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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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November 10, 2005

. . .And That Settles It

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Posted by Derek

You know, after all the philosophical wrangling that's gone around here the last couple of days (I refer to those record-setting comment threads below), I have to say that there's something about scientific research that I really appreciate: things get resolved.

Not everything gets resolved, true, which is also part of the fun. But enough things do get settled to provide a person with a sense of accomplishment. In medicinal chemistry, we have to come to some firm conclusions about things, for example: Is Drug Candidate X more efficacious than Drug Candidate Y? How long does it last in the blood after an oral dose? Is it more toxic? What will it cost to make?

Naturally, there's room to argue about the details of all those things. Try "efficacious", for example - in which model of the disease are we talking efficacy? Efficacious by which biological criterion? Are those both the right ones to use to try to predict clinical success, or are we just kidding ourselves? (A constant temptation, that). The other questions can be exfoliated in the same way. Which species are we measuring blood half-life in? Is that the relevant one? How long do you think the half-life should be, and why do you think so?

And you'll have to define "toxic" in the same manner that you had to define "efficacious". Toxic at what level, in what way, and in what species? Is that result relevant to man, or just another stupid distraction? How do you know, and just how much are you willing to bet on that opinion? A million dollars for multiweek tox studies? Tens of millions to get started in clinical trials? Hundreds of millions to get the thing to market? The whole company if you're wrong even after that?

No, there's enough uncertainty to keep things lively, all right. But there are still a lot of things that get settled along the way, once and for all. This reaction really is more reliable than that one. That chiral methyl group really is pointing in that direction. This compound really does bind more tightly to the target than that one and no, we really, really aren't going to develop that other one that just killed off all the rats. After a week of philosophical tug-of-war (for which I have only myself to blame; no one forced me to write about Intelligent Design), I do enjoy the certainties of a clean NMR spectrum

Comments (2) + TrackBacks (0) | Category: Life in the Drug Labs


1. RKN on November 11, 2005 11:59 AM writes...

  But there are still a lot of things that get settled along the way, once and for all.

Here here!

I bet there will always be more interest and money invested in predicting how things will work, and far less retrodicting how they might have. As it should be, imo.

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2. c chad warford on November 11, 2005 3:43 PM writes...

i was lucky enough this week to (finally) isolate a molecule i'd been after for a few weeks. cleanly, that is. here's to beautiful, wonderful, grin-inducing, clean NMR spectra.

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