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 10 EMBO reports VOL 9 | NO 1 | 2008 ©2008 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION viewpoint science & society S S S S S F F ? ? ! F = Flap S = Storm 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 ©2008 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports VOL 9 | NO 1 | 2008 11 science & society viewpoint 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