The article presents the advantages and limitations of adaptive clinical trials for assessing the effectiveness of medical interventions and specifies the conditions that contributed to their development and implementation in clinical practice. I advance two arguments by discussing different cases of adaptive trials. The normative argument is that responsible adaptation should be taken seriously as a new way of doing clinical research insofar as a valid justification, sufficient understanding, and adequate operational conditions are provided. The second argument is historical. The (...) development of adaptive trials can be related to lessons learned from research in cases of urgency and to the decades-long efforts to end the productivity crisis of pharmaceutical research, which led to the emergence of translational, personalized, and, recently, precision medicine movements. (shrink)

Translational research is a buzzword which dominates discussions about the quality, the utilization, and the benefits of medical research. Yet, although translational research has become a prominent topic, no commonly agreed definition of this terminology exists. Instead, experts from different contexts such as biomedical research, clinical practice or nursing discuss translational research in multiple ways depending on how they define the problem that translational research is supposed to be the solution to. In this paper, we do not seek to find (...) a ‘correct’ definition of translational research, but instead ask how actors using this terminology for describing their own research make sense of it. To do so, we asked three questions: Which actors are engaged in the debate about translational research? What kind of different meanings of translational research exist? And, which actors refer to which meaning of translational research when using the term? In answering these questions, we highlight the role this terminology plays in defining what medical science is about today. (shrink)

Research on the human microbiome has gen- erated a staggering amount of sequence data, revealing variation in microbial diversity at the community, species (or phylotype), and genomic levels. In order to make this complexity more manageable and easier to interpret, new units—the metagenome, core microbiome, and entero- type—have been introduced in the scientific literature. Here, I argue that analytical tools and exploratory statisti- cal methods, coupled with a translational imperative, are the primary drivers of this new ontology. By reducing the (...) dimensionality of variation in the human microbiome, these new units render it more tractable and easier to interpret, and hence serve an important heuristic role. Nonetheless, there are several reasons to be cautious about these new categories prematurely ‘‘hardening’’ into natural units: a lack of constraints on what can be sequenced metagenomically, freedom of choice in taxonomic level in defining a ‘‘core microbiome,’’ typological framing of some of the concepts, and possible reification of statistical constructs. Finally, lessons from the Human Genome Project have led to a translational imperative: a drive to derive results from the exploration of microbiome variation that can help to articulate the emerging paradigm of per- sonalized genomic medicine (PGM). There is a tension between the typologizing inherent in much of this research and the personal in PGM. (shrink)

Translational research in medicine requires researchers to identify the steps to transfer basic scientific discoveries from laboratory benches to bedside decision-making, and eventually into clinical practice. On a parallel track, philosophical work in ethics has not been obliged to identify the steps to translate theoretical conclusions into adequate practice. The medical ethicist A. Cribb suggested some years ago that it is now time to debate ‘the business of translational’ in medical ethics. Despite the very interesting and useful perspective on the (...) field of medical ethics launched by Cribb, the debate is still missing. In this paper, I take up Cribb’s invitation and discuss further analytic distinctions needed to base an ethics aiming to translate between theory and practice. (shrink)

Philosophy of medicine has traditionally examined two issues: the scientific ontology for medicine and the epistemic significance of the types of evidence used in medical research. In answering each question, philosophers have typically brought to bear tools from traditional analytic philosophy. In contrast, this volume explores medical knowledge from the perspective offered by social epistemology.While many of the same issues are addressed, the approach to these issues generates both fresh questions and new insights into old debates. In addition, the broader (...) purview offered by social epistemology opens up opportunities to address new topics such as the role of consensus conferences, epistemic injustice, the value of medical knowledge, continuing medical education, and industry funding. This article situates and summarizes the contributions to this special issue. (shrink)

Advances at the interface between the biological sciences and engineering are giving rise to emerging research fields such as synthetic biology. Harnessing the potential of synthetic biology requires timely and adequate translation into clinical practice. However, the translational research enterprise is currently facing fundamental obstacles that slow down the transition of scientific discoveries from the laboratory to the patient bedside. These obstacles including scarce financial resources and deficiency of organizational and logistic settings are widely discussed as primary impediments to translational (...) research. In addition, a number of socio-ethical considerations inherent in translational research need to be addressed. As the translational capacity of synthetic biology is tightly linked to its social acceptance and ethical approval, ethical limitations may—together with financial and organizational problems—be co-determinants of suboptimal translation. Therefore, an early assessment of such limitations will contribute to proactively favor successful translation and prevent the promising potential of synthetic biology from remaining under-expressed. Through the discussion of two case-specific inventions in synthetic biology and their associated ethical implications, we illustrate the socio-ethical challenges ahead in the process of implementing synthetic biology into clinical practice. Since reducing the translational lag is essential for delivering the benefits of basic biomedical research to society at large and promoting global health, we advocate a moral obligation to accelerating translational research: the “translational imperative.”. (shrink)

This article explores the role scientists at the National Cancer Institute, a US federal science agency, played in researching and testing vaccines against the human papillomavirus. Drawing upon archival sources and oral history interview data, I challenge narratives that attribute the design of HPV vaccines to profit motive. Instead, I show that the researchers who developed the technology attempted to construct ethical approaches to vaccine development based on the values that emerged from their situated environments of technological, organizational, and institutional (...) constraint. I argue that interpretations of “translational research” native to the NCI influenced these researchers’ efforts to design and test HPV vaccines. The organizational culture of translational research emerging in the NCI positioned intramural research as a countervailing and supplementary force to market-oriented translational research and development. Over time, NCI researchers’ conceptions of the Institute’s role allowed them to develop understandings of ethical HPV vaccine research as oriented toward addressing cervical cancer health disparities, especially in developing nations. NCI scientists’ understanding of their role in serving the public good through continued HPV vaccine innovation reflects the material and political economic environment they faced at different historical junctures that constrained the possibilities for innovation and ethical action. (shrink)

In this chapter I investigate the prospects of integrated history and philosophy of science, by examining how philosophical issues raised by “hidden entities”, entities that are not accessible to unmediated observation, can enrich the historical investigation of their careers. Conversely, I suggest that the history of those entities has important lessons to teach to the philosophy of science. Hidden entities have played a crucial role in the development of the natural sciences. Despite their centrality to past scientific practice, however, several (...) of them (e.g., phlogiston, caloric, and the ether) turned out to be fictitious. For this reason, they have figured prominently in recent debates on scientific realism. The issues I explore in this paper are entangled with those debates. I argue that our understanding of hidden entities and their role in experimental practice can be enhanced by adopting an integrated historical-cum-philosophical approach. On the one hand, philosophical reflection on the reality of those entities has a lot to gain by examining historically how they were ntroduced and investigated. On the other hand, the historical reconstruction of the careers of those entities may profit from philosophical reflection on their existence. (shrink)

In this paper, we explore the recent creation of “iBlastoids,” which are 3-D structures that resemble early human embryos prior to implantation which formed via self-organization of reprogrammed ad...

It is widely accepted that translational research practitioners need to acquire special skills and knowledge that will enable them to anticipate, analyze, and manage a range of ethical issues. While there is a small but growing literature that addresses the ethics of translational research, there is a dearth of scholarship regarding how this might apply to engineers. In this paper we examine engineers as key translators and argue that they are well positioned to ask transformative ethical questions. Asking engineers to (...) both broaden and deepen their consideration of ethics in their work, however, requires a shift in the way ethics is often portrayed and perceived in science and engineering communities. Rather than interpreting ethics as a roadblock to the success of translational research, we suggest that engineers should be encouraged to ask questions about the socio-ethical dimensions of their work. This requires expanding the conceptual framework of engineering beyond its traditional focus on “how” and “what” questions to also include “why” and “who” questions to facilitate the gathering of normative, socially-situated information. Empowering engineers to ask “why” and “who” questions should spur the development of technologies and practices that contribute to improving health outcomes. (shrink)

The label ‘Translational Research’ (TR) has become ever more popular in the biomedical domain in recent years. It is usually presented as an attempt to bridge a supposed gap between knowledge produced at the lab bench and its use at the clinical bedside. This is claimed to help society harvest the benefits of its investments in scientific research. The rhetorical as well as moral force of the label TR obscure, however, that it is actually used in very different ways. In (...) this paper, we analyse the scientific discourse on TR, with the aim to disentangle and critically evaluate the different meanings of the label. We start with a brief reconstruction of the history of the concept. Subsequently, we unravel how the label is actually used in a sample of scientific publications on TR and examine the presuppositions implied by different views of TR. We argue that it is useful to distinguish different views of TR on the basis of three dimensions, related to (1) the construction of the ‘translational gap’; (2) the model of the translational process; and (3) the cause of the perceived translational gap. We conclude that the motive to make society benefit from its investments in biomedical science may be laudable, but that it is doubtful whether the dominant views of TR will contribute to this end. (shrink)

This paper argues that the cognitive neuroscientific use of ordinary mental terms to report research results and draw implications can contribute to public confusion and misunderstanding regarding neuroscience results. This concern is raised at a time when cognitive neuroscientists are increasingly required by funding agencies to link their research to specific results of public benefit, and when neuroethicists have called for greater attention to public communication of neuroscience. The paper identifies an ethical dimension to the problem and presses for greater (...) sensitivity and responsibility among neuroscientists regarding their use of such terms. (shrink)

The label ‘Translational Research’ (TR) has become ever more popular in the biomedical domain in recent years. It is usually presented as an attempt to bridge a supposed gap between knowledge produced at the lab bench and its use at the clinical bedside. This is claimed to help society harvest the benefits of its investments in scientific research. The rhetorical as well as moral force of the label TR obscure, however, that it is actually used in very different ways. In (...) this paper, we analyse the scientific discourse on TR, with the aim to disentangle and critically evaluate the different meanings of the label. We start with a brief reconstruction of the history of the concept. Subsequently, we unravel how the label is actually used in a sample of scientific publications on TR and examine the presuppositions implied by different views of TR. We argue that it is useful to distinguish different views of TR on the basis of three dimensions, related to (1) the construction of the ‘translational gap’; (2) the model of the translational process; and (3) the cause of the perceived translational gap. We conclude that the motive to make society benefit from its investments in biomedical science may be laudable, but that it is doubtful whether the dominant views of TR will contribute to this end. (shrink)

The question we raise in this paper is, whether patient involvement might be a beneficial way to help determine and achieve the aims of translational research and, if so, how to proceed. TR is said to ensure a more effective movement of basic scientific findings to relevant and useful clinical applications. In view of the fact that patients are supposed to be the primary beneficiaries of such translation and also have relevant knowledge based on their experience, listening to their voice (...) early on in the innovation process might very well increase the effectiveness of the translation. After explaining how the concept of TR emerged and what it entails, this paper shows through a literature review which arguments have been put forward to promote patient involvement in health care research in a more general sense. We examine whether, and if so how, these arguments are relevant for the discourse on TR and we identify pitfalls and dilemmas. Ultimately, we conclude that it may be worthwhile to experiment with patient involvement in TR but that the design of such involvement requires careful consideration. (shrink)

Research on the human microbiome has generated a staggering amount of sequence data, revealing variation in microbial diversity at the community, species (or phylotype), and genomic levels. In order to make this complexity more manageable and easier to interpret, new units—the metagenome, core microbiome, and enterotype—have been introduced in the scientific literature. Here, I argue that analytical tools and exploratory statistical methods, coupled with a translational imperative, are the primary drivers of this new ontology. By reducing the dimensionality of variation (...) in the human microbiome, these new units render it more tractable and easier to interpret, and hence serve an important heuristic role. Nonetheless, there are several reasons to be cautious about these new categories prematurely ‘‘hardening’’ into natural units: a lack of constraints on what can be sequenced metagenomically, freedom of choice in taxonomic level in defining a ‘‘core microbiome,’’ typological framing of some of the concepts, and possible reification of statistical constructs. Finally, lessons from the Human Genome Project have led to a translational imperative: a drive to derive results from the exploration of microbiome variation that can help to articulate the emerging paradigm of personalized genomic medicine (PGM). There is a tension between the typologizing inherent in much of this research and the personal in PGM. (shrink)

Commentators on the ethics of translational research find it morally problematic. Types of translational research are said to involve questionable benefits, special risks, additional barriers to informed consent, and severe conflicts of interest. Translational research conducted on the global poor is thought to exploit them and increase international disparities. Some commentators support especially stringent ethical review. However, such concerns are grounded only in pre-approval translational research (now called T1 ). Whether or not T1 has these features, translational research beyond approval (...) ( T2 : phase IV, health services, and implementation research) is unlikely to and, when conducted on the global poor, may support development. Therefore, insofar as T1 is morally problematic, and no independent objections to T2 exist, the ethics of translational research is diverse: while some translational research is problematic, some is not. Funding and oversight should reflect this diversity, and T2 should be encouraged, particularly when conducted among the global poor. (shrink)

Commentators on the ethics of translational research find it morally problematic. Types of translational research are said to involve questionable benefits, special risks, additional barriers to informed consent, and severe conflicts of interest. Translational research conducted on the global poor is thought to exploit them and increase international disparities. Some commentators support especially stringent ethical review. However, such concerns are grounded only in pre-approval translational research. Whether or not T1 has these features, translational research beyond approval is unlikely to and, (...) when conducted on the global poor, may support development. Therefore, insofar as T1 is morally problematic, and no independent objections to T2 exist, the ethics of translational research is diverse: while some translational research is problematic, some is not. Funding and oversight should reflect this diversity, and T2 should be encouraged, particularly when conducted among the global poor. (shrink)

The Belmont Report’s distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole (...) exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. (shrink)

Translational research is a buzzword which dominates discussions about the quality, the utilization, and the benefits of medical research. Yet, although translational research has become a prominent topic, no commonly agreed definition of this terminology exists. Instead, experts from different contexts such as biomedical research, clinical practice or nursing discuss translational research in multiple ways depending on how they define the problem that translational research is supposed to be the solution to. In this paper, we do not seek to find (...) a ‘correct’ definition of translational research, but instead ask how actors using this terminology for describing their own research make sense of it. To do so, we asked three questions: Which actors are engaged in the debate about translational research? What kind of different meanings of translational research exist? And, which actors refer to which meaning of translational research when using the term? In answering these questions, we highlight the role this terminology plays in defining what medical science is about today. (shrink)

In his 1987 book "Controlling Life: Jacques Loeb and the Engineering Ideal in Biology", Philip Pauly presented his readers with the biologist Jacques Loeb and his role in developing an emphasis on control of life processes. Loeb's work on artificial parthenogenesis, for example, provided an example of bioengineering at work. This paper revisits Pauly's study of Loeb and explores the way current research in regenerative medicine reflects the same tradition. A history of regeneration research reveals patterns of thinking and research (...) methods that both echo Loeb's ideology and point the way to modern studies. Pauly's work revealed far more than we readers realized at the time of its publication. (shrink)

The rapid, recent emergence of new medical knowledge models has engendered a dizzying number of new medical initiatives, programs and approaches. Fields such as evidence-based medicine and translational medicine all promise a renewed relationship between knowledge and medicine. The question for philosophy and other fields has been whether these new models actually achieve their promises to bring about better kinds of medical knowledge—a question that compels scholars to analyze each model’s epistemic claims. Yet, these analyses may miss critical components that (...) explain how these models actually work and function. Using the case of translational medicine, this paper suggests that analyses which treat these models as a primarily epistemic interventions miss the way that new approaches are increasingly shaped by specific financial and commercial agendas. Ultimately, social epistemological analyses that are attentive to market forces are required to make sense of emerging bioscientific research models, which are increasingly tethered to or a manifestation of increasingly financialized models of science research and innovation. (shrink)

Because no single person or group holds knowledge about all aspects of research, mechanisms are needed to support knowledge exchange and engagement. Expertise in the research setting necessarily includes scientific and methodological expertise, but also expertise gained through the experience of participating in research and/or being a recipient of research outcomes. Engagement is, by its nature, reciprocal and relational: the process of engaging research participants, patients, citizens and others brings them closer to the research but also brings the research closer (...) to them. When translating research into practice, engaging the public and other stakeholders is explicitly intended to make the outcomes of translation relevant to its constituency of users. In practice, engagement faces numerous challenges and is often time-consuming, expensive and ‘thorny’ work. We explore the epistemic and ontological considerations and implications of four common critiques of engagement methodologies that contest: representativeness, communication and articulation, impacts and outcome, and democracy. The ECOUTER methodology addresses problems of representation and epistemic foundationalism using a methodology that asks, “How could it be otherwise?” ECOUTER affords the possibility of engagement where spatial and temporal constraints are present, relying on saturation as a method of ‘keeping open’ the possible considerations that might emerge and including reflexive use of qualitative analytic methods. This paper describes the ECOUTER process, focusing on one worked example and detailing lessons learned from four other pilots. ECOUTER uses mind-mapping techniques to ‘open up’ engagement, iteratively and organically. ECOUTER aims to balance the breadth, accessibility and user-determination of the scope of engagement. An ECOUTER exercise comprises four stages: engagement and knowledge exchange; analysis of mindmap contributions; development of a conceptual schema ; and feedback, refinement and development of recommendations. ECOUTER refuses fixed truths but also refuses a fixed nature. Its promise lies in its flexibility, adaptability and openness. ECOUTER will be formed and re-formed by the needs and creativity of those who use it. (shrink)

Early in his career Thomas Hunt Morgan was interested in embryology and dedicated his research to studying organisms that could regenerate. Widely regarded as a regeneration expert, Morgan was invited to deliver a series of lectures on the topic that he developed into a book, Regeneration (1901). In addition to presenting experimental work that he had conducted and supervised, Morgan also synthesized and critiqued a great deal of work by his peers and predecessors. This essay probes into the history of (...) regeneration studies by looking in depth at Regeneration and evaluating Morgan's contribution. Although famous for his work with fruit fly genetics, studying Regeneration illuminates Morgan's earlier scientific approach which emphasized the importance of studying a diversity of organisms. Surveying a broad range of regenerative phenomena allowed Morgan to institute a standard scientific terminology that continues to inform regeneration studies today. Most importantly, Morgan argued that regeneration was a fundamental aspect of the growth process and therefore should be accounted for within developmental theory. Establishing important similarities between regeneration and development allowed Morgan to make the case that regeneration could act as a model of development. The nature of the relationship between embryogenesis and regeneration remains an active area of research. (shrink)

Extensive conflicts of interest at both individual and institutional levels are identifiable in scientific research and healthcare in China, as in many other parts of the world. A prominent new case from China is He Jiankui’s experiment that produced the world’s first gene-edited babies and that raises numerous ethical, political, socio-cultural, and transnational questions. Serious financial and other COI were involved in He’s genetic adventure. Using He’s infamous experiment as a case study, this paper explores the wider issue of financial (...) and other COI in scientific research and healthcare in China, especially institutional conflict of interest and policy-related COI. Taking a socio-ethical perspective, it examines China’s state policies and its massive efforts to transform and commercialize scientific research, the lack of policies and oversight mechanisms for regulating COI, as well as major ethical issues arising from COI including the undermining of public trust. Some practical suggestions are offered for institutional reform and institutional development so that COI, particularly ICOI, can be avoided or more effectively managed in scientific research in China. (shrink)