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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: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline

« Needs and Wants | Main | The Old Stuff »

October 10, 2005

Time and Chance

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Posted by Derek

A recent comment here says:

Scientific progress, ie medical breakthroughs, are just as likely to come through dumb luck or chance as from having the most briliant mind thinking about them. Its about having larger numbers of scientists working, rather than having larger numbers of "smart" people working. In some respects, it might be better to have more people who are not all that careful, ie, more accidents = more progress."

I know what this person is trying to say, but I think that this is only about half right. I'd be the last person to minimize the role of chance in scientific discovery. It's not something that everyone likes to talk about, or sometimes even admit to themselves, but it's true. People get ideas from all sorts of places. If you didn't pick up the journal article that you did one day, or talk to the right colleague, or just look out the window at the right time, you might not have had the ideas come to you that later on looked so inevitable.

But that said, bringing in more people to have accidents is a little like washing your car to make it rain. The problem is, you need accidents and you need people who know what they're looking at when they happen. The kinds of people who slop around the lab the most are, sad to say, often the ones who don't realize when something big is happening right in front of them. What you'd want is to find some Alexander Flemings, people who are meticulously messy. Pasteur was absolutely right about fortune favoring the prepared mind.

Comments (9) + TrackBacks (0) | Category: Who Discovers and Why


COMMENTS

1. Still Scared of Dinosaurs on October 11, 2005 2:41 AM writes...

Real Science, science that matters, is often not about finding answers but recognizing the questions that are themselves important regardless of what the eventual answers might be. “Can I get it to work?” rarely qualifies, and “Can I stumble across a way to get it to work?” rates a lot lower. A number of recent posts here have dealt with an issue that I always find interesting, which is the decision between pursuing some idea at the risk of finding it a dead end versus passing on it and wondering if something was really there (or watching someone else credited with having pursued it). Statisticians call these, respectively, Type I and Type II errors and I find people balancing them all the time without expressing it as such. If you pursue every chance oddity because it might lead to something you run the risk of following up on other things that you boss put on your to-do list because they might also lead to something. All too often the “value” of pursuing the question depends on what the answer turns out to be, but instead of thinking about the few cases where big discoveries hinged on chance think of all the diligently and efficiently derived answers that equated to “Nope” or its maddening variant “Not in my lifetime because of…”. If the question was Something Science Needed to Know then the pursuit was worth it.

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2. Grubbs the cat on October 11, 2005 3:14 AM writes...

What I am really missing in the pharmaceutical industry is the 'commitment to the unexpected'. I guess in the majority of companies the high-level management believes that every project should be pursued using only rational arguments.
How many medicinal chemists feel encouraged (by their management, not by their curiosity) to isolate and submit every side-product of their reactions to give chance a success?

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3. LNT on October 11, 2005 8:35 AM writes...

Grubbs the cat,
I feel free to isolate side products and pursue my own ideas if I so choose. However, virtually every chemist here realizes that "the clock is ticking". Management only gives a finite period of time for each project before it is axed. (here, about 2 years) Should I spend my limited time pursuing side reactions or making molecules that we are relatively certain will be active? I try to keep an "80:20" balance -- about 80% of my time is spent pursuing my primary lead series while I spend about 20% of my time on my own stuff (side reactions, new scaffolds that fall outside our patent, etc.).

Permalink to Comment

4. Tom Bartlett on October 11, 2005 8:57 AM writes...

Was it Einstein, Sherlock Holmes, or someone else who said: "Chance favors the prepared mind." I have discovered some cool stuff by "accident". My current project is an example. But, you have be pretty observant and analytical to bring your baby home.

Permalink to Comment

5. weirdo on October 11, 2005 9:31 AM writes...

>

Managers who do not encourage such scientific curiosity should be fired. Period. To not turn in by-products (or intermediates, for that matter) because they weren't the "target" molecule is just plain stupid. If you know so well what you should make, just make the clinical candidate first, why don't you?

This type of thinking drives me nuts. As do mass-gated mass specs and biologists who want some kind of justification for running new molecules that "look funny" through primary screens.

Permalink to Comment

6. jim on October 11, 2005 11:02 AM writes...

It seems to me that if you're in a situation where any side reaction or other whim deserves just as much effort as something in the lead series, then the hypothesis behind the lead series isn't that strong. I'm not saying that other curiosities shouldn't be tested, but there has to be a process behind the whole thing- the time for throwing everything at the wall to see what sticks is early on, and may not be appropriate later.

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7. Morten on October 11, 2005 1:53 PM writes...

I prefer when people defect from the hypothesis out of sheer laziness - then they actually know what it was that unexpectedly worked. And they'll go back and do it again right if it doesn't work.

Permalink to Comment

8. JSinger on October 11, 2005 3:50 PM writes...

Back to the original question...

Towards the end of grad school, I started noticing how most of the big-shot PIs (both senior big-shots and new professors coming off a flashy paper in Cell) who were fawned over by everyone else, didn't seem to produce all that much better than anyone else. Given the advantages they held -- the pick of grad students and postdocs, more grant money, an edge in publishing -- they still didn't do all that much.

There are exceptions, certainly, but on the whole I've grown significantly less impressed by big names as time has passed.

Permalink to Comment

9. weirdo on October 11, 2005 5:53 PM writes...

Precisely my point. Hypotheses cannot be proven. They can only be tested and disproven. When one decides to only submit molecules that one expects to be active, one stops being a scientist.

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