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Multi-User Virtual Environments (MUVEs) are often used to support learning in formal and informal educational contexts. A technology-based educational experience consists of several elements: content, syllabus, roles, sequence of activities, assignments, assessment procedures, etc. that must be aligned with the affordances of the technologies to be used. The design process, therefore, has to follow a dual track: the design of the educational experience as a whole and the design of the MUVE. Each design process has some degree of independence, while, at the same time, the two design processes are also deeply intertwined. The paper proposes a novel approach to design (both for the educational experience and the MUVE): a “biological lifecycle” design, where evolution (for survival and fitness) is crucial, while anticipating all the requirements (creating an engineering blueprint) is very challenging. This paper is based upon a number of large-scale case studies, involving nearly 9,000 high-school students from 18 countries in Europe, Israel, and the United States. Substantial educational benefits were achieved by these learning experiences, at the center of which were MUVEs. It cannot be claimed that MUVEs were the only factors for generating these benefits, but for sure they were exceptionally important components.