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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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April 18, 2004

The March of Folly Leader Board

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Posted by Derek

The first comment to the original March of Folly post below mirrors the e-mail I've received: the people's choice for the technology most-likely-to-be-embarrassing is. . .(rustling of envelope): RNA interference.

There's a good case to be made for that, and it doesn't contradict my oft-stated opinion that RNAi is going to be good for one or more Nobel prizes. The big challenge will be how to divide things up correctly - we may well see some spillover into Chemistry from the Medicine/Physiology category. Believe me, there are several folks who should keep their eyes open for discount fares to Stockholm. This will probably happen in about five years or so, given the usual pace of the Nobel folks.

But industrial enthusiasm for RNAi may well have gotten out of hand in the last year or two. There are a number of small companies frantically trying to take the technique into the clinic; the whole thing reminds everyone of the heyday of antisense therapeutics. Remember antisense DNA? People are still out there trying to make it work, but it's been a lot harder than anyone would have wanted to believe. If you'd been able to show folks the future back in the late 1980s, a bunch of venture capitalists would have had rug-biting fits.

And RNA-based therapies suffer from almost exactly the same problems, and for the same reasons. Delivery of the molecule and its stability once dosed are going to be very tricky. One of the first things being targeted is macular degeneration, because the inside of the eye is a rather tranquil pond, pharmacokinetically speaking, and the cells there are known to take things up rather freely. But once you get out of that best-case situation, well, good luck. With any luck, RNAi might be able to adapt a successful antisense technique - if someone finds one.

Comments (5) + TrackBacks (0) | Category: Drug Development | Drug Industry History | Pharmacokinetics


1. mike on April 18, 2004 11:33 PM writes...

i beleve the only approved indication for an anti-sense drug is still for herpes simplex virus retinitis given by intravitreal injecton

also besides the retina being a tranquil pond pharmacokinetically it is a relatively accessable site-

I know there has been some little success in
crohn's disease but even if this is successful it is still slim pickens after all these years

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2. Klug on April 19, 2004 12:42 PM writes...

That antisense DNA comment reminds me of the summer before my high school senior year (1993), where I was at a conference for science interns. We were assured by a molecular biologist that antisense DNA was going to cure HIV and that they simply had to determine how to get it into the cell.

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3. David on April 19, 2004 1:15 PM writes...

Antisense is a classic case of biologists selling a good one to venture capitalists without ever having the critical eye of a pharmacology guy look at the technology.

You could just look at the molecules Isis was trying to make work and know it was never getting into a cell. Period.

I have a bit more hope for 2nd and 3rd generation antisense where the drugs are greasier and more likely to make it inside the cell. We'll see. There will be no great revolution though--it'll be like antibodies. Some will work, some (most?) won't.


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4. mike on April 19, 2004 11:43 PM writes...

This is my second comment but how about Hemoglobin based blood substitutes as a folly-if they are given quickly they bind NO and cause deleterious effects particularly-constricton of the pulmonary vasculature-

If they are given slowly-why do you need them?
They been in development since the late 80's

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5. Derek Lowe on April 20, 2004 9:35 PM writes...

Y'all have suggested some worthy candidates, all right. It's to the point now, though, that people start to roll their eyes at any word that ends in "omics", so I don't know if proteomics will blow up into quite as big a bubble.

I like that line about just having to figure out how to get the antisense into the cell. And if that molecular biologist had some ham, he could make a ham sandwich, if he had some bread.

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