18 RESEARCH
BRIEFS
Promise of genomics research needs a realistic view In the ten years since the human genetic code was mapped, expectations among scientists, health care industry, policy makers, and the public have remained high concerning the promise of genomics research for improving health. But, in a new commentary, four internationally prominent genetic medicine and bioethics experts caution against the dangers of inflated expectations—an unsustainable genomic bubble—and offer ways to avoid it while still realizing “the true— and considerable—promise of the genomic revolution.” “This commentary is an attempt to bring some balance to the hopes and claims that swirl around the issue of genomic medicine. It is a cautionary essay that James Evans, MD, PhD tries to extol the real and formidable potential of genomic medicine but also attempts to counter what we see as exaggerated claims, said lead author medical geneticist James P. Evans, MD, PhD, Bryson Distinguished Professor of genetics and medicine at the University of North Carolina at Chapel Hill and the UNC Lineberger Comprehensive Cancer Center. “Our fear is that, if we are uncritical and naïve in our enthusiasm for these exciting technologies, we risk both diversion of precious resources and premature implementation which could hurt patients—as well as a backlash which will hurt our field,” Evans warns. The commentary appeared in the February 18, 2011 issue of the journal Science. Co-authors with Evans are Eric M. Meslin, PhD, director, Center for Bioethics, Indiana University, Indianapolis; Theresa M. Marteau, PhD, FMedSci, professor of health psychology, Kings College, London, UK; and Timothy Caulfield, LLM, FRSC, Canada Research Chair in Health Law & Policy, University of Alberta, Edmonton, Alberta. “Breathtaking” is how the authors describe the progress already made in genomic research. But, they caution, the considerable promise of genomics must be evaluated through a realistic lens. Advances in individualized medicine, or pharmacogenetics for example, still require the importance of human behavior in health outcomes: the most powerful predictor of a drug’s efficacy depends less on genetics than whether the patient takes the drug. Among the reasons they cite making genomics the persistent recipient of “hyperbole” and inflated expectations, some are tied to impatience for practical applications, market forces and unbridled (but uncritical) enthusiasm. The news media also is named for “playing an obvious role in the creation of unrealistic hopes.” “These forces act together to produce a kind of ‘cycle of hype’ that drive overly optimistic representations of the research,” said co-author Timothy Caulfield. In their short-list of recommendations for avoiding inflation of the “genomic bubble,” Evans and his co-authors offer the following: (1) reevaluate funding priorities to stress behavioral and social science research aimed at behavior change for improving health; (2) foster a realistic understanding “of the incremental nature of science and the need for statistical rigor” within the
SPRING 2011
scientific community and that the media make more responsible claims for genomic research; (3) maintain a focus on developing high-quality evidence before integrating good ideas into medical practice. “By highlighting the risks of continuing to promise results from genomic science, we were hoping to draw attention to a more sustainable approach to reaping the benefits from genomic science,” said co-author Eric Meslin. The authors assert their belief that the current age of genomics will provide great benefits to human health: “Ours is not a call to gut existing research or too-rigidly tie funding to degree of disease burden ... The pursuit of our common goal—improved human health—demands that we take a hard look at disease causation and order our priorities accordingly.” UNC researchers identify a gene critical for heart function Everyone knows chocolate is critical to a happy Valentine’s Day. Now scientists are one step closer to knowing what makes a heart happy the rest of the year. It’s a gene called DOT1L, and if you don’t have enough of the DOT1L enzyme, you could be at risk for some types of heart disease. These findings from a study led by researchers at the UNC School of Medicine appeared in the Feb. 1, 2011 issue of the journal Genes and Development. The team created a special line of mice that were genetically predisposed to dilated cardiomyopathy, a condition in which the heart expands like a balloon, causing its walls to thin and its pumping ability to weaken. About one in three cases of congestive heart failure is due to dilated cardiomyopathy, a condition that also occurs in children. These mice lack DOT1L. The big discovery came when the researchers were able to prevent the mice from developing the disease by re-expressing a single downstream target gene, Dystrophin. “We saw this phenotype in the heart and it could be attributed to anywhere between 1 and 1,000 genes. But when we just added back this one gene, the heart function was completely rescued,” said the study’s lead author, Anh Nguyen, a graduate student in the lab of biochemist Yi Zhang, PhD, at UNC’s Lineberger Comprehensive Cancer Center. “It was very surprising to us,” Nguyen added. “Normally you’d think you’d have to add in a number of genes to really see that effect.” The researchers discovered that the gene depends on the enzyme DOT1L to activate it. If DOT1L levels fall too low, dystrophin ceases to perform its function, eventually leading to heart disease. “We’ve identified a new function of DOT1L, which has been linked to leukemia before, but never linked to heart defects,” said Zhang, Kenan Distinguished Professor of biochemistry and biophysics and an investigator of the Howard Hughes Medical Institute. Learning how the DOT1L affects dystrophin could eventually help to improve diagnosis and treatment of patients with dilated cardiomyopathy and other conditions. “The more we know about the protein, the better we can use it,” Zhang said. The protein could be a target for gene therapy, for example.