INTRODUCTION: WELCOME BACK TO THE GENOME

Every one of the trillions of cells in your body contains DNA-from the blood cells that course through your veins to the nerve cells in your brain to the hair follicle cells that line your scalp. The tightly coiled DNA in a single cell, 6 feet long and just one molecule wide when unraveled, packs more than 3 billion bits of information. This complete set of information is your genome. The approximately 20,000 genes in your genome (a figure that has been revised down significantly since we wrote the first edition of this book more than a decade ago), interacting with each other and with your environment, help shape the development of a new human being and are constantly at work instructing our bodies to create new cells, digest food, fend off disease, and store thoughts. Genes and DNA capture our imagination because of their impact on why we are the way we are. But how much control do genes and DNA really have over our bodies and our behavior? And to what extent will our changing understanding of the human genome change who we are and how we see the world? Are our genes our destiny? Are our genomes our fate?

Such questions captured our imagination in the midst of the genomic revolution-the international multi-billion-dollar effort to sequence, interpret, and exploit the human genetic code. It was believed that a map of our genome would offer boundless potential to sequence, interpret, and then exploit the information contained in the genetic code. The excitement over the potential to improve our health-to stave off disease, to apply genomic tools to feed the world's growing population, to save species on the brink of extinction-captured the imaginations of scientists around the globe in the opening decade of the genomic revolution.

In June 2000, scientists triumphantly announced they had sequenced the human genome. (1) By sequencing those 3.2 billion units of our DNA, researchers sparked a firestorm of discovery and ushered in a new age. At a White House ceremony to announce the completion of a draft sequence of the human genome, President Bill Clinton called the genome God's handiwork. "Today," Clinton stated, "we are learning the language in which God created life." (2) Clinton's vision of the genome was one that mixed a metaphor of scientific advancement with a divine spirit. This image of the human genetic code is a fairly common one. The genome has also been called the book of life, biology's Rosetta Stone, humanity's instruction manual, and biology's Holy Grail. Each of these metaphors conveys a slightly different meaning, and each suggests a subtly different aspect of the genome. Not so hidden in these metaphors is the hope that biology will provide clear-cut answers to long-asked questions regarding the nature of the human soul, the power of science to heal and rebuild the human body, and the role of nature in human social behavior. The genome will indeed provide some answers to these questions, but not the simple answers that many of these metaphors suggest.

The media both anticipated and echoed the hyperbole of that White House ceremony. Headlines like "Long Held Beliefs Are Challenged by New Human Genome Analysis" (New York Times, 2001), "Reading the Book of Life: Genome Shows Evolution Has an Eye for Hyperbole" (New York Times, 2001), and "Double Helix Is Starting To Make Its Mark In Medicine" (Financial Times, 2003) underscored the genome's complexity, allure, and promise. (3) But did we oversell the genome? Has the early allure and promise translated into meaningful scientific results?

Looking back at the sequencing stage of the genomic revolution (1988-2001), it is important to consider whether we were even asking the right questions in the first place about what the genome could tell us about the relationship between our genes and our health. It isn't simply that we spoke in hyperbolic terms about the secrets the human genome would reveal (which we ourselves were somewhat guilty of in the first edition of this book). It was that the language used and the metaphors employed to describe genomics limited our ability to capitalize on the work being done in laboratories around the globe. In other words, the way we described genomics circumscribed how we carried out genomics' research. Think of some of the most popular metaphors used-the book of life, a genetic code, life's blueprint. They suggested, in their simplest terms, that our genomes contained information to read, or as some have suggested, the blueprint from which humanity and other species are built. Some observers have argued that this blueprint approach both reflected and reinforced the type of reductionist thinking that was commonplace in the early years of genomic sequencing (4) and that has its roots in the founding of the field of genetics a century ago.

Today, the language of the genome is changing, and so too is our scientific understanding of the information it contains. A book of life that can reveal the essence of what it means to be human (or any other species, for that matter) has given way to new metaphors that reflect (and perhaps limit) the current science, which seems to value complexity over simplicity.

Let's start with the term post-genomics-a widely used term meant to signify the post-sequencing era we currently inhabit during which science is working to make sense of billions of bits of sequenced genomic information. By calling it the post-genome era, we are implying a break from the discovery phase of the genomic revolution to an era in which gathered information is analyzed. Some have speculated that the post-genome genome is less a linear string of genes that produce traits (alone and in concert with one another) than an organic and dynamic mechanism that responds to both biological and environmental stimuli to produce the proteins that regulate the life of an organism. (5) It is in the complexity of the post-genomic genome where natural and social scientists will untangle the complicated relationship between organism, genes, and environments that the challenges and surprises of life await discovery.

One thing that the old reductionist model has over the new models of genomic complexity is clarity. It would have been a difficult task to sell the genome-at the height of its popularity in the 1990s-as a complex mechanism that regulates life. Indeed, the reductionist model has had its utility in discovering simple, mostly Mendelian, genetic traits. But as we have come to understand genomes as biological systems rather than blueprints or Rosetta Stones, the genomic sciences have come to rely more and more on fields like computer science and bioengineering to make sense of the post-genome.

Genomics is a synthesis of many disparate fields, including biology, public health, engineering, computer science, and mathematics. What makes genomics even more distinctive is that the social sciences and humanities are an integral component of the genomic revolution. Philosophers, ethicists, and historians are helping to lay the foundation of the genomic revolution by pushing for and playing a role in the creation of policies and laws that will guide the integration of genomics into scientific practice and health care. Participants in the genomic revolution, as well as the biologists and others who preceded them, will, we believe, be thought of much in the same way that Newton is remembered for his role in the birth of calculus and physics or the way in which Darwin is remembered as the progenitor of modern biology. However, because genomics is an evolving science that encompasses so many different disciplines, it is hard to find one person who embodies the entire field. Indeed, it will be a group of genomic scientists who will be recorded in history books as pioneers.

The arrival of the genomic age was the culmination of efforts of over a century of science. From the work of Gregor Mendel in the mid-nineteenth century (it was Mendel who formalized the rules of heredity and hypothesized that something like genes must underpin heredity), to the announcement of the discovery of the structure of DNA in 1953 by James Watson and Francis Crick, to the genetic sequencing technologies developed by biologists like Frederick Sanger and Leroy Hood in the closing decades of the twentieth century, the path to genomics has been arduous but has yielded the richest source of biological data we have ever known. This age of discovery is where our journey in this book begins-the first four chapters look at the historical moments in biology over the past 100 or so years that made the sequencing of genomes possible. These chapters will be particularly rewarding to readers with an interest in the science behind genomics, but you do not need to comprehend everything in these chapters to appreciate the material in the rest of the book. Don't get hung up on some of the nitty-gritty science. Utilize the figures to help make sense of difficult concepts, and don't be afraid to look up technical sounding words.

The remainder of the book looks at the interplay of how scientists are coming to make sense of genomic information and how they are applying this information to genomic technologies in evolutionary biology, health-related fields, and agriculture. Chapters look at how the discovery and exploration of the human genome is yielding to the more practical task of sorting through the scientific...