Preventing Toxicity With a Gene Test
The Twists and Turns in BRCA's Path
Race and Medicine
Genomics and Global Health: Time for a Reappraisal
D. J. Weatherall
Genomic Priorities and Public Health
K. R. Merikangas and N. Risch
Reverse Vaccinology and Genomics
R. Rappuoli and A. Covacci
Attrition and Translation
Molecular Imaging: Looking at Problems, Seeing Solutions
H. R. Herschman
Also see related material on Science's STKE; related Reports by Manke et al. and Yu et al. (with a Perspective); related Report by King et al. (with a Perspective); and related editorial.
Of course we are not there yet, if “there” means that genomic information is now a fundamental part of standard medical care. Getting from point A (a gene or genes) to point B (a sick patient) is not as straightforward as some had hoped. Although a starting point of a genomic approach to medicine is identifying the genes associated with disease, sometimes success means knowing where not to go. Merikangas and Risch note that for certain diseases, such as type II diabetes or alcohol dependence, resources might be better placed in environmental or behavioral interventions that can have a major impact on public health rather than in gene-hunting.
In some cases, the roadblocks have arisen from the sheer complexity of the biology, as Couzin describes in a News story (p. 591). When the mutated BRCA genes were discovered in the mid-1990s, researchers thought they were close to solving the enigma of breast cancer. A decade later, that disease remains mysterious, but the BRCA genes are illuminating a network of defects that drive a variety of other cancers. Meanwhile, a report from the New York Breast Cancer Study Group (p. 643) and the associated Perspective (Levy-Lehad and Plon, p. 574) describe the genetic and nongenetic factors influencing the risk of breast cancer in a large cohort.
Increasing evidence suggests that genetic changes may partially explain why people of different ancestry experience disease or metabolize drugs differently. But, as Holden reports in a News story (p. 594), scientists are sharply divided on whether such genetic clues are firm enough to guide medical practice. Even when the biology is clear and a gene test can help flag fatal drug reactions, as Marshall describes in a News story (p. 588), physicians may be reluctant to embrace the technology.
In other areas, genomic knowledge is slowly wending its way into medical practice. For instance, researchers are using the rapidly expanding knowledge about the genomes of microorganisms to speed efforts to develop vaccines, as Rappuoli and Covacci (p. 602) describe, promising widespread benefits in the fight against infectious diseases. Molecular imaging is providing increasing power to studies of animal models of disease and is beginning to be used in clinical trials as a noninvasive means of monitoring disease progress and response to therapeutic agents (Herschman, p. 605). On the Signal Transduction Knowledge Environment Web site, Perspectives describe the therapeutic potential of antisense strategies (Opalinska and Gewirtz) and the application of microarray analysis to pharmacogenomics (Levy).
Translating genomic information into successful clinical trials will require advances on several fronts. Despite extensive preclinical studies, the vast majority of clinical trials fail because the drugs don't work as anticipated in patients or lead to intolerable side effects. According to Duyk (p. 603), the lack of basic information about physiology is a major roadblock to predicting which drugs are likely to succeed.
The payoff from genomics should benefit all nations, not just the rich. Some of these benefits are beginning to be felt in the developing world, notes Weatherall (p. 597), especially in regard to monogenic and infectious diseases. But we will not truly be “there” in genomic medicine until we have followed Sydney Brenner's prescription (p. 533) to “stand up for all humanity.”