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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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January 17, 2006

Dangerous Thoughts

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Posted by Derek

Not being a world-famous scientist, I wasn't asked to contribute to the "Dangerous Ideas" festschrift (see the post below). Of course, I also don't have their founder John Brockman as my literary agent, either. . .but if his people (or any other good agents!) call, I'll definitely pick up the phone.

But I'd like to start a related discussion over here. I'm inviting comments on what people think the most dangerous idea in drug research might be. I realize that we may not all assign the same value (or even sign) to "dangerous", but let's see what happens. Update: What I mean by that is, do we call an idea dangerous because it's false, and its adoption would be damaging to drug research? Or do we mean dangerous, in the sense that it's something that's true but too unpleasant or politically difficult to face? I'll take suggestions in either category. . .

I'll start things off with this one: There are diseases that aren't worth the money it would take the treat them.

Comments (35) + TrackBacks (1) | Category:


1. NJbiologist on January 17, 2006 7:16 AM writes...

Derek, I'm surprised you didn't pick the Lipinski rules. But to me, the most dangerous idea might be that drugs should be absolutely safe.

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2. UndergradChemist on January 17, 2006 7:50 AM writes...

Perhaps something in the vein of "We should also develop agents that are actually enhancement-oriented instead of therapeutically oriented."

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3. tom bartlett on January 17, 2006 8:25 AM writes...

To Undergradchemist: we already have them; Viagra, etc. Actually, I look forward to the idea of sports, cognition, and life-expectancy enhancement. It is man's duty to correct nature's deficiencies.

It's not DRUG related, but I am disturbed by people who believe GM foods are without potential unexpected tox. I am not anti-GM food; I am anti complacency on this matter.

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4. qetzal on January 17, 2006 8:59 AM writes...

I second NJbiologist's entry, and would like to add this most dangerous corollary: that properly informed patients and their doctors can't be allowed to make their own risk/benefit decisions.

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5. RKN on January 17, 2006 9:41 AM writes...

The most dangerous idea in drug research, as we know it, is its eventual demise. There will come a day when the structure and regulation of the entire Biosome is understood to atomic detail. Gone will be the days of artificial regulation of gene products; disease will be vanquished by altering or replacing the faulty genes that would have otherwise caused it. Drugs, to the extent they are needed at all, will be designed on computers with mathematical precision on an individual basis. Statistical approximations via experiments on animals will be a thing of the past. Cancer will no longer kill millions, as the mysteries of apoptosis will be solved. Human beings, and if they choose their animal companions as well, for better or worse will live dramatically longer lives.

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6. LNT on January 17, 2006 9:51 AM writes...

Derek's dangerous idea: There are diseases that aren't worth the money it would take the treat them.

Derek, this happens all the time. My 90 year old grandmother needs a hip replacement. Is it worth the cost? To her, YES. To society, probably not. How long will she likely use that "new" hip she's going to get?
My grandfather who had a bad heart and advanced alzhiemers also had skin cancer. The doctors opted not to bother treating the skin cancer because he'd likely die of something else before the skin cancer got him.
Everyone dies of something -- and there comes a point at which the desease is not worth treating, even though we have a perfectly good treatment avaliable. It's an unrealistic expectation here in the US that everyone should live to 95 and die in thier sleep. Diseases are part of life, we'll never be rid of them completely, and unfortnuately we will always have to make judgement calls about whether the treatment is worth the cost.

I think you were likely refering to the treatment of deseases for a population that can't afford to pay for the treatment. I agree it's a dangerous idea, but it's an "idea" that has been reduced to practice for decades. How big is your "tropical disease" group at Bayer? It's nonexistant at Wyeth.

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7. schinderhannes on January 17, 2006 10:06 AM writes...

To me the most dangerous idea in drug research is to patent targets.
If this really gets going we will end up with one drug per class (and very few new drugs...)
But how often was the first drug in a class close to perfect? (O.K. maybe Omeprazol, there I don´t see any noticable benefit in newer "improved" versions).
Apart from this example there are dozens of examples where it took three or four shots to find a really good one (a good example would be the chinolones and ciprofloxacin).
BTW I don´t see this so much as a threat to pharma industry but more to patients!

Another nightmare of mine is that at some point in the near future there won´t be any unpatented druglike chemical space left :-)

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8. tom bartlett on January 17, 2006 10:13 AM writes...

" There will come a day when the structure and regulation of the entire Biosome is understood to atomic detail."

Speed that day! But I won't look at changing careers just yet.... ;)

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9. SLM on January 17, 2006 10:17 AM writes...

My Dangerous thought is; what comes next? Once we have cured cancer and HIV (AIDS), do we have stronger more resistant forms of the diseases, to a greater degree than we have now, or will we have to tackle something bigger than the two put together?
How can you start to research what you do not yet know exists?

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10. Novak on January 17, 2006 10:38 AM writes...

The most dangerous idea? That compounds which cost the greater fraction of a billion dollars to develop should, somehow, be freed from the inevitability of economic principles.

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11. Emma Jean on January 17, 2006 10:52 AM writes...

Dangerous Idea? All drugs must be blockbusters.

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12. Dr Snowboard on January 17, 2006 11:23 AM writes...

That in silico drug design and modelling can replace rather than augment chemical synthesis and biological testing.

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13. Demosthenes by day on January 17, 2006 11:25 AM writes...

Dangerous idea? That Big Pharma has to see a double digit increase in revenues every year. We're already beginning to see that this is not sustainable and companies are making poor choices in an attempt to feed Wall St.'s expectations. There is a bubble here waiting to burst once this expectation comes crashing to earth.

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14. SteveSC on January 17, 2006 11:54 AM writes...

The most dangerous idea that is false and damaging to drug research is that government should block the availability of drugs it deems unworthy.

This prevents doctors and patients from determining each individual's personal risk/benefit, leaving some (e.g., terminal cancer patients) undertreated and increasing the potential for others to be overtreated (e.g., Vioxx--if it's approved it must be safe...).

It has essentially prevented the use of concepts of continuous improvement in manufacturing. And by creating a huge bureaucracy whose decisions can kill a company, it has created an industry that lacks innovation, preferring to market the hell out of a few blockbusters than doing R&D on multiple small creative projects. R&D funds that ARE allocated go to bureaucratic busywork rather than really new stuff (why does it cost $10,000 per clinical subject?).

If we had a Federal Computer Agency to parallel the FDA, we would still be typing text commands onto a blue screen with white block letters.

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15. tc on January 17, 2006 12:00 PM writes...

Not that dangerous, but: drug researchers have gone astray in recent years by pursuing fun fads (e.g. combi-chem) instead of boring, but tried-and-true approaches.

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16. TFox on January 17, 2006 12:34 PM writes...

Here's a dangerous idea: patent rights are unnecessary, even detrimental for drug research as a whole.

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17. qetzal on January 17, 2006 12:46 PM writes...

TFox wrote:

Here's a dangerous idea: patent rights are unnecessary, even detrimental for drug research as a whole.

Probably true. Unfortunately, drug development is a very different matter.


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18. Still Scared of Dinosaurs on January 17, 2006 1:42 PM writes...

SteveSC wrote: If we had a Federal Computer Agency to parallel the FDA, we would still be typing text commands onto a blue screen with white block letters.
Why do FDA-bashers make such uninformed statements? Federal involvement in computers for the development of military and scientific applications WAS the industry at the start.
They invented the internet too, BTW.
On the other hand, prior to federal regulation the pharmaceutical industry had a long history of selling crap, often poisonous crap, for a profit. The belief that informed patients and their MDs can make suitable risk/reward decisions is predicated on adequate information being available, and that is what the FDA is regulating.
It's funny how often people who complain about the FDA inhibiting their rights to make informed decisions for themselves do so in a manner that argues against their ability to perform that objective.

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19. SteveSC on January 17, 2006 2:59 PM writes...

'Still Scared' says "Why do FDA-bashers make such uninformed statements..." and then goes on to compare the FDA to DARPA and the development of ARPANet and the early Internet. A better comparison would be comparing DARPA to NIH, since DARPA funds research, but does not prevent computer companies from marketing their products (except perhaps for super duper advanced code breaking, if you believe the conspiracy theorists ;-)

The next statement is "prior to federal regulation the pharmaceutical industry had a long history of selling crap...for a profit." The scare term 'profit' is a red herring, since I doubt it would make much difference to anyone if 'crap' was being sold for a loss. And although Federal regs have inhibited sales at legitimate pharmaceutical companies (although we all know some crap gets through anyway), it has done essentially nothing to keep crap in general off the market. It is just now sold as 'dietary supplements', or 'nutriceuticals', or 'ancient Chinese herbs', etc.

Finally, the assertion is made that the FDA is regulating only the availability of "adequate information" to "make suitable risk/reward decisions." If this was indeed the case, the FDA would be a much less pernicious force. Estimates are that over 50% (some up to 70%) of all medication usage is 'off-label', used for non-FDA approved indications. The FDA does regulate how pharmaceutical companies can use such information in advertising, but does not significantly interfere with physician's ability to evaluate the risk/benefit to a particular patient. For the most part, adequate information is developed and shared by academic researchers. A system somewhat similar to this could be used to allow new drugs on the market also.

I agree with 'Still Scared' that the FDA is a dinosaur. I also think a lot of innovative drugs and research are squashed underfoot as it thrashes around trying to eliminate all political risk.

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20. tom bartlett on January 17, 2006 3:40 PM writes...

The FDA IS a dinosaur, keeping good stuff off the market too long.

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21. Milo on January 17, 2006 4:42 PM writes...

This may not be the most dangerous idea to pharma, but the idea of discarding potential compounds because of assumptions can't be good. By assumptions I mean: high IC50 in an in vitro assay translates to low in vivo efficacy, or, a half life in rats of 5 minutes translates to a half life in man that is too short. I realize everything can't be tried in man, I just worry that we are throwing a lot of good compounds away.

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22. Daniel Newby on January 17, 2006 5:47 PM writes...

Dangerous idea: That personal financial interest is bad.

A previous commenter's comparison between DARPA and NIH is apt. Many types of DARPA proposal are required to include a commercialization plan, basically the PI's wildest dream about people throwing fistfuls of money at him for the product. (If nobody else will ever pay for the discoveries, why should DARPA?) Contrast this with NIH, where apparently the PI's goal is supposed to be "live like the civil service version of a grad student, forever". The DARPA Grand Challenge winners are thinking about where to invest their prize, while NIH folks are thinking about which investments to liquidate so they won't get locked up on "ethics" charges. Who would you rather work for?

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23. Chris on January 17, 2006 8:41 PM writes...

Dangerous idea:

The human lifespan will never exceed a hundred and twenty years for any large segment of the population, even in first world countries. The ‘cure for cancer’ will never be found. Sure, some types will become easily prevented, but there will be no effective therapy that works on the general features of cancers (angiogenesis, disabling apoptotic pathways, etc).

Cancer treatment will probably improve to the point that general mechanical failure is just as likely to kill you. We will discover that human beings, like very well designed cars, reach a point where everything fails at pretty much the same time.

I really hope I’m wrong about that this one.

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24. virtualhealth on January 18, 2006 12:21 AM writes...

Dangerous idea: If governments/pharmas really wanted to help patients, they would prohibit/stop marketing of drugs and require/do valid clinical comparison trials (best dose of each agent).

Individual pharmas wouldn't do this on their own as they'd lose ground against their competitors. The government would have to step in (like they required insurers to cover for their missteps on Medicare). Of course then fewer drugs would be sold, and a lot of conference organizers, journal publishers, and other organizations would need to find replacement funding.

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25. marcus newberry on January 18, 2006 7:29 AM writes...

That the FDA should consider social implications of drugs in the approval process.

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26. robopox on January 18, 2006 7:35 AM writes...

Infections are less important than erections.

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27. Jeff Bonwick on January 18, 2006 8:10 AM writes...

... but I'll take a hard-off if you get this lard off!

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28. Still Scared of Dinosaurs on January 18, 2006 9:32 AM writes...

"it has done essentially nothing to keep crap in general off the market. It is just now sold as 'dietary supplements', or 'nutriceuticals', or 'ancient Chinese herbs', etc."
Well the FDA has requested the authority to regulate these products also, or at least the claims made for these products, and has been denied. Can't blame them for that.

"The scare term 'profit' is a red herring, since I doubt it would make much difference to anyone if 'crap' was being sold for a loss."
No, if the sales don't generate profits they'll stop before anyone notices-that's the only form of self-regulation that actually works in the private sector.

If companies can't provide a compelling case for how their drugs are to be used then let them go out of business. Less competition for me. And in the overwhelming majority of my interactions with FDA I've found them to take a hard but justifiable line on what they want. I've seen a lot more innovation squashed by corporate infighting and senior execs who replace leadership with decision making.

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29. Kay on January 18, 2006 9:39 AM writes...

1) I second Milo's opinion above.
2) Pfizer's situation is sustainable.
3) Prescribers have the knowledge to choose unapproved therapies.

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30. Sigivald on January 18, 2006 1:02 PM writes...

The most dangerous idea in drug research is that trained wolverines can cure anything.

Fortunately, this idea is not widely held and probably never will be.

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31. Defensive Michigander on January 18, 2006 6:16 PM writes...

Hey, c'mon, Sigivald--trained Wolverines have been curing just about anything and everything since before Jonas Salk arrived in Ann Arbor.

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32. PS on January 18, 2006 7:31 PM writes...

Now if only the wolverines could win a meaningful football game!

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33. SRC on January 18, 2006 11:35 PM writes...

Another nightmare of mine is that at some point in the near future there won´t be any unpatented druglike chemical space left :-)

Fear not. Wait 20 years - then it'll all be in the public domain.

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34. SRC on January 18, 2006 11:37 PM writes...

My contribution for the most dangerous idea: that there's something more important in life than merely extending it.

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35. Joss Delage on January 24, 2006 3:14 PM writes...

My Dangerous thought is: "Free healthcare for all"

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Listed below are links to weblogs that reference Dangerous Thoughts:

Dangerous ideas in science from Kristofer's computational biology blog
Very cool article, What is your dangerous idea?, in the Edge. The history of science is replete with discoveries that were considered socially, morally, or emotionally dangerous in their time; the Copernican and Darwinian revolutions are the most obv... [Read More]

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