Platt's 1964 essay on strong inference [1] illuminates a rational approach to scientific inquiry that integrates seamlessly with current investigations on the operation of complex biological systems. Yet in re-examining the 1964 essay in light of current trends, it is apparent that the groundbreaking approach has failed to become universal. Here it is argued that both the opportunity and the need to follow Platt's advice are now greater than ever. A revised method of strong inference for systems biology is presented and applied to analyze longstanding questions in cardiac energy metabolism. It is shown how this logical framework combined with computational-based hypothesis testing illuminates unresolved questions regarding how the energetic state of the heart is maintained in response to changes in the rate of ATP hydrolysis.
展开▼
