About this Author
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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May 25, 2005

The Voice of Experience

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Posted by Derek

During a meeting today, some of us were making a decision about whether or not to take a look at a particular series of compounds in some assays. I spoke up, saying "Hey, if we've got 'em, why not? Never talk yourself out of something that's easy to test."

"The voice of pragmatism", said someone else, and I responded "Darn right!" It's a real temptation in this business to think that you know more than you do. The alternative, a realistic appraisal of just how lost you (and everyone else) is, can be a bit disconcerting, and that's why I think people overvalue their expertise. "Those compounds never work," "We did something like that before," "We already know what the answer is" - these are the sounds that people make when they're trying to sound wiser than they probably are.

I have to look out for these tendencies in my own work, too. I've seen enough different sorts of projects that I do have some valuable experience to draw on. But not all of it is valuable all the time, and it's very hard to know when you're being fooled by a false correlation with something that's happened before. I don't know when something is going to be orally active, and I don't know what its blood levels are going to be like. Much as I would like to, I don't know exactly how a given compound binds to its protein target, and neither, in almost every case, does anyone else. I sure can't predict toxicity, either, and it's not for lack of motivation. One of the most valuable things I can take away from all my experience is the willingness to step back and let the results sort themselves out.

Now, there are times when you really shouldn't try something. But those times occur much less frequently than you'd think, and usually for lack of time or resources. But if both of those are available, I'm up for taking a flyer on all kinds of odd stuff. Some of the best things I've ever done looked pretty weird while I was doing them, that's for sure. But I'm at the point in my career where I'm less concerned about looking like a fool, so perhaps my best work is still to come.

Comments (3) + TrackBacks (0) | Category: Life in the Drug Labs


1. J. Harris on May 26, 2005 5:28 AM writes...

You describe a very wise approach. Perhaps a large part of today's low productivity relative to dollars can be explained by having too many know-it-alls on board. I submit as evidence the commercial success of predictive PK and toxicology packages and the continued existence of Lipinski's rules.

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2. jeet on May 26, 2005 1:07 PM writes...

speaking of toxicitiy and other fairly unpredictable properties involved in drug development, maybe Derek could offer his thoughts on the risks of small molecule vs. protein/ antibody development.

I was mainly thinking about the effects that will knock a compound out of clinical testing. Of course there is a large possibility that I'm really reacting to Genetech's ridiculous hit rate over the last 12-18 months.

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3. PsychicChemist on May 26, 2005 7:40 PM writes...

I agree with the philosphy that "lets test them since we have them" because it is a lot lot easier to test compounds than it is to make them.

But I do not proscribe to the philosphy that "lets make them because we can".

I guess it goes back to the time of combichem and everyone knows how well that turned out.

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