, Monika Hassel2 and Maura Grealy3
(1)
Centre of Organismal Studies, University of Heidelberg, Heidelberg, Germany
(2)
Spezielle Zoologie, Universität Marburg FB Biologie, Marburg, Germany
(3)
Pharmacology and Therapeutics, National University of Ireland Galway, Galway, Ireland
1.1 Development as Self-Construction
1.1.1 Living Beings Construct and Organize Themselves on the Basis of Inherited Information
Development and reproduction are basic features of living beings. In the context of this book development means ontogeny, the development of an individual life, typically beginning with the fertilization of an egg, and ending with the death of the individual. Development in the sense of phylogeny or evolution, which becomes apparent as a gradual change of form and behaviour of the organisms in the course of long sequences of generations, is dealt with only insofar as we shall discuss some evolutionary variations of ontogenetic patterns in Chap. 6 and more so in Chap. 22.
The essential principles of development are conveyed by terms such as self-construction and self-organization. The development of a multicellular organism starts, as a rule, with a single, seemingly unstructured cell – the fertilized egg cell which hardly approaches the complexity of single-celled organisms. It was reserved to the eyes of former naturalists endowed with vivid imagination to see in the tiny sperm cell a complete homunculus, a little human being (Fig. 1.1). The present day scientist (cell biologist, biochemist, molecular biologist) finds in the fertilized egg cell constituents not much more diverse than those of any other cell. The size of an egg cell can be huge but its internal structures appear not to be more intricate and elaborated, even in the electron microscope, than those seen in many other cell types. Yet, without the intervention of an external designer, from this modest cell with its simple spherical shape a being arises with a highly complex form and many thousands of diverse cells. These arrange themselves to form the new organism in a highly ordered cooperation and interplay of forces.
Fig. 1.1
Homunculus in a sperm cell, seen with the eyes of Nicolas Hartsoeker (1694)
Similarly, when a creature such as the freshwater polyp reproduces itself by a process of asexual reproduction through buds (Fig. 4.12), it is an association of only a few, poorly differentiated cells that constitutes the starting material for the development of the new organism. Whether egg or bud: the fully developed creature will have an internal complexity that surpasses our imagination. We are all familiar with the avian egg from our breakfasts – it is the amorphous yellow ball that constitutes the egg cell proper. But who is able to visualize the 100 billion nerve cells of our brain and their 1014–1015 synaptic connections in their three-dimensional architecture?
All of the many and diverse somatic cells that originate from generative starting cells do not, however, attain autonomy as do the cells which arise from dividing single-celled protists. Somatic cells are viable only in the community of the cell association. For the sake of the supraindividual society – the organism or individual – the cells assume different responsibilities and tasks. They differentiate morphologically and functionally, together construct multicellular structures, tissues and organs. In this process, cells form the same structures and patterns in the same temporal and spatial order, from generation to generation.
The increase in complexity and diversity during embryogenesis and the autonomous shaping of form (morphogenesis) from simple, seemingly amorphous starting matter stimulated curiosity about the causal, organizing principles since thousands of years. Aristotle saw the ultimate form-determining principle in the soul (Box 1.1); nowadays the leading role is assigned to genetic information.
The ability to reproduce themselves is conferred upon organisms through genetic information (DNA in the nucleus and mitochondria of animal cells) and through further information-carrying structures in the egg cell (maternal information, cytoplasmic determinants); but it is not the finished organization that this information encodes directly.
It is commonly stated that the genome incorporates a Bauplan (construction plan, body plan): an architectural plan or blueprint of the body. Actually, this is not the case in the strict sense of the term: the genome is not a sketch or design of the finished body. The informational capacity of DNA is simply too low to store blueprints of the very complex final pattern of an organism. For example, a detailed design of the one hundred trillion to one quadrillion synaptic contacts in our brain alone would greatly exceed the capacity of the genomic memory.
What then does the genome (sum of genes) really encode?
The double-helix structure of the DNA provides information how to make two exactly identical replicas of the DNA itself which subsequently can be allocated from the mother cell to its two daughter cells in cell division.
The genome is subdivided in sections, called genes. Part of these genes, recently defined as ‘coding’ genes, contains information on the sequential order in which amino acids have to be linked to form distinct chains, so that all the many proteins a cell needs get their correct primary and secondary structure. For this in the process of transcription the information of the gene is copied in form of mRNA (messenger RNA) and the copy exported into the cytoplasm. Mediated by this copy a specific protein can be produced (translation), instantly or at any appropriate time point later. Transcription and translation together are subsumed under the term gene expression.
Other types of genes contain information enabling the production of essential tools for protein synthesis, in particular tRNAs and rRNAs. Further sections of the DNA code for short-chain microRNA molecules which fulfil important regulatory functions that will be dealt with in Chap. 12.
The genome embodies some hierarchical organization: master genes (Chap. 12) dominate, via their products, whole sets of subordinate genes.
In the genome a spatio-temporal organization is realized. For instance, some classes of regulatory genes are arranged in an order that corresponds to the spatial and temporal pattern of their expression. Such correspondences (colinearity) apply to the Hom/Hox gene clusters (Chaps. 4 and 12).
Also the ‘non-coding’ sections of the genome can contain information in a concealed form, for instance, when they offer binding sites for regulatory transcription factors and thus become controlling regions for coding genes. In this function these sections are called promoters or enhancers. Further potential roles of non-coding DNA sections will be discussed in Chap. 12.
How a developing organism arises by self organization on the basis of such minimal information, or how many organisms are able to regenerate lost structures surpasses our imagination.
Box 1.1 History: From the Soul to Information
The Dawn of Developmental Biology in Ancient Greece
Although embryos were described in ancient Sanskrit and Egyptian documents, the Macedonian Aristotle (384–322 BC), son of a physician, was the first to perform developmental studies in a systematic way, to interpret his observations in written words and to coin lasting terms. An acknowledged philosopher and academic teacher (e.g. of the prince that was to become King Alexander the Great) as well as an enthusiastic naturalist, he wrote the first textbooks of zoology and treatises on reproduction and development.
The multivolume “History of Animals” (Peri ta zoa historai, in Latin: Historia animalium) contains several chapters on development. Most treatises are compiled in five volumes entitled “On the Generation and Development of the Animals” (Peri zoon geneseos; Lat.: De generatione animalium). Some more expositions on development are found in the books “On the Soul (Mind)” (Peri psyche; Lat.: De anima) and in the Metaphysics (Metaphysika).
Aristotle distinguished four possibilities as to how organisms might arise: (1) spontaneous generation from rotting substrate, where flies and worms were thought to originate; (2) budding; (3) hermaphroditism; and (4) bisexual reproduction. In his view, the egg was the instrument of reproduction in oviparous species. Mammals, human beings and some other viviparous species lacked eggs. Females contributed to offspring by supplying unstructured material, males by supplying semen, the purveyor or causative principle of form.
Aristotle described the development of the chick in the egg. Eggs were incubated for varying periods of time and opened. According to his observations there is an initially unstructured material, which in the course of morphogenesis or epigenesis acquires form. In the midst of the emerging figure he observed a “jumping point”, the beating heart.
He considered the aim of development to be the ergon, the finished work as it is the aim of the artisan. The modelling principle he thought of as energeia (energy), also called entelecheia, the principle bearing its aim, goal and end in itself. Energy is both the efficient and final cause. To reach a particular species-specific end, the forming principle must have a “pre-existing idea” of the final outcome. Hence the ultimate cause, the ultimate energy would be the soul (mind, spirit, psyche).
To quote Aristotle, “It (the soul) causes the production … of another individual like it. Its essential nature already exists; … it only maintains its existence… The primary soul is that which is capable of reproducing the species” (De anima, 416b1–b27).
Following Plato, Aristotle discriminated between the vegetative soul, which brings about life as such, the animal sensitive soul, which enables sensations, and the spiritual soul, which enables thinking.
The vegetative soul endows plants with the ability to regenerate. The vegetative soul also includes the formative power of animal development. In animals the mother (mater) supplies the matter (Latin: materia); in mammals the matter is supplied in the form of the menses (as the menses are cancelled if pregnancy occurs). The semen was thought to coagulate the female material and to trigger and govern its development. Aristotle’s exposition on the residence and inheritance of the vegetative soul are not unequivocal: is it in the female matter or in the semen? In contrast, the second degree of soul, the animal soul, is inherent only in the semen and is transferred from the father to the future child in begetting. The animal soul then governs sensitivity and movement. The spiritual soul is eternal, immortal, painless, sheer energy, and enters human beings from outside “through a door”.
Aristotle’s imprint on the western educated world has endured for centuries. With all due respect for his great stature, what he said about begetting, fertilization and determination of the female sex may be courteously passed over in silence.
The Renaissance of Developmental Biology
Embryology revived in the sixteenth century. In the school of Padua (Vesalius, Fallopio, Fabricius de Aquapendente) the anatomy of ovaries and testes were studied. The idea of an egg arising in the ovary and the embryo arising in the egg was conceived by the Dutch physician Volcher Coiter (1514–1576) upon completing his detailed study of chick embryo development, a study for which he has finally been recognized as the father of embryology.
The English anatomist and physician William Harvey (1578–1657), best known as the discoverer of the (greater) blood circulation in the vertebrate body, resumed the embryological studies of Aristotle, extending his research to insects and mammals (sheep and deer). Though he was an admirer of “The Philosopher” (i.e. Aristotle), he maintained that spontaneous generation was restricted to lower organisms. But in insects, development implies “metamorphosin” or metamorphosis – the transformation of already existing forms into other forms. Harvey considered the pupa as an egg, as did Aristotle before and several other investigators after him.
In higher animals, however, Harvey regarded development to be not merely transformation but “epigenesin” or epigenesis – creative synthesis, incremental formation of a new entity out of non-structured matter. And Harvey wrote, “We, however, maintain … that all animals whatsoever, even the viviparous, and man himself not excepted, are produced from ova; that the first conception, from which the foetus proceeds in all, is an ovum of one description or another, as well as the seeds of all kinds of plants”.
Later literature shortened Harvey’s phrase to “omne vivum ex ovo” (“all life from an egg”), probably inspired from the frontispiece of Harvey’s embryological treatise “Exercitationes de Generatione Animalium”, where an egg bears the inscription “ex ovo omnia” (“everything out of the egg”). However, Harvey’s mammalian egg was not the same entity we have in mind today but the blastocyst (young embryo) within the “shell” of the uterus. It was Carl Ernst von Baer (below) who discovered the real mammalian egg.
Preformation and Mechanicism
When the Swiss naturalist and physician Conrad Gessner (1516–1565) author of the famous works Historia animalium and Bibliotheca universalis, following the Roman naturalist Pliny, reported that the female bear gives birth to a lump of meat, thereafter licking it into shape, he probably was not yet influenced by the philosophy of mechanicism. In contrast, his later compatriot scholar Albrecht von Haller (1708–1777) categorically maintained: “nulla est epigenesin” (“there is no epigenesis”).
With this notion he followed the founders of microscopic anatomy. In 1683, Anton van Leeuwenhook (1632–1723) wrote “that the human foetus, though not bigger than a pea, yet is furnished with all its parts”. Leeuwenhook discovered “animalcules” or “zoa” within semen as did others before him. (Later, von Baer renamed the zoa spermatozoa). Several microscopists of those days saw or conjectured that they would see “homunculi” − minute preformed human beings within the animalcules (e.g. Hartsoecker, Fig. 1.1). Embryos were thought to result from enlargement of homunculi.
Likewise, in the ‘eggs’ (pupae) of insects, adult ants and butterflies were seen to be already prefigured in miniature, as are leaves and blossoms in the buds of trees. The pre-existing beings only needed to be ‘evolved’: unrolled and unwrapped. Such views advanced to meet the views of the mechanicists, who held that life merely obeys the laws of mechanics. Living beings were regarded as ingenious clockworks comparable to the marvellous astronomic clocks built by contemporary artisans. Whether these machines were viewed as soulless or animated entities depended on the religious and ideological position of the respective author.
In 1672 Marcello Malpighi published the first compelling account of chick development with detailed figures. For the first time he depicted the neural folds, the muscle- and vertebrae-forming somites and the blood vessels leading to and coming from the yolk. Nevertheless, Malpighi questioned epigenesis and adhered to the preformationist view. This view appeared to be better in accord with the narrations of the bible. God created living beings only once and then settled down, and because all beings and their organs were prefigured when created in the paradise, no further intervention of divine creativity is needed in development because prefigured structures need merely be unrolled.
The doctrine of preformation quickly led to some awkward problems:
If ontogenetic development is only mechanical unwrapping of prefigured forms, must not all generations have been in existence from the very beginning of the world? “Emboitment” (encapsulation) was the answer: One generation lies within another generation like one Russian doll lies within another. According to computations of Vallisneri (1661–1730), the ovary of the primordial mother Eve contained 200,000,000 human burgeons, packed into one another. This stock should suffice until the end of all days. The French-Genevan Charles Bonnet (1720–1793), who accurately described parthenogenesis in aphids (Fig. 1.4) wrote in 1764: “Nature works as small as it wishes”.
The microscope showed cells and with cells a lower limit to the size of the preformed organisms. Microscopists showed not only egg cells but also spermatozoa. Now the prefigured “homunculus” was claimed to be prefigured and visible in the egg (ovists) or in the sperm (animalculists, homunculists). Among the ovists were the renowned anatomists Marcello Malpighi (1628–1694) and Jan Swamerdam (1637–1680).
How can regeneration of body parts be explained, if lost parts can only be made from preformed parts?
Lazzaro Spallanzani (1729–1799) was the first to perform artificial insemination. He reported that frog eggs degenerated in the absence of sperm. Working with dogs, Spallanzani finally laid preformation arguments to rest by proving that both the egg and the male semen are necessary to produce a new individual (although he erroneously believed that the animalcules swimming in semen were mere parasites). In its extreme form preformation soon was mere history.
Epigenesis and Vitalism
Caspar Friedrich Wolff (1738–1794) who worked and taught in St. Petersburg and Berlin resumed the study of the chick embryo and again saw new formation – morphogenesis out of structureless yolk material. Wolff planted the seed, so to speak, of the germ layer theory by describing “Keimblaetter” (germ leaves) which later transform into adult structures. Like Aristotle before him, and all further vitalists after him, Wolff concluded that there are ‘immaterial’ (non-corpuscular) virtues, a “vis essentialis” or “vis vitalis” – a force specific for life. The academic colleague of Immanuel Kant, Friedrich Blumenbach (1742–1840) postulated a particular, physically acting “Bildungstrieb” (propensity, formative compulsion) that is inherited via the germ cells. Many important biologists were vitalists, among them Carl Ernst von Baer (1792–1876), who discovered eggs in several mammalian species, and performed extensive comparative studies. Von Baer concluded that all vertebrates develop in a fundamentally similar way from germ layers, and he established a rule, now known as von Baer’s law, which states that all vertebrates go through a very similar embryonic stage and only thereafter do the developmental pathways diverge. Based on this rule, Ernst Haeckel (1834–1919) formulated his much disputed “ontogenetic” or “biogenetic law” (Chaps. 6 and 22). The theorem maintains that ontogeny is an abbreviated recapitulation of phylogeny.
Interest in human embryology was stimulated in 1880 by the Swiss anatomist Wilhelm His with the publication of The Anatomy of Human Embryos .
Experimental embryology began in France in the tradition of morphology. The former theologian and later zoologist Etienne Geoffry Saint–Hilaire (1772–1844), one of the founders of the theory of evolution, and opponent of the very influential Georges Cuvier, sought to elucidate the causes of developmental anomalies (“terata”) and disturbed, with crude methods, the development of the chick. In 1886, his compatriot Laurent Chabry began studying teratogenesis in the more readily accessible tunicate egg (Ascidia aspersa). Although the tunicate egg is tiny (0.16 mm) Chabry succeeded in performing localized defects with self-made surgical instruments. Henceforth, invertebrates became preferred sources of eggs for studying very early animal development.
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