Why and how to expand the role of systems biology in pharmaceutical research and development

Seen from the perspective of funding organizations, investors, and the general public, the productivity of our world-wide biomedical research enterprise is declining despite increased investment. This opinion piece suggests a cause and a solution. The cause is the enormous complexity of human biology and pathophysiology. The unsolved human diseases involve so many interacting variables that single research laboratories headed by skilled principal investigators doing innovative experimental work cannot be expected to assemble the reductionist pieces into an integrated working model. Systems biology offers a solution, but it will require teamwork. Co-equal teams of experimental and computational biologists can construct multiscale differential equation models and test them against experimental data. A successful model provides actionable evidence-based guidance to the entire research and development team. These integrative biology teams may, for historical and cultural reasons, be unsustainable in academia, but they seem naturally suited to modern pharmaceutical research and development. One way to organize such teams and their workflow is described in detail.