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796 VOLUME 23 | NUMBER 7 | JULY 2017 NATURE MEDICINE grown into rectal organoids1. These balls of cells, similarly to the human rectum, contain a hollow space known as a lumen in between two cell layers. The lumen is a crucial medium for the flow of water between the layers. According to Clevers, who is director of the nonprofit organization Hubrecht Organoid Technology (HUB), rectal tissue is ideal for observing cystic fibrosis because CFTR is highly expressed in this tissue. In those with another disease-causing mutation called G551D, Vertex Pharmaceuticals’ Kalydeco works by potentiating the action of the CFTR protein, which helps to regulate the ion channels that control the flow of water in and out of cells. This in turn helps to maintain healthy levels of the mucus that surrounds most organs in the body. In those with cystic fibrosis, mutations in the CFTR gene lead to interruptions in the normal exchange of water, as well as impaired maintenance of mucus, which results in the accumulation of the thick mucus that is characteristic of the disease. When the team applied Kalydeco to the organoids created from the cells of the 17-year-old boy, the organoids, previously after four weeks on this treatment, the boy’s symptoms dramatically improved. He had gained some weight and reported being able to breathe more easily—so much so that he had taken up playing field hockey. “I’m very sure he would not have survived if it wasn’t for the treatment,” van der Ent says. “I had been treating patients [with cystic fibrosis] for many years, and had never seen such positive effects—it was so amazing to see.” Van der Ent’s choice to administer the drug wasn’t just based on hope. He had been inspired to use the medicine—despite the fact that it was not approved for those with F508del/G1249R mutations—by how well it had performed in an organoid model that scientists had created using the boy’s own cells. This approach comes from the lab of Jeffrey Beekman, head of pediatric pulmonology at UMC. Beekman, along with organoidtechnology pioneer Hans Clevers, had previously established an assay in which rectal-biopsy samples taken from patients with cystic fibrosis could be coaxed into induced pluripotent stem cells, which were in turn Put to the test: Organoid-based testing becomes a clinical tool