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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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August 19, 2013

An Inspirational Quote from Bernard Munos

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Posted by Derek

In the comments thread to this post, Munos has this to say:

Innovation cannot thrive upon law and order. Sooner or later, HR folks will need to come to grips with this. Innovators (the real ones) are rebels at heart. They are not interested in growing and nurturing existing markets beccause they want to obliterate and replace them with something better. They don't want competitive advantage from greater efficiency, because they want to change the game. They don't want to optimize, they want to disrupt and dominate the new markets they are creating. The most damaging legacy of the process-minded CEOs who brought us the innovation crisis has been to purge disrupters from the ranks of pharma. Yes, they are tough to manage, but every innovative company needs them, and must create a climate that allows them to thrive. . .

I wanted to bring that up to the front page, because I enjoy hearing things like this, and I hope that they're true.

Comments (73) + TrackBacks (0) | Category: Who Discovers and Why


COMMENTS

1. bhip on August 19, 2013 1:31 PM writes...

Very true. Yes-men (or women) when, in science, the answer is usually "no" leads to the progression of junk out of Discovery & into Development where we spend real $$.

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2. milkshaken on August 19, 2013 1:44 PM writes...

a bunch of prima donnas; why can't they just fall in lane and do as told like everyone else.

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3. Kelvin on August 19, 2013 1:53 PM writes...

@2: Because "fall(ing) in line and do(ing) as told like everyone else" is precisely what innovation *isn't* - by definition. ;-)

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4. Anon on August 19, 2013 2:01 PM writes...

HR is a cookie cutter role and pharma R&D isn't. They will apply the same techniques almost regardless of industry. That's going to cause problems, especially in one this unique.

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5. sgcox on August 19, 2013 2:07 PM writes...

#3 have you not noticed a sarcasm in milkshake post ? He is known for it.

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6. jrftzgb on August 19, 2013 2:08 PM writes...

We need to fight rent seeking behavior so much. It's one of the biggest things killing our society in the name of efficiency and profit.

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7. John Wayne on August 19, 2013 2:10 PM writes...

I certainly hope this is true, but that is because I am an intellectually rebellious person. You can potentially succeed by taking a chance, or manage out the risk leading into failure.

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8. bluefoot on August 19, 2013 2:15 PM writes...

This reminds me of a scientific staff meeting at a former company when HR was rolling out new rules for reviews and compensation. There was a lot of pushback from the scientific staff - and not really because of money either, more about how the new rules would severely restrict opportunities for growth - and HR said that the new policies were "in line with other companies our size." One of the scientists stood up and said "So what you're saying is that we should be striving to be average?"

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9. Kelvin on August 19, 2013 2:15 PM writes...

@5: Thanks, I did wonder, though ironically it does sum up very well the attitude of most pharma management to such innovators as rebels, rule breakers and trouble makers. :-(

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10. Anonymous on August 19, 2013 2:26 PM writes...

We're not tough to manage. We're all unemployed already.

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11. Anonymous on August 19, 2013 2:31 PM writes...

@10: That would be very funny - if it weren't so true.

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12. Anonymous on August 19, 2013 2:38 PM writes...

Unfortunately, it wasn't intended to funny............

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13. RealityCheck on August 19, 2013 3:10 PM writes...

What Munos says sounds good but I don't think it works in practice. I saw lots of loose cannons and mavericks @GSK who drew large salaries for doing little except driving their colleagues to distraction with their "blue skies" thinking. R&D was blighted by outsize egos preaching how some sort of "omics" crap or some other fad was going to solve all our problems. Current management don't get the credit they deserve for calling these guys to account. And before someone tries to say what "expertise" was lost, tell me what these guys have achieved since their departures!

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14. Anonymous on August 19, 2013 3:22 PM writes...

@13: Fair point, but there's a big difference between taking good risks (small, exploratory bets on big ideas) and stupid risks (going "all in"), as pharma has done with target-based HTS, genomics, etc.

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15. RealityCheck on August 19, 2013 3:31 PM writes...

Agree totally @14 but some of these guys had 100s of FTEs, I'm thinking of the old GSK DR and GR divisions here who were into target-based HTS and genomics big time but delivered practically nothing. Egotistical posturing and self-congratulation were the hallmarks of the leadership!

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16. captaingraphene on August 19, 2013 3:39 PM writes...

"Innovators (the real ones) are rebels at heart".

True, and these are exactly the kind of people who find it more and more difficult to thrive in the modern day corporate environment. They are also much more likely to be discarded by the educational system, as they are non-conformist. They typically don't wait to get spoon fed information, but find out things on their own, and quite fast too.

These 'rebels' don't want to be kept on a short leash by HR drones or micromanaging principal investigators sucking the life out of them for up to a dozen years.

The innovator aspires to be a captain on the very ship he or she built, not an ensign on a ship captained by somebody else.

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17. Anonymous on August 19, 2013 3:52 PM writes...

@15: At that level of seniority, innovators should grow and adapt into leaders by enabling and empowering others to innovate and try out their own ideas, rather than managing them to pursue only the (egotistic) supervisor's own single "big idea". In other words, they must learn to "let go".

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18. RealityCheck on August 19, 2013 3:57 PM writes...

@17, I agree and admire your idealist outlook but if you ever met the guys who headed up the divisions I mentioned, you would quickly realize that such an outlook would be entirely futile!

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19. rico on August 19, 2013 3:59 PM writes...

@13 RealityCheck: "loose cannons and mavericks" does not equal non-conformist innovators. It's exactly this type of assertion equating the two that drives curious and driven researchers away. You are right that putting what Munos says into practice is hard (maybe impossible) in most corporate cultures and that is exactly what Bernard is saying: one function of senior leadership is to create a an environment and culture where Innovators can operate and thrive, regardless of hard it is to "manage" them.

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20. Anonymous on August 19, 2013 4:57 PM writes...

Instead of having philosophical debates on drug discovery innovation, how about brainstorming some truly discruptive ideas of yours?

I'll kickstart with mine--I propose the Drug Industry Consortium Kingdom (NASDAQ: DICK) establish the Homo neanderthalensis as the future gold-standard preclinical species for all PK and efficacy studies. Jurassic Pharma CRO Services co-founded by Drs. Spillburg & Cryshiton will supply the cohort from a scenematic tropical island owned by Dr Allison.

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21. Biotechtranslated on August 19, 2013 5:02 PM writes...

This sounds eerily familiar to the "move fast and break things" mantra of the start-up tech world.

It's a lot easier to do that when you can come up with a finished product for $2M and your mistakes don't kill people.

Drug development has a huge regulatory component that doesn't respond well to the "mavericks and rebels".

I don't think anyone can argue that management can have a very negative impact on innovation, but claiming that "I would come up with the cure for cancer if John Bain, MBA would just leave me alone" is a little self-aggrandizing.

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22. Validated Target on August 19, 2013 5:19 PM writes...

@19 (and others): "loose cannons and mavericks" does not equal non-conformist innovators. The history of Drug Disco is filled with examples of the latter.

1. Cimetidine started out as a two-person project (chemist and biologist) who were inspired by Black's work on H2R antagonists. As it was told to me by those who were there, they were repeatedly told to stop work on the (back burner) project. As other SKF projects withered and died, pre-cimetidine results FINALLY merited further examination, the project was green lighted. Cimetidine / Tagamet saved SKF. The two guys who took the heat were non-conforming innovators.

2. I've heard that Prozac was a 2-man (chem + bio) project for a while at Lilly until it picked up speed. I think it was the biologist who, from the literature or a meeting, first wanted to go after an SRI. It was not some corporate committee that set a mandate or a glorified thought leader. It was a scientist with an idea and it worked and everybody took a pill and chilled out (and cashed in!).

3. I can't think of others cases at the moment. (IBM threatened to fire Bednorz and Mueller if they didn't stop work on the unofficial yet Nobel worthy superconductor project.)

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23. lynn on August 19, 2013 5:47 PM writes...

I think what's been killed off is the lower level rebels in Pharma. As #22 said, many drugs came from a single scientist or small teams of scientists who worked on projects with their own hands, and argued them up the ladder. But they were rebels...and in latter days, as HR and upper management started to value "being nice" and get rid of those - at the lower levels - who disagreed with those above, the rebel scientist-innovator got short shrift and an escort to the door. I don't think the "loose cannons" who manage 100 FTE's is where innovation ever starts.

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24. Esteban on August 19, 2013 5:59 PM writes...

@22: I long ago heard a tale from someone who should know that the champions of atorvastatin (forget the names) were at one point told to stop working on the molecule and were basically doing it on the sly. Maybe there is an ex-WarnerLambert person reading this who can confirm.

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25. weirdo on August 19, 2013 6:01 PM writes...

There is a fine line between "innovation" and "stupidity". Unfortunately, not many can recognize that line.

HTS was innovative. Network pharmacology was innovative. Combinatorial chemistry was innovative. Microdosing was innovative. Now, big data is innovative.

We're doing it to ourselves.

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26. hibob on August 19, 2013 6:35 PM writes...

while I'm all in favor of rebooting Pharma, could anyone who worked through previous "Think outside the box" management consulting fads compare them to Munos's Disruptive Innovation © management. consulting fad?

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27. srp on August 19, 2013 7:07 PM writes...

It's a commonplace in management studies that innovation as an activity is often illegitimate in large, going concerns, even ones that pay lip service to or have units dedicated to innovation. One consultant put it neatly in a WSJ column that CEOs like the results of innovation but not the necessary process of innovation itself, because the latter is full of false starts, embarrassing mistakes, uncertainty, anxiety, discord, etc. And there are many things we take for granted, ranging from Sidewinder missiles to plastic trash bags with built-in handle/ties, that were created in the face of management opposition, sometimes using bootlegged resources in a quasi-fraudulent way.

It's a little more disturbing that pharmas, expressly set up to do nothing other than discover and bring new things to market, have trouble avoiding this syndrome. I suspect that there is a fundamental misunderstanding and expectation about what it means to "routinize innovation." It doesn't mean having a regular flow of successes trackable on some grid. It means treating false starts, embarrassing mistakes, uncertainty, anxiety, discord, etc. as routine parts of organizational life. But everybody, not just managers, often finds such an environment undignified and stressful.

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28. rtw on August 19, 2013 8:38 PM writes...

@24 Esteban - You are correct. The biologist heading up the project originally was a large group leader. By the time clinical trials had started he had lost all his group members. When the drug hit it big he was invited to leave the organization when he wanted to reboot/follow up with new ideas in LDL, HDL.

Marketing and Management didn't think yet another Statin would make any money. (7th on the market maybe?) Little did they know at the time the drug would turn out to be a superior agent.

The primary Chemists involved in the end didn't fair much better. They lost their jobs when the facility was closed. The company killed the goose that laid the golden egg.

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29. Bernard Munos on August 20, 2013 1:17 AM writes...

@hibob,

I claim no trademark over the concept of disruptive innovation, which long predates me. Disruptive innovation lies at the heart of translational research, which seeks to turn breakthrough discoveries into commercial drugs. Far from being a fad, it is what built the drug industry -- the ability to disrupt itself deliberately and repeatedly over most of the past century. Lilly did not need to embrace rDNA technology in the late 70s. Why take a risk on something unproven? There was plenty of money to be made by producing marginally better versions of its antibiotics. The same reasoning applies to every breakthrough that made the industry great: monoclonal antibodies, vaccines, antibiotics, insulin, etc. At every step along the way, there were low-risk opportunities to produce marginally better versions of existing drugs, and use marketing muscle to make them succeed. But this did not square with the leaders's vision of what the industry was about -- the Paul Janssens, George Mercks, Robert Wood Johnsons, Eli Lillys, and others.

Unfortunately, few of the CEOs of the last 15 years have been of that caliber. More than a few were scientifically untrained, risk-averse, and short of vision. Their lack of qualification for their jobs is attested by their performance. Thankfully, this has started to change, with new courageous leaders willing to acknowledge and roll back the mistakes of their predecessors.

I agree with you that the industry does not need another fad. Just the opposite. It needs to scrap the fads that got it into trouble -- such as six sigma -- and reconnect with its roots and what made it successful. It needs to discard its process culture, and return to a culture of innovation.

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30. London Chemist on August 20, 2013 4:31 AM writes...

@24 Don't know about atorvastatin, but the Germans working on gabapentin were repeatedly told to stop working on it by W-L's US management.

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31. Anonymous on August 20, 2013 5:30 AM writes...

@26/hibob: Perhaps you are right that disruptive innovation was a fad - which is a shame, because it's precisely what the industry is now lacking, and so desperately needs to bring back.

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32. Lyle Langley on August 20, 2013 7:28 AM writes...

Talk like this always brings me back to a friends plaque from VW/Audi that I inherited upon his untimely passing (don't know if this is where it originated):
"The manager administers, the leader innovates. The manager maintains, the leader develops. The manager relies on systems, the leader relies on people. The manager counts on controls, the leader counts on trust. The manager does things right, the leader does the right thing."

I think if most people take this to heart, "managers" might actually become "leaders" and we'd be much better off.

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33. Anonymous on August 20, 2013 7:39 AM writes...

@32: Or to put it more succinctly, managers require control, leaders and innovators are prepared to let go of it.

Perhaps it is no accident, then, that managers do everything they can to take control away from the leaders and innovators?

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34. Kling on August 20, 2013 7:41 AM writes...

Something to keep in mind.
The vast majority of research projects fail, whether they are initiated by an innovator or not.
It is one thing to be rebellious and maverick, it is another to have a successful track record of outstanding projects.

Also rebels and maverick innovators- can they actually lead a lab and get results on track? perhaps the best teams are innovators paired with expert people-managers to give projects the best chance of success.

Metrics like this are not aligned in a big pharma, as far as I know.

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35. Lyle Langley on August 20, 2013 7:43 AM writes...

The above quote, or at least some, should be credited to Warren G. Bennis.

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36. petros on August 20, 2013 7:50 AM writes...

Nifedipine (Adalat)- Bay a1040 was another maverick product which led to multiple blockbusters for many companies.

The story I was told was that the (old) chemist who made it was told not to work on 1,4-dihydropyridines. But he kept churning them out after cycling into work each day. In the week he retired he submitted nifedipine and a large number of related compounds. Some 15 years later Bayer ws trying to develop such chemotypes for most therapeutic indications!

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37. stilltenuous on August 20, 2013 8:18 AM writes...

Quick poll: Who here feels secure enough in their jobs to wander off the reservation and start doing work that isn't directly tied to "portfolio support?" The latter term meaning projects that were started only after getting explicit approval from multiple levels of managers, and includes enough partners to assure distributed blame when it doesn't produce a candidate.

Where is the opportunity for "reverse translation" that we development scientists heard so much about a few years ago? As far as I can see, reverse translation must be associated with early phase clinical successes. Given how many failures must come before even FIH, plenty of opportunities for true innovation and reverse translation die at the hands of a desire for indoor living and quality healthcare.

Unless we change the job security situation, Pharma will remain paralyzed.

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38. Anonymous on August 20, 2013 8:26 AM writes...

@37: An alternative poll: Who here feels secure enough in their jobs in the event that pharma *doesn't* fix its innovation problem?

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39. Ben Zene on August 20, 2013 9:46 AM writes...

Those of us with MBA's (boo hiss) are pretty familiar with the concept of disruptive change. As stated above it's been around for years. George Bernard Shaw summed it up quite nicely with his all progress depends on the unreasonable man quote.

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40. Ginsberg on August 20, 2013 9:47 AM writes...

Every company could use a group of scientists whose job is to poke holes in the theories of the companies R&D. Call them the Cargo Cult Science dept. They don't have to be rebels who are tough to manage. The job itself is to disrupt.

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41. Vader on August 20, 2013 9:50 AM writes...

As soon as management decides that rewarding mavericks is the key to future income streams, all the company men will start talking and acting like mavericks.

When the management decides that that didn't work so well, and decides to reward "team players", all the company men will start talking about consensus and be all sweetness and light.

When the consultants loudly announce that managers need to be able to see through this gaming of the system -- thereby, as consultants always do, collecting their fees for pointing out that which is both obvious and insoluble -- the upper-level managers will assume this means middle-level managers and put yet another set of perverse incentives in place.

Real innovation comes from folks who don't feel accountable to anyone and whose incentives are largely internal and inarticulate. Such people are, by objective measures, a little unbalanced; and folks who are both brilliant and unbalanced are rather scarce in any society. Ours are mostly gravitating somewhere other than pharmaceuticals or my own field of applied and computational physics. They're mostly visible in information technologies nowadays, having been responsible for both the dot-com bubble and the Ipod.

I don't know where they're gravitating now, because I'm not one of them. I am reasonably bright, but I've also never been particularly risk-averse and I'm all too keenly attuned to the incentive structure. In other words, little more than a highly paid technician. :(

(With lasers the size of a small moon to play with, muh hah hah hah ...)

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42. Suleman on August 20, 2013 9:55 AM writes...

Nothing to do with research, but when I joined a patent firm in 1996 we still had people running it who were 'visionaries'. Within about 5 years they retired and we had people who 'managed' very well, just as everyone now seems to in every sector.

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43. anon on August 20, 2013 10:24 AM writes...

@22

The non-sedating antihistamines (Allegra, Claritin, etc.) were slow-developing submarine projects, since marketers asserted to the corporate bosses that people just don't want to pay for antihistamines.

Of course, it is true that people just don't want to pay for antihistamines that make you fall asleep in 30 minutes and keep you fogged over for hours if you happen to force yourself to stay awake.

Antihistamines that worked, however, without doing all that stuff made their own enormously huge market.

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44. emjeff on August 20, 2013 10:26 AM writes...

Hear, hear!!

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45. Anonymous on August 20, 2013 10:33 AM writes...

Love the quote. Funny, I just started rereading Sagan's "Demon-Haunted World" last night, and his first chapter is basically about how the distinction between science and pseudoscience is that scientists aren't afraid to be wrong, and thrive on challenging their assumptions and having their assumptions challenged. The quote above is right in line with that, and I'm all fired up and ready to slay dragons now.

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46. Anonymous on August 20, 2013 10:38 AM writes...

Also, don't kid yourself. Rebels have always had it hard - it's human nature. The ones who succeeded were the ones who kept putting one foot in front of the other.

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47. a. nonymaus on August 20, 2013 11:15 AM writes...

We're easy to manage. Pay us regularly (in cash, vacation time, and democratic shared ownership of the firm), and stay out of the way. Oh, you want innovation from wage-slaves?

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48. CMCguy on August 20, 2013 12:28 PM writes...

Some people make this all sound so simple: Give the Innovators freedom and then results will be out pops new drugs. I see several problems with that concept. Firstly, Real innovators are few and far between (and many probably are in Academia with a different mission). Typically it takes a combination of ideas or underlying knowledge/disciplines that collide just at the right time to achieve an initial breakthrough. This leap forward probably then has to be pursued diligently, including likely a few blind alleys, and frequently requires a different focus and skill set beyond the innovators. There has to be good and clear communications with ability to learn to convey complex arguments so other understand and can build on (and Real Innovators usually are able to translate well). Importantly it takes adequate resource of people, facilities , equipment and money to support.

While certainly poor CEO and R&D Leadership, with conventionally HR being a over willing compliant control tool, can stifle an innovative culture, it is by no means true a science-friendly more free environment automatically will achieve the desired progress. The last several decades in Biotech probably has provided examples of all types but suggest the majority set out to attempt to build and maintain a climate to support innovation and even with a few successes not very many have ever succeeded. Maybe much has already been squeezed out of Big Pharma, and innovation isno longer at their core but its hard to believe Biotech, Academia and/or Government won't end up spending more and continue to stumble along in attempting to create new drugs any better.

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49. Electrochemist on August 20, 2013 1:30 PM writes...

By its very definition, disruptive innovation cannot come from Pharma (at least big Pharma). True disruptive innovation in the space where Pharma plays today is more likely to come from stem cell research, gene therapy, or some other advance that will make chronic treatment of disease with synthetic molecules (or even monoclonal antibodies) obsolete. Ways to "cure" diseases (addressing the root causes rather than treating the symptoms) will be disruptive, not a different colored tablet or a trendy new injection device.

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50. hibob on August 20, 2013 2:45 PM writes...

@Bernard Munos #29: Thank you for responding to me. I apologize for the harshness of my tone. My worries aren't directed towards your and Christensen's Disruptive Innovation concepts. My worry is that "Disruptive Innovation" as a label and family of products (management consulting, seminars, books etc) will follow the same path as other management consulting movements: it will gain value via expansion to business areas where it is completely inappropriate to the mission but highly useful for career advancement and selling consulting services.

You brought up six sigma. Six Sigma was and is a method of examining manufacturing process data so as to decrease variance in the products. Need to punch the same shape of hole in the same place in an aluminum panel every single time? Six Sigma.

It was intended for the opposite end of the pipeline as far as Pharma and Disruptive Innovation are concerned, and it was an awesome development. It has probably underlain QA/production at many of the companies you have worked with in the past 15-20 years; it also probably improved all of the instrumentation those companies purchased in the past 15-20 years. Six Sigma was so awesome that everyone heard about it.
So what happened?
Disruptive Innovation happened - to Six Sigma.

Six Sigma was reinvented by management consultants (and Jack Welch) in new configurations to accomodate every sector of a business operation, from HR to marketing to research. Six Sigma branded products and people were able to create and exploit new markets and value networks for the management consulting field. It completely upended management consulting. It was contorted and applied to people instead of processes, departments instead of data. This resulted in Six Sigma's memorable roles in pharma R&D: which projects to fund, where to put how many HPLCs in which buildings, which people should be talking to which people when and how often, etc.

So what happens when consultants try to apply the Disruptive Innovation concept to "Disruptive Innovation" products and services so that they too can exploit a new "Disruptive Innovation" consulting market? Probably not more disruptive innovations, but you can already google "disruptive innovation agile lean" to see some of the outcomes."Disruptive Innovation", the family of products, expands to include linear processes and buzzwords to be packaged and sold to everyone who needs the bullet point on their res