The interests of synthetic biologists may appear to differ greatly from those of evolutionary biologists. The engineering of organisms must be distinguished from the tinkering action of evolution; the ambition of synthetic biologists is to overcome the limits of natural evolution. But the relations between synthetic biology and evolutionary biology are more complex than this abrupt opposition: Synthetic biology may play an important role in the increasing interactions between functional and evolutionary biology. In practice, synthetic biologists have learnt to submit (...) the proteins and modules they construct to a Darwinian process of selection that optimizes their functioning. More importantly, synthetic biology can provide evolutionary biologists with decisive tools to test the scenarios they have elaborated by resurrecting some of the postulated intermediates in the evolutionary process, characterizing their properties, and experimentally testing the genetic changes supposed to be the source of new morphologies and functions. This synthetic, experimental evolution will renew and clarify many debates in evolutionary biology: It will lead to the explosion of some vague concepts as constraints, parallel evolution, and convergence, and replace them with precise mechanistic descriptions. In this way, synthetic biology resurrects the old philosophical debate about the relations between the real and the possible. (shrink)

In this accessible and fascinating book, Michel Morange draws on recent advances in molecular genetics, evolutionary biology, astrobiology, and other disciplines to find today’s answers to the question of life.

Synthetic biology emerged around 2000 as a new biological discipline. It shares with systems biology the same modular vision of organisms, but is more concerned with applications than with a better understanding of the functioning of organisms. A herald of this new discipline is Craig Venter who aims to create an artificial microorganism with the minimal genome compatible with life and to implement into it different 'functional modules' to generate new micro-organisms adapted to specific tasks. Synthetic biology is based on (...) the possibilities raised by genetic engineering, but it aims to engineer organisms, and not simply to modify them, mimicking the practice of computer engineers. Three points will be discussed: In what regard does synthetic biology represent a new epistemology of the life sciences? What are the relations between synthetic biology and evolutionary biology? What is the raison d'être of synthetic biology as a discipline independent of nanotechnologies? (shrink)

This Special Issue of Origins of Life and Evolution of Biospheres contains papers based on the contributions presented at the Conference "Defining Life" held in Paris (France) on 4-5 February, 2008. The main objective of this Conference was to confront speakers from several disciplines--chemists, biochemists, biologists, exo/astrobiologists, computer scientists, philosophers and historians of science--on the topic of the definition of life. Different viewpoints of the problem approached from different perspectives have been expounded and, as a result, common grounds as well (...) as remaining diverging arguments have been identified. In addition to individual talks, two large roundtables gave ample room for speakers to discuss their diverging viewpoints. This volume collects almost all the contributions presented during the Conference and provides a rich spectrum of renewed answers to the ever-standing question "What is Life?". Besides the arguments directly regarding this question, more philosophical or historical reflections are also proposed in this issue that were not presented during the Conference. This volume also offers a synthesis written by J. Gayon taking each contribution into account. To conclude this foreword, we would like to thank all the participants and speakers who made this Conference a most stimulating event. Each provided novel ideas to "Defining Life" while highlighting the extreme difficulty to reach a consensus on this topic. We are also very grateful to the French CNRS Interdisciplinary Program Origines des Planètes et de la Vie (Origins of Planets and Life) for its generous support, as well as to the National Museum of Natural History in Paris for hosting the Conference. We also thank Alan W. Schwartz for generously offering this space for publishing the Proceedings of the Conference. (shrink)

This special issue of Biological Theory is focused on development; it raises the problem of the temporal and spatial boundaries of development. From a temporal point of view, when does development start and stop? From a spatial point of view, what is it exactly that "develops", and is it possible to delineate clearly the developing entity? This issue explores the possible answers to these questions, and thus sheds light on the definition of development itself.

It is frequently said that biology is emerging from a long phase of reductionism. It would be certainly more correct to say that biologists are abandoning a certain form of reductionism. We describe this past form, and the experiments which challenged the previous vision. To face the difficulties which were met, biologists use a series of concepts and metaphors - pleiotropy, tinkering, epigenetics - the ambiguity of which masks the difficulties, instead of solving them. In a similar way, the word (...) “post-genomics” has different meanings, depending upon who uses it. Which of these meanings will become dominant in the future is an open question. (shrink)

The convergence of developmental biology — embryology — and molecular biology was one of the major scientific events of the last decades of the twentieth century. The transformation of developmental biology by the concepts and methods of molecular biology has already been described. Less has been told on the reciprocal transformation of molecular biology on contact with higher organisms. The transformation of molecular biology occurred at the end of a deep crisis which affected this discipline in the sixties and seventies (...) and which led to a cruel criticism of the preexisting models of gene regulation. Numerous new, sometimes heterodox, models were proposed to describe the level at which gene regulation took place and its underlying mechanisms. The crisis resolved itself at the beginning of the eighties with the rapid accumulation of results from genetic engineering techniques and, above all, a displacement of the descriptive level from the molecule to the cell. This displacement gave molecular biologists the 'explanandum' which had been cruelly lacking during their initial study of higher organisms. The new molecular cell biology is an interfield explanation of living phenomena, relating a description and an interpretation localized at different levels of organization. (shrink)

A great deal of progress has recently been made in characterizing the “mechanisms of aging.” A comparison with the mechanisms of development shows that the two sets of mechanisms are different; nevertheless, mechanisms of aging are conditioned by what happens during development. Aging and development also share some characteristics, such as a similar difficulty in attributing a precise temporal boundary to these processes. Other characteristics seem more specific to aging, such as the role of external and stochastic events in its (...) progression. In fact, both development and aging are historical processes with a mixture of stochastic events and deterministic processes, the ratio of the two being different in each process. Therefore, it is concluded that aging does not fit with a broad, lifelong conception of development. (shrink)

In recent decades the expression "molecular biology" has progressively disappeared from journals, and no longer designates new chairs or departments. This begs the question: does it mean that molecular biology is dead, and has been displaced by new emerging disciplines such as systems biology and synthetic biology? Maybe its reductionist approach to living phenomena has been substituted by one that is more holistic. The situation, undoubtedly, is far less simple. To appreciate better what has happened it is necessary to acknowledge (...) the following: the intial project of molecular biologists was not a reductionist one, but an attempt to naturalize the phenomena of life by using the epistemological principles of physics as a model; and, it is necessary to distinguish the early stages of molecular biology, and the later aggregating process which gave it its present characteristics. Only one of these characteristics, the importance of the informational vision, has been seriously challenged in recent years. But it is obvious that the ambition of most early molecular biologists to discover simple rules and principles explaining all of biological facts has vanished. The pendulum has now moved toward the study of the diversity generated by a long evolutionary history. (shrink)

The modern synthesis has been considered to be wrongly called a “synthesis”, since it had completely excluded embryology, and many other disciplines. The recent developments of Evo-Devo have been seen as a step in the right direction, as complementing the modern synthesis, and probably leading to a “new synthesis”.My argument is that the absence of embryology from the modern synthesis was the visible sign of a more profound lack: the absence of functional biology in the evolutionary synthesis. I will consider (...) the reasons for this absence, as well as the recent transformations which favoured a closer interaction between these two branches of biology. Then I will describe two examples of recent work in which functional and evolutionary questioning were tightly linked. The most significant part of the paper will be devoted to the transformation of evolutionary theory that can be expected from this encounter: a deep transformation, or simply an experimental confirmation of this theory? I will not choose between these two different possibilities, but will discuss some of the difficulties which make the choice problematic. (shrink)

Relations between physics and biology have been always difficult. One reason is that physical approaches to the phenomena of life have frequently been conceived by their authors as alternatives to biological explanations. My argument is that molecular descriptions and explanations have been pushed so far that they have reached their limits: these limits constitute a favourable niche in which physical explanations can develop. I will focus on the field of molecular and cell biology and give many examples of these recent (...) physical studies made possible by the precision of molecular observations. The nature of these niches is probably diverse. I consider that it is too early to have a global view of the interactions between biological and physical explanations, and to organize them into different categories. Such interactions are not new within the life sciences: the history of biology reveals a complex, permanently moving landscape of interactions between biological and physical explanations. (shrink)

The construction of synthetic life might appear to be the natural objective of the emerging discipline of synthetic biology. The situation, though, is not that simple. Plans to synthesize life appeared quite early, at the beginning of the 20th century (Bensaude-Vincent 2009; Deichmann 2009; Fox Keller 2002; Pereto and Catala 2007). Nor can synthetic biology be identified with work on the origin of life. Nevertheless, it is remarkable that a new, more integrated approach to the origin of life appeared exactly (...) when synthetic biology was emerging (Szostak, Bartel, and Luisi 2001).Most synthetic biologists have the more limited ambition of modifying existing organisms by giving them new functionalities. Synthetic .. (shrink)

The comparison between natural evolution and the action of a tinkerer has become highly popular since its reintroduction by François Jacob at the end of the 1970s. It has been used as a weapon against the existence of an “intelligent design” as well as a way for synthetic biologists to promote their ambitious projects. I will describe the complex history of this metaphor, and examine its pertinence. Whereas Darwin considered it as a way to describe how evolution proceeded, Jacob linked (...) it with a description of the imperfections of organisms, while Stephen Jay Gould and Richard Lewontin criticized what they called the “Panglossian” vision of most evolutionary biologists. The distinction between the work of engineers and that of tinkerers is not obvious. There are limits to the process of evolution, but their alleged description so far reflects the limits of knowledge on the part of evolutionary biologists more than the existence of true barriers to the evolutionary process. And, in their work, synthetic biologists crucially need the optimizing action of natural selection. To give a definition of synthetic biology is no easy task; the false distinction drawn between the work of synthetic biologists and the action of evolution is of no help. (shrink)

The existence of a genetic program of development was proposed by molecular biologists in the nineteen-sixties. Historians and philosophers of science have since thoroughly criticized this notion. To fully appreciate its significance, it is interesting to consider the research which was pursued during this period by molecular biologists who proposed this notion. This study focuses on François Jacob's work and on the model of development supported by his lab in the early seventies, the T-complex model. This episode of Jacob's scientific (...) activity has since been forgotten. Characterization of this model shows that the notion of program was used in a metaphoric way and that it did not put any constraint on the work pursued in the lab at that time. Some attention is devoted to the origin of this metaphor in the context of the nineteen-seventies. (shrink)

The increasing place of evolutionary scenarios in functional biology is one of the major indicators of the present encounter between evolutionary biology and functional biology (such as physiology, biochemistry and molecular biology), the two branches of biology which remained separated throughout the twentieth century. Evolutionary scenarios were not absent from functional biology, but their places were limited, and they did not generate research programs. I compare two examples of these past scenarios with two present-day ones. At least three characteristics distinguish (...) present and past efforts: An excellent description of the systems under study, a rigorous use of the evolutionary models, and the possibility to experimentally test the evolutionary scenarios. These three criteria allow us to distinguish the domains in which the encounter is likely to be fruitful, and those where the obstacles to be overcome are high and in which the proposed scenarios have to be considered with considerable circumspection. (shrink)

Between 1975 and 1985 a series of experiments demonstrated that cancer, whatever its causative agent, is due to the activation, by modification or overexpression, of a family of genes highly conserved during evolution, called the cellular oncogenes. These genes participate in the control of cell division in every living cell. Their products belong to the regulatory network relaying external signals from the membranes towards the nucleus and allowing cells to adapt their division rate to the demand of the organism. These (...) discoveries constitute what may be called the 'oncogene paradigm'. Although the existence of cellular oncogenes, assumed in early models of oncogenesis, was demonstrated as early as 1976, we will show in this article that this discovery was not sufficient for the development of the new paradigm. We will describe its slow and complex formation between 1980 and 1985 followed by its rapid acceptance by the scientific community. (shrink)

There are two facets to the central dogma proposed by Francis Crick in 1957. One concerns the relation between the sequence of nucleotides and the sequence of amino acids, the second is devoted to the relation between the sequence of amino acids and the native three-dimensional structure of proteins. 'Folding is simply a function of the order of the amino acids,' i.e. no information is required for the proper folding of a protein other than the information contained in its sequence. (...) This protein side of the central dogma was elaborated in a scientific context in which the characteristics and functions of proteins, and the mechanisms of protein folding, were seen very differently. This context, which made the folding problem a simple one, supported the bold proposition of Francis Crick. The protein side of the central dogma was not challenged by the discovery of prions if one adopts the definition of information given by Francis Crick. It might have been challenged by the discovery that regulatory enzymes exist in different conformations, and the evidence for the existence of chaperones assisting protein folding. But it was not, and folding remains what it was for Francis Crick, 'simply a function of the order of amino acids'. But the meaning of 'function' has dramatically changed. It is no longer the result of simple physicochemical laws, but that of a long evolutionary process which has optimized protein folding. Molecular mechanistic explanations have to be allied with evolutionary explanations, in a way characteristic of present biology. (shrink)

In this second decade of the 21st century, we find the pervasive influence of synthetic biology everywhere, not only in research laboratories, but also in the discourses of politicians and ethicists. Despite its ubiquity, the precise meaning of the notions of "synthetic biology" and "synthetic life," as well as their history, potential, and risks, remain obscure not only to the layperson, but also to most biologists.The aim of this special issue is twofold. First, it is intended to help the reader (...) better appreciate what synthetic biology is all about and what are its roots. Second, once the overall picture has been expounded and made clearer, the questions of whether research in synthetic biology raises new and .. (shrink)

The Britten–Davidson model of genetic regulation was well received by American molecular biologists and embryologists, but not by the members of the French School of molecular biology. In particular, François Jacob considered it too abstract and too removed from experiments. I re-examine the contrast between the Britten–Davidson model and the operon model by Jacob and Monod, the different scientific contexts in which they were produced and the different roles they played. I also describe my recent encounters with Eric Davidson, and (...) how I discovered the extraordinary continuity of his work on the development of the sea urchin, as well as his rich personality. (shrink)

The development of the genome editing system called CRISPR–Cas9 has opened a huge debate on the possibility of modifying the human germline. But the types of changes that could and/or ought to be made have not been discussed. To cast some light on this debate, I will describe the story of the CRISPR–Cas9 system. Then, I will briefly review the projects for modification of the human species that were discussed by biologists throughout the twentieth century. Lastly, I will show that (...) for plenty of reasons, both scientific and societal, germline modification is no longer a priority for our societies. (shrink)

Between November 30th and December 2nd, 2015, the Jacques Loeb Centre for the History and Philosophy of the Life Sciences at Ben-Gurion University of the Negev in Beer Sheva held its Eighth International Workshop under the title “From Genome to Gene: Causality, Synthesis and Evolution”. Eric Davidson, the founder of the concept of developmental Gene Regulatory Networks, had regularly attended the previous meetings, and his participation in this one was expected, but he suddenly passed away 3 months before. In this (...) paper, we provide an introduction and overview on five papers that were presented at the workshop and examine the importance of genomes and gene regulatory networks in extant biology, developmental biology, evolutionary biology and medicine, as well as a collection of remembrances of Eric Davidson, of his personality as well as of his scientific contributions. Historical perspectives are provided, and the ethical issues raised by the new tools developed to modify the genome are also discussed. (shrink)

For molecular biologists, the question What is Life?" disappeared in the 1960s to reemerge recently. The reasons for this reemergence will be analysed: they tell us much about the recent transformations of biology, and its present state. This question can be considered as a thermometer, which measures the balance between reductionist vs. holist explanations in biology: when the question disappears, reductionist approaches are dominant; when the question reappears, the reductionist vision is challenged.

The history of research on pseudoalleles, closely linked genes that have similar functions, is rich and complex. Because pseudoalleles’ proximity on the chromosome makes their distinction by the complementation tests traditionally used by geneticists difficult, and because they have similar functions, they were initially often considered as allelic forms of the same gene, hence their name. The Hox cluster is an emblematic example of a pseudoallelic gene complex. The first observations of pseudoalleles were made very early but remained puzzling until (...) a simple model explaining their formation and characteristics emerged in the middle of the 1930s. This model suggested that pseudoalleles originated by gene.. (shrink)

Different types of explanations coexist in present-day biology. Functional explanations describe mechanisms, whereas evolutionary explanations provide answers to the question “why?” mostly by appealing to the past and present action of natural selection. But the relations between these two types of explanations, as well as the relative insights they offer, vary from one domain of research to another. We will illustrate this complex landscape of biological explanations with three examples involving aging, the sex ratio, and the phenomenon of genomic imprinting. (...) We will show that the two types of explanations have recently often progressed towards each other. In consequence, they cease to be “pure” functional or evolutionary explanations and become explanations that may be alternatively considered as functional or evolutionary. (shrink)

Il y a trente ans, Georges Canguilhem montrait que la question « Qu'est-ce que la vie ? » avait eu une histoire, qui semblait s'être arrêtée avec l'avènement de la biologie moléculaire. Nous montrons que la question a réémergé ces dernières années. Nous analysons les raisons de cette renaissance, et la nature des réponses qui lui sont aujourd'hui apportées. 30 years ago, Georges Canguilhem showed that the question « What's life ? » had its own story, which seemed to have (...) stopped with the surge of molecular biology. We show that the matter has recently been raised anew. We analyze the reasons for such a rebirth and the nature of the answers that may today be given for such a phenomenon. (shrink)