: This paper examines the nature of the harm-benefit tradeoff in early clinical research for interventions that involve remote possibility of direct benefit and likelihood of direct harms to research participants with fatal prognoses, by drawing on the example of gene transfer trials for glioblastoma multiforme. We argue that the appeal made by the component approach to clinical equipoise fails to account fully for the nature of the harm-benefit tradeoff—individual harm for social benefit—that would be required to justify such research. (...) An analysis of what we label "collateral affective benefits," such as the experience of hope or exercise of altruism, shows that the existence of these motivations reinforces rather than mitigates the necessity of justification by reference to social benefit. Evaluations of social benefit must be taken seriously in the research ethics review process to avoid the exploitation of research participants' motivations of hope or altruism and to avoid the possibility of inadvertent exploitation of high-risk research participants and the harms that would associate with such exploitation. (shrink)