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Putting the Systems back into Systems Biology

This page is the third of a series containing the article Putting the Systems back into Systems Biology by Athel Cornish-Bowden, published in Perspectives in Biology and Medicine (2006) 49, 475–489. A PDF file is also available.


Locke, J. (1689) An essay concerning human understanding, Book 2, Chapter 27, Section 5.

In an animal the fitness of the organization, and the motion wherein life consists, begin together, the motion coming from within; but in machines the force coming sensibly from without, is often away when the organ is in order, and well fitted to receive it.

John Locke (1689)

Cornish-Bowden, A., M. L. Cárdenas, J.-C. Letelier, J. Soto-Andrade, and F. Guíñez Abarzúa (2004) Understanding the parts in terms of the whole, Biol. Cell 96, 713–717

Letelier, J.-C., J. Soto-Andrade, F. Guíñez Abarzúa, A. Cornish-Bowden, and M.L. Cárdenas (2006) Organizational invariance and metabolic closure: analysis in terms of (M,R) systems, J. Theor. Biol. 238, 949–961

We are still far from full and satisfying answers to the questions that Rosen asks about what makes a living organism alive. In general terms his view of the essential difference between a machine and an organism was foreshadowed by John Locke more than three centuries ago, but his detailed analysis is mathematically very demanding. It has been followed up by few other authors, and asserting that the organization is circular is not the same as the same as explaining exactly how the circularity is achieved. The essential point is to recognize that there is a real problem: as he said, the questions are real, and will not go away by virtue of not being addressed—so it is not sufficient to say that we do not like Rosen’s answer. If we regard it as unsatisfactory or just wrong we need to propose an alternative; we cannot pretend that there is no question to be answered. In summary, the classical reductionist approach to science can be understood as a way of understanding the functioning of a whole system in terms of the properties of its parts, but now we must learn to understand the parts in terms of the whole (Cornish-Bowden et al., 2004). To make Rosen’s ideas more easily intelligible to biologists they will need to be put in the context of current knowledge of biology, and the limits within which his interpretation of the circular organization of living organisms can apply need to be specied (Letelier et al., 2006).

Hofmeyr, J.-H. S. (2006) The biochemical factory that autonomously fabricates itself: a systems-biological view of the living cell, in Systems Biology: philosophical foundations

Kauffman, S. (1993) The origins of order: self-organization and selection in evolution, Oxford: Oxford University Press

Maturana, H. R. and F. J. Varela (1980) Autopoiesis and cognition: the realisation of the living, Dordrecht: D. Reidel Publishing Company

Neumann, J. von (1966) Theory of self-reproducing automata, Urbana: University of Illinois Press

I have concentrated here on Robert Rosen’s ideas, because of all the current approaches to our understanding of the nature of life they appear to me to be the most promising. Being also among the least well known they are also more in need of development by other researchers than, for example, the self-reproducing automata of John von Neumann (1966), the autopoiesis of Humberto Maturana and Francisco Varela (1980) and the autocatalytic networks of Stuart Kauffman (1993). Autopoiesis is currently receiving much attention, especially from neuroscientists, and a possible synthesis of Rosen’s and von Neumann’s ideas may be found in an article by Jan-Hendrik Hofmeyr (2006). Rosen often seemed to be so anti-reductionist that he ignored the known facts of the structure and physical organization of biological organisms altogether: these aspects are far more prominent in Kauffman’s approach.

Dobzhansky, T. (1973) Nothing in biology makes sense except in the light of evolution, Amer. Biol. Teacher 35, 125–129

A problem that worries some biologists is the lack of any mention of reproduction and evolution in Rosen’s approach. Surely, they argue, these are the fundamental facts of life as we know it? Theodosius Dobzhansky’s famous statement that nothing in biology makes sense except in the light of evolution (Dobzhansky, 1973) is often quoted, because it expresses an idea that is central to modern biological thinking. Rosen’s omission therefore appears serious at first sight, but until our early ancestors had solved the problem of staying alive—existing as organisms in Rosen’s sense—questions of reproduction and evolution could not arise. Dobzhansky’s statement, important though it is, refers to what has happened since the first organism managed to stay alive.


I thank María Luz Cárdenas and Herbert Friedmann for useful comments on an earlier version of this essay.