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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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February 19, 2006

Because I Never Lie, and I'm Always Right

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Posted by Derek

Something recently made me think back to an undergraduate physics lab that I once had to do. This was elementary optics, so we had the standard collection of lenses on a beaten-up optical bench as we did our Newtonian thing. There would be little reason for me to remember it if it hadn't been for the comment of one of my lab partners.

We were setting up another phase of the experiment, and the instructions said for us to put the lenses in a set configuration and see if we got such-and-such effect. "That can't be right", this guy said, moving them to a different spot that he thought would work better. They didn't, and we ended up doing it the way the lab manual had laid out. But I've returned to that scene several times over the last twenty-five years, trying to figure out what bothered me about his response.

After all, a good researcher shouldn't just take someone else's word for everything, right? And if you have a hypothesis, and can test it, you should go ahead and do it, right? On the face of it, my old partner's attitude towards our lab that day shouldn't have gotten on my nerves, but it did. There was something wrong about it, but I kept trying to work out what it was - in a way that didn't put me on the just-follow-the-lab-book side of the argument, where I didn't want to be.

It finally dawned on me. My problem with the guy wasn't that he didn't trust the lab manual. It was that he trusted himself way too much. It would have been one thing to try what was in the book, then say "I wonder what happens if you move this lens out here?" That would actually be a good sign. But the statement "That can't be right"isn't one, especially not from an undergrad doing an optical demonstration whose results have been known for three hundred years.

Now, of course, I have a lot more room to maneuver as a scientist. Most of the experiments I run are things that no one has ever done before, not on these particular molecules in this particular way. I'm pretty sure I know what's going to happen, but I get surprised a lot. And when it comes to the effect of my compounds on cells and animals, I get surprised all the time.

But it's surprisingly easy to forget how little I know. After sixteen-plus years doing this, I have to watch my tendency to talk to younger colleagues as if I know what's going to happen with their ideas. I don't. I have my experience to draw on, of course, which makes me say things like "Are you sure you want to put a napthyl in that molecule?" or "Cyclohexyl groups are a metabolism magnet - that's going to get torn up". I'd say that a good solid majority of the time, those two statements are correct. But once in a while they're not, and most of the time I don't have as much evidence to back up my prejudices as I do with those two examples.

So now I know why I've never forgotten the guy who said "That can't be right". I've been trying, all this time, to keep from turning into him. The struggle continues.

Comments (5) + TrackBacks (0) | Category: Who Discovers and Why


1. Demosthenes by day on February 20, 2006 11:03 AM writes...

I too with 22+ years in the business understand this attitude. I am more like your lab partner as I've been on the side of "just let me run the experiment, please". Two of the projects that I have worked on which led to drugs went through the "that won't work don't waste your time" phase. Thankfully, I didn't listen and in both cases I was able to make the change and the common wisdom ended up being wrong and those features ended up in the eventual drug product. This lesson has been reinforced time and time again to me that while you should be aware of the potential drawbacks you shouldn't let that talk you out of getting the data and knowing for sure. You can't reduce drug discovery down to dogma because if you could the the guys from the Yeknom company in the career builder ads would be doing this.

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2. daen on February 20, 2006 11:18 AM writes...

The longevity of a demonstration doesn't necessarily grant it immunity to change (admittedly, rarely by big-headed students). I wonder how explanations of Snell's Law will be reacted to when left-handed materials are more commonplace in optics demonstrations?

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3. dlib on February 20, 2006 2:02 PM writes...

I recently read the preface of Antoine Lavoisier's " Elements of Chemistry " and realized what a great touchstone it is for scientists of all disciplines.

I heartily recommend it. What he says is as true today as it was back in 1789 when he wrote it.

( remember the S's look like F's but you get used to it ).



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4. Worried chemist on February 20, 2006 7:06 PM writes...

On a completely different note... I guess most of you heard that P&G is laying off 300 researchers at thier Cincinatti site. Unbelievable. First J&J, now P&G. Both were completely "out of the blue", so-to-say. It's a scarry time to be a medicinal chemist, that's for sure!

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5. DRogers on February 21, 2006 5:51 PM writes...

Maybe I'm missing something about the point of your angst here, but I find that the best scientists work by building strong mental models of the world, adjusting them only "on failure". So I look at the fact that this person had such as model already built in a newly-acquired domain as a positive sign, even if it was still facing some adjustments.

I could contrast this to rigid, recipe-dependent, students who will blindly follow poorly-worded and typo-laden experimentals even after it is long obvious that something-ain't-working... at least the overconfidence of the former group can be punctured by reality!

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