Showing posts with label scientific method. Show all posts
Showing posts with label scientific method. Show all posts

Monday, October 20, 2014

What Do Mirror Neurons Really Do? (Brain Science Podcast 112, w/ Gregory Hickok)


Gregory Hickok is the author of The Myth of Mirror Neurons: The Real Neuroscience of Communication and Cognition (2014), and he was the guest on the most recent episode of the Brain Science Podcast, hosted by Dr. Ginger Campbell.

This is from the Amazon ad copy for the book:
In The Myth of Mirror Neurons, neuroscientist Gregory Hickok reexamines the mirror neuron story and finds that it is built on a tenuous foundation—a pair of codependent assumptions about mirror neuron activity and human understanding. Drawing on a broad range of observations from work on animal behavior, modern neuroimaging, neurological disorders, and more, Hickok argues that the foundational assumptions fall flat in light of the facts. He then explores alternative explanations of mirror neuron function while illuminating crucial questions about human cognition and brain function: Why do humans imitate so prodigiously? How different are the left and right hemispheres of the brain? Why do we have two visual systems? Do we need to be able to talk to understand speech? What’s going wrong in autism? Can humans read minds?

The Myth of Mirror Neurons not only delivers an instructive tale about the course of scientific progress—from discovery to theory to revision—but also provides deep insights into the organization and function of the human brain and the nature of communication and cognition.
Sounds like a great book and an important counter-balance to all of the hype being piled on the concept of mirror neurons since their discovery.

What Do Mirror Neurons Really Do? (BSP 112)

October 16, 2014/ Ginger Campbell, MD

Greg Hickok, PhD 

Ever since their chance discovery back in 1992 mirror neurons have captured the imagination of both scientists and nonscientists, but their actual role remains mostly speculative. In The Myth of Mirror Neurons: The Real Neuroscience of Communication and Cognition, Dr. Gregory Hickok (UC-Irvine) explains why the most popular theory is probably wrong. He also provides a fascinating account of how science is really done and the sobering lesson that scientists can fall prey to the same cognitive biases (and tendencies toward laziness) that plague all humans.

I first discussed the discovery of mirror neurons back in BSP 35 when I featured Mirrors in the brain: How our minds share actions, emotions, and experience (2008) by Giacomo Rizzolatti and Corrado Sinigaglia. At that time what I found most fascinating was that since mirror neurons fire both when a subject (usually a monkey) performs an action and when a similar action is observed, this proves that single neurons are not necessarily purely motor or purely sensory. This surprising discovery seems to have been overshadowed in the rush to use mirror neurons to explain everything from autism to language evolution.

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Monday, October 06, 2014

Serotonin, Depression, Neurogenesis, and the Beauty of Science

http://static.squarespace.com/static/52ec8c1ae4b047ccc14d6f29/t/5359e9dfe4b0e4fde0889f5e/1398401503422/Neuron_in_tissue_culture.jpg

From Neuroscientifically Challenged, this is an excellent explainer on the state of research into depression, including the rise and fall of the serotonin theory and the rise and struggle of the neurogenesis model. Fortunately, there is science, and the scientific method.

Serotonin, depression, neurogenesis, and the beauty of science



If you asked any self-respecting neuroscientist 25 years ago what causes depression, she would likely have only briefly considered the question before responding that depression is caused by a monoamine deficiency. Specifically, she might have added, in many cases it seems to be caused by low levels of serotonin in the brain. The monoamine hypothesis that she would have been referring to was first formulated in the late 1960s, and at that time was centered primarily around norepinephrine. But in the decades following the birth of the monoamine hypothesis, its focus shifted to serotonin, in part due to the putative success of antidepressant drugs that targeted the serotonin transporter (e.g. selective serotonin reuptake inhibitors, or SSRIs). The monoamine/serotonin hypothesis eventually became generally recognized as viable by the scientific community. Interestingly, it also became widely accepted by the public, who were regularly exposed to television commercials for antidepressant drugs like Prozac, Lexapro, and Celexa--drugs whose commercials specifically mentioned a serotonin imbalance as playing a role in depression.

Over the years, however, the scientific method quietly and efficiently went to work. Evidence gradually accumulated that indicated that the serotonin hypothesis does a very inadequate job of explaining depression. For example, although SSRIs increase serotonin levels within hours after drug administration, if their administration leads to beneficial effects--a big if--it usually takes 2-4 weeks of daily administration for those effects to appear. One would assume that if serotonin levels were causally linked to depression, then soon after serotonin levels increased, mood would begin to improve. Also, reducing levels of serotonin in the brain does not cause depression. The list of studies that don't fully support the serotonin hypothesis of depression is actually quite lengthy, and most of the scientific community now agrees that the hypothesis is insufficient as a standalone explanation of depression.

In the 1990s another hypothesis, known as the neurogenic hypothesis, was proposed with the hopes of filling in some of the holes in the etiology of depression that the monoamine hypothesis seemed to be unable to fill. The neurogenic hypothesis suggests that depression is at least partially caused by an impairment of the brain's ability to produce new neurons, a process known as neurogenesis. Specifically, researchers have focused on neurogenesis in the hippocampus, one of the only areas in the brain where neurogenesis has been observed in adulthood (the other being the subventricular zone).

The neurogenic hypothesis was formulated based on several observations. First, depressed patients seem to have smaller hippocampi than the general population, and their hippocampi also appear to be smaller during periods of depression than during periods of remission. Second, glucocorticoids like cortisol are elevated in depression, and glucocorticoids appear to inhibit neurogenesis in the hippocampus in rodents and non-human primates. Finally, there is evidence that the chronic administration of antidepressants increases neurogenesis in the hippocampus in rodents.

The neurogenic hypothesis thus suggests that depression is associated with a reduction in the birth of new neurons in the hippocampus, an area of the brain important to stress regulation, cognition, and mood. According to this hypothesis, when someone takes antidepressants, the drugs do raise levels of monoamines like serotonin, but they also enact long-term processes that increase neurogenesis in the hippocampus. This neurogenesis is hypothesized to be a crucial part of the reason antidepressants work, and the fact that it takes some time for hippocampal neurogenesis to return to normal may help to explain why antidepressants take several weeks to have an effect.

This may all sound logical, but the neurogenic hypothesis has its own share of problems. For example, while stress-related impairment of neurogenesis has been observed in rodents, we don't have definitive evidence it occurs in humans. Human studies thus far have relied on comparing the size of the hippocampi in depressed and non-depressed patients. While smaller hippocampi have been observed in depressed individuals, it is not clear that this is due to reduced neurogenesis rather than some other type of structural changes that might have occurred during depression.

Similarly, while the administration of antidepressants has been associated with increased neurogenesis in rodent models of stress, we don't have clear evidence of this in humans. In humans we again have to rely on looking at things like hippocampal size. Because there could be a number of explanations for changes in the size of the hippocampi, we can't assume neurogenesis is the sole factor involved--or that it is involved at all. Additionally, some studies in rodents have found that antidepressants lead to a reduction in anxiety or depressive symptoms in the absence of increased hippocampal neurogenesis.

Another problem is that when neurogenesis is experimentally decreased in rodents, the animals don't usually display depressive symptoms. Experiments of this type haven't been performed with humans or non-human primates, so we don't know if a reduction in neurogenesis in any species is actually sufficient to cause depression. And no studies have found that increasing neurogenesis alone is enough to alleviate depressive-like symptoms.

Of course none of this means the neurogenic hypothesis is incorrect, but it does suggest there is a long way to go before we can feel confident about incorporating it fully into our understanding of depression. In the reluctance of the scientific community to embrace this hypothesis is where I see the beauty of science. Although it took decades of testing and revising before the monoamine hypothesis became a widely accepted explanation for depression, one could argue (based on its now recognized shortcomings) that we accepted it too readily.

However, it seems that many in the scientific community have learned from that mistake. Although there is no shortage of publications whose authors may be too willing to anoint the neurogenic hypothesis as a new unifying theory of depression, overall the tone when speaking of the neurogenic hypothesis seems to be cautious and/or critical. There is also a great deal of discussion now in the literature about the complexity of mood disorders like depression, and how it is unlikely to be able to explain their manifestation in a diverse population of individuals with just one mechanism, whether it be impaired neurogenesis or a serotonin deficiency.

Thus, the neurogenic hypothesis will require much more testing before we can consider it an important piece in the puzzle of depression. Even if further testing supports it, however, it will likely be considered just that--a piece in the puzzle, instead of an overarching explanation of the disorder. And that circumspect approach to explaining depression represents an important advancement in the way we look at psychiatric disorders.

See also: http://www.neuroscientificallychallenged.com/blog/2008/04/serotonin-hypothesis-and-neurogenesis
Miller, B., & Hen, R. (2015). The current state of the neurogenic theory of depression and anxiety Current Opinion in Neurobiology, 30, 51-58 DOI: 10.1016/j.conb.2014.08.012

Wednesday, September 03, 2014

Willis F. Overton - Relationism and Relational Developmental Systems: A Paradigm for Developmental Science in the Post-Cartesian Era


This article is actually a book chapter from Embodiment and Epigenesis: Theoretical and Methodological Issues in Understanding the Role of Biology within the Relational Developmental System (Advances in Child Development and Behavior, Vol. 44), edited by In R. M. Lerner & J. B. Benson (2013). The article is posted by the author at Research Gate.

As so often happens, I came across this term - Relational Developmental Systems (a good primer here) - in another article and was curious to know more, so I went to Google Scholar and found several articles (most of them paywalled) and this book chapter (the author's copy, posted at the link above). I will post the article that led me to this one tomorrow.

I am including the introduction and the 2nd section below - there is a lot to chew on here, but this feels like an important move forward for develomental theory - and a necessary move toward a more integral model. Be sure to read the whole chapter at the link provided above or below.

Relationism and Relational Developmental Systems: A Paradigm for Developmental Science in the Post-Cartesian Era

By Willis F. Overton
Abstract
This chapter argues that the Cartesian-split-mechanistic scientific paradigm that until recently functioned as the standard conceptual framework for subfields of developmental science (including inheritance, evolution, and organismic—prenatal, cognitive, emotional, motivational, sociocultural—development) has been progressively failing as a scientific research program. An alternative scientific paradigm composed of nested metatheories with relationism at the broadest level and relational developmental systems as a midrange metatheory is offered as a more progressive conceptual framework for developmental science. Termed broadly the relational developmental systems paradigm, this framework accounts for the findings that are anomalies for the old paradigm; accounts for the emergence of new findings; and points the way to future scientific productivity.
Discerning trends in any scientific field is a dangerous undertaking, as an individual’s trend may well be another’s random walk. Nevertheless, between 2001 and 2010 or so, there seems to be clearly identifiable trends in several subfields of developmental science. One such trend involves the most recent recycling of the nature–nurture debate (i.e., the issue of inheritance). Here, advances in epigenetics and a broader understanding of the genome itself have made the route from genotype to phenotype complex to the point that the classic position claiming that who we are and what we become to be a simple additive function of gene × environment interactions has become highly untenable (see, e.g., Charney, 2012; Gottlieb, 1997, 2003; Gottlieb, Walhsten & Lickliter 2006; Greenberg, 2011; Joseph, 2010; Keller, 2010; Lerner, 2012a; Meaney, 2010; Moore, 2001; Partridge, 2005; Wahlsten, 2012).

The second trend entails the relation of evolution and development. Here, the field is rapidly moving from the traditional Modern Synthesis (Pigliucci & Mueller, 2010a)—integrating Mendelian genetics with neo-Darwinian variation and natural selection, and split-off from individual development—to a position in which individual development has become an integral part of the fabric of evolution (e.g., Batson & Gluckman, 2011; Gilbert & Epel, 2009; Gottlieb, 2002; Ho, 2010; Jablonka & Lamb, 2005; Jablonka & Raz, 2009; Lickliter & Schneider, 2006; Laubichler, 2010; Pigliucci & Mueller, 2010b; Robert, 2004; West-Eberhard, 2003). This second trend is intertwined with the first as any analysis of evolution—given the Modern Synthesis—necessarily involves a discussion of population genetics.

The third trend concerns cognition and cognitive development. Here, the standard position that mental processes are exclusively located in the brain is increasingly being challenged by the view that mental processes extend out into the body and into the technological and cultural worlds (e.g., Marshall, 2009; Menary, 2010; Overton, 2006; Rowlands, 2010; Stewart, Gapenne, & Di Paolo, 2010).

Finally, in the area of sociocultural development, there appears to be a clear trend away from the positions that identify individual development and culture as separate and distinct, if interacting, entities, and toward the position that recognizes their coconstruction, codetermination and codevelopment (e.g., Eckensberger, 2003; Mistry, Contreras, & Dutta, 2012).

As these trends advance empirically with increasing frequency, there are also suggestions that earlier conceptual frameworks that have contextualized these fields have proven, at best, inadequate to the task of integrating the new empirical advances, and, at worst, a major obstacle to integration and to scientific advancement. For example, Lickliter and Honeycutt (2010), exploring changes in the understanding of evolution, explicitly capture this sentiment in the very title of their chapter, Rethinking Epigenesis and Evolution in the Light of Developmental Science. Similarly, West-Eberhard (2003) addressing the genotype–phenotype issue in both individual development and evolution argues, “The need for a conceptual framework for the study of organization lies at the heart of unsolved problems in both ontogeny and phylogeny (p. 16).” Rowlands (2010), calling for a new science of mind in which embodied processes, the environment, and culture all enter as constitutive features of mind, expresses the need for conceptual reflection in this field when he says that this “new science…is aspirational rather than descriptive…It’s premature to say it because the new science, as yet, has no clear conceptual foundation.” (p. 25, emphasis added). Charney (2012), in an exceptionally valuable review and analysis of the significant new empirical findings in genetics and epigenetics, expresses the need for conceptual reflection in his argument that although the new evidence creates virtually insurmountable obstacles for the population (quantitative) behavior genetics paradigm, and while the evidence moves genetics into a postgenomic era, it does not itself yet constitute a paradigm because, “the postgenomic perspective has not yet coalesced around a core set of principles or assumptions characteristic of a paradigm (2012, p. 332 emphasis added).” Finally, Keller (2010), in trying to bring new light to the nature–nurture debate, finds a “morass of linguistic and conceptual vegetation grown together in ways that seem to defy untangling (p. 9; emphasis added),” and ultimately concludes:
Daily, we are discovering new and extraordinarily ingenious ways in which noncoding DNA sequences participate in the mammoth projects of regulating the spatially and temporally specific transcription of DNA, the construction and translation of messenger RNA and the positioning, conformation, and activity of proteins. Early concepts of the gene were predicated on the assumption of a relatively simple transformation from genotype to phenotype, but now we are beginning to understand just how enormously complex that process is. Such findings not only require us to rethink basic assumptions in biology, they also create the opportunity for such reconceptualizations (p. 78; emphasis added).
In this chapter, I will argue that a good deal of rethinking, conceptual reflection, and reconceptualization has already occurred with respect to these and other issues in the field of developmental science (Lerner, 2012b). Further, I will argue that this conceptual work does, in fact, offer a clear conceptual framework entailing a core set of principles or assumptions that taken together constitute a new scientific paradigm for developmental science, including each of the subfields (inheritance, evolution, and organismic development—including prenatal, cognitive, emotional, motivational, and sociocultural) mentioned above.

* * * *

2. ALTERNATIVE PARADIGMS FOR DEVELOPMENTAL SCIENCE

With an understanding of scientific paradigms and their implications as background, we may turn to an examination of the paradigm that has been the standard model across the developmental sciences—the Cartesian-split-mechanistic worldview and its midrange metatheories—and to an examination of the paradigm that Lerner and I have argued (Lerner, 2006, 2011; Lerner & Overton, 2008; Overton & Lerner, 2012; Overton, 2006, 2010, 2012) better accommodates the new data emerging in developmental science—the relationism and relational developmental systems paradigm.

2.1. The Cartesian-Split-Mechanistic Worldview and Split-Mechanistic Midrange Metatheories as Scientific Paradigm

The worldview that constitutes the broad abstract framework for the paradigm to be described here is the Cartesian-split-mechanistic worldview, while metatheories of the midrange subsumed within this worldview vary across subfields of developmental science. Thus, in the field of population genetics, a midrange metatheory has involved the Fisher–Wright ANOVA model; in traditional evolutionary biology, a midrange metatheory is the Modern Synthesis; in cognition, the computational model of mind is a midrange metatheory, and in traditional cultural approaches, it has been the person–culture dichotomy.

The Cartesian worldview as paradigm hard core is, as suggested earlier, the “Cartesian metaphysics, that is, the mechanistic theory of the universe—according to which the universe is a huge clockwork (and system of vortices) with push as the only cause of motion (Lakatos, 1978, p. 47)” and in which fundamental features of this world are split into dichotomous pure forms. A worldview is rarely, if ever, developed by one individual and this point holds for the Cartesian-split-mechanistic worldview. The early protagonists who developed the basic tenets of this broad metatheory were Galileo Galilei, and his physics of a natural world disconnected from mind; Rene Descartes, whose epistemology elevated disconnection or splitting to a first principle and whose ontology began the path to viewing the world in terms of the categories of the machine, later elaborated by Newton’s admirers such as John Locke; and Thomas Hobbes who envisioned both mind and nature in terms of an ontology of mechanically operating atomistic materialism. Of the three main figures, Descartes was, perhaps, to have the greatest and the most lasting impact on the text and subtexts of this particular metatheoretical story.

Here I focus primarily on Descartes major epistemological contributions, although the ontological contribution of Hobbs static, fixed materialism cannot be ignored. Descartes epistemological contributions consisted of the introduction of splitting, foundationalism, and atomism as key interrelated themes in the story of scientific knowing. Splitting is the separation of components of a whole into mutually exclusive pure forms or elements. In splitting, these ostensibly pure forms are cast into an exclusive “either/or” framework that forces them to be understood as contradictions in the sense that one category absolutely excludes the other (i.e., follows the logical law of contradiction that it is never the case that A = not A). But, in order to split, one must accept the twin principles of foundationalism and atomism. These are the metatheoretical axioms that there is ultimately a rock bottom unchanging nature to Reality (i.e., with a capital R, distinguishing this ultimate real from the commonsense reality of everyday objects [Putnam, 1987]). This conception is Descartes’ foundationalism, describing a final fixed secure base. It constitutes an absolute, fixed, unchanging bedrock; a final Archimedean point (Descartes, 1969). Further, this rock bottom is composed of elements—pure forms—(the atoms of atomism) that preserve their identity regardless of context. A corollary principle here is the assumption that all complexity is simple complexity or simply complicated in the sense that any whole is taken to be a purely additive combination of its elements.

Splitting, foundationalism, and atomism are all principles of decomposition; breaking the aggregate down to its smallest pieces, to its bedrock (Overton, 2006). This process also goes by other names, including reductionism and the analytic attitude (Overton, 2002, 2006). Split metatheory, however, requires another principle to reassemble or recompose the whole. This is the principle of unidirectional, linear and additive associative or causal sequences. The elements must be related either according to their contiguous cooccurrence in space and time, or according to simple efficient or material mechanical cause–effect sequences that proceed in a single direction (Bunge, 1962; Overton & Reese, 1973). In fact, split metatheory admits no determination other than individual efficient and material causes, or these individual causes operating in a conjunctive (i.e., additive) plurality. Truly reciprocal causality <-->, or circular causality, are not permitted in this system (Bunge, 1962; Overton & Reese, 1973; Witherington, 2011).

2.1.1. Implications of the Cartesian-Split-Mechanistic Worldview for Developmental Science

The standard traditional frame for the issues of developmental science that are the focus of this chapter has been the principles of this Cartesian-split-mechanistic worldview. In classic genetics, the gene was introduced as an analog to the chemical element as the foundational biological element (Keller, 2010); the gene was conceptualized as the “master molecule” that “causes” the production of proteins; a linear additive, unidirectional causal path was asserted to operate from DNA to RNA to protein as defined by the “central dogma of molecular biology” (Gottlieb, 2000). With respect to population (quantitative) genetics, the relation of genes to environment is conceptualized within a completely additive (Lewontin, 1974; Overton & Reese, 1973) model, and statistical gene × environment interactions are themselves completely decomposable into strictly additive elements. As Turkheimer (2011) points out, this assumption of additivity is “the foundation of modern quantitative genetics”. And Partridge (2005, 2011), supporting Turkheimer’s point, goes on to describe how advances in the Fisher–Wright ANOVA model, such as extensions to multivariate and latent variable models and multilevel models, adhere to the same additive structure as the original Fisher model.

For the evolutionary Modern Synthesis, development and evolution are split (see, e.g., Lickliter & Honeycutt, 2010). Further, internal is splitoff from external, yielding an isolated internalism of gene centrism (i.e., gene as the sole unit of variation), and an isolated externalism of change (i.e., emphasis on natural selection as the virtually sole vehicle of change) (see, e.g., Pigliucci & Mueller, 2010a). The Modern Synthesis also entails commitment to evolutionary “gradualism” (i.e., additive continuity) that derives from the same mathematical formalism identified above that Pigliucci and Mueller (2010a) refer to as the “backbone” of population genetics, and, hence the backbone of the Modern Synthesis.

The field of cognition and cognitive development, more than the biological or cultural fields of developmental science, has most frequently given explicit recognition to the fact that, at least until recently, the discipline has been framed by the Cartesian metatheory (e.g., Marshall, 2009; Mueller & Newman, 2008; Rowlands, 2010; Varela, Thompson, & Rosch, 1991). Early in this field’s emergence—known as the Cognitive Revolution—what became termed “cognitivism” was based on the midrange metatheory of the computational model of mind. Not only did this midrange metatheory strictly follow the dictates of the Cartesian worldview of splitting mind from body, it also explicitly framed itself within the worldview’s basic category system, the machine. As Marshall (2009) describes it, “The ascent of cognitivism depended on making the mind more transparent by using computers to model mental processes…. The Cartesian foundation of this approach has inspired a rising tide of criticism over the last three decades, mainly centered around the problem that the computational mind of cognitivism lacks a brain, a body, and a culture (p. 120).” Later, as Rowlands (2010) pointed out, “from the mid-1980s on, this [computer model of mind] emphasis gradually gave way to a renewed emphasis on ‘hardware’ in the form of connectionist or neural network approaches (p. 2).” These models attempt a mechanical modeling of cognition that, while perhaps more neurobiologically realistic (see, however, Edelman, 1992), continues to adhere to Cartesian dictates, thereby leaving mental process locked in the brain, split-off from the full functioning of the body and from culture. This Cartesian position is clearly articulated by Adams and Aizawa (2010) in their argument that “There are processes that (1) are recognizably cognitive, (2) take place in the brain, (3) do not take place outside of the brain, and (4) do not cross from the brain into the external world (p. 69).” In the end, as Goode (2007) notes, “on the cognitivist view…the starting point is the solitary Cartesian subject detached from the world and its objects (including other people). Thus, the cognitivist has to account for the way the knower ‘hooks on to’ the world and to other people in it (p. 272).”

In the area of culture and development, Cartesian tracks are found in a number of areas where individual and culture are viewed as split-off pure forms. For example, in their analysis of the culture and development literature, Mistry et al. (2012) point to the fact that in both crosscultural and ecological approaches, culture is treated as an antecedent variable that influences, but is not constitutive of, the individual and development:
On the issue of how culture should be conceptualized, cross-cultural psychologists tended to view culture as an ‘independent variable’ that influenced human behavior. Some cross-cultural psychologists suggested that culture should be operationalized as a set of conditions … For example Poortinga (1997) defined the cross-cultural approach as: ‘… a tendency to take cultural context, including ecological as well as sociocultural variables, as a set of antecedent conditions, while behavior phenomena, including attitudes and meanings as well as observed behaviors as outcomes or consequents’ (p. 350). In the ecological model (Bronfenbrenner, 1979, 1986), which had been particularly influential in developmental psychology, culture was operationalized as the macro (pervasive) influence on the developing person.
Although still an influential worldview, the Cartesian metatheory and the midrange metatheories it subsumes have come under increased criticisms as an adequate scientific paradigm for developmental science. These criticisms are cross-disciplinary, coming both from those cited above and, more generally, from biology and neuroscience (e.g., Damasio, 1994; Gallese & Lakoff, 2005), philosophy (Gallagher, 2005; Taylor, 1995), anthropology (Ingold, 2000; Sheets-Johnstone, 1990), and psychology (Barsalou, Simmons, Barbey, & Wilson, 2003; Colombetti & Thompson, 2008; Hobson, 2002; Mueller & Newman, 2008; Smith, 2005).

2.2. Relationism and Relational Developmental Systems: A Paradigm for Developmental Science

The question arises as to whether these conceptual criticisms raised against the Cartesian-split-mechanistic worldview and its midrange metatheories; the empirical anomalies faced by the paradigm; and failures of the paradigm to generate new ideas and new data are sufficient to conclude that this paradigm should be rejected as invalid? The answer is no. While these may be necessary conditions for dismissing the Cartesian-split-mechanistic metatheory and its subsumed midrange metatheories, only an available alternative paradigm constitutes a sufficient condition for rejection. It is argued here that there is such a paradigm available; one that (1) better accommodates the new data from several fields; (2) overcomes the conceptual problems of the Cartesian-split-mechanistic metatheory and its subsumed midrange metatheories, and (3) generates novel and empirically productive predictions for the field of developmental science. This is the relationism (as worldview) and relational developmental systems (as midrange metatheory) paradigm, which I next describe.

2.2.1. Relationism

Relationism finds its historical origins in Aristotle’s insistence that form and matter cannot be separated into two discrete elements, and later in Kant’s attempt to reconcile empiricism and rationalism and in Hegel’s elaboration of dialectical logic. One broad effect of adopting relationism as a paradigm worldview is that it leads to the healing of the classic fundamental antimonies (e.g., subject–object, mind–body, nature–nurture, culture–individual, culture–biology, self–other) (Table 2.1) and provides concepts that are inclusive and concepts that adequately ground science generally and developmental science specifically. In an analysis of the historical failures of classical split metatheory, as well as the emptiness of its seeming rival—postmodern thought—Bruno Latour (1993, 2004) proposed a move away from the extremes of Cartesian splits to a center or middle kingdom position where entities and ideas are represented, not as pure forms, but as forms that flow across fuzzy boundaries. This movement is one toward what Latour terms relationism, a metatheoretical space where foundations are groundings, not bedrocks of certainty, and analysis is about creating categories, not about cutting nature at its joints. The present version of relationism builds on Latour’s proposal.



Relationism is a worldview formed as a principled synthesis of Pepper’s (1942) organicism and contextualism (for details, see Overton, 2007a; Overton & Ennis, 2006a, 2006b).[3] As a worldview, it is composed of a coherent set of intertwined ontological and epistemological principles. The ontology of relationism offers a Real based on process-substance rather than a split-off substance (Bickhard, 2008). This ontology is what Gadamer (1989) argues to be the movement of to and fro and what has been sometimes defined as an ontology of Becoming (Allport, 1955; Overton, 1991). It includes process, activity, dialectic change, emergence, and necessary organization as fundamental defining categories, but it does not exclude categories of substance, stability, fixity, additivity, and contingent organization.

The epistemology of relationism is, first and foremost, a relatively inclusive epistemology, involving both knowing and known as equal and indissociable complementary processes in the construction, acquisition, and growth of knowledge. It is relatively inclusive, because inclusion itself—much like Hegel’s master–slave dialectic—can be grasped only in relation to its complement exclusion. Thus, just as freedom must be identified in the context of constraint, inclusion must be identified in the context of exclusion. Relational epistemology specifically excludes Cartesian dualistic ways of knowing because Cartesian epistemology trades on absolute exclusivity; it constitutes a nothing but epistemology. For the same reason, relationalism rejects both the mechanistic worldview and a strict contextualist interpretation of the contextualist worldview (Overton, 2007a; Witherington, 2007, 2011). Epistemologically, relationism begins by clearing the “nothing but” splitting, foundationalism, atomism, and objectivism from the field of play and in so doing, it moves toward transforming antinomies into coequal, indissociable complementarities. In the relational frame, fixed absolute elements are replaced by contextually defined parts.

In place of the rejected splitting, foundationalism and atomism, relationism installs holism as the overarching epistemological first principle. Building from the base of holism, relationism moves to specific principles that define the relations among parts and the relations of parts to wholes. In other words, relational metatheory articulates principles of analysis and synthesis necessary for any scientific inquiry. These principles are (1) The Identity of Opposites, (2) The Opposites of Identity, and (3) The Synthesis of Wholes.

2.2.2. Holism

Holism is the principle that the identities of objects and events derive from the relational context in which they are embedded. Wholes define parts and parts define wholes. The classic example is the relation of components of a sentence. Patterns of letters form words and particular organizations of words form sentences. Clearly, the meaning of the sentence depends on its individual words (parts define whole). At the same time, the meaning of words is often defined by the meaning of the sentence (wholes define parts). Consider the word meanings in the following sentences: (1) The party leaders were split on the platform; (2) The disc jockey discovered a black rock star; and (3) The pitcher was driven home on a sacrifice fly. The meaning of the sentence is obviously determined by the meaning of the words, but the meaning of each italicized word is determined by context of the sentence it is in. Parts determine wholes, and wholes determine their parts (Gilbert & Sarkar, 2000).

Holistically, the whole is not an aggregate of discrete elements but an organized system of parts, each part being defined by its relations to other parts and to the whole. Complexity in this context is organized complexity (Luhmann, 1995; von Bertalanffy, 1968a, 1968b), in that the whole is not decomposable into elements arranged in additive sequences of mechanistic cause–effect relations (Overton & Reese, 1973). In the context of holism, principles of splitting, foundationalism, and atomism are, by definition, rejected as meaningless approaches to analysis, and fundamental antimonies are similarly rejected as false dichotomies (Table 2.1). In an effort to avoid standard (i.e., neopositivistic and conventionalist) misunderstandings here, it must be strongly emphasized that nondecomposability does not mean that analysis itself is rejected. It means that analysis of parts must occur in the context of the parts’ functioning in the whole. The context-free specifications of any object, event, or process—whether it be a DNA, cell, neuron, evolution, the architecture of mind, or culture—are illegitimate within a holistic system (see, e.g., Ingold, 2000). Bunge (2003) well[4] captures both the problem of reductionism and the issue of holism in the following:
At first sight, the discovery that genetic material is composed of DNA molecules proves that genetics has been reduced to chemistry …. However, chemistry only accounts for DNA chemistry: it tells us nothing about the biological functions of DNA – for instance that it controls morphogenesis and protein synthesis. In other words, DNA does not perform any such functions when outside a cell, anymore than a stray screw holds anything together. Besides, DNA does nothing by itself: it is at the mercy of the enzymes and RNAs that determine which genes are to be expressed or silenced. In other words, the genetic code is not the prime motor it was once believed to be. This is what epigenesis is all about (p. 138).
Although holism is central to relationism, holism does not in itself offer a detailed program for resolving many dualisms that have framed scientific knowing and knowledge. A complete relational program requires principles according to which the individual identity of each concept of a formerly dichotomous pair is maintained, while simultaneously it is affirmed that each concept constitutes, and is constituted by, the other. This understanding is accomplished by considering identity and differences as two moments of analysis. The first moment is based on the principle of the identity of opposites; the second moment is based on the principle of the opposites of identity.

2.2.3. The Identity of Opposites

The principle of the identity of opposites establishes the identity among parts of a whole by casting them, not as exclusive contradictions as in the split epistemology but, as differentiated polarities (i.e., coequals) of a unified (i.e., indissociable) inclusive matrix—as a relation. As differentiations, each pole is defined recursively; each pole defines and is defined by its opposite. In this identity moment of analysis, the law of contradiction is suspended and each category contains and, in fact, is its opposite. Further—and centrally—as a differentiation, this moment pertains to character, origin, and outcomes. The character of any contemporary behavior, for example, is 100% nature because it is 100% nurture; 100% biology because it is 100% culture. There is no origin to this behavior that was some other percentage—regardless of whether we climb back into the womb, back into the cell or back into the DNA—nor can there be a later behavior that will be a different percentage. There are a number of ways to illustrate this principle; one particularly clear illustration is found in the famous ink sketch by M. C. Escher titled Drawing Hands (Overton, 2006). In this sketch, a left and a right hand assume a relational posture according to which each is simultaneously drawing and being drawn by the other (Fig. 2.2(a) is a schematic illustration). In this matrix, there is a sense in which each hand is different (opposite left and right hand) and a sense in which the hands are identical (each is drawing and being drawn). In the latter analytic Identity of Opposites moment, the hands are identical (i.e., A = Not A), thus coequal and indissociable.This moment of analysis is one in which the law of contradiction (i.e., not the case that A = not A) is relaxed and identity (i.e., A = Not A) reigns. In this identity moment of analysis, pure forms or the notion of “natural kinds” collapse and categories flow into each other. Here, each category contains, and is, its opposite. As a consequence, there is a broad inclusivity established among categories.

Within the identity moment of analysis, it is often a useful exercise to write on each hand (or the arrows of the schematic) one of the bipolar terms of an often split dualisms (e.g., genotype and phenotype, development and evolution, encapsulated and extended mental processes, person, and culture) and to explore the resulting effect (see, for example, Fig. 2.2(b), (c)). This exercise is quite different than an illustration of a familiar bidirectionality of mechanical cause and effects. This exercise makes tangible a central tenet of the relational metatheory; seemingly dichotomous ideas often thought of as competing alternatives (Table 2.1) can, in fact, enter into inquiry as coequal and indissociable. This exercise also concretizes the meaning of “causality” within relationism. In this framework, the concepts reciprocal determination (Overton & Reese, 1973), coaction (Gottlieb, Wahlsten, & Lickliter, 2006), fusion (Greenberg, 2011; Partridge, 2011) as well as relational bidirectional (<-->) causality (Lerner, 2006), relational causality (Gottlieb, 2003), and circular causality (Witherington, 2011) are relatively similar terms used to differentiate the positive and negative feedback loops of relationism from additive (even bidirectionally additive) causality of the Cartesian-split-mechanistic worldview.



The principle of the identity of opposites imposes theoretical and methodological constraints on any field of inquiry—biological, evolutionary, individual, and cultural—just as other metatheories impose constraints on any field of inquiry. The primary constraints within relationism are that (1) splits are not permitted (e.g., the split of genotype and phenotype in genetics, the split of internalism and externalism in the Modern Synthesis, the split of brain, body, and culture in cognitivism, and the cultural split of individual and culture) and (2) phenomena cannot be thought of as being decomposable into independent and additive pure forms (e.g., the Fisher–Wright AVOVA model in genetics and in the Modern Synthesis).[5]

If the principle of the identity of opposites introduces constraints, it also opens possibilities. One of these is the recognition that—to paraphrase Searle (1992)—the fact that a behavior implicates activity of the biological system does not imply that it does not implicate activity of the cultural system, and the fact that the behavior implicates activity of the cultural system does not imply that it does not implicate activity of the biological system. In other words, the identity of opposites establishes the metatheoretical rationale for the theoretical position that biology, person, and culture operate in a truly interpenetrating relational manner.

2.2.4. The Opposites of Identity


Although the identity of opposites sets constraints and opens possibilities, it does not in itself set a positive agenda for empirical scientific inquiry. The limitation of the identity moment of analysis is that, in establishing a flow of categories of one into the other, a stable base for inquiry that was provided by bedrock material atoms of the split metatheory is eliminated. In the split approach, no relativity entered the picture; all was absolute. Reestablishing a stable base—not an absolute fixity, nor an absolute relativity, but a relative relativity (Latour, 1993)—within relational metatheory requires moving to a second moment of analysis. This is the oppositional moment, where the figure of identity and ground of opposites reverses and opposites become figure. This moment becomes dominated by a relational exclusivity. Thus, in this opposite moment of analysis, it becomes clear that despite the earlier identity, the schematic of Escher’s sketch does illustrate both a right hand and a left hand (see Fig. 2.3 for culture and person). In this moment of opposition, the law of contradiction is reasserted and categories again exclude each other. As a consequence of this exclusion, parts exhibit unique identities that differentiate each from the other. These unique differential qualities are stable within any holistic system and, thus, may form relatively stable platforms for empirical inquiry. The platforms created according to the principle of the opposites of identity become standpoints, points-of-view, or lines-of-sight, in recognition that they do not reflect absolute foundations (Latour, 1993, 2004) but perspectives in a multiperspective world. They may also be considered under the common rubric levels of analysis when these are not understood as bedrock foundations.

Again, thinking of the Escher sketch (or the schematic of Fig. 2.3), when left hand as left hand (A) and right as right (Not-A) are separately the focus of attention, it then becomes quite clear that, were they large enough, one could stand at either hand and examine the structures and functions of that location, as well as its relation to the other location (i.e., the coactions of parts). Thus, to return to the example of nature–nurture, although explicitly recognizing that any behavior is both 100% biology and 100% culture, alternative points of view permit the scientist to analyze the acts of the person from a biological or from a cultural standpoint. Biology and culture no longer constitute competing alternative explanations; rather, they are two points of view on an object of inquiry that has been created by, and will be fully understood only through, multiple viewpoints. More generally, the unity that constitutes the organism and its development becomes discovered only in the diversity of multiple interrelated lines of sight.



2.2.5. The Synthesis of Wholes

Engaging fundamental bipolar concepts as relatively stable standpoints opens the way, and takes an important first step toward establishing a broad stable base for empirical inquiry within relational metatheory. However, this solution is incomplete as it omits a key relational component, the relation of parts to the whole. The oppositional quality of the bipolar pairs reminds us that their contradictory nature still remains, and still requires a resolution. Further, the resolution of this tension cannot be found in the split approach of reduction to a bedrock absolute reality. Rather, the relational approach to a resolution is to move away from the extremes to the center and above the conflict, and there discover a novel system that will coordinate the two conflicting systems. This principle is the synthesis of wholes, and the synthesis itself is another standpoint.

The synthesis of interest for the general metatheory would be a system that is a coordination of the most universal bipolarity that can be imagined. Arguably, there are several candidates for this level of generality, but the polarity between matter or nature, on the one hand, and society, on the other, is sufficient for present purposes (Latour, 1993). Matter and society represent systems that stand in an identity of opposites. To say that an object is a social or cultural object in no way denies that it is matter; to say that an object is matter in no way denies that it is social or cultural. And further, the object can be analyzed from either a social–cultural or a physical standpoint. The question for synthesis becomes the question of what system will coordinate these two systems. Arguably, the answer is that it is life or living systems that represent the coordination of matter and society. Because our specific focus of inquiry is the psychological subject, we can reframe this matter–society polarity back into a nature–nurture polarity of biology (matter) and culture (society). In the context of psychology, then, as an illustration, if we again write biology on one and culture on the other Escher hand (or schematic figure), and question what system represents the coordination of these systems, it is life, the human organism, the person (Fig. 2.4). That is, the person is the relational synthesis of biological and sociocultural processes.

At the synthesis, then, a standpoint coordinates and resolves the tension between the other two components of the relation. This synthesis provides a particularly broad and stable base for launching empirical inquiry. A person standpoint opens the way for the empirical investigation of universal dimensions of psychological structure–function relations (e.g., processes of perception, thought, emotions, values), the particular variations associated with these wholes, their individual differences, and their development across the life span. Because universal and particular are themselves relational concepts, no question can arise here about whether the focus on universal processes excludes the particular; it clearly does not as we already know from the earlier discussion of relations. The fact that a process is viewed from a universal standpoint in no way suggests that it is not situated and contextualized; the fact that it is viewed from an individual standpoint in no way denies its universality.



It is important to recognize that one standpoint of synthesis is relative to other synthesis standpoints. Life and Society are coordinated by Matter. As a consequence, if we are broadly considering the scientific field of psychology, biology represents a standpoint as the synthesis of person and culture (Fig. 2.4). The implication of this idea is that a relational biological approach to psychological processes investigates the biological conditions and settings of psychological structure–function relations and the actions they express. This exploration is quite different from split foundationalist Cartesian- split-mechanistic approaches to biological inquiry that assumes an atomistic and reductionistic stance toward the object of study. Neurobiologist Antonio Damasio’s (1994, 1999) work on the brain–body basis of a psychological self and emotions is an excellent illustration of this biological relational standpoint. In the context of this standpoint, Damasio (1994) is emphatic that:
A task that faces neuroscientists today is to consider the neurobiology supporting adaptive supraregulations [e.g., the psychological subjective experience of self] … I am not attempting to reduce social phenomena to biological phenomena, but rather to discuss the powerful connection between them. … Realizing that there are biological mechanisms behind the most sublime human behavior does not imply a simplistic reduction to the nuts and bolts of neurobiology [emphasis added] (pp. 124–125).
A similar biological example comes from the Nobel laureate neurobiologist Gerald Edelman’s (1992; 2006) work on the brain–body base of consciousness:
I hope to show that the kind of reductionism that doomed the thinkers of the Enlightenment is confuted by evidence that has emerged both from modern neuroscience and from modern physics. … To reduce a theory of an individual’s behavior to a theory of molecular interactions is simply silly, a point made clear when one considers how many different levels of physical, biological, and social interactions must be put into place before higher order consciousness emerges. (Edelman, 1992, p. 166).
And finally, Gilbert and Epel (2009) in presenting ecological developmental biology (eco-devo) describe several “revolutions” occurring in biology, including a new relational orientation: “Rather than analyzing independent ‘things’ a new focus of developmental biology concerns ‘relationships’. Nothing , it seems, exists except as part of a network of interactions (p. xiii, emphasis added).”

A third synthesis standpoint recognizes that Person and Matter are coordinated by Society, and again granting that our domain of scientific interest is psychological inquiry about psychological processes, then culture or sociocultural represents a standpoint as the synthesis of person and biology (Fig. 2.4). Thus, a relational cultural approach to psychological processes explores the cultural conditions and settings of psychological structure–function relations. From this cultural standpoint, the focus is on cultural differences in the context of psychological functions as complementary to the person standpoint’s focus on psychological functions in the context of cultural differences.

Valsiner (1998) gives one illustration of a relational, developmentally oriented cultural standpoint in his examination of the “social nature of human psychology”. Focusing on the “social nature” of the person, Valsiner stresses the importance of avoiding the temptation of trying to reduce person processes to social processes. To this end, he explicitly distinguishes between the dualisms of split foundationalist metatheory and dualities of the relational stance he advocates.

When the three points of synthesis—biology, person, and socioculture—are cast as a unity of interpenetrating coacting parts, there emerges what Greenberg and Partridge (2010) describe as a biopsychosocial model of the organism. In their tripartite relational approach, each part interpenetrates and coconstructs the other or coevolves with the other. Development of the biological organism begins from a relatively undifferentiated biosocial action matrix, and through coconstructive interpenetrating coactions, the biological, the cultural, and the psychological or person part systems emerge, differentiate, and continue their interpenetrating coconstruction, moving through levels of increased complexity toward developmental ends.

2.2.6. Relational Developmental Systems

Taken as a whole—including both its ontological and epistemological assumptions—relationism operates as the contextual frame for the construction of midrange metatheories. These latter metatheories are less broad in scope, more specific to particular domains of inquiry, and together with relationism, constitute a conceptual framework for a scientific paradigm. Relational developmental system is itself the broadest of these midrange metatheories, all of which incorporate systems concepts, including developmental, dynamic, dialectical, transactional systems, and enaction.[2] Relational developmental systems represents an extension (Lerner, 2006, 2011; Lerner & Overton, 2008; Overton & Lerner, 2012; Overton, 2006, 2010, 2012) of the original developmental systems “theory” described by Ford and Lerner (1992) and Gottlieb (1996) (see also Lerner, 2002). This extension was motivated by an increasing recognition of relationism as a central feature of the conceptual framework of an alternative scientific paradigm to that formulated within the Cartesian-split-mechanistic worldview.

Relational developmental systems is a perspective on developmental science (i.e., development [behavioral, cognitive, motivational, emotional, and sociocultural], inheritance, and evolution). The relational nature of the system emphasizes causality as reciprocal bi- or multidirectional (<-->) or circular (positive and negative feedback loops).[6] All facets of the individual and the context exist in mutually influential relations (Elder, 1998; Molenaar, 2007). Accordingly, the potential for plasticity (Batson & Gluckman, 2011; Charney, 2012; West-Eberhard, 2003) of intraindividual change is a hallmark of Relational developmental systems.

This metatheory conceptualizes living organisms as active agents, (Overton, 1976) that is, as relational, spontaneously active, complex adaptive systems, that are self-creating (i.e., enactive; autopoetic), self-organizing (i.e., process according to which higher level system organization arises solely from the coaction of lower level components of the system), and self-regulating. Further, the development process—including embryogenesis, ontogenesis, and phylogenesis—is conceptualized as entailing, five defining features: (1) nonlinearity (i.e., inputs are not proportional to outputs), (2) order and sequence, (3) direction, (4) relative permanence and relative irreversibility, and (5) epigenesis and emergence. Epigenesis is conceptualized as “probabilistic epigenesis” (Gottlieb, 1992), which designates a holistic approach to understanding developmental complexity. Probabilistic epigenesis is the principle that the role played by any part of a relational developmental system—DNA, cell, tissue, organ, organism, physical environment, and culture—is a function of all of the interpenetrating and coacting parts of the system. It is through complex reciprocal bidirectional and circular reciprocal interpenetrating actions among the coacting parts that the system moves to levels of increasingly organized complexity. Thus, epigenesis identifies the system as being completely contextualized and situated.

Epigenesis entails the closely related feature of emergence of system novelty.[7] As systems change, they become increasingly complex. This increased complexity is a complexity of form rather than an additive complexity of elements. The butterfly emerges from the caterpillar through the differentiation and reintegration of organization, the frog from the tadpole, the plant from the seed, and the organism from the zygote. In an identical manner, higher order psychological structures emerge from lower order structures; also in an identical manner, new forms of organization exhibit novel features that cannot be reduced to (i.e., completely explained by) or predicted from earlier forms. The novel features are termed systemic, indicating that they are properties of the whole system and not properties of any individual part. This emergence of novelty is commonly referred to as qualitative change in the sense that it is the change that cannot be represented as purely additive. Similarly, reference to “discontinuity” in development is simply the recognition of emergent novelty and qualitative change of a system.

System constitutes the core concept of this metatheory and this concept has been defined in various ways. For example, van Geert (2003) offers “any collection of phenomena, components, variables” (p. 655). However, this conception and other “collection” or aggregate-like definitions are inconsistent with holism and, consequently, inconsistent with relational developmental systems. A more adequate relational definition of system is “a whole which functions as a whole by virtue of the interdependence of its parts” (Overton, 1975). Thus, a system is by its nature organized and organized holistically. Further, the relational system is an adaptive system. Here, adaptation refers to how the system responds to changing environments—“perturbations” in systems language—so as to increase its probability of survival, not in the sense of adjusting to an environment. Adaptive systems are defined in contrast with “determined” systems. In determined systems, the relation between inputs and outputs are exactly and reproducibly connected. For example, an automobile is a determined system. When the driver presses the accelerator or turns the steering wheel, both driver and passenger expect the auto to speed up or turn. All components of the auto must be fully determined to achieve this collective response. And determined systems are linear—small inputs resulting in small outputs; large inputs in large outputs—thus, outputs are predictable. In adaptive systems, the parts follow simple rules, whereas the behavior of the whole system is not determined.

The second core concept of relational developmental systems is action. The relational developmental system is the source of action. At subpersonal levels, where it is not necessary to limit a definition to organismic development or even to living systems, action is defined as the characteristic functioning of any complex adaptive self-creating and system-organizing system. For example, weather systems form high-and low-pressure areas and move from west to east. Living systems, on the other hand, organize, and adapt to, their biological, sociocultural, and environmental worlds. At the person level, organismic development action is defined as intentional activity (i.e., meaning giving activity). Intentionality, however, is not to be identified solely with consciousness. While all acts are  intentional, only some intentions are conscious or self-conscious. In a similar manner, intention is not to be identified solely with a symbolic or reflective level of knowing. Following Brentano (1973), all acts, even those occurring at early sensorimotor levels of functioning, intend some object. 

The primary function of action is that at the microscopic level, it represents the general mechanism for all development. It is through the coconstituting actions of any target system of interest (e.g., genetic, epigenetic, cell, zygote, embryo, fetus, infant…species) with its environments, as well as the resistances (perturbations) the target system encounters that the system changes and, hence, becomes differentiated and reintegrated at increasingly complex and novel levels of organization.

The final core concept is that of embodiment (Overton, 1994, 2008). All acts are embodied acts and, consequently, the general case is that embodied action is the general mechanism for all development. Embodiment represents the interpenetrating relations between person, biology, and culture. It is the claim that perception, thinking, feelings, and desires—the way we behave, experience, and live the world—are contextualized by our being active agents with this particular kind of body (Taylor, 1995). The kind of body we have is a constitutive precondition for having the kind of behaviors, experiences, and meanings that we have. Embodiment includes not merely the physical structures of the body but the body as a form of lived experience, actively engaged with the world of sociocultural and physical objects. The body as form references the biological point of view, the body as lived experience references the psychological subject standpoint, and the body actively engaged with the world represents the sociocultural point of view. Within a relational context, embodiment is a concept that bridges and joins in a unified whole these several research points of synthesis without any appeal to splits, foundationalism, elements, atomism, and reductionism.[8]


NOTES (for these sections):
3. Witherington (2007, 2011) employs a similar organicism–contextualism integration to distinguish between dynamic systems metatheories based on a strict contextualist worldview (e.g., Thelen & Smith, 1994; Spencer, Perone, & Johnson, 2009) from those based on an organicist–contextualist integration (e.g., van Geert, 2003; van der Maas & Molenaar, 1992; Lewis, 2011).

4. I am indebted to Gary Greenberg for pointing me to this quote.

5. West-Eberhard’s (2003) evolutionary work provides a biological example of the identity of opposites in her resolution of the conflict between the quantitative genetics of continuous variation and the developmental biology of the discrete traits. This resolution is “a theory of the phenotype based on the complementarity of continuous and discrete variation (p. 13 emphasis added).” All antimonies are best viewed as complementaries. Relationism articulates the meaning of complementarity.

6. In order to avoid serious conceptual confusion, it is essential to differentiate this type of causality from “mechanical” or “mechanistic” causality. An example of the failure to make this distinction appears in the writings of Pigliucci and Mueller (2010a) and Mueller (2010). In discussions of new trends in evolution, these authors acknowledge the centrality of systems concepts, but simultaneously describe this as “a shift towards a causal-mechanistic approach,” “a shift…to a causal-mechanistic theory (Pigliucci & Mueller, 2010a, p. 12),” and a “turn towards the mechanistic explanation of phenotypic change (Mueller, 2010, p. 309)”. There is a profound difference between the claim that there has been a trend away from correlational approaches to causal approaches, and the claim that there has been a trend away from correlational approaches to mechanistic causal approaches.

7. For an extensive, in-depth analysis of meanings of “emergence,” which are and are not compatible with an integrated organism–contextualism (i.e., relationism) worldview, see Witherington (2011).

8. See Withherington (this volume) for a discussion of alternative interpretations of “embodiment” within a strictly contextualist and within an organismic–contextualist (relationism) worldview.

Saturday, August 23, 2014

William P. Hanage - Microbiome Science Needs a Healthy Dose of Skepticism

I am a huge fan of the new research being done on the microbiome, the small universe of bacteria (intestinal flora) living with us. I have seen convincing evidence of the role played by the microbiome in mental illness (depression, especially), obesity, and compromised immunity (our intestines are, in many ways, the home of the immune system). Because we do not yet fully understand this incredibly diverse ecosystem, many of the studies are correlational, unable to show concrete cause and effect.

But I also agree with this editorial from Nature - we need to resist the urge to jump to conclusions and make assertions based solely on correlation. We know so little about this system that the methods we are currently using seem almost child-like. For example,
Much work relies on analysis of 16S rRNA, an ancient gene that tolerates little variation and so is reliably found across the bacterial kingdom. But this allows only a coarse sorting. For example, microbiomes associated with obesity have been distinguished by different ratios of bacterial phyla, which encompass a staggering range of diversity. If this criterion were used to characterize animal communities, an aviary of 100 birds and 25 snails would be considered identical to an aquarium with 8 fish and 2 squid, because each has four times as many vertebrates as molluscs. Even within a single species, strains often differ greatly in the genes they contain.
Sorting and ratios can tell us very little about the genetic and epigenetic mechanisms at work. It may be decades before we can identify with any certainty what is going on in our guts.

Full Citation:
Hanage, WP. (2014, Aug 21). Microbiology: Microbiome science needs a healthy dose of scepticism. Nature; 512:247–248. doi:10.1038/512247a

Microbiology: Microbiome science needs a healthy dose of skepticism

To guard against hype, those interpreting research on the body's microscopic communities should ask five questions, says William P. Hanage.


William P. Hanage
20 August 2014


Eye of Science/SPL - A scanning electron micrograph of bacteria in human faeces, in which 50% of species originate from the gut.

Explorations of how the microscopic communities that inhabit the human body might contribute to health or disease have moved from obscure to ubiquitous. Over the past five years, studies have linked our microbial settlers to conditions as diverse as autism, cancer and diabetes.

This excitement has infected the public imagination. 'We Are Our Bacteria', proclaimed one headline in The New York Times. Some scientists have asserted that antibiotics are causing a great 'extinction' of the microbiome, with dire consequences for human health [1]. Companies offer personalized analysis of the microbial content of faecal samples, promising consumers enlightening information. Separate analyses from the same person can, however, vary considerably, even from the same stool sample. Faecal transplants have been proposed — some more sensible than others — for conditions ranging from diabetes to Alzheimer's disease. With how-to instructions proliferating online, desperate patients must be warned not to attempt these risky procedures on themselves.

Microbiomics risks being drowned in a tsunami of its own hype. Jonathan Eisen, a microbiologist and blogger at the University of California, Davis, bestows awards for “overselling the microbiome”; he finds no shortage of worthy candidates.

Previous 'omics' fields have faltered after murky work slowed progress [2]. Technological advances that allowed researchers to catalogue proteins, metabolites, genetic variants and gene activity led to a spate of associations between molecular states and health conditions. But painstaking further work dampened early excitement. Most initial connections were found to be spurious or, at best, more complicated than originally believed.

The history of science is replete with examples of exciting new fields that promised a gold rush of medicines and health insights but required scepticism and years of slogging to deliver even partially. As such, the criteria for robust microbiome science are instructive for all researchers. As excitement over the microbiome has filtered beyond academic circles, the potential mischief wrought by misunderstanding encompasses journalists, funding bodies and the public.

Crucial questions
Here are five questions that anyone conducting or evaluating this research should ask to keep from getting carried away by hype.

Can experiments detect differences that matter? Profiling a microbiome could produce a catalogue at the level of phyla, species or genes. Much work relies on analysis of 16S rRNA, an ancient gene that tolerates little variation and so is reliably found across the bacterial kingdom. But this allows only a coarse sorting. For example, microbiomes associated with obesity have been distinguished by different ratios of bacterial phyla, which encompass a staggering range of diversity. If this criterion were used to characterize animal communities, an aviary of 100 birds and 25 snails would be considered identical to an aquarium with 8 fish and 2 squid, because each has four times as many vertebrates as molluscs. Even within a single species, strains often differ greatly in the genes they contain.

Modern technology now allows for finer distinctions: we can study more genes in a sample, an ability that may enable us to decipher 'metabolic networks' revealing the biochemical reactions that a microbiome can perform. This kind of analysis could identify gene combinations, potentially from multiple species across a microbial community, that affect health for good or ill. However, pinning an outcome to any particular entity is likely to be hard unless the networks are already well characterized.

To take a simple example from a single bacterial species, we could show that vaccination eliminated 30% of known pneumococcal strains in a human population — but only because we knew in advance to focus on the genes targeted by the vaccine [3]. Our ability to identify functional differences in closely related genes is rarely sophisticated enough to pull out important genes or networks if we do not know what to look for in the first place. Moreover, genomes are littered with clues both true and false, such as 'hypothetical proteins' and genes that are understood poorly or not at all, but could make for important differences in what metabolic networks do.

We need to be able to identify functional differences in closely related genes from sequence alone. Until then, we must remember that apparent similarities might cloak important differences.

Does the study show causation or just correlation? A separate question is raised when distinct microbiomes can be identified and associated with diseases or other conditions. Then we are left with the chestnut of causes and correlates. Sometimes, a particular microbiome found in association with disease will be merely a bystander [4].

A 2012 article comparing the gut microbiomes of old people living in care homes with those of old people living in the community found distinct microbiomes that correlated with multiple scores of frailty [5]. After accounting for some potentially confounding factors, the authors proposed a causal relationship: diet altered the microbiome, which in turn altered health. This explanation fits the data, but the reverse causality — the potential for poor health to alter the gut microbiome — was not explored. Frailer people probably have less active immune systems and differences in digestion (such as the time required for food to pass through the stomach and intestines) — factors that could change the microbiome. This work is not the only example of this sort of confusion.

What is the mechanism? All scientists are taught the catechism that correlation is not causation, but correlation almost always implies some sort of causal relationship. We just don't know what it is. We must determine it with careful experiments.

In the past three or four years, studies have advanced from characterizing a broad community of mainly unculturable microbes to identifying functional elements, individual taxa or particular properties. We can now design experiments to precisely define actions of components of the microbiome [6], for example by reconstituting communities but leaving out specific taxa, or by precisely measuring the biochemical activity of an experimental microbiome in an 'organ on a chip' [7]. A return to a reductionist approach is essential if we are to pinpoint both whether the microbiome affects human health, and exactly how it does so.

How much do experiments reflect reality? Even if the microbiome can have an experimental effect, it may not be an important cause of the symptoms seen in ill people.

Much work has addressed the role that gut flora have in obesity, and several studies have found associations between the gut microbiome and weight gain [8]. To assess whether this association was cause or consequence, researchers collected gut-microbiome samples from human twins (one obese, one not) and introduced the microbiota to mice. Mice previously colonized with an 'obese' microbiome lost weight when supplied with a 'lean microbiome', but only if also fed a normal or low-fat diet. Diet alone had little effect [9]. Although this elegantly controlled experiment suggests great potential for the microbiome and related therapies to affect health, it also shows the microbiome's limits: the effect was dependent on other factors, in this case diet.

Microbiome studies often rely on germ-free mice. These animals allow researchers to readily introduce an experimental microbiota. But they do not represent the animals' natural state and are typically unhealthy owing to the lack of a microbiome. So results may not predict responses in animals with flourishing microbiomes. Mice and their microbiomes are also adapted to a rather different niche from humans, so results may not be generalizable.

Could anything else explain the results? There are good reasons to think that bacteria influence us in a host of ways. But there are many other — possibly more important — influences, such as diet in the earlier example. Whenever a study links a microbiome to a disease, wise critics should ask whether other contributors to disease are considered, compared and reported.

The hype surrounding microbiome research is dangerous, for individuals who might make ill-informed decisions, and for the scientific enterprise, which needs to develop better experimental methods to generate hypotheses and evaluate conclusions. Funding agencies must not let their priorities be distorted by the buzz around the field, but look dispassionately at the data. Press officers must stop exaggerating results, and journalists must stop swallowing them whole. In pre-scientific times when something happened that people did not understand, they blamed it on spirits. We must resist the urge to transform our microbial passengers into modern-day phantoms.

References
  1. Blaser, M. J. Missing Microbes: How the Overuse of Antibiotics is Fueling our Modern Plagues (Henry Holt and Co., 2014).
  2. Wilkins, M. R. et al. Proteomics 6, 4–8 (2006). Article  PubMed
  3. Croucher, N. J. et al. Nature Genet. 45, 656–663 (2013).  Article   PubMed
  4. Shanahan, F. Nutr. Rev. 70 (suppl. 1), S31–S37 (2012).  Article  PubMed
  5. Claesson, M. J. et al. Nature 488, 178–184 (2012). Article  PubMed
  6. Goodman, A. L. et al. Proc. Natl Acad. Sci. USA 108, 6252–6257 (2011). Article  PubMed
  7. Huh, D. et al. Nature Protocols 8, 2135–2157 (2013). Article
  8. Ley, R. E. Curr. Opin. Gastroenterol. 26, 5–11 (2010).  Article   PubMed
  9. Ridaura, V. K. et al. Science 341, 1241214 (2013).  Article  PubMed
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William P. Hanage is associate professor of epidemiology at the Harvard School of Public Health in Boston, Massachusetts, USA.

Corresponding author: Correspondence to William P. Hanage