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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

In the Pipeline

« Osmium Tetroxide, Of All Things | Main | Reality's Revenge »

April 13, 2004

It's a Bacterial Planet, You Know

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Posted by Derek

You've probably heard of the hypothesis that a reasonable amount of dirt is good for you, especially in childhood. (My kids are certainly taking no chances.) The idea is that the immune system needs a certain amount of challenge to develop properly, so trying to live too antiseptic a life is a mistake. I think that this is very likely correct, and it turns out that it's especially correct if you're a zebrafish.

Not many of my readers are zebrafish, at least as far as I can tell from my referral logs, but they're an influential demographic. Danio rerio isn't as well known outside biology as say, the fruit fly, but it's a workhorse model organism for vertebrate development. Zebrafish are small, fast-growing, and the embryos are nearly transparent in their earlier stages. (Xenopus frogs share these characteristics, and have their partisans, too.)

The March 30th issue of the Proceedings of the National Academy of Sciences, with a Warholian zebrafish cover, features a study from Washington U. where the fish were raised under strictly aseptic (gnotobiotic) conditions. That's not easy to do, but if you make absolutely sure that no bacteria are present, it turns out that the embryos don't even develop properly. The defects are in the gut, which makes a lot of sense.

It turns out that colonization by normal intestinal flora is vital - zebrafish and their bacteria have become evolutionarily entangled. The bacteria actually induce some crucial gene expression by their presence, and the developmental program just doesn't have an aseptic default setting. There hasn't been an aseptic zebrafish since the beginning of biological time.

OK, these guys swim around in tropical pools, floating in a bacterial soup. But we're floating in one, too, just at a slightly lower density. Every part of a human body that can be easily (benignly) colonized by bacteria already is. Are there similar developmental effects in man? It wouldn't surprise me at all. No one's going to be running that exact embryo experiment, needless to say, but there are probably ways to sneak up on the answer using cell cultures. There's never been an aseptic human baby, either. . .although this is enough to make a person wonder about situations where a pregnant mother has had to take a long course of powerful antibiotics.

Comments (0) | Category: Biological News | Infectious Diseases


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