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The paper addresses the formation of striking patterns within originally near-homogenous tissue, the process prototypical for embryology, and represented in particularly puristic form by cut sections of hydra regenerating a complete animal with head and foot. Essential requirements are autocatalytic, self-enhancing activation, combined with inhibitory or depletion effects of wider range - “lateral inhibition”. Not only de-novo-pattern formation, but also well known, striking features of developmental regulation such as induction, inhibition, and proportion regulation can be explained on this basis. The theory provides a mathematical recipe for the construction of molecular models with criteria for the necessary non-linear interactions. It has since been widely applied to different developmental processes.
Physical principles underlying biological pattern formation are discussed. In particular, the combination of local self-enhancement and long-range (“lateral”) inhibition (Gierer and Meinhardt, 1972) accounts for de-novo pattern formation, and for striking features of developmental regulation such as induction, spacing and proportion regulation of centers of activation in tissues and cells. Part I explains physical principles of spatial organisation in biological development. Part II demonstrates in mathematical terms that and how short-range activation and long-range inhibition are conditions for the generation of spatial concentration patterns. The conditions can be expressed in terms of ranges, rates and orders of reactions. These conditions, in turn, can also be derived by analysis of dynamic instabilities by means of Fourier waves, showing the neither obvious nor trivial relation between the latter approach and the theory based primarily on autocatalysis and lateral inhibition.
Modern brain research related to consciousness has resulted in many interesting in- sights, for example into the neurobiological basis of attention and of language. In biological terms, human consciousness appears as a system’s feature of our brain, with neural processes strictly following the laws of physics. This does not necessarily imply, however, that there can be a general and comprehensive scientific theory of consciousness. Predictions of the extent to which such a theory may become possi- ble vary widely in the scientific community. There are reasons - not only practical but also epistemological - why the brain-mind relation may not be fully decodable by finite procedures. In particular, analogies with mathematical theorems of un- decidability suggest that self-referential features of consciousness, such as multiple self-representations like those involved in strategic thought, may not be fully resolv- able by brain analysis. Assuming such limitations exist, this implies that ob jective analysis cannot exhaust sub jective experience in principle. A person’s consciousness and will are accessible to external observation only within limits. In some respects, we do not even learn to know ourselves except by our actions. It thus appears that a scientific look at consciousness and the human mind, combining universal physi- calism with epistemological scepticism, is not inconsistent with certain concepts of sub jectivity that are current in the humanities, despite all the differences in the style and terminology of discourse.
Aside from the increasing, impressive evidence on chemical identification of graded molecules involved, it is the capability of axons for approaching the target position from different aspects in a two-dimensional field which is per se a strong indication for the involvement of gradients. Targeting requires, in the target field, counter-graded effects, either by antagonistic gradients, or by a single gradient in each dimension exerting attractive effects at low, reverting to inhibitory (repulsive) effects at high concentrations. A further requirement for mapping is the modulation of the counter-graded effects by components of the growth cone itself which depends on the origin of the corresponding axon.Transduction and processing of graded signals in the navigating growth cones are proposed to be strongly enhanced by intra-growth-cone pattern formation. The concept also encompasses regulatory and branching processes including the formation of the terminal arbors.
Ancient Greek philosophers were the first to postulate the possibility of explaining nature in theoretical terms and to initiate attempts at this. With the rise of monotheistic religions of revelation claiming supremacy over human reason and envisaging a new world to come, studies of the natural order of the transient world were widely considered undesirable. Later, in the Middle Ages, the desire for human understanding of nature in terms of reason was revived. This article is concerned with the fundamental reversal of attitudes, from “undesirable” to “desirable”, that eventually led into the foundations of modern science. One of the earliest, most ingenious and most interesting personalities involved was Eriugena, a theologian at the Court of Charles the Bald in the 9th century. Though understanding what we call nature is only one of the several aspects of his theological work, his line of thought implies a turn into a pro-scientific direction: the natural order is to be understood in abstract terms of ‘primordial causes’; understanding nature is considered to be the will of God; man encompasses the whole of creation in a physical as well as a mental sense. Basically similar ideas on the reconciliation of scientific rationality and monotheistic religions of revelation were conceived, independently and nearly simultaneously, by the Arab philosopher al-Kindi in Bagdad. Eriugena was more outspoken in his claim that reason is superior to authority. This claim is implicit in the thought of Nicholas of Cusa with his emphasis on human mental creativity as the image of God’s creativity; and it is the keynote of Galileo’s ‘Letter to the Grand Duchess Christina’ some 800 years later, the manifesto expressing basic attitudes of modern science. This article in English is based on the monography (in German): A. Gierer “Eriugena, al-Kindi, Nikolaus von Kues - Protagonisten einer wissenschaftsfreundlichen Wende im philosophischen und theologischen Denken”, Acta Historica Leopoldina 29 (1999), Barth Verlag in MVH Verlage Heidelberg, ISBN: 3-335-00652-6
Applying mild methods of preparation, part of the ribosomes of rabbit reticulocytes are found in aggregates (later called polyribosomes) of up to six ribosomal units. Upon treatment with RNA-ase, they desintegrate into single ribosomes. The fast-sedimenting aggregates are found to be more active in protein synthesis in terms of incorporation of radioactive amino acids, whereas the single ribosomes are more receptive to stimulation by the artificial messenger RNA poly-U. The findings indicate that the linkage of ribosomes into aggregates is due to the messenger RNA. They support a tape-reading mechanism of protein synthesis whereby growth of the peptide chain is accompanied by shifting the active site of the ribosome from one coding group of nucleotides of the messenger RNA to the next.
Modern science, based on the laws of physics, claims validity for all events in space and time. However, it also reveals its own limitations, such as the indeterminacy of quantum physics, the limits of decidability, and, presumably, limits of decodability of the mind-brain relationship. At the philosophical level, these intrinsic limitations allow for different interpretations of the relation between human cognition and the natural order. In particular, modern science may be logically consistent with religious as well as agnostic views of humans and the universe. These points are exemplified through the transcript of a discussion between Kurt Gödel and Rudolf Carnap that took place in 1940. Gödel, discoverer of mathematical undecidability, took a proreligious view; Carnap, one of the founders of analytical philosophy, an antireligious view. By the time of the discussion, Carnap had liberalized his ideas on theoretical concepts of science: he believed that observational terms do not suffice for an exhaustive definition of theoretical concepts. Then, responded Gödel, one should formulate a theory or metatheory that is consistent with scientific rationality, yet also encompasses theology. Carnap considered such theories unproductive. The controversy remained unresolved, but its emphasis shifted from rationality to wisdom, not only in the Gödel-Carnap discussion but also in our time.
Biological evolution and technological innovation, while differing in many respects, also share common features. In particular, the implementation of a new technology in the market is analogous to the spreading of a new genetic trait in a population. Technological innovation may occur either through the accumulation of quantitative changes, as in the development of the ocean clipper, or it may be initiated by a new combination of features or subsystems, as in the case of steamships. Other examples of the latter type are electric networks that combine the generation, distribution, and use of electricity, and containerized transportation that combines standardized containers, logistics, and ships. Biological evolution proceeds, phenotypically, in many small steps, but at the genetic level novel features may arise not only through the accumulation of many small, common mutational changes, but also when distinct, relatively rare genetic changes are followed by many further mutations. New evolutionary directions may be initiated by, in particular, some rare combinations of regulatory sections within the genome. The combinatorial type of mechanism may not be a logical prerequisite for biological innovation, but it can be efficient, especially when novel features arise out of already highly developed systems. Such is the case with the evolution of general, widely applicable capabilities of the human brain. Hypothetical examples include the evolution of strategic thought, which encompasses multiple self-representations, cognition-based empathy, meta-levels of abstraction, and symbolic language. These capabilities of biologically modern man may have been initiated, perhaps some 150 000 years ago, by one or few accidental but distinct combinations of modules and subroutines of gene regulation which are involved in the generation of the neural network in the cerebral cortex. This hypothesis concurs with current insights into the molecular biology of the combinatorial and hierarchical facets of gene regulation that underlie brain development. A theory of innovation encompassing technological as well as biological development cannot per se dictate alternative explanations of biological evolution, but it may help in adding weight and directing attention to notions outside the mainstream, such as the hypothesis that few distinct genetic changes were crucial for the evolution of modern man.
This is the invited evening lecture of the biannual workshop on hydroid development of 1999. Its topic is the role of hydra as a rather puristic model for the de-novo generation of spatial patterns in development, and our work in this field. Emphasis is placed not only on experimental studies, but also on theoretical analysis, because the understanding of spatial order requires a systems approach involving the combination of knowledge on molecules, cells and tissues with mathematical analysis, laws and facts.
Understanding cooperative human behaviour depends on insights into the biological basis of human altruism, as well as into socio-cultural development. In terms of evolutionary theory, kinship and reciprocity are well established as underlying cooperativeness. Reasons will be given suggesting an additional source, the capability of a cognition-based empathy that may have evolved as a by-product of strategic thought. An assessment of the range, the intrinsic limitations, and the conditions for activation of human cooperativeness would profit from a systems approach combining biological and socio-cultural aspects. However, this is not yet the prevailing attitude among contemporary social and biological scientists who often hold prejudiced views of each other's notions. It is therefore worth noticing that the desirable integration of aspects has already been attempted, in remarkable and encouraging ways, in the history of thought on human nature. I will exemplify this with the ideas of the fourteenth century Arab-Muslim historian Ibn Khaldun. He set out to explicate human cooperativeness - "asabiyah" - as having a biological basis in common descent, but being extendable far beyond within social systems, though in a relatively unstable and attenuated fashion. He combined psychological and material factors in a dynamical theory of the rise and decline of political rulership, and related general social phenomena to basic features of human behaviour influenced by kinship, expectation of reciprocity, and empathic emotions.
Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.
The short paper introduces the concept of possible branches of double-stranded DNA (later sometimes called palindromes): Certain sequences of nucleotides may be followed, after a short unpaired stretch, by a complementary sequence in reversed order, such that each DNA strand can fold back on itself, and the DNA assumes a cruciform or tree-like structure. This is postulated to interact with regulatory proteins.
The development of modern science has depended strongly on specific features of the cultures involved; however, its results are widely and transculturally accepted and applied. The science and technology of electricity, for example, emerged as a specific product of post-Renaissance Europe, rooted in the Greek philosophical tradition that encourages explanations of nature in theoretical terms. It did not evolve in China presumably because such encouragement was missing. The transcultural acceptance of modern science and technology is postulated to be due, in part, to the common biological dispositions underlying human cognition, with generalizable capabilities of abstract, symbolic and strategic thought. These faculties of the human mind are main prerequisites for dynamic cultural development and differentiation. They appear to have evolved up to a stage of hunters and gatherers perhaps some 100 000 years ago. However, the extent of the correspondence between some constructions of the human mind and the order of nature, as revealed by science, is a late insight of the last two centuries. Unless we subscribe to extreme forms of constructivism or historical relativism, we may take the success and the formal structure of science as indications of a close, intrinsic relation between the physical and the mental, between the order of nature and the structure of human cognition. At the metatheoretical level, however, modern science is consistent with philosophical and cultural diversity.
The generation of viral mutants in vitro was demonstrated by treatment of the isolated RNA of Tobacco Mosaic Virus by nitrous acid. This agent causes deaminations converting cytosine into uracil, and adenine into hypoxanthine. Our assay for mutagenesis was the production of local lesions on a tobacco variety on which the untreated strain produces systemic infections only. A variety of different mutants are generated in this way. Quantitative analysis of the kinetics of mutagenesis leads to the conclusion that alteration of a single out of the 6000 nucleotides of the viral RNA is sufficient for causing a mutation.
Aggregates of previously isolated cells of Hydra are capable, under suitable solvant conditions, of regeneration forming complete animals. In a first stage, ecto- and endodermal cells sort out, producing the bilayered hollow structure characteristic of Hydra tissue; thereafter, heads are formed (even if the original cell preparation contained no head cells), eventually leading to the separation of normal animals with head, body column and foot. Hydra appears to be the highest type of organism that allows for regeneration of the entire structure from random cell aggregates. The system is particularly useful for studying cell interactions, tissue polarity, pattern formation, and cell differentiation.
Validity of physical laws for any aspect of brain activity and strict correlation of mental to physical states of the brain do not imply, with logical necessity, that a complete algorithmic theory of the mind-body relation is possible. A limit of decodability may be imposed by the finite number of possible analytical operations which is rooted in the finiteness of the world. It is considered as a fundamental intrinsic limitation of the scientific approach comparable to quantum indeterminacy and the theorems of logical undecidability. An analysis of these limits, applied to dispositions of future behaviour, suggests that limits of decodability of the psycho-physic relation may actually exist with respect to brain states with self-referential aspects, as they are involved in mental processes. Limits for an algorithmic theory of the mind-body problem suggested by this study are formally similar to other intrinsic limits of the scientific method such as quantum indeterminacy and mathematical undecidability which are also related to self-referential operations. At the metatheoretical level, hard sciences, despite their reliability, universality and objectivity, depend on metatheoretical presuppositions which allow for multiple philosophical interpretations.
Socioeconomic inequalities are functions not only of intrinsic differences between persons or groups, but also of the dynamics of their interactions. Inequalities can arise and become stabilized if there are advantages (such as generalized wealth including “human capital”) which are self-enhancing, whereas depletion of limiting resources is widely distributed. A recent theory of biological pattern formation has been generalized, adapted and applied to deal with this process. Applications include models for the non-Gaussian distribution of personal income and wealth, for overall economic growth in relation to inequalities and for effects of uncoupling strategies between developing and developed countries. Note added after publication: The equations (14) for the model of the income distribution, with its characteristic non-Gaussian extension towards higher incomes (fig.4), are closely related to the Fokker-Planck equation that is widely applied in many fields of physics.
Within the sedimentation diagram of infective RNA preparations isolated from Tobacco Mosaic Virus, undegraded molecules form a sharp peak with a molecular weight corresponding to the total RNA content of the virus particle. Degradation kinetics by ribonuclease is of the linear, single-target type, indicating that the RNA is single-stranded. The intact RNA of a virus particle thus forms one big single-stranded molecule. Quantitative evaluation of the effect degradation by RNA-ase on the infectivity of the RNA shows that the integrity of the entire molecule is required for its biological activity.
The introductory personal remarks refer to my motivations for choosing research projects, and for moving from physics to molecular biology and then to development, with Hydra as a model system. Historically, Trembley’s discovery of Hydra regeneration in 1744 was the begin¬ning of developmental biology as we understand it, with passionate debates about preformation versus de novo generation, mechanisms versus organisms. In fact, seemingly conflicting bottom-up and top-down concepts are both required in combination to understand development. In modern terms, this means analysing the molecules involved, as well as searching for physical principles underlying development within systems of molecules, cells and tissues. During the last decade, molecular biology has provided surprising and impressive evidence that the same types of mol¬ecules and molecular systems are involved in pattern formation in a wide range of organisms, including coelenterates like Hydra, and thus appear to have been “invented” early in evolution. Likewise, the features of certain systems, especially those of developmental regulation, are found in many different organisms. This includes the generation of spatial structures by the interplay of self-enhancing activation and “lateral” inhibitory effects of wider range, which is a main topic of my essay. Hydra regeneration is a particularly clear model for the formation of defined patterns within initially near-uniform tissues. In conclusion, this essay emphasizes the analysis of development in terms of physical laws, including the application of mathematics, and insists that Hydra was, and will continue to be, a rewarding model for understanding general features of embryogenesis and regeneration.
Full applicability of physics to human biology does not necessarily imply that one can uncover a comprehensive, algorithmic correlation between physical brain states and corresponding mental states. The argument takes into account that information processing is finite in principle in a finite world. Presumbly the brain-mind-relation cannot be resolved in all essential aspects, particularly when high degrees of abstraction or self-analytical processes are involved. Our conjecture plausibly unifies the universal validity of physics and a logical limitation of human thought, and it does not regard consciousness -the most basic human experience - as a marginal phenomenon. ++++ RATIO appeared up to 1987 in both a German and an English version. The German title of this article: Alfred Gierer, Der physikalische Grundlegungsversuch in der Biologie und das psychophysische Problem. RATIO XII, Heft 1, 1970, S. 40-54.