The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases (‘the tetranucleotide hypothesis’); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these (...) cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts. (shrink)

In 2003, biophysicist and Nobel Laureate Maurice Wilkins published his autobiography entitled The Third Man. In the preface, he diffidently points out that the title was chosen by his publisher, as a reference to the famous 1949 movie no doubt, featuring Orson Welles in his classical role as penicillin racketeer Harry Lime. In this paper I intend to show that there is much more to this title than merely its familiar ring. If subjected to a comparative analysis, multiple correspondences between (...) movie and memoirs can be brought to the fore. Taken together, these documents shed an intriguing light on the vicissitudes of budding life sciences research during the post-war era. I will focus my comparative analysis on issues still relevant today, such as dual use, the handling of sensitive scientific information and, finally, on the interwovenness of science and warfare. Thus, I will explain how science autobiographies on the one hand and genres of the imagination on the other may deepen our comprehension of tensions and dilemmas of life sciences research then and now. For that reason, science autobiographies can provide valuable input for teaching philosophy and history of science to science students. (shrink)

We trace the history of the Modern Evolutionary Synthesis, and of genetic Darwinism generally, with a view to showing why, even in its current versions, it can no longer serve as a general framework for evolutionary theory. The main reason is empirical. Genetical Darwinism cannot accommodate the role of development (and of genes in development) in many evolutionary processes. We go on to discuss two conceptual issues: whether natural selection can be the “creative factor” in a new, more general framework (...) for evolutionary theorizing; and whether in such a framework organisms must be conceived as self-organizing systems embedded in self-organizing ecological systems. (shrink)

According to vitalism, living organisms differ from machines and all other inanimate objects by being endowed with an indwelling immaterial directive agency, ‘vital force,’ or entelechy . While support for vitalism fell away in the late nineteenth century many biologists in the early twentieth century embraced a non vitalist philosophy variously termed organicism/holism/emergentism which aimed at replacing the actions of an immaterial spirit with what was seen as an equivalent but perfectly natural agency—the emergent autonomous activity of the whole organism. (...) Organicists hold that organisms unlike machines are ‘more than the sum of their parts’ and predict that the vital properties of living things can never be explained in terms of mechanical analogies and that the reductionist agenda is doomed to failure. Here we review the current status of the mechanist and organicist conceptions of life particularly as they apply to the cell. We argue that despite the advances in biological knowledge over the past six decades since the molecular biological revolution, especially in the fields of genetics and cell biology the unique properties of living cells have still not been simulated in mechanical systems nor yielded to reductionist—analytical explanations. And we conclude that despite the dominance of the mechanistic–reductionist paradigm through most of the past century the possibility of a twentyfirst century organicist revival cannot be easily discounted. (shrink)

In the 1950s and 1960s, an interfield interaction between molecular biologists and biochemists integrated important discoveries about the mechanism of protein synthesis. This extended discovery episode reveals two general reasoning strategies for eliminating gaps in descriptions of the productive continuity of mechanisms: schema instantiation and forward chaining/backtracking. Schema instantiation involves filling roles in an overall framework for the mechanism. Forward chaining and backtracking eliminate gaps using knowledge about types of entities and their activities. Attention to mechanisms highlights salient features of (...) this historical episode while providing general reasoning strategies for mechanism discovery. (shrink)

Philosophers have proposed various kinds of relations between Mendelian genetics and molecular biology: reduction, replacement, explanatory extension. This paper argues that the two fields are best characterized as investigating different, serially integrated, hereditary mechanisms. The mechanisms operate at different times and contain different working entities. The working entities of the mechanisms of Mendelian heredity are chromosomes, whose movements serve to segregate alleles and independently assort genes in different linkage groups. The working entities of numerous mechanisms of molecular biology are larger (...) and smaller segments of DNA plus related molecules. Discovery of molecular DNA mechanisms filled black boxes that were noted, but unilluminated, by Mendelian genetics. (shrink)

In this paper I present a model of rational belief change, and I show how to use it to obtain a better insight into the debate about the nature of pneumococcal transformation, genes and DNA that took place in the forties, as a result of Oswald T. Avery’s work. The model offers a particular elaboration of the concept of inference to the best explanation, along decision theoretic lines. Within this framework, I distinguish different senses in which Avery’s team can be (...) said to have proceeded with caution, thus throwing some light upon a persistent source of disagreement among researchers in the history of genetics. In addition, I explain why we are entitled to say that rival parties such as physicist Maclyn McCarty and biochemist Alfred Mirsky were epistemically rational, in spite of the fact that they reached different conclusions on the basis of the same evidence. (shrink)

Recent completion of the human genome sequence is a spectacular achievement of the 20th-century biology. This achievement has opened the door for future revolutions in biological and medical sciences. By learning about the gene sequences and the individual genetic differences, scientists hope to understand the molecular basis of the normal state and the diseased state of life on one hand, and individualize medicine on the other hand. However, the human genome sequencing project was not an isolated, spectacular undertaking. Rather, it (...) was a natural extension and the culmination of the advances in the science and techniques of molecular biology. The present article is an attempt to summarize these major landmarks in the history of DNA research, beginning from the identification of “nuclein.”. (shrink)

The Central Dogma of molecular biology, which holds that DNA makes protein and not the other way around, is as influential as it is controversial. Some believe the Dogma has outlived its usefulness, either because it fails to fully capture the ins-and-outs of protein synthesis (Griffiths and Stotz, 2013; Stotz, 2006), because it turns on a confused notion of information (Sarkar, 2004), or because it problematically assumes the unidirectional flow of information from DNA to protein (Gottlieb, 2001). This paper evaluates (...) an underexplored defense of the Dogma, which relies on the assumption that the Dogma and the Inheritance of Acquired Traits, a principle which dates as far back as Jean Baptiste-Lamarck, are incompatible principles (Smith, 1993; Judson, 1979; Dawkins, 1970; Cobb, 2017; Wilkins, 2002; Graur, 2018). By appealing to empirical evidence in molecular science, I argue that this apparent incompatibility is indeed merely apparent. I conclude by briefly demonstrating how these considerations bear on the topic of conceptual pluralism in the philosophy of science (Stencel and Proszewska, 2018; Lu and Bourrat, 2018). (shrink)

In this study we have examined the reception of Mendelism in France from 1900 to 1940, and the place of some of the extra-Mendelian traditions of research that contributed to the development of genetics in France after World War II.

Philosophers of science turned to historical case studies in part in response to Thomas Kuhn's insistence that such studies can transform the philosophy of science. In this issue Joseph Pitt argues that the power of case studies to instruct us about scientific methodology and epistemology depends on prior philosophical commitments, without which case studies are not philosophically useful. Here I reply to Pitt, demonstrating that case studies, properly deployed, illustrate styles of scientific work and modes of argumentation that are not (...) well handled by currently standard philosophical analyses. I illustrate these claims with exemplary findings from case studies dealing with exploratory experimentation and with interdisciplinary cooperation across sciences to yield multiple independent means of access to theoretical entities. The latter cases provide examples of ways that scientists support claims about theoretical entities that are not available in work performed within a single discipline. They also illustrate means of correcting systematic biases that stem from the commitments of each discipline taken separately. These findings illustrate the transformative power of case study methods, allow us to escape from the horns of Pitt's "dilemma of case studies," and vindicate some of the post-Kuhn uses to which case studies have been put. (shrink)

The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases (...) as proceeding via the elimination of candidate structures through the successive application of component-level information and interpretations of X-ray diffraction photographs, each of which serves as a kind of constraint on structure. Then, I argue that although each kind of constraint enables the elimination of a considerable proportion of candidate structures, component-level constraints are significantly more likely to do so correctly. Thus, considering them before X-ray diffraction photographs is a better heuristic than one that reverses this order. Because the synthetic approach that resulted in the determination of the protein and DNA structures exemplifies such a heuristic, its use can help account for these discoveries. (shrink)

Scientific research is constrained by limited resources, so it is imperative that it be conducted efficiently. This paper introduces the notion of epistemic expression, a kind of representation that expedites the solution of research problems. Epistemic expressions are representations that (i) contain information in a way that enables more reliable information to place the most stringent constraints on possible solutions and (ii) make new information readily extractible by biasing the search through that space. I illustrate these conditions using historical and (...) contemporary examples of biomolecular structure determination. Then, I argue that the notion of epistemic expression parts ways with pragmatic accounts of scientific representation and an understanding of models as artifacts, neither of which require models to accurately represent. Explicating epistemic expression thus fills a gap in our understanding of scientific practice, extending Morrison and Morgan's (1999) conception of models as investigative instruments. (shrink)

Diauxie is at the origin of research that led Jacques Monod, François Jacob, and André Lwoff to win the Nobel Prize in Physiology or Medicine in 1965 for their description of the first genetic regulatory model. Diauxie is a term coined by Jacques Monod in 1941 in his doctoral dissertation that refers to microbial growth in two phases. In this article, we first examine Monod’s thesis to demonstrate how and why Monod interpreted diauxie as a phenomenon of enzyme inhibition or (...) suppression of adaptive enzymes. We also briefly investigate prior enzyme suppression studies, before Monod’s work, which indicate that he is the first person to observe diauxic growth. Second, we analyse Monod’s post-thesis publications throughout his scientific career, revealing that diauxic inhibition was a significant part of Monod’s scientific activities and greatly fascinated Monod until the end of his life. Paradoxically, Monod’s work and interest on diauxic inhibition are still neglected in historical recounts, focused mostly on Monod’s enzymatic adaptation studies. Indeed, we uncovered a statement by Monod’s colleague, Lwoff, who transformed a quotation from Monod by replacing the word phenomenon with enzymatic adaptation, which we believe has influenced historians. Finally, we offer hypotheses to explain why Lwoff altered Monod’s statement. (shrink)

The recent historiography of molecular biology features key technologies, instruments and materials, which offer a different view of the field and its turning points than preceding intellectual and institutional histories. Radioisotopes, in this vein, became essential tools in postwar life science research, including molecular biology, and are here analyzed through their use in experiments on bacteriophage. Isotopes were especially well suited for studying the dynamics of chemical transformation over time, through metabolic pathways or life cycles. Scientists labeled phage with phosphorus-32 (...) in order to trace the transfer of genetic material between parent and progeny in virus reproduction. Initial studies of this type did not resolve the mechanism of generational transfer but unexpectedly gave rise to a new style of molecular radiobiology based on the inactivation of phage by the radioactive decay of incorporated phosphorus-32. These ‘suicide experiments’, a preoccupation of phage researchers in the mid-1950s, reveal how molecular biologists interacted with the traditions and practices of radiation geneticists as well as those of biochemists as they were seeking to demarcate a new field. The routine use of radiolabels to visualize nucleic acids emerged as an enduring feature of molecular biological experimentation. (shrink)

The traditional practice of establishing morphological types and investigating morphological organization has found new support from evolutionary developmental biology (evo-devo), especially with respect to the notion of body plans. Despite recurring claims that typology is at odds with evolutionary thinking, evo-devo offers mechanistic explanations of the evolutionary origin, transformation, and evolvability of morphological organization. In parallel, philosophers have developed non-essentialist conceptions of natural kinds that permit kinds to exhibit variation and undergo change. This not only facilitates a construal of species (...) and higher taxa as natural kinds, but also broadens our perspective on the diversity of kinds found in biology. There are many different natural kinds relevant to the investigative and explanatory aims of evo-devo, including homologues and developmental modules. (shrink)

Unlike in physics, the category of thought experiment is not very common in biology. At least there are no classic examples that are as important and as well-known as the most famous thought experiments in physics, such as Galileo’s, Maxwell’s or Einstein’s. The reasons for this are far from obvious; maybe it has to do with the fact that modern biology for the most part sees itself as a thoroughly empirical discipline that engages either in real natural history or in (...) experimenting on real organisms rather than fictive ones. While theoretical biology does exist and is recognized as part of biology, its role within biology appears to be more marginal than the role of theoretical physics within physics. It could be that this marginality of theory also affects thought experiments as sources of theoretical knowledge. Of course, none of this provides a sufficient reason for thinking that thought experiments are really unimportant in biology. It is quite possible that the common perception of this matter is wrong and that there are important theoretical considerations in biology, past or present, that deserve the title of thought experiment just as much as the standard examples from physics. Some such considerations may even be widely known and considered to be important, but were not recognized as thought experiments. In fact, as we shall see, there are reasons for thinking that what is arguably the single most important biological work ever, Charles Darwin’s On the Origin of Species, contains a number of thought experiments. There are also more recent examples both in evolutionary and non-evolutionary biology, as we will show. Part of the problem in identifying positive examples in the history of biology is the lack of agreement as to what exactly a thought experiment is. Even worse, there may not be more than a family resemblance that unifies this epistemic category. We take it that classical thought experiments show the following characteristics: They serve directly or indirectly in the non-empirical epistemic evaluation of theoretical propositions, explanations or hypotheses. Thought experiments somehow appeal to the imagination. They involve hypothetical scenarios, which may or may not be fictive. In other words, thought experiments suppose that certain states of affairs hold and then try to intuit what would happen in a world where these suppositions are true. We want to examine in the following sections if there are episodes in the history of biology that satisfy these criteria. As we will show, there are a few episodes that might satisfy all three of these criteria, and many more if the imagination criterion is dropped or understood in a lose sense. In any case, this criterion is somewhat vague in the first place, unless a specific account of the imagination is presupposed. There will also be issues as to what exactly “non-empirical” means. In general, for the sake of discussion we propose to understand the term “thought experiment” here in a broad rather than a narrow sense here. We would rather be guilty of having too wide a conception of thought experiment than of missing a whole range of really interesting examples. (shrink)

This paper proposes an experiment-based methodology for both classical genetics and molecular biology by integrating Lindley Darden’s mechanism-centered approach and C. Kenneth Waters’s phenomenon-centered approach. We argue that the methodology basing on experiments offers a satisfactory account of the development of the two biological disciplines. The methodology considers discovery of new mechanisms, investigation of new phenomena, and construction of new theories together, in which experiments play a central role. Experimentation connects the three type of conduct, which work as both ends (...) and means, occurring in a circular way and constituting an overall process of scientific practice from classical genetics to molecular biology. (shrink)

Erwin Schrödinger’s 1944 publication What is Life? is a classic of twentieth century science writing. In his book, Schrödinger discussed the chromosome fibre as the seat of heredity and variation thanks to a hypothetical aperiodic structure – a suggestion that famously spurred on a generation of scientists in their pursuit of the gene as a physico-chemical entity. While historical attention has been given to physicists who were inspired by the book, little has been written about its biologist readers. This paper (...) examines the case of the English evolutionary botanist and cytologist Irène Manton, who took an interest in What is Life? for its relevance to her own research in chromosome structure as a clue to plant phylogeny. Drawing on recently discovered correspondence between Manton and Schrödinger, the paper reconstructs Manton ‘s path to the book and her response to it by way of throwing new light on a pivotal moment in the history of the debate on chromosome structure. (shrink)

Bruno Latour, as part of his advocacy of science studies urges us to move beyond what he calls ‘the Modernist Settlement’ that, among other things, separated science from politics and subject from object. As part of this project he has frequently called for the abolition of epistemology, including quite specifically the historical epistemology/epistemological history of Gaston Bachelard and Georges Canguilhem. Pierre Bourdieu, on the other hand, deploys the resources of historical epistemology, to dismiss Latour’s science studies. After examining the charges (...) against historical epistemology and their rebuttal, I rule in favor of the defense. However, I also suggest that Latour raises genuine concerns about how to equip ourselves to tackle problems such as those associated with climate change; these are problems that require engagement with the politics of nature, with the politics of the sciences of nature and with the epistemological challenges associated with the need to deploy multiple disciplines in the service of complex, practical, policy-relevant problem solving. (shrink)

Historians tend to speak of the problem of the origin of species or the species question, as if it were a monolithic problem. In reality, the phrase refers to a, historically, surprisingly fluid and pluriform scientific issue. It has, in the course of the past five centuries, been used in no less than ten different ways or contexts. A clear taxonomy of these separate problems is useful or relevant in two ways. It certainly helps to disentangle confusions that have inevitably (...) emerged in the literature in its absence. It may, secondly, also help us to gain a more thorough understanding, or sharper view, of the history of evolutionary thought. A consequent problem-centric look at that history through the lens of various origin of species problems certainly yields intriguing results, including and particularly for our understanding of the genesis of the Wallace–Darwin theory of evolution through natural selection. (shrink)

Historians tend to speak of the problem of the origin of species or the species question, as if it were a monolithic problem. In reality, the phrase refers to a, historically, surprisingly fluid and pluriform scientific issue. It has, in the course of the past five centuries, been used in no less than ten different ways or contexts. A clear taxonomy of these separate problems is useful or relevant in two ways. It certainly helps to disentangle confusions that have inevitably (...) emerged in the literature in its absence. It may, secondly, also help us to gain a more thorough understanding, or sharper view, of the history of evolutionary thought. A consequent problem-centric look at that history through the lens of various origin of species problems certainly yields intriguing results, including and particularly for our understanding of the genesis of the Wallace–Darwin theory of evolution through natural selection. (shrink)

There has been a long-standing opposition to genetically modified organisms worldwide. Some studies have tried to identify the deep-lying philosophical, conceptual as well as psychological motivations for this opposition. Philosophical essentialism, psychological essentialism, and vitalism have been proposed as possible candidates. I approach the plausibility of the claim that these notions are related to GMO opposition from a historical perspective. Vitalism and philosophical essentialism have been associated with anti-GMO stance on account of their purported hostility to species and organismic mutability. (...) I show that vitalism has often been associated to various mutabilist theories, whereas the case for philosophical essentialism as motivating GMO opposition depends on the now discredited Essentialism Story that had constructed essentialism as a predominant view in pre-Darwinian science. Further, as philosophical essentialism taken seriously is incompatible with the reality of genetic engineering, it is unlikely to be a reason for opposition. Psychological essentialism, involving an instinctive repulsion from the practice of manipulating what is thought to be the essence of living beings, is a more likely reason for resistance to transgenesis. Yet even here, historical considerations are crucial. Not only lay people tend to essentialize genes, but scientists themselves can be shown to have been complicit in essentialist tendencies. From the advent of modern genetics, the imagery of the all-powerful genes, often depicted by scientists themselves metaphorically as material counterparts of the now obsolete vitalistic agent, has permeated the language of leading scientific figures, whose influence in shaping public opinion should not be downplayed. Enthusiasm for genetic engineering and the abhorrence from it might both derive from the same unrealistic image of the essential gene, the revision of which thus holding out the hope for transcending the present impasse of the GMO controversy. (shrink)

A central idea of developmental systems theory is ‘parity’ or ‘symmetry’ between genes and non-genetic factors of development. The precise content of this idea remains controversial, with different authors stressing different aspects and little explicit comparisons among the various interpretations. Here I characterise and assess several influential versions of parity.

In the advertising discourse of human genetic database projects, of genetic ancestry tracing companies, and in popular books on anthropological genetics, what I refer to as the anthropological gene and genome appear as documents of human history, by far surpassing the written record and oral history in scope and accuracy as archives of our past. How did macromolecules become "documents of human evolutionary history"? Historically, molecular anthropology, a term introduced by Emile Zuckerkandl in 1962 to characterize the study of primate (...) phylogeny and human evolution on the molecular level, asserted its claim to the privilege of interpretation regarding hominoid, hominid, and human phylogeny and evolution vis-à-vis other historical sciences such as evolutionary biology, physical anthropology, and paleoanthropology. This process will be discussed on the basis of three key conferences on primate classification and evolution that brought together exponents of the respective fields and that were held in approximately ten-years intervals between the early 1960s and the 1980s. I show how the anthropological gene and genome gained their status as the most fundamental, clean, and direct records of historical information, and how the prioritizing of these epistemic objects was part of a complex involving the objectivity of numbers, logic, and mathematics, the objectivity of machines and instruments, and the objectivity seen to reside in the epistemic objects themselves. (shrink)

This paper explores the special problems encountered by the biographer of a living scientific subject. In particular, it explores the complex of problems that emerges from the intense interpersonal dynamic involving issues of distance, privacy and trust. It also explores methodological problems having to do with oral history interviews and other supporting documentation. It draws on the personal experience of the author and the biographical subject of G. Ledyard Stebbins Jr., the botanist, geneticist and evolutionist. It also offers prescriptives and (...) recommendations for future research. (shrink)

Forty years’ experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements revealed multiple (...) widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell–cell signaling, symbiosis and pathogenesis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of ‘higher’ plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings. (shrink)

Forty years’ experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements revealed multiple (...) widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell–cell signaling, symbiosis and pathogenesis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of ‘higher’ plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings. Previous article in issue. (shrink)

Patricia Smith Churchland's Neurophilosophy argues that a mind is the same thing as the complex patterns of neural activity in a human brain and, furthermore, that we will be able to find out interesting things about the mind by studying the brain. I basically agree with this stance and my comments are divided into four sections. First, comparisons between human and non?human primate brains are discussed in the context, roughly, of where one should locate higher functions. Second, I examine Churchland's (...) views on reduction and levels of organization, which I find mostly congenial. Third, a key point of disagreement about the relationship and importance of language to specifically human cognition is taken up. I like Churchland's critique of certain sentential paradigms, but I try to show using an analogy with cellular coding systems why we need to get a better theory of ?sentences?. Finally, I discuss how the models introduced in the last chapter might be extended to make better contact with neurobiology and language. (shrink)

The thesis of theory-ladenness of observations, in its various guises, is widely considered as either ill-conceived or harmless to the rationality of science. The latter view rests partly on the work of the proponents of New Experimentalism who have argued, among other things, that experimental practices are efficient in guarding against any epistemological threat posed by theory-ladenness. In this paper I show that one can generate a thesis of theory-ladenness for experimental practices from an influential New Experimentalist account. The notion (...) I introduce for this purpose is the concept of ‘theory-driven data reliability judgments’, according to which theories which are sought to be tested with a particular set of data guide reliability judgments about those very same data. I provide various prominent historical examples to show that TDRs are used by scientists to resolve data conflicts. I argue that the rationality of the practices which employ TDRs can be saved if the independent support of the theories driving TDRs is construed in a particular way. (shrink)