Anzaldo, Armando Aranda

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BACK TO THE FUTURE:ARISTOTLE AND MOLECULAR BIOLOGYARMANDO ARANDA ANZALDOMolecular biology was born in the first half of the twentieth century whensome European physicists decided to apply the methodology of physicsto the detailed study of biological molecules so as to establish how molecu-lar structure determines biological function. This scientific approach impliedthe Aristotelian axiom: function follows form, which was impressivelyinstantiated by the discovery of DNA structure by Watson and Crick in1953, a feat that immediately lead to depth insights into the functioning ofthe genetic material. Thus, genetics also became molecular and in spite of thefurther successes of molecular biology in clarifying the relationship be-tween form and biological function at the molecular level, the fascinationwith genes—identified within the neo-Darwinian paradigm as the ulti-mate targets upon which the sieve of natural selection acts by differentialreproduction of the organisms carrying such genes and then usheringchanges in their frequency within a given population1 —led to a gene-cen-tered notion of biology and so genes became the all-powerful determi-nants of organismic structure 2. Indeed, the genes constituted by specificstrings of DNA have been endowed with almost magical properties suchas the capacity for “self-replication” (a completely meaningless term) and,in the same vein, it is thought that an atomized jumble of gene products(i.e., proteins) taking place within cells, that grow, proliferate and gettogether but always by unfathomed ’genetic’ reasons, nevertheless con-forms organisms endowed with complex structure and behavior. Thisrather odd logic culminated in the expensive sequencing of the DNAnucleotides constituting the human genome that was justified on the basisthat knowing the genome was equal to knowing the organism. However,as Richard Lewontin has clearly stated: “genes can make nothing” sincethe proteins coded by such genes are the result of a very complex systemof chemical production involving a pre-existing and renewable molecularmachinery 3. Proteins cannot be produced without either the genes or theLaboratorio de Biología Molecular, Facultad de Medicina, Universidad Autónoma del Estadode México. Apartado Postal 428, C.P. 50000, Toluca, Edo. Méx., México. / aaa@uaemex.mxLast contribution to Ludus Vitalis: “Naturalistic Ethics. Is there such a thing?”, vol. XIV, num25, 2006, pp. 217-220.Ludus Vitalis, vol. XV, num. 28, 2007, pp. 195-198.molecular machinery. On that account, regarding the gene as the “mastermolecule” is more an ideological posture than a true scientific statement.In any case, what is being reproduced is the entire organism as a complexsystem and not only the genes or the genome. A further derive of thisgene-centered ideology arrived to the rather silly notion that by compar-ing the human genome with that of the chimpanzee we would know whatgenes actually hold the key to humanness. Yet the result of such an effortshowed that humans and chimps are basically isogenic and so no specifichuman genes responsible for our human properties could be identified 4.Given the failure of the aforementioned enterprise now the trend is to assumethat modifications of gene-regulatory networks in the course of evolution-ary time are behind the fact that animals with isogenic genomes like therat, mouse, dog, chimp and human, nevertheless display clearly disparatefeatures at both structural and behavioral levels 5. Such an assumption iscurrently very difficult to prove but is the stepping-stone for the actualhijacking of the new research program of evo-devo by genetic reductionism.Evo-devo, the marriage of evolutionary and developmental biology, is apossible path for recovering the organism as the centre of biologicalthought. Indeed, neo-Darwinism explains evolution as the effect of differ-ential fitness of different phenotypes but tells nothing about the actualorigin of such phenotypes. To enunciate that the adaptive traits of thefittest are passed on to its progeny says nothing about the origin of suchtraits, thus evolutionary biology needs developmental biology to adum-brate the problem of origins. Yet development is much more than the sumof the expression patterns of a long list of genes and it is certainly not theresult of a “genetic program” loaded into the zygote analogized as acomputer, because the distinction between ’genetic’ and ’epigenetic’ is notthe same as the distinction between ’program’ and ’data’ 6, and in the gameof analogies the genetic information might actually be a set of data to beprocessed by the program embodied in the structure of the cell. So far cellsbeget cells and after each cell division what is inherited is more than agenome: a complex structural and spatio-temporal order that is certainlynot codified in the genes and yet it is fundamental for understanding thecomplex behavior of the cell. Self-assembly of molecular constituents is notthe answer for building a cell: a new cell needs a pre-existing cell astemplate. In multicellular organisms development can be understood asa self-perpetuating dynamic resulting from the coupling of molecularsynthesis, gene activation, spatial patterning of substances, cell interac-tions, cell sorting and morphogenetic movements 7, thus achieving thetransmission of structure and form that is not exclusively dependent ongenetic information 8. Moreover, a lot of fundamental physics is involvedin the many morphogenetic and patterning effects in living systems thatare the outcome of the basic physical properties of cells and tissues.196 / LUDUS VITALIS / vol. XV / num. 28 / 2007Therefore, generic mechanisms are equally or more important than ge-netic mechanisms in determining organic form 9.For Aristotle, form was the principle of intelligibility since it is throughforms that we apprehend the complexity of the world; in this way Aristotlefounded natural history or what we actually know as biology with thecentral aim of understanding how organic form comes into being 10.Biological development implies the process of morphogenesis consistingin the formation of biological structure by changing the spatial relation-ships of cells and tissues, leading to several intermediate forms in thepathway that culminates in achieving the full organic form which isproper to an individual organism of a given species. Several years ago itwas suggested that this process unfolds upon an ’epigenetic landscape’ ofnecessary paths or chreodes that canalize development towards definiteend points 11. Moreover, the overwhelming experimental evidence show-ing that cellular developmental fate is a function of position implies thatmaterial (molecular) constituents acquire the power to produce specificmorphological structures as a result of qualitative changes in their spatialrelationships, but since spatially-related entities are not connected, it islogically necessary to assume the existence in developing organisms of aspatially organized system of constitutive relations: a morphogenetic fieldlike the other fields currently known to physics (gravitational, magnetic,electrical, etc.) that guides and controls interactions between matter andenergy. Current evidence suggests that morphogenetic fields are wholesactively organizing themselves since they posses active powers and theiressence is a dynamical structure within which genetic and environmentalfactors determine parametric values in the equations describing the actualstructure of the field, thus acting as stabilizers of one empirical form froma set of forms that are possible for a particular type of field 12. In recentyears, the late René Thom lead the effort to create a general mathematicaltheory of morphogenesis that might help to understand and model anykind of morphological process, be it related to language, behavior orbiological development 13.My view is that molecular biology must go back to its roots in physicsand in the foundational axiom that function follows form so as to under-take the study of development and morphogenetic fields. Yet for thatpurpose molecular biology must leave behind the narrow-minded notionof causality that permeates the neo-Darwinian gene-centered view, andrecover the spirit of classical natural history and its four types of causation:material, efficient, formal and final, in their original non-theological butAristotelian fashion. For Aristotle it is not the end or telos that directs orcauses a given process from its inception, yet it is form that directs theprocess of its own development from a potential to an actual condition.For Aristotle potential form is a natural force operating in nature, matterARANDA-ANZALDO / BACK TO HE FUTURE / 197is endowed with certain necessary properties, but the necessity that is trulyimportant in the process of organic generation is the hypothetical neces-sity (to anakaion ex hypotheseos: Physica II.9, 200a13); such is a necessity thatflows backwards from the achieved telos to the process that leads to suchan end or towards the structure of the parts that contribute to such an end 14.The several global or local organizers described in varied embryonicdevelopmental processes, such as the Spemann organizer in amphibians,the Hensen node in the chick, and the equivalent node region in themouse, might be the embodied manifestations of the hypothetical neces-sity that establishes a set of ’attractors’ along the developmental pathwaythat allow us to rationalize in a retrospective fashion the process ofontogeny, in the same way that a satellite view of an earthly landscapeallows us to understand and then predict the course taken by waterflowing upon such a landscape in its relentless voyage towards the ocean.By linking the spatio-temporal order and underlying structural con-straints that control cellular physiology to the field properties manifestedin the process of ontogeny, molecular biology might finally explain theorganism and thus find its meaning as a true science.REFERENCES1 Dobzhansky, Th., Ayala, F.J., Stebbins, G.L. and Valentine, J.W. (1977), Evolu-tion. San Francisco: W.H. Freeman and Co., p. 16.2 Gehring, W.J. (1998), Master Control Genes in Development and Evolution. NewHaven: Yale University Press.3 Lewontin, R.C. (1991), Biology as Ideology: the Doctrine of DNA. New York:Harper Collins, p. 48.4 The Chimpanzee Sequencing and Analysis Consortium (2005), “Initial se-quence of the chimpanzee genome and comparison with the humangenome,” Nature 437: 69-87.5 Gerhart, J., and Kirschner, M. (1997), Cells, Embryos and Evolution: Toward aCellular and Developmental Understanding of Phenotypic Variation and Evolution-ary Adaptability. Malden MA.: Blackwell, 6 Keller, E.F. (2000), The Century of the Gene. Cambridge Mass.: Harvard Univer-sity Press, p. 287.7 Goodwin, B.C, Kauffman, S.A., and Murray, J.D. (1993), “Is morphogenesis anintrinsically robust process?” J. Theor. Biol. 144: 303-319.8 Minelli, A. (2003), The Development of Animal Form. Cambridge: CambridgeUniversity Press, p. 27.9 Newman, S.A., and Comper, W.D. (1990), “ ’Generic’ physical mechanisms ofmorphogenesis and pattern formation,” Development 110: 1-18.10 Aranda-Anzaldo, A. (2002), “Towards a morphogenetic perspective on can-cer,” Riv. Biol/Biology Forum 95: 35-62.11 Waddington, C.H. (1957), The Strategy of the Genes. London: Allen and Unwin,chap. 2.12 Webster, G., and Goodwin, B.C. (1996), Form and Transformation. Cambridge:Cambridge University Press, p. 99.13 Thom, R. (1990), Semiophysics: A Sketch. Redwood City, Menlo Park: Addison-Wesley.14 Aranda Anzaldo, A. (1999), “La importancia de la teleología y la necesidadhipotética en la biología aristotélica”, Pensamiento 5: 93-99.198 / LUDUS VITALIS / vol. XV / num. 28 / 2007

Back to the future: Aristotle and molecular biology

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Back to the future: Aristotle and molecular biology

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