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It has been the mantra of genomics researchers for nearly 20 years now: understanding the genome will yield better and more affordable drugs that will cure even the deadliest diseases. But in the thick of this much ballyhooed genomic revolution, newcomers to the pharmacy shelf are few and far between and seem to offer (with a handful of notable exceptions) only trivially new ways to lower cholesterol and boost sex lives. Why? After all, researchers have in hand a draft of the human genome, the parts list for the hundreds of thousands of proteins that carry out the body’s biological business. And they have already discerned that hundreds of those proteins – ones that go awry in cancer, for instance – would make obvious targets for new drugs.

The problem is that there’s a yawning gap between traditional pharmaceutical companies and genomics research. Genomics, still largely an academic pursuit, might divulge a specific protein’s role in cell division, say, and what chemical probe blocks the protein’s action. That may be important for understanding how tumors grow, but it is years away from where the pharmaceutical industry would begin developing a new cancer drug. In practice, most companies avoid novel targets because they are unproven, tied to unwanted effects downstream, or just too hard to hit with familiar drug compounds. The result: a no man’s land of unpursued protein targets, half-baked chemical probes, and what-might-have-been drugs.

What could help bridge this gap is the emerging science of chemical genomics, which uses vast libraries of “small molecules” – synthetic compounds that bind to proteins and alter their functions – to probe how all the proteins encoded by the genome work in concert. Small molecules, it turns out, are a big deal for drug companies, too. From 1980 to 2003, 90 percent of new drugs approved by the U.S. Food and Drug Administration were made from small molecules. From aspirin to allergy pills, most small-molecule drugs are cheap and easy to produce – in stark contrast to the protein-based and other “large molecule” drugs on which biotech companies tend to place their bets. Combining the convenience of small-molecule drugs with the intelligence of genomic science could revitalize the lumbering drug industry and greatly improve health care.


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