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Harvard Program to Apply Systems Approach to Drug Discovery

Pills (USA.gov)

(USA.gov)

Harvard Medical School is launching an Initiative in Systems Pharmacology, to develop what it calls a comprehensive strategy to transform drug discovery. The program aims to reverse the slowdown in the development of new therapies and involve a range of disciplines and methods outside the usual collection of life scientists and clinicians.

Marc Kirschner, who chairs the systems biology department at Harvard’s medical school, attributes much of the problem to current methods that attack specific targets with candidate drugs. This process can often result in clinical trials — that occur late in the development calendar and after considerable investments — which find the candidate drugs ineffective or reveal unanticipated toxicity or side effects.

Kirschner advocates researchers consider at the outset the complex biological network that the candidate drug must navigate. “It’s as if we have a map of a highway system that only contains small pieces extending a few miles here and there, without any connectivity on a large scale,” says Kirschner. “It’s our inability to develop a coherent picture that has stymied drug discovery for so long.”

The new initiative is expected to build a better understanding of the whole system of biological molecules that controls medically important biological behavior, to help industry identify the best drug targets and biomarkers. Kirschner will lead the program, joined by systems biology colleagues, as well as faculty from Harvard departments and research institutes in cell biology, genetics, immunology, neurobiology, pharmacology, medicine, physics, computer science, and mathematics.

The Initiative in Systems Pharmacology plans as well to adopt different analytical methods not normally applied to the life sciences. One approach under consideration, for example, is failure analysis similar to the process used by the aircraft industry to investigate accidents to learn what went wrong, a practice not common in the pharmaceutical business.

“What’s amazing is how little we know even about many drugs that work,” says systems biology professor Peter Sorger. “A systems approach could help tailor existing treatments to specific patients, and find new uses for therapies we already have.”

Several studies involving systems biology are already underway, funded by NIH and involving industry partners Boehringer-Ingelheim, Novartis, Roche, and Vertex. The initiative is also expected to have an educational component, to train new physicians and scientists in this systems approach.

Read more: Math Methods Devised to Design Chemical Catalysts

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