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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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October 26, 2011

A Note to Andy Grove

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Posted by Derek

Readers will recall my occasional pieces on Intel legend Andy Grove's idea for drug discovery. (The first one wasn't too complimentary; the second was a bit more neutral). You always wonder, when you have a blog, if the people you're writing about have a chance to see what you've said - well, in this case, that question's been answered. Here's a recent article by Lisa Krieger in the San Jose Mercury News, detailing Grove's thoughts on medical innovation. Near the end, there's this:

Some biotech insiders are angered by Grove's dismissal of their dedication to the cause.

"It would be daft to suggest that if biopharma simply followed the lead of the semiconductor industry, all would be well," wrote Kevin Davies in the online journal Bio-IT World.com. "The semiconductor industry doesn't have the complex physiology of the human body -- or the FDA, for that matter, to contend with."

In his blog "In The Pipeline," biochemist Derek Lowe called Grove "rich, famous, smart and wrong." Grove's recent editorial, Lowe said, "is not a crazy idea, but I think it still needs some work. ... The details of it, which slide by very quickly in Grove's article, are the real problems. Aren't they always?"

Grove sighed.

"Sticks and stones. ... There were brutal comments but I don't care. The typical comment is 'Chips are not people, go (expletive) yourself.' But to not look over to the other side to see what other people in other professions have done -- that is a lazy intellectual activity."

My purpose in these posts, of course, has not been to insult Andy Grove. That doesn't get any of us anywhere. What I'd like to do, though, since he's clearly sincere about trying to speed up the pace of drug discovery (and with good reason), is to help get him up to speed on what it's like to actually discover drugs. It's not his field; it is mine. But I should note here that being an "expert" in drug discovery doesn't exactly give you a lot of great tools to insure success, unfortunately. What it does give you is the rough location of a lot of sinkholes that you might want to try to avoid. ("So you can go plunge into new, unexplored sinkholes", says a voice from the back.)

Grove's certainly a man worth taking seriously, and I hope that he, in turn, takes seriously those of us over here in the drug industry. This really is a strange business, and it's worth getting to know it. People like me - and there are still a lot of us, although it seems from all the layoffs that there are fewer every month - are the equivalents of the chip designers and production engineers at Intel. We have one foot in the labs, trying to troubleshoot this or that process, and figure out what the latest results mean. And we have one foot in the offices, where we try to see where the whole effort is going, and where it should go next. I think that perspectives from this level of drug research would be useful for someone like Andy Grove to experience: not so far down in the details that you can't see the sky, but not so far up in the air that all you see are the big, sweeping vistas.

And conversely, I think that we should take him up on his offer to look at what people in the chip industry (and others) have done. It can't hurt; we definitely need all the help we can get over here. I can't, off the top of my head, see many things that we could pick up on, for the reasons given in those earlier posts, but then again, I haven't worked over there, in the same way that Andy Grove hasn't worked over here. It's worth a try - and if anyone out there in the readership (journalist, engineer, what have you) would like to forward that on to Grove himself, please do. I'm always surprised at just how many people around the industry read this site, and to start a big discussion among people who actually do drug discovery, you could do worse.

Comments (46) + TrackBacks (0) | Category: Drug Development


COMMENTS

1. RB Woodweird on October 26, 2011 8:10 AM writes...

Grove is a smart guy, but he should be able to realize that he was fortunate to jump into an industry in which there was a lot of low-hanging fruit. Pharma was once like that, but it is not anymore. If Grove were to just be getting into the computer industry in 2030, he wouldn't be able to be Andy Grove.

Grove is jumping into a field where the equivalent law to Moore's is linear and wondering where the curve went as if curvature were the natural and proper order of things.

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2. anon on October 26, 2011 8:23 AM writes...

Let's get rid of this idea for once and for all. Low hanging fruit only exists with 20/20 hindsight, after all the work has been done and the picture has become clear. New discoveries are hard for the reason that they are new and the outcome is still uncertain.

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3. RB Woodweird on October 26, 2011 8:30 AM writes...

anon alleges that "Low hanging fruit only exists with 20/20 hindsight...."

Vilfredo Pareto begs to differ.

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4. Matt on October 26, 2011 9:04 AM writes...

I can see this from both sides. Before working in Drug development, I managed projects in Drug manufacturing where we spent a lot of time looking over the fence at fortunate, less regulated manufacturers, and often we picked things up but the benefits were always tempered by our tough regulatory environment. Jumping over the fence into Clinical development I initially could not understand some things, like the lack of pace, I still don't in some places, but I echo the view "This really is a strange business". There are things to learn from over the fence, failing fast, learning from failing, autonamous teams competing for budget, shorter but lighter governance intervals. These things can help but there are no golden bullits. Just lots of small changes, that can cumulatively help.

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5. DCRogers on October 26, 2011 9:41 AM writes...

> What it does give you is the rough location of a lot of sinkholes that you might want to try to avoid.

One of the lessons of early AI work was "don't be dumb" -- programs that tried to do the smart thing kept failing miserably in people's estimations, while programs that simply avoided doing dumb things were deemed quite interesting.

Closely related is Roger Schank's early work on scripts, specifically "learn on fail". We are all rather mindlessly executing scripts we have learned about interacting with reality; the only time we wake up and learn is when part of the script fails, and we need to edit it to take into account a novel outcome.

Back to Mr. Grove -- I welcome him, and wish him well in his efforts -- but I am cautioned at the number of well-intentioned people who try to take their successes in one field and try to leap into another, to find it rough-going. (Nobel Prize-winners are one common example.) Better be ready to edit your scripts, dude!

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6. John Wayne on October 26, 2011 9:43 AM writes...

Derek, I think you are being too nice. The article summarizing Andy's thoughts had some observations of pharma that are factually incorrect. The best example is that 'pharma execs don't care about when a project will make money.' You rightfully called him out on it, and his ignorance on that topic made the rest of us laugh in front of our hoods. Good times.

Andy's actual intention may have been to start a dialogue to determine if our two industries can help each other. If so, we should definitely give it a try. We can be a frustrating industry due to the pitfalls you've mentioned, combined with the slow and ponderous pace of the FDA. He may have said something inflammatory to get some free publicity, or the journalist in question may have exaggerated his criticism of the industry to create some buzz. It wouldn't be the first time the press misquoted somebody; on that note, Derek, you are a biochemist now?

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7. DCRogers on October 26, 2011 9:48 AM writes...

> And conversely, I think that we should take him up on his offer to look at what people in the chip industry (and others) have done.

Maybe someone from Formula One racing could help unknot the thorny problems of drug development -- lots of fields out there to learn from!

(Sorry, I couldn't resist...)

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8. bad wolf on October 26, 2011 9:52 AM writes...

"But to not look over to the other side to see what other people in other professions have done -- that is a lazy intellectual activity."

Isn't that exactly what Grove has done here? Is this quote meant to be ironic?

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9. MTK on October 26, 2011 10:08 AM writes...

@8,

I was sort of thinking the same thing. The quote that got me was "There were brutal comments, but I don't care."

I went back and looked at some of the comments from the second post and I didn't think they were that brutal nor did I see an overwhelming "Go eff yourself" attitude. What I saw were people bringing up legitimate criticisms of his ideas and shortcomings based on a seeming lack of knowledge.

Instead of addressing those issues, however, Grove fires back by saying he doesn't care, while at the same time calling us out as intellectually lazy for not looking at other professions.

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10. CMCguy on October 26, 2011 10:26 AM writes...

I think you have been more than even handed in analysis of Grove's comments on pharma and although there are always things that can be garnered from other industries to aid drug R&D if not properly adapted can do more harm than good. I cringe at his comment "Manage science like a business project" as believe that is the direction phrama has gone in past few decades with MBA's applying their trade to misdirect efforts. As industry insiders we probably are even more frustrated than anyone at lack of production and lost potential however enduring many fades and paradigm shifts will greet any "new idea" with skepticism unless the details do align more concretely with probable progress.

I would think being called a biochemist is a insult although since that's my wife's degree I just got kicked in the shins.

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11. RD on October 26, 2011 10:31 AM writes...

Why not offer Andy an opportunity to work in a lab for a few weeks? Put him on a project and make him sit through several hours of biologists presenting slides of gels (they could be the same gel every time, how would we know?) and let him listen to the "We have been using assay Bleep for the past year but it turns out that it doesn't measure the inhibition of bleep cells by our lead series like we thought it might. And the lead series seems to work fine in yerp cells. But we need to find a cell that works for the out of house series and our lead series so we're going to start looking at fizbit cells from now on. We should have some results next month"
Or I just love it when the biologist tells you that your compound does inhibit the activity you want but has a boomerang effect and upregulates the enzyme you were inhibiting and now you have to look at inhibiting the enzyme that is upstream as well. Fun, fun! All that will take several hours and then the biolgists will get bored when the chemists have to present those weird stick figure thingies.
Andy and his chips have it easy. But he'll never know that until he dons a labcoat and digs right in.

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12. Paul on October 26, 2011 11:05 AM writes...

but I am cautioned at the number of well-intentioned people who try to take their successes in one field and try to leap into another, to find it rough-going. (Nobel Prize-winners are one common example.)

But occasionally they hit a home run, like Luis Alvarez and the detection of iridium in the clay layer at the end of the Cretaceous. Perhaps his son (a geologist) kept him on track.

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13. Dickweed Jones on October 26, 2011 11:18 AM writes...

Why don't we see how smart Grove is. See how he does with the following questions:
1. What is the impact of a t-butyl group in the 4-position of a cyclohexane ring?
2. Which nitrogen in phenylhydrazine is more basic?
3. Why is polymorphism a problem in drug discovery?
4. Why do rhodanines show up so often in enzyme-based screens?
5. What do you do when your flask falls off the rotovap into the water bath, and when is it hopeless to even try.

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14. DLIB on October 26, 2011 11:20 AM writes...

I've actually worked in both industries...the designing the chip analogy simply doesn't work at all. End of story. Although there is some interesting math and algorithms to simplify chip designing ( translating C into verilog ) that is not trivial and still doesn't really work.

I worked at a startup ( Brion technologies ) that was acquired by ASML. Now ASML is involved in some engineering that although the analogy is imperfect, it gets closer. They are the top manufacturer in the world of high-end lithography systems ( these are the things that image the circuits onto the silicon wafer ). The latest thing I was working on was the 16nm node optical correction schemes ( this thing uses 13nm light and in theory go down to 5nm lines). The problem is that the system ( the latest in EUV ) is really at the cutting edge of physics and the task ahead is herculean and actually they are testing theories to see if it will work for the customer at all. They have spent billions on this project and it still doesn't work well enough ( this tool demand is driven by the makers of flash memory ) to go into production. The tool will cost ca. 100million dollars a piece - takes 3 747s to deliver. The light bulb is drops of molten tin that get vaporized by a laser....the problem - light bulb still not bright enough.

The one thing i could see where the pharma industry could learn from the semi-industry is in better industry cooperation and the uses of consortia. In the transition ( potentially ) to 450mm wafers the industry has to get together ( and spend money together ) to help the tool makers in developing a new toolset for the fabs ( serious money is spent ). Gobbling up companies does not count for building a consortia or cooperation :-)

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15. johnnyboy on October 26, 2011 11:23 AM writes...

re #11 "But he'll never know that until he dons a labcoat and digs right in."

How could he possibly be interested in how things work in this field ? He would have to deal with the details (ie. reality), and if there's one thing CEOs are not interested in, it's details and processes - they're "Big Idea" people, don't you know. As in, "I just had this Big Idea, your department has 6 months to implement it, if you don't here's the door".

There's nothing wrong with looking at what other fields are doing in order to improve yours. And this happens very often in good research labs. But you have to look at a field that has at least some common measure with yours. And therein lies the rub: chip-making is about making things. Drug research is about research, ie. understanding things. There is no commonality there. The only area of pharma that could possibly learn from chip-makers would be manufacturing.

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16. Drug Developer on October 26, 2011 12:01 PM writes...

In the open-minded spirit of "What might we learn from other industries?", has anyone in pharma ever looked at oil exploration? Constantly developing science (geology), incomplete knowledge of "what's down there", compelling business need for new successes, expensive "trials" that don't often succeed, etc.? Are there things we could learn from their business?

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17. Anonymous on October 26, 2011 12:16 PM writes...

This seems an awful lot like a violinist trying to give piano lessons........

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18. MolecularGeek on October 26, 2011 1:50 PM writes...

Not much I can say here that hasn't already been said. I'd sum it up by telling Mr. Grove that there is a difference between science and engineering. It's great that the laws of physics are homogeneous down to the atomic scale, but that doesn't carry over to biology in a useful way. How would the chip industry look if when they started going from 2.2 gHz cores to 3.0 gHz cores, the resistance of gallium-doped silicon suddenly changed in a non-linear way, or if quartz lost its ability to vibrate at a stable frequency in the presence of di-substituted pyridines (for a silly example)? Being able to assume that physical laws behave in a predictable manner is a key assumption for most engineers that I know. If the constraints on a system and its behavior away from equilibrium are not well understood, all the six-sigma process and lean internal organization in the world won't save your R&D process.

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19. emjeff on October 26, 2011 1:56 PM writes...

#16 - I don't think that is a good analogy at all. Yes, geologists are continually trying to find oil, but there are established ways of doing it and they work. Also, there is no way that Big Oil pays the kind of R&D costs we do. Finally, they are not nearly as regulated as we are - do they have to prove that the oil they get from a new well will be useful before they start selling it?

This Andy Grove is no better than a carny, he's trying to get VC, and he'll waste a bunch of it on meeting and plane trips, and then short the stock and make a killing.

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20. The Force of Cluelessness on October 26, 2011 2:14 PM writes...

Looky here, Derek Lowe is violating his own contract in giving airtime to a blowhard (And Grove) who doesn't know what he is talking about.

The shame.

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21. Anonymous on October 26, 2011 3:07 PM writes...

Derek,

Maybe you can pass the following reading list on to your good buddy, Andy. Once he has read and understood these volumes then we can talk, otherwise he is just another ignorant F spouting off about things and a world he has no idea about.

• Pharmaceutical Manufacturing Handbook: Regulations and Quality (Pharmaceutical Development Series); ed. Shayne Cox Gad; Wiley-Interscience; 2008
• Clinical Trials Handbook (Pharmaceutical Development Series); ed. Shayne Cox Gad; Wiley-Interscience; 2008
• Pharmaceutical Manufacturing Handbook: Production and Processes (Pharmaceutical Development Series); ed. Shayne Cox Gad; Wiley-Interscience; 2008
• Preclinical Development Handbook: Toxicology (Pharmaceutical Development Series); ed. Shayne Cox Gad; Wiley-Interscience; 2008
• Preclinical Development Handbook: ADME and Biopharmaceutical Properties (Pharmaceutical Development Series); ed. Shayne Cox Gad; Wiley-Interscience; 2008
• Drug Safety Evaluation (Pharmaceutical Development Series); ed. Shayne C. Gad; Wiley-Interscience; 2009
• Pharmaceutical Manufacturing Handbook: Regulations and Quality; ed. Shayne Cox Gad; Wiley-Interscience; 2008
• Development of Therapeutic Agents Handbook; ed. Shayne Cox Gad; Wiley-Interscience; 2011
• Drug Discovery Handbook (Pharmaceutical Development Series); ed. Shayne Cox Gad; Wiley-Interscience; 2005
• Drug Discovery and Evaluation: Methods in Clinical Pharmacology; ed. H. Gerhard Vogel, Jochen Maas and Alexander Gebauer; Springer; 2011
• Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays; ed. H. Gerhard Vogel, Franz Jakob Hock, Jochen Maas and Dieter Mayer; Springer; 2006
• Drug Discovery and Evaluation: Pharmacological Assays, 3rd edition; ed. Hans Vogel; Springer; 2007
• Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research; Robert M. Rydzewski; Elsevier Science; 2008
• Early Drug Development: Strategies and Routes to First-in-Human Trials; ed. Mitchell N. Cayen; Wiley; 2010
• Integration of Pharmaceutical Discovery and Development : Case Histories Pharmaceutical Biotechnology Volume 11; ed. Borchardt, R. T., Freidinger, R. M., Sawyer, T. K., Smith, P. L.; Plenum Press; 1998
• Burger's Medicinal Chemistry, Drug Discovery and Development, Volumes 1-8 ; ed. Donald J. Abraham and David P. Rotella; Wiley-Interscience; 2010
• Comprehensive Medicinal Chemistry II, Volumes 1-8; ed. David J Triggle and John B Taylor; Elsevier Science; 2006
• The Practice of Medicinal Chemistry, 3rd Edition; Camille Georges Wermuth; Elsevier Science; 2008
• Process Understanding: for Scale-Up and Manufacture of Active Ingredients; ed. Ian Houson; Wiley-VCH Verlag; 2011
• Active Pharmaceutical Ingredients Development, Manufacturing, and Regulation (Drugs and the Pharmaceutical Sciences, Volume 151); ed. Stanley Nusim; Marcel Dekker; 2005
• Pharmaceutical Dosage Forms, Volumes 1-3; ed. Herbert Lieberman, Martin Rieger, Gilbert S. Banker; Informa Healthcare;1996
• Practical Process Research & Development; Neal G. Anderson; Academic Press; 2000
• Drug Discovery and Development, Drug Discovery Volumes 1 and 2; ed. Mukund S. Chorghade, Wiley; 2006/2007• Guide to Drug Development: A Comprehensive Review & Assessment; Bert Spilker; Lippincott; 2008
• ADMET for Medicinal Chemists: A Practical Guide; ed. Katya Tsaioun and Steven A. Kates; Wiley; 2011
• Drug Development: From Laboratory to Clinic; Walter Sneader; Wiley-Blackwell; 1986
• Drug Discovery. A History; Walter Sneader; Wiley; 2005
• Evens, R.P., ed., Drug and Biological Development: From Molecule to Product and Beyond. Springer Science + Business Media, LLC, New York, NY, 2007.
• Gassmann, O., et al., Leading Pharmaceutical Innovation: Trends and Drivers for Growth in the Pharmaceutical Industry. Springer-Verlag, Berlin – Heidelberg, 2004.
• Ng, R., Drugs: From Discovery to Approval. John Wiley & Sons, Inc., Hoboken, NJ, 2009.
• Pisano, G. P., Science Business. Harvard Business School Press, Boston, MA, 2006.
• Nighil, William L., ed., Research and Development in the Pharmaceutical Industry. Nova Science Publishers, New York, 2009.
• Rang, H.P., ed., Drug Discovery and Development: Technology in Transition. Elsevier Limited, Philadelphia, PA, 2006.
• Spilker, B., Multinational Drug Companies: Issues in Drug Discovery and Development. Raven Press, New York, NY, 1989.

Permalink to Comment

22. Todd on October 26, 2011 3:44 PM writes...

My biotech-molecular oncology perspective:

The tumor actively evolves to avoid the target you are blocking. Unfortunately, preclinical models are inadequate for predicting how they will do this.

Ergo, high Phase II failure rates.

To my knowledge, the chips do not actively evolve to combat your design strategies.

Todd

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23. Twelve on October 26, 2011 4:38 PM writes...

I've been having a look at the silicon chip business and I see that they run them at rediculously low voltages - no wonder the processing speeds have stagnated! Boost them up to 1000, 10,000, 100,000 V! Don't like getting ideas from med chemists who haven't taken an electrical engineering course in their lives? Well it just shows that they're narrow-minded and prejudiced and don't know how to think outside the box. And any comments disagreeing with my scintillating new idea are brutal and pathetic.

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24. Handles on October 26, 2011 6:59 PM writes...

@Dickweed Jones

re #5: My PhD supervisor told the story of his flask falling in the rotavap bath one time. He turned off the heat, and the compound simply crystallised out on cooling :)

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25. biff on October 26, 2011 7:03 PM writes...

#16 - yes, many pharma firms have looked at other industries -- and even collaborated with them -- to compare notes on R&D and to try to bring in new ideas for structuring research programs and fostering innovation. I've been involved personally with pharma initiatives involving industries such as (1) oil, (2) computer sciences, (3) transportation, (4) entertainment (the process of deciding which movies to make and bring to market has some stunning similarities to pharma R&D portfolio management), (5) financial services, and others.

There are even a few former oil industry execs working in the pharma industry. (Not because the industries are both vilified, but because both have similar risk profiles.)

#19 - You might be surprised at how much the oil/energy industry spends on R&D. Not as much as big pharma, but it's within the same order of magnitude. It also has to deal with piles of regulation, although much of it is in different parts of the product life cycle than what pharma experiences.

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26. Spiny Norman on October 26, 2011 7:18 PM writes...

Grove is exceptionally bright, and he works on computer hardware. Yet he hasn't he solved the problem of big software project management.

Perhaps drug development is easier. Or perhaps that's what he thinks.

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27. Gaussling on October 26, 2011 9:41 PM writes...

Groves' success relates to the ability to achieve a continuous increase in the number of semiconductor junctions per manhour of labor. This kind of lithographic efficiency translates to ever increasing device performance. He was in the game during the steep part of the S-curve. What is the corresponding boom in pharma R&D? What is the bottleneck in pharma R&D that limits such growth? Is it regulatory compliance? Is it clinical testing? Is it in the process development? I don't know.

Permalink to Comment

28. Daniel Newby on October 26, 2011 11:11 PM writes...

Chip factories are basically giant chemically plants: organic, inorganic, photochem, pyrolysis, ozone, vacuum ultraviolet photochem, you name it. There are not enough PhDs alive to run even a single factory by hand, so it all gets automated, damn the expense. If it takes $500M to automate a step of the process, so be it, it gets automated.

If you put Grove in a lab for two weeks, he would spend the entire time saying things like "Holy crap! You moron! You just hand-carried a sample from the centrifuge station to the electrophoresis station! That will never scale to 50 million assays a quarter!" A couple of years later he would be running a completely robotic service that you FedEx a frozen rat to. The service dices the rat into voxels, identifies the tissue each voxel belongs to, and for selected voxels does genetic and protein gels, and does chromatography/mass-spec for small molecules. It could also optionally do immunofluorescence assays on slices. It would become standard at the end of a project to dump the entire vivarium in liquid nitrogen and ship it off to see if any potentially valuable effects turned up.

Likewise, every experimental animal should have a camera watching it 24/7 to watch for behavioral changes. Odds are that we have discovered a ton of interesting CNS drugs and not known it because nobody was watching limb movement patterns, eye movements, etc. Similar per-animal measurements can be made on things like breath CO2, urinalysis, and so forth.

One of the problems with combinatorial chemistry was that the math just didn't work out. A sample of randomly created brown sludge will very likely contain a compound that binds well to some protein or regulatory element. The trouble is that the combi-chem folks were testing against one protein at a time. Whoops. The mindset of the chip folks is that you run each exemplar against a giant battery of tests. Give Grove this problem to solve and you'd get a building full of bioreactors, each one producing a cell line overexpressing one of the known receptors. Yeah, it's expensive, but so is hand-crafting drug candidates and hand-testing them against one receptor at a time: it is not getting the job done.

From what Derek writes, it sounds like a medicinal chemist spends a lot of time working as a sous chef with a very, very diverse pantry. Why doesn't he have a robotic lab to send instructions to? Get the reaction to the point where the robot can get any measurable yield, then let it automatically vary parameters to optimize yield. Want to stick on a side chain? Insert a few steps in the process and tell the computer what to look for. The cycle is slower and indirect, but once a process is discovered anybody can turn out kilogram quantities merely by asking for it.

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29. WB on October 26, 2011 11:56 PM writes...

@13

Those are some of the questions I ask the BSc/MSc people applying for positions in my group. :-)

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30. Anonymous on October 27, 2011 2:53 AM writes...

Anon 21 - the arrogance of your post actually makes me laugh and neatly sums up the stinking attitude of some of the folks in this industry.

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31. Anonymous on October 27, 2011 8:26 AM writes...

#30

I have worked 40 years in the pharma/biotech industry and have seen it all. I stand by by my position: Andy Groves does not know jack about this business, the science, the regulatory constraints, the history of drug discovery or the psychology of the people striving to invent drugs. He is a rich a-hole who thinks because he was highly successful in high tech he now qualifies to advise us on the biomedical product invention. If all we needed was just Groves' brilliance, we would have long ago won the war on cancer. It is 40 after after that war started and we are still losing it. It is not because we lacked Groves' insights.

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32. Anonymous on October 27, 2011 9:10 AM writes...

Well #21/31, I also stand by my position that your attitude stinks. You might have 'seen it all' in your 40 years of glorious brilliance in the industry, but calling someone an 'ignorant F' and a 'rich a-hole' for expressing an opinion speaks volumes about you.

Oh, and for the record, I don't much agree with Groves' position and commentary but at least there are a few new ideas and thoughts there. That's what this industry desperately needs, not a list of 50 textbooks for God's sake!

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33. David Borhani on October 27, 2011 9:27 AM writes...

@28

Interesting idea, slicing and dicing the frozen rat. It could turn into yet another "feed the machine" approach, however (i.e., HTS was supposed to solve all our problems...).

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34. Dickweed Jones on October 27, 2011 10:22 AM writes...

@Handles- Groves probably doesn't understand that the probability of something falling off a rotovap is directly proportional to the number of synthetic steps required to make the stuff. And that there is an inverse relationship between the same event and LogP.

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35. Algirdas on October 27, 2011 11:27 AM writes...

@ Daniel Newby (#28)

"A couple of years later he would be running a completely robotic service that you FedEx a frozen rat to."

If you haven't yet, you may enjoy reading Vernor Vinge's SF novel "Rainbows End". The rodents there are not frozen, but the idea rather similar.

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36. watcher on October 27, 2011 6:32 PM writes...

Derek,

Stop trying to attach wind-mills. Get off of your preaching high-horse. Give it up. Grove is has been a wizard in his area of expertise, which is not pharmaceutical R&D. That's all you need to recognize, and be done with it. You should be so successful, and well known for accomplishments other than yapping and blogging. Get off of your preaching high-horse.

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37. MIMD on October 27, 2011 7:45 PM writes...

Sticks and stones. ... There were brutal comments but I don't care.

Those comments were not very brutal.

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38. MIMD on October 27, 2011 7:48 PM writes...

watcher on October 27, 2011 6:32 PM writes...

Derek,

You should be so successful, and well known for accomplishments other than yapping and blogging. Get off of your preaching high-horse.

You, sir/madam, are truly in the 19th century regarding New Media.

The information and opinions Derek provides are interesting and useful to those in medicinal chemistry and beyond; all you provide is useless information.

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39. Twelve on October 27, 2011 9:58 PM writes...

@28: Your remarks ring a bell for this medicinal chemist - they are literally 'sophomoric', in that we generally get these sort of gee-whiz musings from our new hires around about their second year in industry. They've gotten over their awe at what high throughput screening can do and start to storm about asking why we don't do EVERYTHING in high throughput mode with combinatorial mixtures??!! Screening, expression profiling, imaging, PK, PD, efficacy, solubility, clinical studies, for Pete's sake!! The wiser ones sense that maybe they're not the very first people to think of this. They sit down with their biologists or a med chemist who's been around the block a few times. They come to understand that rat studies only tell you about rats (and inbred ones, at that), and that new molecules which you hope have excitingly good properties often have perplexingly bad properties that confound any study of a mixture with them present. The really gifted ones don't give up when they learn this, not at all - they still aspire to revolutionize our field, but not by paying attention to someone who tells you all you need to know about him by looking at his last name.

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40. watcher on October 28, 2011 7:02 AM writes...

#38:

You are like so many in the industry who have to a attack those who feels threatened by anyone who comments on drug R&D in non-traditional approached and can't see any horizon beyond their noses:

-arrogant
-trying to look confident but is really insecure
-needing justification
-scared of what's coming to the industry (& you)

Go back to your texting....


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41. Anonymous FDA lurker on October 28, 2011 9:38 AM writes...

A thing that Grove fails to truly appreciate: Drug development is a constantly evoving risk-benefit relationship with multiple stakeholders that have a say, i.e, pharma companies, physicians, FDA/EMA, payors, patients (congress!). Not so simple as improvivng a machine design and letting the markets determine success.

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42. Spiny Norman on October 28, 2011 11:08 AM writes...

Wow, Watcher. You have an astonishing willingness to psychoanalyze other people you've probably never met, based on reading a few words in a blog post comment.

Since you got the ball rolling, allow me to make my own inference: you're either really smart, or really dumb.

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43. MIMD on October 29, 2011 1:36 PM writes...

#40 watcher

You proffer still more useless information.

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44. watcher on October 30, 2011 1:15 PM writes...

#43 MIMD:
In the eyes of the beholder. You obviously feel entitled to give opinion freely and generously, but not liking any discussion, debate, or differing view of the world. So sad, so sad.....but fun to push your buttons!

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45. Jerry on October 31, 2011 5:02 PM writes...

Hey Andy Grove - Shut Your Face!

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46. fajensen on November 1, 2011 12:21 PM writes...

... all the six-sigma process and lean internal organization in the world won't save your R&D process.

No - because it is not even the purpose of an R&D process, even in "simple" fields like software and engineering, to yield a steady stream of product with no failure allowed. Bringing quality into R&D kills the process.

One uses R&D to find the edges/limits of what can be done, then back down a little for production where the quality process is then used, and rightly so, to steer production and keep away from that edge. OTOH: If one does not fail during R&D, one is not even close to producing new, valuable, results; it is merely sloppy custom manufacture.

I have filled buckets with dead semiconductors and even blown a couple of deadlines to learn enough to know that the end product, a solid state RADAR modulator, *never* blows up in the field.

That is why sensible companies never put R&D on the critical path: It might not pan out and then what do you sell?

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