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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.
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.
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.
The topic of this article is the relation between bottom-up and top-down, reductionist and “holistic” approaches to the solution of basic biological problems. While there is no doubt that the laws of physics apply to all events in space and time, including the domains of life, understanding biology depends not only on elucidating the role of the molecules involved, but, to an increasing extent, on systems theoretical approaches in diverse fields of the life sciences. Examples discussed in this article are the generation of spatial patterns in development by the interplay of autocatalysis and lateral inhibition; the evolution of integrating capabilities of the human brain, such as cognition-based empathy; and both neurobiological and epistemological aspects of scientific theories of consciousness and the mind.
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.
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.
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.
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.
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.
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.