Handling technology with care: The introduction of next-generation sequencing in diagnostic clinical practice

When the human genome was first mapped at the beginning of the 2000s, the expectations for its impact on our understanding of human health and clinical care were high. The gained knowledge and related enthusiasm for future achievements propelled the development of faster and more cost-effective DNA sequencing techniques. This Next Generation of Sequencing (NGS) allows big components, or even the whole human genome, to be mapped in a rapid, efficient, low-cost, and accurate manner. While the implementation of NGS in diagnostic clinical practice is progressing rapidly, NGS and its results come with their own set of complexities and uncertainties that are often related to the interpretation of the vast amount of data they produce. Despite NGS testing significantly improving the chances of finding a genetic diagnosis, results are often more fluid and complex than those coming from more traditional forms of testing, making the interpretation a time-consuming and costly endeavour. Apart from more technical and practical issues, the main challenges coming with NGS techniques seem to revolve around their potential individual and societal impact and the ethical and legal issues that emerge in their implementation. The terms and boundaries of diagnostic NGS care are still very much being defined, impacting more broadly what constitutes care, a diagnosis, health, and illness.

As Science and Technology Studies (STS) have pointed out extensively, the translation of technology into the context of use, in this case, the diagnostic clinical practice, plays a crucial role in defining the value and meaning of a technology (Webster, 2002). Building on a multi-sited case study at two large European centres for human genetics, this study takes a sociological perspective to explore what happens on the floors of these centres for human genetics around NGS, scrutinising the processes involved in shaping NGS care and genomic medicine. Specific attention has been given to the decision-making, communication processes, and standardisation in the different steps of the diagnostic process in NGS care. Using a practice-based approach that builds on the principles of constructivist grounded theory (Charmaz, 2006), I have observed and analysed how NGS technologies are positioned, valued, and given meaning in clinical practice by analysing the local practices in which they are used.  Following the multiple steps of a diagnostic NGS test - from the offering, via the interpretation, to the result discussion - allowed me to see these processes unfold over time. The additional interviews, document analysis, and informal conversations and observations helped to see the congruence – or the lack of it – between words and actions, between intent and outcome, and between frontstage and backstage discourse (Goffman, 1959). This research brings to the foreground the values, interests, habits, practices, and practical circumstances implicitly and explicitly shaping NGS care. By studying this technology-in-the-making in practice, I was able to assess not only how it takes shape but also under which influences it is taking shape and what this means for those receiving and providing this care, providing the insight needed to adjust when necessary.

As this study shows, making the new type of care NGS ‘work’ in practice meant confronting uncertainty and ambivalence and engaging in ‘boundary work’ (Gieryn, 1983) to demarcate the field and underline its credibility, authority, and relevance. It meant engaging with standardisation efforts, issues of technology adoption, ethical questions, and changes in organisation and in what it means to provide care. Reflecting the ethical, legal, and social implications (ELSI) literature on the implementation of NGS testing, discussions on important aspects such as variants of unknown significance (VUS), informed consent, and the perceived future use of genomic testing were frequently taking place on the floors of the clinic. More so, however, these discussions were taking place performatively in the practices of the centres of human genetics. What became clear is that the answers to questions related to how to set up ‘good’ NGS care were not considered straightforward. Without many clear underpinnings for their decision-making on the heavily intertwined scientific and ethical dimensions of their care, much of this needed to be figured out in practice. It was in navigating the issues that arise in taking care of their patients using NGS that the stances and practices on these topics were created. The observed bending, working around, and creatively dealing with existing care practices and structures most clearly revealed the points of tension in NGS care. 

In this study I show how in response to the ethical, technical, and practical points of tension in NGS care, ambivalence and uncertainty contributed to an incremental practice-building in which the relevance of the expertise of the genetic healthcare professionals (GHCPs) was emphasised. Collectively working through uncertainty, for instance in the multidisciplinary team meetings, helped to ongoingly define the boundaries of, e.g., what is considered enough evidence, what is valuable enough to report to patients, and what constitutes a genetic diagnostic answer. With the field of genomic medicine developing rapidly, this collective uncertainty work (Star, 1985) helped to keep questioning the shifting boundaries and the direction they are headed towards. Whilst uncertainty and ambivalence may cause unease, throughout this thesis I also show the productive sides of these experiences. Uncertainty does not need to be resolved through stringent standardisation, as this may increase the risk of avoiding an open debate on what genetic care practices should look like. Similarly, explicitly examining instances of ambivalence can help locate tension points and stimulate an open discussion.

The significant role of collective and reflexive work in the multidisciplinary bioclinical collectives allowed for a level of flexibility in shaping ‘good’ genomic care. In my fieldwork, the importance of clinical judgement, intuition, and collective decision-making in NGS care was underlined. These types of local and tacit knowledge helped to deal with (unwanted) uncertainty and balance interests: they provided space to shape care based on more than molecular evidence or other purely rational forms of argumentation and make it fit the GHCPs perspectives and their patient’s interests.  While it may not always be recognised as such but rather seen as a regular part of work, much of the work involved in dealing with uncertainty and ambivalence for both GHCPs individually and as a team could be considered ethical work. Shaping NGS care involves more than just technical decision-making; the care practices I observed were packed with ethical and normative questions, concerns, and queries. By putting forward their distinct capabilities of dealing with the complexities of NGS, the GHCPs were able to underline the relevance of the profession and the CHGs in offering and shaping NGS care. Whilst the GHCPs clearly were led by the intention to provide good care to their patients and support their interests, in this thesis I show how there was a lack of transparency on the values and interests behind certain ambivalent care practices, such as when to offer whom NGS and how far to go to find a particular result. Making interests, values, and differing positions visible does, however, also entail loosening up the boundaries that are now securely placed around the field.

Overall, the study establishes that for genomic medicine to continue to develop firmly and steadily, an explicit and multidisciplinary ‘ethical choreography’ (Thompson, 2014) should be facilitated. This will help ensure that the current complexities, uncertainties, and ambivalence in implementing next-generation sequencing in diagnostic care are dealt with in iterative, reflexive, and widely supported ways (Timmermans, 2018). To ensure good genomic care, other voices may need to be invited in to help reflect, represent, and guide. As the NGS implementation reconfigures boundaries around illness, diagnosis, and care, I argue for open and collective scrutiny of the current direction healthcare is taking, further involving the public, the patient, and other disciplines such as social scientists, ethicists, and psychologists. More attention should be paid to the power of the local everyday care practices in the production and reproduction of what constitutes care and which voices are heard and served in this. If the prediction is followed and genomics soon moves from rather specialised diagnostic care to broadly applied preventative care, we will have to ensure that it fits our broader societal interests.