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November 10, 2005
. . .And That Settles It
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
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