Books,

  A Member of the Perseus Books Group

  All rights reserved. No part of this book may be reproduced in any manner whatsoever without written permission except in the case of brief quotations embodied in critical articles and reviews. For information, address Basic Books, 250 West 57th Street, 15th Floor, New York, NY 10107.

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  A grant from the Alfred P. Sloan Foundation supported the research and writing of this book.

  Designed by Timm Bryson

  Library of Congress Cataloging-in-Publication Data

  Church, George M. (George McDonald)

  Regenesis : how synthetic biology will reinvent nature and ourselves / George M. Church and Ed Regis. — 1st ed.

  p. cm.

  Includes bibliographical references and index.

  ISBN 978-0-465-03329-4 (e-book) 1. Synthetic biology. 2. Genomics—Social aspects. 3. Genetics—Social aspects. 4. Nature. 5. Bioengineering. I. Regis, Edward, 1944- II. Title.

  QH438.7.C486 2012

  572.8'6—dc23

  2012013274

  10 9 8 7 6 5 4 3 2 1

  GEORGE CHURCH

  dedicates this book to his family and to his colleagues

  who have been so very supportive of technology

  development and regenerative biology.

  ED REGIS

  dedicates this book to his wife, Pamela Regis.

  CONTENTS

  PROLOGUE

  FROM BIOPLASTICS TO H. SAPIENS 2.0

  CHAPTER 1

  -3,800 MYR, LATE HADEAN

  At the Inorganic/Organic Interface

  CHAPTER 2

  -3,500 MYR, ARCHEAN

  Reading the Most Ancient Texts and

  the Future of Living Software

  CHAPTER 3

  -500 MYR, CAMBRIAN

  The Mirror World and the Explosion of Diversity.

  How Fast Can Evolution Go and How Diverse Can It Be?

  CHAPTER 4

  -360 MYR, CARBONIFEROUS

  “The Best Substitute for Petroleum Is Petroleum”

  CHAPTER 5

  -60 MYR, PALEOCENE

  Emergence of Mammalian Immune System. Solving the

  Health Care Crisis Through Genome Engineering

  CHAPTER 6

  -30,000 YR, PLEISTOCENE PARK

  Engineering Extinct Genomes

  CHAPTER 7

  -10,000 YR, NEOLITHIC

  Industrial Revolutions. The Agricultural Revolution and

  Synthetic Genomics. The BioFab Manifesto

  CHAPTER 8

  -100 YR, ANTHROPOCENE

  The Third Industrial Revolution. iGEM

  CHAPTER 9

  -1 YR, HOLOCENE

  From Personal Genomes to Immortal Human Components

  EPIGENETIC EPILOGUE

  + 1 YR, THE END OF THE BEGINNING,

  TRANSHUMANISM, AND THE PANSPERMIA ERA

  Societal Risks and Countermeasures

  Acknowledgments

  Selected References

  Illustration Sources

  Notes: On Encoding This Book into DNA

  Index

  PROLOGUE

  FROM BIOPLASTICS TO

  H. SAPIENS 2.0

  In December 2009, patrons of the John F. Kennedy Center for the Performing Arts in Washington, DC, experienced a mild jolt of biological future shock when their pre-performance and intermission drinks—their beers, wines, and sodas—were served to them in a new type of clear plastic cup. The cups looked exactly like any other transparent plastic cup produced from petrochemicals, except for a single telling difference: each one bore the legend, “Plastic made 100% from plants.”

  Plants?

  Indeed. The plastic, known as Mirel, was the product of a joint venture between Metabolix, a Cambridge, Massachusetts, bioengineering firm, and Archer Daniels Midland, the giant food processing company that had recently constructed a bioplastics production plant in Clinton, Iowa. The plant had been designed to churn out Mirel at the rate of 110 million pounds per year.

  Chemically, Mirel was a substance known as polyhydroxybutyrate (PHB), which was normally made from the hydrocarbons found in petroleum. But starting in the early 1990s, Oliver Peoples, a molecular biologist who was a cofounder of Metabolix, began looking for ways to produce polymers like PHB by fermentation, by the action of genetically altered microbes on a feedstock mixture.

  After seventeen years of research and experimentation (and having been laughed out the doors of several chemical companies), Peoples had developed an industrial strain of a proprietary microbe that turned corn sugar into the PHB plastic polymer. In its broadest outlines, the process was not all that different from brewing beer, which was also accomplished by fermentation: microorganisms (yeast cells) acted on malt and hops to produce ethanol. In the case of Mirel, the microbial fermentation system consisted of a large vat that combined the engineered microbes with corn sugar and other biochemical herbs and spices. The microbes metabolized the corn sugar and turned it into bioplastic, which was then separated from the organisms and formed into pellets of Mirel. Ethanol was a chemical, and so was PHB, but in both cases microbes effected the transformation of organic raw material into a wholly different kind of finished product.

  The microbial-based PHB had some key environmental advantages over the petrochemical-derived version. For one thing, since it wasn’t made from petroleum, it lessened our dependence on fossil fuels. For another, its chief feedstock material, corn, was an agriculturally renewable and sustainable resource, not something we were going to run out of any time soon. For a third, Mirel bioplastic resins were the only nonstarch bioplastics certified by Vinçotte, an independent inspection and certification organization, for biodegradability in natural soil and water environments, such as seawater. If any of the plastic cups used at the Kennedy Center ended up in the Potomac River, they would break down and be gone forever in a matter of months. (Biodegradation is not necessarily the panacea it was once thought to be, since it releases greenhouse gases, while non-degradation, ironically, sequesters carbon.)

  Constructing a microbe that would convert corn into plastic, in a process akin to beer brewing, was just one example of the transformations made possible by the emerging discipline of synthetic biology—the science of selectively altering the genes of organisms to make them do things that they wouldn’t do in their original, natural, untouched state.

  But the feat of turning corn into plastic was merely the tip of the synthetic biology iceberg. By the first decade of the twenty-first century microbe-made commodities were yielding up products that nobody would have guessed were manufactured by bacteria in three-story-high industrial vats. Carpet fibers, for example.

  In 2005 Mohawk Industries introduced its new SmartStrand carpet line. It was based on the DuPont fiber Sorona, which was made out of “naturally occurring sugars from readily available and renewable crops.” The Sorona fiber had a unique, semicrystalline molecular structure that made it especially suitable for clothing, automobile upholstery, and carpets. The fiber had a pronounced kink in the middle, and the shape acted as a molecul
ar spring, allowing the strands to stretch or deform and then automatically snap back into their original shape. That attribute was perfect for preventing baggy knees or elbows, or for making carpets that were highly resilient, comfortable, and supportive.

  Sorona’s main ingredient was a chemical known as 1,3-propanediol (PDO), which was classically derived from petrochemicals and other ingredients that included ether, rhodium, cobalt, and nickel. In 1995 DuPont had teamed up with Genencor International, a genetic engineering firm with principal offices in Palo Alto, to research the possibility of producing PDO biologically. Scientists from the two companies took DNA from three different microorganisms and stitched them together in a way that resulted in a new industrial strain of the bacterium Escherichia coli. Specifically, they programmed twenty-six genetic changes into the microbe enabling it to convert glucose from corn directly into PDO in a fermenter vat, like beer and Mirel.

  In 2003 DuPont trademarked the name Bio-PDO and started producing the substance in quantity. The company claimed that this was the first time a genetically engineered organism had been utilized to transform a naturally occurring renewable resource into an industrial chemical at high volumes. The US Environmental Protection Agency, which regarded Bio-PDO as a triumph of green chemistry, gave DuPont the 2003 Greener Reaction Conditions Award (a part of the Presidential Green Chemistry Challenge). And why not? The biofiber used greener feedstocks and reagents, and its synthesis required fewer and less expensive process steps than were involved in manufacturing other fibers. The production of Sorona consumed 30 percent less energy than was used to produce an equal amount of nylon, for example, and reduced greenhouse gas emissions by 63 percent. For its part, Mohawk touted its Sorona carpeting as environmentally friendly: “Every seven yards of SmartStrand with DuPont Sorona saves enough energy and resources to equal one gallon of gasoline—that’s 10 million gallons of gasoline a year!” Here it was, finally: the politically correct carpet.

  What these examples hinted at, however, was something far more important than mere political correctness, namely, that biological organisms could be viewed as a kind of high technology, as nature’s own versatile engines of creation. Just as computers were universal machines in the sense that given the appropriate programming they could simulate the activities of any other machine, so biological organisms approached the condition of being universal constructors in the sense that with appropriate changes to their genetic programming, they could be made to produce practically any imaginable artifact. A living organism, after all, was a ready-made, prefabricated production system that, like a computer, was governed by a program, its genome. Synthetic biology and synthetic genomics, the large-scale remaking of a genome, were attempts to capitalize on the facts that biological organisms are programmable manufacturing systems, and that by making small changes in their genetic software a bioengineer can effect big changes in their output. Of course, organisms cannot manufacture just anything, for like all material objects and processes they are limited and circumscribed by the laws of nature. Microbes cannot convert lead into gold, for example. But they can convert sewage into electricity.

  This astonishing capacity was first demonstrated in 2003 by a Penn State team headed by researcher Bruce Logan. He knew that in the United States alone, more than 126 billion liters of wastewater was treated every day at an annual cost of $25 billion, much of it spent on energy. Such costs, he thought, “cannot be borne by a global population of six billion people, particularly in developing countries.” It was widely known that bacteria could treat wastewater. Separately, microbiologists had known for years that bacteria could also generate electricity. So far, nobody had put those two talents together. But what if microbes could be made to do both things simultaneously, treating wastewater while producing electrical energy?

  Key to the enterprise would be the microbial fuel cell—a sort of biological battery. In ordinary metabolism, bacteria produce free electrons. A microbial fuel cell (MFC) consists of two electrodes—an anode and a cathode. A current is set up between them by the release of electrons from bacteria in a liquid medium. Electrons pass from the bacteria to the anode, which is connected to the cathode by a wire.

  Logan and his colleagues constructed a cylindrical microbial fuel cell, filled it with wastewater from the Penn State water treatment plant, and then inoculated it with a pure culture of the bacterium Geobacter metal-lireducens. Lo and behold, in a matter of hours the microbe had begun purifying the sewage while at the same time producing measurable amounts of electricity. These results “demonstrate for the first time electricity generation accompanied by wastewater treatment,” Logan said. “If power generation in these systems can be increased, MFC technology may provide a new method to offset wastewater treatment operating costs, making advanced wastewater treatment more affordable for both developing and industrialized nations.”

  The general setup wasn’t difficult to replicate and within a few years a sophomore at Stuyvesant High School in New York City, Timothy Z. Chang, was designing, building, and operating microbial fuel cells at home and in his high school lab. He had experimented with some forty different strains of bacteria to discover which was best suited to maximum electricity production. “It may be possible to achieve even higher power yields through active manipulation of the microbial population,” he wrote in a formal report on the project.

  By 2010 several teams of researchers were working on scaling up bacterial electricity production from sewage to make it into a practical, working, real-world option. By this time, synthetic biologists had gotten microbes to perform so many different feats of creation that it was clear that many of nature’s basic units of life—microbes—were undergoing an extreme DNA makeover, a major course of redesign from the ground up. Engineered microbes produced diesel oil, gasoline, and jet fuel. Microbes were made to detect arsenic in drinking water at extremely low concentrations (as low as 5 parts per billion) and report the fact by changing color. There were microbes that could be spread out into a biofilm. By producing a black pigment in response to selective illumination, they could copy superimposed patterns and projected images—in effect, microbial Xerox machines.

  A student project reprogrammed E. coli bacteria to produce hemoglobin (“bactoblood”), which could be freeze-dried and then reconstituted in the field and used for emergency blood transfusions. In 2006, just for fun, five MIT undergrads successfully reprogrammed E. coli (which as a resident of the intestinal tract smelled like human waste) to smell like either bananas or wintergreen.

  E. coli was so supple, pliable, and yielding that it seemed to be the perfect biological platform for countless bioengineering applications. One of its greatest virtues was that the E. coli bacterium (and cousins, the Vibrio) are the world’s fastest machines at doubling, small or large.* It reproduced itself every twenty minutes, so that theoretically, given enough simple food and stirring, a single particle of E. coli could multiply itself exponentially into a mass greater than the earth in less than two days.

  Still, as malleable as it was, University of Wisconsin geneticist Fred Blattner decided he could materially improve the workhouse K-12 strain of the microbe to make it an even better chassis for synthetic biology engineering projects. The microbe had some 4,000 genes; many had no known function, while others were nonessential, redundant, or toxic. So Blattner stripped 15 percent of its natural genes from the K-12 genome, making it a sort of reduced instruction set organism, a streamlined, purer version of the microbe. Blattner described it as “rationally designed” and said that his genetic reduction “optimizes the E. coli strain as a biological factory, providing enhanced genetic stability and improved metabolic efficiency.” With forty genome changes, he had pre-engineered the microbe in order to make it easier to engineer.

  In 2002 Blattner founded Scarab Genomics to sell his new and improved organism, now billing it as “Clean Genome E. coli” and marketing it under the slogan “Less is better and safer!” Researchers can buy quantities of the microbe
, online or by fax, for as little as $89 a shot (plus a $50 shipping fee).

  The upshot of all this is that, at least at the microbial level, nature has been redesigned and recoded in significant ways. Genomic engineering will become more common, less expensive, and more ambitious and radical in the future as we become more adept at reprogramming living organisms, as the cost of the lab machinery drops while its efficiency rises, and as we are motivated to maximize the use of green technologies.

  Given the profusion and variety of biological organisms, plus the ability to reengineer them for a multiplicity of purposes, the question was not so much what they can be made to do but what they can’t be made to do, in principle. After all, tiny life forms, driven solely by their own natural DNA, have, just by themselves, produced large, complex objects: elephants, whales, dinosaurs. A minuscule fertilized whale egg produces an object as big as a house. So maybe one day we can program an organism, or a batch of them, to produce not the whale but the actual house. We already have bio-plastics that can be made into PVC plumbing pipes; biofibers for carpeting; lumber, nature’s own building material; microbe-made electricity to provide power and lighting; biodiesel to power the construction machinery. Why can’t other microbes be made to produce whatever else we need?

  In 2009 Sidney Perkowitz, a physicist at Emory University in Atlanta with a special interest in materials science, was asked to speculate about the future of building materials. “Think about the science-fictionish possibility of bioengineering plants to produce plastic exactly in a desired shape, from a drinking cup to a house,” he said. “Current biotechnology is far short of this possibility, but science fiction has a way of pointing to the future. If bioplastics are the materials breakthrough of the 21st century, houses grown from seeds may be the breakthrough of the 22nd.”

  Similar proposals have been made by others, and they may be much closer than the twenty-second century; for example, using modified gourds and trees to grow a primitive, arboreal house (inhabitat.com/grow-your-own-treehouse). The technology of determining the shape and chemical properties of plants by making them sensitive to simple cues of light and scaffolding is improving rapidly.