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In the fall of 1906, two separate groups of doctors from throughout Oregon met to discuss the creation of an academy of medicine where doctors could meet to discuss advancements in the medical field. On November 9, these groups merged to establish the Portland Academy of Medicine, located in Portland, Oregon. Modeled after the New York Academy of Medicine, the Portland Academy's goals focused on the investigation and promotion of the science and art of medicine and the creation and maintenance of a public medical library located at the University of Oregon Medical School.

The original members consisted of Drs. Simeon E. Josephi, Richard Nunn, Otto S. Binswanger, William Jones, George B. Story, A. J. (Andrew Jackson) Giesy, George F. Wilson, and John F. Dickson. After the merger, additional doctors were invited to become charter members of the Academy and to participate in the creation of the constitution and bylaws and the election of its first officers. The additional members included Drs. Albert E. MacKay, James F. Bell, Kenneth A. J. MacKenzie, Ernest F. Tucker, E. H. Parker, R. Kelly, C. H. Wheeler, F. B. Eaton, Andrew Smith, A. C. Panton, J. D. Fenton, George F. Wilson, W. L. Wood, and William Boys. Membership into the academy was by invitation only and had to be voted on before new members were accepted. The members of the Academy were known as Fellows and were split into four categories: Active, Senior, Honorary, and Non-resident. Each category paid a different dues fee. The Senior fellows did not pay dues and this status was only granted if the fellow had been active for over 20 years. Non-resident status was granted to doctors who did not live near Portland. Many of the fellows in the academy were notable doctors at the University of Oregon Medical School, which is now the Oregon Health & Science University.

One third of the membership dues supported the purchasing of books and publications for the Medical School Library. The Academy also provided honorariums for invited guest lecturers, prominent local and international doctors, to speak at their meetings. In the 1940s, the Academy created the Medical Research Foundation, which would provide funding grants for the exploration and advancement of medical research.