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The current unprecedented expansion of infrastructure promises to enhance human wellbeing but risks causing substantial harm to natural ecosystems and the benefits they provide for people. A framework for systematically and proactively identifying the likely benefits and costs of such developments is badly needed. Here, we develop and test at the subregional scale a recently proposed global scheme for comparing the potential gains from new roads for food production with their likely impact on biodiversity and ecosystem services. Working in the Greater Mekong—an exceptionally biodiverse subregion undergoing rapid development—we combined maps of isolation from urban centres, yield gaps, and the current area under 17 crops to estimate where and how far road development could in principle help to increase food production without the need for cropland expansion. We overlaid this information with maps summarising the importance of remaining habitats to terrestrial vertebrates and (as examples of major ecosystem services) to global and local climate regulation. This intersection revealed several largely converted yet relatively low-yielding areas (such as central, eastern, and northeastern Thailand and the Ayeyarwady Delta), where narrowing yield gaps by improving transport links has the potential to substantially increase food production at relatively limited environmental cost. Concentrating new roads and road improvements here while taking strong measures to prevent their spread into areas which are still extensively forested (such as northern Laos, western Yunnan, and southwestern Cambodia) could thus enhance rural livelihoods and regional food production while helping safeguard vital ecosystem services and globally significant biological diversity.

Getting Road Expansion on the Right Track: A Framework for Smart Infrastructure Planning in the Mekong