Paper short abstract:

In order to make therapeutic inferences, genomic-driven cancer clinical trials resort to treatment algorithms that establish meaningful connections between genomic, drug, and other datasets. Algorithms redefine the epistemic significance of translational processes and entities.

Paper long abstract:

We recently witnessed the emergence of clinical trials that focus on drug allocation based on genomic alterations. These trials face a major challenge: the interpretation of genomic sequencing data is a moving target, insofar as it needs to articulate four shifting reference poles: pharmaceutical drug portfolios, biopathological targets, patient populations and sequencing technologies.

Treatment algorithms, understood as predefined sets of rules for transforming sequencing and other data into evidence for therapeutic choices, are at the core of a restricted number of cutting edge trials. They act as tools that temporarily stabilize relations across the aforementioned reference poles, selecting treatment options for tumors carrying specific mutations, as detected by sequencing technologies. The analysis of how algorithms are deployed in clinical research allows us to gain a number of basic insights into the transformations introduced by precision medicine. The paper examines, in particular: (a) How algorithms manage the tension between the regulatory requirement of replication, and the clinical and scientific value of thoroughness; (b) How algorithms inflect the epistemic significance of clinical trials; and (c) How algorithms generate a new kind of experimental space by connecting heterogeneous entities.

More generally, we will show that algorithms can be understood as translational tools used to generate clinical knowledge based on genomic information. To examine this claim we resort to empirical case studies of the deployment of algorithms within four international cancer clinical trials, complemented by interviews with clinical researchers and bioinformatics specialists, and by documentary analysis of major North American and European cancer initiatives.

Paper short abstract:

Through a recent case of scientific misconduct in Japanese stem cell research (STAP cells), this paper suggests we have entered an age of accelerated ‘virtual witnessing’ in biomedical discovery. We argue that this affects the sociotechnical expectations but also the traditional moral economy of science.

Paper long abstract:

Attaining clinical translation in stem cell science requires a supply of consistent and safe-enough biological sources. Therefore high social and economic expectations are placed on basic research and its capacity to provide reprogramming technologies that can yield high-quality stem cells. This paper studies a recent case in stem cell research where political expectations, the closed peer-review-based moral economy of science and new social media-based action entangled in an unprecedented way. In 2014 Dr. Haruko Obokata and her co-authors caused a global media storm when they published two papers in Nature on what they claimed was a surprisingly simple method of reprogramming cells, called the stimulus-triggered acquisition of pluripotency (STAP). To the dismay of many, the case evolved into a full-blown data fabrication scandal and both papers were retracted. Japanese stem cell-centered science policy provides one perspective to make sense of how cutting-edge research could engender such conduct. To fully understand the case, however, the role of social media has to be analyzed alongside its sociotechnical context. The international research community contributed on ipscell.com, a blog run by stem cell scientist Paul Knoepfler, and PubPeer, an online journal club, to expose data fabrication and to confirm the irreproducibility of the sensational new method. Our paper shows that we have entered what could be termed the age of accelerated 'virtual witnessing' (Shapin and Schaffer, 1985). We suggest that web-based forums can reshape the traditional moral economy of science and, directly or indirectly, also the translational landscape of biomedical research.

Paper short abstract:

Although translational research (TR) is an omnipresent topic, there exists no commonly shared definition of it. Based on a qualitative content analysis, we map the landscape of TR by correlating the justifications of the need for TR with the understandings about TR procedures.

Paper long abstract:

In recent years, translational research (TR) has become recognized as the panacea for the "valley of death" (Butler 2008) and "waste in research" (see The Lancet 2014). Since the 1990s, new funding programs and research organizations have been established to promote TR. Publications have increased significantly and even new journals have been issued.

Yet, although TR is an omnipresent topic in (bio-)medical research, clinical care, health politics, and pharma industry, there exists no commonly shared definition of it. Different justifications imply different perspectives on problems and solutions that render the understanding of TR as a distinctive practice and a locally and temporally determined phase within the (bio-)medical knowledge production continuum in different ways.

In order to shed light on the different understandings and corresponding justifications, we conduct a qualitative content analysis of 345 articles from (bio-)medical journals that discuss concepts and practices of TR. First, we analyze the proposed chains of cause and effect that theorize and justify (1) why TR is needed, (2) which goals are sought to be achieved by implementing TR, and (3) which solutions are proposed as viable for enhancing TR. Second, we code where and when TR is understood to take place. Finally, we correlate the justifications of the need for TR with the understandings about TR procedures thereby mapping the landscape of TR in (bio-)medical knowledge production. This mapping allows us to see how TR is currently understood, justified, and thus translated into actions and organizational structures.

Paper short abstract:

This paper contributes to the on-going debate on the emergence of translational biomedicine, introducing the notion of technomimicry to theoretically capture the cognitive, social and material strategies involved in the translation of materials and information across laboratories and clinics.

Paper long abstract:

This paper, based on ethnographic research conducted in a major Italian institution specialising in cancer care and research, contributes to the on-going debate on the emergence of translational biomedicine. In the presentation, I will unfold the clinical and research laboratory practices performed around an experimental protocol designed to develop a biomarker to support the personalisation of treatments for patients suffering from colorectal cancer.

In particular, it will pay special attention to how the patient's living body involved in the experimentation process is configured as an 'experimental subject'. I will argue that the experimental subject is shaped through the relationships between human agents and technologies, differently localized across bench and bedside. These sociomaterial relationships imply the coordination and epistemological congruence between laboratories and clinical settings, in order to translate laboratory facts into clinical activities, and clinical evidence into researchable issues. In order to theoretically capture the ways in which the epistemological congruence is performed, I propose the notion of technomimicry. Technomimicry, in its dual acceptation in the clinical and experimental sense, allows to understand the cognitive, social and material strategies involved in the translation of materials and information across scientific laboratories and clinics. Specifically, clinical technomimicry highlights how the laboratory itself can be reframed to render scientific phenomena congruent with the clinical management of patients. Similarly, experimental technomimicry puts into light how the clinic itself can be reconfigured as a research terrain where patients are enrolled not only for care purposes, but also as participants in biomedical research activities.

Paper short abstract:

Exome sequencing is transitioning from laboratory to clinic to diagnose patients. Geneticists exert epistemic authority by going beyond the laboratory report while offering parents insight into their judgment. We relate these findings to the literature on standardization, uncertainty, and big data.

Paper long abstract:

Exome sequencing is a technological platform making the transition from "bench" to "bedside," meaning that a technology used for research purposes needs to meet demanding federal quality requirements of clinical laboratories. Social scientists have noted that the introduction of innovative technologies into work settings is a particularly critical time in a technology's life cycle because implementation requires the articulation of assumptions that will quickly slide back into a taken-for-granted infrastructure once a technology is routinized. Such introductions constitute a handover from the people designing, packaging, and marketing a technology to the users of the technology—although the distinction between user and designer remains blurry. We examine geneticists returning exome sequencing results to families. We find that in genetic consultations, clinical geneticists exert epistemic authority by interpreting genomic findings in ways that go beyond the laboratory report while also offering parents insight into the basis of their judgment. This news delivery approach facilitates parents' involvement in the determination of genetic causality and allows physician and parent to collectively define the boundaries of uncertainty. We then show that that the match between phenotype and genotype is circumscribed by the management of the causal ambiguities of genomic findings. We relate these findings to the literature on standardization, uncertainty, and management of big data.

Paper short abstract:

Systems medicine is seen as the translation of knowledge from systems biology into clinical practice. Up to now it is still disputed what the term translations means and comprises. This paper presents and discusses empirical findings on how researchers in systems medicine conceptualize translation.

Paper long abstract:

The paper focusses on translation in Systems Medicine, which is conceived as the implementation of Systems Biology approaches in medical concepts, research and practice, through iterative and reciprocal feedback between data-driven computational and mathematical models as well as model-driven translational and clinical investigations. However, what exactly is meant by translational research or translation in this context? Often both terms are used interchangeably with implementation. However, in contrast to implementation, translation refers less to the application of verified knowledge, but more to the transfer of knowledge from one realm of epistemic and social practice to another one. Although some definitions of translation have been proposed, there is no common understanding of what it involves in more detail. Some scholars have pointed out that the overall process has to be conceived as a heterogeneous, multidimensional endeavor, which comprises epistemic, clinical, organizational, ethical, social, and legal aspects. In order to gain a closer, empirically grounded understanding of how translation is actually understood, we conducted interviews with researchers from different specialties involved in translational research in Systems Medicine in order to explore their conception of the term and related practices. By doing it, we were especially interested in the question how researchers thought about bridging the epistemic and cultural gaps between the many disciplines participating in translation. Furthermore, we aim at systematizing the different socio-technical activities involved in such processes. In our presentation, we will describe and discuss some results of our investigation, thereby contributing to the emerging STS-field of analyzing translation in biomedicine.

Paper short abstract:

This paper considers discourses on biomedical translation by discussing the incorporation of genetic diagnostics in European health care. While not explicitly framed in terms of translation, the contextual specificity and stakes of this case provide important insights for positioning translational rhetoric.

Paper long abstract:

The question how to make medical innovations available to patients has been high on science policy agendas in recent years. Under the banner of 'translation', a plethora of epistemic, institutional and regulatory reforms have been proposed to ostensibly smoothen the integration of new diagnostics and treatments in health care. But while this translational imperative is of relatively recent vintage, the problem of access to innovative health care has long presented a formidable challenge to health care policy. In this paper, I therefore interrogate the recent rhetoric around translation by analyzing logics of making innovative medical technologies available that preceded the translational framing. I do so by presenting a comparative analysis of the incorporation of genetic diagnostics in health care delivery arrangements in Germany, the Netherlands and the United Kingdom. I demonstrate how in each of these distinct national contexts, epistemic, regulatory and institutional distinctions intersect in attempts to balance broad public access to medical care with availability of novel procedures. Bringing my observations back to current discourses on translation, I juxtapose the universal and linear assumptions in these discourses with the situated negotiations required for public health care provision. On the one hand, my comparative perspective suggests that such context-specific routines deserve more careful consideration when thinking of translation in biomedicine. At the same time, I propose that present translational rhetoric in many ways builds on the tension between welfare reforms and technological innovation I sketch, raising further questions about distributive justice in the translational enterprise.

Paper short abstract:

This paper examines how notions of ‘attuning-to-local-contexts’ are articulated in global innovation practices for TB and HIV point-of-care tests and to what effect. How do innovators perform/enact the translation of scientific and clinical knowledge and local settings into diagnostic technologies?

Paper long abstract:

Point of care (POC) tests promise to bring more diagnostic precision and rapidly available results at lower cost, with lower maintenance and user skills in settings without timely access to laboratory-based testing. The technology is presented as a way to overcome challenges that did not allow former technologies (laboratory-based testing) to function fully, by being more attuned to local contexts of use. STS scholars have long argued that healthcare technologies have to be adjusted to particular contexts of use to be effective. The aim of this paper is to examine how notions of 'attuning-to-local-contexts' are articulated in POC test innovation practices and to what effect for these processes. Adding to an emerging literature on the sociology of diagnostics and a recent STS interest in clinical translation, this paper asks how the translation of biomedical, clinical and engineering knowledge into diagnostics for the POC is performed and enacted. The analysis draws on semi-structured interviews with global health actors (diagnostic manufacturers, donors, civil society, industry consultants, international organisations, and researchers) involved in diagnostic development for tuberculosis and HIV. How do innovators of POC diagnostics incorporate local settings into the innovation process? How and what forms of expertise and knowledge are made accessible? What policy and regulatory approaches govern these practices? What are implications of these innovation and translation practices for meeting promises of what is considered a good POC test? The paper concludes by reflecting on opportunities for evaluation and intervention for STS scholars in how POC tests are developed and implemented.