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Challenges of Identifying Potentially Transformative Research

corn genome History shows that it is difficult to predict which research projects will result in transformative results before the research is conducted and the scientific community has assimilated the findings.

A classic example of this challenge is Barbara McClintock's pioneering cytogenetic research in maize. In 1944 McClintock theorized that genes are transposable on and between chromosomes. After years of observation and controlled experiments she published her first work on genetic transposition in 1948. Because her research challenged conventional wisdom it was not accepted by the scientific community until many years later. A decade passed before the importance of McClintock's discovery was accepted by the scientific community. In the early 60s, research on genetic regulation demonstrated some of the same concepts that McClintock had championed. Molecular techniques developed in the late 60s and 70s demonstrated the molecular-genetic mechanisms of transposition discovered by McClintock. With time, the significance and transformative nature of her research became widely accepted and her accomplishments were honored with the National Medal of Science in 1971 and the Nobel prize in 1983. Advances in Maize genomics that have resulted from the Plant Genome Research Program continue to echo the relevance of McClintock's controversial but transformative research.

scientific image Although identifying transformative research in the early stages is a challenge, NSF recognizes the enormous importance of distinguishing proposals that contain potentially transformative ideas or concepts. For example, potentially transformative research proposals may request support for dramatically new ways of conceptualizing and addressing major scientific or technological challenges. Other potentially transformative research proposals may request support for key incremental or threshold advances (e.g., new methods or analytical techniques) that, if successful, could put a discipline on a new scientific trajectory, provide tools that allow unprecedented insights, or radically accelerate the rate of data collection. Alternatively, some proposals may generate serendipitous transformative results that would have been almost impossible to predict prior to conducting the research (e.g., research on small, ribonucleic acids (RNAs), and the unanticipated discovery of their pervasive role in gene regulation).

Fundamental research in one discipline can often have a profound influence on another. Three scientists with vastly different backgrounds and experiences all share the Nobel Prize for Chemistry. The serendipitous discovery of green fluorescent protein (GFP) by a marine biologist interested in bioluminescence in jelly fish, resulted in an amazingly useful biological tag that allows scientists to track cellular processes. Osamu Shimomura isolated GFP from the bioluminescent jellyfish Aequorea victoria in 1962. Shimomura's fundamental research was aimed at explaining how marine organisms produce light. In 1988 Cell biologist Martin Chalfie put GFP to use as a cellular marker in studies of nerve cell development. Chalfie introduced the gene for GFP into the DNA of C. elegans and demonstrated that it could be used to monitor gene expression and protein localization in living organisms. Chemist Roger Tsien later developed GFP as a fluorescent probe and produced additional colors. Although GFP is now considered an incredibly important tool, it all started with the search for fundamental knowledge.

While acknowledging that there is no ideal way to determine a priori which research proposals will ultimately yield transformative results, NSF must ensure its funding programs have review practices that help identify those proposals that are highly innovative. This is particularly challenging because innovative proposals often involve an element of risk if they are using new or novel methods. Reviewers find preliminary data convincing, but truly new ideas may not have been tested to the point that such data are available. NSF must also ensure that potentially transformative research proposals are not adversely considered because of scientific bias, lack of appropriate reviewer expertise, or low risk tolerance associated with constrained funding.