https://science.sciencemag.org/content/368/6494/948The possibility of performing controlled human challenge trials,in which a small number of volunteers are vaccinated and subsequently challenged with SARS-CoV-2, has been suggested. Such experiments, if designed to define potential immune correlates or winnow out less effective vaccineapproaches, may have utility. However, this approach has shortcomings with respect to pathophysiology and safety(_*12*_). Although the risk of severe disease or death in young healthy individuals from COVID-19 is quite low, it isnot zero, and we do not yet have proven effective therapies for COVID-19 to rescue volunteers with complicationsfrom such a challenge. It is likely that a SARS-CoV-2 challenge strain will, by design, cause mild illness in mostvolunteers and thus may not recapitulate the pulmonary pathophysiology seen in some patients. Moreover, partial efficacy in young healthy adults does not predict similar effectiveness among older adults with major cofactorsassociated with COVID-19 disease, nor would it prove reduction of transmissibility to major susceptibility groups. Whether such experiments may be worthy of pursuit or would have a beneficial impact on timelines for vaccine development needs careful evaluation by an independent panel of ethicists, clinical trialists, and experts on vaccine development.