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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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July 31, 2006

Hobson's Choice

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Posted by Derek

One of the things I've noticed over the years is that I rarely stay on a project long enough to have the kind of familiarity with the molecules that I had with the ones I worked with in graduate school. I'm not complaining. I knew my PhD project molecules like an infantryman knows the hundred-pound pack on his back - that is, much more than I ever wanted to or believed possible. I knew tiny details in their NMR spectra, things like long-range coupling constants and NOE enhancements, and the moment something changed I would point like a hunting dog.

But now, my lab stays on a project for a few months, maybe a year at the outside. And during that time, we'll work on several varied groups of molecules - usually with the same core, but with all sorts of things coming off of it. We get a working knowledge of them, but we're always being surprised by little details that would have been second nature after a good solid three years of the same series. Of course, after that good solid three years we'd all be good and solidly sick of the chemistry, too, but that's the price tag.

I used to tell people in grad school, while I hauled yet another load of synthetic intermediates up the mountainside, that the grunt work left me a choice of two moods: bored, or angry. If everything was working just the way it always had, I was bored. And if a reaction decided to unexpectedly fail, then. . .not much of an emotional range, is it? No, I'll take what I have now, where boredom doesn't have as much of a shot at me, and I don't have the chance to stay angry about any one thing for long. Variety, the spice of chemistry. (One of my "Laws of the Lab" covers this topic - I'll get to that later in the week).

Comments (12) + TrackBacks (0) | Category: Graduate School


1. Squin on July 31, 2006 8:54 PM writes...

I'm glad it gets better. I'm coming up on three years with my favourite natural product and I AM VERY BORED and/or FRUSTRATED. My enthusiasm for chemistry used to be limitless but lately I've been pondering alternate career paths after my PhD.
I don't want to feel like this for the rest of my carerer and I like to hear that it's not all just stress/pressure/nights/weekends.

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2. Alica on August 1, 2006 1:53 AM writes...

Ditto about everything Squin. Doing many large scale syntheses of natural product intermediates at the moment, in the hope of getting enough material to finish the total synthesis before the end of the year and the end of my canditure. Just put on my biggest HF desilylation reaction ever! I am working weekends for the first time during my PhD, in the hope that the end will come quicker. I have read what you have said about being a slave to the lab as a graduate student, and I haven't been until now. I spent lots of time playing Ultimate Frisbee and going to various tournaments around the country and now that the clock is ticking down, the lab is calling.

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3. LNT on August 1, 2006 7:05 AM writes...

Do you really mean that you only stay on a given project for a few months to a year at most? That's highly unusual in this industry, is it not? The medchem projects that I have worked on have generally been 1 year minimum, and typical projects last 2-3 years (sometimes more) from initial lead to preclinical candidate. Yes, we do move to new series and sub-series durring that time -- but usually they are closely related classes of molecules.

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4. vent on August 1, 2006 7:39 AM writes...

I stay on projects for a few months as well. Only discovery; from Hit to Lead... ehhh... mostly from Hit to garbage can. If lucky, a Lead moves to the Lead Optimization guys where it stays 2-3 years. I like it. I see a lot of projects and compound classes.

The evil demon around the corner that I try to avoid is all those biologicals.. I want to do LMW compound chemistry, not being bored by a peptide synthesizer, solid-phase and scary-NMR's. Unfortunately the Bog Bosses here think otherwise.

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5. Mike on August 1, 2006 8:00 AM writes...

Natural products are fun. Try working in an analytical process lab where you just run samples all day. I enjoy when the mass spec breaks down, it gives me a chance to flex/improve my troubleshooting skills.


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6. Syn on August 1, 2006 12:09 PM writes...

Yeah Mike, try troubleshooting ONE problem for 2 years. The fun ceases rather quickly after say a month.

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7. Portnoy on August 1, 2006 12:44 PM writes...

My PhD was a very nice mix of methology, mechanistic studies and total synthesis (applying the methodology of course). For my postdoc I felt it was necessary to do total synthesis, but now that I'm halfway through, I am extremely bored. As Derek suggests, 98% of my time is spent manufacturing, and that's extremely boring...which brings me to my real point:

I'm trying to decide between pursuing med chem or process chem jobs within the next year. I'd like to hear from people in industry their thoughts about each; likes and dislikes etc, the nature of the chemistry, and how each compares with a 'methodology' versus 'synthesis' experience in academia.

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8. secret milkshake on August 1, 2006 2:22 PM writes...

I have a great respect for process chemists and I am glad that I don't have their job - the pressure (they cannot afford to lose a batch), the unrealistic deadlines imposed by management, the regulatory burden, the need to optimise the chemistry, necessity to cut out chlorinated solvents and column purifications, to find out about exotherms.

I have done some scaleups by myself and I love it but I would not ike to do it for living. Medchem is much easier way of making living.

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9. tom bartlett on August 1, 2006 2:54 PM writes...

" I'm trying to decide between pursuing med chem or process chem jobs within the next year"

Sounds like you wouldn't like process.

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10. waiting4data on August 1, 2006 4:02 PM writes...

"I have a great respect for process chemists and I am glad that I don't have their job .... the unrealistic deadlines imposed by management"

Secret, you don't have unrealistic deadlines imposed by management in medchem? Wow! I need to get a job where you work ;) I agree with your overall assessment, though. At least with optimization, there is a considerable amount of variability in the chemistry, and analog design is fun. Also, having to know everyone else's stuff, i.e. pharmacology, ADME, patent law, formulation, pharmaceutical properties, etc. sure keeps us from having enough free time to get bored.

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11. secret milkshake on August 1, 2006 5:22 PM writes...

Well then, come to Scripps Florida. (Jupiter/Abacoa, north of Palm Beach). The only problems is we just finished hiring (we had a couple of postdosc and few junior-level staff positions to fill and I hink these are gone already)

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12. Chris C on August 2, 2006 8:14 PM writes...


After following this blog for at least a couple of years I am concerned that the graduate school experience has left you deeply scarred. As a graduate student I can appreciate this. I just hope that in time I will be rehabilitated.

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