The NIH system stifles creativity. Why not empower the R21?

Dario Maestripieri pointed to an Opinion by Fred Southwick in The Scientist over at The Creativity Post. Southwick’s point, in part:

The maladaptive insistence that research scientists obtain their financial support by continually writing federal, state, and private grants often prevents scientists from stepping outside the boundaries established by this grant process. Because the success rate is now down to 10 percent, academic scientists are forced to spend much of their time writing proposals, rather than performing creative research.

The balance of his remarks seem mostly directed at what University changes are needed.

Maestripieri adds a bit more finger-pointing at the NIH (and other major granting agencies):

Obtaining research grants has become an increasingly competitive business. Many more people apply for grants now than in the past while the amount of funds available has remained the same or decreased. Federal funding agencies fund only about 10% of the applications and grant review panels have become highly risk-averse. They tend to fund proposals by well established investigators, which often represent replications or minor extensions of previous work, while creative, original, and riskier proposals by young researchers are penalized. The funding issue has its origin outside of academia and its solution must also come from outside of academia: a political decision to allocate more funding to research.

More money, yes. But let us not take our eye off the ball.

Those of you* who have been with me for all these years should remember from whence this blog voice came.

One of the problems that I have always had in my head, driving my comments about fairness to young investigators, is that of the inherent conservatism of the NIH granting system. This comes from two major sources. First, the peer review by those who are already well-ensconced in the system. That means people who were selected by that system for success. You have to have been awarded an R01 to serve on a review panel, mostly speaking. This means you have to be able to at least fake writing the grants the way the established folks “expect” to see them. If you can’t….you are going to fail. It means that you have to propose science that those who are already on the inside “get” in some way. Sorry, but even in the 25 page days, that wasn’t necessarily long enough to get three people totally on board with your ideas. It helps a lot if the reviewers are already predisposed to see things your way.

The second major driver is the review culture often expressed in words such as “risky”, “feasibility”, “fishing expedition”, “insufficient supporting preliminary data”, “untried investigator”….and “highly productive scientist can solve any problems that may arise”

It can sometimes** be appallingly conservative on panels.

Being something of a student of the past few decades of research supported in my areas of interest, mainly by NIDA, I’ve been bothered by all of this and the Street Lamp Problem***. The SLP is common in science, far too common. And before you get all huffy, yes we all suffer from this on occasion. It may not be such a bad thing for labs but it is death for a broad-based funding agency such as the individual ICs of the NIH.

To give you a flavor, that has trickled through my posts now and again, the preclinical drug abuse world has two theoretical poles that have driven much of the research modelling. One is the “feel good” or reinforcement side. The notion being that if we understand why drugs make us feel good and why they may stop making us feel quite as good (for a given dose) then we’re on to something. The other pole says, nonsense, this is about feeling bad. Everyone feels good on drugs but not all become addicted****. What really matters is that some people start to feel so crappy when they are not intoxicated that it drives them to take more just to feel normal.

For a very long period of time the reinforcement types ruled the day. They had the tools, the simplest models, the biological targets were obvious. Cocaine, meet dopamine transporter. easy peasy.Ditto heroin. Methamphetamine? No problem. And the current midcareer “reinforcement” butt kickers sucking up all the NIDA money are at least three scientific generations removed from the start of this.

umm, “feeling crappy”? where’s the target? how do you even define that in a mouse?.

Anything rats won’t readily self-administer intravenously (THC, nicotine) or where the targets weren’t known (THC, Alcohol)….well, shrug. The light isn’t very good over there. So they received short shrift. At NIDA. Luckily in the case of alcohol there was a whole ‘nother IC devoted to it. It is no coincidence that one of the the main drivers of the “feel bad” pole is dug in much more deeply at NIAAA than ever at NIDA.

Things eventually opened up. The CB1 receptor was cloned and the streetlight flickered into life above THC research. Some folks finally worked out what was UP with nicotine self-admin and that started rolling. People flogged the hell out of “reinstatement” and “escalation” models to try to get past a couple of problems with the straight-up acute “feel good” models.

Funding-wise, it took some heroic efforts, if you ask me. Remember, all the while the scientists were working through this, the Program staff was getting their best intel from those scientists. People made discoveries and published papers and kept getting high grant scores. So Program thought they must know what they are talking about. The fringe complainers? Bitching about their biased grant reviews? Failing to publish their ideas convincingly (because they can’t get the awards, of course)? Chalk them up to lunatic fringe, right? “Come back when you convince us all”, they are told.

But we haven’t learned our lesson, I have little doubt. In fact, we (as a whole enterprise- scientists and Program staff are doubling down. Kill the R21! Circle the wagons on feasible projects where the “significance” and “likely impact” is obvious to all. Demand more Preliminary Data. Save the Small Town Grocer and the Noonans. Just keep plodding along with your models, the same as half a dozen others, and you deserve “your piece of the pie”.

“Innovation” can only come from within a defined space of the “feasible”.

I could cry for wholesale changes. Dismantle everything. Break down the large, established groups, radically restructure grant review panels and turnover your entire Program Staff with their “established relationships”. But that’s not going to happen.

What we can push for is the restoration of the R21. The expansion of it, perhaps. With the very, very firm goal of making sure the ones getting high scores are “Exploratory”, “Developmental” or both. It can be done. The simplest way would be to give extra bennies on an R01 application that arose from a prior interval of R21 support. But you could get the right reviewers and instruct them properly as well. Some of us get R21s. Some of us can’t help but talk about supporting data and whether it is going to “work”. SROs know who is who.

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*PP and maybe one or two others.

**often. Not always, often.

***Policeman comes across obviously drunk guy searching through gutter at night under a street lamp and inquires as to the problem.
“Lost m’ keys” slurs the drunkard.
“And where did you lose them”, queries our intrepid flatfoot.
“Up the block on my way home from the bar.” is the reply.
“So why on earth are you looking here, my friend?”, puzzles the copper.
“The light is better”, comes the response.

****Ok, in fairness while that is my take, it is only recently that people are coming around to this extent.