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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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January 31, 2005

Does Your Labmate Have the Hands?

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Posted by Derek

How do you know if someone's a good chemist? For now, I'll restrict that to "good bench chemist", because that's hard enough to answer on its own. People can put up a surprisingly good front, but there are some things to watch out for.

Knowing things like name reactions is just as often a blind as a good indicator. Those are a charmingly antiquated part of organic chemistry where reactions are referred to by their original discoverers (or popularizers, in some cases.) So you have ancient classics like the Dieckmann condensation or the Williamson ether synthesis, both of which are still in use every day of the week despite their 19th-century pedigrees, and more modern ones like the Suzuki coupling or the Heck reaction. There are scores of these things - one of these days I'll go on about them some more - and they're a semi-beloved, semi-loathed feature of all introductory organic classes. It's nice to have a good familiarity with them, because many of them are quite important, but name-dropping can also be a noisy distraction that tyros use to hide their other deficiencies.

Being quick with ideas and mechanisms up on the blackboard is usually a good sign, but not being so isn't always a bad one. Some people think differently than others, and at different paces. There are always people who need to go look out the window for a few minutes before coming up with the answer. The biggest quick-draw artists I've seen with blackboard reaction pathways have clustered at the top and bottom of my personal rankings. They were either very good chemists indeed, or that was about the only thing that they were good for.

Productivity at the bench is harder to fake, but it can be done in some cases. In the early days of combinatorial chemistry, some folks would hit on an easy-to-extend series of analogs (often by working out some handy way to set up and purify the reactions faster than usual), and run these out to impressive lengths to wow the onlookers. Back in the early 1990s you could really impress folks by suddenly turning in, say, 112 sulfonamides all at the same time, but now it's become a bit more commonplace. But being able to produce that many compounds means that you're at least fairly hard-working and organized, traits not to be underestimated.

One thing to watch is whether a person's chemistry can be duplicated by anyone else, and how good they are at duplicating things in turn. If someone consistently gets lower yields or messier products than other people running the same kind of thing, it's probably a warning sign. And if no one else can get a person's reactions to work as well as they did originally, it's almost always a red flag. It's very rare that someone has such consistently good hands that they always get higher yields. More likely, they're pulling the wool over your eyes, or over their own as well.

If you have a very green chemist coming into a lab - say, a summer undergrad or a first-year graduate student in academia - there's a foolproof way to test their bench skills. Have them reproduce a preparation from Organic Syntheses. That's a series (over 80 volumes worth) of useful procedures in organic chemistry. They're either preparations of particularly useful intermediates or illustrate new reactions and the preferred ways to run them. They're more detailed than the standard writeup in a chemical journal or patent (especially some patents I've seen), and they're checked by another research group entirely, with their comments appended. They're completely foolproof, and if you find someone who can't get one to work, odds are that you are, in fact, dealing with a fool.

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


1. Tony on February 1, 2005 2:11 PM writes...

Derek, you are right on with your analysis. By my 4th year in grad school, I could easily identify the good prospects from the bad. It mostly had to do with how committed they were to their research. If they were attached to the bench at 11:30 at night and back by 9:00 the next day, then it was a good sign that they liked to do the work. The pretenders thought that grad school was a 9-5 job. You have to love to do your work to be a good bench chemist. In pursuit of this daytime-only work regimen, these students missed out on the real drive and focus that many of us in the afterhours knew so well. Not that I subscribe to this lifestyle today. I paid my dues and have learned to use my benchtime wisely and efficiently through all my years of sleep deprivation and practice for presentations and meetings.

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2. D Henkel-Wallace on February 1, 2005 4:45 PM writes...

Another good sign: are they completely open? For one example: consider your case of the guy with "really good hands" -- better than anyone else. If he is really enthusiastic about showing others _what_ he does (not just the results), basically trying to help others do what he does, then that's a great sign.

The second is how open you are to ideas from others. Yesterday I was visiting a couple of friends. We have been puzzling over a curious (non-work) thermodynamics problem for a few weeks, making slow but steady progress whenever we get together. They had a visitor, and he was interested in the problem. He began to think out loud, throwing around the lingo quite confidently. That's a good process. But when he ran into a wall he wasn't very good about recognizing it, and when we pointed out ratholes (after all we all fall into them from time to time) he wasn't good about looking for other avenues but would just stick to what he was saying.

Frankly the best people are the most fun to work with. And the ones who are the most fun to work with are often also the best.

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3. qetzal on February 1, 2005 6:31 PM writes...

What about just watching over someone's shoulder as they set up and run various reactions?

My doctoral training was in mol biol, and "good hands" matter there as well. I've found one of the big challenges is trying to figure out if a potential new hire has good hands.

Once, several years ago, we hired a new person into our mol biol group. She had a good resume, interviewed well, had some co-authorships, and had a strong recommendation from her previous boss in academia. (She wanted to move to industry.)

We all agreed she was the best candidate, and we hired her.

It was a disaster. Turned out that she had the opposite of good hands. Most of her experiments didn't work. Even simple things like restriction digests often failed. Her direct line manager (who reported to me) started observing her more closely in the lab, and quickly saw that her technique was just really poor. She did the right steps in the right order, but clearly hadn't learned all the minor little tricks that make everything work smoothly. Hence her inability to generate good data.

She left shortly thereafter, so we needed to refill that position, but we didn't want to repeat our previous mistake. So, we decided to have the next batch of candidates go through a few simple tests.

First, they had to solve some simple job-related problems. As I recall, one was as basic as how to prepare a working solution at some desired concentration, given a known stock solution. Others were more open-ended; something like, "You are trying to develop a new PCR protocol, and you have encountered the following problems. Describe the experiments you would do to solve them."

We only tested candidates who passed the screeing interview and had good resumes with several years bench experience. (We warned them of the test before they came to interview in person.) Yet, even though most of the questions were quite basic, several candidates did surprisingly poorly.

The second half of the test was hands-on. We sat each candidate at fully equipped bench. Then we asked them to set up a common enzymatic reaction. We made sure everything they needed was available, answered any questions they had (just like you would for a current employee), and then we just watched their technique.

It was amazing how informative that was. Some candidates who did perfectly on the written problems had obvious flaws in their technique. One candidate performed very well on both parts of the test, but was very resentful that we felt the need to supervise their work. (Not a good quality in drug development!) We hired the candidate who did well on paper and at the bench, and who didn't get defensive or confrontational about the whole thing. He turned out to be a great employee.

All in all, it was a very valuable learning experience for me. I realize it's often impossible to take this sort of approach, but I highly recommend it where possible.

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