The target was ripe, the potential huge.
Epidemiologists had linked elevated blood levels of an amino acid called homocysteine with an increased risk of cardiovascular disease. And lowering homocysteine levels couldn’t be easier: folic acid and other B vitamins did the trick. So roughly a decade ago a number of large-scale heart studies went about determining just how many deaths the simple treatment could prevent.
The answer was effectively zero.
“It was a simplistic view of the problem,” said Joe Loscalzo, HMS Hersey Professor of the Theory and Practice of Physic and head of the Department of Medicine at Brigham and Women's Hospital, whose own research has shed light on just how much complexity lies beneath the apparently simple correlation with homocysteine. “But if you put on blinders, you’d assume it would work.”
Today, Loscalzo and others at HMS are leading the charge to tear off those blinders. In publications, symposia and a planned course, research and clinical leaders are challenging their colleagues to move beyond the reductionist model that has propelled biomedicine since the 19th century. Instead, they argue, the health challenges of the 21st century require a new approach: network medicine.
The reductionist trend that has dominated disease research relies on single molecules or single genes to provide robust insights into the pathophysiology of complex diseases. Similarly, current drug development strategies target single molecules that frequently fail because of unforeseen effects.
“Over 100 years, the reductionist model held us in good stead,” said Loscalzo. “But there are flaws, especially regarding chronic disease.” Research on the most common cancers has produced a legion of drug candidates that hit their target without stopping the disease.
In contrast, network medicine emphasizes a more holistic approach through the identification and investigation of networks of interacting molecular and cellular components. When network medicine is integrated into biomedical research, it has the potential to transform investigations of disease etiology, diagnosis and treatment.
Network medicine considers a biological system as a network of interactors: Genes encode proteins, which interact with genes and other proteins within and between cells and even organs. Targeting a single node in that network may have unintended consequences—or no consequence at all—without some understanding of the target’s role in the network. To build that understanding, network medicine draws together biomedical researchers, computer scientists, mathematicians and engineers to combine approaches from a number of established and emerging fields.
“The ability to combine systems biology, systems pharmacology and computational biology in the new discipline of network medicine has the potential to transform the way we think about diseases and treatments for them,” said Elliott Antman, HMS professor of medicine at Brigham and Women’s and associate dean for clinical and translational research at HMS. Antman is leading Harvard Catalyst’s efforts to offer educational resources about network medicine to the Harvard community.
Those efforts began with a June symposium, which featured presentations from leading investigators in the field, including Loscalzo and Albert-László Barabási of Brigham and Women’s and Northeastern University, and Roy Kishony and Peter Sorger of the HMS Department of Systems Biology. Topics included the identification and behavior of networks in biology and disease; how network models can integrate vast troves of -omics data to help understand disease and systems pharmacology approaches for the development and evaluation of effective therapies for complex disease.
Last month, 100 researchers and clinicians from across the HMS community explored similar topics in greater detail at an introductory course in network medicine. Additional short courses are planned for 2013.
“It’s such a new discipline that we’re trying to highlight many of the fields in which network principles apply,” said Edwin Silverman, HMS associate professor of medicine at Brigham and Women’s and one of the course developers. “There’s not a set body of knowledge. We’re trying to show them the potential of the field so they can apply those principles to their work.”
The institutional challenges are significant. The reductionist model has influenced the evolution of preclinical and clinical departments of medical schools and hospitals, as well as the structure of research grants, journals and the National Institutes of Health.
For Silverman, the field’s rapid changes include his address: On July 1, he became chief of the Channing Division of Network Medicine at Brigham and Women’s, created from the restructuring of the Channing Laboratory.
“Traditional research is reductionist: ‘Find that key molecule and understand everything you can,’ ” Silverman said. “But there is no single magic bullet, no single key molecule, for the complex diseases that plague society now.”
