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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 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.
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.
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.
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.
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.
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.
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.
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 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.