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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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October 16, 2007

Three Things You Need

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Posted by Derek

Scientists who’ve spent a lot of time in research labs will have noticed that self-confidence seems to pay big dividends. If you think back to the people you’ve worked with who got the most things to work (especially the difficult things), you’ll likely also recall them as people who set up experiments relatively fearlessly, with expectations of success. Meanwhile, the tentative, gosh-I’m-just-not-sure folks generally compiled lesser records.

You can draw several conclusions from these observations, but not all of them are correct. For example, a first-order explanation would be to assume that experiments can sense the degree of confidence with which they’re approached and can adjust their outcomes accordingly. And sometimes I’m tempted to believe it. I’ve seen a few ring systems that seem to have been able to sense weakness or fear, that’s for sure, and other molecular frameworks that appear to have been possessed by malign spirits which were just waiting for the right moments to pounce.

But besides being nuts, this explanation is complicated by the few (but statistically significant) number of confident fools who thing everything they touch will work, no matter how ridiculous. These people tend to wash out of the field, for obvious reasons, but there’s a constant trickle of them coming in, so you’re never without a few of them. If self-assurance were all you needed, though, they’d be a lot more successful than they are.

No, I think that confidence is necessary, but not sufficient. Brains and skilled hands are big factors, too – but they aren’t sufficient by themselves, either. You need all three. Most people have them in varying quantities, of course, but you can learn a lot by looking at the extreme cases.

For example, I’ve seen some meticulous experimenters, not fools, who were undone in the lab by their lack of the confidence leg of the tripod. Their tentative natures led them to set up endless tiny series of test reactions, careful inch-at-a-time extensions into the unknown. This sort of style will yield results, although not as quickly as onlookers would like, but will probably never yield anything large or startling. Still, you can hold down a job with this combination, which is more than I can see for the next category.

Those are the confident fools mentioned earlier, who lack the brains part of the triad. They get involved in no-hope reactions (and whole no-hope lines of research) because they lack the intelligence to see the fix they’ve gotten themselves into. The whole time they essay, with reasonable technical competence and all kinds of high hopes, experiments which are doomed. As I said above, these people don’t necessarily have such long careers, but in the worst cases they can pull others of similar bent in their wake (while their more perspicacious co-workers leave, if possible, when they catch on to what’s happening).

Then there are the folks who lack the skilled hands. “Lab heads,” I can hear a chorus of voices say. “These are the people who become lab heads and PhD advisors.” There’s a lot of truth to that. Plenty of people can have good, bold ideas, but be incapable of physically carrying them out at the bench. Even controlling for age and lack of experience, there are plenty of Nobel-caliber people you wouldn’t want near your lab bench. Some of them are out of practice, but many of them were just as destructive when they were younger, too. Surrounded with good technicians, though, they can do great things. Many just face facts and confine themselves to the blackboard and the computer screen.

But if you have reasonable amounts of all three qualities, you’re set up to do well. Confidence is perhaps the limiting reagent in most natures, which is why it stands out so much when it’s combined with the others. A scientist with a lot of nerve is more likely to discover something big, and more likely to recognize it when it comes, than someone who undervalues their own abilities. They’re more prone to setting up weird and difficult experiments, knowing that the chances of success aren’t high, but that sometimes these things actually come through. That’s probably the source of the correlation that I lead off this post with: it’s not that confidence makes these ideas work. Rather, if you don’t have it you probably don’t try many such things in the first place.

Comments (19) + TrackBacks (0) | Category: Who Discovers and Why


1. Milo on October 16, 2007 7:10 PM writes...

Confidence is paramount. It can also be the most fragile of the three legs. I have seen many people myself included, lose a great deal of confidence because of a poorly phrased or timed remark by a superior. But, confidence is also one of the few things that one can gain over time. People with bad lab hands tend to forever have bad lab hands.

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2. Polymer Bound on October 16, 2007 7:41 PM writes...

It took me a long time to realize that it wasn't me causing the reaction to not work and that it was the bloody reaction conditions I was trying. It wasn't until I got to grad school that I realized that no amount of care and argon purging will make a flawed idea work.

Now I'm a vial on a hotplate cowboy and I've never been so productive.

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3. LNT on October 16, 2007 9:02 PM writes...

Plenty of people have good ideas -- ideas are a dime a dozen when you are amoung a bunch of smart chemists. In my mind, what separates the "wheat from the chaff" is the ability to get your hands dirty and actually TRY some these ideas and prioritize the ideas based on thier probability of success.

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4. psi*psi on October 16, 2007 9:42 PM writes...

A bad project can kill off confidence very effectively. My first project was miserable--I was shocked when I started on something better and discovered I wasn't a total screwup.

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5. katre on October 16, 2007 10:05 PM writes...

Hey, #3, that's me. I was a mess in the lab, back when I was in the lab. Got smart and switched fields to an area where being terrifically uncoordinated doesn't cause hundreds of dollars of damage a week, and I bet everyone (including my former advisor) is happier!

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6. Dangerdog on October 16, 2007 10:54 PM writes...

Looks like I have a mixture of all three qualities. Usually I follow the rule "if the boss (those lacking skilled hands) says don't do it, it won't work" I do it anyway.
Has several reasonable results that way.

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7. milkshake on October 17, 2007 1:29 AM writes...

You need a mix of people with different level of experience and personality types on the project. The most gifted people often get bored or frustrated easily. You need enough chemists on the team that are steady and unflappable and they push the project and crank out compounds when most their colleagues bang their head against the wall in despair. Then you need the starry-eye high-energy novice and also the jaded types that know everything but most of time do nothing (the activation barrier for setting an experiment often grows with experience). Most importantly you need pleasant considerate personalities, you cannot afford to have rivalry and competition within the team or in the lab. You also need generous boss that is not too pushy but has subtle way to motivate people when the morale goes down.

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8. lone electron on October 17, 2007 6:53 AM writes...

I think you left off one last characteristic: Drive. I worked with someone that has all three of the features you described but spent most of his time messing around outside of the lab. The few reactions they did worked great, but they were still few.

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9. Derek Lowe on October 17, 2007 7:29 AM writes...

Lone, that's a good point, and worth a lengthy post of its own. "Drive" is a hard quality to define, and it does seem to be orthogonal to those others. But without it you're sunk. . .

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10. Monte Davis on October 17, 2007 9:21 AM writes...

...knowing that the chances of success aren’t high, but that sometimes these things actually come through

The scientific eminences I've known (theorists as well as experimenters) have often cited as the essential gift the ability to assess that balance -- to select a target risky enough to be interesting, but still do-able. Unfortunately, like the gift of balancing risk and ROI in finance or anywhere else, at the highest levels it's hard to formalize or teach, and they end up talking of experience, art, tacit knowledge, fingerspitzgefuhl.

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11. S on October 17, 2007 9:32 AM writes...

Wonderful post! Absolutely fantastic timing as well. I am going through the "utterly abysmal" portion of my project currently.Reading this and the comments gives me hope.

Cannot agree with you more. I remember what a boost of confidence and energy it was to work on something totally new, even if it was just for a while before heading back to the grunge.

Mix of people is good. I work alone on my projects. And sometimes that it just PAINFUL.

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12. Green Koala on October 17, 2007 10:49 AM writes...

I'd add another one: efficiency.

I've seen bright, skilled, confident medicinal chemists either pokey-butt their way though an idea while not trying other alternatives or try too many things at once with the shots-on-goal mentality, only to show little progress in the end.

As a corollary, as mentioned by a previous poster, the ability to prioritize and focus seems to go hand-in-hand with an efficient chemist.

One of the most prolific colleagues I've ever had, both in synthetic/medicinal chemistry while on the bench and in driving programs into the clinic, was the most efficient person I've ever come in contact with. This was someone who worked an 8 hr day, took a set time for lunch, got chemistry done, had good chemistry and med chem ideas, and executed them. He listened to people around him and interacted well with colleagues BUT he had absolutely no time for bs'ing, he blew off people he thought were knuckleheads, he focused on getting the job in hand done - not just pleasing the bosses, and he minimized his time on corporate crap (think about any committee you were volunteered for in large pharma).

I learned not what to do, but how to do your job from just watching this guy. He had faults, but they tended not to affect his performance.


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13. CMC guy on October 17, 2007 11:11 AM writes...

I would offer patience/persistent although may be intertwined with personal drive element.

I agree whole-heartily with milkshake that often a balanced group can collectively combine to create atmosphere so all can achieve. Unfortunately in grad school tendency is much more toward loner approach (as S indicates) rather than a team project however if you are surrounded by good group/department can get support (isn’t that what Friday night happy hours are for?).

My advisor was a “that will never work” type so indeed we attempted to prove him wrong. On the other end I also had a boss who would try anything/everything regardless if it made sense which was exciting although failure was an acceptable option.

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14. Betsy on October 17, 2007 1:19 PM writes...

I agree with Green Koala that efficiency and knowing your priorities is also key. I once heard a prominent biologist say that the most important thing you can learn in your training is what NOT to do. You've often got a million ideas and things you want to test, but the smart people can sift through those and focus on the things that are most important.

I disagree that people with bad lab hands are on track to become PhD advisors. In the ultra-competitive world of academic research, if you're not good at the bench, you're not going to produce, and you won't get a tenure-track position. I agree that many advisors would do best to stay away from the lab, but I think that's a trait they develop AFTER they've gotten the job.

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15. Canuck Chemist on October 17, 2007 3:04 PM writes...

Green Koala:
Regarding your prolific colleague, was his efficiency properly rewarded with promotions? Or was he at a disadvantage at some stage to corporate butt-kissing types? Just curious... In general, I wonder how scientists who are ambitious and looking to move up the corporate ladder are treated if they are also extremely productive on the bench. Why promote someone if they are cranking out compounds?

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16. Chuck McKay on October 17, 2007 7:38 PM writes...

"undone in the lab by their lack of the confidence leg of the tripod."

Beautifully stated.

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17. Green Koala on October 18, 2007 11:48 AM writes...


No, he has been properly rewarded. It was obvious to management and his colleagues that this guy was someone you wanted to keep. He received and continues to receive proper recognition and compensation from the company, both in resposibilities, promotions, and flexibility certain aspects of the job.

It's been a win-win for everyone; however, he's probably starting to ceiling-out due to politics.


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18. Gibbie on October 18, 2007 4:14 PM writes...

Confidence is hard to come by when you are crushed by the weight of your own stupidity.

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19. Boger on October 18, 2007 11:30 PM writes...

"I think you left off one last characteristic: Drive. I worked with someone that has all three of the features you described but spent most of his time messing around outside of the lab."

You guys are seriously bent. You are lab technicians with dwindling prospects. In twenty years robots and 3rd world slave labor will do most of what you suggest others should WASTE WASTE WASTE their limited lifespan on. I see it time and again. People get seriously brainwashed in grad school then spend the rest of their lives pushing their BS vision of 'extreme work ethic' on others.

Get a life already. You're one step away from lettuce pickers.

The market has spoken.

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