An appreciation of the prescience of Don Gilbert (1930-2011): master of the theory and experimental unravelling of biochemical and cellular oscillatory dynamics

Abstract

We review Don Gilbert's pioneering seminal contributions that both detailed the mathematical principles and the experimental demonstration of several of the key dynamic characteristics of life. Long before it became evident to the wider biochemical community, Gilbert proposed that cellular growth and replication necessitate autodynamic occurrence of cycles of oscillations that initiate, coordinate and terminate the processes of growth, during which all components are duplicated and become spatially re-organised in the progeny. Initiation and suppression of replication exhibit switch-like characteristics, that is, bifurcations in the values of parameters that separate static and autodynamic behaviour. His limit cycle solutions present models developed in a series of papers reported between 1974 and 1984, and these showed that most or even all of the major facets of the cell division cycle could be accommodated. That the cell division cycle may be timed by a multiple of shorter period (ultradian) rhythms, gave further credence to the central importance of oscillatory phenomena and homeodynamics as evident on multiple time scales (seconds to hours). Further application of the concepts inherent in limit cycle operation as hypothesised by Gilbert more than 50 years ago are now validated as being applicable to oscillatory transcript, metabolite and enzyme levels, cellular differentiation, senescence, cancerous states and cell death. Now, we reiterate especially for students and young colleagues, that these early achievements were even more exceptional, as his own lifetime's work on modelling was continued with experimental work in parallel with his predictions of the major current enterprises of biological research.

Keywords: cell differentiation and oncogenesis; cell division cycle dynamics; cellular ageing and senescence; limit cycle oscillations; temporal controls; ultradian rhythms of enzyme amounts and activities.