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He served as Vice-President of the European Commission and Commissioner for Enlargement, Environment and Nuclear Safety in the Jenkins Commission from 1977 to 1981. He then served as Vice-President and Commissioner for Mediterranean Policy, Enlargement and Information in the Thorn Commission from 1981 to 1985. He was Vice-President and held the portfolio of Cooperation, Development Affairs and Enlargement in the Delors Commission from 1985 to 1989. He was a government minister in Italy from 1966 to 1972 and served as Minister of Agriculture from 1970.
The Lorenzo Natali Prize is named in his honour.