In 2013, the MBL became an affiliate of the University of Chicago. However, this was not the first time that the two institutions considered setting-up an alliance. By 1900, after 12 years of operation, the MBL was in dire financial straights. The cost of running an ever-expanding research and teaching laboratory, independent of a university setting, had proved too costly to maintain. Then-director Charles Otis Whitman sought financial support for the MBL, which was offered by L.L. Nunn and a group of business representing the University of Chicago, in return for some simple expectations of financial accountability. The MBL Board of Trustees refused the offer, despite Whitman's wishes that it go through.
In addition to financial history, there is a long connection between the MBL and the University of Chicago in terms of research and education. Charles Otis Whitman, the founding director of the MBL, established the biology department at the University of Chicago in 1892. Among his first faculty members was Jacques Loeb, the noted biologist who became famous for his parthenogenesis experiments at the turn of the 20th century, and who also founded the MBL's Physiology course in 1893. The MBL's second director, Frank R. Lillie, arrived at the MBL in 1892 for the Embryology course. Whitman quickly directed his work towards cell lineage studies in freshwater mussels (Unio), and lured Lillie to University of Chicago to become his graduate student. Lillie graduated with his PhD in 1894, and after working at the University of Michigan and Vassar College for several years, returned to the University of Chicago as a professor in 1900. Lillie stayed with the department for the next 30 years.