Post-genomics, Evo-Devo and the recurrence of teleologic thought^†

The last half century has experienced an unmatched triumph of molecular biology, to which - as their mainstays - genomics, molecular cell and developmental biology, epigenetics and stem cell biology have contributed. Together, these disciplines have led biosciences into the so-called “postgenomic era”. Instead of a narrowed view into the cell nucleus and its DNA, the biologists’ visor has opened onto a dynamically changing cellular environment. Mutual actions between the molecular, cellular, organismic, and up to ecological hierarchical levels -ever up- and downwards interacting - brought into the scene postgenomic concepts of nature. Concomitantly, skepticism about the so-called standard evolutionary theory (SET), also known as population genetics or Neo-Darwinism, became audible (2, 3, 4). Indeed, gaps within the standard teaching of evolution had been outlined much earlier (5, 6, 7). For instance, proponents of SET had ridiculed ideas of the inheritance of acquired traits, e.g., Lamarckism. But notably, exposing flies to heat stress demonstrated that a stress-induced novel morphologic trait could eventually occur in the progeny without applying stress (after about twenty generations), i.e., an individual alteration was now genetically assimilated (8). The field of molecular epigenetics reveals that parental acquired attributes can indeed be transferred to their progeny (9,10). For instance, methylation and acetylation of DNA or of histones are effective mechanisms to functionally switch genes on or off (see Fig. 1b: molecular switch). Epigenetic processes depend substantially on the individual’s experiences (e.g., stress, food, climate, etc.), which during a lifetime will imprint a specific epigenetic landscape onto its genome (11,12). Furthermore, epigenetic effects can become fixed in germ cells (13,14), and thus – contrary to Weismann’s barrier (10), and occasionally denoted as Neolamarckism (see glossary) – be transmitted into the next generation. Thus, epigenetics provides strong evidence against unlimited validity of SET.

See for terms in italic in glossary.

Figure 1

Nonetheless, how could Neo-Darwinism be established so successfully as a standard theory (SET) during the first half of the 20th century (details in (15, 16, 17)? SET is based on Darwin’s two grounding assumptions of random individual change of organisms (mutations), and their subsequent competitive selection (fitness differences leading to cumulative differential reproduction; (18,19). First, it was an advancing knowledge of chromosome structure as well as of the chemical nature of genes, and the comprehension that selection takes place predominantly at the level of populations (16). Accordingly, new species arise through changes in the gene pool of populations. Following the model of allopatric speciation (holding for the bulk of animal species (10)), this occurs in a way that a population is split, for instance by expanding ice shields. Further on, both subpopulations will develop divergently, and – at a later contact of their individuals – will not mix again. As Ernst Mayr expressed the point “the individual mutates, and the population evolves” (16). Notably, Darwin’s two basic assumptions were not touched substantially. Neo-Darwinism traced phenotypic changes back to the level of genes, thus to spontaneous changes of DNA sequences. From bacteria it was well known that mutations occur randomly. Accordingly, it stood to reason to propose random genetic changes for all organisms; moreover, the genetic transmission of alleles in sexually reproducing organisms is distributed stochastically within their progeny (recombination). This in turn led to the far-reaching postulate that evolutionary change occurs purely at random, and over long evolutionary periods should occur evenly and slowly (gradualism, see glossary), much as Darwin had imagined. In particular, the postulated randomness of the individual genomic sources of variation led to the assumption that evolutionary change would proceed entirely without direction (20). Only later would this concept lead to interpretative difficulties since it adhered to a narrowed understanding of gene functioning (see below; Fig. 1).

Eventually, Neo-Darwinism was drawn into a momentous dead end through the “one gene-one protein dogma” (Fig. 1a; 16). As a standard point of view until into the 1970s, this conception, while comprehensible in its original Beadle-Tatum formulation (21) led to a fallacy within Neo-Darwinism, namely, that there existed a fixed relationship between the genetic makeup (genotype, or genome) and the phenotype of an individual. While this dogma may (partly) apply for simple organisms, it rarely reflects the functionalities of genes of eukaryotic organisms, e.g., developmental genes of plants or animals (cf., Fig. 1b). This is because genes often code for several different proteins, where each could subserve several different functions, and which in turn can interact via complex reaction networks in diverse manners (22). Thus commonly, genes are involved in the shaping of several features (pleiotropy). Findings of epigenetics render the spectrum of regulated gene actions and their effects at the phenotypic level even more complex (briefly mentioned above). On top, we may ask whether there is a fixed phenotype at all, when all organisms keep changing at every instant (physiology, growth, degeneration, behaviour, etc.)? In fact, the theory of process ontology perceives living organisms (in fact the entire universe) not as three-dimensional objects or things, but rather as ever interacting processes, asking for a complete rethinking of evolution (23). Clearly, the realization of genetic activities depends therefore predominantly on specific spatiotemporal environments (24). Hence, gene expression turns out to be a highly non-linear process (see below), exhibiting not one-to-one, but many-to-one and one-to-many causal dependencies and relationships.

Evo-Devo is acronym of evolutionary developmental biology.

Indeed, in retrospect it is astounding how from the beginning of the 20th century onwards Neo-Darwinism could turn aside valid objections by established biologists from various fields (3,6,7,17,25,26); see glossary, epistemic closure (27)). As only one example, briefly consider the concept of gradualistic evolution. Based upon the fossil record, the course of evolution presents itself as everything but slow and continuous. Long periods of stability persisted, which were followed by short periods during which individual features changed drastically. In particular, the so-called Cambrian Revolution about 540 mya ago was a period of “productive instability”, during which practically all presently existing major animal groups (approx. 35; (10,28,29) appeared within a short period of time. Later, similar phenomena of rapid diversification reoccurred several times. After massive waves of extinction (in particular, the big five), each time the animal kingdom has regenerated swiftly, whereby the major bauplans existing since Cambrian times emanated into ever new forms which then could exist unchanged over long periods. Gould and Eldredge have explained the phenomenon of long periods of stasis interrupted by relatively short periods of extinction and regeneration by their concept of punctuated equilibrium (punctualism; theory of disrupted equilibrium; (29). During periods of stasis representing the default state of nature, species would remain mostly unchanged. Notably, the ornithologist Otto Kleinschmidt discovered that it was not continuous change and drifts of avian populations, but rather their persistence (stability, constancy, stasis and coherence) characterizing their essence (30).

For instance, the white wagtail (Motacilla alba) has presumably existed without any change for at least 60 million years. Moreover, Kleinschmidt realized that certain features of a bird’s population (e.g., beak shape, patterns, colors of plumage) varied within a given local area, but - notably - without presenting a distinct maximum within that sample (Fig. 2; called Formenkreise, what Ernst Mayr later denoted as superspecies). As soon as birds were dwelling in urban areas, or even more so, when bred as domestic animals (e.g., urban, homing pigeons), the band widths became wider, while their distinct features became blurred, thus questioning Darwin’s postulate that evolution could be compared to animal breeding (see for details, (31). Only when populations come under pressure by extreme conditions (e.g., stress, environmental catastrophes, etc.) the equilibrium becomes distorted, followed by rapid variability and emergence of new species.

Figure 2

This pattern, which occurs repeatedly over Earth history, suggests a non-random sequence of events. The conquest of land by flora and fauna exemplifies a directed evolutionary step (1, 32). It can be shown that for a successful transition, the land not only first needed to be settled by plants to exploit minerals from the soil, but in addition, plants had to develop elongated, vertically high rising forms to prepare the atmosphere for animals living on land. With this, plants abandoned their spherical shape, which had been well established in the aquatic milieu (e.g., Volvocales), and transformed for a predominantly elongated growth on land. Animals, on the other side, could further differentiate their round shape, which originates from the egg, to further develop it into diverse adult forms. If we consider how life on land became evolutionarily possible for animals, this temporal sequence accompanied by morphologic adaptations on the plant’s side were mandatory. Thus, it is the given physical earthly structure, not the genes alone that decided whether and when animals could move on to the land. Fields and Levin propose that the entire course of evolution could be conceived as a planetary developmental event, whereby at all organismic levels strong attractors direct the non-random emergence of - what they call - target morphologies (33). Accordingly, Conway-Morris presumes that, if biologic evolution on this planet would be repeated, the same organismic groups including humans would reoccur in a similar sequence (convergence, (34)).

The appearance of new morphologic constructions raises the question, how can fundamental novelties develop during evolution, such as a placenta or mammary glands with mammals. Could it suffice to accumulate minor changes from generation to generation (microevolution) to achieve eventually a major transformation (macroevolution)? Hitherto, Neo-Darwinism could not provide a satisfying answer. Instead, isn’t it more likely (even necessary) that some complex novelty appears abruptly on the scene, like a phoenix from the ashes, which immediately presents new functional possibilities and target points for a transforming selection (see also threshold model, (35)? In this respect, discoveries of molecular developmental biology provide remarkable progress with a research program, which has become known as Evo-Devo (17,28,36,37,38). Here, this exciting field can be highlighted only with a few sentences.

The development of most eukaryotic organisms depends on a manageable number of important developmental genes and molecular signal cascades (10). This molecular basic set-up, also known as a molecular toolbox (tinkering), existed already before the Precambrian period and has been highly preserved until the present. These molecular tools regulate ontogenesis of plants and animals in a combinatorial manner, where a particular molecular module can exert different functions in different organisms; this applies even for different places or times of action within the same organism (Fig. 1b). If mutations of single components of such molecular networks occur, then this can entail - at best - meaningful or functional transformations of the phenotype (Fig. 3, possible transformation from a saurian to a serpent habitus; cf. below, polydactyly). Thus, an abrupt branching of the phenotype can become intelligible based on only minor changes of the genotype (see more examples in (24,39,40,41). Hence, preconditions for the origin of new forms are fulfilled, i.e., for macroevolution. In this respect it is of utmost importance that the respective environment (molecular, cellular, up to ecological) can canalize (“bias”) such processes, and - as constraints - can even initiate them by feedback actions on the genetic material (cf. Fig. 1b, blue arrow; see Fig. 4, four-legged bird).

Figure 3

Figure 4

Given this restricted molecular toolbox, then formation of bodily patterns should become easily predictable. Indeed, computer simulations based on molecular reaction-diffusion mechanisms can model natural patterns at high fidelity and impressive esthetic beauty (42,43,44). The interplay between longranged inhibitors and local autocatalytic activators can reproduce – besides others – repetitive threshold values, leading from gradually changing patterns to bifurcations, producing borders, dots, stripes, or duplicate them, whereby the particular outcome depends on minor changes of parameters.

However, simulations and real life are different topics, since only rarely in development situations might exist, where the interplay of two molecular factors alone will cause a certain phenotypic feature. Rather, seemingly simple phenotypic characters often depend on complex environmental networks (from molecular up to organismic levels). For instance, formation of digits on hands and feet, and their quite frequent malformations, known as polydactyly, depend on a rather large number of molecular factors (e.g., Shh, Wnt, Fgf8, retinoic acid). But notably, fields of digit cartilage formation are not defined by diffusion of morphogens. Rather, bistable states of neighboring cells determine their numbers, as revealed by a threshold model for polydactyly (9,35). The respective ON or OFF states can depend on only a few factors, with minor genetic alterations causing additional threshold peaks, which will cause supernumerary digits. Certain numbers of discrete characters occur preferentially, i.e., their distributions are biased (cf., the “missing variant” of centipedes; (28). Evolutionarily, polydactyly shows that novel morphological entities can occur abruptly in a one-step manner. Phenotypic variations i) are driven towards modular wholeness (see also Fig. 4, supernumerary chicken leg pair), and ii) can occur discontinuously, supporting punctual macroevolution (45).

In fact, multiple examples from the field of regeneration biology present aspects of target-directed self-organization, which could be conceived as bias of development, as directionality, or, as a drive to wholeness (see glossary; (10). Historically, the famous Schüttelversuche by Hans Driesch at the end of the 19th century set a cornerstone to embryology known as embryonic regulation, by analyzing the behavior of dispersed cells from the 4- to 8-cell stages of sea urchin embryos. As a former student of August Weismann (see Weismann’s barrier; (10,27), Driesch expected that from each individual cell – if anything – only parts of an embryo should develop, e.g., only muscle, or nerve tissue, etc. To his perplexity, however, he found that whole embryos, including all cell types, could develop from an individual cleavage cell. Today, this phenomenon is conceived as a genetic de-differentiation of individual cells into the state of a fertilized egg, a return to (nearly) the zygote, which as an early embryonic stem cell then can generate a whole larva under the given in vitro culture conditions. With his discovery, Driesch laid the grounds for regeneration biology and eventually to stem cell biology.

Another striking demonstration of an inherent systems property to maintain wholeness was provided by Fankhauser’s famous study on the regulation of cell size (46). Some variants of newts are found with more than a double set of chromosomes (polyploidy). Fankhauser found that as polyploidy increases, the cell size increases in all tissues, while the total size of the animals remains unchanged. This effect was particularly obvious in the larvae’s pronephric canal (precursor of kidneys). Even Albert Einstein was puzzled by this finding and drove him into puzzlement; he noted „…The importance of the cell as ruling element of the whole had been overestimated previously. What the real determinant of form and organization is, seems quite obscure” (cited from (47). Clearly, in this instance a drive to achieve a certain body size, i.e., a certain wholeness, cannot be neglected.

Whether considering normal development or regulation, it is difficult to distinguish experimentally nature from nurture effects in forming a complex tissue. Let us consider, for instance, the making of a vertebrate retina. In all vertebrates, eye cup formation and the ensuing differentiation of retina and pigmented epithelium (RPE) follow molecularly and histologically similar, seemingly determinative paths. But are these processes indeed purely autonomous and target-directed (biased)? If one attempts to analyze them in absence of external factors as acting in vivo, in vitro experiments using dispersed cells from a certain tissue are instrumental, to then follow their behavior in a rotating in vitro culture setup (Schüttelversuche). Studies on histotypic reaggregation of embryonic stem cells from the avian and mouse retina were telling, which historically can be traced back to researchers like Wilson and/or Driesch (Fig. 5), and eventually contributed to the breakthrough of current stem cell biomedicine (reviewed in (48,49,50).

Figure 5

Since the early 1950s, Malcolm Steinberg and Aaron Moscona had – independently from each other – discovered histotypical structures in reaggregated cell spheres from the chick embryonic retina (reviewed in (51). The vertebrate retina is particularly suited as a model tissue for such studies, due to its simple cell type composition, its threefold laminar structure, and its easy access (Fig. 6d, right; 7e). Briefly, all cell bodies are arranged in three layers: an outer (ONL), an inner nuclear layer, and a ganglion cell layer (GCL). The ONL holds photoreceptors consisting of rods and cones (note: ratios of rods, and types and ratios of color-sensitive cones, vary in different species), horizontal (HCs) and bipolar cells (BCs) constitute the INL, and ganglion (GCs) and displaced amacrine (dACs) cells compose the GCL. Within two synaptic layers, called outer plexiform (OPL), and inner plexiform layer (IPL), PRs connect with BCs and HCs in the OPL, and BCs with ACs and GCs in a multilaminar IPL (further see below). Radial Müller glial cells (MC), that span through the entire width of the retina, have tremendous developmental and physiological impacts.

Figure 6

Depending on the species (avian, Fig. 6; mammalian, Fig. 7), the chosen culture conditions, in particular the composition of the culture media (salts, growth factors, sera, etc.) and the type of rotation, the emerging histologic structure within forming retinospheroids can be altered (Figs. 6, 7). With chicken embryonic retina (Fig. 6), dispersed cells quickly reaggregate and begin to sort out. As a first sign of self-organization, internal rosettes will form holding mitotic cells and (later) future PRs (Fig. 6b, c). In between rosettes, INL cells become neatly arranged, which surround a cell-free space (Fig. 6c, e), resembling an IPL (here called ipl). As in vivo, so-called starburst amacrine cells (SACs) are the first to differentiate, which send their neurites into the ipl. Amazingly, they form two synaptic subbands, which lay the grounds for further complex in vitro IPL network formation (Fig. 6e).

Figure 7

Notably, dispersed cells from the neonatal gerbil retina (Mongolian desert rat) behave differently. Rosettes are not found; instead, already in minute spheroids SACs begin to sort out, arrange pairwise and send out processes to organize an IPL network (Fig. 7a-c). As another leading process in both species, the inside-out polarity of reconstituted segments of layers could be reverted, depending on media supplements (e.g., RPE, or MCs, cf. Fig. 6b, d), eventually leading to nearly fully laminated spheroids. With chick retina, RPE induced a reversion from rosetted to fully stratified spheroids (Fig. 6b, d), leading to a normal laminar spherical composite in vitro (retinospheroid; now generally called retinal organoid, (50). With gerbil retina (Fig. 7), addition of RPE induces a laminar spheroid with the GCL, IPL and INL oriented outside (Fig. 7d, cf. 7a). A combination of RPE and Wnt-3b again reverts the layering to produce a fully laminated spheroid, achieving an advanced IPL towards its inner core (Fig. 7f).

These findings documented for the first time (52), that originating from dispersed stem cells a) it is possible to reach a nearly complete retinal tissue formation in vitro, and that b) this phenomenon not only depends on retinal genes alone, but as well on the prevailing culture conditions (e.g., neighboring cells, growth factors, etc.). In both species, a complex ipl network formation revealed that – dependent on the chosen in vitro culture conditions – different developmental paths can lead to a similar target (e.g., many roads to Rome; (53), namely a wired IPL-like network. Even if a complete laminar structure was not achieved in each experimental set-up, cells within their artificial surrounding were always biased towards retinal wholeness. The cells were “attempting to build” a structured retina. This is what Fields and Levin mean with “target morphology” – an attractor that directs the organization of tissue formation non-randomly at various levels (33).

Such a target directionality could not be denied. In all instances it became evident (Figs. 6, 7) that not only genes direct developmental processes, but the given cellular environments set multiple switch points to reach a final tissue structure. Thus, development is a product of gene actions interacting with cells, tissues and with the environment to result in emergent features. Accordingly with such in vitro retinal approaches, self-organizing emergent processes presumably direct the outcome of each experiment (53). The number of possible environmental parameters and each of their prevailing impacts are immense, and therefore de facto are not controllable. Notwithstanding, the often-observed target orientation and accuracy with many developmental processes are perplexing. To avoid the term directionality, generally the term robustness of biologic processes is preferred (27,54). For warranting a normal course of development in vivo, it is robustness which acts as its foremost directive. Irrespective of countless developmental possibilities, which were – in principle – realizable on basis of the given genome and its associated molecular modular networks (which could be called the individual “genomic potential”), the realized developmental path will be channeled and restricted (i.e., biased) by the actual spatiotemporal environment. Not genes alone, but the environment channels and secures robustness (55).

This characterizes what in the present context is meant by self-organization and emergence (56,57,58), and what Kirschner et al. describe when they speak of a universe of possible phenotypes: “The genotype, however deeply we analyze it, cannot be predictive of the actual phenotype, but can only provide knowledge of the universe of possible phenotypes. Biological systems have evolved to restrict these phenotypes, and in self-organizing systems the phenotype might depend as much on external conditions and random events as the genome-encoded structure of the molecular components” (cited from (59)).

The insight, that genes alone do not determine ontogenesis and phylogenesis, brought Kirschner and colleagues to their provocative title of “molecular vitalism” of their abovementioned article. They conclude that “At the turn of the twenty-first century, we take one last wistful look at vitalism, only to underscore our need ultimately to move beyond the genomic analysis of protein and RNA components of the cell (which will soon become a thing of the past) and to turn to an investigation of the “vitalistic” properties of molecular, cellular, and organismal function.” How can modern cell biologists speak of vitalism, a concept holding that living organisms would be driven by vital forces, and which had completely vanished after the advent of Darwinism?

In fact, it was Driesch who had revitalized these ideas to become founder of Neovitalism. When he had summed up his findings by the telling sentence that “the prospective potency of a blastomere is higher than its prospective fate”, then it was not defined cell fates which determined the future of his cells in a glass dish, but – as Driesch postulated - somehow rather a certain knowledge, an image of wholeness, resident in each blastomere, which directed the generation of a complete organism. For Driesch himself his observations were most bewildering, entirely overturning his worldview. He could not manage to explain them on a purely reductionist basis, but he postulated a non-material, transcendental Lebenskraft (vital force, gk. Entelechy, according to Aristotle), supposedly residing in each cell and entailing a “drive to wholeness” (holism; (27)). His neovitalistic holism was also denoted as teleology. Based on modern conceptions of self-regulating complex systems, probably most (if not all) of these phenomena can be perceived as robustness, and would figure under teleonomy, which denies - in contrast to teleology - any metaphysical influence on target-directed, purposeful processes.

What precisely do Kirschner et al. mean with their vitalism? Do they make another turn to transcendence, as Driesch did? No, certainly not. Yet, like Driesch, they insist that living organisms cannot be fully explained on a purely mechanistic or “bottom-up” physicalist basis, and that the often-applied machine comparison fails (see also Discussion in (58). They wonder how in a potentially non-deterministic world the development of organisms and their physiology can reach their admirable robustness, which appears to suggest vitalist forces. Since they repudiate an Entelechy, that is, a transcendental vital force, they rely on explaining the chemical basis of robustness by applying methods of artificial intelligence (AI). They hope that interactions between countless molecular-genetic networks with indeterminable environmental influences may become decodable, to then discover the causes of biologic robustness, eventually even decoding the phenomenon of life (s. also (22,23,57,60). Accordingly, these authors do not advocate for a transcendent vitalism, but take a teleonomic view of complex emergent processes in nature.

The post-genomic era has realized that expression of many genes is environmentally directed (see glossary: Nature-vs.-Nurture-discussion, phenotypic plasticity; Fig. 1), to which research on Evo-Devo and epigenetics have substantially contributed. Their discoveries finally revealed that the standard teaching of Neo-Darwinism (SET, modern synthesis, population genetics) requires supplementation by an extended evolution theory (EET; (3). Some authors were even speaking out for a complete restart of evolutionary theory (3,4,17,37,55). For instance, Ron Amundson stated (17) “Developmental types and exclusive population thinking are incompatible. One or the other (or both) must go before a new synthesis is possible” (whereby developmental types refers to Evo-Devo, and population thinking to SET). Even if the genomic potential of each individual organism – under all random influences occurring during its ontogeny – would suggest an infinite number of possible phenotypes (estimates reach numbers more than the number of atoms in the entire universe; see also, (22,60), then evolution still proceeded anything but purely randomly. Directed during ontogenesis by a restricted number of molecular-genetic networks, the evolutionary events are neither fully determined, nor are they completely random, since evolutionary history ever was and remains environment-dependent. Novel forms act back on and shape their environments. Evolution presents signs of abrupt breaks and biased advances. Its future proceeding as well as its final aim cannot be predicted.

Anyhow it appears – with respect to the complexities of organic structures – that with the appearance of Homo sapiens and the outstanding performances of its brain, evolution has reached a unique target state, since the human brain generally is considered the most complex structure in the universe.

Both, during individual development (ontogenesis) as in evolutionary history (phylogenesis), we can observe a drive to wholeness. In ontogenesis (as well as during regeneration phenomena) it is a drive to produce a whole organism (or, entire structures, see Fig. 4: the additional pair of legs at the bird’s caudal end as an individual extremity presents wholeness, being formed as threefold structure). Phylogenesis could be conceived as one targeted developmental process, extended over the entire period of life on earth (33). Thus, in both spheres - ontogenesis and phylogenesis - a procedural directionality becomes apparent. What under Driesch was considered as teleology and vitalism, nowadays is debated under the names of teleonomy and robustness. Notably, the term teleonomy is not instrumental to reach a philosophical conception of evolution since it cannot resolve basic questions of causality and finality. The origin of life on earth remains unsolved, whether from a primordial soup, or germs from outer space (61), and whether the final aim of evolution is the emergence of H. sapiens – as is often presumed – also remains undecided. Notwithstanding that evolution appears to some scientists and philosophers as clearly biased (62), the concept of teleology must be considered as scientifically inappropriate, since it does – as defined above – assume transcendental influences on natural phenomena.

Yet, questions regarding teleology and vitalism are neither absurd nor illegitimate: they do constitute the core of philosophical thought on nature. So, one wonders whether in a causally open world the phenomenon life can be scientifically resolved at all. Living creatures do present specific and inextricable features. Do these features represent specific signs of vitalism? In his engaging book Purpose and Desire, Scott Turner characterizes life as “striving for something”, a postulated feature that all living objects are aiming at something, i.e., are characterized by some intentionality (27). He points out that questions of teleology and vitalism are scientifically still timely (see also (23,54).

Unfortunately, they put the biologist into the dilemma of a destructive dilemma: either a) one performs science legitimately, i.e., strictly by materialistic methods and reasoning, or b) one integrates transcendency into one’s thought, therewith avowing oneself as a vitalist, to leave the field of accepted natural science. Science cannot solve this problem. In the post-genomic era, the following conclusions appear to be important: that a) questions of teleology and vitalism are still prevailing, while b) they cannot be answered scientifically; thus, c) biologists should content themselves with these insights. While the popular idiom of survival of the fittest aptly reflects and justifies our turbo-capitalist’s world, Evo-Devo research has more appropriately converted it into arrival of the fittest, adapting to the discovery that the first step to evolutionary change must happen in the embryo (10,17). Post-genomic considerations reveal that onto- and phylogenetic processes are neither purely random nor fully determined, but certainly they represent directed events. The question whether it is more genes that change their environments, or whether possibly it is more so the other way round, is worthwhile contemplating (23,63).