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Monday, November 23, 2009

Measuring a Chemist

My boss stands in front of the group of 40 chemists, speaking Chinese. A visionary speaking with passion. I can follow only a little of his speech, but the tone in unmistakable. Serious problems have surfaced, the client grows frustrated, our productivity lags the competition, storm clouds loom and danger gathers. Our widgets too slowly move off the assembly line. He changes to English to say “And this is entirely Paul’s fault.”

Medicinal chemistry projects are difficult to measure. Many properties of a single compound must be optimized simultaneously, though it only takes one compound to make a program a success. But progress on properties comes in fits and starts, an art more than a science, difficult to measure, unsatisfyingly fuzzy metrics. What can be easily measured are more concrete, but perhaps less useful areas, such as number of reactions run, number of compounds completed. Production numbers. The chemist as factory worker.

In big pharma, producing one compound a week is an acceptable production number. Enough to evade scrutiny of effort. Free from questioning of work ethic, one could focus more on intelligent design. Design creatively, thoughtfully, methodically to achieve all the properties you seek in a single compound.

Now, in the CRO a different standard applies. Perhaps legacy from the not so distant past when targets were given and progress towards specific known objectives was tracked with anxious energy. Much focus still zeros in on production. “We are paying for chemists well outside of our direct control, across the globe, on whose work our career depends” goes the potential thought process of the anxious manager. Crank and crank harder! We are expected to crank and design, judged by both metrics simultaneously.

Our group has taken a one year old project from a major big pharma site, taken the lead compound and reduced MW by 40%, increased potency by 2x, reduced off target liability by 60x in less than six months with significant cost savings. Now that we have improved properties, hopefullly cranking is easy. Perhaps communication is harder.

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