1 Boring Old Man

Transforming Drug Development
Focus: Harvard Medical School
by R. Alan Leo
October 17, 2011

^{Harvard Medical School launches major initiative to address crisis in drug development}

^{Taking aim at the alarming slowdown in the development of new and lifesaving drugs, Harvard Medical School is launching an Initiative in Systems Pharmacology, a comprehensive strategy to transform drug discovery by convening biologists, chemists, pharmacologists, physicists, computer scientists and clinicians to explore together how drugs work in complex systems. “With this Initiative in Systems Pharmacology, Harvard Medical School is reframing classical pharmacology and marshaling its unparalleled intellectual resources to take a novel approach to an urgent problem,” said Jeffrey S. Flier, dean of the Faculty of Medicine at Harvard University, “one that has never been tried either in industry or academia.”}

^{Modern drug discovery has focused on the interaction between a candidate drug and its immediate cellular target. That target is part of a vast and complex biological network, but because studying the drug in the context of a living system is profoundly difficult, scientists have largely avoided this approach. As a result, predicting the effects of a particular candidate drug in humans is currently all but impossible, and many initially promising drugs have been found to lack efficacy or to have unsupportable levels of toxicity — typically at a late stage of a clinical trial, at a cost of years of effort and up to $1 billion.}

^{“Right now in the world of drug discovery, 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,” said Marc Kirschner, the John Franklin Enders University Professor of Systems Biology and chairman of the HMS Department of Systems Biology. “If you try to plan a trip on such fragmentary information, you’ll fail. It’s our inability to develop a coherent picture that has stymied drug discovery for so long.” As drug makers exhaust the most promising candidate areas, the number of new drugs brought to patients has actually decreased in recent years, even as the cost of discovery has soared.…}

^{The science of analyzing specific biological processes within the context of an entire living system, called systems biology, is relatively new. Harvard Medical School is a world-leader in this area, having established one of the first department-level programs in 2003. Building on this success, Harvard’s new effort will apply systems biology’s innovative approaches to the understanding and prediction of drug activity, drawing on the vast range of biomedical expertise available at the medical school and its affiliated teaching hospitals and research institutes.}

^{Led by Kirschner and systems biology professors Peter Sorger and Tim Mitchison, the Initiative in Systems Pharmacology will include faculty from a broad array of disciplines: systems biology, cell biology, genetics, immunology, neurobiology, pharmacology, medicine, physics, computer science and mathematics. The initiative will be fueled by a strong and diverse group of existing faculty and new recruits who will be based in several departments, and will be supported by an ambitious fundraising effort.  New approaches could include use of chemical biology to develop probes of biological pathways and failure analysis on unsuccessful drugs, similar to how the aviation industry scrupulously analyzes accidents to learn what went wrong. Such a practice is not common in today’s pharmaceutical industry…}

^{The Initiative in Systems Pharmacology is a signature component of an HMS Program in Translational Science and Therapeutics. There are two broad goals: first, to increase significantly our knowledge of human disease mechanisms, the nature of heterogeneity of disease expression in different individuals, and how therapeutics act in the human system; and second — based on this knowledge — to provide more effective translation of ideas to our patients, by improving the quality of drug candidates as they enter the clinical testing and regulatory approval process, aiming to increase the number of efficacious diagnostics and therapies reaching patients…}

The world seems divided into two camps on the issue of the slowdown in new drug development. Some see it as a national emergency requiring something like the Manhattan Project or DARPA – an initiative to keep the drugs coming our way like the "spice trade" in Herbert’s sci-fi classic, Dune. Others see the hiatus as a godsend – a break to catch our breath and put safeguards back in place for patient safety and the ethical medicine – a time to get the pharmaceutical industry out of academic research departments. So my first reaction to this article was a mild cringe, a near shudder, something like that. "Uh Oh. Here we go again."

But reading it over again, I noticed an absence. It didn’t say "partnering with industry…" anywhere, and I began to change my mind a bit. It didn’t say they weren’t going to do that, but at least it didn’t say they were. The open door was there, however, in the phrase "and will be supported by an ambitious fundraising effort." I’m surprised at how suspicious I’ve become over the months of reading about clinical trials, key opinion leaders, ghostwriting, just plain fraud. My immediate reaction to this announcement was to start looking for the angle – another TMAP? another Childhood Bipolar craze? more stealth? which PHARMA is funding it? etc.

aek