Paradigm Lost

Will translational medicine alter the discovery landscape?

Anyone who has been involved in the drug discovery and biotech arenas for any time knows, there is a simple paradigm that holds the universe together: basic research begets drug development begets clinical research begets healthcare. The mantra is as fundamental—nay, visceral—as DNA begets RNA begets protein.

And yet, even as modern biology has shown us that RNA can form DNA and proteins can "replicate" themselves (think prions), so too are we facing the possibility of another paradigm lost; that the healthcare process may not be unidirectional afterall. If explored to its fullest potential, this new paradigm—translational medicine or translational research—will have a significant impact on how we explore human health at all levels.

As indicated in several articles published in Drug Discovery News in recent months, including our coverage of the Windber Research Institute's licensing of InforSense technologies in the current issue (page 12), researchers and the companies for which they work are beginning to realize that scientific exploration doesn't have to run in one direction. Rather, the new philosophy argues that we can learn as much by moving from bedside to bench as we can moving from bench to bedside, applying lessons learned at the clinical stage to improve our fundamental understanding of human disease and drug action.

In some respects, the key driving force behind the adoption of translational medicine will be financial. As the editors of the Journal of Translational Medicine explained in a recent editorial (J. Transl. Med. 2004, 2, 14): "The current uni-directional paradigm of bench to bedside translational research is not cost-effective when one considers the long-term expenditure of testing new drugs pre-clinically, obtaining regulatory approval for testing in humans, and organizing increasingly larger clinical studies to demonstrate long-term clinical efficacy."

In other words, by improving our understanding of human health by incorporating new knowledge throughout the discovery, development, and testing processes, companies will be less likely to face the prospects of clinical trial cancellation or post-approval drug recalls. In theory, this will lead to a drop in the costs associated with getting a drug to market—currently in the $800 million to $1.5 billion range.

To release scientists from their philosophic shackles, however, companies, government agencies, and academia will have to find a way of sharing relevant information across the many stages of the therapeutic development process, breaking down the knowledge silos that have stood the test of time and forcing researchers to speak in a common tongue so that information is not lost in translation. Informatics tools will be critical to achieving this goal, but it will also require a major change in the way scientists and larger organizations work together.

As Drs. Heidi Hörig of Columbia University Medical Center and William Pullman of Sanofi-Aventis recently wrote (J. Transl. Med. 2004, 2, 44): "Translational research represents a team effort, since no single constituency can be fluent in all aspects, and thus a concerted effort is needed amongst translational researchers to convince stakeholders and legislators of the need to support translational research efforts, and thus maximize its potential."

More to the point, from a purely economic perspective, translational medicine will require companies and groups to come together to achieve shared goals, as none but the largest pharmaceutical or biotech companies will have sufficient resources in-house to accomplish each of the required steps. To compete, smaller companies will be forced to merge or otherwise collaborate to share their human and technical resources—a move that the industry is seeing with increasing frequency.

The question then arises as to how this transition will manifest itself in the industry. Will we see another round of acquisitions and mergers that will alter the industrial landscape as it did in the 1980s and '90s? Or will synergies be developed more peacefully this time around?