Blind Watchmaker Research Articles

Antibiotic Skeletal Diversification via Differential Enoylreductase Recruitment and Module Iteration in trans-Acyltransferase Polyketide Synthases.

Microorganisms are remarkable chemists capable of assembling complex molecular architectures that penetrate cells and bind biomolecular targets with exquisite selectivity. Consequently, microbial natural products have wide-ranging applications in medicine and agriculture. How the "blind watchmaker" of evolution creates skeletal diversity is a key question in natural products research. Comparative analysis of biosynthetic pathways to structurally related metabolites is an insightful approach to addressing this. Here, we report comparative biosynthetic investigations of gladiolin, a polyketide antibiotic from Burkholderia gladioli with promising activity against multidrug-resistant Mycobacterium tuberculosis, and etnangien, a structurally related antibiotic produced by Sorangium cellulosum. Although these metabolites have very similar macrolide cores, their C21 side chains differ significantly in both length and degree of saturation. Surprisingly, the trans-acyltransferase polyketide synthases (PKSs) that assemble these antibiotics are almost identical, raising intriguing questions about mechanisms underlying structural diversification in this important class of biosynthetic assembly line. In vitro reconstitution of key biosynthetic transformations using simplified substrate analogues, combined with gene deletion and complementation experiments, enabled us to elucidate the origin of all the structural differences in the C21 side chains of gladiolin and etnangien. The more saturated gladiolin side chain arises from a cis-acting enoylreductase (ER) domain in module 1 and in trans recruitment of a standalone ER to module 5 of the PKS. Remarkably, module 5 of the gladiolin PKS is intrinsically iterative in the absence of the standalone ER, accounting for the longer side chain in etnangien. These findings have important implications for biosynthetic engineering approaches to the creation of novel polyketide skeletons.

Bifurcation drives the evolution of assembly-line biosynthesis

Reprogramming biosynthetic assembly-lines is a topic of intense interest. This is unsurprising as the scaffolds of most antibiotics in current clinical use are produced by such pathways. The modular nature of assembly-lines provides a direct relationship between the sequence of enzymatic domains and the chemical structure of the product, but rational reprogramming efforts have been met with limited success. To gain greater insight into the design process, we wanted to examine how Nature creates assembly-lines and searched for biosynthetic pathways that might represent evolutionary transitions. By examining the biosynthesis of the anti-tubercular wollamides, we uncover how whole gene duplication and neofunctionalization can result in pathway bifurcation. We show that, in the case of the wollamide biosynthesis, neofunctionalization is initiated by intragenomic recombination. This pathway bifurcation leads to redundancy, providing the genetic robustness required to enable large structural changes during the evolution of antibiotic structures. Should the new product be non-functional, gene loss can restore the original genotype. However, if the new product confers an advantage, depreciation and eventual loss of the original gene creates a new linear pathway. This provides the blind watchmaker equivalent to the design, build, test cycle of synthetic biology.

The Blind Watchmaker: Investigating the nuclear response to changes in mitochondrial gene expression

The Blind Watchmaker: Investigating the nuclear response to changes in mitochondrial gene expression

How Mustard Gas Broke the Blind Watchmaker

How Mustard Gas Broke the Blind Watchmaker

Techno Hybridity and Symptoms of the Posthuman Crisis Seen through the Scientific Novel The Blind Watchmaker

Techno Hybridity and Symptoms of the Posthuman Crisis Seen through the Scientific Novel The Blind Watchmaker

Was the Watchmaker Blind? Or Was She One-Eyed?

The question whether evolution is blind is usually presented as a choice between no goals at all (‘the blind watchmaker’) and long-term goals which would be external to the organism, for example in the form of special creation or intelligent design. The arguments either way do not address the question whether there are short-term goals within rather than external to organisms. Organisms and their interacting populations have evolved mechanisms by which they can harness blind stochasticity and so generate rapid functional responses to environmental challenges. They can achieve this by re-organising their genomes and/or their regulatory networks. Epigenetic as well as DNA changes are involved. Evolution may have no foresight, but it is at least partially directed by organisms themselves and by the populations of which they form part. Similar arguments support partial direction in the evolution of behavior.

Exploration on the Possibility of Science Fiction-based Convergence Education -focused on ‘The Blind Watchmaker’-

Exploration on the Possibility of Science Fiction-based Convergence Education -focused on ‘The Blind Watchmaker’-

Some Reflections on Dawkins

Studies • volume 106 • number 422 179 Some Reflections on Dawkins Bill Toner SJ Some weeks ago I was sitting in a quiet Dublin pub with a Jesuit friend talking about Richard Dawkins and the impact he seemed to be having on religious belief through his books, such as The Blind Watchmaker and The God Delusion.1 As is well known, Dawkins’main area of interest is evolution. He relies heavily on the process of evolution to show that there is no need for a concept of a God or Creator to explain the existence of the living beings that we have on our planet. For Dawkins, evolution is a mechanical process which was set in motion as a result of a couple of primeval accidents. This process, he believes, led inexorably to a proliferation of stable structures – ‘machines’ – of greater and greater complexity, of which the human being is probably the most interesting production to date. Dawkins generally writes convincingly about the process of evolution, especially in The Selfish Gene, with many original explanations for curious anomalies of animal behaviour that do not, at first sight, appear to confer any evolutionary advantage.2 He argues well the case for his view that, once set in motion, evolution did not need continuous prompting by some superior being to ‘achieve’ what it has achieved. However, as we sat in the pub, it struck me how little of what we could see around us had evolved. Certainly, Dawkins and many others would assert that the people sitting there drinking had evolved (though in fact it would probably be more logical to claim only that their distant human ancestors had). But none of the artefacts we could see had evolved – the bar counter, bottles, drinks, televisions, tables, stools, pictures and posters, clothes and so on. All of these had been designed and manufactured by human beings, just as had all the material objects outside in the city – houses and shops, cars and buses, streets, bridges and office blocks. The capacity to envision and design these things is dependent on human consciousness, and on the capacity to reflect, which the standard theory of evolution is at a loss to explain. Dawkins himself concedes that the emergence of subjective consciousness is ‘the most profound mystery facing modern biology’. Not every writer on evolution has been so reluctant to take on the puzzle of Some Reflections on Dawkins 180 Studies • volume 106 • number 422 the emergence of consciousness in the process of evolution. The French Jesuit palaeontologist, Pierre Teilhard de Chardin, explored the issue at great length in his The Phenomenon of Man. Basically, Teilhard argues that consciousness ‘bursts forth’ during the process of evolution because it has always been there, in what Teilhard calls the ‘within’ of matter. In the world, he states, ‘Nothing could ever burst forth as final, across the different thresholds successively traversed by evolution, which has not already existed in an obscure and primordial way … a certain mass of elementary consciousness was originally imprisoned in the matter of earth’.3 An unexpected ally of Teilhard in his scrutiny of the ‘within’ of matter is Friedrich Engels. Engels was the philosophical brain behind the theory of dialectical materialism, exploited by his friend Karl Marx to provide an ideological foundation for his particular brand of socialism. Engels also focuses on the ‘within’ of matter, but particularly on the concepts of motion and becoming. ‘We have once again returned’, he says, ‘to the mode of contemplation of the great founders of Greek philosophy; that all nature, from the smallest thing to the biggest, from grains of sand to suns, from protista to man, has its existence in eternal coming into being and going out of being, in ceaseless flux, in unresting motion and change’.4 He goes on to say that, ‘The motion of matter is not merely crude mechanical motion, mere change of place; it is heat and light, electric and magnetic stress, chemical combination and disassociation, and, finally, consciousness’.5 He speculates whether the future ‘dead remnants’ of our solar system will ever again be converted into the raw material of new solar systems. He continues, ‘Here again either we must have recourse...

Subhuman Remainders: The Unbuilt Subject in Francis Bacon’s “Study of a Baboon”, Jan Švankmajer’s <em>Darkness, Light, Darkness</em>, and Patricia Piccinini’s “The Young Family”

Subhuman Remainders: The Unbuilt Subject in Francis Bacon’s “Study of a Baboon”, Jan Švankmajer’s <em>Darkness, Light, Darkness</em>, and Patricia Piccinini’s “The Young Family”

Biological Timekeeping: The Business of a Blind Watchmaker

Fundamental understanding of life depends on both structural and functional details at the molecular level. Continually improving means of measurement of spatial and dynamic properties of biochemical constituents and cellular components complement studies of whole organisms. Integration of the interaction of components to provide coherent behaviour depends on highly elaborate orchestration in space and time. Whereas spatial information on a nanometre resolution is available, and fast dynamic analyses provide biochemical reaction rates measured in nanoseconds, functional coordination of the system requires integrated time dependence. While we are well aware of the special complexity of living organisms, appreciation of temporal scales and their organisation in time is still fragmentary. This article summarises current developments in research on biological time on scales from nanoseconds to years, the networks that connect different time domains and the oscillations, rhythms and biological clocks that coordinate and synchronise the complexity of the living state. “It is the pattern maintained by this homeostasis, which is the touchstone of our personal identity. Our tissues change as we live: the food we eat and the air we breathe become flesh of our flesh, and bone of our bone, and the momentary elements of our flesh and bone pass out of our body every day with our excreta. We are but whirlpools in a river of ever-flowing water. We are not the stuff that abides, but patterns that perpetuate themselves”60. Wiener, 1954 “What are called structures are slow processes of long duration, functions are quick processes of short duration”61. Von Bertalanffy, 1952

Inclusive fitness and the sociobiology of the genome

Inclusive fitness theory provides conditions for the evolutionary success of a gene. These conditions ensure that the gene is selfish in the sense of Dawkins (The selfish gene, Oxford University Press, Oxford, 1976): genes do not and cannot sacrifice their own fitness on behalf of the reproductive population. Therefore, while natural selection explains the appearance of design in the living world (Dawkins in The blind watchmaker: why the evidence of evolution reveals a universe without design, W. W. Norton, New York, 1996), inclusive fitness theory does not explain how. Indeed, Hamilton’s rule is equally compatible with the evolutionary success of prosocial altruistic genes and antisocial predatory genes, whereas only the former, which account for the appearance of design, predominate in successful organisms. Inclusive fitness theory, however, permits a formulation of the central problem of sociobiology in a particularly poignant form: how do interactions among loci induce utterly selfish genes to collaborate, or to predispose their carriers to collaborate, in promoting the fitness of their carriers? Inclusive fitness theory, because it abstracts from synergistic interactions among loci, does not answer this question. Fitness-enhancing collaboration among loci in the genome of a reproductive population requires suppressing alleles that decrease, and promoting alleles that increase the fitness of its carriers. Suppression and promotion are effected by regulatory networks of genes, each of which is itself utterly selfish. This implies that genes, and a fortiori individuals in a social species, do not maximize inclusive fitness but rather interact strategically in complex ways. It is the task of sociobiology to model these complex interactions.

Henri Poincaré: A Scientific Biography, by Jeremy Gray

Henri Poincare: A Scientific Biography, by Jeremy Gray. Princeton, New Jersey, Princeton University Press, 2013, xvi, 592 pp. $35.00 US (cloth). Henri Poincare: A Scientific Biography is a welcome addition to the historiography of science. We have our biographies of political figures, activists, and literati but there is less material on scientists. This book makes a contribution by examining the life of an important scientist. Poincare was of course more than a scientist. He was a mathematician, a philosopher of science, and a popularizer. The latter role is particularly important because every generation needs its public intellectuals who transmit the science of their day into language suitable for the layperson. In this sense Poincare was a public intellectual in the same way that Richard Dawkins, in The Blind Watchmaker (Norton, 1986) and other works, makes evolutionary biology comprehensible to nonscientists. Author Jeremy Gray notes that Henri Poincare is the first book-length monograph on this important figure. In this regard Henri Poincare occupies a place of distinction in the literature about Poincare. In essence Gray gives the reader Poincare the thinker, the man who understood that the history of science is a history of failed theories replaced, but perhaps not supplanted, by new ones. This insight appears to square with Thomas Kuhn's The Structure of Scientific Revolutions (Chicago, 1962). Contrary to Aristotle's teachings, Poincare and, later, Ludwig Wittgenstein doubted that humans could directly apprehend reality. This new concept was a leap forward in humanity's understanding of the cosmos. It is easy for the layperson to convince himself or herself that the senses grasp reality, and it took a scientist and popularizer of the eminence of Poincare to convince people otherwise. Gray rates Poincare as a mathematician above all else and asserts that Poincare's major contributions were to this branch of knowledge. One perhaps hears the echo of Plato--in several of his dialogues--urging that one should immerse oneself in mathematics. Within the discipline of mathematics, Gray argues that Poincare's chief contribution was the formulation of algebraic topology. Also significant were his studies of algebraic geometry, the theory of transformation groups, and number theory. Yet much of his professional life revolved around physics and astronomy, where his work in electricity and magnetism owed much to his absorption of the physics of James Clerk Maxwell. Provocative is Gray's mention of World War I, beginning just a few years after Poincare's death. The war killed young scientists and mathematicians, just the sort of people who might have carried forward Poincare's legacy had they lived. War's end saw few scientists and mathematicians eager to champion Poincare's ideas to a new generation. Perhaps the war, if Gray is right, truncated Poincare's legacy for future generations. Even today he is not a household name. When one ponders the nineteenth century, one thinks, at a minimum, of Darwin and Nietzsche, not Poincare. Despite this state of affairs, Gray takes on the task of bringing to the fore Poincare's lasting influences on mathematics and science. …

Guest editorial: special issue on biologically inspired music, sound, art and design

The idea of using evolutionary computation for artistic purposes can be traced back to Dawkins. In his 1987 book, The Blind Watchmaker [1], Dawkins presents a program that allows the evolution of the morphology of ‘‘virtual creatures’’. The user guides the genetic algorithm, indicating the favorite biomorphs, avoiding the need to develop a fitness function. Using a similar approach, the seminal works of Sims [2], where genetic programming was used to evolve populations of images, and of Todd and Latham [3], where evolutionary techniques are used to evolve 3D forms with organic appearance, led to the emergence of a new research area, evolutionary art, which is characterized by the use of nature-inspired computing for artistic purposes. At the same time, early works in the field of evolutionary music explored the development of hard-wired functions [4] and of artificial neural networks [5] to assign fitness. Soon afterwards, Baluja et al. [6] applied artificial neural networks to guide the evolution of images. As is often the case in new research areas, particularly interdisciplinary ones, the first years were characterized by individual efforts and uncoordinated research, which often led to the reinvention of the wheel. This problem was amplified by the lack of scientific events specifically dedicated to the area, which led to the publication of these early efforts in generic evolutionary computation, artificial intelligence, neural networks or computer music conferences and journals.

Darwin, Darwinism, and Uncertainty by Charles M. Woolf

NEWMAN STUDIES JOURNAL 96 book reViews Darwin, Darwinism, and Uncertainty. By Charles M.Woolf. Chino Valley,AZ: One World Press,2012.Pages viii +168.Paper:ISBN–13:978–1–938043–02–4.$11.95. This book is a brief introduction to a larger philosophical and theological issue surrounding Darwinian theory—the role of chance in evolution and how this bears on a theistic view of the human person. The first portion of the book (94 pages) is a summary of Darwin’s biography,discussing his scientific achievements from his early work aboard the HMS Beagle to his final work on earthworms and orchids. Effort is made to relate this work to his changing views on science and religion and to some of the controversy surrounding his views on theism and naturalism. For those aware of the voluminous literature on these matters, there is little to note here. The author has taken account of the recent masterful biography by Janet Browne,1 but has not attempted to delve more deeply into the Darwin revealed by the massive Darwin Correspondence project.2 As a result, reliance is placed on the now badly obsolete Life and Letters, edited by Francis Darwin in 1887.3 The biographical sketch forms the backdrop to the two succeeding sections of the book, with Part II giving a brief sketch of scientific theories of the origins of the universe,running from the Big Bang,through the early“RNAWorld,”the origins of life, and the subsequent development of living beings up to the mass extinctions of the Cambrian and Cretaceous periods. The third portion of the book—“A Probabilistic Model for the Origin of Life Forms on Earth”—is the intended culmination of the argument.The author here plays on a theme made familiar by Richard Dawkins in his The Blind Watchmaker4 — human beings are the product of “the blind action and non-directionality of natural selection” (153). This is assumed to create considerable problems for all theistic religions, especially the Abrahamic traditions. John Henry Newman himself had seen the weakness of this way of posing questions even before Darwin, writing in his lecture“Christianity and Physical Science”in 1858 that “PhysicalTheology...is pretty much what it was two thousand years ago. . . .; it has been taken out of its place, has been put too prominently forward, and thereby has almost been used as an instrument against Christianity. . . .”5 In an overly brief concluding discussion, the author develops a probabilistic model of creation which “allows Darwinism to be made compatible with various different religions throughout the world whose 1 E. Janet Browne, Charles Darwin, Volume I, Voyaging (London: Jonathan Cape, 1995),Volume II, The Power of Place (London: Jonathan Cape, 2002). 2 Available at: http://www.darwinproject.ac.uk/. 3 The Life and Letters of Charles Darwin, 3 volumes, edited by his son, Francis Darwin (London: John Murray, 1887), available at: http://darwin-online.org.uk/converted/published/1887_Letters_F1452/ 1887_Letters_F1452.1.html. 4 Richard Dawkins, The Blind Watchmaker:Why the Evidence of Evolution Reveals a Universe Without Design (New York:W.W. Norton, 1986). 5 JHN,Idea of a University,450–451,available at:www.newmanreader.org/works/idea/article7.html. I am indebted to the excellent article by Ryan Vilbig,“John Henry Newman’s View of the ‘Darwin Theory’,” (Newman Studies Journal 8 (2011); 52–61) for leading me to this quotation and other comments by Newman on Darwin cited in this article. 97 doctrines and practices are not driven by creation myths and the primitive science of ancient times” (159, italics in original). There is little in this book to recommend to the readership of this journal. Like so many commentators whose perspective has been formed from a combination of Darwinian polemics against the flat-footed natural theology of Victorian England and an unreflective elevation of the concept of “chance” in relation to evolution, the whole issue of “creation” as understood in the central Judeo-Christian tradition is misconceived.“Evolution” and “creation” are presented as opposing explanations at the same level, and we simply replay a tedious story of oppositions that runs back to the conflicts of Stoics and Epicureans in Antiquity.6 Newman with rare perception, had...

We need a new language for evolution… everywhere

To help address public misunderstanding of evolution, we must find alternatives to anthropomorphic terminology, and I have some suggestions. In this issue Jacques Dubochet asserts that a major reason for the lack of public acceptance of evolution is a fundamental misunderstanding of its core concepts: many people think of evolution producing modifications with an aim, e.g. ‘eyes in order to see’, ‘legs for walking’, rather than in terms of directionless variation, and natural selection without motivation, design or strategy. And yet the latter two concepts are used by many biologists at some point when discussing evolution, be it in the scientific literature or in popular books. The conceptual problem is even deeper: for example Richard Dawkins cast evolution in the guise of a ‘blind watchmaker’ in his book of the same name, a concept that, whilst successfully communicating one aspect of evolution, might reinforce the notion that evolution works towards producing a particular entity with a pre-defined use: in this case a watch. The problem here is that the watchmaker (a defined professional), even if blind, must know the aim to which he is working, in order to be able to assess the success of his, albeit random, work. It is about time that we stopped such anthropomorphic terminology and thinking, and confronted the likelihood that – far from being ‘excusable shorthand’ – it is an important contributor to a false impression of evolution among many non-scientists. I feel that much of the ‘excuse’ for using terms that evoke will, direction and strategy in evolutionary processes is a problem of finding the right words; or at least of not falling so easily into the anthropomorphisms that we use in other realms of experience. A banal example shows how an apparently trivial change in words can radically change perceived meaning: to accomplish metabolic process X, enzyme Y evolved a specificity for Z. In an objective scientific sense, we should phrase this as ‘in accomplishing X, Y concomitantly evolved a specificity for Z’. It is that innocent little word ‘to’ that transforms the meaning, giving enzyme Y the essence of ‘will’ – ‘to’ being short for ‘in order to’, or ‘with the purpose of’. Purpose can only be exercised by a supernatural entity in this situation. There have even been meetings organised under titles such as ‘Molecular Strategies in Biological Evolution’. This and other examples impose a fallacious sense of direction of causality in evolution, and that is completely consistent with a common misconception of evolution facilitating organisms towards certain aims or goals. Another concept that arises from the ‘anthropomorphisation’ of evolution is the ‘problem’: in other words, an organism or system evolves towards what we, retrospectively, identify as a barrier, or ‘problem’ that had to be ‘solved’, and we wonder how it was overcome. Nature doesn't solve anything. ‘Evolved towards’ is another trap: we can only say ‘towards’ in retrospect. The system cannot actually evolve towards anything. So I have a few suggestions (see box). I believe that a large part of our difficulty in avoiding the invocation of agency and direction in evolutionary processes is our persistent inability to define natural selection in terms of physical laws and processes. The spread of information theory into biology would, in my opinion, greatly help. In the meantime, anthropomorphic terminology in evolution might persist just because scientists like using it. But it is one of the worst things we can do, given widespread public misunderstanding of the fundamental principles of evolution. And I bet that it even leads scientists themselves astray sometimes…

Creating prebiotic sanctuary: self-assembling supramolecular Peptide structures bind and stabilize RNA.

Any attempt to uncover the origins of life must tackle the known 'blind watchmaker problem'. That is to demonstrate the likelihood of the emergence of a prebiotic system simple enough to be formed spontaneously and yet complex enough to allow natural selection that will lead to Darwinistic evolution. Studies of short aromatic peptides revealed their ability to self-assemble into ordered and stable structures. The unique physical and chemical characteristics of these peptide assemblies point out to their possible role in the origins of life. We have explored mechanisms by which self-assembling short peptides and RNA fragments could interact together and go through a molecular co-evolution, using diphenylalanine supramolecular assemblies as a model system. The spontaneous formation of these self-assembling peptides under prebiotic conditions, through the salt-induced peptide formation (SIPF) pathway was demonstrated. These peptide assemblies possess the ability to bind and stabilize ribonucleotides in a sequence-depended manner, thus increase their relative fitness. The formation of these peptide assemblies is dependent on the homochirality of the peptide monomers: while homochiral peptides (L-Phe-L-Phe and D-Phe-D-Phe) self-assemble rapidly in aqueous environment, heterochiral diastereoisomers (L-Phe-D-Phe and D-Phe-L-Phe) do not tend to self-assemble. This characteristic consists with the homochirality of all living matter. Finally, based on these findings, we propose a model for the role of short self-assembling peptides in the prebiotic molecular evolution and the origin of life.

Mechanical Birds and Shapes of Ice: Hardy’s Vision of the ‘Blind Watchmaker’

Gillian Beer a mis en évidence l'impact de Darwin sur la littérature victorienne, comme si l'évolution s'était substituée à l'intrigue traditionnelle du roman. Métaphores et symboles permettent de rendre compte des mutations idéologiques issues des bouleversements scientifiques. Tel est bien le cas pour Thomas Hardy, dont l'œuvre porte l'empreinte des interrogations scientifiques et épistémologiques de son époque. Cet article s'inspire de la lecture que fait Richard Dawkins du Darwinisme, et notamment du concept de l'horloger aveugle, pour interroger, à travers quelques poèmes et Tess of the d'Urbervilles, deux images clefs de Hardy, l'oiseau mécanique et l'iceberg, et la façon dont le motif des rouages de la destinée révèle une mutation conceptuelle paradigmatique.

What's in a title? A two‐step approach to optimisation for man and machine

The point about peer review should be clear, because the title and abstract are all that is usually sent to prospective peer reviewers in the invitation email. However, if you genuinely have something new to say, how to write a title that will catch other scientists' eye, against the high background of titles with similar keywords in them? Though an article title will rarely be remembered as book titles are, at the point of first reading, the two have at least a couple things in common: placement of the most important concept at or near the beginning (where it most readily catches the reader's eye), and a construction that stimulates curiosity and is informative. Whether or not Darwin consciously thought about this, his title ‘On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life’ is arguably better than the following, possible, alternative: ‘The role of natural selection in the preservation of favoured races in the struggle for life, and production of new species’. The appearance of species was the riddle that he sought to explain – i.e. the object of his research and of public curiosity and controversy surrounding the origin of life on Earth – and he placed that concept first in the title. The terms ‘favoured races’ and ‘struggle for life’ added a bit of spice, as well as being informative of his thesis. With the benefit of over 100 years of research and the discovery of genes, Richard Dawkins wrote books with the both attractive and highly memorable titles ‘The Selfish Gene’ and ‘The Blind Watchmaker’, albeit for a broad public. ‘Titleology’ is quite a refined science, and publishers know all too well that the title of a book can seal its fate. The point about Google is a bit more subtle, but still very important. Despite a wonderful new search interface, launched last Autumn, PubMed is having a tough time competing with Internet search engines, king among these being Google. Certain journals already receive half of their article accesses via a combination of such search engines (percentage rising), and less than one fifth via PubMed (percentage falling). Whether this is good or bad is not for me to say here; the fact is that Google is an increasingly popular way of finding scientific literature (and my bet is that a significant proportion of such searches goes through plain old Google, rather than Google Scholar). In generating a ranking (position in the list) in their search results, Google, Excite and Lycos (but not Yahoo) ignore keywords that are designated as such (using the metadata tag ‘keywords’) in the html version of an article. That means that unless good keywords are placed in a title, these search engines will come to their own conclusion as to what the main topic of the article is. The ‘title’ tag receives a relatively high weighting in the Google algorithm, and it doesn't stop there: Google, unlike PubMed, indexes the full text of an article: titles of sections in an article – coded as h1, h2, h3, etc. (or similarly denoted) in the html version of the article – are also weighted relatively highly, decreasing in influence from h1 (heading), down to h3 (sub-sub-heading), for example. So, it pays to spend some time on keyword optimisation there too. Which keywords you use will depend on who you want to find your article, and why. Given the increasingly hard fight for citations, it is not a bad idea to consider the broadest audience that would cite your work, and not be narrowed to the peer group that attends the same conferences as you (this applies to the rest of the article too). Consider this process of optimisation for search engines as a second step of refining your title (and sections headings) after getting the acceptance letter from the editor. Ultimately, the knack is to combine the considerations of peer review with those of findability on the Internet, and create an interesting and informative title. Punctuation can help here, for example by separating the title into two parts. This is often done with a colon ‘:’ or a so-called ‘en-dash’. And as long as the title does not change its meaning, I believe that a two-step approach to optimising titles, as described above, is justified. After all, the context in which a reviewer is invited to review an article is significantly different from the context in which it is found among a multitude of competing titles in the jungle of the Internet…

Two Birds of Paradise in North Holland, 1592: The Gift in the Exotic

Two Birds of Paradise in North Holland, 1592: The Gift in the Exotic

Synthetic Biology, Gödel, and the Blind Watchmaker

Historically, biology is a science that has been caught up in the debate of how to approach living beings: from the analytical or synthetic viewpoint. The analytical view encompasses the most successful biological sciences, particularly genetics, molecular biology, and evolutionary biology. They are considered to be models of a reductionist approach to appraising living beings because, with few exceptions, the conceptual tools and methods they have developed focus on parts, components, or particular traits. In genetics the basic features are the Mendelian trait, the mechanics of inheritance, and the laws governing transmission from one generation to the next. Molecular biology focuses on the chemical nature of genetic traits (i.e., genes) and on the molecular machinery involved in their expression and regulation, giving rise to a particular function. Evolutionary biology focuses mainly on the study of how an organism’s fitness is affected by certain genetic traits. Eventually a trait can evolve differentially with respect to any other trait, with or without similar fitness. All three sciences can be considered gene-oriented, which is an accurate description, and during the last 50 years the biology syllabus has been greatly dominated by this gene-centered analytical view. But there is more to the analytical view than that. Analysis means the study of an entity by breaking it down into its parts, and the vast majority of sciences are analytical by definition. Genetics, molecular biology, and evolutionary biology have developed successful methodological tools to study those parts of living organisms that are genes. However, there are many other biological sciences that are analytical, which approach the living entity by focusing on particular parts. Probably one can state that the analytical view is a permanent methodological approach to living beings, no matter which organizational or hierarchical level we consider (Ayala 1968). Historically, biological sciences approaching living entities analytically have been unequally successful, and it is a matter of fact that those sciences focusing on genes have achieved greater success than others focusing on other areas. Current genomic sciences are the typical by-product of the gene-centered approach to living beings. But can we approach a living being in a different way? Yes and no. The basic perception of many biologists and scientists in general is that living entities (complex entities, broadly speaking) cannot be appraised via an approach that adds up their parts and, less so, by considering that one single part (for instance, the gene, the genome) is enough to gain sufficient understanding of the living entity as a whole. I would like to point out the difference between analytical and reductionist approaches to science, particularly in biology. Analytic approaches do not discard the combination of parts and, then, the rules and/or laws derived by working separately with the parts could eventually be joined in the hope of achieving an increasingly better explanation of the living being as a whole. On the contrary, the reductionist approach discards the explanatory relevance of many parts of the living system because it assumes that once we have discovered the laws governing one particular and essential part, the rest and the whole can be explained. It has been argued that the analytical view is a reductionist view of science when, in reality, it is not. The analytical view probably constitutes the primary methodology of scientific method. Although both approaches take a different stand on the understanding of complex features, they share a common problem: How to approach or explain the appearance of emergent properties? For the analytical approach, this question is normally solved a posteriori as follows: The emergent property,