Ehsani, Sepehr

PhilPapers

BOOK REVIEWRelativism as a means to alleviate biology from genomicreductionism: But is the remedy effective?Denis Noble: Dance to the Tune of Life: Biological Relativity.Cambridge University Press, December 2016, 302pp, £17.99 HBSepehr Ehsani1,2Published online: 11 September 2017 The Author(s) 2017. This article is an open access publicationFor the past several decades, biomedical research has principally been centered onmolecular biology and genomic science. Although many molecular pathways andplayers in different disease and normal biological processes have been elucidatedover this period, the much hoped-for ‘‘true’’ understanding of cellular and organismicfunctions has arguably not been achieved. Furthermore, current mainstream researchparadigms from neurodegenerative disease to oncology to evo-devo research do notsignal a clear path forward as to how that desired ‘‘true’’ understanding could beachieved. Here three questions can be raised: Why are we where we are in biology?What is the level and type of understanding that should and can be reached? And howdo we get there? Denis Noble’s recent book makes illuminating contributions toanswering these questions, providing a thoughtful analysis of the historical andcontextual basis of the current state of biological research.Noble is a noted cardiovascular physiologist with interests in mathematical andsystems biology. He taught at Oxford for 41 years and has been an EmeritusProfessor since 2004. In Dance to the Tune of Life, he details how his undergraduateand graduate education at University College London from 1955 to 1961 not onlyallowed him to study and excel in physiology, but also led him to voluntarilyexplore physics, mathematics, philosophy and computer science, a background thatallows for a unique perspective to be brought to biomedical research. It is thisperspective that has enabled the book’s nine chapters and detailed endnotes to haveelements of physiology, history and philosophy of science, and philosophy itself, allcombined in one place. It is therefore a very informative read.& Sepehr Ehsaniehsani@csail.mit.edu1 Computation and Biology Group, MIT Computer Science and Artificial IntelligenceLaboratory, Cambridge, MA, USA2 Department of Philosophy, University College London, London, UK123Metascience (2018) 27:111–115https://doi.org/10.1007/s11016-017-0255-1Beginning with a history of Copernican, Galilean and Newtonian science,Noble’s main focus is a critique of Neo-Darwinism and gene-centric views ofbiology propagated in the past century. He writes that ‘‘twentieth-century scientistsridiculed the great French biologist Jean-Baptiste Lamarck and sidelined almostcompletely the brilliant developmental biologist and polymath Conrad Wadding-ton’’ and that ‘‘unnecessary dogmatism has unfortunately haunted evolutionarybiology.’’ He identifies with the molecular biologist Max Perutz who thought ofDNA as the ‘‘score of life’’ rather than the ‘‘secret of life’’ and reminds us ofcytogeneticist Barbara McClintock’s prescient statement that the genome is ‘‘ahighly sensitive organ of the cell’’ (McClintock 1984). Reiterating this point in acommentary written with other colleagues in 2016, Noble writes:The fashion was that all would be revealed once we had read the ‘book of life,’the complete human genome. It took a mere decade of the present century forit to become clear that the ‘book’ is an almost illegible ‘database’ rather than areadable ‘program of life’ that would automatically lead to advances inphysiology and medicine (Noble et al. 2016).I think given the multitude of evidence currently available, most scientists, even thosewho previously supported an entirely gene-centric view of biology, would support thisdiagnosis. Moreover, it is unfortunate that the field had to go through a circular path toreach a conclusion that might have appeared obvious from the outset, a conclusion setforth, for example, beginning with the work of Waddington. Nevertheless, given wherewe are now, the question is where we go from here, and how we retool our methods toreach a more thorough understanding of the workings of the cell. To that end, inChapter 6, Noble formulates a theory of ‘‘Biological Relativity,’’ which proposes that noprivileged level of causation exists in biology, and to understand the whole one mustadopt an integrative approach with an emphasis on ‘‘multi-level interactions’’ in theorganism. The theory espouses the position that biological phenomena in an organismare parts of an open system and that we should be against ‘‘unwarranted explanatoryreductionism.’’ As an example, Noble states that ‘‘spiral arrhythmia’’ in the heart appearsrandom at the cellular level, but is ordered at the level of the whole organ. Therefore,even a seemingly ‘‘uncomplicated’’ arrhythmia cannot be reduced to its encompassingparts. Noble has since further underscored the need for a new theoretical framework thatcould guide biomedical research beyond what has already been achieved:What is needed is a framework of theory within which we can see our waythrough the forest of data to find the clues to understanding complexity. I seephilosophy as playing a major role here since what is required is a mind-shiftaway from the naı̈ve reductionist paradigm that dominated twentieth centurybiology. We need reductionist science. But we don’t need the naı̈ve andexclusive philosophy that often accompanies it. Reduction and integration inbiology go together, rather as they do also in the mathematics of calculus.(Noble 2017b)When we as readers consider Biological Relativity as one such framework oftheory, certain ambiguities and questions might arise that warrant further112 Metascience (2018) 27:111–115123consideration and could perhaps be addressed in future work. To begin with, ifgenes are always ‘‘passive, not active, causes,’’ how would we account formonogenic diseases with a very clear cause-and-effect relationship to thephenotype? This causal structure could also manifest itself not at the level ofgenes, but at the level of proteins, for example in human amyloid diseases (Wanget al. 2017) or heritable yeast prions (Newby and Lindquist 2013), to name a few.Furthermore, if there is no ‘‘privileged scale,’’ how can there be any structure inbiology, and anything beyond ameboid organisms? Hierarchies and ‘‘privilegedscales,’’ if I understand the latter phrase correctly, abound in biology, from embryodevelopment all the way to the language faculty. In this context, Noble quotes fromthe philosopher Nicholas of Cusa that ‘‘the world will have its centre everywhereand circumference nowhere.’’ But, analogously, can we say that the cell has itsnucleus everywhere and plasma membrane nowhere? A cell’s nucleus and plasmamembrane are not mere conventions and metaphors. This is not to say thateverything inside the cell is orchestrated in the nucleus, but rather that everybiological structure has an inherent nonrelativistic framework. Moving beyond thecell and to the level of the organism, does relativism hold at that larger scale? I thinkthe answer is still unclear even there. For example, if we consider the languagefaculty [‘‘I-language’’ (Chomsky 2006) to be precise], what arguably makes ushuman (Berwick and Chomsky 2015), can we say that our inherent language facultyis part of an open system, one that ‘‘dance[s] to the tune of the organism and itssocial context?’’Furthermore, there is always room for pause when concepts and ideas fromphysics are applied to biology, which is many orders removed from the physicalsciences and where scientific reasoning and explanations cannot be as exact. Forexample, describing ‘‘stochasticity’’ and randomness in a recent article, Noblewrites:Stochasticity is harnessed by organisms to generate functionality. Randomnessdoes not, therefore, necessarily imply lack of function or ‘blind chance’ athigher levels. In this respect, biology must resemble physics in generatingorder from disorder (Noble 2017a).As concepts, ‘‘generating order from disorder,’’ are valuable guideposts in framingour perspective toward biological questions, how can they be applied to formulatingan inherently testable hypothesis? Many ‘‘laws’’ of physics do not even completelyand accurately describe and predict atomic-scale physical phenomena. So how canbiological phenomena be reasonably explained by them? This is not to suggest thatconcepts from physics have no use in biology. For example, I found two ideas aboutrandomness and the ascribing of functions particularly interesting in the book. Asfor randomness, Noble suggests an alternative definition of ‘‘random with respect towhat?’’ framework. And as for functionality, he writes: ‘‘It is an importantconsequence of the theory of Biological Relativity that we should ascribe functionsand purposes to the level at which they make sense, which is the level at which theyconstrain the interactions of the system at lower levels.’’Another reservation with Biological Relativity, a theory that may be categorizedas a branch of systems biology, is whether it can really simplify our understandingMetascience (2018) 27:111–115 113123of cellular phenomena and contribute to science’s ultimate goal of simplifyingcomplexity. Research programs exist in the physical sciences that focus on complexadaptive systems, perhaps best epitomized by the work of the Santa Fe Institute inNew Mexico founded in 1984. ‘‘Complexity science’’ in general utilizes mathe-matical modeling to tackle topics such as emergence, chaos theory and complexnetworks, among other topics. It remains to be seen if these lines of research canreally simplify the cloud of uncertainty and noise that separates us from a trueunderstanding of the workings of a biological cell, even before we get to the level ofthe organism.To gain deeper insights into cellular functions, perhaps a good working plancould be to go back to serious and elementary rational inquiry, starting with the low-hanging fruit(s), in any discipline that we choose to study. If we decide to study thebehavior of a collection of cells in an organ, one could start by looking at thesystems dynamics of the interacting proteins in each cell or deciphering thetranscriptional and epigenetic network behind those protein interactions. But howcan we arrive at a serious understanding of these cellular events if we are stillunclear about the structural elements and ‘‘disordered’’ regions of each singleprotein, or what really constitutes an ‘‘interaction’’ between two proteins? Thesequestions are not meant to imply that we are aiming to reduce cellular functions tostructural elements at a single protein level, but they do suggest that rational inquiryshould proceed in a hierarchical fashion. Biology cannot reasonably be reduced tochemistry and physics, but should eventually be unified with them, and we cannotget there before seriously pursuing the basic and seemingly pedantic questions thatare still unanswered in biology.Noble’s Dance to the Tune of Life is an illuminating account of why philosophyis necessary in doing science. Philosophy was always part and parcel of science andit must remain so if we are to achieve science’s enduring goal of simplifying ourunderstanding of the world around us. Following with this theme, Noble writes:[Immanuel Kant] showed that we always need a framework within which tointerpret the world, but that the framework itself may not be derivable fromwhat we already know. That is why all science requires a metaphysics if it isnot to be mere cataloguing. That metaphysics may not be derivable frompurely empirical observations.The quest for that ideal framework continues.Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, dis-tribution, and reproduction in any medium, provided you give appropriate credit to the originalauthor(s) and the source, provide a link to the Creative Commons license, and indicate if changes weremade.ReferencesBerwick, R.C., and N. Chomsky. 2015. Why only us: Language and evolution. Cambridge: MIT Press.Chomsky, N. 2006. Language and mind. Cambridge: Cambridge University Press.114 Metascience (2018) 27:111–115123McClintock, B. 1984. The significance of responses of the genome to challenge. Science 226 (4676):792–801.Newby, G.A., and S. Lindquist. 2013. Blessings in disguise: Biological benefits of prion-like mechanisms.Trends in Cell Biology 23 (6): 251–259. doi:10.1016/j.tcb.2013.01.007.Noble, D. 2017a. Evolution viewed from physics, physiology and medicine. Interface Focus 7 (5):20160159. doi:10.1098/rsfs.2016.0159.Noble, D. 2017b. Systems biology beyond the genome. In Philosophy of systems biology. History,philosophy and theory of the life sciences, vol. 20, ed. S. Green. Berlin: Springer.Noble, D., J. Chan, P. Hansen, W. Boron, and P. Wagner. 2016. The landscape of physiology. Physiology(Bethesda) 31 (1): 2–4. doi:10.1152/physiol.00052.2015.Wang, H., D. Williams, J. Griffin, T. Saito, T.C. Saido, P.E. Fraser, E. Rogaeva, and G. Schmitt-Ulms.2017. Time-course global proteome analyses reveal an inverse correlation between a beta burdenand immunoglobulin M levels in the APPNL-F mouse model of Alzheimer disease. PLoS ONE 12(8): e0182844. doi:10.1371/journal.pone.0182844.Metascience (2018) 27:111–115 115123

Relativism as a means to alleviate biology from genomic reductionism: But is the remedy effective?: Denis Noble: Dance to the Tune of Life: Biological Relativity. Cambridge University Press, December 2016, 302pp, £17.99 HB

https://philpapers.org/archive/EHSRAA.pdf

Relativism as a means to alleviate biology from genomic reductionism: But is the remedy effective?: Denis Noble: Dance to the Tune of Life: Biological Relativity. Cambridge University Press, December 2016, 302pp, £17.99 HB

Abstract

Similar works

Full text

Available Versions

PhilPapers