In modern biophysics there is a need for principles. An attempt at finding principles can be found in the miracle book by Bill Bialek: Biophysics, that some of you have used as a textbook in the course of Theoretical Biophysics. This 1983 article by John A. Wheeler, founder of modern gravitational theory and influential figure of the physics of XX century candidly outline the epistemology of complex situations. To my knowledge this is a pioneering paper also in the context of modern biophysics.