By Kevin Davies
June 15, 2003 | For many scientists, educators, and journalists (who really ought to know better), the temptation to fetishize DNA is all but irresistible. Even as we pay lip service to the danger of genetic determinism, we remain enthralled by this beautiful yet inert macromolecule. Madison Avenue invokes DNA to sell everything from cars to cologne, and what image-conscious biotech company does not incorporate the double helix into its logo?
The ongoing worldwide festivities to mark the double helix's golden anniversary were perfectly understandable. But with the human genome sequence moving into the complete column, the daunting challenge now is to leverage this wealth of sequence data. In this new era, DNA is little more than software — a "reagent" in the view of Rainer Fuchs, Biogen's director of bioinformatics.
"DNA, on its own, does nothing," smirked The New York Times science writer Natalie Angier recently. "It can't divide, it can't keep itself clean or sit up properly — proteins that surround it do all those tasks. Stripped of context within the body's cells ... DNA is helpless, speechless — DOA."
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The vision of the genome era, laid out in April by Francis Collins and colleagues from the National Human Genome Research Institute (NHGRI), is an ambitious agenda to be sure — one the authors acknowledge could be considered "overly bold." With input from hundreds of scientists and policy leaders, the NHGRI's architectural plan is represented as a house with three floors — Genomics to Biology, Genomics to Health, and Genomics to Society — built upon the "firm bedrock foundation" of the Human Genome Project.
The ground floor, Genomics to Biology, includes priorities such as building an Encyclopedia of DNA Elements (ENCODE), a dictionary of all functional motifs in the genome. Proteomics and metabonomics will help reveal "the difference between a 'bag of molecules' and a functioning biological system."
In Genomics to Health, the NHGRI seeks to shift attention from the genome toward the environment, revealing factors that influence complex diseases including cancer, heart disease, and mental illness. Looking enviously at bio-bank efforts in the United Kingdom and Estonia (see "Decoding Estonia," Feb. 2003 Bio·IT World), the authors argue that "a large population-based cohort study that includes full representation of minority populations is also needed." This could include a search for genetic variants in individuals apparently resistant to certain diseases — chain smokers, for example, mysteriously avoiding lung cancer.
The third floor, Genomics to Society, follows a long-standing funding commitment since the beginning of the genome project to study ethical, legal, and social issues. Despite considerable research, however, the ethical and political quagmire surrounding genome and medical research grows ever more complicated. A key tenet is to investigate the impact of genomics of race and ethnicity, an issue already engendering widespread debate (see Paper View, Sept. 2002 Bio·IT World).
Bridging these floors are six crosscutting elements: resources, technology, training, ethics, education, and computational biology. The latter is of vital importance: "All future biomedical research will integrate computational biology and experimental components ... Computational capability is increasingly becoming a critical skill."
Specific priorities include algorithm development, database technologies for data integration and visualization, and knowledge management. The authors go on: "Investment in the creation and maintenance of effective databases is as important a component of research funding as data generation" — a point underscored in this month's timely "Mouse Hunt" story.
The genome era will continue to be shaped by revolutionary and unexpected developments in technology, much as the miraculous arrival of PCR (polymerase chain reaction) transformed molecular biology in the 1980s. The authors present a wish list to inspire "creative dreaming," including the $1,000 genome; the $10,000 genotype (2,000 individuals screened with 400,000 markers); and a complete protein profile of a cell.
If the science of genetics kicked off at the dawn of the 20th century with the rediscovery of Gregor Mendel's laws, then, as University of Wisconsin geneticist James Crow puts it, the completion of the genome project is merely halftime. The task of leveraging the genome for research and medicine will occupy the best minds in science and IT for a century to come.
Leading biomedical institutions are already shifting strategies for the genome era, with the emphasis firmly on multidisciplinary research. The Howard Hughes Medical Institute recently unveiled its impressive Janelia Farm research campus, and Stanford University's $150-million Bio-X project is moving into its new Clark Center (see news stories on pages 26 and 14). Meanwhile, the Bill & Melinda Gates Foundation donated $70 million to the University of Washington School of Medicine for a new genome science facility.
Arizona State University named George Poste, former research chief at SmithKline Beecham, to direct the Arizona Biodesign Institute, a multidisciplinary center focusing on IT, biotechnology, and nanotechnology. And Duke University has recruited geneticist Huntington Willard to direct its $270-million Institute for Genome Sciences and Policy.
So the halftime festivities are over. The teams are heading back onto the field, and the second half is about to get under way. It should be nothing short of a classic ...
Kevin Davies, Ph.D.