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| At first glance, it is difficult to see
how the urgent nature of critical care medicine relates to the highly
technical, research-centered field of functional genomics. The typical
portrait of intensive care comprises beeping monitors, tubes, multiple
laboratory tests, IVs full of broad spectrum antibiotics, and, often,
uncertainty about whether a patient will survive. By contrast, the
popular notion of genetic technologies is DNA fingerprinting and the
investigation of rare diseases caused by single gene mutations. Neither
conception reflects the whole picture. The recent completion of the
human genome project and parallel developments in high-throughput
biology have made it possible to examine complex diseases in unprecedented
detail. Knowledge of species-specific biological responses to injury
and infection at the molecular level, gleaned through functional genomics,
has the potential to launch critical care medicine into a new, more
refined, era. The example of multiple organ dysfunction syndrome (MODS) illustrates a specific potential application of functional genomics to critical care: Severe infection and traumatic injury are often complicated by multiple organ failures that cause substantial illness and death. Components of MODS include septic shock, acute respiratory distress syndrome, acute renal failure, hepatic injury, myocardial dysfunction, coagulopathic states, and encephalopathy, all of which may be viewed as host responses to a critical insult. Alone and cumulatively, each of these conditions increases the risk of death even after successful treatment of the underlying infection or injury. Yet, despite substantial effort, treatments directed at a single mediating gene or inflammatory pathway have done little to alter the outcomes of critically ill patients. With a functional genomic approach, however, these conditions could be viewed and interpreted at multiple levels--from the organ to the genome--more accurately reflecting the interactive, emergent properties of adaptive and maladaptive host responses. As functional genomics begins to translate knowledge from the research laboratory to the bedside, intensivists will have a new set of tools to complement or even replace the old ones: high-throughput technologies such as microarrays, highly parallel single nucleotide polymorphism analysis, and proteomics. As always, their goal will be to develop a more global understanding of complex biologic processes and systems, integrating pathophysiology, cell biology, and prewired genetic programs. |
| Dates November 17- 18, 2003 Location National Institutes of Health Natcher Conference Center Bethesda, Maryland
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