Gatherer BMC Systems Biology 2010, 4:22 http://www.biomedcentral.com/1752-0509/4/22 CORRESPONDENCE Open Access So what do we really mean when we say that systems biology is holistic? Derek Gatherer Abstract Background: An old debate has undergone a resurgence in systems biology: that of reductionism versus holism.At least 35 articles in the systems biology literature since 2003 have touched on this issue. The histories of holism and reductionism in the philosophy of biology are reviewed, and the current debate in systems biology is placed in context. Results: Inter-theoretic reductionism in the strict sense envisaged by its creators from the 1930s to the 1960s is largely impractical in biology, and was effectively abandoned by the early 1970s in favour of a more piecemeal approach using individual reductive explanations. Classical holism was a stillborn theory of the 1920s, but the term survived in several fields as a loose umbrella designation for various kinds of anti-reductionism which often differ markedly. Several of these different anti-reductionisms are on display in the holistic rhetoric of the recent systems biology literature. This debate also coincides with a time when interesting arguments are being proposed within the philosophy of biology for a new kind of reductionism. Conclusions: Engaging more deeply with these issues should sharpen our ideas concerning the philosophy of systems biology and its future best methodology. As with previous decisive moments in the history of biology, only those theories that immediately suggest relatively easy experiments will be winners. Introduction time this argument has arisen, but we have been here An old debate has made a surprising, or perhaps not so before on several occasions.Thereductionist-holist surprising, reappearance in systems biology: that of debate emerged in biology in the 1920s out of the ear- reductionism versus holism. Surprising: in the sense that lier disputes between mechanists and vitalists,and the mainstream of molecular biology has for at least 30 between neo-Darwinians and neo-Lamarckians, although years been relatively uninterested in the matter, content it should not be thought that all the corresponding with a compromise that allows lab work to proceed terms on the left or right sides of each pair are in any without too much philosophical agonizing. Unsurprising: way necessarily equivalent. One would not expect any in that general systems theory has churned with the aspiring modern holist within the systems biology com- debate for nearly 75 years. Once systems theory met munity to be a vitalist or a neo-Lamarckian. Neverthe- molecular biology, it was probably only a matter of time less, broadly speaking, it is possible to see general before the controversy went pandemic. At least 35 arti- continuities that allow one to posit what might be called cles in the systems biology literature from 2003 to the mechanist-Darwinian-reductionist and vitalist-Lamarck- early part of 2009 touched on this issue [1-35]. How- ian-holist lineages, respectively, and an understanding of ever, much confusion is apparent in the variation in how these debates unfolded serves to illuminate how what is understood by the term holistic,andalsofrom any modern reductionist-holist conversation within sys- overstatements as to the degree that “traditional” mole- tems biology may develop. Those systems biologists who cular biology is truly reductionist. Some of the systems seethemselvesasholistsneed to know what kind of biology articles give the impression that this is the first holists they are. Then they can be more explicit about what aspects of reductionism they are opposed to. Many Correspondence: [email protected] holistically inclined systems biologists seem to be MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, arguing against a classical and now rather outdated Glasgow G11 5JR, UK © 2010 Gatherer; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gatherer BMC Systems Biology 2010, 4:22 Page 2 of 12 http://www.biomedcentral.com/1752-0509/4/22 version of reductionism, designed for physics and never more a laboratory man than a philosopher, so the main really implemented in molecular biology, and are appar- defence of the principles of mechanism, that all living ently unaware of the new developments in the philosophy processes “can be unequivocally explained in physico- of biology, what one might call the neo-reductionism, of chemical terms” [quoted in [41], p.430] fell to Jacques the last 20 years. Bringing systems biology face to face Loeb [42]. That Loeb was a biochemist, rather than a withthelatestversionsofreductionismshouldbethe developmental biologist like Roux, was no accident, next step in the process. First, some of the previous since the discovery of cell-free fermentation by Eduard rounds in the contest are reviewed. Buchner in 1897 is regarded as both one of the founda- tions of modern biochemistry and also a major experi- The Death of Vitalism mental nail in the coffin of vitalism. By the 1920s, Vitalism is the belief that some special life-force (the vitalism had been almost completely abandoned, not hormic schema, sentiment intérieur, élan vital or entele- just because it had failed to convince practising biolo- chy depending on the author) is necessary to differenti- gists on a theoretical level but also on account of its ate the living from the inanimate. For vitalists, no inability to provide a basis for any experimental research matter how much detail is understood about the physi- programme, despite some interesting efforts in embryol- cal and mechanistic nature of living things, no matter ogy by Driesch. Mechanism, by contrast, suggested how much was known in the 19th and early 20th centu- numerous avenues of experimental analysis. Vitalism in ries about their anatomy, physiology and biochemistry, its death throes was largely constituted as a denial of or since the mid-20th century about their molecular the possibilities of progress in understanding biological biology and genetics, this knowledge can never explain systems through mechanistic methods and this was a why they are alive. This, of course, is a position with difficult position to hold when experimental progress very deep religious roots. Reference to vital spirits as was so obvious. Mechanism won the philosophical animatory factors in living matter was current among debate, as far as any philosophical debate can ever be the biologists of the 17th century, and there was an said to be won, but more importantly for everyday active anti-mechanistic movement among the group of science, it won on the practical level. 17th century philosophers and liberal theologians known In the aftermath of Darwin’s triumphant bicentenary, as the Cambridge Platonists [36], although vitalism was it is easy to forget that his centenary year and the two only first coined as a phrase by Paul-Joseph Barthez as decades following it were difficult times for Darwinians. late as 1778 [37]. The problems of reconciling Darwin’s gradualist view of Just as vitalism had deep theological roots, its great evolution with the saltationist or macro-mutationist rival mechanism was the product of many centuries of views common among the early Mendelian geneticists practical problem solving with engineering devices, long had given rise to a climate where the theories of Dar- predating science, but the integration of the device- win’s predecessor Lamarck, or a mutated form of them centred world of the artist-engineer with the mathema- known as neo-Lamarckism which emphasised the inheri- tico-theoretical one of the scientist-scholar was not tance of traits developed during the lifetime of the commonplace until the time of Kepler and Galileo in organism through interaction with its environment, thelate16th and early 17th centuries [36]. Modern wri- were once again resurgent. Evolution in the Light of ters often point to Galileo’s younger contemporary René Modern Knowledge [43], a multi-author volume pub- Descartes as the man who first synthesized these influ- lished in 1925 and typical of its time, contains neo- ences into a mechanistic theory of biology, although Lamarckian contributions from psychologist Conwy Cartesian specialists are often unsure if Descartes can Lloyd Morgan, botanist E.O. Bower and zoologist Ernest really be interpreted in that way [38]. However, many of MacBride, all leading representatives of their disciplines. Descartes’s followers certainly held this view - the title There is not a single article that is recognizably Darwinian of Julian Offray de La Mettrie’s L’Homme Machine of to modern eyes, and the only references to Darwin are 1748 speaks for itself. attempts to co-opt Darwin’s later theories as a kind of The philosophical basis for vitalism in its most recent early neo-Lamarckism. Lloyd Morgan retains a lasting form is often taken to be the work of Henri Bergson influence within the reductionist-holist debate via his [39], and its last great scientific exponent was the development of the antireductionist concept of emergent embryologist Hans Driesch [40]. Driesch’s work is still evolution, still used today [44]. However, just as the often studied at second-hand today by way of contrast mechanists had gained the upper