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Wednesday, November 30, 2011

Follow up #2 to Why we must generously fund NIH: Budget pressures stifle scientific creativity

Part 2 of a 3-part follow up

Part 1 can be found here

Budget pressures on NIH are stifling scientific creativity, and creativity is what makes great science. Budget pressures amplify the risk-aversion noted by Tim Harford in his May 2011 Slate article “Positive Black Swans”, which described the career and life of Nobel Laureate Mario Capecchi, whose 2007 Nobel Prize winning idea in mouse genetics initially was rejected in 1980 by NIH grant reviewers because it was deemed too risky and speculative:

“The NIH's expert-led, results-based, rational evaluation of projects is a sensible way to produce a steady stream of high-quality, can't-go-wrong scientific research. But it is exactly the wrong way to fund lottery-ticket projects that offer a small probability of a revolutionary breakthrough. It is a funding system designed to avoid risks—one that puts more emphasis on forestalling failure than achieving success. Such an attitude to funding is understandable in any organization, especially one funded by taxpayers. But it takes too few risks.”

An analysis by MIT economists Pierre Azoulay, Joshua Zivin, and Gustavo Manso supports the idea that funding strategy strongly influences the degree of creativity, exploration, and innovation that can be achieved by scientists. Their study entitled “Incentives and Creativity: Evidence from the Academic Life Sciences”, began by highlighting the example of Mario Capecchi noted above, and compared productivities of researchers supported by NIH funding to those supported by funding from the Howard Hughes Medical Institute (HHMI). HHMI provides substantial flexibility to the Principal Investigators it funds by offering long grant funding periods (5 years for a first award) and by encouraging creativity that may result in initial failures but lead to long-term successes. By contrast, NIH research grant durations tend to be shorter, about 3 years, and creativity is not fostered by the system which now seems less tolerant of out of the box thinking and of the potential for failures than ever before.

After controlling for the fact that HHMI researchers tend to be more “accomplished” than the average NIH-supported investigator (by comparing the HHMI sample to early career prizewinning NIH researchers, a matched-by-accomplishment sample), Azoulay and colleagues reported major differences between HHMI and NIH researchers. HHMI researchers had more freedom to experiment, fail, and ultimately innovate. The study concluded that the different incentive schemes offered by HHMI and NIH have dramatic effects on creativity and innovation.

This difference is important, as the ability to explore, and fail, is key to scientific innovation and discovery. Neuroscientist David Eagleman, writing about his wide-ranging research in a New Yorker piece entitled “The Possibilian” (April 25, 2011), described an encounter with Nobel Prize winner Francis Crick, who offered advice about a career in research, saying “…The way real science goes is that you come up with lots of ideas, and most of them will be wrong.”

Scientists know that this is true. Ideas are hypothesized, tested, and refined, and many of them are discarded. Sometimes along the way, new ideas germinate from serendipitous observations that were not planned at the outset of an experiment that lead to breakthroughs. Perhaps the most famous “accident” of science involved Alexander Fleming, who in 1928 was researching bacterial cultures. He discovered a mold that was killing his cultures and ruining his experiment—today we know that mold as the antibiotic penicillin, which has saved countless lives.

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Another Nobel Laureate, Arthur Kornberg, writing on this theme in an article entitled “Of Serendipity and Science” (published in Stanford Medicine Magazine, Summer, 1995), lamented the lack of funding for science: “…today we are suffering from the lack of adequate financial support for basic science, a poverty worsened by severe pressures to engage in "strategic" research…the pursuit of curiosity about the basic facts of nature has proved throughout the history of medical science to be the most practical, the most cost-effective route to successful drugs and devices…Investigations that seemed totally irrelevant to any practical objective have yielded most of the major discoveries of medicine”.

So, it seems that offering flexibility, allowing creativity, and supporting seemingly basic and sometimes apparently esoteric research are the most efficient ways to lead to scientific breakthroughs.

While it would not likely be possible for NIH to broadly review and fund research like HHMI, the point here is that subjecting NIH to any budget contraction, either by direct budget cuts or by appropriating flat budgets that don’t take into account inflation, will amplify risk-aversion at the NIH reviewer and program levels. This could squeeze out creativity and innovation and result in fewer bricks being added to our collective wall of scientific knowledge, which could undercut our ability to achieve future scientific and medical breakthroughs.

This is a very bad idea, not only because our investment in NIH has resulted in tremendously positive public health benefits, but also because NIH-funded research is a major economic engine for the United States (see Part 3 to follow).

A summary of this article series can be found at:


http://www.cpddblog.com/2011/11/open-letter-to-congress-why-we-must.html


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