Welcome to the Genome. Michael Yudell
Читать онлайн книгу.
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 and social meaning of all of the data being generated by genomics, particularly in the context of ethics and how we understand and define ourselves as humans, especially given the long history of using genetics to divide and harm ourselves. The choices, social proscriptions, and laws that we develop now around genomic technologies will be an essential part of ensuring the success of genomic technologies in the future. Challenges include creating policies that will help integrate genomics technologies into contemporary medicine and public health practice, and defining the roles and responsibilities of scientists, health care professionals, ethicists, clergy, and lawmakers in the development of these policies. Also, how can we best ensure the safety of genomic technologies? The remaining chapters of the book look at how advances in genomic science—from evolutionary thinking to agriculture biology—are altering scientific practice and impacting our lives. For example, new tools such as clustered regularly interspaced short palindromic repeats–CRISPR‐associated protein 9 (CRISPR/Cas9) technology have been developed that allow for the direct editing of genomes and may usher in a new age of gene therapy (7) with many of the caveats we initially formulated in the first edition of this book. In the first edition of this book, we suggested that “it will still take years, if not decades before genomic medicine will significantly enhance current practice, let alone replace it.” But CRISPR/Cas9 gene editing technology has the potential to bring us directly into the realm of directed gene therapy, in both human and non‐human species.
We have set out to write a book that readers with little or no prior knowledge of biology can pick up and enjoy, gaining along the way a deeper understanding of the phenomenon that has become known as genomics. Genomics should not be treated lightly, however, and we hope to reward your interest with more than a nominal exploration