Biology Is Technology: The Promise, Peril, and New Business of Engineering Life

Biology Is Technology

BIOLOGY IS TECHNOLOGY

The Promise, Peril, and New Business

of Engineering Life

ROBERT H. CARLSON

HARVARD UNIVERSITY PRESS

Cambridge, Massachusetts

London, England

For Pascale

Copyright © 2010 by the President and Fellows

of Harvard College

All rights reserved

Printed in the United States of America

First Harvard University Press paperback edition, 2011

Library of Congress Cataloging-in-Publication Data

Carlson, Robert.

Biology is technology : the promise, peril, and new business of engineering life / Robert Carlson.

     p. cm.

Includes bibliographical references and index.

ISBN 978-0-674-03544-7 (cloth: alk. paper)

ISBN 978-0-674-06015-9 (pbk.)

1. Biotechnology.   2. Biology—Philosophy.   3. Bioethics.   I. Title.

TP248.2.C37 2010

660.6—dc22             2009029637

Contents

Acknowledgments

1What Is Biology?

2Building with Biological Parts

3Learning to Fly (or Yeast, Geese, and 747 s )

4The Second Coming of Synthetic Biology

5A Future History of Biological Engineering

6The Pace of Change in Biological Technologies

7The International Genetically Engineered Machines Competition

8Reprogramming Cells and Building Genomes

9The Promise and Peril of Biological Technologies

10 The Sources of Innovation and the Effects of Existing and Proposed Regulations

11 Laying the Foundations for a Bioeconomy

12 Of Straitjackets and Springboards for Innovation

13 Open-Source Biology, or Open Biology?

14 What Makes a Revolution?

Afterword

Notes

Index

Acknowledgments

THIS BOOK is the sum of more than a decade of discussions, research, and travel. The effort was made possible only through the generosity and patience of friends, colleagues, and family.

The first draft was written while I was a Visiting Scholar in the Comparative History of Ideas Program at the University of Washington; many thanks to John Toews and the late Jim Clowes.

I am especially grateful to Dianne Carlson, Eric Carlson, Drew Endy, Sarah Keller, Rik Wehbring, and anonymous reviewers for reading drafts, providing invaluable comments, and for asking hard questions.

My journey into thinking about biology’s role in the economy benefited at every step from conversations with my colleagues Stephen Aldrich and James Newcomb at Bio Economic Research Associates (Bio-era). Our intellectual travels through biofuels, pandemics, vaccines, commodities trading, the oil and gas business, and international finance, supplemented by our real-world travels through North America, Asia, and Europe, provided an unparalleled education.

I owe thanks to many others for conversations, however brief or involved, that provided welcome critique and insight, including Drew Endy, Stewart Brand, Kevin Kelly, Freeman Dyson, Emre Aksay, W. Brian Arthur, Ralph Baric, Sydney Brenner, Roger Brent, Ian Burbulis, Charles Cantor, Denise Caruso, Jamais Cascio, Joseph Chao, Napier Collyns, David Grewal, Lauren Ha, Andrew Hessel, Janet Hope, Richard Jefferson, Tom Kalil, John Koschwanez, Tom Knight, Ed Lazowska, Emily Levine, Barry Lutz, John Mulligan, Oliver Morton, Kenneth Oye, Bernardo Peixoto, Arti Rai, Brad Smith, Richard Yu, Steve Weber, and last, but certainly not least, Ben and Margit Rankin. I thank my editor, Michael Fisher, for his patience over many years.

CHAPTER ONE

What Is Biology?

BIOLOGY IS TECHNOLOGY. Biology is the oldest technology. Throughout the history of life on Earth, organisms have made use of each other in sophisticated ways. Early on in this history, the ancestors of both plants and animals co-opted free-living organisms that became the subcellular components now called chloroplasts and mitochondria. These bits of technology provide energy to their host cells and thereby underpin the majority of life on this planet.

It’s a familiar story: plants, algae, and cyanobacteria use sunlight to convert carbon dioxide into oxygen. Those organisms also serve as food for a vast pyramid of herbivores and carnivores, all of whom produce carbon dioxide and other wastes that plants then use as resources.

Interactions between organisms constitute a global natural economy that moves resources at scales from the molecular to the macroscopic, from a few nanometers (10-9) to many megameters (106). Humans have always explicitly relied on this biological economy to provide food, oxygen, and other services. Until recently, our industrial economy relied primarily on nonbiological technologies; the industrial revolution was built primarily on fire, minerals, and chemistry. Now, however, our economy appears to be changing rapidly, incorporating and relying upon new organisms whose genomes have been modified through the application of human effort and ingenuity.

In 2007, revenues in the United States resulting from genetic modification of biological systems were the equivalent of almost 2 percent of gross domestic product (GDP). The total includes all the products we include under the moniker biotechnology—drugs, crops, materials, industrial enzymes, and fuels (see Chapter 11). Compare that 2 percent to the percent added in 2007 to GDP from the following sectors: mining, 2 percent; construction, 4.1 percent; information and broadcasting, 4.7 percent; all of manufacturing, 11.7 percent; transportation and warehousing, 2.9 percent; finance, 20.7 percent; and all of government, 12.6 percent.1 (One might expect the contribution from finance to be somewhat smaller in the future.)

While still modest in size compared with other sectors, biotech revenues are growing as fast as 20 percent annually. Moreover, the sector is extremely productive. During the years 2000–2007, the U.S. economy expanded by about $4 trillion, and biotech revenues grew by almost $200 billion. Biotechnology companies currently employ about 250,000 people in the United States, out of a total labor force of 150 million.2 Therefore, less than one-sixth of 1 percent of the national workforce generated approximately 5 percent of U.S. GDP growth during those seven years. Despite the fact that the underlying technology is presently immature compared with other sectors of the economy, current biotechnology demonstrates impressive and disproportionate economic performance.

Rapid revenue growth in the sector is the result of new products that create new markets, such as drugs and enzymes that help produce fuels. It also comes from displacing products made using older industrial methods. Bioplastics that started entering the market in 2007 and 2008 appear to require substantially less energy to produce than their petroleum-based equivalents.

Yet, as with any other technology, biological technologies are subject to the hard realities of the market. New products may fail for many reasons, including both overoptimistic assessment of technical capabilities and customer inertia. In addition, biotechnology must compete with alternate methods of producing materials or fuels, methods that may have a century’s head start. Biological production must also compete for feedstocks with other human uses of those feedstocks, as is now occurring in the commercialization of first-generation biofuels produced from sugar, corn, and vegetable oil. It is no surprise that many biofuel producers are presently caught up in the collision between food and fuel; crops, and the resources used to grow them, are likely to have higher value as food than as fuel.

The economic system that governs these products is today primarily composed of interconnected marketplaces, full of businesses large and small. Those markets are increasingly global, and the flow of information is at least as important as the flow of physical goods. Technology supports the spread of those markets, and technology is the subject of many of those markets. New technologies provide opportunities to expand markets or launch entirely new ones. Here I use the word market in the broadest sense, which Wikipedia (presently) defines as any of a variety of different systems, institutions, procedures, social relations and infrastructures whereby persons are coordinated, goods and services are exchanged and which form part of the economy.3 I do not mean any particular market, nor necessarily the free market, nor any particular set of transactions governed by any particular set of rules and denominated in any particular currency.

In general, as we shall see, there is no reason to think that any country’s lead in developing or using biological technologies will be maintained for long. Nor will the culture and experience of any given country dominate the discussion. Access to biological technologies is already ubiquitous around the globe. Many countries are investing heavily to build domestic capabilities with the specific aim of improving health care, providing fuels and materials, and increasing crop yields.

Research efforts are now accelerating, aided by rapid advances in the technology we use to manipulate biological systems. It is already possible to convert genetic information into electronic form and back again with unprecedented ease. This capability provides for an element of digital design in biological engineering that has not heretofore been available. More important, as measured by changes in commercial cost and productivity, the technology we use to manipulate biological systems is now experiencing the same rapid improvement that has produced today’s computers, cars, and airplanes. This is evidence that real change is occurring in the technologies underlying the coming bioeconomy.

The influence of exponentially improving biological technologies is only just now starting to be felt. Today writing a gene from scratch within a few weeks costs a few thousand dollars. In five to ten years that amount should pay for much larger constructs, perhaps a brand-new viral or microbial genome. Gene and genome-synthesis projects of this larger scale have already been demonstrated as academic projects. When such activity becomes commercially viable, a synthetic genome could be used to build an organism that produces fuel, or a new plastic, or a vaccine to combat the outbreak of a new infectious disease.

This book is an attempt to describe a change in technology that has demonstrably profound social and economic implications. Some parts of the story that follows I know very well, either because I was fortunate to witness events or because I was in a position to participate. Other parts of the story come in because I had to learn something new while attempting to paint a picture of the future. Delving into details is necessary in places in order to appreciate the complexity of biological systems, the challenge of engineering those systems, and the implications of that technology for public policy, safety, and security. Whatever else the reader takes from this book, the most important lesson is that the story is incomplete. Biology is technology, and as with any other technology, it is not possible to predict exactly where the project will go. But we can at least start with where that technology has been.

Engineering Organisms Is Difficult, for Now

Explicit hands-on molecular manipulation of genomes began only in the mid-1970s, and we are still learning the ropes. Most genetically modified systems do not yet work entirely as planned. Biological engineering as practiced today proceeds by fits and starts, and most products on the market now result from a process that remains dominated by trial and error. The primary reason that the engineering of new organisms has been slow in coming is that simply understanding naturally occurring organisms remains hard.

The initial phase of biological engineering, covering the last thirty years or so, coincided with efforts to describe the fundamentals of molecular biology. In that time we moved from discovering the number of genes in the human genome to building automated machines that read entire microbial genomes during a lunch break. Science has accumulated enough knowledge to support basic genetic changes to microbes and plants; those changes enable a wide range of first-generation products.

What was cutting-edge technology three decades ago is today routine in university lab courses and has already been included in the curricula of many high schools. While simple modifications of single-celled organisms are now commonplace, the scientific frontier has, of course, moved. Today, academic and industrial researchers alike are working with multicellular organisms and contending with the attendant increase in biochemical and developmental complexity.

And yet progress can appear slow, particularly to those who have followed the information technology revolution. Governments and big business once dominated computing. Today, entrepreneurs and garage hackers play leading roles in developing computing technologies and products, both hardware and software.

Thus, Stewart Brand, founder of the Whole Earth Catalog, organizer of the first Hackers’ Conference in 1984, and cofounder of the Whole Earth ’Lectronic Link (WELL) and the Global Business Network, wonders: Where are all the green biotech hackers?4 To which I answer: They are coming. The tools necessary to understand existing systems and build new ones are improving rapidly. As I will discuss in Chapter 6, the costs of reading and writing new genes and genomes are falling by a factor of two every eighteen to twenty-four months, and productivity in reading and writing is independently doubling at a similar rate. We are just now emerging from the slow part of the curves, by which I mean that the cost and productivity of these technologies are now enabling enormous discovery and innovation. Consequently, access to technology is also accelerating. Garage biology is here already; in Chapter 12 I share a bit of my own experience sorting out how much innovation is possible in this context.

Public Expectations for Advances in Biological Technologies

The new knowledge and inventions that science provides can take many decades to become tools and products—things people can buy and use—that generate value or influence the human condition. That influence is, of course, not uniformly beneficial. But we generally cannot know whether a technology is, on balance, either valuable or beneficial until it is tested by actual use. It is in this context that we must examine new biological technologies.

Biological technologies are subject to both unreasonable expectations and irrational fear. Practitioners and policy makers alike must contend with demands by the citizenry to maximize benefit speedily while minimizing risk absolutely. These demands cannot be met simultaneously and, in many cases, may be mutually exclusive. This tension then produces an environment that threatens much-needed innovation, as I argue in detail in the latter half of this book.

Often sheer surprise can play as great a role in public responses as the science itself. By the nature of the scientific process, most results reported in the press are already behind the state of the art. That is, while ideally science is news of the future, the press actually reports the past. Scientific papers are submitted for publication months after work is finished, go through a review and editing process consuming additional months, and finally appear in print many months after that, all the while being surpassed by ongoing research. Given the pace of technological improvement and consequent increased capabilities in the laboratory, more and more new science is being squeezed into the time between discovery and publication of old results.

Only if we recognize that organisms and their constituent parts are engineerable components of larger systems will we grasp the promise and the peril of biological technologies. Conversely, failing in this recognition will cloud our ability to properly assess the opportunity, and the threat, posed by rapid changes in our ability to modify biological systems.

We are in the midst of realizing capabilities first forecast more than fifty years ago. The development of X-ray crystallography and nuclear magnetic resonance in the decades before 1950 opened a window to the molecular world, providing a direct look at the structure of natural and synthetic materials. During that same time period the elucidation of information theory, cybernetics, and basic computational principles set the stage for today’s manipulation of information. Biology is the fusion of these two worlds, in which the composition and structure of matter determines its information content and computational capabilities. This description may also be applied to computers, but biology is in addition a state of matter, if you will, that is capable of self-editing and self-propagation. It is no surprise, then, that given our improving abilities to measure and manipulate molecules, on the one hand, and to apply powerful computational techniques to understand their behavior, on the other, biology is today consuming considerable attention. Today’s science and technology provide a mere glimpse of what is in store, and we should think carefully about what may happen just down the road.

What Is Biological Engineering?

As we shall see in the following chapters, the development of new mathematical, computational, and laboratory tools will facilitate the building of things with biological pieces—indeed, the engineering of new biological artifacts—up to and including new organisms and ecosystems. The rest of this book explores how this may transpire. But first we have to understand what engineering is.

Aeronautical engineering, in particular, serves as an excellent metaphor when considering the project of building novel biological systems. Successful aeronautical engineers do not attempt to build aircraft with the complexity of a hawk, a hummingbird, or even a moth; they succeed by first reducing complexity to eliminate all the mechanisms they are unable to understand and reproduce. In comparison, even the simplest cell contains far more knobs, bells, and whistles than we can presently understand. No biological engineer will succeed in building a system de novo until most of that complexity is stripped away, leaving only the barest essentials.

A fundamental transformation occurred in heavier-than-air-flight, starting about 1880. The history of early aviation was full of fantastical machines that might as well live in myth, because they never flew. The vast majority of those failed aircraft could, in fact, never leave the ground. They were more the product of imagination and optimism than of concrete knowledge of the physics of flight or, more important, practical experience with flight.

In about 1880, Louis-Pierre Mouillard, a Frenchman living in Cairo, suggested that rather than merely slapping an engine on a pair of wings and hoping to be pulled into the air, humans would achieve powered flight only through study of the practical principles of flight. And that is just the way it worked. Aviation pioneers made it into the air through careful observation and through practice. These achievements were followed by decades of refinement of empirical design rules, which were only slowly displaced in the design process by quantitative and predictive models of wings and engines and control systems. Modern aircraft are the result of this process of learning to fly.

And so it goes with virtually every other human technology, from cars to computers to buildings to ships, dams, and bridges. Before inanimate objects are constructed in the world today, they are almost uniformly first constructed virtually—built and tested using sophisticated mathematical models. Analogous models are now being developed for simple biological systems, and this effort requires molecules that behave in understandable and predictable ways. The best way to understand how biological technology is changing is by starting with another metaphor, one that relies on the best toy ever devised: LEGOS.

CHAPTER TWO

Building with Biological Parts

BUILDING WITH LEGOS is an excellent metaphor for future building with biology. The utility and unifying feature of LEGOS, Tinkertoys, Erector Sets, Zoob, or Tente is that the pieces fit together in very understandable and defined ways. This is not to say they are inflexible—with a little imagination extraordinary structures can be built from LEGOS and the other systems of parts. But it is easy to see how two bricks (or any of the other newfangled shapes) will fit together just by looking at them.

The primary reason that we fret about bioterror and bioerror is that in human hands biological components aren’t yet LEGOS. But they will be, someday relatively soon.

Every Piece Has Its Purpose

LEGOS are so broadly used and understood in our culture that they are employed to advertise other products. There is a metaphorically and visually elegant television commercial for the Honda Element that opens with an image of a single LEGO-style brick. That computer-generated brick is soon joined by a myriad of others, with different shapes and colors, each flying into its assigned place with inspiring precision. The wheels and floor of the vehicle quickly take shape, followed by clever folding seats, and finally the sides and roof. It is clear that all the parts of this building-block car are carefully conceived, designed, and built. At the end of the spot, a smooth voice-over brings it all together: Every piece has its purpose.1

The implication is clear: Honda has built a new vehicle, and each and every part does exactly what it is supposed to. We can feel confident that each part performs precisely as intended. This, after all, is a modern car and the fruit of sophisticated modern engineering practice.

There are many unspoken assumptions built into this representation of engineering. Among the most important are that (1) all the parts are the result of a careful design process, (2) the parts can be constructed to function according to the design, and (3) when assembled from those parts, the resulting whole actually behaves as predicted by the design.

The experience of everyone who watches the commercial contributes to the communication of these unspoken assumptions. Not only do we the viewers have considerable exposure to other products of this engineering process, but, given the number of Honda cars and trucks on the road, many of us demonstrate confidence in the engineering and manufacturing prowess of Honda in particular.

Just as the broad public understanding of LEGOS can be used to imbue a sense of careful design and manufacturing into a new Honda, the notion that the products of modern engineering are safe and predictable can be used to sell other technologies.

Unfortunately, in comparison, current genetic engineering techniques are quite primitive, akin to swapping random parts between cars to produce a better car. Biological engineering in general does not yet exist in the same way that electrical, mechanical, and aeronautical engineering do. Mature engineering fields rely on computer-aided design tools—software packages like SolidWorks for mechanical engineering and Spice or Verilog for circuit simulation—that are based upon predictive models. These predictive models are constructed using a quantitative understanding of how parts of cars and airplanes behave when assembled in the real world. Unlike the vast majority of modified biological systems, for which there are no design tools, the behavior of a finished engine or integrated circuit can be predicted from the behavior of a model, which today is universally determined using computer simulation.

Implementation of computer-based automotive, electronics, and aircraft design efforts is aided by standardized test and measurement gear, such as oscilloscopes, network analyzers, stress meters, pressure gauges, etc. The combination of these items with predictive models constitutes an engineering toolbox that enables the construction of physical objects. Facilitating this construction process, programs like SolidWorks and Spice can send instructions to automated manufacturing tools, turning design into artifact in relatively short order. Although biological raw materials are quite different from gears, engines, and circuits, biology will soon have its own engineering toolbox.

The development of relevant tools is already well under way. Technologies used to measure and manipulate molecules and cells will be critical components of the toolbox. Laboratory instruments such as DNA sequencers and synthesizers, which read and write genetic instructions, respectively, are plummeting in price while becoming exponentially more powerful. This technology is changing so rapidly that, within just a few years, the power of today’s elite academic and industrial laboratories will be affordable and available to individuals.

Toward Biological Composability

There are different ways of using biology as technology. Farming and breeding are obviously fundamental technologies. Bioremediation is ever more widely used to clean up messes—made by other human technologies—through the clever selection of plants and animals that thrive on materials we now generally consider waste. Bacteria have been used to produce electricity from sewage, and, as I will explore in detail in Chapter 11, micro-organisms are being genetically manipulated to produce fuels.2 The products of genetically modified systems are already used in homes and businesses worldwide, from laundry enzymes to powerful new medicines. Recombinant DNA is the technology that makes this possible.

The phrase recombinant DNA is derived from the earliest techniques developed to directly manipulate the genomes of bacteria. Without delving into the details, suffice it to say for the moment that recombination is an ancient biological process, wherein two pieces of DNA with ends that have similar chemical structure are pasted together by the preexisting molecular machinery of the cell. After this process takes place, the seam between the two ends is effectively invisible. The resulting DNA is chemically indistinguishable from the original, save that the new sequence can now code for new instructions. This process—this technology—appears to have evolved early in the history of life on this planet, as a mechanism to repair broken DNA strands.

The technological aspects of biology thus go down to the very molecules that underlie life itself. Nucleic acids, assembled into chains, constitute the molecular repository of instructions required to build any organism. Deoxyribonucleic acid (DNA) is the primary storage medium for all organisms composed of cells, whereas viruses may use either DNA or ribonucleic acid (RNA). While the DNA describing how to build higher organisms such as humans is largely static over the lifetime of an individual, bacteria may alter their DNA content through the exchange of small bits of DNA, arranged in stable, circular elements called plasmids. Plasmids are extraordinarily useful bits of technology, a kind of standard packaging for DNA, which I will return to time and again in this book. Plasmids can serve as the medium for the transfer between individuals of useful genes, such as those for antibiotic resistance, and can also be passed along to offspring. Humans have for decades made use of this packaging technology by applying a high-voltage jolt to open temporary pores in microbes through which plasmids can migrate. But it has only recently been demonstrated that humans merely reinvented this trick, known as electroporation. Certain soil-dwelling microbes are particularly likely to take up plasmids from the environment after lightning strikes, a trait that enhances the ability of the microbes to sample the diversity of DNA lying around in the environment and thus to pick up genes that, if they are fortunate, are useful.3

Yet more sophisticated are natural schemes to respond to specific threats in the environment. The genome of Vibrio cholerae, the organism that causes cholera, possesses in its chromosome another sort of DNA-packaging technology, integrated conjugative elements (ICEs), which contain genes that confer resistance to particular antibiotics. The remarkable thing about this technology is that exchange of these ICEs between bacteria is inhibited except when those antibiotics threaten the bacteria.4

There is a significant evolutionary advantage for microbes that develop mechanisms that allow them to defend against human attacks. Prior to 1993, the ICE in Asian V. cholerae strains that confers antibiotic resistance against ciprofloxacin (Cipro) was not found in nature. It is now present in almost all samples isolated from cholera victims in Asia. Of specific interest (and perhaps worry) in this case, the bacteria have developed a mechanism in which the presence of Cipro actually promotes the spread of genes that code for antibiotic resistance, which accounts for the wide distribution of Cipro-resistant cholera infections. This exchange of genetic material, while by no means intentionally managed by microbes, provides a set of tools that allow organisms to adapt to, and even manipulate, environments that would otherwise be fatal.

Ultimately, however, we humans are the most successful organisms on the planet when it comes to using biology as both tool and raw material. We have, intentionally or otherwise, manipulated many species of plants, animals, fungi, and bacteria for thousands of years. It is now clear that humans cultivated corn at least nine thousand years ago, selecting plants with useful (or tasty) random genetic changes, combining those mutations into a single plant via breeding, and then propagating its seeds.5 Even with this relatively sophisticated genetic manipulation, we are certainly late to the game; other organisms have been at it far longer. Yet humans make use of a greater diversity of species than any other organism on Earth. This reliance has long nourished both the human body physical and the human body social. It is unlikely we will find an alternative to this habit anytime soon, even if we actively sought it.

Adaptation of all the found technology of molecular biology to human ends was first demonstrated in the early 1970s and was rapidly adopted to produce proteins on a commercial scale. The process works as follows: First, instructions for making a protein are inserted into a cell via recombination. Those instructions come in the form of genes, whose chemical composition contains specific information a cell uses to build proteins. Originally the gene of interest was recombined with the cell’s own DNA. Today the gene is frequently carried on an independent bit of plasmid DNA, which the cell treats as its own. Second, the cell is encouraged to multiply in large vats in a process quite similar to brewing beer. At some point in the cell’s growth cycle, it is induced to make the protein of interest. Finally, the protein is purified from the population of cells and becomes just another product in modern commerce.

These recombinant proteins, as they are called, are cropping up everywhere, including the pharmacist’s counter. Epoetin alpha (also known as Epogen and Procrit) is a recombinant protein used to increase the production of oxygen-carrying red blood cells. Diabetics worldwide use recombinant human insulin. The antiarthritis drug Enbrel directly interferes with the molecular pathway that causes inflammation. These drugs are all derived from recombinant protein technology and produced in the manner described above.

The next steps in developing biological technology involve programming combinations of cells to do interesting things, such as produce valuable goods. This is already being undertaken in the case of insect larvae, plants, goats, and cows modified to produce drugs and useful proteins in their tissues and milk. Understanding and controlling consortia of cells, from novel networks of single cells to multicellular organisms, will open many interesting possibilities.

If you pause to consider it for a moment, we ourselves are sophisticated examples of just this sort of biological technology.

The human body consists of between 1013 (ten million million) and 1014 cells. That sum does not include the microbes living on and in our bodies, of which there about twenty times as many as our own cells. Some human cells are structural, some measure the environment, some process food into nutrients that other cells use, many communicate with each other within the body, and not one of them can survive without the rest.

Through this symbiosis, systems of human cells cooperate to produce the astonishing behaviors of speech, art, love, scientific inquiry, and religious devotion. If too many cells are damaged or otherwise begin to fail in significant numbers, all of the other interesting phenomena we can measure soon fade as well. So it is with the cells composing (virtually) every multicellular plant and animal.

Within the cells comprising organisms, intricate molecular systems process material and information. Some systems handle metabolism, taking care of the moment-to-moment processes necessary to sustain life. Other molecules maintain a cell’s structural integrity or are involved in deciding how to respond to outside stimuli. This integrated molecular technology is ultimately controlled in the nucleus, where genetic instructions reside in DNA.

The elaboration of the function of all these molecules is inevitably obscured by a fog of jargon. Even though many names of molecules and processes are fairly straightforward, they often appear in complicated combinations that obscure simple details. For many readers the juxtaposition of familiar and unfamiliar makes the whole thing incomprehensible.

For example, outside of biology, the word transcription elicits thoughts of writing out or copying information from one format or medium to another. And this is precisely what transcription means in biology. Information stored in DNA must be transferred to a medium more suitable for handling and processing by cellular machinery, which in this case is messenger RNA (mRNA). The chemical code in the two media is very similar, and the molecular copy machine that transfers the information from one polymer to the other is a polymerase (figure 2.1).

Similarly, outside of biology the word translation conveys the notion of converting information from one language to another. Inside a cell, translation refers to the process of switching from the chemical code of mRNA, composed of nucleic acids, to the chemical code of proteins, composed of amino acids. The molecular machine responsible for translation is a ribosome.

Everyone understands what transcription and translation are in the context of normal usage in the English language, but add DNA, RNA, amino acids, polymerases, and ribosomes to a sentence and suddenly most people find it difficult to follow. It is a rare exposition that manages to convey details of molecular biology and chemistry while keeping the average reader’s attention.

This difficulty exists in part