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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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September 25, 2005

Report From What I Think is the Frontier

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Posted by Derek

It's been a while since I spoke about the run of experiments that I've been doing. Things are going very well, although not quickly. The combination that seemed to work for me back in June (see the 6/23 post here) has repeated cleanly several times now, with new control experiments and fresh solutions of everything. And since then, I've found a couple of others that also seem to give the effect I'm after and they hold up, too. I'm having to make the mental adjustment of realizing that this stuff is real and reproducible.

I mentioned that I was going to present my results inside my company. That went fine, I think, with about the same number of people leaving the room thinking that I was nuts as came in. Mind you, there was some turnover in the rosters of people holding each opinion. But I've been given a bit of room to work on what's now generally known as Derek's Crazy Idea. I have a two-week experiment going on to get some kinetic data on things - how quickly does this stuff come on, how high can it go, when does it start to level off, and so on. And I'm getting geared up for an extension to a completely different system, one that's much less of a test bed and much more of a real-world application.

That makes me rather nervous, because there's plenty of twangy tightrope stretched between those two platforms. My preparations include gearing up for a huge range of reaction conditions, because what my work thus far has shown is that I don't have a clue - yet, anyway - about what's going to work and what isn't. When I think about how close I came in the first system to never seeing anything at all, it makes me want to sit down for a while. How many other interesting things have I missed in my research career, slipping past me by only a couple of millimeters and still leaving no trace?

Comments (5) + TrackBacks (0) | Category: Birth of an Idea


1. Eric th e.5b on September 26, 2005 1:17 AM writes...

Good luck with the Crazy Idea. :)

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2. daen on September 26, 2005 5:27 AM writes...

I've only ever written software in my working life. As any programmer knows, what with the bugs in your own code, bugs in other people's, dodgy hardware etc, that glittering cathedral of the mind often falls down around your feet. All very maddening and time consuming, but you've usually got at least three other ways to get to the finished result - including abandoning your current development platform in favour of something else. Since I started working with chemists and molecular biologists, I've realized that the "sod it, let's start over" approach doesn't really work when the literature is sparse, every positive result you get in the lab is meaningful (but you don't necessarily know why) and every failure is meaningful too (but you don't necessarily know why and you wish it was a positive result instead).

Good luck, Derek!

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3. Anonymous on September 26, 2005 12:51 PM writes...

Derek writes: "When I think about how close I came in the first system to never seeing anything at all, it makes me want to sit down for a while. How many other interesting things have I missed in my research career, slipping past me by only a couple of millimeters and still leaving no trace?"

I've often thought and worried about this as well. Perhaps it's the ability to detect and identify these interesting things that distinguishes an outstanding from an average chemist. I'll have to admit that on more than one occasion in graduate school I failed to isolate and identify minor reaction side-products; when the goal is the total synthesis of a natural product, we can tend to get a little tunnel-visioned. However, when I did take the time to do so, it was quite frequently fascinating to observe the new structure and propose a means by which this transformation had taken place. I have heard that Prof. Kishi at Harvard is particularly rigorous about side-product identification. This is a great approach, since knowing what the side-products are will often allow one to modify the reaction conditions and/or substrates to improve the efficiency of the reaction.

I keep a folder of all of the interesting side reactions I've observed thus far in my research career. I'm hoping to either develop some of them into useful methods or apply them to new total syntheses. Of course, this all has to happen on the side since my top priority (and my job) is drug discovery!

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4. Brad on September 26, 2005 12:53 PM writes...

Oh how I miss the bench. I am a MS med chemist who worked in big pharma. Then I had to move to Seattle (I suffer from ring strain) and now am working as an analytical chemist. But I love reading about all the exciting morsels you post about life at the bench.

Did you get my joke?

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5. Giagan on September 26, 2005 12:55 PM writes...

Sorry, didn't mean to make that last comment anonymous. It was me, I admit it! :)

Back to the bench.

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