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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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« Prasugrel: Come Back This Fall | Main | Funding in the EU: The Simple Way »

June 25, 2008

(No) Anarchy in the EU: A Report From Inside

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Posted by Derek

My post a few days ago on research in the EU, quoting a letter to Nature from Dr. Theo Wallimann in Zurich, started off a long comment thread. And now I've heard from Dr. Wallimann himself, who has a wealth of personal experience with research funding, with the EU, and with large consortia of academic groups.

He's sent along a very interesting commentary, which I'm going to post in two parts. Today is on what EU research funding is like, and tomorrow it'll be on what it could (or should) be. So here's Dr. Wallimann with a report from the field:

I did by no means intend to say that important findings can only be made by lone wolf scientists, but wanted to say that if (and I am talking here about basic science, not industrial applied science), small groups are left to work independently, with passion, in the realm of those things that interest them from the inside of their spirit and heart, then the chances of making an unexpected finding are statistically much higher - compared to a granting agency telling you what topics should be worked on in order to qualify for funding.

Once an important finding in basic science has been made, it is relatively easy to find partners and to build up from the bottom a collaborative interdisciplinary team, even up to Manhattan Project-like applications. The latter step is mostly a matter of finances, for one knows what has to be done, since the basic findings and ground-work has been done by the basic scientists.

It is fact that the EU agencies (and probably most of the research funding agencies) want to see such interdisciplinary research networks even before any novel findings have been made. They tend to focus on relevant societal problems, like cancer, obesity, climate change, etc. And this is bloody ridiculous, for this encompasses only (or mostl) those scientists who just happen to work in these areas and who may happen to be excellent or mediocre. But it excludes other groups, mostly younger ones, who may not directly work on such a topic, but whose findings may turn out to be most important for them in the future.

What I would like to stress fervently is that true science is not predictable. If you already know what you want to find out it is no longer truly innovative science: this is exactly what Albert Einstein meant (and explicitly said), and what Albert Szent-Gyorgyi, the archetype of a "Free Radical", said as well. The latter Nobelist (for Vitamin C and on muscle contraction) never received substantial research money from NIH, for he refused to write a 50 page grant proposal exactly delineating and spelling out what he wanted to do during the next 3-5 years. He said, "How can I say what I am going to do in the laboratory in 3-5 years, if I don't even know today what I shall do there tomorrow".

I have been working in an "enforced" consortium of a EU program with a total of 26 laboratories Europe-wide. The sheer size of the consortium, with all of its members focusing on different aspects of the same global question, apparently seems to have been the most convincing argument for the EU administrators The program was substantially funded and we all profited indeed from this financial support, although the administration and book-keeping and report-writing efforts were horrendous. However, as it turned out, when the members met and got acquainted and divided into sub-groups (so-called “work-packages”), one had to realize relatively quickly that one was sitting on a table with competitors who worked on the very same problems as oneself. And example would be wanting to grow crystals of an important enzyme to solve its X-ray structure and from there, to design inhibitors or activators for pharmacological intervention.

So my question now is: how are you going to communicate in such a group? Which of your secrets that would give an advantage to the competitors are you going to spell out? Which hints does your neighbor disclose to you? And so on. This fact led to some rather awkward situations where people were sort of lingering around the real questions and problems and all tried to talk about those results that had just been accepted in a publication and were to be in press very soon. So here is the situation, we were forced to officially "collaborate" by the EU program, in order to get at the EU research financial honey-pot. But once we had the money, we would rather have preferred to work independently again and not share bench data with competitors.

By contrast, if the EU would foster independent smaller groups and if one then made an important finding, they themselves could go out and look for ideal collaboration partners on the spot without any granting agency telling them what to do and whom to consider. This gives a project a real kick-off, since such partners can be specifically selected for mutual compatibility and collaboration. Certainly, they would have to be as passionate as the original about the new finding and call in some other colleagues who would complete a strong team. Finally, such self-organization leads to true potentiation, but desktop planners can definitely not enforce this, I am convinced.

I was participating yet in another consortium program that was overshadowed by its own so-called steering committee. They felt responsible for the success of this program, so they started to strongly interfere and prescribe to us what to do, out of anxiousness that something unpredictable could happen. This simply shut down any possible creative outcome for this program.

As mentioned above, if a basic science program is successful in finding something really novel and important, only then can a "Manhattan Project"-like application of the basic research lead to an applied mega-project.

Many of the commenters here seem to have a misconception about the difference between basic science versus a Manhattan Project. I hope that this helps to clarify some of these issues, and I wish that you could come to work in a basic research laboratory for at least 10 years. You could easily grasp then what I mean to say here, I think. Thanks for your consideration and patience.

Comments (13) + TrackBacks (0) | Category: Who Discovers and Why


COMMENTS

1. cookingwithsolvents on June 25, 2008 8:15 AM writes...

Well said!!

I would contend that it might be easier for funding agencies (and the public) to think of basic research as more of an art than a "science". It always seems to me that in many minds science is something akin more to engineering or development. I wonder if that fundamental misconception arises of how science is taught in school. . . i.e. "this and that are known" which lead to tang, ipods, and heart bypasses.

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2. Still Scared of Dinosaurs on June 25, 2008 9:50 AM writes...

"Once an important finding in basic science has been made, it is relatively easy to find partners and to build up from the bottom a collaborative interdisciplinary team, even up to Manhattan Project-like applications."

That statement cannot be allowed to pass unchallenged on a biopharma-industry blog. Well, maybe it's easy to build the team, but to get anything useful out of it you need huge amounts of hard work, timely bits of good luck, and, most importantly, predominantly non-negative contributions from its leadership.

That's what we're up against and we see it fail every day. Well, come to think of it, I've never seen one fail due to lack of effort, and only occasionally due to bad luck. I wonder what it could be...

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3. pi* on June 25, 2008 11:08 AM writes...

"That statement cannot be allowed to pass unchallenged on a biopharma-industry blog."

You miss the whole point, then you agree with him. I think you just like to hear yourself talk.

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4. Brazillions of drugs on June 25, 2008 12:45 PM writes...

Can we please stop comparing everything to the Manhattan Project? It's a bad example because it's an exceptional one when people got together essentially because they were scared to death of the Nazis dropping an atomic bomb on Washington. How many times exactly do we face such a scenario?

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5. Cellbio on June 25, 2008 12:48 PM writes...

"Once an important finding in basic science has been made, it is relatively easy to find partners and to build up from the bottom a collaborative interdisciplinary team"

Oh yeah? While I agree with much of what has been said, this is silly. Why would the human dynamic discussed in terms of basic research not apply to teams executing their crafts in the development phase? I worked in this environment for years, both in the trenches and in management. The issues of competition, recognition and reward for individuals within a group are all reflective of human factors that apply here as well. It takes quite a bit of skill and leadership to make this work well. Poor leadership and corporate culture are significant contributors, in my opinion, to the failure of so many teams of highly skilled individuals.

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6. milkshake on June 25, 2008 2:16 PM writes...

EU has to do something because it has fallen behind US scientifically. There is much better public financing in US, with more money going into acedemia so the academic groups are larger (and PhD and postdoc both take one year longer than in Europe so there is plenty of low-paid lab slaves available).

Not all of it leads to better science of course but my exposure to some famous synthestic groups in US convinced me that they not necessarily had more brilliant PIs than other less famous groups - but they were very persistant, motivated and self-disciplined bosses who could motivate their students and postdoc to work hard in one particular direction and over the years pursuing their program they eventually went further than anybody else before and were hence in position of profiting from the unexpected findings there. The positive momentum of a well-run group makes it easier to have more success and so on. (The negative momentum builds up in the same way - frustrated and discouraged people, poor funding etc - I new this one from East Bloc; mostly the younger people there were still doing interesting work, others got already resigned)

Grant and publication-output system of rewarding money for research is painful for the PI and it leads to abuse when applied incorrectly - but with all its flaws it is the best system devised so far because it allows to weed out the unproductive groups. People tend to be more rational when they have clearly defined (limited) budget and can make free choices about how they spend it and are required then to provide account of their work and need results to ensure their research survival.

Bottom-up approach in collaboration is inherently better than anything a wise committe can come up with

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7. Canuck Chemist on June 25, 2008 2:31 PM writes...

I think a lot of you are still missing the point. No, development (i.e. creating practical applications from established basic science) is far from trivial-- just look at the current difficulties with pharma and biotech. I'm sure that our guest did not intend to frame development (or applied research) as trivial, but the point is that it is very different, and requires a different structure, from purely basic science, which by definition is difficult (if not impossible) to plan for. I don't think any of us have easy answers for how to make funding decisions involving basic science, but I am in complete agreement with Dr. Wallimann that big committees and huge collaborations is definitely NOT a good approach for breakthrough science.

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8. CMC guy on June 25, 2008 2:34 PM writes...

Although I can see expected nuances between someone from academia setting verses industry in comments I think Dr. Wallimann is right on track. I am looking forward to 2nd half exploring options fro change.

Perhaps he meant to express "relatively easy to find interested partners" as he does not seem to trivialize what is needed for compatible teams to be successful. Several statements point to need for good leadership theme.

I don't like comparison to art as would favor comparison to exploration of a new jungle. Some Adventurers cut the first trails and be windy and hard to follow. Later others follow or diverge from those initial trails. Eventually roads may follow the paths laid down.

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9. Anonymous on June 25, 2008 2:58 PM writes...

"You miss the whole point, then you agree with him. I think you just like to hear yourself talk."

Well, thanks for the in-depth analysis. My point was that pharma people spend their careers fighting to hold development plans together after the basic discoveries have been made. Walliman dismisses that effort. Maybe I should have given a bigger quotation, "The latter step is mostly a matter of finances, for one knows what has to be done, since the basic findings and ground-work has been done by the basic scientists."

Either he is not including clinical development or he is delusional.

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10. Counterview on June 26, 2008 1:06 AM writes...

"So my question now is: how are you going to communicate in such a group? Which of your secrets that would give an advantage to the competitors are you going to spell out? Which hints does your neighbor disclose to you?"

This is exactly the inefficiency that is spawned by lots of small groups working independently rather than larger groups working with a common goal.

"It is amazing what you can accomplish if you don't care who gets the credit." --Harry S. Truman

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11. Theo Wallimann on June 26, 2008 4:40 AM writes...

OOPS-

"Once an important finding in basic science has been made, it is relatively easy to find partners and to build up from the bottom a collaborative interdisciplinary team, even up to Manhattan Project-like applications."

sorry, by any means, I did not intend to discredit translational research and development, my view may be tinted from my own mis-education in academia.

A perfect example of what I mean by discovery via serendipity has just been published in the most recent Nature issue. I would bet that this project combining biology with material science in a rather exotic way did never appear in a research proposal (or may I be wrong?) and it may be very interesting to see what comes out of it.
Now, the translational phase, e.g. from the computer industry could set in and perhaps one can to something useful or even amazingly new things


see under : Research Highlights

Nature 453, 1146 (26 June 2008)
Published online 25 June 2008
Materials science: Diatomic power
Adv. Mater. doi:10.1002/adma.200800292 (2008)
Materials science: Diatomic power

Single-celled plankton that have been duped into doping their silica-based shells with germanium can be incorporated into semiconductor chips and made to glow.

Gregory Rorrer of Oregon State University in Corvallis and his colleagues report that the siliceous shells from diatoms (Pinnularia sp., pictured) that were grown for some of their lives in a germanium-rich solution can be incorporated into the devices. On application of an electric field, the shells emit light.

The researchers found resonant frequencies in these emissions that they explain by the geometry of the shells' latticework of pores. They hope that further combinations of semiconductor technology and biologically produced nanostructures may yield novel devices.

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12. A-non-y-mous on June 26, 2008 4:57 AM writes...

Prof. Wallimann makes some very good points, and expresses himself very well, but I have 2 quick points.

1) If you're in a "work package" and worried about spilling your secrets, then you don't belong there. That person is more interested in themselves than the project at hand. When asked, I'm sure these scientists will say they do their work to advance the human condition, cure disease, and unravel the mysteries of the universe, all for the love of science, but when push comes to shove, it's all abut them and their ego. I find it sad.

2) Never underestimate the power of money. Money drives science. Always.

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13. Theo Wallimann on June 26, 2008 6:26 AM writes...

To: 12) A-non-y-mous
You make a very valid point: it is indeed very sad that often "the ego rather than advancing the hiuman condition" is what counts, yes!
However, one needs to realize how science works in these days. As you may know, in order to receive a research grant one needs to produce and show results. For example, if your group is involved in trying to solve an X-ray atomic structure of a protein, there will be only one structure to be reported for the first time, and the group that successfully solved such a new structure first, will be able to publish it in a very high impact journal and due to this fact, again, will be successful in attracting more grant money and so on, a self-amplification effect.
So, due to limitation of research money, basic science is indeed very competitive and truly Darwinian.
And this fact can be, as mentioned, an especially serious problem in large Research consortia. Unless one would make, as I would propose, an agreement at the start of consortium work, that would oblige to really share all results, worked out within the realm of overlapping projects within such consortia, and at the end would publish the results together.
This, however, may be entirely naive, since some of these research groups are huge and are supported by a number of other research grants. This may complicate things a lot. In other words, if things go bad, a group within a consortium can use consortium information and transmit it, although there is a confidentiality agreement, to a co-worker who is not paid by said consortium, but by an independent separate grant. So it can happen, that information disclosed or cDNA plasmids given to members of the consortium to produce a protein and solve its X-ray structure, can be advantageously used to rig-up a competitive parallel research activity from which, however, no information flows back into the consortium. You would say that such behavior is entirely unethical and you are absolutely right, but how do you want to control and prove such misbehavior ? Many of such project run for many years and are dynamic and change all the time such that reconstruction of research paths are extremely difficult in hindsight.
Thus, we would badly need solid new ethic rules for research in larger consortia that can be enforced, e.g. by punishing offenders by having to pay back the money received from the consortium.
But at the end it is, as you mention, the ethical behavior of each individual researcher participating in a consortium. Competition and pressure, however, and sheer striving for survival in academia can undermine ethical behavior as the number of falsified and muted results is on the increase. Thus, there seem to be inherent problems in the Science System that need to be recognized and talked about.

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