基于哲学思维的“分子生物学”教法改革初探

针对“分子生物学”教学中出现的问题,通过分析“分子生物学”中哲学思想及其认知特点,文章进行了基于哲学思维的“分子生物学”教学方法改革初步探讨。期望通过引入哲学思维,培养学生的哲学思想,开拓学生的创新思维,提升他们的认知水平,增强自然科学学生的人文素养,进一步提升“分子生物学”的教学效果。     

A priority paper for the societal and ethical aspects of synthetic biology

As synthetic biology develops into a promising science and engineering field, we need to have clear ideas and priorities regarding its safety, security, ethical and public dialogue implications. Based on an extensive literature search, interviews with scientists, social scientists, a 4 week long public e-forum, and consultation with several stakeholders from science, industry and civil society organisations, we compiled a list of priority topics regarding societal issues of synthetic biology for the years ahead. The points presented here are intended to encourage all stakeholders to engage in the prioritisation of these issues and to participate in a continuous dialogue, with the ultimate goal of providing a basis for a multi-stakeholder governance in synthetic biology. Here we show possible ways to solve the challenges to synthetic biology in the field of safety, security, ethics and the science–public interface.     

A parsimonious view of the parsimony principle in ecology and evolution

The idea that simplicity of explanation is important in science is as old as science itself. However, scientists often assume that parsimonious theories, hypothesis and models are more plausible than complex ones, forgetting that there is no empirical evidence to connect parsimony with credibility. The justification for the parsimony principle is strongly dependent on philosophical and statistical inference. Parsimony may have a true epistemic value in the evaluation of correlative and predictive models, as simpler models are less prone to overfitting. However, when natural mechanisms are explicitly modelled to represent the causes of biological phenomena, the application of the parsimony principle to judge the plausibility of mechanistic models would entail an unsupported belief that nature is simple. Here, we discuss the challenges we face in justifying, measuring, and assessing the trade‐off between simplicity and complexity in ecological and evolutionary studies. We conclude that invoking the parsimony principle in ecology and evolution is particularly important in model‐building programs in which models are viewed primarily as an operational tool to make predictions (an instrumentalist view) and in which data play a prominent role in deciding the structure of the model. However, theoretical advances in ecology and evolutionary biology may be derailed by the use of the parsimony principle to judge explanatory mechanistic models that are designed to understand complex natural phenomena. We advocate a parsimonious use of the parsimony principle.     

Philosophical ideas and scientific practice: A note on the empiricism of T.H. Morgan

In a reply to Marga Vicedo the philosophical inconsistency of Morgan is emphasized. It is argued that even if a strict classification of scientists according to their philosophical position is not possible, their science may still be influenced by their philosophical ideas. Finally it is suggested that philosophical ideas influence science less by a direct effect on the scientists than indirectly through science policy and administration.     

In Silico Analysis of Crop Science： Report on the First China-UK Workshop on Chips, Computers and Crops

A workshop on ＂Chips, Computers and Crops＂ was held in Hangzhou, China during September 26-27, 2008. The main objective of the workshop was to bring together China and UK scientists from mathematics, bioinformatics and plant molecular biology communities to exchange ideas, enhance awareness of each others＇ fields, explore synergisms and make recommendations on fruitful future directions in crop science. Here we describe the contributions to the workshop, and examine some conceptual issues that lie at the foundations and future of crop systems biology.     

Thinking about evolution: combinatorial play as a strategy for exercising scientific creativity

An enduring focus in education on how scientists formulate experiments and ‘do science’ in the laboratory has excluded a vital element of scientific practice: the creative and imaginative thinking that generates models and testable hypotheses. In this case study, final‐year biomedical sciences university students were invited to create and justify a taxonomy of selected vertebrates on the basis of their brain organisation, as part of an exercise exploring the evolution of embryonic development. While raising a number of issues surrounding the context and methods of comparative zoology, this exercise also invoked a set of cognitive processes that can neither be adequately characterised as role‐play nor critical thinking. By contrast, the act of formulating and justifying taxonomy identifies a style of creative thought that is a prerequisite for hypothesis formation. A defining characteristic of this exercise is that it engages activities that are independent of disciplinary perspective. This flexibility in approach may provide a route through to defining what qualifies as a creative teaching exercise in science.     

Algorithms in nature: the convergence of systems biology and computational thinking

Computer science and biology have enjoyed a long and fruitful relationship for decades. Biologists rely on computational methods to analyze and integrate large data sets, while several computational methods were inspired by the high‐level design principles of biological systems. Recently, these two directions have been converging. In this review, we argue that thinking computationally about biological processes may lead to more accurate models, which in turn can be used to improve the design of algorithms. We discuss the similar mechanisms and requirements shared by computational and biological processes and then present several recent studies that apply this joint analysis strategy to problems related to coordination, network analysis, and tracking and vision. We also discuss additional biological processes that can be studied in a similar manner and link them to potential computational problems. With the rapid accumulation of data detailing the inner workings of biological systems, we expect this direction of coupling biological and computational studies to greatly expand in the future.     

The science of research: The principles underlying the discovery of cognitive and other biological mechanisms

Studies of cognitive function include a wide spectrum of disciplines, with very diverse theoretical and practical frameworks. For example, in Behavioral Neuroscience cognitive mechanisms are mostly inferred from loss of function (lesion) experiments while in Cognitive Neuroscience these mechanisms are commonly deduced from brain activation patterns. Although neuroscientists acknowledge the limitations of deriving conclusions using a limited scope of approaches, there are no systematically studied, objective and explicit criteria for what is required to test a given hypothesis of cognitive function. This problem plagues every discipline in science: scientific research lacks objective, systematic studies that validate the principles underlying even its most elemental practices. For example, scientists decide what experiments are best suited to test key ideas in their field, which hypotheses have sufficient supporting evidence and which require further investigation, which studies are important and which are not, based on intuitions derived from experience, implicit principles learned from mentors and colleagues, traditions in their fields, etc. Philosophers have made numerous attempts to articulate and frame the principles that guide research and innovation, but these speculative ideas have remained untested and have had a minimal impact on the work of scientists. Here, I propose the development of methods for systematically and objectively studying and improving the modus operandi of research and development. This effort (the science of scientific research or S2) will benefit all aspects of science, from education of young scientists to research, publishing and funding, since it will provide explicit and systematically tested frameworks for practices in science. To illustrate its goals, I will introduce a hypothesis (the Convergent Four) derived from experimental practices common in molecular and cellular biology. This S2 hypothesis proposes that there are at least four fundamentally distinct strategies that scientists can use to test the connection between two phenomena of interest (A and B), and that to establish a compelling connection between A and B it is crucial to develop independently confirmed lines of convergent evidence in each of these four categories. The four categories include negative alteration (decrease probability of A or p(A) and determine p(B)), positive alteration (increase p(A) and determine p(B)), non-intervention (examine whether A precedes B) and integration (develop ideas about how to get from A to B and integrate those ideas with other available information about A and B). I will discuss both strategies to test this hypothesis and its implications for studies of cognitive function.     

The scientific research programmes of Lakatos and applications in parasitology

The methodology of scientific research programme (MSRP) proposed by Lakatos was in the line of the proposals made by Popper. MSRP were intended for constructing and evaluating research programme, which is unique among philosophers of science. Surprisingly, scientists dedicated to research in mathematics, physic or biology have not used much MRSP. This could be due to the fact that scientists are not aware of the existence of MSRP, or they find it difficult to apply to their own investigations. That is why we present firstly the main characteristics of this methodology (hard core--the group of hypothesis that are admitted by experts in the field, auxiliary hypotheses--which are intended to protect and refine the hypotheses of the hard-core, and heuristics for mending and evaluating the MSRP) and, secondly, propose an example in helminthology. We think that the methodology of Lakatos, is a useful tool, but it cannot encompass the large flexibility of investigations pathways.     

Reverend Paley's naturalist revival

This paper analyzes the remarkable popularity of William Paley's argument from design among contemporary naturalists in biology and the philosophy of science. In philosophy of science Elliott Sober has argued that creationism should be excluded from the schools not because it is not science but because it is 'less likely' than evolution according to fairly standard confirmation theory. Creationism is said to have been a plausible scientific option as presented by Paley but no longer to be acceptable according to the same standards that once approved it. In biology C. G. Williams and Richard Dawkins have seen in Paley a proto-adaptationist. This paper shows that the historical assumptions of Sober's arguments are wrong and that the philosophical arguments themselves take alternatives to science to be alternatives in science and conflate the null hypothesis, chance, with a competing explanatory hypothesis. It is also shown that the similarity of Paley's adaptationism to that of contemporary biology is not what it is made out to be.     

Purple Matter, Membranes and ‘Molecular Pumps’ in Rhodopsin Research (1960s–1980s)

In the context of 1960s research on biological membranes, scientists stumbled upon a curiously coloured material substance, which became called the “purple membrane.” Interactions with the material as well as chemical analyses led to the conclusion that the microbial membrane contained a photoactive molecule similar to rhodopsin, the light receptor of animals’ retinae. Until 1975, the find led to the formation of novel objects in science, and subsequently to the development of a field in the molecular life sciences that comprised biophysics, bioenergetics as well as membrane and structural biology. Furthermore, the purple membrane and bacteriorhodopsin, as the photoactive membrane transport protein was baptized, inspired attempts at hybrid bio-optical engineering throughout the 1980s. A central motif of the research field was the identification of a functional biological structure, such as a membrane, with a reactive material substance that could be easily prepared and manipulated. Building on this premise, early purple membrane research will be taken as a case in point to understand the appearance and transformation of objects in science through work with material substances. Here, the role played by a perceptible material and its spontaneous change of colour, or reactivity, casts a different light on objects and experimental practices in the late twentieth century molecular life sciences. With respect to the impact of chemical working and thinking, the purple membrane and rhodopsins represent an influential domain straddling the life and chemical sciences as well as bio- and material technologies, which has received only little historical and philosophical attention. Re-drawing the boundary between the living and the non-enlivened, these researches explain and model organismic activity through the reactivity of macromolecular structures, and thus palpable material substances.     

How to use Hydra as a model system to teach biology in the classroom

As scientists it is our duty to fight against obscurantism and loss of rational thinking if we want politicians and citizens to freely make the most intelligent choices for the future generations. With that aim, the scientific education and training of young students is an obvious and urgent necessity. We claim here that Hydra provides a highly versatile but cheap model organism to study biology at any age. Teachers of biology have the unenviable task of motivating young people, who with many other motivations that are quite valid, nevertheless must be guided along a path congruent with a 'syllabus' or a 'curriculum'. The biology of Hydra spans the history of biology as an experimental science from Trembley's first manipulations designed to determine if the green polyp he found was plant or animal to the dissection of the molecular cascades underpinning, regeneration, wound healing, stemness, aging and cancer. It is described here in terms designed to elicit its wider use in classrooms. Simple lessons are outlined in sufficient detail for beginners to enter the world of 'Hydra biology'. Protocols start with the simplest observations to experiments that have been pretested with students in the USA and in Europe. The lessons are practical and can be used to bring 'life', but also rational thinking into the study of life for the teachers of students from elementary school through early university.     

The origin of modern plant virology

Plant virology, born with Mayer's work, saw a first (embryonic) phase of development during two decades (1900-1920) with outstanding contributions from Dimitri Ivanovski, Martinus Beijerinck, Erwin Baur and Harry Allard. Between 1920 and 1930 a second phase saw the elaboration of surprising hypotheses concerning the enigmatic nature of viruses and experimental evidence of great stress was obtained. Revolutionary renewal began from the mid-1930s on the basis of a body of knowledge which was organically assembled into the first textbook of plant virology published by Kenneth Smith in 1933. In 1922, the geneticist Hermann Muller put forward the hypothesis that considered viruses as possible genes. The theory was resumed in an apparently independent way by Benjamin Duggar and Joanne Karrer Armstrong in 1923, who considered TMV a biocolloidal self-reproducing protein, like genes appeared to be. This hypothesis, even if neglected by virologists, anticipated by some decades the functional nature of viruses and represented the first conceptual response to virus enigma. Considerable experimental results were obtained by James Johnson, who showed that plants could be infected by different viruses and who introduced a first rational system of plant virus classification. Harold McKinney showed that TMV could mutate. Harold Storey, Kenneth Smith and Harry Severin demonstrated that several viruses could be transmitted by insects and supplied the first interpretation of the relationship between virus and insect. Mayme Dvorak and Helen Purdy obtained the first experimental evidence of the antigenic power of plant viruses. Virus purification, first tentatively accomplished with physical methods, was brilliantly performed by chemical means. Finally, Francis Holmes elaborated the first suitable test to estimate virus infectivity. The evolution of plant virology from an empirical discipline to a biological science took place thanks to the work of one group of American and English scientists who must be regarded as the fathers of modern plant virology.     

What does robotics offer animal behaviour?

There is a growing body of robot-based research that makes a serious claim to be a new methodology for biology. Robots can be used as models of specific animal systems to test hypotheses regarding the control of behaviour. At levels from learning algorithms to specific dendritic circuits, implementing a proposed controller in a robotic device tests it against real environments in a way that is difficult to simulate. This often provides insight into the true nature of the problem. It also enforces complete specifications and combines bodies of data. Current work can sometimes be criticized for drawing unjustified conclusions given the limited evaluation and inevitable inaccuracies of robot models. Nevertheless, this approach has led to novel hypotheses for animal behaviour and seems likely to provide fruitful results in the future. Copyright 2000 The Association for the Study of Animal Behaviour.     

Scientific perspectivism: A philosopher of science's response to the challenge of big data biology

Big data biology—bioinformatics, computational biology, systems biology (including ‘omics’), and synthetic biology—raises a number of issues for the philosophy of science. This article deals with several such: Is data-intensive biology a new kind of science, presumably post-reductionistic? To what extent is big data biology data-driven? Can data ‘speak for themselves?’ I discuss these issues by way of a reflection on Carl Woese’s worry that “a society that permits biology to become an engineering discipline, that allows that science to slip into the role of changing the living world without trying to understand it, is a danger to itself.” And I argue that scientific perspectivism, a philosophical stance represented prominently by Giere, Van Fraassen, and Wimsatt, according to which science cannot as a matter of principle transcend our human perspective, provides the best resources currently at our disposal to tackle many of the philosophical issues implied in the modeling of complex, multilevel/multiscale phenomena.     

The PAL+ program, an incentive concerted action about malaria and associated infectious diseases, for developing countries

The French Ministry in charge of Research has launched a multi-institutional incentive concerted action to assist Southern countries on malaria: the PAL+ program. PAL+ aims at bringing out: 1) conditions to promote novel preventive and therapeutic tools adapted to existing situations in the countries concerned; 2) a contribution to help research teams in Southern countries become competitive. PAL+ plans to strengthen cooperative relationships with developing countries (subsaharian Africa, South East Asia and South American countries). Research programs were oriented towards public health needs in malaria-endemic countries and thus mainly focused on: i) development of new antimalarial drugs and new therapeutical strategies: new targets and new leads for drugs, clinical assays for recognition of malaria and optimization of effective treatment or prophylactic drug dosage; ii) pathophysiology of severe malaria: mechanisms of immunity, biology and genome of host and parasite and research leading to vaccine trials; iii) basic and field research on mosquito genetics and biology which may lead to new prevention and control opportunities; iv) social studies on behaviours and habits around prevention and medication of malaria. The objective is to help Southern countries increase their capacity in clinical research, epidemiology, therapeutics, public health and social science (e.g. behaviours and habits accompanying medicine-taking). This means a true partnership and training adapted to specific needs and based on sound science. Research was therefore largely pursued in the laboratories of Southern countries and PAL+ supported the initiative in different ways by: i) providing easier opportunities for scientists from the North to collaborate with scientists from the South; ii) supporting networks of scientist collaborations. This was achieved by setting up a new type of relationships between scientists, based on a continuous dialogue and on bringing them together in small meetings on thematic discussions, the so-called Ateliers de PAL+. The Ateliers should play a major role in increasing the scientific capacity in developing countries. PAL+ program is a commitment to speed up better understanding of the disease by helping endemic countries contribute to research for their own benefit.     

Biohumanities: rethinking the relationship between biosciences, philosophy and history of science, and society

We argue that philosophical and historical research can constitute a "Biohumanities" that deepens our understanding of biology itself engages in constructive "science criticism," helps formulate new "visions of biology," and facilitates "critical science communication." We illustrate these ideas with two recent "experimental philosophy" studies of the concept of the gene and of the concept of innateness conducted by ourselves and collaborators. We conclude that the complex and often troubled relations between science and society are critical to both parties, and argue that the philosophy and history of science can help to make this relationship work.     

小型哺乳动物种群周期性波动的自我调节假说

种群调节是种群生态学的一个核心问题。文章主要阐述了小型哺乳动物种群在其低数量期自我调节的4 种可能假说和相关的实验证据。其中, 有关衰老—母体效应假说近年已受到普遍重视, 而支持多态行为假说、社会生物学假说和远交假说的证据较少, 尚需更多的实验来加以验证。衰老—母体效应假说是在应激假说的基础上发展而成的。该假说认为, 母体质量会在整个高峰期的动物中发生改变, 并能够延续到衰减期和低数量期。在低数量期, 种群内的老年个体增多, 导致它们不能维持内分泌的自稳态, 可能通过影响后代的存活和生殖而维持低数量, 进而起到调节种群周期的作用。针对国际上研究的发展趋势, 我们还对未来的研究方向提出了一些建议。     

Reuniting philosophy and science to advance cancer research

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer.     

Convenience experimentation

Systems biology aims at explaining life processes by means of detailed models of molecular networks, mainly on the whole-cell scale. The whole cell perspective distinguishes the new field of systems biology from earlier approaches within molecular cell biology. The shift was made possible by the high throughput methods that were developed for gathering 'omic' (genomic, proteomic, etc.) data. These new techniques are made commercially available as semi-automatic analytic equipment, ready-made analytic kits and probe arrays. There is a whole industry of supplies for what may be called convenience experimentation. My paper inquires some epistemic consequences of strong reliance on convenience experimentation in systems biology. In times when experimentation was automated to a lesser degree, modeling and in part even experimentation could be understood fairly well as either being driven by hypotheses, and thus proceed by the testing of hypothesis, or as being performed in an exploratory mode, intended to sharpen concepts or initially vague phenomena. In systems biology, the situation is dramatically different. Data collection became so easy (though not cheap) that experimentation is, to a high degree, driven by convenience equipment, and model building is driven by the vast amount of data that is produced by convenience experimentation. This results in a shift in the mode of science. The paper shows that convenience driven science is not primarily hypothesis-testing, nor is it in an exploratory mode. It rather proceeds in a gathering mode. This shift demands another shift in the mode of evaluation, which now becomes an exploratory endeavor, in response to the superabundance of gathered data.