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12-2006

Integration without Unification: An Argument for Pluralism in the Biological Sciences

Sandra D. Mitchell University of Pittsburgh

Michael R. Dietrich Dartmouth College

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Dartmouth Digital Commons Citation Mitchell, Sandra D. and Dietrich, Michael R., "Integration without Unification: An Argument for Pluralism in the Biological Sciences" (2006). Open Dartmouth: Published works by Dartmouth faculty. 2077. https://digitalcommons.dartmouth.edu/facoa/2077

This Article is brought to you for free and open access by the Faculty Work at Dartmouth Digital Commons. It has been accepted for inclusion in Open Dartmouth: Published works by Dartmouth faculty by an authorized administrator of Dartmouth Digital Commons. For more information, please contact [email protected]. vol. 168, supplement the american naturalist december 2006

Integration without Unification: An Argument for Pluralism in the Biological Sciences

Sandra D. Mitchell1,* and Michael R. Dietrich2,†

1. Department of History and Philosophy of Science, University of ological practice? Is it a mark of the immaturity of bio- Pittsburgh, Pittsburgh, Pennsylvania 15260; logical theory? Will today’s pluralism give way to a grand 2. Department of Biological Sciences, Dartmouth College, unified theory of biology in the image of Newtonian phys- Hanover, New Hampshire 03755 ics? Or does pluralism indicate a healthy competition among biologists about what is the singular true account of why a system behaves the way it does? Or is it something altogether different? abstract: In this article, we consider the tension between unifi- In this article, we will consider the tension between cation and pluralism in biological theory. We begin with a consid- unification and pluralism in biological theory. We begin eration of historical efforts to establish a unified understanding of with a consideration of historical efforts to create uni- evolution in the neo-Darwinian synthesis. The fragmentation of the fication in biology on a large scale through the neo- evolutionary synthesis by molecular evolution suggests the limita- tions of the general unificationist ideal for biology but not necessarily Darwinian synthesis. The fragmentation of the evolution- for integrating explanations. In the second half of this article, we ary synthesis with the rise of molecular evolution suggests defend a specific variety of pluralism that allows for the integration the limitations of the unificationist ideal for biology. In required for explanations of complex phenomena without unification the second half of this article, we will defend a specific on a large scale. variety of pluralism that allows for the integration required for explanations of complex phenomena without unifi- Keywords: integration, unification, pluralism, evolutionary synthesis, cation on a large scale. molecular evolution.

The Fragmentation of the Evolutionary Synthesis Biology studies complex, developing, and evolving organ- isms and populations. Developing sea urchins, division of Theodosius Dobzhansky’s well-worn declaration that labor in social insect colonies, and predator-prey inter- “nothing in biology makes sense except in the light of actions, for example, are all compositionally and dynam- evolution” was a testament to his faith in the unifying ically complex. Their behavior depends on multiple levels power of the evolutionary synthesis (Dobzhansky 1973). of organization and multiple causal components. Addi- From the late 1930s, Dobzhansky, Ernst Mayr, and G. G. tionally, ever since Niko Tinbergen’s articulation of four Simpson organized a loose array of biologists interested questions and Ernst Mayr’s distinction between ultimate in evolution into members of a new discipline of evolu- and proximate causes, there is general recognition of mul- tionary biology. The circumstances of this neo-Darwinian tiple levels of analysis (function, cause, development, evo- or evolutionary synthesis are still a matter of debate among lution) or questions (why and how) that can be brought historians, but certainly a unified understanding of the to bear to explain a biological property or behavior. This foundational principles of evolutionary biology was the generates a plurality of models and explanations aiming goal of the synthesis’s architects (Smocovitis 1996). As to get scientific traction on the “blooming buzzing con- Dobzhansky put it, biology without evolution “becomes fusion” that constitutes life (James 1911, p. 50). But how a pile of sundry facts some of them interesting or curious are we to understand the pluralism of contemporary bi- but making no meaningful picture as a whole” (Dob- zhansky 1973, p. 125). * E-mail: [email protected]. While historians rightly emphasize the discipline- † E-mail: [email protected]. building work of getting paleontologists and geneticists to Am. Nat. 2006. Vol. 168, pp. S73–S79. ᭧ 2006 by The University of Chicago. communicate and agree about the processes of evolution, 0003-0147/2006/1680S6-41915$15.00. All rights reserved. the hallmark of the evolutionary synthesis in terms of S74 The American Naturalist biological theory was the developing consensus about the made his modest proposal that most allele substitutions and primacy of natural selection (Provine 1988; Cain 1993; polymorphisms do not substantially affect an organism’s fit- Smocovitis 1996). The rising panselectionist belief that ness and are governed, not by positive or balancing selection, natural selection was the most important mechanism of but by random drift. (Kondrashov 2005, p. 1106) evolutionary biology was dubbed the “hardening” of the synthesis by Stephen Jay Gould (Gould 1983). A hardened While Kondrashov’s fractured fairy tale approach is com- synthesis provided a foil for biologists’ intent of setting pelling, the challenge of neutrality to panselectionism war- themselves apart from the “evolutionary orthodoxy.” rants more careful scrutiny. While, in fact, there was never complete agreement among First, Kimura, King, and Jukes initially encouraged this evolutionary biologists about the importance and power idea of opposition. When King and Jukes titled their article of natural selection, there was enough agreement to make “Non-Darwinian Evolution,” they were deliberately trying divergence from the perceived orthodoxy seem revolu- to set their work apart from that of the neo-Darwinian tionary. Motoo Kimura took advantage of these percep- synthesis. This oppositional approach certainly contrib- tions in his advocacy of the neutral theory of molecular uted to the polarization of the neutralist-selectionist con- evolution, beginning in 1968 (Kimura 1968; Dietrich troversy in the early 1970s. This sense of polarization ex- 1994). tended beyond debates about the relative importance of As molecular biology rose in prominence in the 1960s, drift and selection to the place of molecular evolution molecular evolution emerged from the intersection of relative to evolutionary biology in general. While molec- fields such as evolutionary genetics, systematics, biochem- ular biologists described evolutionary biology as old- istry, molecular biology, anthropology, and microbiology. fashioned and compared it to stamp collecting, evolution- As biologists began to compare biochemical similarities ary biologists attacked molecular biology as a fad and a and differences in order to make evolutionary inferences, bandwagon. Molecular evolution arose right in the middle they began to entertain the idea that not all molecular of this larger turf war (Dietrich 1998; Hagen 1999). From changes had been subject to natural selection (Zuckerkandl the first conferences on molecular evolution in 1962, mo- and Pauling 1965; Dietrich 1994). The possibility of neu- lecular evolutionists such as Emile Zuckerkandl had been tral mutations had been previously posited by Dobzhansky clashing with architects of the synthesis, especially G. G. and others but was not taken seriously as an alternative Simpson. Zuckerkandl was interested in using molecular to natural selection (Dobzhansky 1955). When Motoo Ki- comparisons to infer phylogenetic relationships. His ad- mura, Jack King, and Tom Jukes began to advocate the vocacy with Linus Pauling of the molecular clock and his importance of neutral mutations and random drift in 1968 disagreement with Simpson’s primate phylogeny drove a and 1969, attitudes about drift and neutrality began to wedge between molecular and morphological approaches shift (Kimura 1968; King and Jukes 1969). Many molecular to evolution and systematics. When Kimura, Alan Wilson, evolutionists with biochemical training were willing to ac- and others began to argue that the apparent constancy of cept neutral mutations on the basis of detected biochem- the molecular clock could be explained by the neutral ical differences and molecular variability, but many biol- theory, the clock controversies became enmeshed with the ogists trained in evolutionary biology and steeped in the neutralist-selectionist controversies, and the split between evolutionary synthesis were much more skeptical (Dietrich neutrality and selection became identified with a split be- 1998). tween evolution as it occurred at the molecular and mor- The controversy between the neutralists and selection- phological levels (Dietrich 1998). ists that emerged in the 1970s and arguably continues to One of the most important outcomes of these early this day is usually understood as pitting drift against se- controversies concerning molecular evolution was a di- lection. Even though the neutral theory includes a signif- vision of the domain of evolutionary biology into molec- icant role for natural selection, it is perceived as opposing ular and morphological levels. Evolution at the molecular panselectionism because it also advocates a significant role level is marked by a significant role for random drift but for neutrality and drift at the molecular level. The jux- does not exclude natural selection. In contrast, evolution taposition of neutrality and panselectionism was beauti- at the morphological level is marked by the predominance fully captured by Alexey Kondrashov when he recently of natural selection. So in what sense did the rise of the wrote, neutral theory of molecular evolution contribute to the decline of panselectionism? Once upon a time, the world seemed simple when viewed In order to answer this question, we need some analysis through the eyes of evolutionary biologists. All genomes were of what constitutes panselectionism. We propose a three- tightly controlled by various forms of natural selection. … fold distinction that mirrors different forms of adapta- This idyllic world began to crumble in 1968, when Kimura tionism proposed by Peter Godfrey Smith. Smith distin- Pluralism in the Biological Sciences S75 guished empirical, methodological, and explanatory senses 1980s led to a series of statistical tests that could reliably of adaptationism in order to clarify both the claims and distinguish drift from selection at the molecular level disputes swirling about adaptationist approaches to evo- (Kreitman 1983; Hudson et al. 1987; Kreitman 2000). lution. When applied to panselectionism, three kinds of Where selectionists’ hypotheses were once the starting panselectionist claims can be distinguished. First, empirical point and ending point of the research for virtually all panselectionism would claim that “natural selection is a evolutionary biologists, by the 1990s the neutral theory powerful and ubiquitous force, and there are few con- had become established as a null model and a starting straints, except general and obvious ones, on the biological hypothesis for molecular evolution research (Crow 1987; variation that fuels it.” Second, methodological panselec- Kreitman 2000). This represents a significant methodo- tionism would assert that “the best way for scientists to logical reversal. Even for biologists predisposed to favor approach biological systems is to look for evidence of nat- selectionists’ explanations, if they are using nucleotide se- ural selection in some form.” Third, explanatory pan- quence data, the neutral model is the starting place for selectionism would argue that explaining the effects of their investigation. Methodological panselectionism, then, selection is “the core intellectual mission of evolutionary has been seriously undercut by the rise of neutral models theory” (Godfrey Smith 2001, pp. 335–357). and sequence data. With these distinctions in hand, we can now evaluate Explanatory panselectionism may be the last refuge of the extent to which they make sense of the impact of the ardent panselectionist. In declaring what the explan- neutralism in evolutionary biology. The claim of empirical atory agenda of evolutionary biology ought to be, explan- panselectionism in its strongest form of advocating that atory panselectionists assert, as Richard Dawkins has, that all molecular and morphological characters are the prod- adaptations constitute the business of evolutionary biol- ucts of only selection was probably never held. That said, ogists (Dawkins 1983). While Dawkins may have empirical at the height of the neutralist-selectionist controversy, reasons for making this claim, it solves the problem of Christopher Wills mounted a defense of “naive panselec- dealing with drift and neutrality only by dismissing it as tionism,” where he argued that “virtually any change in a legitimate object of explanation. This strategy of nar- amino acid composition of any protein molecule produces rowing the domain of evolution to include only the pro- a molecule of slightly different properties and therefore of cesses and products of selection would certainly preserve slightly different selective value from the original” (Wills panselectionism, but at the cost of disregarding a signif- 1973, p. 23). Wills’s defense of panselectionism did not icant portion of molecular evolution. As biology enters a extend to the DNA sequences, where synonymous mu- postgenomic era, it is hard to imagine biologists embracing tations were held as strong evidence that some nucleotide this alternative seriously. substitutions were in fact neutral. As in many controversies The idyll of panselection has crumbled when given its in biology, the empirical extent of neutrality and selection strongest formulations, but selection remains the predom- is not an all-or-nothing affair but a matter of the relative inant cause invoked in most biological explanations. The frequencies of each (Beatty 1987, 1995, 1997; Dietrich inroads made against panselectionism are directed at mo- 2006). If some cases of neutrality are accepted, then the lecular phenomena and techniques analyzing molecular strongest forms of empirical panselectionism can no longer data. Insofar as evolutionary biology wishes to include be defended. both molecular and morphological phenomena, it must The most significant impact of neutralism, however, is recognize that the domain of evolutionary explanations methodological, not empirical. When Stephen Jay Gould has been significantly expanded with the advent of mo- and Richard Lewontin launched their now famous attack lecular biology. In his review of tests of neutrality and on adaptationism in “The Spandrels of San Marco and the selection, Martin Kreitman claims that “Kimura’s theory Panglossian Paradigm,” they argued broadly against pan- of neutrally evolving mutations is the backbone for evo- selectionism (Gould and Lewontin 1979). In his response, lutionary analysis of DNA sequence variation and change” Ernst Mayr defended adaptationism in methodological because a “substantial fraction” of the genome is best mod- terms. For Mayr, seeking adaptations was the best method eled as selectively neutral, because selective neutrality is a available because drift simply could not be detected (Mayr “useful null hypothesis,” and because “statistical analysis 1983). Undoubtedly, Mayr had in mind earlier debates of (potentially) neutral variation in a gene (or other region over whether drift could be detected at the morphological of the genome) can be informative about selection acting level, while Gould and Lewontin were watching the rise at linked sites” (Kreitman 2000, pp. 541–542). The em- of molecular evolution as well as that of sociobiology pirical and methodological prominence of neutrality and (Beatty 1987). While the early statistical tests of the neutral drift at the molecular level that Kreitman argues for in- theory were plagued with problems of low statistical power, dicates that the hardening of the evolutionary synthesis the introduction of DNA sequence information in the late was short-lived and inadequate. While the neutralist and S76 The American Naturalist selectionist positions have been refined into more nuanced capture the actual etiology, and tests to distinguish them and complicated models in light of new evidence and on- are needed to determine which of them is, in fact, correct. going debate, neither the nearly neutral models articulated Not only is our knowledge of population dynamics and by Tomoko Ohta nor the fluctuating selection models ar- selection regimes enhanced by understanding whether a ticulated by John Gillespie, to cite just two examples, deny pathogen is endemic or novel, but as the authors point a role to either drift or selection (Gillespie 1991; Ohta out, the answer makes a difference to the conservation 2002). Rather than seek a new unifying theory of evolution, strategies that can successfully address the problem. however, current evolutionary biologists seem to accept This structure of competing explanations driven from multiple causal processes and types of explanations offered exclusive hypotheses is common currency in the philos- for evolutionary phenomena at the molecular and mor- ophy of science. Indeed, in an early articulation of sci- phological levels. The result is explanatory and method- entific method, Francis Bacon ([1620] 1902) explored the ological pluralism in contemporary evolutionary biology. idea of an experimentum crucis where mutually exclusive alternatives are set up, to be decided by experiment and observation, and then as the finger post points in the Integrative Pluralism direction of the truth, the scientist follows, leaving behind As we have suggested, there is a long history of attempts the defeated hypothesis and moving on to suggest further to impose unity upon the diversity that is found in biology. alternatives among which tests of nature will decide. It is our contention that though there is something to be It is well known that this type of inductive inference is learned by adopting these unificationist approaches, they inconclusive, given that there are bound to be more al- do not account for the explanations that biologists seek. ternative hypotheses than the two posed to be tested. Thus, In place of unification, we counsel pluralism. At first blush, while one of the two posed may be logically refuted by this would seem to invite disdain similar to Herschel’s the observational evidence, the one left standing is not admonition of Darwin’s Origin of Species as the “law of thereby proven to be true. It may account for the test case higgledy-piggledy” (Darwin letter to Lyell, 1837). But there at hand but later be defeated in another bout with a third are other varieties of pluralism. What we defend here is alternative hypothesis. Indeed, the assumptions and in- integrative pluralism, a view of the diversity of scientific terpretations required to generate observable tests of ex- explanations that endorses close study and modeling of clusive hypotheses themselves are implicated in the “ref- different causes and different levels of organization but utation” of the losing side, and hence there is no guarantee calls for integration of the multiple accounts in the ex- that the one inconsistent with a current observational test planation of concrete phenomena. might not be revived to fight again with the help of other Some explanations offered for a given phenomenon are auxiliary assumptions. Thus, modern versions of the struc- exclusive alternatives, of which at most one can be correct. ture of competing explanations in science are more modest Consider, for example, alternative hypotheses about the in the conclusions that can be drawn by any experimental origin of an infectious disease that has been implicated in test. They nevertheless account for alternative approaches the recent amphibian decline. Some have suggested that and explanations in terms of their competitive relation the fungal pathogen Batrachochytrium dendrobatidi is en- and look into the future for the resolution to a single true demic, while others say it is novel. account. Take, for example, Kitcher’s (1990) endorsement of a plurality of explanations in science. He argues that Emerging infectious diseases originate in two ways. The novel because of our fallibility in determining which hypothesis pathogen hypothesis states that the pathogen (or a newly is true based on finite observational evidence, it is rational evolved virulent strain of the pathogen) has recently spread to keep alternative competing accounts around. The aim, into a new geographic area, encountering naive host individ- though, is to ultimately resolve the conflict, or, in his uals or species that are highly susceptible to infection (Alford words, “the community goal is to arrive at universal ac- 2001). The endemic pathogen hypothesis suggests that it has ceptance of the true theory” (Kitcher 1990, p. 19). Thus, been present in the environment but has entered new host while pluralism is acknowledged and even defended on species or increased in pathogenicity because of environmental this approach, it is only as a means to a unified end. changes or, possibly, simply escaped previous human notice. While testing competing hypotheses does account for Strategies for disease management will differ substantially, de- some of the pluralism characterizing biological explana- pending on which of these hypotheses is correct (CDC 1994). tions, not all explanations compete. In the case of the (Rachowitz et al. 2005, p. 1441) decline of amphibians, scientists have collectively explored It is clear that the logic of these hypotheses is one of a number of possible alternative causes, including habitat exclusion. They could not both be correct for the same destruction, climate change, increasing levels of ultraviolet species or set of species at the same time. Only one can radiation, environmental contamination, disease, and the Pluralism in the Biological Sciences S77 introduction of nonnative species. Blaustein and Kiesecker into levels of evolutionary origin, current reproductive (2002) present the case that ecosystem complexity is re- function, ontogeny, and mechanism. Naturally, questions sponsible for the failure of consensus on which of these at different levels require different answers. In some sense, is the cause or the most significant cause. They give evi- the questions are not addressing the same problem, and dence that multiple factors in interaction are responsible hence, the answers given cannot be taken as competing. for amphibian decline. Additionally, they claim that dif- As Sherman put it, “every hypothesis within biology is ferent constellations of causes in different contexts are subsumed within this framework; competition between generating this effect. Thus, not only is it unlikely that one alternatives appropriately occurs within and not among cause is responsible for global decline, it is unlikely that levels” (Sherman 1988, p. 616). But is this erotetic stra- the same collection of causes is responsible for every case tigraphy the right way to describe the relations among the of decline. plurality of compatible explanations? Different levels of Thus, pluralism in the explanations of some feature of analysis might target different partial causes, but will there the biological world might refer to competing hypotheses be no competition between levels? Different constellations (endemic vs. novel in a particular population) or multiple of partial causes at different levels may represent com- contributing causes (climate change and disease acting patible harmony, but how on this framework does one jointly) or multiple constellations of causes (climate account for context contingency? change and disease in one population and disease and For example, explaining ontogenetically how a verte- nonnative species in another) acting in different contexts brate limb develops by detailing the cell-cell interactions or at different times. There is little evidence to suggest that determine the axes upon which the limb is patterned that any single causal factor typically accounts for the total does not immediately implicate the fitness consequences effect or that any successful causal explanation appealing or the hormonal or genetic triggers for cell differentiation to one or many causal factors will account for all cases in and thus is in a sense autonomous from selectionist or all contexts. Thus, any simple hypothesis will fail to gen- mechanism explanations. Yet, especially salient with the eralize and thus fail to adequately explain similar effects increasing interest in evolutionary-developmental biology, in all situations. Distinguishing among this plurality of the relationship between evolutionary questions and de- pluralisms, that is, competing hypotheses, partial causes, velopmental questions and the answers to them can no and contingent causes, aids in determining where real con- longer be left in oblivious isolation. Answers to questions flict exists among different explanatory models and where posed at the different levels of analysis cannot be satis- compatibility lies and integration is possible. factorily answered without consideration of the other lev- This situation is typical of evolved, dynamically robust els. Evolution without development is empty, and devel- biological systems. The different hypotheses that scientists opment without evolution is blind (to butcher an old propose to identify causes of an effect of interest are more Kantian chestnut). The pluralism of levels of analysis iden- probably not solely determinant but rather contribute in tifies strata in which explanations do not directly compete context-dependent ways to bring about the effect. But how with each other; however, an isolationist stance with regard does one then study complex causality? A successful meth- to these levels would be mistaken. odology has been decomposition (see Bechtel and Rich- Competition does occur between hypotheses within a ardson 1992). That is, take a complex system, and inves- level, but not only within those confines. Developmental tigate the subsystems that constitute it. Take the set of explanations suggest limits to the range of variability that potential causes, and investigate what power each of them is and might have been available for selection to have acted has individually in generating the effect. Thus, the nature on. Fitness consequences of early developmental alterna- of the complexity of the systems studied by biology in tives might constrain the range of subsequent develop- conjunction with a decomposition methodology necessi- mental processes that are accessible. The relationship tates a plurality of causal hypotheses that are not com- among prima facie compatible alternative explanations peting but compatible. posed at different levels of analysis should be one not of Biologists have long recognized the existence of com- isolation but of integration. A consequence of such an patible alternative explanations, and there have been at- integrative strategy is the recognition of a new location tempts to partition the plurality in ways that locate areas for competition among hypotheses. Which collection of of compatibility and areas of competition. Tinbergen causal processes at all levels characterizes the etiology of (1963), in an influential article, outlined a four-part clas- a targeted effect? What contribution does each potentially sification of questions one might ask of a biological phe- contributing cause make? In different particular cases, nomenon. More recently, Sherman (1988; see also Reeve there will be different answers, but in any given case only and Sherman 1993) revived this classification and dubbed one answer will map onto the actual processes that brought it “levels of analysis.” Biological questions are stratified about the trait (Mitchell 2002, 2003). A “levels of analysis” S78 The American Naturalist framework recognizes the plurality of partial causes but phenomena we investigate. But contingency, context sen- obscures rather than highlights the means of integrating sitivity, and nonlinear interaction among contributing them. causes preclude the success of these types of unification. Complexity, we have claimed, invokes multiple levels of The “levels of analysis” framework describes the territory organization and multiple causal factors in generating an of pluralistic investigations, but it is only by integration effect. Evolved complexity introduces historical contin- of the multiple levels and multiple causes, including at- gency, and ecological complexity introduces distributional tention to the diverse contexts in which they occur, that contingency into the mix. That is, how a complex organism satisfactory explanations can be generated. develops is in part a result of the particular evolutionary trajectory its lineage traversed. There are alternative de- Conclusion velopmental schemas; which one is present in which in- dividual may not result from physical or chemical necessity The lure of a general and unified theory of evolutionary but rather from its evolution. There are multiple me- biology was powerfully appealing to the founders of neo- chanical triggers for behavior for a complex system. Which Darwinism. While we do not deny the appeal of this vision, ones are present and active may well be a function of the the expanding domain of evolutionary biology has com- ecological context in which the system is located. Explain- plicated this supposed selectionist unification. Finding ing complex, evolved biological systems is not a “one-size- ways to integrate molecular and phenotypic (i.e., mor- fits-all” enterprise. phological, physiological, and behavioral) levels represents Consider again the case of multiple causal contributors a new challenge for contemporary evolutionary biologists. to generating a complex effect. In the example of am- It is our contention that explanations of complex phe- phibian decline, the increase in UV radiation has been nomena in biology regularly integrate phenomena across implicated as a cause by means of its effect on hatching levels. These integrative explanations result in a type of success. Of course, it may be that the competing hypoth- pluralism that does not require general unification and esis, that UV radiation plays no role in amphibian decline, that explains why innovative and productive explanations may turn out to be correct. However, even if UV radiation are possible in the absence of a unified theoretical frame- does causally contribute to amphibian decline, its effect is work. not consistent across all species or taxa. Some populations show marked decrease in hatchlings in the presence of Literature Cited increased UV, but others show no decrease. When and Alford, R. A. 2001. Testing the novel pathogen hypothesis. Page 20 why does the effect vary? 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