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Vaccines are among the greatest tools for prevention and control of disease. They have eliminated smallpox from the planet, decreased morbidity and mortality for major infectious diseases like polio, measles, mumps, and rubella, significantly blunted the impact of the COVID-19 pandemic, and prevented viral induced cancers such as cervical cancer caused by human papillomavirus. Recent technological advances, in genomics, structural biology, and human immunology have transformed vaccine development, enabling new technologies such as mRNA vaccines to greatly accelerate development of new and improved vaccines. In this review, we briefly highlight the history of vaccine development, and provide examples of where advances in genomics and structural biology, paved the way for development of vaccines for bacterial and viral diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Collaborative studies open doors to breakthroughs otherwise unattainable by any one laboratory alone. Here we describe the initial collaboration between the Griffith and de Lange laboratories that led to thinking about the telomere as a DNA template for homologous recombination, the proposal of telomere looping, and the first electron micrographs of t-loops. This was followed by collaborations that revealed t-loops across eukaryotic phyla. The Griffith and Tomáška/Nosek collaboration revealed circular telomeric DNA (t-circles) derived from the linear mitochondrial chromosomes of nonconventional yeast, which spurred discovery of t-circles in ALT-positive human cells. Collaborative work between the Griffith and McEachern labs demonstrated t-loops and t-circles in a series of yeast species. The de Lange and Zhuang laboratories then applied super-resolution light microscopy to demonstrate a genetic role for TRF2 in loop formation. Recent work from the Griffith laboratory linked telomere transcription with t-loop formation, providing a new model of the t-loop junction. A recent collaboration between the Cesare and Gaus laboratories utilized super-resolution light microscopy to provide details about t-loops as protective elements, followed by the Boulton and Cesare laboratories showing how cell cycle regulation of TRF2 and RTEL enables t-loop opening and reformation to promote telomere replication. Twenty years after the discovery of t-loops, we reflect on the collective history of their research as a case study in collaborative molecular biology., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Developments in proximity ligation methods and sequencing technologies have provided high-resolution views of the organization of the genome inside the nucleus. A prominent feature of Hi-C maps is regions of increased self-interaction called topologically associating domains (TADs). Despite the strong evolutionary conservation and clear link with gene expression, the exact role of TADs and even their definition remains debatable. Here, I review the discovery of TADs, how they are commonly identified, and the mechanisms that lead to their formation. Furthermore, I discuss recent results that have created a more nuanced view of the role of TADs in the regulation of genes. In light of this, I propose that when we define TADs, we also consider the mechanisms that shape them., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Jacques Monod (1971) argued that certain molecular processes rely critically on the property of chemical arbitrariness, which he claimed allows those processes to "transcend the laws of chemistry". It seems natural, as some philosophers have done, to interpret this in modal terms: a biological relationship is chemically arbitrary if it is possible, within the constraints of chemical "law", for that relationship to have been otherwise than it is. But while modality is certainly important for understanding chemical arbitrariness, understanding its biological role also requires an account of the concrete causal-functional features that distinguish arbitrary from non-arbitrary phenomena. In this paper I elaborate on this under-emphasised aspect by offering a general account of these features: arbitrary relations are instantiated by mechanisms that involve molecular adapters, which causally couple two properties or processes which would otherwise be uncorrelated. Additionally, adapters work by acting as intermediate rather than cooperating causes., (Copyright © 2019. Published by Elsevier Ltd.)

Here, I discuss the development and future of structural molecular biology, concentrating on the eukaryotic transcription machinery and reflecting on John Kendrew's legacy from a personal perspective., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

By celebrating the 100th anniversary of John Kendrew's birth in 1917, the Journal of Molecular Biology recognizes his seminal contributions to science in general and structural biology in particular. John was first to use X-ray diffraction to solve the 3-dimensional structure of a protein, sperm-whale myoglobin, worthy of a Nobel Prize in Chemistry in 1962. John was the Founder and first Editor-in-Chief of the Journal of Molecular Biology, Deputy Chairman of the Laboratory of Molecular Biology and Head of its Division of Structural Studies, a Founder of the European Molecular Biology Organization, first Director-General of the European Molecular Biology Laboratory, and 33rd President of St. John's College, Oxford. In this personal perspective I relate how I came to know John as his postdoctoral fellow at the Laboratory of Molecular Biology in 1967 and as his biographer 45 years later., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this paper, I revisit the development of the repression model of genetic regulation in the lac operon to challenge a common application of a conceptual framework in the history of biology. I take Allen's (1978) account of the changes in the life sciences during the early and mid-twentieth century as an example of a common application of a framework based on the dichotomy between a mechanistic, or reductionist, approach to science and a holistic one. From this conceptual framework, Allen infers two general claims about the process of science and its goals: (1) that "mechanistic materialism" has often presented a more practical way to begin the study of complex phenomena in the life sciences, and (2) that the approach described as "holistic materialism" provides a more complete or accurate description of the natural world. The development of the lac operon model does not fit Allen's generalizations about scientific developments, and it can be used to cast some doubt on the scope of application of that conceptual framework. I argue that a better framework to interpret particular episodes in the history of molecular biology is to consider the ways in which biologists prioritize and track different aspects of the phenomena under study, rather than to focus on whether certain scientific practices are best described as developing from mechanistic to more holistic approaches. I end with some implications for the historiography of science by considering the appropriateness of different conceptual frameworks for different grains of resolution in the history of biology., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This symposium marks the achievement of a transformation in the history of science. Whereas in the 1960s, the study of modern developments was marginal to the field, it has now become a key part of the discipline's central concerns. The contrast between this conference and a 1960 symposium is illuminating. The paper reflects on the tensions over the future direction of the discipline expressed at the 1974 semi-centenary conference of the History of Science Society. Today, genomics with its vast demand for resources and its challenges to traditional boundaries is not untypical of a wide range of scientific activities. Its study can serve as a pioneering case study interesting for itself and important for a wider understanding of science. Papers at this meeting show the implications for the understanding of methods, appropriate targets of study, the interpretation of images and the preservation of archives., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The essay is an empirical case study of famed British scientist Francis Crick. Viewing him as a 'cross-worlds influencer' who was moreover dedicated to a cause, I have tried to understand how these two characteristics influenced the trajectory of his long career and how they shaped his contributions to the diverse research fields in which he was active, and concluded that these characteristics reconfigure Crick's career into a coherent whole. First, I identify a major thread running through Crick's career: helping organise 'un-disciplined' new research fields, and show that his successive choices were not serendipitous but motivated by what he construed as a crusade against 'vitalism': anti-vitalism was a defining driver of his career. I then examine how Crick put his skills as a crossworlds influencer to the service of his cause, by helping organise his chosen fields of intervention. I argue that his activities as a cross-worlds influencer were an integral part of his way of 'doing science' and that his contributions to science, neuroscience in particular, should be re-evaluated in this light. This leads me to advance a possible strategy for historians to investigate big bioscience fields. Following Abir-Am, I propose to trace their genealogies back to the fluctuating semi-institutional gatherings and the institutional structures that sustained them. My research on Crick supports the view that such studies can bring insights into the question of why the contours of contemporary big bioscience endeavours have come to be shaped the way they are. Further, the essay provides a heuristic device for approaching these enquiries: 'follow the cross-worlds influencers' who worked to build and organise these semi-institutional gatherings and institutional structures., (Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.)

For scientific claims to be reliable and productive they have to be justified. However, on the one hand little is known on what justification precisely means to scientists, and on the other the position held by philosophers of science on what it entails is rather limited; for justifications customarily refer to the written form (textual expressions) of scientific claims, leaving aside images, which, as many cases from the history of science show are relevant to this process. The fact that images can visually express scientific claims independently from text, plus their vast variety and origins, requires an assessment of the way they are currently justified and in turn used as sources to justify scientific claims in the case of particular scientific fields. Similarly, in view of the different nature of images, analysis is required to determine on what side of the philosophical distinction between data and phenomena these different kinds of images fall. This paper historicizes and documents a particular aspect of contemporary life sciences research: the use of the molecular image as vehicle of knowledge production in cell studies, a field that has undergone a significant shift in visual expressions from the early 1980s onwards. Focussing on textbooks as sources that have been overlooked in the historiography of contemporary biomedicine, the aim is to explore (1) whether the shift of cell studies, entailing a superseding of the optical image traditionally conceptualised as primary data, by the molecular image, corresponds with a shift of justificatory practices, and (2) to assess the role of the molecular image as primary data. This paper also explores the dual role of images as teaching resources and as resources for the construction of knowledge in cell studies especially in its relation to discovery and justification. Finally, this paper seeks to stimulate reflection on what kind of archival resources could benefit the work of present and future epistemic historians in particular those interested on the role of images as sources of training and knowledge production in scientific disciplines., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The invention of DNA-RNA hybridization in 1960 by Ben Hall and Sol Spiegelman had a powerful impact on the theory and discourse of molecular biology. Yet, despite its importance, the story of this invention has barely been told. Hybridization allowed biologists to bridge the theoretical realm and the material world of organisms, to correlate a hypothetical concept of biological information transfer with a mechanism capable of making an RNA copy of DNA. During the early 1960s, Spiegelman and coworkers employed hybridization to investigate the origin of RNAs found in cells. They operationally defined messenger RNA and elucidated several aspects of genome organization. For Spiegelman, this was the culmination of his longstanding interest in the mechanism of enzyme/protein synthesis; for Hall, it was the beginning of a successful career in genetics. Other scientists immediately recognized the power of the technique and introduced improvements. In 1965, Gillespie and Spiegelman combined several modifications and described a procedure for hybridization that became standard. Since the 1970s, it has become an essential tool in biology and in biotechnology, and a core component in molecular techniques such as DNA microarrays. Notwithstanding its current success, the inventors' names have disappeared from the literature. This curiosity is discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In this personal, historic account of macromolecular transmission electron microscopy (TEM), published data from the 1940s through to recent times is surveyed, within the context of the remarkable progress that has been achieved during this time period. The evolution of present day molecular structural biology is described in relation to the associated biological disciplines. The contribution of numerous electron microscope pioneers to the development of the subject is discussed. The principal techniques for TEM specimen preparation, thin sectioning, metal shadowing, negative staining and plunge-freezing (vitrification) of thin aqueous samples are described, with a selection of published images to emphasise the virtues of each method. The development of digital image analysis and 3D reconstruction is described in detail as applied to electron crystallography and reconstructions from helical structures, 2D membrane crystals as well as single particle 3D reconstruction of icosahedral viruses and macromolecules. The on-going development of new software, algorithms and approaches is highlighted before specific examples of the historical progress of the structural biology of proteins and viruses are presented., (Copyright © 2014 Elsevier Inc. All rights reserved.)

These essays in this special issue follow cancer viruses as a means of better understanding the history of biomedicine. Spanning the worlds of chronic and infectious disease research, the history of cancer viruses touches upon an enormous diversity of settings and scientific disciplines. Cancer viruses appeared during the twentieth century as vaccine targets, vaccine contaminants, laboratory anomalies, and tools for molecular biology. Rather than picking one discipline or setting to privilege above others, this issue suggests what can be learned, not only about cancer viruses but also about the character of modern biomedicine, from following these viruses through their different historical trajectories.

In 1960, J. Anthony Morris, a molecular biologist at the US National Institutes of Health conducted one of the only non-therapeutic clinical studies of the cancer virus SV40. Morris and his research team aimed to determine whether SV40 was a serious harm to human health, since many scientists at the time suspected that SV40 caused cancer in humans based on evidence from in vivo animal studies and experiments with human tissue. Morris found that SV40 had no significant effect but his claim has remained controversial among scientists and policymakers through the present day--both on scientific and ethical grounds. Why did Morris only conduct one clinical study on the cancer-causing potential of SV40 in healthy humans? We use the case to explain how empirical evidence and ethical imperatives are, paradoxically, often dependent on each other and mutually exclusive in clinical research, which leaves answers to scientific and ethical questions unsettled. This paper serves two goals: first, it documents a unique--and uniquely important--study of clinical research on SV40. Second, it introduces the concept of "the stowaway," which is a special type of contaminant that changes the past in the present moment. In the history of science, stowaways are misfortunes that nonetheless afford research that otherwise would have been impossible specifically by creating new pasts. This case (Morris' study) and concept (the stowaway) bring together history of science and philosophy of history for productive dialog., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Although this volume is dedicated to honoring François Jacob, I would like my contribution to broaden the context by recalling the background within which the scientists of those times operated. The specific scientific accomplishments of Jacob will certainly be covered by the other contributors who collaborated with him. My handful of recollections presented here largely as vignettes is intended to give the reader a feeling for the elements, many social, that shaped the generation of scientists that included such central figures, Jacob, Lwoff, Monod. It is the tale of a generation trying to express its creativity in a world caught up in war, irrational values and unforgivable inhumanity. Even this limited account is a great story bringing us important lessons for thought., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

François Jacob tackled embryonic development from 1972 onwards, in the "Génétique cellulaire" Unit of the Molecular Biology Department at the Pasteur Institute, taking as models teratocarcinoma and the early stages of mouse embryo development. Studies on teratocarcinoma provided no major information about developmental processes, but they were the essential step without which embryonic stem cells (ES, iPS) would probably not have been discovered. The mechanisms of development were revealed by genetic approaches coupled to molecular biology, but with the Drosophila model rather than the mouse embryo. Since these studies, it has been revealed that developmental mechanisms among animals have proven to be universal. None of these results were predicted in 1972., (Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)