This week's cover story on systems biology provides a fascinating glimpse into the future of medicine (see page 17). It is a future of personalized medicine, with drugs tailored to treat specific populations of patients. It is a future in which medicine's focus will shift from disease treatment to health maintenance and disease prevention.
The cover story was written by Senior Editor Celia Henry Arnaud. In her lead, she writes: "Imagine going to a doctor's office. Your complete genome sequence, which provides a probabilistic prediction of your future health, is part of your medical file. To see how that genetic component is playing out and to obtain a snapshot of your current health status, your doctor orders a standard test of more than 2,000 proteins and metabolites. According to the results of those tests, your doctor recommends ways for you to maintain or improve your health through either medication or behavior modification.
"Sounds futuristic? Perhaps, but it's not as far off as it seems, and systems biology will help make it a reality."
At its core, systems biology represents a shift from a reductionist approach to biology—studying genes and proteins one at a time to understand their function—to an embrace of the elemental complexity of biological systems. As Arnaud writes, "The goal of systems biology is to combine molecular information of various types in models that describe and predict function at the cellular, tissue, organ, and even whole-organism levels."
Many diseases, such as obesity, diabetes, and many heart diseases, will only be successfully treated with a systems approach, a number of researchers Arnaud interviewed point out. Joseph H. Nadeau, chairman of the genetics department at Case Western Reserve University School of Medicine, told Arnaud, "Look at all the things that are problematic, compromised, or dysfunctional in an obese individual. To think that we can go into a laboratory and synthesize some drug that will fix all the problems and not cause any adverse side effects, the premise is goofy."
But Nadeau also noted that even diseases viewed as relatively simple, like cystic fibrosis or sickle cell anemia, both of which are caused by a single gene defect, are not as straightforward as once thought. "Other genes in the genome influence the age of onset, the severity, and the clinical associations," Nadeau said. "The biology of individuals with cystic fibrosis is telling us that it may be a simple genetic cause, but there are many systems properties that confound it."
Huge challenges remain before systems biology has a major impact on clinical practice, of course, and chemistry will play a major role in overcoming them. Currently, data are not being collected from enough patients to be able to determine the extent to which changes in genes, proteins, and other pathway components will actually be predictive of health and disease, Arnaud writes.
Another roadblock to advancing systems biology into the clinic is the lack of analytical technologies to make a broad range of measurements of biological molecules with high sensitivity at a low enough cost. H. Steven Wiley, director of the biomolecular systems initiative at Pacific Northwest National Laboratory, told Arnaud, "What you really want to do is take a drop of blood from a patient and look at every protein, every metabolite, everything that's in the blood."
Arnaud interviewed a number of scientists at universities, national labs, and companies who are working to develop just such analytical systems and the bioinformatics tools that will be able to handle the avalanche of data they will produce. One such scientist is James R. Heath, a chemistry professor at California Institute of Technology, who told Arnaud, "Finding molecules that have the same specificity for proteins that antibodies do, that can distinguish between slightly modified proteins versus unmodified ones, that are stable, that are relatively inexpensive to make, and that can be prepared in high throughput is a really tough chemical problem."
Moving systems biology from the powerful research tool it already is into the clinical setting is not going to happen overnight, but the progress Arnaud outlines in her story is remarkable. As Leroy E. Hood, cofounder and president of the Institute for Systems Biology in Seattle, told Arnaud, "Here's a model for medicine of the future."
Thanks for reading.
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