Covid-19 has infected thousands and killed hundreds in prisons, jails, and immigration detention facilities across the United States. Responding to this crisis, leading medical researchers have called for expanding opportunities for people in prison to participate in vaccine trials. These calls, like current regulations, focus on individualized risk assessments around consent, coercion, and harm, while ignoring the unnaturalness of deprivation conditions in U.S. prisons. We need new frameworks of analysis that refocus on structural, rather than individual, risk assessments. Integrating structural perspectives-including skepticism of claims of scarcity, avoidance of representational distortions, and attention to institutional agency-into our existing, overly individualistic frameworks might permit the design of more ethical research projects involving people who are incarcerated. Still, the unnatural deprivations of incarceration might be so great that research subjects might need to be removed from prison entirely in order to ethically participate in research.