Discussion: Turing's theory of morphogenesis—Its influence on modelling biological pattern and form

The evolution of spatial pattern is a central issue in developmental biology. Turing's (Phil. Trans. R. Soc. Lond. B237, 37–72, 1952) chemical theory of morphogenesis is a seminal contribution. In this talk I give a personal and necessarily limited view of its impact on mathematical and developmental biology. I briefly describe some of the interesting mathematical aspects of Turing's reaction-diffusion mechanism and discuss some of the different models which Turing's vision inspired. The emphasis throughout is on the practical biological applications of the various theories.     

Shifting to structures in physics and biology: a prophylactic for promiscuous realism

Within the philosophy of science, the realism debate has been revitalised by the development of forms of structural realism. These urge a shift in focus from the object oriented ontologies that come and go through the history of science to the structures that remain through theory change. Such views have typically been elaborated in the context of theories of physics and are motivated by, first of all, the presence within such theories of mathematical equations that allow straightforward representation of the relevant structures; and secondly, the implications of such theories for the individuality and identity of putative objects. My aim in this paper is to explore the possibility of extending such views to biological theories. An obvious concern is that within the context of the latter it is typically insisted that we cannot find the kinds of highly mathematised structures that structural realism can point to in physics. I shall indicate how the model-theoretic approach to theories might help allay such concerns. Furthermore, issues of identity and individuality also arise within biology. Thus Dupré has recently noted that there exists a 'General Problem of Biological Individuality' which relates to the issue of how one divides 'massively integrated and interconnected' systems into discrete components. In response Dupré advocates a form of 'Promiscuous Realism' that holds, for example, that there is no unique way of dividing the phylogenetic tree into kinds. Instead I shall urge serious consideration of those aspects of the work of Dupré and others that lean towards a structuralist interpretation. By doing so I hope to suggest possible ways in which a structuralist stance might be extended to biology.     

The biochemical challenge of microbial pathogenicity

In the past decade there has been a revival of interest in microbial pathogenicity. The reasons for this revival are two-fold. First, infectious disease is still with us despite the impact of the antibiotic era; for example, the rise of bacterial and fungal infections in compromised patients and the lack of a good general antiviral drug. Second, the subject of microbial pathogenicity is ripe for application of techniques of biochemistry, molecular biology and genetics that have developed in other areas of biology over the past twenty years; and the potential of these techniques is particularly attractive to young people, who are entering the field in increasing numbers.
In this lecture I shall survey the methods and difficulties of investigating microbial pathogenicity and what we know of the main aspects of the subject at the molecular level. I shall use bacteria as examples because more is known about them than other types of microbes. Lack of space prevents quoting original papers in such a wide-ranging task; in most cases reference is made to authorative reviews.     

Mathematical models for the control of pests and infectious diseases: a survey.

Most of the recent applications of mathematical optimisation theory to the optimal or other control of pests and infectious diseases are surveyed here. Comments are made on some of the difficulties encountered in solving the resulting mathematical problems and in applying the relevant conclusions to real biological systems. At the end of the survey some further problems are suggested whose study might give satisfaction to both mathematicians and those interested in the practical problems of controlling biological populations.     

The mathematical biophysics of Nicolas Rashevsky

N. Rashevsky (1899-1972) was one of the pioneers in the application of mathematics to biology. With the slogan: mathematical biophysics : biology :: mathematical physics ; physics, he proposed the creation of a quantitative theoretical biology. Here, we will give a brief biography, and consider Rashevsky's contributions to mathematical biology including neural nets and relational biology. We conclude that Rashevsky was an important figure in the introduction of quantitative models and methods into biology.     

Modelling strategies for the industrial exploitation of lactic acid bacteria

Lactic acid bacteria (LAB) have a long tradition of use in the food industry, and the number and diversity of their applications has increased considerably over the years. Traditionally, process optimization for these applications involved both strain selection and trial and error. More recently, metabolic engineering has emerged as a discipline that focuses on the rational improvement of industrially useful strains. In the post-genomic era, metabolic engineering increasingly benefits from systems biology, an approach that combines mathematical modelling techniques with functional-genomics data to build models for biological interpretation and--ultimately--prediction. In this review, the industrial applications of LAB are mapped onto available global, genome-scale metabolic modelling techniques to evaluate the extent to which functional genomics and systems biology can live up to their industrial promise.     

Diversity: between neutrality and structure

Here I present an integrated framework for species abundance distributions (SADs) that goes beyond the neutral theory without relying on complex mechanistic models. I give some general mathematical results on the relationship between SADs and their underlying dynamics, and analyse an extensive set of marine phytoplankton data in order to test the neutral theory against this broader framework.
The main theoretical and empirical results are: (i) the logseries, which is the SAD produced by simple neutral models without migration, is quite robust in response to additional factors, including some forms of niche segregation; (ii) when there is a small but significant deviation from a logseries, the SAD will generally have the form of a power law, regardless of the specific mechanisms; (iii) when the deviation is moderate, the SAD will generally have the form of a lognormal, regardless of the specific mechanisms; (iv) although in a wide range of situations neutral and non-neutral dynamics cannot be distinguished from the SAD alone, some empirical SADs do have the fingerprint of non-neutrality: this is the case of marine dinoflagellates, in contrast to marine diatoms, which adjust to neutral theory predictions. The results for marine phytoplankton illustrate that both neutral and non-neutral mechanisms coexist in nature, and seem to have different weights in different groups of organisms.
In addition to the above findings, I discuss several related contributions and point out some important pitfalls in the literature.     

Understanding the evolution of restriction-modification systems: clues from sequence and structure comparisons

Restriction-modification (RM) systems comprise two opposing enzymatic activities: a restriction endonuclease, that targets specific DNA sequences and performs endonucleolytic cleavage, and a modification methyltransferase that renders these sequences resistant to cleavage. Studies on molecular genetics and biochemistry of RM systems have been carried out over the past four decades, laying foundations for modern molecular biology and providing important models for mechanisms of highly specific protein-DNA interactions. Although the number of known, relevant sequences 3D structures of RM proteins is growing steadily, we do not fully understand their functional diversities from an evolutionary perspective and we are not yet able to engineer new sequence specificities based on rational approaches. Recent findings on the evolution of RM systems and on their structures and mechanisms of action have led to a picture in which conserved modules with defined function are shared between different RM proteins and other enzymes involved in nucleic acid biochemistry. On the other hand, it has been realized that some of the modules have been replaced in the evolution by unrelated domains exerting similar function. The aim of this review is to give a survey on the recent progress in the field of structural phylogeny of RM enzymes with special emphasis on studies of sequence-structure-function relationships and emerging potential applications in biotechnology.     

Karl-Peter Hadeler: His legacy in mathematical biology

Journal of Mathematical Biology - Karl-Peter Hadeler is a first-generation pioneer in mathematical biology. His work inspired the contributions to this special issue. In this preface we give a...     

Chance as an explanatory factor in evolutionary biology.

Darwinian evolutionary biology has often been criticized for appealing to the notion of 'chance' in its explanations. According to some critics, such appeals exhibit the explanatory poverty of evolutionary theory. In response, defenders of Darwinism sometimes downplay the importance of 'chance' in evolution. I believe that both of these approaches are mistaken. The main thesis of this paper is that the term 'chance' encompasses a number of distinct concepts, and that at least some of these concepts serve essential explanatory functions in evolutionary biology. This claim is defended by way of an historical survey of the major concepts of 'chance' in the history of evolutionary biology, especially the concepts used by Jean Baptiste Lamarck, Charles Darwin, and Sewall Wright. An examination of their biologies shows how the concepts of 'chance' used cohere with their major scientific objectives and methods. These concepts survive and continue to function as important explanatory factors in contemporary evolutionary biology. Examples of such usage are given, and the explanatory status of 'chance' assessed.     

Toward computational systems biology

The development and successful application of high-throughput technologies are transforming biological research. The large quantities of data being generated by these technologies have led to the emergence of systems biology, which emphasizes large-scale, parallel characterization of biological systems and integration of fragmentary information into a coherent whole. Complementing the reductionist approach that has dominated biology for the last century, mathematical modeling is becoming a powerful tool to achieve an integrated understanding of complex biological systems and to guide experimental efforts of engineering biological systems for practical applications. Here I give an overview of current mainstream approaches in modeling biological systems, highlight specific applications of modeling in various settings, and point out future research opportunities and challenges.     

小角X-射线散射法解析多结构域蛋白质或复合物的溶液结构

随着同步辐射装置的建设与发展及各种建模方法的产生与完善,小角X-射线散射（small angle X-ray scattering,SAXS）法已经逐渐成为结构生物学中的一种重要的工具。SAXS可以用于研究溶液中生物大分子的结构及构象变化,蛋白质的组装、折叠等动态过程。本文对SAXS的基本原理、常用的研究技术和建模方法及其应用进行了综述。     

Biological applications of the theory of birth-and-death processes

In this review, we discuss applications of the theory of birth-and-death processes to problems in biology, primarily, those of evolutionary genomics. The mathematical principles of the theory of these processes are briefly described. Birth-and-death processes, with some straightforward additions such as innovation, are a simple, natural and formal framework for modeling a vast variety of biological processes such as population dynamics, speciation, genome evolution, including growth of paralogous gene families and horizontal gene transfer and somatic evolution of cancers. We further describe how empirical data, e.g. distributions of paralogous gene family size, can be used to choose the model that best reflects the actual course of evolution among different versions of birth-death-and-innovation models. We conclude that birth-and-death processes, thanks to their mathematical transparency, flexibility and relevance to fundamental biological processes, are going to be an indispensable mathematical tool for the burgeoning field of systems biology.     

Permanence and the dynamics of biological systems.

A basic question in mathematical biology concerns the long-term survival of each component, which might typically be a population in an ecological context, of a system of interacting components. Many criteria have been used to define the notion of long-term survival. We consider here the subject of permanence, i.e., the study of the long-term survival of each species in a set of populations. These situations may often be modeled successfully by dynamical systems and have led to the development of some interesting mathematical techniques and results. Our intention here is to describe these and to consider their application to several of the most frequently used models occurring in mathematical biology. We particularly wish to include and cover those models leading to problems that are essentially infinite dimensional, for example reaction-diffusion equations, and to make the discussion accessible to a wide audience, we include a chapter outlining the fundamental theory of these.     

由微分方程所描述的微生物连续培养动力系统(II)

该文为论文 [1 ]的继续 ,主要介绍具有时间滞后的微生物连续培养模型     

Implementation of DNA chips obtained by microprojection for diagnostic and personalized medicine.

It is expected that rapidly emergent new fields of application for DNA chips will be Diagnostic and Personalized Medicine. These new applications will require a limited number of probes, generally from 100 to 1000. So, after a brief review of the existing techniques to manufacture DNA chips, which are efficient for R&D applications and which often require a higher number of probes, we shall first report some advances in the silanization of the substrates and the grafting of probes to improve the robustness and the reliability of the devices. Then we shall discuss two manufacturing processes working at the scale of a nanoliter of reactant: ex situ and in situ fabrication by microprojection. We shall see how these processes are complementary and may be used to design and produce chips, at a large scale, for these new applications.     

Can biology make ethics objective?

A familiar position regarding the evolution of ethics is that biology can explain the origin of morals but that in doing so it removes the possibility of their having objective justification. This position is set fourth in detail in the writings of Michael Ruse (1986, 1987, 1989, 1990a, 1990b) but it is also taken by many others, notably, Jeffrie Murphy (1982), Andrew Oldenquist (1990), and Allan Gibbard (1990), I argue the contrary view that biology provides a justification of the existence of morals which is objective in the sense of being independent of people's moral views and their particular desires and preferences. Ironically, my argument builds on the very premises which are supposed to undermine the objectivity of morals. But my argument stops short of claiming that biology can give us a basis for justifying some particular system of morals. Drawing on an analogy with social contract theory, I offer a general reason why this more ambitious project cannot be expected to succeed if the argument is pursued along the same lines. Finally, I give reasons why the possibility of objective justification for a particular morality cannot be ruled out in general on evolutionary grounds.     

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.     

Evolutionary Psychology: The Burdens of Proof

I discuss two types of evidential problems with the most widely touted experiments in evolutionary psychology, those performed by Leda Cosmides and interpreted by Cosmides and John Tooby. First, and despite Cosmides and Tooby's claims to the contrary, these experiments don't fulfil the standards of evidence of evolutionary biology. Second Cosmides and Tooby claim to have performed a crucial experiment, and to have eliminated rival approaches. Though they claim that their results are consistent with their theory but contradictory to the leading non-evolutionary alternative, Pragmatic Reasoning Schemas theory, I argue that this claim is unsupported. In addition, some of Cosmides and Tooby's interpretations arise from misguided and simplistic understandings of evolutionary biology. While I endorse the incorporation of evolutionary approaches into psychology, I reject the claims of Cosmides and Tooby that a modular approach is the only one supported by evolutionary biology. Lewontin's critical examinations of the applications of adaptationist thinking provide a background of evidentiary standards against which to view the currently fashionable claims of evolutionary psychology.     

Constructivist Models of Mind, Contemporary Psychoanalysis, and the Development of Culture Theory

Researchers in a number of fields, including contemporary psychoanalysis, are contributing to the development of a dynamic model of mind that acknowledges the contributions of biology and social experience to the construction of human consciousness and subjectivity. In this paper, I examine this emerging model of mind and I discuss its implications for the development of Culture theory. I argue that theories of culture must reflect the fluidity and complexity of the psychological states that underlie the culture process, and I suggest that even highly conventional models of action, thought, and feeling are rarely, if ever, internalized, appropriated, or reproduced without some degree of modification, refashioning, and personalization. I propose person-centered ethnography as one of the methods by which we can explore the complex relations among culture, mind, and behavior, [constructivist models of mind, contemporary psychoanalysis, culture theory, self and subjectivity, person-centered ethnography]