Although “theory” has been the prevalent unit of analysis in the meta-study of science throughout most of the twentieth century, the concept remains elusive. I further explore the leitmotiv of several authors in this issue: that we should deal with theorizing (rather than theory) in biology as a cognitive activity that is to be investigated naturalistically. I first contrast how philosophers and biologists have tended to think about theory in the last century or so, and consider recent calls to upgrade (...) the role of theory in the life sciences against the background of the recent “data deluge” in molecular biology, systems biology, etc. I then review thinking about theory in biology in relation to physical theory as a positive or negative exemplar. I conclude by discussing various aspects of a positive program for “naturalizing theorizing.”. (shrink)

The three processes needed to create life, compartmentalization, metabolism, and information transfer (memory stored in nucleic acids and manipulation operated by proteins) are embedded in organized genome features. The core of life puts together growth and maintenance (which drives survival), while life in context explores and exploits specific niches. Analysis of gene persistence in a large number of genomes shows that the former constitutes the paleome, which recapitulates the three phases of the origin of life: metabolism of small molecules on (...) surfaces, substitution of surfaces by an RNA-world where transfer RNA played a central role, and invention of template mediated information transfer. Colonization of each niche is performed using an almost unlimited set of genes, forming the cenome. The agreement of the paleome structure with a consistent scenario for the origin of life is such that we may consider extant genomes as providing us with an archive of the origin rather than as a palimpsest where most of our past would be irremediably hidden. (shrink)

Ranging from Alan Turing’s seminal 1936 paper to the latest work on Kolmogorov complexity and linear logic, this comprehensive new work clarifies the relationship between computability on the one hand and constructivity on the other. The authors argue that even though constructivists have largely shed Brouwer’s solipsistic attitude to logic, there remain points of disagreement to this day. Focusing on the growing pains computability experienced as it was forced to address the demands of rapidly expanding applications, the content maps the (...) developments following Turing’s ground-breaking linkage of computation and the machine, the resulting birth of complexity theory, the innovations of Kolmogorov complexity and resolving the dissonances between proof theoretical semantics and canonical proof feasibility. Finally, it explores one of the most fundamental questions concerning the interface between constructivity and computability: whether the theory of recursive functions is needed for a rigorous development of constructive mathematics. This volume contributes to the unity of science by overcoming disunities rather than offering an overarching framework. It posits that computability’s adoption of a classical, ontological point of view kept these imperatives separated. In studying the relationship between the two, it is a vital step forward in overcoming the disagreements and misunderstandings which stand in the way of a unifying view of logic. (shrink)

In the context of scientists' reflections on genomics, we examine some fundamental issues in the emerging postgenomic discipline of systems biology. Systems biology is best understood as consisting of two streams. One, which we shall call ‘pragmatic systems biology’, emphasises large‐scale molecular interactions; the other, which we shall refer to as ‘systems‐theoretic biology’, emphasises system principles. Both are committed to mathematical modelling, and both lack a clear account of what biological systems are. We discuss the underlying issues in identifying systems (...) and how causality operates at different levels of organisation. We suggest that resolving such basic problems is a key task for successful systems biology, and that philosophers could contribute to its realisation. We conclude with an argument for more sociologically informed collaboration between scientists and philosophers. BioEssays 27:1270–1276, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The “DNA is a program” metaphor is still widely used in Molecular Biology and its popularization. There are good historical reasons for the use of such a metaphor or theoretical model. Yet we argue that both the metaphor and the model are essentially inadequate also from the point of view of Physics and Computer Science. Relevant work has already been done, in Biology, criticizing the programming paradigm. We will refer to empirical evidence and theoretical writings in Biology, although our arguments (...) will be mostly based on a comparison with the use of differential methods (in Molecular Biology: a mutation or alike is observed or induced and its phenotypic consequences are observed) as applied in Computer Science and in Physics, where this fundamental tool for empirical investigation originated and acquired a well-justified status. In particular, as we will argue, the programming paradigm is not theoretically sound as a causal(as in Physics) or deductive(as in Programming) framework for relating the genome to the phenotype, in contrast to the physicalist and computational grounds that this paradigm claims to propose. (shrink)

Progress in molecular biology has revealed profound relations between linguistic and genomic sciences, mainly through advances in bioinformatics. The structural symmetries between biochemical and verbal syntaxes raise the question of their origins: did they emerge independently, or did one arise from the other? Does the genetic code contain the traces of a protolanguage, a universal grammar whose gradual evolution and successive mutations progressively led to the polymorphism of natural languages? To explore this question, we review the isomorphism of the genetic (...) code and verbal codes from lexical, syntactic, semantic and pragmatic standpoints. We discuss the limits of these symmetries and their anthropomorphic connotations. We observe the gradual evolution of species and languages according to parallel mechanisms, and the genetic roots of the physiology of language. In conclusion, we hypothesize that human observers may not be projecting linguistic frameworks onto genomic structures. Rather, it could be their linguistic faculties that reflect the grammatical structure of genetic code. (shrink)

Philosophers of science diverge on the question what drives the growth of scientific knowledge. Most of the twentieth century was dominated by the notion that theories propel that growth whereas experiments play secondary roles of operating within the theoretical framework or testing theoretical predictions. New experimentalism, a school of thought pioneered by Ian Hacking in the early 1980s, challenged this view by arguing that theory-free exploratory experimentation may in many cases effectively probe nature and potentially spawn higher evidence-based theories. Because (...) theories are often powerless to envisage workings of complex biological systems, theory-independent experimentation is common in the life sciences. Some such experiments are triggered by compelling observation, others are prompted by innovative techniques or instruments, whereas different investigations query big data to identify regularities and underlying organizing principles. A distinct fourth type of experiments is motivated by a major question. Here I describe two question-guided experimental discoveries in biochemistry: the cyclic adenosine monophosphate mediator of hormone action and the ubiquitin-mediated system of protein degradation. Lacking underlying theories, antecedent data bases, or new techniques, the sole guides of the two discoveries were respective substantial questions. Both research projects were similarly instigated by theory-free exploratory experimentation and continued in alternating phases of results-based interim working hypotheses, their examination by experiment, provisional hypotheses again, and so on. These two cases designate theory-free, question-guided, stepwise biochemical investigations as a distinct subtype of the new experimentalism mode of scientific enquiry. (shrink)

The Tree of Life has traditionally been understood to represent the history of species lineages. However, recently researchers have suggested that it might be better interpreted as representing the history of cellular lineages, sometimes called the Tree of Cells. This paper examines and evaluates reasons offered against this cellular interpretation of the Tree of Life. It argues that some such reasons are bad reasons, based either on a false attribution of essentialism, on a misunderstanding of the problem of lineage identity, (...) or on a limited view of scientific representation. I suggest that debate about the Tree of Cells and other successors to the traditional Tree of Life should be formulated in terms of the purposes these representations may serve. In pursuing this strategy, we see that the Tree of Cells cannot serve one purpose suggested for it: as an explanation for the hierarchical nature of taxonomy. We then explore whether, instead, the tree may play an important role in the dynamic modeling of evolution. As highly-integrated complex systems, cells may influence which lineage components can successfully transfer into them and how they change once integrated. Only if they do in fact have a substantial role to play in this process might the Tree of Cells have some claim to be the Tree of Life. (shrink)

Science is founded on a method based on critical thinking. A prerequisite for this is not only a sufficient command of language but also the comprehension of the basic concepts underlying our understanding of reality. This constraint implies an awareness of the fact that the truth of the World is not directly accessible to us, but can only be glimpsed through the construction of mod- els designed to anticipate its behaviour. Because the relationship between models and reality rests on the (...) interpretation of founding postulates and in- stantiations of their predictions (and is therefore deeply rooted in language and culture), there can be no demarcation between science and non-science. However, critical thinking is essential to ensure that the link between models and reality is gradually made more adequate to reality, based on what has already been established, thus guaranteeing that science progresses on this basis and excluding any form of relativism. (shrink)

Two decades ago, Rolf Landauer (1991) argued that “information is physical” and ought to have a role in the scientific analysis of reality comparable to that of matter, energy, space and time. This would also help to bridge the gap between biology and mathematics and physics. Although it can be argued that we are living in the ‘golden age’ of biology, both because of the great challenges posed by medicine and the environment and the significant advances that have been made—especially (...) in genetics and molecular and cell biology—we feel that information as an essential aspect of life has been neglected, or at least misunderstood. We therefore summon Maxwell’s Demon and its distant relative the ratchet, and apply these to biology. (shrink)

Science and engineering rely on the accumulation and dissemination of knowledge to make discoveries and create new designs. Discovery-driven genome research rests on knowledge passed on via gene annotations. In response to the deluge of sequencing big data, standard annotation practice employs automated procedures that rely on majority rules. We argue this hinders progress through the generation and propagation of errors, leading investigators into blind alleys. More subtly, this inductive process discourages the discovery of novelty, which remains essential in biological (...) research and reflects the nature of biology itself. Annotation systems, rather than being repositories of facts, should be tools that support multiple modes of inference. By combining deduction, induction and abduction, investigators can generate hypotheses when accurate knowledge is extracted from model databases. A key stance is to depart from ‘the sequence tells the structure tells the function’ fallacy, placing function first. We illustrate our approach with examples of critical or unexpected pathways, using MicroScope to demonstrate how tools can be implemented following the principles we advocate. We end with a challenge to the reader. (shrink)

To construct a synthetic cell we need to understand the rules that permit life. A central idea in modern biology is that in addition to the four entities making reality, matter, energy, space and time, a fifth one, information, plays a central role. As a consequence of this central importance of the management of information, the bacterial cell is organised as a Turing machine, where the machine, with its compartments defining an inside and an outside and its metabolism, reads and (...) expresses the genetic program carried by the genome. This highly abstract organisation is implemented using concrete objects and dynamics, and this is at the cost of repeated incompatibilities (frustration), which need to be sorted out by appropriate «patches». After describing the organisation of the genome into the paleome (sustaining and propagating life) and the cenome (permitting life in context), we describe some chemical hurdles that the cell as to cope with, ending with the specific case of the methionine salvage pathway. (shrink)

The development of synthetic biology calls for accurate understanding of the critical functions that allow construction and operation of a living cell. Besides coding for ubiquitous structures, minimal genomes encode a wealth of functions that dissipate energy in an unanticipated way. Analysis of these functions shows that they are meant to manage information under conditions when discrimination of substrates in a noisy background is preferred over a simple recognition process. We show here that many of these functions, including transporters and (...) the ribosome construction machinery, behave as would behave a material implementation of the informationmanaging agent theorized by Maxwell almost 150 years ago and commonly known as Maxwell’s demon (MxD). A core gene set encoding these functions belongs to the minimal genome required to allow the construction of an autonomous cell. These MxDs allow the cell to perform computations in an energy-efficient way that is vastly better than our contemporary computers. (shrink)