Contrasting theories of life: Historical context, current theories. In search of an ideal theory.

Most attempts to define life have concentrated on individual theories, mentioning others hardly at all, but here we compare all of the major current theories. We begin by asking how we know that an entity is alive, and continue by describing the contributions of La Mettrie, Burke, Leduc, Herrera, Bahadur, D'Arcy Thompson and, especially, Schrödinger, whose book What is Life? is a vital starting point. We then briefly describe and discuss (M, R) systems, the hypercycle, the chemoton, autopoiesis and autocatalytic sets. All of these incorporate the idea of circularity to some extent, but all of them fail to take account of mechanisms of metabolic regulation, which we regard as crucial if an organism is to avoid collapsing into a mass of unregulated reactions. In a final section we study the extent to which each of the current theories can aid in the search for a more complete theory of life, and explain the characteristics of metabolic control analysis that make it essential for an adequate understanding of organisms.

Special issue: mathematical methods in the biosciences.

The special issue is available from: https://www.aimspress.com/newsinfo/1079.html/.

Systems biology of meristems: an interview with Teva Vernoux.

Teva Vernoux is a plant developmental biologist and holds positions as the Director of the Institute for Reproduction and Development of Plants at ENS de Lyon, and as a Research Director at Centre National de la Recherche Scientifique. Teva spoke to us about the need for multidisciplinary approaches to tackle multi-scale problems, how to go beyond a list of genes, and the importance of constructive reviews.

Homage to Eric Davidson.

The Britten-Davidson model of genetic regulation was well received by American molecular biologists and embryologists, but not by the members of the French School of molecular biology. In particular, François Jacob considered it too abstract and too removed from experiments. I re-examine the contrast between the Britten-Davidson model and the operon model by Jacob and Monod, the different scientific contexts in which they were produced and the different roles they played. I also describe my recent encounters with Eric Davidson, and how I discovered the extraordinary continuity of his work on the development of the sea urchin, as well as his rich personality.

Hierarchy, determinism, and specificity in theories of development and evolution.

The concepts of hierarchical organization, genetic determinism and biological specificity (for example of species, biologically relevant macromolecules, or genes) have played a crucial role in biology as a modern experimental science since its beginnings in the nineteenth century. The idea of genetic information (specificity) and genetic determination was at the basis of molecular biology that developed in the 1940s with macromolecules, viruses and prokaryotes as major objects of research often labelled "reductionist". However, the concepts have been marginalized or rejected in some of the research that in the late 1960s began to focus additionally on the molecularization of complex biological structures and functions using systems approaches. This paper challenges the view that 'molecular reductionism' has been successfully replaced by holism and a focus on the collective behaviour of cellular entities. It argues instead that there are more fertile replacements for molecular 'reductionism', in which genomics, embryology, biochemistry, and computer science intertwine and result in research that is as exact and causally predictive as earlier molecular biology.

TRIENNIAL LACTATION SYMPOSIUM/BOLFA:Historical perspectives of lactation biology in the late 20th and early 21st centuries.

The latter half of the 20th century and the early portion of the 21st century will be recognized as the "Golden Age" of lactation biology. This period corresponded with the rise of systemic, metabolomic, molecular, and genomic biology. It includes the discovery of the structure of DNA and ends with the sequencing of the complete genomes of humans and all major domestic animal species including the dairy cow. This included the ability to identify polymorphisms in the nucleic acid sequence, which can be tied to specific differences in cellular, tissue, and animal performance. Before this period, classical work using endocrine ablation and replacement studies identified the mammary gland as an endocrine-dependent organ. In the early 1960s, the development of RIA and radioreceptor assays permitted the study of the relationship between endocrine patterns and mammary function. The ability to measure nucleic acid content of tissues opened the door to study of the factors regulating mammary growth. The development of high-speed centrifugation in the 1960s allowed separation of specific cell organelles and their membranes. The development of transmission and scanning electron microscopy permitted the study of the relationship between structure and function in the mammary secretory cell. The availability of radiolabeled metabolites provided the opportunity to investigate the metabolic pathways and their regulation. The development of concepts regarding the coordination of metabolism to support lactation integrated our understanding of nutrient partitioning and homeostasis. The ability to produce recombinant molecules and organisms permitted enhancement of lactation in farm animal species and the production of milk containing proteins of value to human medicine. These discoveries and others contributed to vastly increased dairy farm productivity in the United States and worldwide. This review will include the discussion of the centers of excellence and scientists who labored in these fields to produce the harvest of knowledge we enjoy today.

Mechanists Must be Holists Too! Perspectives from Circadian Biology.

The pursuit of mechanistic explanations in biology has produced a great deal of knowledge about the parts, operations, and organization of mechanisms taken to be responsible for biological phenomena. Holist critics have often raised important criticisms of proposed mechanistic explanations, but until recently holists have not had alternative research strategies through which to advance explanations. This paper argues both that the results of mechanistic strategies has forced mechanists to confront ways in which whole systems affect their components and that new representational and modeling strategies are providing tools for understanding these effects of whole systems upon components. Drawing from research on the mechanism responsible for circadian rhythms in mammals, I develop two examples in which mechanistic analysis is being integrated into a more holist perspective: research revealing intercellular integration of circadian mechanisms with those involved in cell metabolism and research revealing that stable␣rhythms are dependent on how individual cells in the suprachiasmatic nucleus synchronize with each other to generate regular rhythms. Tools such as network diagramming and computational modeling are providing means to integrate mechanistic models into accounts of whole systems.

Ludwig von Bertalanffy's organismic view on the theory of evolution.

Ludwig von Bertalanffy was a key figure in the advancement of theoretical biology. His early considerations already led him to recognize the necessity of considering the organism as a system, as an organization of parts and processes. He termed the resulting research program organismic biology, which he extended to all basic questions of biology and almost all areas of biology, hence also to the theory of evolution. This article begins by outlining the rather unknown (because often written in German) research of Bertalanffy in the field of theoretical biology. The basics of the organismic approach are then described. This is followed by Bertalanffy's considerations on the theory of evolution, in which he used methods from theoretical biology and then introduced his own, organismic, view on evolution, leading to the demand for finding laws of evolution. Finally, his view on the concept of homology is presented.

Metabonomics and systems biology.

Systems biology represents an integrative research strategy that studies the interactions between DNA, mRNA, protein, and metabolite level in an organism, thereby including the interactions with the physical environment and other organisms. The application of metabonomics, or the quantitative study of metabolites in biological systems, in systems biology is currently an emerging area of research, which can contribute to the discovery of (disease) signatures, drug targeting and design, and the further elucidation of basic and more complex biochemical principles. This chapter covers the contribution of metabonomics in advancing our understanding in systems biology.