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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

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December 28, 2011

Nowhere to Go But Up?

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Posted by Derek

I wanted to let people know that I've got a "Perspective" piece in ACS Medicinal Chemistry Letters, entitled "Nowhere to Go But Up?". The journal is starting to run these opinion/overview articles, and contacted me for one - I hope it's the sort of thing that they were looking for!

Comments (38) + TrackBacks (0) | Category: Drug Industry History | The Scientific Literature


COMMENTS

1. LegacyMerckGuy on December 28, 2011 1:33 PM writes...

I liked the article Derek. Even though I know your stance on the Chindia thing, I thought that you wrote a rather non-argumentative commentary. Although I would have liked to have seen you take a shot at the crazy business models that are supposedly saving money but that's just me.

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2. John on December 28, 2011 1:36 PM writes...

Derek,
I would insist on a dual-listing in the future [med chem, Vertex; author, In the Pipeline], and blog/personal email. Lifetime employment is dead, and employee rights in the US are marginal. Nothing should be passing through your corporate email except directly work-related matters.

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3. LegacyMerckGuy on December 28, 2011 1:57 PM writes...

That is a good point John. Really good point. You never know if you're going to be the next person that they can't "place" in the organization.

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4. LegacyMerckGuy on December 28, 2011 2:00 PM writes...

That is a good point John. Really good point. You never know if you're going to be the next person that they can't "place" in the organization.

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5. PharmaHeretic on December 28, 2011 3:59 PM writes...

Nowhere to go but up- through the smokestacks?

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6. jackass on December 28, 2011 4:22 PM writes...

Medicinal Chemistry in the west is a dying profession.

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7. Nick K on December 28, 2011 4:30 PM writes...

Good article, but I still feel you missed an opportunity to discuss the fundamental malaise in Pharma, namely the broken and increasingly unworkable business model. The huge contraction and retrenchment of Big Pharma since 2000 is merely a reaction to this underlying reality.

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8. Anonymous on December 28, 2011 7:25 PM writes...

As a graduate student, the suggestions you give for what Medicinal Chemists could contribute to Biologics is kind of funny. At least in my department, and I'm guessing in many others based on my conversations at conferences, labs that do those types of Chemistry are considered by the "real chemists" to be Biochemists, which obviously no self-respecting chemist would want to be. At least that's the attitude I seem to sense. Also, I don't think most of the modifications you list really require a synthetic guru to accomplish.

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9. TX Raven on December 28, 2011 8:42 PM writes...

Derek,
Just out of curiosity: was this article peer-reviewed?

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10. clueless on December 28, 2011 8:56 PM writes...

what a shame

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11. milkshake on December 28, 2011 9:53 PM writes...

1) The big pharma got taken over by zombies. It has been a lively spectacle while they were infecting and devouring but now things are slowing down a bit, with fewer undead shambling around in dark streets. Give them 20 more years and they will starve out eventually. (And don't ask where did the brains go).

2) Bio-related work has limited attraction to organikers - it is a yawn to work with plates, eppendorf tubes and pipetors. But there is one notable exception: Polymer chemistry applied to medicine. Synthesizing polymers with narrow PDI and high purity, tailor-made for drug delivery is actually quite hard. Polymer chemists sometimes employ elaborate Schlenk-like setups, are obsessive about starting material purity and work under strict air-free conditions that would be perfectly at home in an organometallic lab (rather than medchem group). There is a lot of interesting process techniques that synthetic chemist can learn from polymer dudes. And since the polymer chemists might have a somewhat narrow specialization, they can benefit from having organikers with medchem background working with them. So my suggestion, if you are a looking outside the medicinal chemistry, is to go to biopolymers and material science. Idrally a project that combine biology, small molecule drug formulation and polymer process chemistry.

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12. anon2 on December 28, 2011 10:21 PM writes...

To Anon #8, don't let your ego get in the way. Derek is suggesting that you are more capable than other applicants(if you get your mind right). This puts you in a rather enviable position, if approached correctly at an interview. Consider the person hiring you has less(or different) training and more success. Do you really want to send the message that you think you are overqualified for his/her job.

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13. Anonymous on December 29, 2011 1:06 AM writes...

I think my previous post came off wrong. My background isn't in a typical organic lab, but one where we do a lot of protein modification. I guess I was more amused by the article because most of the synthesis people I know have a major bias against people who work with biomolecules. Maybe people in industry are more openminded and don't consider people with backgrounds in chemical biology "lesser chemists". I do worry sometimes however that my background will cause problems with people thinking that since I'm not an expert in a particular field my multidisciplinary background will cause problems with employment.

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14. anonymous on December 29, 2011 9:30 AM writes...

Derek:
Regarding your statement "This means that the best advice is not to be ordinary. That is not easy, and it is no guarantee, either, but it is the only semisafe goal for which to aim. Medicinal chemists have to offer their employers something that cannot be had more cheaply in Shanghai or Bangalore. New techniques, proficiency with new equipment, ideas that have not become commodified yet: Those seem to be the only form of insurance, and even then, they are not always enough."

As a longtime (20+ year) biochemist in MRL, I can assure you that the consistent refrain from Senior Merck Mgmt has been that "we only hire the best". From my own observations, I would say that this statement is certainly more true that not. On the other hand, given the (ongoing) purge endured by both MRL biology and chemistry over the last several years (including quite a few individuals having the enviable characteristics you defined above), I would respectfully and sadly suggest that your last sentence is probably the most salient of your entire commentary....

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15. Anonymous on December 29, 2011 9:45 AM writes...

So it would not be advisable to follow a career in medicinal chemistry?

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16. anonymous on December 29, 2011 11:15 AM writes...

@15 - How's your Mandarin?

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17. Indy on December 29, 2011 11:20 AM writes...

Derek,

Perhaps you can write a follow up commentary in the same journal this time addressing/discussing many of the points the community is expressing here?

Just a thought.

Keep up the good work and Happy New Year!

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18. Anonymous on December 29, 2011 12:55 PM writes...

my Mandarin?

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19. Anonymous on December 29, 2011 12:57 PM writes...

my Mandarin?

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20. Anonymous on December 29, 2011 1:23 PM writes...

"my Mandarin?"

He's saying that all the med chem jobs are going to China, one of the primary outsourcing countries that American companies use. India would be the other. Both are mentioned in Derek's editorial.

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21. Cadaverine truth on December 29, 2011 1:51 PM writes...

Too many MBAs in the administration hierarchy!! It's a similar situation to the demise of the US auto industry in the late 60's. The key decisions were made by the bean counters to save a quick buck, instead of the engineers who put quality first.

Now look outside and see how many American made cars are in your parking lot...? Sad isn't it!

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22. milkshake on December 29, 2011 4:22 PM writes...

@15: you don't need to learn Mandarin if you are willing to work as a temp lab technician on a 3-6 month contracts for $15 an hour in US, there are some CRO's hiring. So if you are interested in this prospect after your grad school, I should ask instead "How is your gag reflex?"

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23. anonymous on December 29, 2011 9:15 PM writes...

"So it would not be advisable to follow a career in medicinal chemistry?"

I would recommend perusing posts for this blog, starting about 5 years ago. You will quickly find endless posts of misery from current/former medicinal chemists. Your question will be answered, and you could save yourself alot of wasted years.

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24. SwedenCalling on December 30, 2011 4:16 AM writes...

Sorry, but I did not quite get the "enlightened appraisal" part of the article. For a man of your calibre Derek I was hoping for more. Few, if any, new insights. I do however spot signs of 'victim' behaviour? It is time to act now, otherwise it will be to late.

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25. Recycling on December 30, 2011 4:44 AM writes...

Your article nicely highlights the decades of effort by big pharma to find more productive ways to new drugs. Many approaches have been tried, none have proven sufficient. So it feels an inevitability that senior managers have now decided, "well, if we can't find a better way, then let's do it cheaper..."
Can I suggest that as Medicinal Chemists, we should take on a fair bit of the responsibility for the current situation - for taking the money for all those years while not delivering the necessary change in productivity ourselves. Cul-de-sacs such as combinatorial chemistry were maybe an early warning of what happens when we leave the model innovation to MBA's. Now we're reaping the whirlwind.

If we could go back 10 years, knowing what is going to happen, what would we do differently?

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26. anonymous on December 30, 2011 10:17 AM writes...

I know it's easy to blame the MBAs for the current offshoring rage, and to a certain extent, I do. However, at the risk of sounding sympathetic to them, they are, as has been often stated, largely responding to a situation of reduced return on investment in large pharma R&D. That said, we are left with the question of why has R&D productivity diminished over the last decade (or so)? I've always felt that an interesting question in this regard is what portion of this "poor productivity" can be directly ascribed to the rush to push questionable pre-clinical candidates for dubiously validated targets so that deadlines, having large bonuses associated with them, could be met? BTW, didn't most of those large bonuses go to the same individuals who are now leading the outsourcing charge in the labs? It must be easier to be at peace with this style of "management" while watching the waves crash in front of your beachfront vacation home. Just saying...

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27. bbooooooya on December 30, 2011 3:07 PM writes...

"I know it's easy to blame the MBAs for the current offshoring rage"

It is. It's also as incorrect as blaming Walmart for destroying small businesses. Investors demand short term returns. Who are these 'investors'? The majority are those that pay Fideelity and Vanguard small bits of their paychecks each month for their 401ks.

Just like people could keep mom and pop shops in Chanute KS open by not shopping at Walmart, ppl who fund 401Ks can keep workers in big pharma by not demanding rapid returns.

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28. anonymous on December 30, 2011 4:41 PM writes...

@27
Thank you Mr. Cramer....
Oh, and BTW, most "small investors" are NOT demanding "short term returns" and ESPECIALLY not those investing in large Pharma!!!!!

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29. GreedyCynicalSelfInterested on December 31, 2011 3:04 PM writes...

People here are hit with a double or triple-whammy. To be in a declining industry in a declining country is the worst of both worlds.

Be prepared to live with your kids when you're older!

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30. bbooooooya on December 31, 2011 5:07 PM writes...

"most "small investors" are NOT demanding "short term returns"

Ya, they are. People like to see strong 3,6, and 12 month historic returns on those big glossy brochures from Fidelity.

"and ESPECIALLY not those investing in large Pharma"

I'm not talking about individual retail investors (who are pretty insignificant), I mean the thundering heard who invests in mutual funds. Most of them don't have a clue what the funds invest in, just that they like to see their account balances go up.

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31. Anonymous on December 31, 2011 5:46 PM writes...

When a pendulum swings, it does not stop at the resting position and swings back up, it swings through and moves up in the other direction. By that analysis, Derek, bottom out may not necessarily be an up for our American chemist friends. We better pray the pharma Chindia euphoria is ending soon... We will see.

Happy New Year to you all!

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32. Anon on December 31, 2011 9:04 PM writes...

I don't think of the pendulum analogy anymore. When I think of the very depressing reality being discussed here, the very first thing that pops into my mind is the book "the tipping point" by Malcolm Gladwell. If he had written that book 20 years from now, the passages on Chindian Pharma might say something like "... But we never would have had big Pharma in Asia if Pfizer hadn't experimented with segregation of designer and synthesizer chemists. If that hadn't happened, GlaxoZeneca would not have adopted the same strategy, but placed the designers in china from the beginning, leading eventually to the era of off-shoring of senior management positions....". Sorry for the forward(backward?)-looking assumption about a couple companies there, but I couldn't help it. My biggest concern is that, in fact, the situation has already "tipped" and that med chem as we knew it will never come back. Once it is up and running somewhere else, why would it return? Even if cost go up, what would be the incentive for mass upheaval just to bring it back to north America/Europe? Happy F-ing new year .......

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33. anonymous on January 1, 2012 10:21 AM writes...

@32
Take heart, the same doom and gloom was evident during the early phase of the massive effort to off-shore software programming by American companies, but much of that effort was reversed when it became clear that the quality delivered by that cheap labor was NOT SUFFICIENT and their businesses were suffering as a result...

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34. Student on January 2, 2012 3:40 PM writes...

@21 that is a good point. A year before the economic collapse Ford appointed Alan Mulally CEO. The only CEO [of an essentially engineering based organization] that was trained as an engineer...He pushed a turnaround at Ford that led them to be the only one not to require bailout money.

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35. newnickname on January 2, 2012 7:29 PM writes...

Normally, I just scan, read and print PDFs at pubs.acs.org . For the first time, I'm looking for a way to leave comments on articles at acs.org. Is there a way?

I must criticize the simplistic "best advice [] not to be ordinary." In almost all of my experiences, square pegs get pounded into round holes or they are pounded out with the trash. Even in academia, if you are too far out of the ordinary, you will not get funding and fade away with your ideas into oblivion.

Secondly, the history of modern drug discovery shows that many real breakthroughs come unexpectedly from "ordinary" research. I don't mean poor quality, I mean HIGH QUALITY but "ordinary" research. (Yeah, sometimes low quality screw ups turn into blockbusters, too: DES.)

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36. AJB on January 4, 2012 3:42 PM writes...

Typo?

"Most medicinal chemists will be glad to tell you where their place is in drug discovery: why, front and center, where it is always been."

I think this should read: "where it HAS always been" ?

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37. r.pal on January 13, 2012 8:09 PM writes...

I think before we pat ourselves on the back a visit to
www.thennt.com is a good way to get a reality check on how well the efforts of medicinal chemists have borne fruit
this is a must visit site for all medicinal chemists

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38. MK on January 19, 2012 1:58 AM writes...

"There are plenty of interfaces between small-molecule chemistry and biologics: drug–protein conjugates, aptamers, chemically stabilized proteins and oligonucleotides, carbohydrates, modified enzymes, and more. These things are going to need the synthetic organic expertise that we can bring (and that no one else has); no one's going to bioengineer a bacterium to make them."

Bioengineer here. Why couldn't we bioengineer a bacterium to make them? (At least, some of the ones you listed.)

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