Biology coming full circle: joining the whole and the parts

Abstract

The new cover of Experimental Biology and Medicine features the hermeneutic circle of biology, a concept we have adapted from the hermeneutic principle that one understands the whole only in terms of each part and the parts only in terms of the whole. Our hermeneutic circle summarizes the course of experimental biology through 2500 years of the achievements of reductionist research (understanding the parts), which culminates in our ability to rapidly sequence the genome. Rather than returning along the same path in a constructionist approach that simply builds upon this knowledge, but in reverse, an alternative is to close the circle with synthetic constructions that seek to integrate the full complexity of biological and physiological systems (understanding the whole), of which organs-on-chips are one example. This closing of the circle cannot be a comprehensively accurate representation of biology, but it can be a synthetic one that effectively defines particular biological subsystems. The illustration of the hermeneutic circle of biology is also intended to suggest both the multiple cycles that may be required to reach such a synthesis and the expansion of the circle in an outward spiral as knowledge increases. Our commentary explains the symbolism of the new cover in a philosophical and scientific discussion.

Keywords: Hermeneutic circle; physiology; reductionist vs. constructionist; synthetic biology; systems biology.

Figure 1

The new cover for Experimental Biology and Medicine (EBM) that shows the hermeneutic circle of biology on the right (front cover) and the topical areas of EBM on the left (back cover). The circle begins with the animal or organism at the top and progresses counterclockwise through organs, cells, metabolic and signaling networks, biomolecules, and finally the genome at the bottom, thereby representing the reductionist limit of biology. Continuing up the right side through the synthesis of molecules, instrumented and controlled cells, engineered tissues, and engineered organs (including organs for regenerative medicine and organ-on-chip microphysiological systems), the circle closes with a representation of the human that integrates these syntheses. It may be necessary to traverse the circle multiple times, and also to employ corresponding circles for the classic biological model organisms that range from bacteria and yeast to zebrafish

Figure 2

A simplified, linear view of the history of biology and medicine, showing the directions of reduction and construction