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Temple University was founded in 1884 by the Rev. Russell H. Conwell, clergyman, educator, and author of the famed oration, "Acres of Diamonds." It was Pastor Conwell's purpose to make quality education available to all intellectually capable people, regardless of ability to pay. This has remained one of Temple's major goals over the years.

Lewis Katz School of Medicine at Temple University opened its doors to students on September 16, 1901. The first coeducational medical college in Pennsylvania, it began as a night and weekend teaching venture to accommodate working-class citizens who sought to improve their lives — and the lives of others — through medical education. Classes were held initially in College Hall, next to Conwell's Baptist Temple Church, and clinical instruction was given at the Samaritan Hospital farther north on Broad Street. The original medical school faculty numbered 20 with 35 students enrolled during the first year. Tuition for those first students was $635 for the five-year program. In 1904, two men who had entered with advanced standing, Frederick C. Lehman and Frank E. Watkins, became its first graduates. Two years later two women — Sara Allen and Mary E. Shepard — completed the full course and were among 14 who received MD degrees. Two years later, the School graduated its first African American woman, Agnes Berry Montier, who practiced general medicine in Philadelphia until her death in 1961.

In 1907, to meet medical licensure requirements, the “night school” was discontinued and a solely day program instituted. During that year, the medical school joined the Dental and Pharmacy schools in buildings located at 18th and Buttonwood Streets. The Flexner Report of 1910, a critical survey of American medical schools, described Temple as “embryonic.” But despite its tiny beginnings, the school has grown and remained productive through a century. In 1929, Samaritan Hospital was renamed Temple University Hospital and ground was broken for a new medical school building across Broad Street that opened in the following year. Dr. William N. Parkinson, a 1911 graduate, became Dean and served admirably in that position for thirty years. With the opening of the 1930 building, each medical class was increased to 100 students.

Temple Medical School formed its first formal affiliation in 1928 with the Jewish Hospital of Philadelphia, now Albert Einstein Medical Center. This and subsequent hospital and scientific ties opened doors for more variety of instruction and investigation. Innovative faculty members brought luster by their teaching and practice, with national and international recognition. Research activities increased in the expanding medical orbit.

An Act of the Pennsylvania Legislature in 1965 designated Temple University a state-related institution in the Commonwealth System of Higher Education.

In October 2015, the school of medicine was officially named the Lewis Katz School of Medicine at Temple University in honor of Temple alumnus, former trustee, visionary leader and ardent supporter Lewis Katz, CST '63.