Viewpointviewpoint Complexity in Biology

viewpointviewpoint Complexity in biology

Exceeding the limits of reductionism and determinism using complexity theory Fulvio Mazzocchi

he ultimate aim of scientific research scientific knowledge has to provide an objec due course, reductionism proved to be an is to understand the natural world. In tive representation of the external world. The extremely powerful analytical methodology Torder to achieve this goal, Western world’s apparent complexity can be resolved and it enabled scientists to analyse many science has relied on different cognitive by analysis and reducing phenomena to basic molecular and cellular processes. strategies, including simplification, both in their simplest components. “Once you have terms of analysis and explanation. As the done that, [the evolution of phenomena] Complex systems exist at British natural philosopher Sir Isaac Newton will turn out to be perfectly regular, revers (1643–1727) put it, “Truth is ever to be ible and predictable, while the knowledge different levels of organization found in the simplicity, and not in the multi you gained will merely be a reflection of that that range from the subatomic plicity and confusion of things.” In a way, pre-existing order” (Heylighen et al, 2007). realm to individual organisms to examples of simplification include using Ever since Newton formulated the first whole populations and beyond idealized models, such as a ‘perfect sphere laws of gravity, the conceptual model of the rolling down a smooth plane in a vacuum’; physical world had successfully described conducting experiments in a strictly con the shape, movements and actions of the Nonetheless, biologists might be reaching trolled environment such as the laboratory; objects within it. But as physicists began the limits of this approach. Despite their best analysing complex systems by reducing to explore especially the atomic and sub efforts, scientists are far from winning the them to their individual parts; and generally atomic realms in the early twentieth cen war on cancer, owing largely to the complex by using a linear and deterministic concept tury, their observations became partially nature of both the disease and the human of how the world, including life, works. meaningless. The new discoveries required organism. The human brain is a complex, The French philosopher and mathemati a paradigm shift and a new intellectual nonlinear system that defies all reductionistic cian René Descartes (1596–1650) was the framework to understand events at the sub and deterministic attempts to understand it first to introduce reductionism to Western atomic level, which eventually resulted in (Singer, 2007). On a macro level, ecosystems thinking and philosophy. According to his quantum physics. and human societies present the same chal view, the world can be regarded as a clock lenge. What is needed is a new approach to work mechanism; to understand it, one need Since the time of Newton, study these systems. Complexity theory can only investigate the parts and then reassem provide new conceptual tools that will inevi ble each component to recreate the whole. classical mechanics has been tably question many of the assumptions of Descartes’ work was expanded by Newton regarded as the foundation of Newtonian science. (1643–1727) and ultimately culminated in scientific research the Principia Mathematica in 1687—one of omplex systems exist at different the most influential science books ever writ As many of the molecular biologists in the levels of organization that range ten—in which Newton further advanced the 1950s came from physics, it is not surprising Cfrom the subatomic realm to indi idea of a ‘clockwork universe’. that they extended its classical approach vidual organisms to whole populations and Since the time of Newton, classical to the study of living organisms. Molecular beyond. They include, for example, molec mechanics has been regarded as the founda biology, with some exceptions (Westerhoff ules, cells, organisms, ecosystems and tion of scientific research. Scientists, includ & Palsson, 2004), has largely adopted a human societies. Despite their differences, ing biologists, have adopted the Newtonian reductionistic view to explain biological sys these all share common features, such as approach both at the ontological level—in tems according to the physical and chemical emergent properties. In addition, random terms of their conception of the world and properties of their individual components. ness and order are both relevant for the the things of which it is made—and the As Francis Crick (1916–2004) put it, “The behaviour of the overall system. They are, epistemological level—in terms of their ultimate aim of the modern movement in in fact, neither typified by complete deter approach to understanding those things. The biology is to explain all biology in terms minism, such as the phenomena that are Newtonian epistemology, in fact, states that of physics and chemistry” (Crick, 1966). In investigated by Newtonian mechanics, nor

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by total randomness, such as the subjects reductionism, which claims that complex the qualities of its individual parts; a view of statistical mechanics (Heylighen et al, phenomena or systems can and should be now held in a variety of scientific fields 2007). Complex systems exist on the ‘edge understood by means of analysing their ranging from physics to sociology. of chaos’. They might show regular and pre individual parts. Biological organisms show emergent dictable behaviour, but they can undergo properties that arise from interactions both sudden massive and stochastic changes in n increasing number of scientists among their components and with exter response to what seem like minor modifica argue that the reductionist approach nal factors. For example, the properties of tions. The metaphor of the ‘butterfly effect’— Acan no longer cope with both the a protein are not equivalent to the sum of whereby a single butterfly beating its wings enormous amount of information that comes the properties of each amino acid. Proteins can cause a storm—describes, for example, from the so-called ‘-omics’ sciences and are able to specifically catalyse a chemi the dependence of a complex system on its technologies—genomics, proteomics, meta cal reaction, recognize an antigen or move initial conditions. bolomics and so on—and the astonishing along another protein polymer not only It is therefore important to analyse complexity that they reveal. The assumption because their amino acids are arranged in a how the application of complexity theory that complex biological systems can be com specific order, but also because their three- can affect the study of biological sys pletely explained by Descartes’ clockwork dimensional structure and function are tems, in the realm of molecular biology, model has been repeatedly questioned. As additionally determined by external factors. too. This discussion is mainly concerned the Belgian biologist Marc Van Regenmortel The notion of emergence is also associ with the implications that these notions commented, a move away “from the reduc ated with the idea that the natural world have for reductionism and determinism. tionistic viewpoint and toolset is a high pri consists of hierarchical levels of organiza Reductionism in particular can be distin ority for both biological and biomedical tion that range from subatomic particles guished into three types: ontological reduc research” (Van Regenmortel, 2004). to molecules, ecosystems and beyond tionism, which assumes that everything that First, the reductionist approach is not (De Haan, 2006). Each level is both charac exists in nature is constituted by a small able to analyse and properly account for terized and governed by emergent laws that set of primitive elements that behave in a the emergent properties that character do not appear at the lower levels of organiza regular and predictable manner; episte ize complex systems. The Greek philo tion. This implies that, in order to explain the mological reductionism, which argues that sopher Aristotle (384–322 bc) had already features and behaviour of a whole system, fundamental concepts, laws and theories of described emergence in his treatise we require a theory that operates at the cor a given level of organization can be derived Metaphysics as, “The whole is more than responding hierarchical level. For instance, from concepts, laws and theories pertain the sum of its parts.” Thus, the whole system emergent phenomena that occur at the level ing to a lower level; and methodological can neither be reduced nor deduced from of the organism cannot be fully explained

by theories that describe events at the level and has its price—it severs the essential link Biology, when based on reductionism and of cells or macromolecules. However, there between the object and the natural context to determinism, seems to lack a systemic pers are also various general features and charact which it belongs. Phenomena and properties pective that could analyse the interaction of eristics—described in this article—that per that occur only in the living environment the many factors that influence the behaviour meate all levels of organization and that become obscured and skew the results. Field of a system (Van Regenmortel, 2004). allow the study of biological systems in the observations of chimpanzees, for example, framework of complexity science. have shown that these animals have certain ourth, to better understand complex complex behaviours that cannot be observed biological systems and their adaptive …the reductionist approach is in an artificial setting but only in their natural Fbehaviour, we need to consider the environment (Goodall, 1986). phenomenon of self-organization, which not able to analyse and properly incorporates many of the ideas mentioned account for the emergent hird, reductionism is also closely above. Self-organizing systems spontan properties that characterize associated with determinism—the eously arrange their components and their complex systems Tconcept that every phenomenon interactions into adaptive structures with in nature is completely determined by pre- emergent properties. Such structures are able existing causes, occurs because of necessity, to create new and modify existing strategies This hierarchical organization creates and that each particular cause produces a to adapt to changing environmental condi ‘downward causation’ (De Haan, 2006). unique effect and vice versa. This, naturally, tions (Coffey, 1998). Complex biological While the behaviour of the whole is, to some also sustains the idea of predictability. “When systems, in fact, exist at the ‘edge of chaos’ degree, constrained by the properties of you are able to predict the development of a where, according to Kauffman (1993), they its components—‘upward causation’—the system from some predefined condition, then are able to achieve maximum fitness. Self- behaviours of its components are also con you have established a deterministic relation organization seems to take place at differ strained to a certain extent by the properties between the elements which constitute the ent levels of biological organization: as a of the system. The behaviour of a cell, for system” (Emmeche et al, 1997). Nonetheless, general principle in the organization of the example, is controlled both by the properties complex biological systems cannot be fully cell itself (Misteli, 2001); in the response of of its macromolecules and by the properties understood on a purely deterministic basis. bacterial colonies to chemotactic substrates; of the organ of which it is a part. The whole In fact, they often show nonlinear behaviour and in the brain, which reorganizes itself to is not only more than the sum of its parts, but (De Haan, 2006). learn from experience (Coffey, 1998). also less than the sum of its parts because As pointed out above, the individual some properties of the parts can be inhib components in complex systems interact in An epistemological rethink is ited by the organization of the whole. From manifold ways, including highly dynamic an epistemological point of view, this means regulatory and feedback mechanisms needed to instigate a paradigm that it is not enough to analyse each indi (Van Regenmortel, 2004). Within this frame shift from the Newtonian model vidual part (reductionism), nor is it enough work, a single cause can produce multiple that has dominated science, to analyse the system as a whole (holism). and unpredictable effects and even small fluc to an appraisal of complexity A new model of scientific investigation to tuations can have unexpected consequences. that includes both holism and understand complex systems would require Linear casual explanations—that conceive reductionism… shifting the perspective from the whole to the reality as a linear succession of elementary parts and back again (Morin, 1990). events from cause to effect—are therefore possibly unable to describe how complex As mentioned before, adaptation is strictly econd, reductionism favours the systems behave (Kellenberger, 2004). associated with self-organization. While removal of an object of study from its Nevertheless, many molecular biolo the latter is an integral feature of the system Snormal context. Experimental results gists still favour simple models with expla itself, the former shifts the perspective to the obtained under given particular condi nations based on a few individual factors. relationship between the system and the tions or from a particular model—such as For example, knockout experiments— environment. Whatever the pressure from the a mouse, in vitro cell cultures or computer which are widely used to determine the external environment, complex systems— models—are often extrapolated to more functional role of a gene—overemphasize through dynamic variations in the degree of complex situations and higher organisms the role of a single gene and are of limited interactions between the individual compo such as humans. But this extrapolation is at use for understanding complex genetic net nents that form the networks—can adjust and best debatable and at worst misleading or works. As a matter of fact, many knockout reorganize themselves in a new equilibrium even hazardous. The failure of many prom experiments have no or unexpected effects in response to external events. Of course, ising drug candidates in clinical research because any given gene product is only a failures can and do occur, nevertheless, shows that it is not always possible to trans part of a complex network. adaptation seems to be the rule rather than fer results from mice or even primates to In addition, other phenomena can cause the exception (Heylighen et al, 2007). humans (Horrobin, 2003). these unforeseen findings such as gene While arguing about the Darwinian More generally, the strategy of putting the redundancy—the presence of duplicate metaphor of the organism adapting to its object of study in an artificial, controlled and genes in the genome—and gene pleiotropy, environment, the American evolutionary simplified experimental situation, even if it which can lead to several phenotypes based biologist Richard Lewontin showed how this is done for heuristic purposes, is not neutral on the same genotype (Morange, 2001). idea is based on a dichotomy between inside

and outside, which disregards the role of the hereafter. Actually, one avoids the funda these relationships are directly relevant. Even organism in reconstructing its environment mental problem of complexity, which is at a larger scale, the interactions between an (Lewontin, 2000). In fact, organisms nei epistemological, cognitive, paradigmatic. experimental set-up and biological matter ther evolve in isolation nor simply adapt to To some extent, one recognizes complexity, give rise to modifications too; for example, ‘external’ factors. On the contrary, they react but by decomplexifying it. In this way, the bleaching during fluorescence microscopy or to and modify their environment accord breach is opened, then one tries to clog it: the electron-beam-induced alteration—such ing to their own needs. Both organism and the paradigm of classical science remains, as burning or carbonization—of a specimen.” environment therefore undergo a contin only fissured.” (Morin, 2007). (Kellenberger, 2004). uous process of mutual interaction, which Broadly speaking, the reintroduction Lewontin termed co-adaptation. A biologi …key notions such as of the observer has fostered a renewed cal system is constrained by its environment, idea of knowledge. Instead of searching but it also changes its environment. This idea emergence, nonlinearity and for one fundamental point of observation, might be applied by analogy, although with self-organization already scientists need to explore different points different implications, to different levels offer conceptual tools that can of view—which can be vicarious in build of organization including, for example, the contribute to transform and ing a cognitive universe—when describing molecular and the cellular levels (Galtier improve science or explaining a given phenomenon (Ceruti, & Dutheil, 2007). 1986). Different perspectives can, in fact, complement each other and allow scientists n this framework, it seems that biol An epistemological rethink is needed to acquire a more complete knowledge of ogy, and somehow science as a whole, to instigate a paradigm shift from the the phenomenon. Ineeds to reconsider the notion of ‘natu Newtonian model that has dominated sci ral laws’. Recent developments in evolu ence, to an appraisal of complexity that Any constraint can also be an tionary biology suggest replacing the idea includes both holism and reductionism, of a deterministic (prescriptive) law by a and which relaxes determinism in favour of opportunity that, if exploited, non-prescriptive law that just provides a recognizing unpredictability as intrinsic to allows new possibilities to arise number of constraints. More than actually complex systems. Moreover, this ‘complex determining the development of organisms paradigm’ requires us to develop ‘knowl One of the most fundamental relation or other complex systems, such laws—if so edge of knowledge’ and understand its possi ships within this framework is between the intended—rather delimit the framework in bilities and limits. Science should not only system and its environment—the distinc which they occur. In other words, the ‘law continue to develop more refined means tion between a point of view that is within as a constraint’ establishes the ‘rules of the to analyse its subjects, but also investigate the system and one that is external to the game’. It defines a restricted field of possi its own approach to generating knowledge system. These two points of view are irre bilities, within which complex systems (Morin, 1990). ducible and complementary. They emerge develop, but without imposing a unique from and are defined with respect to one way of undergoing this process. Other his raises the important question of the another. The French scientist Henri Atlan, matters should be considered, such as the role of the observer. Classical science one of the first who tried to define com role of contingencies and of chance, and Thas developed by eliminating subjec plexity in biology, investigated biological the way in which the ‘players’ use these tivity in order to create objective knowledge, organization from the perspective of infor and deal with the existing rules (Ceruti, but complexity theory has reintroduced the mation theory. He suggested that, in a hier 1986). It seems that a renewed and more observer as an intrinsic component in the archical system, the external observer can fascinating vision of nature emerges with process of gathering knowledge and per be the higher organizational level (Atlan, much more room for variability. forming research. The famous uncertainty 1979). In explaining the role of ‘noise’, he principle formulated by the German physicist stressed how its ‘meaning’ depends on the …the reintroduction of the Werner Heisenberg (1901–1976) shows how observational perspectives: leading respec the ‘observer modifies the observation’. This tively to a decrease or to an increase in observer has fostered a renewed applies not only to quantum physics, but, by information content “whether one is inter idea of knowledge extension, can also have practical relevance ested in the information transmitted in the in the fields of biochemical and biological channel or in the information transmitted to Of course, many biologists are experimentation. As the Swiss physicist and the observer from a whole system in which well aware of the complexity of living biologist Eduard Kellenberger (1920–2004) the channel is part of a redundant commu systems, but they do not extend this wrote, “for the sub-microscopic world of nication network” (Atlan, 1974). For exam realization to a reappraisal of how to atoms and molecules, it means that the physi ple, a cell would try to suppress noise in its perform science. “When one searches cal properties of a system—for example, its communication pathways as it might lead for the ‘laws of complexity’, one still energy—are uncertain; in particular, these to unexpected and possibly deleterious attaches complexity as a kind of wagon properties depend on the type of observation effects, but an observer at a higher level— behind the truth locomotive, that which that is performed on that system, defined by an organ or the organism—would regard produces laws. A hybrid was formed the experimental set-up. In the fashionable noise as a factor that increases variability between the principles of traditional field of nano-biotechnology, which examines and therefore overall fitness—provided that science and the advances towards its biological structures at the level of atoms, the cell is not killed.

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