Ten years after the Human Genome Project’s completion the life sciences stand in a moment of uncertainty, transition, and contestation. The postgenomic era has seen rapid shifts in research methodology, funding, scientific labor, and disciplinary structures. Postgenomics is transforming our understanding of disease and health, our environment, and the categories of race, class, and gender. At the same time, the gene retains its centrality and power in biological and popular discourse. The contributors to Postgenomics analyze these ruptures and continuities and (...) place them in historical, social, and political context. Postgenomics, they argue, forces a rethinking of the genome itself, and opens new territory for conversations between the social sciences, humanities, and life sciences. Contributors. Russ Altman, Rachel A. Ankeny, Catherine Bliss, John Dupré, Michael Fortun, Evelyn Fox Keller, Sabina Leonelli, Adrian Mackenzie, Margot Moinester, Aaron Panofsky, Sarah S. Richardson, Sara Shostak, Hallam Stevens. (shrink)

Today's science tells us that our bodies are filled with molecular machinery that orchestrates all sorts of life processes. When we think, microscopic "channels" open and close in our brain cell membranes; when we run, tiny "motors" spin in our muscle cell membranes; and when we see, light operates "molecular switches" in our eyes and nerves. A molecular-mechanical vision of life has become commonplace in both the halls of philosophy and the offices of drug companies, where researchers are developing “proton (...) pump inhibitors” or medicines similar to Prozac. Membranes to Molecular Machines explores just how late twentieth-century science came to think of our cells and bodies this way. This story is told through the lens of membrane research, an unwritten history at the crossroads of molecular biology, biochemistry, physiology, and the neurosciences, that directly feeds into today's synthetic biology as well as nano- and biotechnology. Mathias Grote shows how these sciences not only have made us think differently about life, they have, by reworking what membranes and proteins represent in laboratories, allowed us to manipulate life as "active matter" in new ways. Covering the science of biological membranes in the United States and Europe from the mid-1960s to the 1990s, this book connects that history to contemporary work with optogenetics, a method for stimulating individual neurons using light, and will enlighten and provoke anyone interested in the intersection of chemical research and the life sciences—from practitioner to historian to philosopher. (shrink)

Solid state physics, the study of the physical properties of solid matter, was the most populous subfield of Cold War American physics. Despite prolific contributions to consumer and medical technology, such as the transistor and magnetic resonance imaging, it garnered less professional prestige and public attention than nuclear and particle physics. Solid State Insurrection argues that solid state physics was essential to securing the vast social, political, and financial capital Cold War physics enjoyed in the twentieth century. Solid state’s technological (...) bent, and its challenge to the “pure science” ideal many physicists cherished, helped physics as a whole respond more readily to Cold War social, political, and economic pressures. Its research kept physics economically and technologically relevant, sustaining its cultural standing and policy influence long after the sheen of the Manhattan Project had faded. (shrink)

In 1935 geneticist Nikolai Timoféeff-Ressovsky, radiation physicist Karl G. Zimmer, and quantum physicist Max Delbrück published “On the Nature of Gene Mutation and Gene Structure,” known subsequently as the “Three-Man Paper.” This seminal paper advanced work on the physical exploration of the structure of the gene through radiation physics and suggested ways in which physics could reveal definite information about gene structure, mutation, and action. Representing a new level of collaboration between physics and biology, it played an important role in (...) the birth of the new field of molecular biology. The paper’s results were popularized for a wide audience in the What is Life? lectures of physicist Erwin Schrödinger in 1944. Despite its historical impact on the biological sciences, the paper has remained largely inaccessible because it was only published in a short-lived German periodical. Creating a Physical Biology makes the Three Man Paper available in English for the first time. Brandon Fogel’s translation is accompanied by an introductory essay by Fogel and Phillip Sloan and a set of essays by leading historians and philosophers of biology that explore the context, contents, and subsequent influence of the paper, as well as its importance for the wider philosophical analysis of biological reductionism. (shrink)

Collecting, comparing, and computing molecular sequences are among the most prevalent practices in contemporary biological research. They represent a specific way of producing knowledge. This paper explores the historical development of these practices, focusing on the work of Margaret O. Dayhoff, Richard V. Eck, and Robert S. Ledley, who produced the first computer-based collection of protein sequences, published in book format in 1965 as the Atlas of Protein Sequence and Structure. While these practices are generally associated with the rise of (...) molecular evolution in the 1960s, this paper shows that they grew out of research agendas from the previous decade, including the biochemical investigation of the relations between the structures and function of proteins and the theoretical attempt to decipher the genetic code. It also shows how computers became essential for the handling and analysis of sequence data. Finally, this paper reflects on the relationships between experimenting and collecting as two distinct “ways of knowing” that were essential for the transformation of the life sciences in the twentieth century. (shrink)

This article examines to what extent a particular case of cross-disciplinary research in the 1930s was structured by mechanistic reasoning. For this purpose, it identifies the interfield theories that allowed biologists and chemists to use each other’s techniques and findings, and that provided the basis for the experiments performed to identify plant growth hormones and to learn more about their role in the mechanism of plant growth. In 1930, chemists and biologists in Utrecht and Pasadena began to cooperatively study plant (...) growth. I will argue that these researchers decided to join forces because they believed to rely on each other’s findings and methods to solve their research problems adequately. In the course of the cooperation, organic chemists arrived at isolating plant growth hormones by using a test method developed in plant physiology. This achievement, in turn, facilitated biologists’ investigation of the mechanism of plant growth. Researchers eventually believed to have the means to study the relation between a substance’s molecular structure and its physiological activity. The way they conceptualized the problem of identifying hormones and unraveling the mechanism of plant growth, as well as their actual research actions are compatible with the new mechanists’ account of mechanism research. The study illustrates that focusing on researchers’ mechanistic reasoning can contribute considerably to explaining the structure of cross-disciplinary research projects. (shrink)

Alongside the renowned male pioneers of medical cytogenetics, many women participated in investigations at the laboratory bench and the bedside, both in Europe and the Americas. These women were committed to this new biological and clinical practice—cytogenetics, the origins of contemporary genetic diagnosis—and contributed to the creation of new biological concepts and settings centered on the study of chromosome imaging. This paper will review the contributions made by a group of woman scientists from a wide geographical distribution, situating their names (...) and research agendas within the history of a field dating back to early plant and insect cytogenetics. Rather than an exhaustive compendium of women geneticists, this essay presents a kind of historical reconstruction that can be achieved by placing women at center stage in their geographies and networks of circulating cytogenetic knowledge and practices thereby relating a history of genetic images though the work carried out by women, retrieving their agency and constructing an inclusive history of an influential contemporary biomedical practice as it gained increasing influence in the laboratory and the clinic. (shrink)

This essay details a historical crossroad in biochemistry and microbiology in which penicillin was a co-agent. I narrate the trajectory of the bacterial cell wall as the precise target for antibiotic action. As a strategic object of research, the bacterial cell wall remained at the core of experimental practices, scientific narratives and research funding appeals throughout the antibiotic era. The research laboratory was dedicated to the search for new antibiotics while remaining the site at which the mode of action of (...) this new substance was investigated. This combination of circumstances made the bacterial wall an ontology in transit. As invisible as the bacterial wall was for clinical purposes, in the biological laboratory, cellular meaning in regard to the action of penicillin made the bacterial wall visible within both microbiology and biochemistry. As a border to be crossed, some components of the bacterial cell wall and the biochemical destruction produced by penicillin became known during the 1950s and 1960s. The cell wall was constructed piece by piece in a transatlantic circulation of methods, names, and images of the shape of the wall itself. From 1955 onwards, microbiologists and biochemists mobilized new names and associated conceptual meanings. The composition of this thin and rigid layer would account for its shape, growth and destruction. This paper presents a history of biochemical morphology: a chemistry of shape – the shape of bacteria, as provided by its wall – that accounted for biology, for life itself. While penicillin was being established as an industrially-manufactured object, it remained a scientific tool within the research laboratory, contributing to the circulation of further scientific objects. (shrink)

Molecular biologists exploit information conveyed by mechanistic models for experimental purposes. In this article, I make sense of this aspect of biological practice by developing Keller’s idea of the distinction between ‘models of’ and ‘models for’. ‘Models of (phenomena)’ should be understood as models representing phenomena and are valuable if they explain phenomena. ‘Models for (manipulating phenomena)’ are new types of material manipulations and are important not because of their explanatory force, but because of the interventionist strategies they afford. This (...) is a distinction between aspects of the same model. In molecular biology, models may be treated either as ‘models of’ or as ‘models for’. By analysing the discovery and characterization of restriction–modification systems and their exploitation for DNA cloning and mapping, I identify the differences between treating a model as a ‘model of’ or as a ‘model for’. These lie in the cognitive disposition of the modeller towards the model: a modeller will look at a model as a ‘model of’ if interested in its explanatory force, or as a ‘model for’ if interested in the material manipulations it can possibly afford. (shrink)

The concept of ‘Fifth Business’ is used to analyze a minority standpoint and bring serious attention to the role of scientists who play a galvanizing role in a science but for multiple reasons appear less prominently in more common recounts of any particular development. Biochemist Ray Wu published a DNA sequencing experiment in March 1970 using DNA polymerase catalysis and specific nucleotide labeling, both of which are foundational to general sequencing methods today. The scant mention of Wu’s work from textbooks, (...) research articles, and other accounts of DNA sequencing calls into question how scientific collective memory forms. This alternative history seeks to understand why a key figure in nucleic acid sequence analysis has remained less visibly connected or peripheral to solidifying narratives about the history of DNA sequencing. The study resists predictable dismissals of Wu’s work in order to seriously examine the formation of his nucleic acid sequence analysis research program and how he shared his knowledge of sequencing during a period of rapid advancement in the field. An analysis of Wu’s work on sequencing the cohesive ends of lambda bacteriophage in the 1960s and 1970s exemplifies how a variety of individuals and groups attempted to develop protocol for sequencing the order of nucleotide base pairs comprising DNA. This historical examination of the sociality of scientific research suggests a way to understand how Wu and others contributed to the very collective memory of DNA sequencing that Wu eventually tried to repair. The study of Wu, who was a Chinese immigrant to the United States, provides a foundation for further critical scholarship on the heterogeneous histories of Asian American bioscientists, the sociality of their scientific works, and how the resulting knowledge produced is preserved, if not evenly, in a scientific field’s collective memory. (shrink)

In the 1950s and 1960s, the search for the mechanism of oxidative phosphorylation by biochemists paralleled the description of mitochondrial form by George Palade and Fritiof Sjöstrand using electron microscopy. This paper explores the extent to which biochemists studying oxidative phosphorylation took mitochondrial form into account in the formulation of hypotheses, design of experiments, and interpretation of results. By examining experimental approaches employed by the biochemists studying oxidative phosphorylation, and their interactions with Palade, I suggest that use of mitochondrial form (...) as a guide to experimentation and interpretation varied considerably among investigators. Most notably, Peter Mitchell, whose chemiosmotic hypothesis was ultimately the basis of the correct mechanism of oxidative phosphorylation, incorporated crucial aspects of mitochondrial form into his model that others failed to recognize. I discuss these historical observations in terms of the background and training of the biochemists, as well as a proposed heuristic of form, whose use may increase the possibility that biologically meaningful molecular mechanisms will be discovered. (shrink)

Review of: Sophia Roosth, Synthetic: How Life Got Made (University of Chicago Press, 2017); and Andrew S. Balmer, Katie Bulpin, and Susan Molyneux-Hodgson, Synthetic Biology: A Sociology of Changing Practices (Palgrave Macmillan, 2016).

This paper is about the interaction and the intertwinement between history of science as a historical process and history of science as the historiography of this process, taking molecular biology as an example. In the first part, two historical shifts are briefly characterized that appear to have punctuated the emergence of molecular biology between the 1930s and the 1980s, one connected to a new generation of analytical apparatus, the other to properly molecular tools. The second part concentrates on the historiography (...) of this development. Basically, it distinguishes three phases. The first phase was largely dominated by accounts of the actors themselves. The second coincided with the general ‘practical turn’ in history of science at large, and today’s historical appropriations of the molecularization of the life sciences appear to be marked by the changing disciplinary status of the science under review. In a closing remark, an argument is made for differentiating between long-range, middle-range and short-range perspectives in dealing with the history of the sciences. (shrink)

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has (...) been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights. (shrink)

This paper describes the activities of amateur plant breeders and their application of various methods and technologies derived from genetics research over the course of the twentieth century. These ranged from selection and hybridization to more interventionist approaches such as radiation treatment to induce genetic mutations and chemical manipulation of chromosomes. I argue that these activities share characteristics with twenty-first-century do-it-yourself (DIY) biology (a recent upswing in amateur experimental biology) as well as other amateur science and technology of the twentieth (...) century. The characterization of amateur plant breeding as amateur experimental biology offers a corrective to a dominant narrative within the history of biology, in which the turn to experimental research in the early twentieth century is thought to have served as an obvious dividing line between amateur and professional activities. Considered alongside other better-known amateur efforts, it also suggests that we might gain something by taking a more unified approach to the study of amateur science and technology. (shrink)

ABSTRACT Rosalind Franklin is best known for her informative X-ray diffraction patterns of DNA that provided vital clues for James Watson and Francis Crick's double-stranded helical model. Her scientific career did not end when she left the DNA work at King's College, however. In 1953 Franklin moved to J. D. Bernal's crystallography laboratory at Birkbeck College, where she shifted her focus to the three-dimensional structure of viruses, obtaining diffraction patterns of Tobacco mosaic virus (TMV) of unprecedented detail and clarity. During (...) the next five years, while making significant headway on the structural determination of TMV, Franklin maintained an active correspondence with both Watson and Crick, who were also studying aspects of virus structure. Developments in TMV research during the 1950s illustrate the connections in the emerging field of molecular biology between structural studies of nucleic acids and of proteins and viruses. They also reveal how the protagonists of the “race for the double helix” continued to interact personally and professionally during the years when Watson and Crick's model for the double-helical structure of DNA was debated and confirmed. (shrink)

ABSTRACT Rosalind Franklin is best known for her informative X-ray diffraction patterns of DNA that provided vital clues for James Watson and Francis Crick's double-stranded helical model. Her scientific career did not end when she left the DNA work at King's College, however. In 1953 Franklin moved to J. D. Bernal's crystallography laboratory at Birkbeck College, where she shifted her focus to the three-dimensional structure of viruses, obtaining diffraction patterns of Tobacco mosaic virus (TMV) of unprecedented detail and clarity. During (...) the next five years, while making significant headway on the structural determination of TMV, Franklin maintained an active correspondence with both Watson and Crick, who were also studying aspects of virus structure. Developments in TMV research during the 1950s illustrate the connections in the emerging field of molecular biology between structural studies of nucleic acids and of proteins and viruses. They also reveal how the protagonists of the “race for the double helix” continued to interact personally and professionally during the years when Watson and Crick's model for the double-helical structure of DNA was debated and confirmed. (shrink)

This last result leads, rather naturally, to some concluding observations and a series of questions for further investigation. These case studies show that in all of the sites examined, the institutionalization of molecular biology as a “discipline” was primarily driven by the need to separate groups of practitioners with divergent but overlapping interests within the local context. Thus molecular biology was contingently separated from agricultural or medical biochemistry, virology, work on the physiology of nucleic acids, and so forth for contingent (...) local institutional reasons. This makes it even more pressing to try to understand how molecular biology came to be delimited on a larger scale. How did it come to be a discipline with specific intellectual content (or did it?), including some problems, tools, and practices and excluding others? How did it gain authority as the forefront biological science by the mid-1960s? We need to understand the ways in which the tensions between different practices, projects, aims, understandings of the goals of molecular biology, and so on were resolved, on what scale and in what venues, so that something approximating the political character of a discipline, rather than a federation, was achieved. If these case studies provide a sound starting point, it will nevertheless prove difficult to answer the interconnected questions implicit here satisfactorily.One means of getting at such questions that should prove of considerable interest is to examine carefully the work of those who were widely cited in the papers of the late fifties through the mid-seventies by the people now considered major founders of molecular biology. By studying the contributions of those who are now omitted in the standard histories and recollections, we will gain a clearer sense of the possibilities that were open as molecular biology took shape. It is already widely recognized that the contributions of a number of biochemists have been given short shrift, but (as the example of Ernest Gale in Rheinberger's study illustrates) there are a great many more figures whose line of work were then crucial but who are now overlooked.6 To understand both what molecular biology was at the time of its early institutionalization and what is has become, it will be enormously helpful to understand at what point the definition or ideology “hardened” and the grounds for inclusion and exclusion of individuals and lines of work were reformed. Studies of this sort are appropriate in many other areas as well, of course; in general, they should different histories, political standing, and institutional bases of those disciplines in their national cultures. It is likely (but a matter for investigation!) that such differences influenced the opportunities for introducing new bench practices, if in no other way than by delimiting the niches within which certain practices could be initiated.7 And since new practices can fail to achieve their objectives, can transform the direction of work and disciplinary allegiances of their practitioners, can lead to only routine results, or can open up important new vistas, the character of the available niches from which to work can prove to have a strong influence on the direction that new work takes if and when it starts to flourish. A key aspect of this problematic (not yet adequately studied, I believe) is the problem of drawing boundaries between different kinds of work and determining where each should fit among established disciplines and/or within some new construct. To the extent that an “international” solution is ultimately achieved to such problems, it must surely be achieved in light of initially different ways of dealing with it in different countries.Underlying work of the sort we have been exploring is the thorny problem of how best to contextualize the work being studied. This, I believe, is one of the major historiographic problems that we must face in the history of science. It is by no means a new problem, of course, but a particularization of the age-old problem of the (seeming) overdetermination of historical events. If we deal with local cultures, to understand how they develop and their fate we need to understand their location within larger cultures. But it is utterly unclear how to draw appropriate boundaries on the relevant larger culture(s). As even this brief discussion has shown, institutional cultures, the cultures of sponsoring agencies, “the” culture of science (or of biological science, physical science, etc., as appropriate), and national cultures all can provide relevant contexts, all can occasionally determine the fate of work undertaken in a particular local context. The potentially intractable problem of delimiting the boundaries of investigation looms large here, but it is one that must be faced explicity if we are to profit fully from the enormously stimulating investigations of local cultures exemplified in the four papers published in this symposium. My own view is that we have no abstract standard available for determining which boundaries are appropriate to a given study, and, indeed, that no single contextualization is adequate to the examination of any given case, but that, nonetheless, we can (at least sometimes) distinguish useful and explanatory delimitations of the larger context from others that prove to be misleading.Against this background, I hope that the four papers published in this special issue will stimulate the readers of the JHB to carry out similar studies—that is, studies that seek to characterize and contextualize local experimental cultures —over a wide range of cases. I also hope that some of those who take up this challenge will deal with the larger questions raised by the need to find a way of balancing different, sometimes competing, contextualizations of such studies. The fact that any given case requires multiple contextualizations, resulting in multifaceted representations no one of which is alone adequate, will surely land us in fascinating, hopefully fruitful and productive, controversies. (shrink)

ArgumentThis paper examines the role of metaphors in science on the basis of a historical case study. The study explores how metaphors of “genetic information,” “genetic code,” and scripture representations of heredity entered molecular biology and reshaped experimentation during the 1950s and 1960s. Following the approach of the philosopher Hans Blumenberg, I will argue that metaphors are not merely a means of popularization or a specific kind of modeling but rather are representations that can unfold an operational force of their (...) own.While the influence of cybernetics and information theory on molecular biology is well documented in historical analysis throughout recent years, this paper offers new insights into the metaphysical and religious resonances of textual metaphors in the life sciences. The main focus will be on developments in Germany, in particular on the work of the German biochemist Gerhard Schramm. In this historical case study the interaction between metaphors and experimental practices will be discussed. The paper analyzes different phases in the use of metaphors during the 1950s and 1960s: it will explore how the metaphors of a “genetic alphabet” or of “genetic code” developed into a new research program and eventually attained ontological status in the early 1960s. At that time Schramm's use of textual metaphors was reminiscent of nineteenth-century German natural philosophy. In this case, the metaphorical shift shows how the metaphor of a “genetic text” or a “genetic code,” which were central for the emerging molecular biology, drew on older cultural traditions with all of their metaphysical and religious preoccupations. (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)

_Philosophy of Molecular Medicine: Foundational Issues in Theory and Practice_ aims at a systematic investigation of a number of foundational issues in the field of molecular medicine. The volume is organized around four broad modules focusing, respectively, on the following key aspects: What are the nature, scope, and limits of molecular medicine? How does it provide explanations? How does it represent and model phenomena of interest? How does it infer new knowledge from data and experiments? The essays collected here, authored (...) by prominent scientists and philosophers of science, focus on a handful of mainstream topics in the philosophical literature, such as _causation_, _explanation_, _modeling_, and _scientific inference_. These previously unpublished contributions shed new light on these traditional topics by integrating them with problems, methods, and results from three prominent areas of contemporary biomedical science: _basic research_, _translational_ and _clinical research_, and _clinical practice_. (shrink)

"Helmreich's analysis--extensive, imaginative, rigorous, and insightful--promises to establish him as "the" cultural authority on A-Life.... He shows that, in the age of complexity, science simultaneously disenchants and re-enchants the world.... The book is written in a personal and engaging style... so full of ideas and interesting asides [that] Helmreich takes on the persona of a smart and well-informed tour guide of the A-Life world [with] an enviable ability to take very complex ideas and discuss them comprehensibly without simplifying them."--Hugh Gusterson, (...) author of "Nuclear Rites". (shrink)

Since the early nineteenth century a membrane or wall has been central to the cell’s identity as the elementary unit of life. Yet the literally and metaphorically marginal status of the cell membrane made it the site of clashes over the definition of life and the proper way to study it. In this article I show how the modern cell membrane was conceived of by analogy to the first “artificial cell,” invented in 1864 by the chemist Moritz Traube (1826–1894), and (...) reimagined by the plant physiologist Wilhelm Pfeffer (1845–1920) as a precision osmometer. Pfeffer’s artificial cell osmometer became the conceptual and empirical basis for the law of dilute solutions in physical chemistry, but his use of an artificial analogue to theorize the existence of the plasma membrane as distinct from the cell wall prompted debate over whether biology ought to be more closely unified with the physical sciences, or whether it must remain independent as the science of life. By examining how the histories of plant physiology and physical chemistry intertwined through the artificial cell, I argue that modern biology relocated vitality from protoplasmic living matter to nonliving chemical substances—or, in broader cultural terms, that the disenchantment of life was accompanied by the (re)enchantment of ordinary matter. (shrink)