Building the Bridge from Bench to Bedside: Ethical Issues in Translational Stem Cell Research

Abstract

Translational stem cell research raises many interesting ethical questions, which have, to a greater or lesser degree, been debated at an international as well as at an interdisciplinary level. Nevertheless, there is still no international consensus regarding how a number of ethical questions related to this research should be answered. Many of these ethical questions create a real challenge to translation of basic research results into clinical applications.<br> The overall aim of the thesis is to analyse some of the major ethical questions arising at different levels of translation of knowledge generated by preclinical and clinical stem cell research. The questions chosen for analysis have either not yet received much attention in the literature (papers I and IV), or could benefit from ethical analysis of specific examples (papers II and III). This thesis suggests ways to address the same problems in clinical translation of stem cell research results, involving other variables, such as different diseases (papers II and III), or ways to address certain types of ethical questions arising in translational stem cell research as well as in some other areas of biomedical research (papers I and IV). Solutions to the problems analysed in this thesis cannot be offered until the state of knowledge has been improved and until certain fundamental moral questions have been tackled; otherwise, the final balancing of interests and concerns will not be well founded as the results of all four studies indicate. <br> The thesis explores: <br> (a) whether there are ethically justified reasons to regulate basic research on human embryonic stem (hES) cells and human-induced pluripotent stem (hiPS) cells differently: a very immediate issue in preclinical research (Paper I); <br> (b) which groups of patients should be asked to participate in first-in-human clinical studies of stem cell-based therapies, and on what grounds: a very immediate issue in translation of preclinical research results into first clinical application on small numbers of human participants (“frontier research”) (Paper II); <br> (c) how to prioritize stem-cell-based therapies if and when they become routine, in the face of limited resources: a highly likely issue in translation of knowledge obtained in clinical trials into clinical practice and daily care of patients (Paper III); <br> (d) whether, under what conditions, and to what extent withdrawal of consent from research involving donated human biological samples should be allowed: an immediate issue in preclinical research (Paper IV). <br> This thesis is a theoretical work, and the methods used are theoretical approaches. In Paper II and Paper III the concept of stakeholder is important, since the perspectives of different stakeholders play an important role in the analysis conducted in these papers. In both papers the current state of knowledge and knowledge gaps are identified on the basis of the available scientific literature. The possible courses of action are outlined, the stakeholders concerned by the alternative courses of action identified. Their interests are then described and evaluated in the light of certain value premises, e.g. values endorsed by major different types of ethical theories (such as utilitarianism, virtue ethics, as well as human dignity and human rights-based theories) or values enshrined in European and international guidelines, declarations, directives or conventions. These values are applied to the alternatives. Arguments are provided concerning what should be done in the light of the knowledge we have and in the light of value premises. In Paper I and Paper IV the discussion of different arguments expressed in the literature play an important role. These arguments are presented and their ethical relevance is discussed in the light of different types of ethical theories, as in Paper I, or attention is drawn to a number of areas that need to receive greater attention in order for the debate to make progress, as in Paper IV.