In this episode of NEJM AI Grand Rounds, guests Drs. Alan Karthikesalingam and Anil Palepu of Google walk co-hosts Raj Manrai and Andy Beam through the making and evaluation of AMIE, an AI system designed to conduct clinical conversations with patients. Alan and Anil explain how AMIE was trained using synthetic doctor-patient interactions generated by LLMs playing multiple roles—doctor, patient, critic, and moderator. They reveal how synthetic dialogue, guided by structured feedback and grounded in search, proved more effective than noisy real-world transcripts in building a model that could reason, ask questions, and show empathy. The discussion also covers what the “long tail” of medicine demands for building robust AI systems and how AMIE might one day augment real clinical workflows. Finally, Alan reflects on how AI has changed—and how it hasn’t—in the two years since he was last on the podcast.   Transcript.