Linking physiological mechanisms of coherent cellular behaviour with more general physical approaches towards the coherence of life

Schr?dinger pointed out that one of the most fundamental properties of life is its coherent behaviour. This property has been approached from a physiological point of view by Ling in his 'association-induction hypothesis' and extended by Pollack (gel-sol theory), by Chaplin and by Kaivarainen (detailed studies of cellular water). The question of coherence has also been attacked from general physics in three independent approaches: from non-linear thermodynamics (Fr?hlich), from quantum field theory (Del Giudice and his group) and from quantum mechanics (Davydov). In this paper all these approaches are unified. The emerging picture constitutes a new paradigm of life.     

Hansemann, Boveri, chromosomes and the gametogenesis-related theories of tumours

Theodor Boveri (1862-1915) is often credited with suggesting (in 1914) the first chromosomal theory of cancer, especially in terms of abnormal numbers of chromosomes arising in cells by multipolar mitoses in adult cells. However, multipolar mitoses in animal cells had been described as early as 1875, and Hansemann (1858-1920), in publications between 1890 and 1919, included this mechanism among various ways by which abnormal chromosome numbers might arise in cells and cause tumour formation. Both theories were conceived in a period when gametogenic ideas of tumour formation were current. Boveri based his theory on the observation that some cells in early sea urchin embryos having abnormal chromosome complements wander from their usual developmental paths. His observation may have been seen by other authors at the time as support for Cohnheim's "embryonic cell rest" theory of cancer. Hansemann's contribution is seen as both the original, and the more significant of the chromosomal theories of cancer.     

Fashioning the Immunological Self: The Biological Individuality of F. Macfarlane Burnet

During the 1940s and 1950s, the Australian microbiologist F. Macfarlane Burnet sought a biologically plausible explanation of antibody production. In this essay, we seek to recover the conceptual pathways that Burnet followed in his immunological theorizing. In so doing, we emphasize the influence of speculations on individuality, especially those of philosopher Alfred North Whitehead; the impact of cybernetics and information theory; and the contributions of clinical research into autoimmune disease that took place in Melbourne. We point to the influence of local experimental and intellectual currents on Burnet’s work. Accordingly, this essay describes an arc distinct from most other tracings of Burnet’s conceptual development, which focus on his early bacteriophage research, his fascination with the work of Julian Huxley and other biologists in the 1920s, and his interest in North Atlantic experimental investigations in the life sciences. No doubt these too were potent influences, but they seem insufficient to explain, for example, Burnet’s sudden enthusiasm in the 1940s for immunological definitions of self and not-self. We want to demonstrate here how Burnet’s deep involvement in philosophical biology – along with attention to local clinical research – provided him with additional theoretic tools and conceptual equipment, with which to explain immune function.     

Pragmatic turn in biology: From biological molecules to genetic content operators

Erwin Schrdinger‘s question "What is life?" received the answer for decades of "physics + chemistry". The concepts of Alain Turing and John von Neumann introduced a third term: "information". This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings "sequence space". Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract "sequence space" concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry.     

From the "Modern Synthesis" to cybernetics: Ivan Ivanovich Schmalhausen (1884-1963) and his research program for a synthesis of evolutionary and developmental biology

Ivan I. Schmalhausen was one of the central figures in the Russian development of the "Modern Synthesis" in evolutionary biology. He is widely cited internationally even today. Schmalhausen developed the main principles of his theory facing the danger of death in the totalitarian Soviet Union. His great services to evolutionary and theoretical biology are indisputable. However, the received view of Schmalhausen's contributions to evolutionary biology makes an unbiased reading of his texts difficult. Here we show that taking all of his works into consideration (including those only available in Russian) paints a much more dynamic and exciting picture of what he tried to achieve. Schmalhausen pioneered the integration of a developmental perspective into evolutionary thinking. A main tool for achieving this was his approach to living objects as complex multi-level self-regulating systems. Schmalhausen put enormous effort into bringing this idea into fruition during the final stages of his career by combining evolutionary theory with cybernetics. His results and ideas remain thought-provoking, and his texts are of more than just historical interest.     

The Biophysics of Regenerative Repair Suggests New Perspectives on Biological Causation

Evolution exploits the physics of non-neural bioelectricity to implement anatomical homeostasis: a process in which embryonic patterning, remodeling, and regeneration achieve invariant anatomical outcomes despite external interventions. Linear “developmental pathways” are often inadequate explanations for dynamic large-scale pattern regulation, even when they accurately capture relationships between molecular components. Biophysical and computational aspects of collective cell activity toward a target morphology reveal interesting aspects of causation in biology. This is critical not only for unraveling evolutionary and developmental events, but also for the design of effective strategies for biomedical intervention. Bioelectrical controls of growth and form, including stochastic behavior in such circuits, highlight the need for the formulation of nuanced views of pathways, drivers of system-level outcomes, and modularity, borrowing from concepts in related disciplines such as cybernetics, control theory, computational neuroscience, and information theory. This approach has numerous practical implications for basic research and for applications in regenerative medicine and synthetic bioengineering.     

Balfour, Garstang and de Beer: The First Century of Evolutionary Embryology

Evolution has been integrated with embryology during two greatperiods: the latter half of the 19th C as evolutionary morphology/embryology,and the latter third of the 20th C as evolutionary developmentalbiology. My mandate was to use the contributions of three embryologists/morphologists:Francis (Frank) Balfour (1851–1882), Walter Garstang (1868–1949)and Gavin de Beer (1899–1972) to discuss the foundationsof evolutionary embryology in the UK from 1870 (when "everyaspiring zoologist was an embryologist, and the one topic ofprofessional conversation was evolution," Bateson, 1922, p.56), through the 1920s ("ontogeny does not recapitulate phylogeny,it creates it," Garstang, 1922, p. 81) to the 1970s ("homologyof phenotypes does not imply similarity in genotypes," de Beer,1971, p. 15). Evolutionary embryology was driven by a comparativeembryological approach that sought homology of adult structuresin germ layers and ancestry in embryos, and sought to differentiatelarval adaptations from retained ancestral characters. An initialemphasis on a phylogenetic mechanism (recapitulation) slowlygave way to more mechanistic approaches that included heterochronyand the integration of embryology with physiological genetics.Germ layers, homology, larval evolution, larval origins of thevertebrates, paedomorphosis and heterochrony underpinned theorigins of evolutionary embryology, and so I discuss each ofthese topics.     

In vitro approaches to the elucidation of mechanisms of chemical teratogenesis.

This article describes some of the contributions that in vitro methods have made to our progress, albeit slow, toward understanding mechanisms of chemical teratogenesis. Emphasis is given to the painstaking and time consuming nature of approaches required to elucidate mechanisms. The examples considered are cyclophosphamide, 2-methoxyethanol, and retinoids. Some of the newer methods that take advantage of the recent advances in molecular biology and analytical chemistry have already been applied to studies on teratogenic mechanisms. Prospects for the 1990s are excellent and promise more rapid progress than during the past decade toward unraveling the mysteries of normal developmental biology. That knowledge in turn should be immediately applicable for investigations on developmental toxicant-induced abnormal development.     

How neurochemistry regained its specific biological components: Experimental and cognitive advance, 1935–1955

Neurochemistry in the 1850s was part of comparative animal chemistry, which became incorporated into physiological chemistry. By 1900, the connection with physiological chemistry had largely lapsed or been vehemently repudiated. Growth of biochemistry, especially from the 1920s to 1950s, provided techniques and findings sufficient to reintegrate chemical knowledge of neural systems with neural functioning. Vitamin, coenzyme, respiratory and other metabolic studies made large contributions to this outcome. Regarding mental illness as a social problem and scientific challenge gave impetus and funds to such work, which resulted in major experimental and cognitive progress.Special issue dedicated to Dr. Louis Sokoloff.     

Systematisch-nomenklatorische Bemerkungen zur Flora Mitteleuropas mit Beziehungen zur südosteuropäischen Flora

The author enumerates all the critical taxonomical-nomenclatural notes to the results of his „Synopsis systematica-geobotanica Florae Vegetationisque Hungariae”︁, I. — V. (1964–1972), and, according to his view, such referring to the modern floras of central Europe (Hegi ed. 2 1957–1970, Janchen 1956–1960, 1963–1967, Rothmaler 1963, Schmeil-Fitschen edit. Rauh-Senghas 1968, Oberdorfer 1970, Hess-Landolt-Hirzel 1970, Dostál 1950, 1958, etc.). He reports on many species aggregates, critical species, and many new combinations. Often he makes references to the near related southeast and east European taxa. Specially he reports on some species of the genera Aconitum, Aquilegia, Centaurea, Dactylorhiza, Dianthus, Festuca, Galium, Melampyrum, Potentilla, Rhinanthus, Thymus, Valeriana, etc. He also deals with such hybrids occuring in central Europe but are missing in Janchen's and Rothmaler's floras.     

Ion mobility–mass spectrometry for structural proteomics

Ion mobility coupled to mass spectrometry has been an important tool in the fields of chemical physics and analytical chemistry for decades, but its potential for interrogating the structure of proteins and multiprotein complexes has only recently begun to be realized. Today, ion mobility–mass spectrometry is often applied to the structural elucidation of protein assemblies that have failed high-throughput crystallization or NMR spectroscopy screens. Here, we highlight the technology, approaches and data that have led to this dramatic shift in use, including emerging trends such as the integration of ion mobility–mass spectrometry data with more classical (e.g., ‘bottom-up’) proteomics approaches for the rapid structural characterization of protein networks.     

From computational quantum chemistry to computational biology: experiments and computations are (full) partners

Computations are being integrated into biological research at an increasingly fast pace. This has not only changed the way in which biological information is managed; it has also changed the way in which experiments are planned in order to obtain information from nature. Can experiments and computations be full partners? Computational chemistry has expanded over the years, proceeding from computations of a hydrogen molecule toward the challenging goal of systems biology, which attempts to handle the entire living cell. Applying theories from ab initio quantum mechanics to simplified models, the virtual worlds explored by computations provide replicas of real-world phenomena. At the same time, the virtual worlds can affect our perception of the real world. Computational biology targets a world of complex organization, for which a unified theory is unlikely to exist. A computational biology model, even if it has a clear physical or chemical basis, may not reduce to physics and chemistry. At the molecular level, computational biology and experimental biology have already been partners, mutually benefiting from each other. For the perception to become reality, computation and experiment should be united as full partners in biological research.     

Comparison of Caplan's Irreversible Thermodynamic Theory of Muscle Contraction with Chemical Data

Recently Caplan (1) applied the concepts of irreversible thermodynamics and cybernetics to contracting muscle and derived Hill's force-velocity relation. Wilkie and Woledge (2) then compared Caplan's theory to chemical rates inferred from heat data and concluded that the theory was not consistent with the data. Caplan defended his theory in later papers (3, 4) but without any direct experimental verifications. As Wilkie and Woledge (2) point out, the rate of phosphorylcreatine (PC) breakdown during steady states of shortening has not been observed because of technical difficulties. In this paper it is shown that the rate equations may be directly integrated with time to obtain relations among actual quantities instead of rates. The validity of this integration is based on experimental evidence which indicates that certain combinations of the transport coefficients are constant with muscle length. These equations are then directly compared to experimental data of Cain, Infante, and Davies (5) with the following conclusions: (a) The measured variations of ΔPC for isotonic contractions are almost exactly as predicted by Caplan's theory. (b) The value of the chemical rate ratio, ν_m/ν_o, obtained from these data was 3.53 which is close to the value of 3 suggested by Caplan (3). (c) The maximum value of the chemical affinity for PC splitting was found to be 10.6 k cal/mole which is as expected from in vitro measurements (2). Because of the excellent agreement between theory and experiment, we conclude that Caplan's theory definitely warrants further investigation.     

Epigenetic landscaping: Waddington's use of cell fate bifurcation diagrams

From the 1930s through the 1970s, C. H. Waddington attempted to reunite genetics, embryology, and evolution. One of the means to effect this synthesis was his model of the epigenetic landscape. This image originally recast genetic data in terms of embryological diagrams and was used to show the identity of genes and inducers and to suggest the similarities between embryological and genetic approaches to development. Later, the image became more complex and integrated gene activity and mutations. These revised epigenetic landscapes presented an image of how mutations could alter developmental pathways to yield larger phenotypic changes. These diagrams became less important as the operon became used to model differential gene regulation.     

AGE, EGG-SIZE AND BREEDING SUCCESS IN THE HERRING GULL LARUS ARGENTATUS

The breeding biology of the Herring Gull Larus argentatus was studied in 1969, 1970 and 1972 on Skokholm, Pembrokeshire. The distribution of laying dates in three years is given; median laying date was always about 10 May. Laying dates of individual pairs were fairly constant between two years, but females up to nine years of age apparently advanced their laying date in successive years. In 1969 there was a decline in clutch-volume index during the season but this was not found in 1970 or 1972. Females laid clutches of similar volume in successive years, although the volume did vary with age, increasing up to 7 or 8 years of age and then declining. Hatching success was highest in the earliest of four periods in 1970 (69%) and lowest in the last (51%); in 1972 the corresponding figures were 71% and 63% and the seasonal trend was not significant. Chick mortality was higher in 1970 (69%) than in 1972 (59%); in 1970 there was significant seasonal variation in chick survival but in 1972 there was not. In 1970 chick survival was positively correlated with hatching weight (and hence egg-size) and chick survival was also related to growth which was itself correlated with hatching weight. There were no such correlations in 1972. Mean chick production in 1970 was 0.60 per pair and in 1972 0.70. In both years later breeders were less successful, but the seasonal range of mean success was less in 1972. In the discussion it is shown that some of these differences between years could be due to changes in the age structure of the population and it is suggested that the correlation between egg-size and chick survival in 1970 may be an artefact of the age structure.     

A bridge-builder: Wolf-Ernst Reif and the Darwinisation of German paleontology

Wolf-Ernst Reif was an outstanding German paleontologist, who, along with his empirical studies (biomechanics, functional and constructional morphology, etc.), paid significant attention to theoretical issues and the history of his discipline. Reif was a bridge-builder, skillfully synthesising history, theory and empirical studies within German-language paleontology. This paper briefly discusses sophisticated relationships between German paleontology and Darwinism based on the historical studies of Wolf-Ernst Reif. German paleontology did not fully embrace Darwinism until the 1970s. There are several reasons for this. First, alternative evolutionary theories (saltationism, neo-Lamarckism, orthogenesis) occupied a significant segment of the theoretical landscape in the German life sciences. Second, typological thinking persisted in German paleontology after the Second World War. Third, German paleontologists were relatively uninterested in discussing mechanisms of evolution, concentrating instead on reconstructing phylogenetic history.     

Bolkian and Bokian Retardation in Homo Sapiens

Although a low genetic barrier is said to separate humans from apes, Homo sapiens is characterized by striking developmental and anatomical particularities. On the one hand, humans have a very extended life history (retardation). On the other hand, human anatomy shows many instances of both neoteny and hypermorphosis.In 1918, Bolk proposed his 'retardation theory' that links both aspects of the human condition. We show in this paper that his theory becomes surprisingly powerful when Bolk's retardation principle is applied to generalized developmental gradients (such as the cephalocaudal gradient that dominates overall ontogeny). In this way, the main particularities of the human body (extended life history; long limbs, and very long legs; very low brachial and crural indices; highly developed pollex and hallux; reduced prognathism; advanced telencephalization etc.) can be reduced to a single developmental matrix.In 1926, Bok noted that, in a series of equivalent organs (such as the finger row), the ontogenetic latecomer tends to be more neotenic than a corresponding forerunner. We show that Bok's observation is a logical corollary of Bolk's retardation theory and that it is important for understanding some pecularities of human anatomy such as the pronounced differentiation between hands and feet.