ontogeny of descendants. This definition is simple enough, but gives rise to a host of practical and theoretical difficulties, and to a rash of consequent literature. Consider just two issues. First, a shift in timing relative to what? Newtonian time in days, developmental time in stages? And what is to be done with paleontological material when no absolute times can be ascertained? Can a surrogate like body size then be used? 1 tricd, with limited success, to develop a ‘clock model’ for resolving these issues (ref. 3, pp. 246- 262), but the later formalization of Alberch et al.i4) is preferable and has generally been accepted as an ‘industry standard.‘ Dissociation and Heterochrony Second, a subject can easily be destroyed by In 1770, Daines Barrington an English jurist and attempting to encompass too much. In one sense, and general scholar, published a paper in the Philosophical almost by necessary logic, all change must involve Transactions of the Royal Society”’ entitled: ‘Account timing. If heterochrony involves any change describable of a very remarkable young musician.’ He wrote of the by speeds of reactions, then we might as well retire the visit to England, six years previously, of a prodigy concept as a synonym of evolution. Heterochrony is a named Johannes Chrysostomus Wolfgangus Theophilus principle of historical legacy and its later, creative Mozart. (Remember that Mozart, during his English conscquences - evolution by relative temporal shift of visit, was an untested and puzzling eight year old features already present in ancestors, as opposed to curiosity, not yet a principal icon of human achieve- introductions of novelties. (I am well aware that ment.) apparent novelty, in morphological or functional Two aspects of young Mozart, united by the single aspects, may be constructed by altering the rates of theme of dissociability, particularly intrigued Barr- ancestral developmental sequences - a fact that ington. First, he marvelled that musical talent could be demands further complexity in definition. See so mature and refined in a young boy, otherwise so Alberch@)for an cxcellent discussion and resolution of typically childish. The musical faculty must be a this issue.) In any event, heterochrony, which once separable component of mental ability. Secondly. he languished in the deepest doghouse of neglected asked Mozart to sit at the harpsichord and improvise concepts. now ranks among the most popular of compositions expressing the single emotions of love and evolutionar topics (see, for instance, recent books by rage. Mozart’s immediate and consummate success McKinney(4 and McKinney and M~Namara(~))and convinced Barrington that the whirligig of human holds greatest promise as a unifier of the cardinal emotional life must be dissectable into separate subjects of ontogeny and phylogeny. essences. This theme of dissociation into separate modules, each subject to largely independent manipulation and A Short History: Haeckel’s Legacy and alteration, lies at the heart of any hope for resolving the Darwinism’s Neglect natural development (ontogeny or phylogeny) of any The study of development should be the unifying point complex system, biological or otherwise. Indeed, the for integrating reductionist and mechanical studies of first great argument against the possibility of evolution genes and cells with historical and narrative accounts of - Cuvier’s correlation of parts - was rooted in a denial life’s phylogeny, in short, the tocus for a truly of dissociability. In his Discours prdliminairei2) of 1812, encompassing biology. Aristotle granted embryology Cuvier portrayed animals as so integrally connected this central role and Darwin’s grandfather Erasmus that a change in one part, however slight or subtle, developed an ontogenetic theory of phylogeny (as were would necessarily require compensatory alteration in most evolutionary accounts in the progressivist climate every other feature in order to maintain a functioning of the Enlightenment). and even expressed it in heroic creature. Since such wholesale restructuring for each couplets: change is inconceivable, evolution becomes an impossi- See, without parents, by spontaneous birth bility. Cuvier’s argument is impeccable in logic and Rise the first specks of animated earth.. . would, indeed, debar evolution if its premise of absolute integration were valid. In Charles Darwin’s age, of course, Haeckel’s Heterochrony achieves its special importance in biogenetic law, or theory of recapitulation, provided studies of development and evolution because it the canonical account of relationship between ontogeny embodies this central enabling theme of modularity and and phylogeny. Expressed in heterochronic terms, dissociation. Heterochrony is defined as phyletic Haeckel’s principle required a virtually universal change in the timing of development, such that features acceleration, or speeding up of devclopment, through of ancestors shift to earlier or later stages in the evolutionary sequences. In this way, adult characters of ancesters could become juvenile features of descend- features back. Darwinian recapitulationists, like ants and, ultimately, ontogeny might be read as an August Weismann, were forced into an uncomfortable epitome of phylogeny: the earlier the stage of argument: we don’t know how heredity works, but development, the longer ago it served as an ancestral when we find out, its mechanics will include a adult form. justification for universal acceleration. Haeckel’s theory had a profound influence across Mendelism, reborn in the early 1900s’ thoroughly Western culture (see chapter 5 in G~uld(~)),probably thwarted this expectation. If inheritance is particulate rivalling that of natural selection itself. Recapitulation in a Darwinian world; if genes make enzymes and directed primary school curricula of the late 19th enzymes control the rates of processes; and if natural century (since young children were like ‘primitive’ selection might favor altered rates in any direction adults, and the legends of these ancient times would (depending on circumstances); then why should univer- therefore resonate with their juvenile souls); it sal acceleration (or any universal trend) take place? buttressed racism and its colonialist extensions (since Phyletic slowing of developmental rates should be as ‘lower‘ people were like juveniles of ‘higher’ races and orthodox in evolution as Haeckel’s speeding up. And, needed the same ‘protection’, read domination, as with no genetic basis for universal (or even preferred) children); and it provided a basis for Freud’s psycho- acceleration. the rationale for recapitulation disappears logical theories (the Oedipus complex repeats, in forthwith. juvenile males, an actual event of parricide once This Mendelian reform should have ushered in a new inflicted by adult sons upon a ruling father - see his life and heyday for study of relationships between books Totem and Taboo, and Moses and Monotheism). ontogeny and phylogeny. The old Haeckelian strangle- Haeckel‘s doctrine suffered a spectacular collapse in hold had been broken and a full taxonomy of late 19th and early 20th century biology, leading to an heterochronies could now be elaborated (slowing down overreaction and a virtual suppression of the large (and and speeding up of various modules with respect to each always vital) subject of relationships between ontogeny other and to ancestral modules) - and their evolution- and phylogeny - a classic illustration of the old clichC ary effects illustrated and evaluated. (Indeed, this (particularly relevant here, given the subject matter), of promise has been fulfilled during the past 20 years and throwing out the baby with the bathwater. Two primary does now underlie the current fruitfulness and excite- reasons underlay Haeckel’s fall and the suppression of ment of the topic). The chief paradox of this subject in evolutionary interest in ontogeny: our century lies in the failure of this renaissance to 1. Temper of the times. Late 19th century biology, occur, and in the occurrence of its opposite, the descent especially in Germany (then the center of advanced of a pall of inattention (if not downright hostility) over research), favored a rigorously mechanistic and exper- the topic until recently. I see two major reasons for thk imental approach embodied in Roux‘s Entwicklungs- paradoxical neglect: mechanik for studies of development. Roux’s school 1. Sociology. The unhappiness of experimentalists viewed the inferential reconstruction of family trees at speculative excesses in Haeckelian ph ylogenizing, from evidence of ontogeny as, at best, of limited value and the sharp disappearance of Haeckel’s needed and merely descriptive in nature and, at worst, as rationale with the rise of Mendelism, gave the entire fatuous. Roux himself wrote (ref. 8, p. 253): ‘To be subject such a bad odor that most sober scientists simply sure, we agree with Haeckel’s dictum ... but the stayed away, even though other aspects of the field biogenetic law merely designates the fact of repetition cried for attention. I will never forget the opening line . .. It teaches us nothing about the operating causes and of harsh criticism poured by a fine biologist upon a their intensities. The cxperimental study of develop- colleague who dared to raise thc subject in 1971, as 1 mental mechanics can bring us this knowledge.’ Less began research for Ontogeny and Phylogeny: ‘There are diplomatically, the great American disciple E. B. still those who would Haeckel biology’ (quoted in Wilson spoke for modernism from the newly-founded ~ouid(~)p. 2). Marine Biological Laboratory at Woods Hole (ref. 9, 2. Theory. Nothing is quite so frustrating as being pp. 103-104): ‘The search after suggestive working ignored; one would rather be explicitly reviled (and hypotheses in embryological morphology has too often thereby taken seriously). Embryological issues received led to a wild speculation unworthy of the name of short shrift under the strict Darwinism that came to science; and it would be small wonder if the modern prevail in evolutionary circles after the movement student, especially after a training in the methods of known as the ‘Modern Synthesis’ took root in the 1930’s more exact sciences, should regard the whole phylogen- and spread to orthodoxy through its time of greatest etic aspect of morphology as a kind of speculative triumph in the Darwinian centennial celebrations of pedantry unworthy of serious attention.’ 1959. Nothing in the strict Darwinian paradigm suggests 2. Logic or argument. Recapitulation’s need for hostility to developmental issues, but the theory’s universal acceleration found its easiest justification central logic offers precious little space for the major under Lamarckian models of inheritance because new internalist and structuralist themes of embryology features acquired in adult life are added to the linear either. Darwinism is fundamentally an externalist sequence of inherited ontogeny, thereby pushing older theory of adaptation, step by insensible step, to changing local environments. Internal genetic factors major reasons for this rerouting in parallel of central for development supply the copious, small-scale, themes that had diverged for bad reasons. fundamentally random variation that acts only as rah 1. Elimination uf theoretical harriers. Strict Dar- material in Darwin’s system. The direction and scope of winism, as argued above, contains little room for the change are externally determined by natural selection internalist themes best illustrated by development: based on selective pressures of surrounding environ- constraints and substantial changes. While strict ments. Darwinism prevailed, development would remain in Why would anyone grant much attention to develop- limbo. However, the hegemony of strict Darwinism has ment in such a system? Development produces been broken in the past twenty years. This has occurred variation, but variation itself plays no directing role in in a fruitful way that leaves the Darwinian mechanism its curiously formless status as an isotropic sphere intact as a centerpiece. while expanding the realm or around a modal morphology. In effect, variation may evolutionary forces and levels to include much else that be taken simply as a ‘given,’ as a ‘primitive term’ in the is centrally concerned with development. The reasons argument. (Darwin himself had no other choice, given for this expansion are many and complex, and far the ignorance of his age about causes of variation and beyond the scope of this article. However, they include. modes of inheritance.) If variation is always present, (i) Expansion of levels above and below Darwinism’s and usually unconstraining, why worry unduly about its nearly exclusive focus on individual bodies and their sources or consequences, so long as one can be struggle for reproductive success - from alleles or confident about its availability. Moreover, Darwinism nucleotides as the focal level in Kimura’s(12)theory ot also downplays the essential internalist theme of small neutralism, to species in the theory of punctuated change amplified through development to large effect equilibrium(13), to clades in theories of mass extinc- on adult phenotypes - for strict Darwinians have always tion(14); (ii) Expansion of causes of change to include favored accumulative models of microevolutionary chance at all levels (allelic neutrality to mass extinction) extrapolation for major changes, that is. step by and developmental constraints as positive channels of countless step, upward from the world of insensible preferred change, not merely as negative forces, increments where development becomes largely irrel- preventing advantageous alteration. evant. Much of this ferment can be captured in the The Modern Synthesis, Darwinism’s triumph, was beautifully apt metaphor first roposed by Darwin’s integrative in two senses: first. in bringing Darwinism brilliant cousin Francis Galton(P 5, in 1S69, and widely and Mendelism together: second, in gathering the invoked by evolutionists (including Bateson and de classical subjects of biology under its umbrella, one by Vries) before development slipped from popularity. one - Mayr for systematics, Simpson for paleontology, Galton argued that we should view organisms as Stebbins for botany, White for cytology, etc. However, polyhedral solids. They may not budge unless pushed embryology and development stayed outside the by the external force of natural selection but, when penumbra. De Beer’s short book Embryos and shoved, they can only move in limited directions Ancestors (1940)(1°),was enjoyed but unexploited while specified by internal features of geometry (built, of Goldschmidt ( 1940)(11), who touted the classical course, by development). This internal architecture internalist themes of constraint and large-scale change, embodies both great development themes: constraint was reviled. Waddington, the embryologist (and ex- (the polyhedron can only move from one facet to paleontologist) who moved most easily in synthetic another, and longer pathways of change are internally circles, would blurt out in frustration that his colleagues specified by the forms and interrelations of facets), and devised elegant models of allelic change in populations, substantial alteration (movement must occur by a flip or studied the most minute shifts of microevolutionary from one stable facet to another). By contrast, in the phenotypes, while he wanted to know how evolution world of strict Darwinism, organisms are spheres and made ’lions and tigers and things.’ Development stood they move wherever the pool cue of natural selection very low on the agenda. if not beyond the pale, of the and thc table of environment specify - without any synthetic theory. ‘pushing back’ from an internal geometry constructed developmentally. So profound is this shift of concern that ‘developmen- tal constraint’ has become one of the hottest topics in The New Potential Union of Evolution and evolution(lb-ls),so much so that it threatens to become Development, and the Centrality of Heterochrony a ‘buzzword’, too loosely defined and too encompass- Nothing in my entire career has brought me more ing. Heterochrony has pride of place among develop- pleasure than watching (largely passively, after provid- mental themes in evolution primarily because it ing a little push by publishing Ontogeny and Phylogeny represents the most fruitful ontogenetic approach to in 1977) the reintegration of evolution and develop- both major internalist themes of constraint and ment, from some cautious forays on heterochronic structurally-aided wbstantial change. Of all constraints, themes to a virtual cascade today as we finally begin to standard sequences of ontogenetic change are the most unlock the genetic basis of development. I see two immediate and powerful on the obvious principle that nature works more easily by rearranging what it has work. Our understanding is still in early infancy, but we than by constructing novelty. Each organism has a great now have the tools (from rapid and routine genetic panoply of evolutionary change available within its own sequencing to labelling and tracing of gene products in growth because so many features alter allometrically ontogeny) to unlock the genetics of development. From through growth, often producing substantial modifi- an immediately heterochronic perspective, specific cations of ontogeny. Given the principle of modularity genes that regulate rates of developrnent have been (see introductory section), these sequences can be identified and characterized in Caenorhabditis eleguns dissociated and the relative timings altered. Hetero- (wherc they have been called ‘heterochronic genes’) chrony is defined as temporal alteration plus dis- and other creatures(”). sociation and it is therefore the chief focus for using More generally, we are beginning to glimpse the current pathways (constraints) in evolutionary change. overall development of some complex creatures as a Similarly, heterochrony has long supplied the pri- hierarchical series of increasing specificity: from, in mary macroevolutionary theme for ontogenetic con- Drosophila for example, basic gradient makers (like cepts, namely the proposal that small genetic changes, b~coid)to segmentation genes (like fushi tarazm) to acting early in development, can cascade to large differentiators of particular segments (the homeotics), phenotypic effects, providing thereby one of the few And the developing explanation of homeotic function, legitimate Darwinian rationales for rapid, large-scale with discontinuous phenotypic effects, arising along a change. Such potential pathways are almost always gradient of concentration, produced by genes arranged heterochronic, as in the putative origin of higher taxa by in the same order, is among the most elegant stories in progenesis (or the early maturation of larvae with all of biology. interesting, and creative, mixtures of juvenile and adult Moreover. the clear genetic homology (using the characters, given modularity and the linkage of some word in its true evolutionary sense of similarity by features, but not others, to accelerated maturation). common descent) between the Drosophila HOM 2. Reduction of practical barriers. We (evolutionists complex and the fourfold-repeated HOX sequences of like myself, that is) have contributed by expanding a mice and other vertebrates shows that these disparate theory to accommodate developmental perspectives phyla still carry complex legacies of common ancestry. but you (developmental biologists who read this essay) (And revives biology’s oldest dream of unification, have made a far more important contribution to our Geoffroy’s early 19th century claim for a common remarriage by devising the techniques that makc architecture to all animal life, as Goethe had advanced development tractable. Although I grant this theme a similar theory for plants, based on a leaf archetype.) relatively little space - because, as an outsider looking The issue of morphological homology is still open for in, 1 understand it so poorly, and would be foolish to homologous genes may commandeer different pheno- pontificate within an issue filled with articles by real typic apparatuses, and the final morphological products experts -this growing tractability formed my reason for need not be homologues. For example, somites and writing this article in the first place. metameres are too structurally and developmentally My frustration was immense when I published different to qualify, and this has led to the traditional Ontogeny and Phylogeny in 1977. I sensed that denial of homology between the phyla. But some development was vital to any fuller and more adequate remarkable similarities have recently been found evolutionary theory, and I recognized that hetero- between arthropod metameres and a second system of chrony would form a practical focus for study. I wrote in vertebrate segmentation centered on rhombomeres of the introduction: ’This book is primarily a long the developing mid and hindbrain, branchial arches and argument for the evolutionary importance of hetero- some cranial nerves. Hunt et a1.(20)have just published chrony - changes in the relative timing of appearance the intriguing discovery that paralogues in the four and rate of development for characters already present vertebrate HOX complexes show identical expression in ancestors.’ But, when I came to examine the causes limits in the rhombomeres. cranial ganglia and of heterochronic change (rather than describing their branchial arches, but do not work in such a coordinated effects), I could find almost nothing, for knowledge of way in the trunk somites. (As a pure speculation, may the genetics of development was then a virtual blank. I this not indicate a phyletically primitive status for the felt as though I stood far away watching the surface of a rhombomeric system, with the somitic system sur- growing ball, without any understanding of what made added, as the HOX duplications continue to build it expand from inside and what produced its surface rhombomeres on the old pattern, while working architecture (not to mention its deep structure). All 1 differently with the unique and later somites)? If a could do was write a slim final chapter with a few brave paleontological word might be in order, early agnathans words (superficial, however well intentioned) on the (and some pre-vertebrate chordates) have very promi- putative difference between structural and regulatory nent branchial baskets, presumably a filtration device genes. I even began the book with a line of apology by original function. with a smaller somitic system, as if (1977, p. 1): ‘I am aware that I trcat a subject currently a ininor trunk and tail were added to a massive frontal unpopular. ’ device. Rhombomeres are now transient in vertebrates All this has changed dramatically, thanks to your (as are branchial arches in tetrapods), but current prominence is no mark of phyletic precedence. (The cosifan tutte (all women are like that - men too, as the frontal segmentation is phylefically confused by the non-sexist opera makes quite clear). Professions, in formation of skeletal structures in the branchial region many ways, are like people. And when they finally join from neural crest, a later and clearly novel vertebrate for the right reason, look for the cascade of fruitful feature, apparently not influenced by HOX genes. progeny. Developmental biologists who wish to explore the possible morphological homology of arthropod meta- meres and vertebral frontal segmentation might try to subtract the neural crest derivatives and focus on References development of what may remain from the old I Barrington, D. (1770). Account of a very remarkable young musician. Phil. branchial basket segmentation.) Trans. Roy. Soc. London 60, 54-64. 2 Cuvier, G. (1812). Discours pr4limiminaire, in Rechercher sur 1cs ossemens In any case, this developing (and fast-breaking) story fossiles. Paris: Dcterville. strongly increases the probable significance of con- 3 Gould, S. J. (1977). Onmgeny and Phylogeny. Cambridge, MA: Harvard Universily Press straint and heterochrony in evolution and greatly 4 Alberch, P., Gould, S. J., Oster, C. F. and Wake, D. B. (1979). Size and diminishes the fading, strict Darwinian idea that shape in ontogeny and phylogeny. Paleobiology 5. 296.317. evolution may be traced as insensibly transitional 5 Alherch, P. (1985). Problems with the interpretation of developmental sequences. .Syst. Zoo/. 34, 46-58. adaptation to external environments, without close 6 McKinney, M. J>., editor (1988). Heterochrony in Evohtion. Kew York: attention to how internal architecture channels and Plenum Press. 7 McKinney, M. L. and McNamara, K. J. (1991). Heterorlzrony. The Ei:olution structures the potential pathways of substantial change. of Onrogeny. New York: Plenum Press. If groups so disparate as arthropods and vertebrates 8 Roux, W. (1W5). Die ~ntwicklungsmcchanili. Eiii neurr Zweig der bear substantial homology in basic morphological biologischen Wissenschaft. VortrPge und Aufsiitze der EntwicklunRsmcchanili dcr Organismen no. 1. Leipzig: W. Engelmann. design, then constraints on pathways arc legion and 9 Wilson, E. B. (1894). The embryological criterion of homology. Uiol. Lect. life’s commonality will be resolved more by the study of Mor. Bid. Lab. Woods Hole, pp. 101-124. development than by adaptation. 10 De Beer, G. K. (1940). Eruhryos urid ancectors. Oxford: Clarendon Press. 11 Goldschmidt, R. R. (1930). TIzr hfatcrinl Basis of Evolurion. New Haven, CT: Yale University Presa. A Mozartian Epilogue: Cosi Fan Tutte 12 Kimura, Motoo (1991). Neutral Evolution. In: S. 0wwa and T. Hoiijo. eds., Evohrrion of Lfe. Tokyo: Springer-Verlag. To end where I began (as I write this article in the very 13 Eldredge, N. and Gould, S. J. (1972). Punctdated equilibria: An alternative month of Mozart’s bicentennial), consider his opera to pliyledc gradualism. In: ’I’.J. M. Schopf, ed.. Models in Paleobiology. San Cosi Fan Tutte as an epitome of the history of Francisco: Freeman. Cooper & Company. 14 Alvarez, L. W., Alvarez, W., Asaro, F. and Michel. H. V. (1980). relationships between developmental and evolutionary Extraterrestrial cause for the Cretaceous-Terliary extinctioI1. Science 208. 1095- biology. The two couples of the opera are initially 1108. 15 Galton, F. (1869). Hereditary Genius. London. joined in tirades of romantic pledges about eternal 16 Stearns, S. C. (1986). Natural selection and fitness, adaptation and devotion, but in total youthful naivete (and therefore constraint. In: D. M. Raup and D. Jablonski, eds.. Patterns and Processes in the with no firm foundation) - just as ontogeny and History of Life. Berlin: Springer-Verlag. 17 Maynard Smith, J., Burian, J., Kauffman, S., Alberch, P., Camphell, J., phylogeny were so strongly fused under the false Goodwin, R., Lande, R., Raup, D. and Wolpert, L. (1Y85). Developmental banner of Haeckel’s biogenetic law. The couples are conatraints and evolution. Quart. Rev. Biol. 60, 265-287. then separated in growing hostility and claims of 18 Gould, S. J. (1989). A developmental constraint in Cerion. with comments on the definition and interpretation of constraint in evolution. Evolution 43(3), betrayal - only to reunite at the end when they accept 516-539. each other’s errors, foibles and failings, thereby forging 19 Amhros, V. (1988). Genetic basis for heterochronic variation. In: h4. L. McKinney. ed., Heterochrony in E1dution: A Multidkciplinary Approach. a true bond based on practical knowledge rather than New York: Plenum Press. inconstant emotion (a favorite theme of the Age of 20 Hunt, P., Gullisano, M., Cook, RI., Sham, W-H., Faiella, A., Wilkinson, Reason, quite explicitly extolled by Mozart against U., Bonrinelli, E. and Krurnlauf, R. (1991). A distinct HOX code for the romanticism). So, too, for development and evolution, hranchial region of the vertebrate head. Narure 353, 861-864. two fields that needed to separate when the false focus of previous union became clear, but that now can Zoology, Harvard University. Cambridge, MA reunite, both older and wiser, with the discovery of a 02138, USA. true and lasting basis for synthesis. It is an old story -