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TSRI's roots can be traced to the Scripps Metabolic Clinic, founded near the current site in 1924 by the philanthropist Ellen Browning Scripps.
In 1946 it evolved into the Scripps Clinic and Research Foundation.
Initially focusing on the study of immune disorders under the leadership of Frank J. Dixon, over the following 25 years the faculty grew and diversified its research interests, precipitating another name change in 1977, to The Research Institute of Scripps Clinic.
In 1991 the Scripps Clinic and research division became separate corporations and The Scripps Research Institute was founded.
In 1989 TSRI started a graduate program.

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