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The Music of Life: Biology Beyond Genes

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Denis Noble describes his short book, "The Music of Life: Biology Beyond Genes", as a polemic. It is, in fact, a clarion call for a rethink to the reductionist dogmas that currently plague--and hinder--so much scientific thinking, particularly in the field of biology and, most especially, genetics. Professor Noble is not, of course, alone in making this call (see, for instance, Stuart Kaufmann's "Reinventing the Sacred" or "Evolution in Four Dimensions" by Eva Jablonka and Marion J. Lamb) but he presents a particularly clear-sighted argument which few others have so far matched. His is a far-reaching and eminently readable disquisition, attacking first the popular metaphor articulated primarily by Richard Dawkins in "The Selfish Gene" (and promulgated endlessly--usually incorrectly--by science popularists ever since) that genes are the engines of evolution and each genome a comprehensive "program of life". Throughout his book, Noble turns that view around with a different and far more accurate metaphor, presenting the genome as a database from which the organism can select in order to call upon an elegant modularity of gene expression in a bewildering display of inventiveness of response to environmental and physiological conditions.

Along the way, the author uses a series of music-related analogies to extend his metaphor and piece together the various fragments of his argument into a coherent look at the biology of the organism as a fully functioning system, operating on and at many levels. He shows that far from the established view where the arrows of explanation all point downwards to the lower, ever more fundamental elements of cellular physiology (ending up ultimately at DNA as the primary explanatory element) there exists in reality a complex system of feedback pathways which enable the organism to act upon its own genetic material, altering the way that each gene is expressed in combination with others as a consequence of their whereabouts within the organism, or the conditions to which the organism may be subjected. Within this systems view of biological functioning, the complex pathways of interaction become the primary explanatory elements, rather than any of the physical components themselves.

This single insight provides several additional mechanisms for the operation of evolution through natural selection over and above the simplistic one of random gene mutation which is held in such high regard by today's neo-Darwinists, and reopens the door to the long-ridiculed notion of so-called Lamarckian inheritance of acquired characteristics. It also calls into question the wisdom of, for instance, neurologists seeking the physical location of "the self" within the prescient organism; within Noble's view of things, such concepts as "the self" cease to have any likelihood of an actual physical presence (as separate, identifiable entities within the organism) but instead become emergent functional properties of a level of operation of the biological system itself.

It should be clear by now that this book presents serious challenges to a great deal of current biological dogma and there will be many readers for whom this book is an eye-opener. It is an easy and entertaining read for anyone with even a smattering of science and regardless of whether or not you finally come to agree with Denis Noble, you can be sure you'll find what he has to say interesting and enlightening.

This is a book that anyone interested in understanding the nature of life should read -- not life as a collection of genes, or even as a collection of proteins, but life as a system of interactions. Denis Noble doesn't try to do away with reductionism altogether, but to use reductionism in a less simple-minded way than is often done. He accepts, as any sensible biologist must, the importance of the genome, but he rejects the idea that the genome is all there is.

In the first chapter he examines the famous passage in which Richard Dawkins first expressed the concept of the selfish gene ("Now they swarm in huge colonies, safe inside gigantic lumbering robots...") and then, without distorting any of the facts, rewords it in a way that totally changes the emphasis ("Now they are trapped in huge colonies, locked inside highly intelligent beings..."). Whether you finish by preferring his version to Dawkins's or not, you can hardly escape feeling that he has raised some serious doubts about an over-simple interpretation of the relationship between genes and organisms. For myself, I think that Dawkins's version was an essential step towards moving from an individual-centred view of evolution towards a view that recognized the importance of the gene, but Noble is right to emphasize that one shouldn't take it too far.

Much later in the book there is a brilliant description of sexual intercourse that should utterly dispose of any simplistic ideas of "Lamarckian" inheritance of acquired characteristics as "wrong" and opposed to the "right" idea of Darwinian natural selection. (I put "Lamarckian" in quotation marks because Noble does, for the very good reason that Darwin was no less of a "Lamarckian" than Lamarck was, and he became more of one with each successive edition of The Origin of Species.) We are back here to points of view: if we consider individuals, then inheritance is by natural selection, but if we consider each (multicellular) individual as a colony of cooperatively interacting cells, then inheritance is "Lamarckian". A liver cell, for example, has exactly the same genome as a muscle cell from the same individual, but liver cells divide to produce liver cells, never muscle cells: clearly some characteristic that a liver cell has "acquired" during its formation (and not just its genome) is being passed on to its descendants.

As a researcher Noble is known for his development over half a century of a mathematical model of the heart that can faithfully reproduce many of its properties. In that sense he was a systems biologist long before anyone thought of this vogue term. The importance of this for the general theme of the book is that it establishes that he is not a holist in the mystical sense of the term, as he clearly recognizes that an organ as complex as the heart can be represented in mathematical equations based on the known properties of its components, but only if their interactions with one another are taken into account.

Noble has summarized the importance of non reductionist thinking in the life sciences extremely well with this book. He has made a compelling argument that is highly relevant to life sciences, using metaphor, analogy and several clear examples from recent developments in genomics and proteomics, that (as Anderson wrote in 1972) - "More is Different."

I intend to use this as a primer in my applied / integrative physiology courses - am hopeful that students in the health sciences would help pave the way toward a more integrated understanding of health through a more integrated understanding of life itself.

Denis Noble describes his short book, "The Music of Life: Biology Beyond Genes", as a polemic. It is, in fact, a clarion call for a rethink to the reductionist dogmas that currently plague--and hinder--so much scientific thinking, particularly in the field of biology and, most especially, genetics. Professor Noble is not, of course, alone in making this call (see, for instance, Stuart Kaufmann's "Reinventing the Sacred" or "Evolution in Four Dimensions" by Eva Jablonka and Marion J. Lamb) but he presents a particularly clear-sighted argument which few others have so far matched. His is a far-reaching and eminently readable disquisition, attacking first the popular metaphor articulated primarily by Richard Dawkins in "The Selfish Gene" (and promulgated endlessly--usually incorrectly--by science popularists ever since) that genes are the engines of evolution and each genome a comprehensive "program of life". Throughout his book, Noble turns that view around with a different and far more accurate metaphor, presenting the genome as a database from which the organism can select in order to call upon an elegant modularity of gene expression in a bewildering display of inventiveness of response to environmental and physiological conditions.

Along the way, the author uses a series of music-related analogies to extend his metaphor and piece together the various fragments of his argument into a coherent look at the biology of the organism as a fully functioning system, operating on and at many levels. He shows that far from the established view where the arrows of explanation all point downwards to the lower, ever more fundamental elements of cellular physiology (ending up ultimately at DNA as the primary explanatory element) there exists in reality a complex system of feedback pathways which enable the organism to act upon its own genetic material, altering the way that each gene is expressed in combination with others as a consequence of their whereabouts within the organism, or the conditions to which the organism may be subjected. Within this systems view of biological functioning, the complex pathways of interaction become the primary explanatory elements, rather than any of the physical components themselves.

This single insight provides several additional mechanisms for the operation of evolution through natural selection over and above the simplistic one of random gene mutation which is held in such high regard by today's neo-Darwinists, and reopens the door to the long-ridiculed notion of so-called Lamarckian inheritance of acquired characteristics. It also calls into question the wisdom of, for instance, neurologists seeking the physical location of "the self" within the prescient organism; within Noble's view of things, such concepts as "the self" cease to have any likelihood of an actual physical presence (as separate, identifiable entities within the organism) but instead become emergent functional properties of a level of operation of the biological system itself.

It should be clear by now that this book presents serious challenges to a great deal of current biological dogma and there will be many readers for whom this book is an eye-opener. It is an easy and entertaining read for anyone with even a smattering of science and regardless of whether or not you finally come to agree with Denis Noble, you can be sure you'll find what he has to say interesting and enlightening.

No one is better qualified to write this book than Denis Noble, a prominent physiologist with half a century of research experience and one of the pioneers and leaders in the emerging field of systems biology. In this book, Noble explains the pressing need for a systems biology approach and he presents the basic concepts at a level which is accessible to general readers familar with the rudiments of biology, yet sophisticated and detailed enough for specialists as well. An added bonus is that Noble also addresses the important foundational philosophical issues in a manner that philosophers of biomedicine should find useful.

Here's a brief summary of what I consider to be the key points from the book:

(1) Systems biology has roots in classical biology and physiology going back over a century.

(2) Systems biology uses data generated by reductionism (especially molecular biology), but then follows with the next step of integration, so that we can understand complex system behavior.

(3) Behavior of biological systems is governed by "messy" networks of nonlinear interactions of many components, at many physical scales, with multiple directions of causality (regulatory feedback processes are an obvious example of downward causation). There is no privileged level or component, and thus no central system controller, but instead something more like a democratic collaboration. The dogma of a genetic program is therefore incomplete to the extent of being wrong because (a) particular genes are often involved in many different biological functions, (b) multiple genes are often involved in a particular biological function, (c) the expression of a given gene is usually affected by interactions with other genes and with proteins, (d) function of proteins is affected by interactions with other proteins, (e) the physical and chemical environment provides a boundary condition for everything that happens with genes and proteins, (f) spatial locations and compartmentalizations of system components matter, and (g) biological levels above that of the cell also matter. Thus, at a minimum, our models need to account for gene-protein networks which (a) have lateral, upward, and downward causality, (b) are affected by particular physical/chemical environments, and (c) are affected by higher biological levels (tissues, organs, etc.).

(4) Evolutionary selection acts on organisms, not individual genes in isolation. Thus, co-evolution of system components and processes is necessarily involved. Related to this, "Lamarckian" inheritance of acquired characteristics is obviously involved at the level of somatic cells within multicellular organisms (with epigenetic mechanisms playing a key role), and there's evidence that such inheritance may sometimes also occur to some extent with germ cells.

(5) The "combinatorial explosion" associated with biological systems makes comprehensive bottom-up modeling very difficult, if not impossible. In this situation, a benefit of top-down modeling is that we can select which lower-level components are of interest. Middle-out models provide the same benefit. Either way, an ultimate objective is to link multiple levels into an integrated model.

(6) There is evidence that biological networks display modularity, and such modules are relatively robust and adaptable, so modularity can be used to help build models more efficiently. Usually, the robustness of a module is partly due to redundancy within the module.

(7) Because evolution is "blind," a biological network or system may evolve in a direction which confers fitness benefits for some time, followed by eventual lack of fitness (leading to extinction).

The vast amount of biomedical data generated during the past decade indicates that complexity is perhaps our greatest challenge in biomedicine, and systems biology is an important approach for dealing with that complexity, so I believe that everyone involved in biomedicine needs to read this book. In that regard, it's unfortunate that "systems biology" isn't mentioned in the title, since many potential readers won't otherwise infer the topic of the book from the title (as suggested by the limited number of Amazon reviews to date).

Using colorful analogies, and lots of amusing parables, Noble offers a convincing alternative to the gene-centered view of evolution and introduces the interesting idea that consciousness is a process involving the endochrine system and nervous system, not just a location in the brain.

Denis Noble has given us a powerful little book to frame our notion of the appropriate role of the genome in science. His approach is called an integrative systems approach and make a lot sense. Instead of the reductionist certainty plaguing the science genetics, Noble encourages a different tack. His use of metaphor and analogy is both illuminating and entertaining; I found his use of music to be the most compelling.

I purchased this book because I've been studying the application of metaphors in different fields, Noble did not disappoint.

This slim volume is excellent and recommended for anyone wishing to become better acquainted with alternative views on the role of genetics, and more importantly a systemic approach to our physiology.

Well done!