A new “lung-on-chip” model, consisting solely of genetically identical cells derived from a single person, has advanced our understanding of tuberculosis, opening the door to personalized treatments. Researchers at the Francis Crick Institute (London, UK) and AlveoliX (Bern, Switzerland) have developed a single-donor human induced pluripotent stem cell (IPSC)-derived lung-on-chip model, which can mimic breathing and simulate lung disease in an individual. It therefore holds promise for personalized medicine in the treatment of lung cancer and respiratory infections, such as tuberculosis. Alveoli –balloon-like air sacs in the lungs – are an essential first line of defence against infection. Traditionally, attempts to understand their inner workings have been limited to animal studies that, while incredibly useful, do not paint a perfect picture of respiratory processes in our own species. Organ-on-chip technologies represent a promising alternative. However, multicellular airway models have, until this point, been based on cell lines and primary cells, or a combination of both, rendering them unable to fully replicate the lung function or disease progression of a single individual. In Focus: New approach methodologies New approach methodologies (NAMs) are rapidly being adopted in the early stages of therapeutics development because they offer researchers more human-relevant models. NAMs encompass a wide range of tools from in vitro to in silico models, offering a varied and innovative toolbox to replace outdated animal models. To circumvent this, the researchers engineered a physiologically inspired human lung-on-chip containing genetically identical cells. Firstly, they used human IPSCs to produce type I and II alveolar epithelial cells. These were then grown on top of a very thin membrane in a device manufactured by AlveoliX,…