One of the most striking examples of digital transformation, with supposedly profound societal and organizational impacts, is the field of personalized medicine. The impact of new technology is huge in healthcare, for example, because genomic data (gene expression profiling and/or alteration detection) will certainly reach the clinical routine with the development of cheap deep sequencing technology and thus make personalized medicine available for everybody. However, digitization does not only has the potential to offer benefits. For example, the changing care model due to personalized medicine is also expected to dramatically change the work practices and the economics of healthcare professionals. Entire medical professions may become obsolete or see their work practices turned upside-down.Even though we are facing striking and massive changes in healthcare due to digital transformation, we currently lack theories to guide us and help us to understand, describe, explain, and predict this phenomenon. One theory that has been deliberately designed to account for a major transformation due to advanced technologies is Zuboff’s (1988) Theory of the Smart Machine (TSM). To date, however, researchers have not test-ed TSM.The objectives of this research project are twofold. First, we are planning to test TSM within the healthcare domain using an empirical study. More specifically, we will investigate within a particular domain (i.e., healthcare and medical work) the effect that the use of a new digital IT artefact, genome sequencing, has on the work processes of researchers and practitioners in a medical work and research context. This will test a research model based on TSM with an advanced IT in a real organizational setting.Second, we are proposing a second study that will develop a new explanatory theory for the phenomenon of digital transformation in healthcare and medical work. In that way, if the first study does not support or refutes TSM, we have a theory grounded in the data that explains what is going on, and we can compare the successful grounded theory with the unsuccessful TSM and reflect what must have changed from one digital transformation to the next, current one. If both studies come to comparable results, then TSM is supported and strengthened even more. Regardless of the outcome whether TSM is refuted or supported, we thus will add to the cumulative tradition of studies on transformations. The results will contribute to the understanding of the effects of advanced IT and help researchers as well as practitioners to investigate if and how the use of IT affects the work process as well as the development outcome and leads to changes in the work environment.