Nature Genetics on conclusion by exclusion


“Science is a way to distinguish things we know not to be true from other things. Large challenges lie ahead as we apply the scientific method to understanding biochemical systems, cellular organization and the functions of complex organs such as the brain.” So begins the February Editorial in Nature Genetics (42, 95; 2010). If the success of the early years of molecular biology can be attributed to the simplicity of the problems to solve, combined with rigorous experimental design including disprovable hypotheses and decisive experiments, what of todays immensely more complex scientific landscape and greatly increased number of scientists, not to mention orders of magnitude more computer power? Are we better equipped to generate, experimentally test, and choose or discard competing hypotheses?

The Editorial argues that “the complexity of a research project does not change the basic requirement for inference so long as the results are intended to be understood by human brains. A model or predictor aids secure inference when it is treated as a falsifiable hypothesis with falsifiable sub-hypotheses. Therefore, we would expect to publish a list of conditions in which the model or predictor is not valid, and tests demonstrating conditions in which it is not valid, as well as hypotheses drawn from the model or predictor and tests that disprove these hypotheses.

There are a number of benefits to separating the logical gems that authors are prepared to have tested by others from their setting of consistent observations and rhetoric that is not directly part of the scientific work of the paper. These pluses are: to allow peer referees to do their job and readers to understand the work; to make clear the caveats and limits to application of results to other fields; to limit proliferation of useless observational studies and reduce duplication and waste of effort.

It may also be possible to distinguish the direct influence of the research independently of the publications that describe it. In order to do this, each of these two components—hypotheses and experiments—will need to be coded with unique identifiers and separately cited. Such an extreme cultural change may not be needed if publications are carefully structured. Surely it is obvious that a study providing strong inferences will be both well used and highly cited.”


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