Jun 30, 2005 - Complexity theory, which describes emer- gent self-organization of complex adaptive systems, has gained a prominent position in.
NATURE|Vol 435|30 June 2005
Now you see it, now you don't Cell doctrine: modern biology and medicine see the cell as the fundamental building block of living organisms, but this concept breaks down at different perspectives and scales. as ‘intracellular’ and ‘extracellular’. The other side of the ancient argument seems to hold: the body is a fluid continuum. Complexity theory, which describes emerIs this merely poetic description? I suggent self-organization of complex adaptive gest not. The fragility of the cell as the funsystems, has gained a prominent position in damental unit has been described before many sciences. One powerful aspect of as ‘cellular uncertainty’, akin to the Heisenemergent self-organization is that scale berg uncertainty principle: any attempt to matters. What appears to be a dynamic, examine a cell, inevitably disrupts its ever changing organizational panoply at microenvironment, thereby changing the the scale of the interacting agents that state of the cell. But are cells fundacomprise it, looks to be a single, funcmentally ‘uncertain’ or is it possible to tional entity from a higher scale. Ant conceive of a technology — a perfect colonies are a good example: from MRI machine, if you will — that afar, the colony appears to be a solid, could collect the data to describe a shifting, dark mass against the earth. cell completely without altering it? But up close, one can discern individComplexity analysis suggests that ual ants and describe the colony as the no machine could ever achieve this. emergent self-organization of these The cell as a definable unit exists only scurrying individuals. Moving in still on a particular level of scale. Higher closer, the individual ants dissolve into up, the cell has no observational myriad cells. validity. Lower down, the cell as an Cells fulfill all the criteria necesentity vanishes, having no indepensary to be considered agents within dent existence. The cell as a thing a complex system: they exist in depends on perspective and scale: great numbers; their interactions “now you see it, now you don’t,” as a involve homeostatic, negative feedback loops; and they respond to local Scale up: hundreds of individual ants form a superorganism. magician might say. This analysis also allows for environmental cues with limited stochasticity (‘quenched disorder’). Like nanoscale, quantum effects may have a hypothesis-based investigations of pheany group of interacting individuals ful- measurable impact, suggest that the nomena considered outside the bounds of filling these criteria, they self-organize answer is yes. In particular, the behaviours ‘traditional’ biology. A prime example is without external planning. What emerges of increasing numbers of biomolecular acupuncture, wherein application of stimis the structure and function of our tissues, ‘machines’ are seen to rely on brownian uli to special points (meridians) on the motion of the watery milieu in which they body accomplishes remote physiological organs and bodies. This view is in keeping with cell doc- are suspended. Previously it was thought effects. The meridians do not correspond trine — the fundamental paradigm of that binding of adenosine triphosphate to identifiable anatomical subunits. So modern biology and medicine whereby (ATP) and hydrolysis releases the energy acupuncture, although testable and useful, cells are the fundamental building blocks that drives these tiny machines. Now, it cannot be explained by cell doctrine and of all living organisms. Before cell doc- seems that this energy is too small to move conventional anatomy. The validity of cell doctrine depends on trine emerged, other possibilities were the molecular machine mechanically, but explored. The ancient Greeks debated is large enough to constrain the brownian- the scale at which the body is observed. To whether the body’s substance was an end- driven mechanics to achieve the required limit ourselves to the perspective of this lessly divisible fluid or a sum of ultimately movement. This constrained movement is model may mean that explications of some indivisible subunits. But when the micro- neither completely stochastic (that is, bodily phenomena remain outside the scopes of Theodor Schwann and Matthias brownian), nor rigidly determined (by capacity of modern biology. It is perhaps Schleiden revealed cell membranes, the structure or by consumption of ATP). time to dethrone the doctrine of the cell, to debate was settled. The body’s substance is Examples of such phenomena include allow alternative models of the body for not a fluid, but an indivisible box-like cell: actin/myosin sliding, the activation of study and exploitation in this new, postthe magnificently successful cell doctrine receptors by ligand binding, and the tran- modern era of biological investigation. ■ scription of DNA to messenger RNA. was born. Neil D. Theise is at the Division of Digestive So, at the nanoscale, cells cease to exist, Diseases, Beth Israel Medical Center, But a complexity analysis presses for consideration of a level of observation at a in the same way that the ant colony van- First Avenue at 16th Street, New York lower scale. At the nanoscale, one might ishes at the perceptual level of an ant. On New York 10003, USA. suggest that cells are not discreet objects; one level, cells are indivisible things; on rather, they are dynamically shifting, adap- another they dissolve into a frenzied, self- FURTHER READING tive systems of uncountable biomolecules. organizing dance of smaller components. Theise N. D. & d’Inverno, M. Blood Cells Mol. Dis. 32, (2004). Do biomolecules fulfill the necessary The substance of the body becomes self- 17–20 Theise N. D. & Krause D. S. Leukemia 16, 542–548 criteria for agents forming complex sys- organized fluid-borne molecules, which (2002). tems? They obviously exist in sufficient know nothing of such delineating concepts Kurakin A. Dev. Genes Evol. 215, 46–52 (2005). quantities to generate emergent phenomena; they interact only on the local level, without monitoring the whole system; and many homeostatic feedback loops govern these local interactions. But do their interactions display quenched disorder; that is, are they somewhere between being completely random and rigidly determined? Analyses of individual interacting molecules and the recognition that at the
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Neil D. Theise