Overcoming the Newtonian paradigm: The unfinished project of theoretical biology from a Schellingian perspective

Defending Robert Rosen's claim that in every confrontation between physics and biology it is physics that has always had to give ground, it is shown that many of the most important advances in mathematics and physics over the last two centuries have followed from Schelling's demand for a new physics that could make the emergence of life intelligible. Consequently, while reductionism prevails in biology, many biophysicists are resolutely anti-reductionist. This history is used to identify and defend a fragmented but progressive tradition of anti-reductionist biomathematics. It is shown that the mathematico–physico–chemical morphology research program, the biosemiotics movement, and the relational biology of Rosen, although they have developed independently of each other, are built on and advance this anti-reductionist tradition of thought. It is suggested that understanding this history and its relationship to the broader history of post-Newtonian science could provide guidance for and justify both the integration of these strands and radically new work in post-reductionist biomathematics.     

Between history and physics

Biology has traditionally occupied a middle ground between the determinism of classical physics and the uncertainties of history. These issues are analyzed with respect to statistical laws which are applied to the prebiotic domain and strategy laws which characterize evolutionary biology. The differences in approach between biology and physics are discussed in detail. The origin of life is discussed in the context of physical chemical laws. A scenario for biogenesis is presented in terms of known molecular hardware. Evolutionary biology is then examined with respect to the kinds of laws that are possible in a domain where thermal fluctuations (mutations) have macroscopic effects. Game theory is employed to demonstrate the kinds of theory appropriate to this historical domain. The transition point between physics and history is the origin and development of the code. This is discussed and it is concluded that we are not yet able to assign the code to either the deterministic domain or to the arena of history.     

Are There Laws of Genome Evolution?

Research in quantitative evolutionary genomics and systems biology led to the discovery of several universal regularities connecting genomic and molecular phenomic variables. These universals include the log-normal distribution of the evolutionary rates of orthologous genes; the power law-like distributions of paralogous family size and node degree in various biological networks; the negative correlation between a gene's sequence evolution rate and expression level; and differential scaling of functional classes of genes with genome size. The universals of genome evolution can be accounted for by simple mathematical models similar to those used in statistical physics, such as the birth-death-innovation model. These models do not explicitly incorporate selection; therefore, the observed universal regularities do not appear to be shaped by selection but rather are emergent properties of gene ensembles. Although a complete physical theory of evolutionary biology is inconceivable, the universals of genome evolution might qualify as "laws of evolutionary genomics" in the same sense "law" is understood in modern physics.     

Methodological problems of the relation of thermodynamics and biology

Methodological problems are considered on the relation of thermodynamic principles in systems far from being equilibrium and processes of biological evolution. Attention is paid that these problems are sometimes erroneously interpreted from the standpoint of reducing biology to physics and chemistry. The analysis of the theories under study shows that they reveal concretely the dialectics of biology reducibility and irreducibility to physics and chemistry. A conclusion is made that the notion of "submission of lower forms of the matter to higher ones" which is insufficiently studied in dialectics may be revealed by means of notions of lower forms regulation and control by higher ones.     

The 'atom-splitting' moment of synthetic biology. Nuclear physics and synthetic biology share common features

Synthetic biology and nuclear physics share many commonalities in terms of public perception and funding. Synthetic biologists could learn valuable lessons from the history of the atomic bomb and nuclear power.On 16 July 1945, in the desert of New Mexico, the first nuclear bomb was exploded. It was a crucial moment in the history of the physical sciences—proof positive of the immense forces at work in the heart of atoms—and inevitably changed the world. In 2010, a team at the J. Craig Venter Research Institute in the USA first created artificial life by inserting a synthetic 1.08 megabase pair genome into a mycoplasma cell that lacked its own. They demonstrated that this new cell with its man-made genome was capable of surviving and reproducing [1]. It was a colossal achievement for biology, and its significance might well rank alongside the detonation of the first atomic bomb in terms of scientific advance.…as with post-war physics, synthetic biology''s promises of a brighter future might not all materialize and could have far-reaching effects on society, science and politicsThere are several similarities between twentieth century physics, and twentieth and twenty-first century biology. The nuclear explosion in New Mexico was the result of decades of research and the first splitting of an atom in Otto Hahn''s laboratory in 1938. It ushered in an era of new ideas and hopes for a brighter future built on the power of the atom, but the terrible potential of nuclear weapons and the threat of nuclear warfare ultimately overshadowed these hopes and changed the course of science and politics. The crucial achievement of synthetic life is a strikingly similar event; the culmination of decades of research that started with its own atom-splitting moment: recombinant DNA technology. It promises to bring forth a new era for biology and enable a huge variety of applications for industry, medicine and the military. However, as with post-war physics, synthetic biology''s promises of a brighter future might not all materialize and could have far-reaching effects on society, science and politics. Biology should therefore take note of the consequences of nuclear physics'' iconic event in 1945 for science, politics and society.To appreciate the similarities of these breakthroughs and their consequences for society, it is necessary to understand the historical perspective. The pivotal discoveries for both disciplines were related to fundamental elements of nature. The rise of nuclear physics can be traced back to the discovery of neutrons by James Chadwick in 1932 [2]. Neutrons are essential to the stability of atoms as they insulate the nucleus against the repulsive forces of its positively charged protons. However, the addition of an extra neutron can destabilize the nucleus and cause it to split, releasing more neutrons and a tremendous amount of energy. This nuclear fission reaction was first described by Otto Hahn and Fritz Strassmann in 1938. Leo Szilard realized the possibility of using the neutrons released from the fission of heavy atoms to trigger a nuclear chain reaction to release huge quantities of energy. The first successful chain reactions took place in 1942 in Germany at Leipzig University in the laboratory of Robert Döpel, and in the USA at the University of Chicago in the so-called Chicago Pile-1 reactor, developed by Enrico Fermi. These first nuclear reactors provided the proof of concept for using a nuclear chain reaction as a source of energy. However, even before that, Albert Einstein and Leo Szilard wrote to US President Franklin D. Roosevelt in 1939, suggesting that the US government should develop a new powerful bomb based on nuclear fission. President Roosevelt created the Manhattan Project, which developed the first atomic bomb in 1945.Similarly to nuclear physics, the advent of rDNA technology has concerned the public…The Cold War and the mutually assured nuclear destruction between the USA and the USSR fanned widespread fears about a nuclear Third World War that could wipe out human civilization; Robert Oppenheimer, one of the physicists who developed the atomic bomb, was actually among the first to warn of the spectre of nuclear war. By contrast, the civilian use of nuclear physics, mainly in the form of nuclear reactors, promised a brave new future based on harnessing the power of the atom, but it also generated increasing concerns about the harmful effects of radioactivity, the festering problems of nuclear waste and the safety of nuclear power plants. The nuclear disasters at the Chernobyl reactor in 1986 and the Fukushima power plant in 2011 heightened these concerns to the point that several nations might now abandon nuclear energy altogether.The fundamental discovery in biology, crucial to the creation of synthetic organisms was the double helix structure of DNA in 1953 by Francis Crick and James Watson [3]. The realization that DNA molecules have a universal chemical structure to store and pass on genetic information was the intellectual basis for the development of recombinant DNA (rDNA) technology and genetic engineering. Twenty years after this discovery, Stanley Cohen and Herbert Boyer first transferred DNA from one organism into another by using endonucleases and DNA ligases [4]. This early toolkit was later expanded to include DNA sequencing and synthesizing technologies as well as PCR, which culminated in the creation of the first artificial organism in 2010. Craig Venter''s team synthesized a complete bacterial chromosome from scratch and transferred it into a bacterial cell lacking a genome: the resulting cell was able to synthesize a new set of proteins and to replicate. This proof of concept experiment now enables scientists to pursue further challenges, such as creating organisms with fully designed genomes to achieve agro-biotechnological, commercial, medical and military goals.Similarly to nuclear physics, the advent of rDNA technology has concerned the public, as many fear that genetically modified bacteria could escape the laboratory and wreak havoc, or that the technology could be abused to create biological weapons. Unlike with nuclear physics, the scientists working on rDNA technology anticipated these concerns very early on. In 1974, a group of scientists led by Paul Berg decided to suspend research into rDNA technology to discuss possible hazards and regulation. This discussion took place at a meeting in Asilomar, California, in 1975 [5].A pertinent similarity between these two areas of science is the confluence of several disciplines to create a hybrid technoscience, in which the boundaries between science and technology have become transient [6]. This convergence was vital for the success of both nuclear physics and later synthetic biology, which combines biotechnology, nanotechnology, information technologies and other new fields that have been created along the way [7]. In physics, technoscience received massive support from the government when the military potential of nuclear fission was realized. Although the splitting of the atom took place before the Manhattan Project, the Second World War served as a catalyst to combine research in nuclear physics with organized and goal-directed funding. As most of this funding came from the government, it changed the relationship between politics and research, as scientists were employed to meet specific goals. In the wake of the detonation of the first atomic bombs, the post-war period was another watershed moment for politics, technoscience, industry and society as it generated new and more intimate relationships between science and governments. These included the appointment of a scientific advisor to the President of the USA, the creation of funding organizations such as the National Science Foundation, or research organizations such as the National Aeronautics and Space Administration, and large amounts of federal funding for technoscience research at private and public universities. It also led to the formation of international organizations such as the civilian-controlled International Atomic Energy Agency [6].There is no global war to serve as a catalyst for government spending on synthetic biology. Although the research has benefited tremendously from government agencies and research infrastructure, the funding for Venter''s team largely came from the private sector. In this regard, the relationship between biological techno-science and industry might already be more advanced than with the public sector given the enormous potential of synthetic life for industrial, medical and environmental applications.Research and innovation at universities has always played a vital role in the success of industry-based capitalism [8]; technoscience is now the major determinant of a knowledge-based economy or ''technocapitalism'' [9]. At the heart of technocapitalism are private and public organizations, driven by research and innovation, which are in sharp contrast to industrial capitalism, where the factories were production-driven and research was of less importance [10]. Furthermore, synthetic biology might provide valuable resources to the scientific community and thereby generate new research opportunities and directions for many biological fields [11].However, given the far-reaching implications of creating synthetic life and the risk of abuse, it is probable that the future relationship between synthetic biology and government will include issues of national security. In the light of potential misuse of synthetic biology for bioterrorism, and the safety risks involved in commercial applications, synthetic biology will eventually require some government regulation and oversight. In contrast to nuclear physics, in which the International Atomic Energy Commission was established only after the atomic bomb, the synthetic biology community should hold a new Asilomar meeting to address concerns and formulate guidelines and management protocols, rather than waiting for politicians or commercial enterprises to regulate the field.So far, synthetic biology differs from nuclear physics in terms of handling information. The Manhattan Project inevitably created a need for secrecy as it was created at the height of the Second World War, but the research maintained this shroud of secrecy after the war. After the bombing of Hiroshima and Nagasaki in August 1945, the US government released carefully compiled documents to the American public. The existence of useable nuclear power had been secret until then, and the control of information ensured that the public further supported or tolerated the technology of nuclear fission and the subsequent use of atomic bombs [12]. This initially positive view changed in the ensuing decades with the threat of a global nuclear war.…synthetic biology has side-stepped the mistakes of nuclear physics and might well achieve a more balanced public integration of future developmentsInformation management in synthetic biology differs from nuclear physics, in that most of the crucial breakthroughs are immediately published in peer-reviewed journals and covered by the media. The value of early public discourse on science issues is evident from the reaction towards genetically modified crops and stem cell research. In this regard, synthetic biology has side-stepped the mistakes of nuclear physics and might well achieve a more balanced public integration of future developments.The main issues that might threaten to dampen public support for synthetic biology and favourable public perception are ethics and biosecurity concerns. Ethical concerns have already been addressed in several forums between scientists and public interest groups; this early engagement between science and society and their continuing dialogue might help to address the public''s ethical objections. In terms of biosecurity, biology might learn from nuclear physics'' intimate entanglement with politics and the military. Synthetic biologists should maintain control and regulation of their research and avoid the fate of nuclear physicists, who were recruited to fight the Cold War and were not free to pursue their own research. For synthetic biology to stay independent of government, industry and society, it must capitalize on its public engagement and heed the lessons and mistakes of nuclear physics'' atom-splitting moment. It should not just evaluate, discuss and address the risks for human or environmental health or biosafety concerns, but should also evaluate potential risks to synthetic biology research itself that could either come from falling public acceptance or government intrusion.? Open in a separate windowAlex J ValentineOpen in a separate windowAleysia KleinertOpen in a separate windowJerome Verdier     

Physical explanations and biological explanations,empirical laws and a priori laws

Philosophers intent upon characterizing the difference between physics and biology often seize upon the purported fact that physical explanations conform more closely to the covering law model than biological explanations. Central to this purported difference is the role of laws of nature in the explanations of these two sciences. However, I argue that, although certain important differences between physics and biology can be highlighted by differences between physical and biological explanations, these differences are not differences in the degree to which those explanations conform to the covering law model, which fits biology about as well as it does physics.     

Towards a theory of meaning in biology: a proposal for an operative definition.

Information is a concept developed inside the context of computational and computer sciences. Entropy is a concept developed inside physics context. The best concept in biology is that of "meaning" which is quite impossible to be measured as stated by some examples which are reported. A suggestion to develop a discussion in order to obtain an integration of these concepts inside the general problems of evolutionary biology is here reported to the attention of researchers.     

The chemical hunt for the identification of drugable targets

Chemical biology has emerged as a new scientific discipline to change the way scientists approach and study the interface between chemistry, biology, and physics. By integrating the knowledge base of the human genome with the power of diverse and flexible chemical technology platforms, the ultimate goal is to define the 'rules of engagement' for small molecules and their use in basic biology and in drug discovery. Herein, we highlight the current counterpoles of the chemical biology philosophy in the framework between conformational diversity and informational complexity. Expanding the growing molecular recognition information matrix into classification of diseases and immediate mechanistic in-vivo proof of concept models represent the next development phase in a field that, unlike any other due to its multidisciplinary nature, unifies basic scientists and drug discoverers.     

The cause of growth processes

Transformation of fundamental ideas of physics into the biology has created biodynamics. In this paper, biodynamics has brought into a greater frame of physics and biology, and so stand out the connections at heart between both branches of knowledge. By the help of the idea of force, it will be possible to develop a bio-technics out of the bio-science, similar the developing of technics out of the physics.     

Combining microscience and neurobiology

There is a wide range of literature on soft lithography, organic surface science (especially self-assembled monolayers of organic thiols adsorbed on gold) and microfluidics. These areas have developed in the fields of physical and surface chemistry, materials science and condensed matter physics, but they offer broad new capabilities in the development of relevant micro- and nanosystems to users in biology in general, and in cell biology in particular. The ability to integrate these techniques for fabricating materials and for controlling the chemistry of surfaces with electrical and electrochemical measurements should be especially relevant in neurobiology. The major impediment to the development of a field of 'microfabrication and measurement' in neuroscience is the absence of effective collaborative interactions between the communities of fabricators and neurobiologists.     

The Hydra model - a model for what?

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 beginning 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 molecules 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.     

Signs and Instruments: The Convergence of Aristotelian and Kantian Intuitions in Biosemiotics

Biosemiotics—a discipline in the process of becoming established as a new research enterprise—faces a double task. On the one hand it must carry out the theoretical and experimental investigation of an enormous range of semiotic phenomena relating organisms to their internal components and to other organisms (e.g., signal transduction, replication, codes, etc.). On the other hand, it must achieve a philosophical re-conceptualization and generalization of theoretical biology in light of the essential role played by semiotic notions in biological explanation and modeling. This paper attempts to contribute to the second task by tracing some aspects of the historical evolution of explanatory models in biology. In so doing, a parallel can be drawn between the present status of biosemiotics and that of physics during the early decades of the last century. By following the career of the concept instrument (organon) in Aristotelian science, we revisit historical stages of the antithetical (but often complementary) roles of mechanical and teleological forms of explanation. The impact of the introduction of the organic codes in biology is seen to be somewhat analogous to that of the introduction of the quantum of action in physics. Faced with intractable empirical facts, physicists combined experimental results and bold philosophical speculation to create quantum physics—a wider, deeper framework that accommodates the new facts through a wholesale reformulation of the classical ideas. Essential to this development was the articulation of the epistemic functions of instruments, which was absent from classical physics. Similarly, the consideration of the role of instruments in biology may lead to a synthesis of Aristotelian and Kantian intuitions within a wider framework capable of joining now separate perspectives, such as Jablonka’s four-fold view of inheritance information, Barbieri’s theory of artifactual copymakers and codemakers, and recently developed models of causation based on the idea of manipulative interventions.

The contribution of statistical physics to evolutionary biology

Evolutionary biology shares many concepts with statistical physics: both deal with populations, whether of molecules or organisms, and both seek to simplify evolution in very many dimensions. Often, methodologies have undergone parallel and independent development, as with stochastic methods in population genetics. Here, we discuss aspects of population genetics that have embraced methods from physics: non-equilibrium statistical mechanics, travelling waves and Monte-Carlo methods, among others, have been used to study polygenic evolution, rates of adaptation and range expansions. These applications indicate that evolutionary biology can further benefit from interactions with other areas of statistical physics; for example, by following the distribution of paths taken by a population through time.     

Biology and mathematics: A fruitful merger of two cultures

The great promise of biological science is not its 'mathematization' per se, but the creative interaction between experimental biology and what one, in analogy to physics, may simply call theoretical biology. The key to, and also the great challenge in, fulfilling this promise is to find the correct fundamental notions to mathematically describe biological reality.     

Extended physics as a theoretical framework for systems biology?

In this essay we examine whether a theoretical and conceptual framework for systems biology could be built from the [Bailly and Longo, 2008] and [Bailly and Longo, 2009] proposal. These authors aim to understand life as a coherent critical structure, and propose to develop an extended physical approach of evolution, as a diffusion of biomass in a space of complexity. Their attempt leads to a simple mathematical reconstruction of Gould’s assumption (1989) concerning the bacterial world as a “left wall of least complexity” that we will examine. Extended physical systems are characterized by their constructive properties. Time is acting and new properties emerge by their history that can open the list of their initial properties. This conceptual and theoretical framework is nothing more than a philosophical assumption, but as such it provides a new and exciting approach concerning the evolution of life, and the transition between physics and biology.     

Bringing physics to bear on the phenomenon of life: the divergent positions of Bohr, Delbrück, and Schrödinger

The received view on the contributions of the physics community to the birth of molecular biology tends to present the physics community as sharing a basic level consensus on how physics should be brought to bear on biology. I argue, however, that a close examination of the views of three leading physicists involved in the birth of molecular biology, Bohr, Delbrück, and Schr?dinger, suggests that there existed fundamental disagreements on how physics should be employed to solve problems in biology even within the physics community. In particular, I focus on how these three figures differed sharply in their assessment of the relevance of complementarity, the potential of chemical methods, and the relative importance of classical physics. In addition, I assess and develop Roll-Hansen's attempt to conceptualize this history in terms of models of scientific change advanced by Kuhn and Lakatos. Though neither model is fully successful in explaining the divergence of views among these three physicists, I argue that the extent and quality of difference in their views help elucidate and extend some themes that are left opaque in Kuhn's model.     

Symmetry laws for interaction between helical macromolecules.

The power of symmetry laws is applied in many scientific areas from elementary particle physics to structural biology. The structures of many biological helices, including DNA, were resolved with the use of pertinent symmetry constraints. It was not recognized, however, that similar constraints determine cardinal features of helix-helix interactions vital for many recognition and assembly reactions in living cells. We now formulate such symmetry-determined interaction laws and apply them to explain DNA "over-winding" from 10.5 base pairs per turn in solution to 10 in hydrated fibers, counterion specificity in DNA condensation, and forces observed over the last 15 A of separation between DNA, collagen, and four-stranded guanosine helices.     

Mapping of statistical physics to information theory with application to biological systems

The problem of achieving a mapping of formalisms in statistical physics and theoretical biology to information theory is discussed using an example for canonical ensembles. We extend the meaning of the Handscomb Monte-Carlo method to a general recipe for the transformation from a "configuration" space to a "sentence" space. The ensemble of "sentences" and its corresponding source uncertainty function are introduced. A possible mapping procedure based on a generalization of the Handscomb representation is described. For a biological illustration, we present a way to introduce a pathway representation to describe metabolic processes in living systems.     

Global radiation oncology waybill

Background/aim

Radiation oncology covers many different fields of knowledge and skills. Indeed, this medical specialty links physics, biology, research, and formation as well as surgical and clinical procedures and even rehabilitation and aesthetics. The current socio-economic situation and professional competences affect the development and future or this specialty. The aim of this article was to analyze and highlight the underlying pillars and foundations of radiation oncology, indicating the steps implicated in the future developments or competences of each.

Methods

This study has collected data from the literature and includes highlights from discussions carried out during the XVII Congress of the Spanish Society of Radiation Oncology (SEOR) held in Vigo in June, 2013. Most of the aspects and domains of radiation oncology were analyzed, achieving recommendations for the many skills and knowledge related to physics, biology, research, and formation as well as surgical and clinical procedures and even supportive care and management.

Results

Considering the data from the literature and the discussions of the XVII SEOR Meeting, the “waybill” for the forthcoming years has been described in this article including all the aspects related to the needs of radiation oncology.

Conclusions

Professional competences affect the development and future of this specialty. All the types of radio-modulation are competences of radiation oncologists. On the other hand, the pillars of Radiation Oncology are based on experience and research in every area of Radiation Oncology.