Abstract
<jats:title>Abstract</jats:title> <jats:p>In controlled human infection (CHI) research, researchers intentionally expose people to pathogens to gain scientific knowledge. Although CHI research has brought scientific breakthroughs and become a critical component of testing interventions for diseases like malaria, it remains controversial. During the COVID-19 pandemic, the possibility of using CHI research to accelerate vaccine development was hotly debated, capturing public imagination and the attention of ethicists. This book demonstrates that a lack of understanding of this research has contributed to ethical controversy. Creating a new model for infecting humans with a pathogen for the first time is ethically complex and typically requires extra scrutiny. Once a model has already been shown to be safe and reliable, however, the ethical issues can usually be managed with standard review approaches and frameworks. This distinction between CHI models and studies does important ethical work and can help determine when extra scrutiny is needed for CHI research. The book first provides a historical overview of CHI research, including during the COVID-19 pandemic, showing how unethical research from the past casts a long shadow and provides reason for caution today. It then analyzes what makes CHI research ethically unusual and provides a framework that can help tailor the level of scrutiny of CHI research to the level of ethical complexity it presents. Surprising and ethically important future uses of CHI research emerge from this analysis—including for long-term pandemic preparedness and to accelerate research in low- and middle-income countries addressing neglected diseases. The book closes with lessons to help advance the ethics of research in general.</jats:p>