The seeds of systems biology were sown 450 years ago by a classic medical text, explains G. Rickey Welch.
The Physiologia of Jean Fernel
Translated and annotated by John M. Forrester American Philosophical Society: 2003. 636 pp. $24(pbk)
The Physiome Project, spearheaded by the International Union of Physiological Sciences, aims to generate a framework for understanding the workings of the entire human organism, from genes and proteins to the whole body. A seminal Latin medical text presaged this venture around 450 years ago.
Its author, Jean Fernel (pictured), was one of the foremost figures of French Renaissance science and medicine, and the first to use the term 'physiology' in its modern scientific sense. At the time, 'physiologia' denoted the study of nature or natural philosophy. First published in 1542, Physiologia underwent more than 30 reissues, and caused debate in Europe for the next 100 years.
Physiologia, together with Pathologia and Therapeutice, was one of three volumes that comprised Fernel's crowning work, Universa Medicina. Physiologia set forth a fundamental theory of the operation of the human body: the nature of the wholly healthy human being, all the powers and functions. This flowed into a description of diseases (Pathologia) and their treatments (Therapeutice). Fernel's opus resonates today in the goal of the Physiome Project, which is 'to understand and describe the human organism, its physiology and pathophysiology, and to use this understanding to improve human health'.
In Fernel's time, medical practice centred on the study of body parts in lavishly illustrated anatomy texts, by authors such as Andreas Vesalius. Fernel attacked this 'shallow and easy art', arguing that it lacked holistic principles of causation and function. His answer, Physiologia, is a brilliantly logical treatise. Fernel begins with a philosophical reflection on the appropriate means of analytical attack, and he settles on a top-down method — one that we recognize in today's physiological practice. He then describes all the known anatomical parts of the human organism and develops his notion of a 'comprehensive physiology.' Seizing on the Aristotelian principles of deductive reasoning, causal analysis and physics of matter, Fernel demonstrates how the elemental attributes of the body parts are woven into a whole that manifests all the temperaments, humours, powers and faculties of the living being. Although he characterizes the causation of bodily processes within the framework of the 'animal spirits' proposed by the ancient Greek physician Galen, Fernel envisaged such 'spirits' in a real material form, breaking from the irrationality of occultism and magic that had dominated medieval natural philosophy and medicine.
Physiologia constitutes the first complete view of what we now call physiology. It is also a forerunner of the systems approach to understanding form and function in living organisms. The field of systems biology today presents us with a challenge similar to that faced by Fernel — to interpret staggering amounts of data depicted in numerous pictographic forms, such as DNA microarray snapshots, proteome network displays and protein–protein interaction maps. Although causation has come to be assigned to a molecule, namely DNA, the way in which we should map from genes to the organism is far from apparent. The Physiome Project embraces the systems-biology movement by showing us how the whole is more than the sum of the parts.
Denis Noble, one of the founders of the project, proffered that “a major part of the future of physiology surely lies in returning to our roots. Higher-level systems biology is, I suggest, classical physiology by another name.” We might say that the Physiome Project began at the dawn of the scientific revolution with Physiologia. Fernel's Renaissance thinking pointed the way to a 'universal medicine' that we are now poised to attain.
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