Hard Drugs: A Conversation with Pharmaceutical Chemist

Armen Hareyan's picture
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Did you know that the Sumerian ideogram for opium means joy? Or that drugs have been around for at least 5,000 years?

Indeed, when you think about it, migratory humans of an even earlier vintage likely learned enough about plants to pick up a few other medicinal tricks, mind-bending or otherwise. And let's not forget about the Wise Man and his gift of myrrh. Myrrh is an anti-inflammatory compound still used today in mouthwashes to relieve sore throat.

In the eons since, we've added to our drug discovery tricks with recombinant DNA techniques, gene chips, computer programs, microarrays, high-throughput systems and a host of other clever technologies. But the promise of modern drug-making chemistry, so proudly touted in media reports, press releases and science journals, has not always yielded products.

True, we have a lot more than 5,000-year-old opium in our apothecary at the moment. But there are still many shelves sitting empty.

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Tom James, PhD, chair of UCSF's Department of Pharmaceutical Chemistry, thinks he knows why.

"University scientists find drug targets [that suggest ways to block or reverse a disease-causing process by binding one chemical compound to another]. Pharmaceutical companies fund therapies. And this being a capitalistic system, there has to be some payoff to the investment." What kind of payoff? A $250 million market per year, give or take a few million, James estimates. "From the industry perspective, it's understandable. The financial risks of developing drugs are huge," he adds.

Among the risks is outright failure. One might argue about the odds, be they 10 to one or 10,000 to one, but the sad truth is that most promising chemical compounds flame out long before they make it to a formulary. Those that do succeed may burn through $800 million or so to make the grade.

The implications are clear, says James, who uses nuclear magnetic resonance techniques to study dynamic structures of proteins and nucleic acids, as well as small molecule-macromolecule interactions in search of molecules that bind together. "Drug targets for chronic diseases like heart disease or high cholesterol, where you have to take medications for the rest of your life, are considered more important than those for acute diseases that can be knocked out with a single treatment."

If your potential drug target happens to counter a disease or condition with a small patient population, even if it's a chronic disease, you slip farther down the money chain. And if the disease is concentrated among the poor in the developing world, your potential drug is a nonstarter

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