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When President Obama appointed Frank Loy as Alternate U.S. Representative to the 66th Session of the UN General Assembly in 2011, it marked the fourth U.S. administration to name him to a senior position in the Department of State.

In the second administration of President Clinton he served as Under Secretary for Global Affairs. His portfolio included developing US international policy and conducting negotiations in the fields of human rights, the promotion of democracy, refugees, population issues and humanitarian affairs, counter-narcotics, and particularly climate change (he was the lead US climate negotiator for three years) and other environmental issues such as trade in genetically modified agricultural products.