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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: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

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January 8, 2003

The Library of Babel

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Posted by Derek

Spent some quality time in the library at work today, digging into another aspect of a project that I'm working on. As you get deeper into the literature on a given scientific subject, some things happen over and over. There will be articles that everyone refers to, the standards that are like showing a form of ID: "Yes, you can take me seriously, because I'm referring to the big papers that everyone in this field should know about."

And there will be papers that somehow got lost in the shuffle, things that are a lot more important than they look, that no one paid enough attention to. You really have to know the field well to recognize these when you see them. And there's always a nagging doubt: "Why doesn't anyone talk about this? What's wrong with it, anyway? If it were good, people would have referenced it. . .right?" The literature-searching tools we have now are gradually giving these papers a better chance to be noticed, but if they're published in an out-of-the-way journal, they still won't get read the way they should be.

Sometimes these papers are lost more in time than in space. More than once I've found that a topic I thought was the latest rage had been anticipated years before. Sometimes the nomenclature has changed enough so that people don't realize that the earlier work is relevant, and sometimes people just don't bother looking at the old literature. A recent project of mine turns out to have relevant papers from thirty years ago, which is remarkable since the same underlying idea is still of interest. Very few modern papers reference these at all; you have to look closely.

What strikes me every time I learn more about a field, though, is how the details start resolving as I get closer. From a distance, when you don't know much about an area, the main points of it look large and chunky: Enzyme X is involved in doing Reaction Y, and it's found in tissue Z. Then as you start to get into the primary literature, all these start breaking into pieces. . .turns out there are several subtypes of Enzyme X - at least, some people say there are, but this other group says that they can't verify that. . .and it does Reaction Y, all right, but it can also do three others, one of them both in forward and reverse - seems to vary depending on the species you look at. . .and here's a paper saying that it's in tissue Z, sure, but it's a lot more important in this other organ where you can barely find it. . .and so on. All these solid rocks of knowledge start turning into mica, exfoliating into piles of complicated details.

The same thing happens when science as a whole approaches a new area. Broad ideas are all we can see at first, but further inspection is rewarded by puzzling anomalies. We may come to a point where we understand things, but the complexity just keeps on increasing the closer we look. It's like a fractal image - just when you think you can see the outline of the whole thing, you realize that those curves have tiny curves on them, which really look as if they themselves have. . .and so it goes. It's just how the world is put together. And I have to say, it would be a lot less interesting if it were easier to understand.

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