During the 1890s, people on the Mississippi River exploited mussel populations to support a thriving button industry. Within a brief time, they noticed significant declines in mussel populations, and called on the U.S. Bureau of Fisheries to save the resource. This paper discusses mussel propagation studies, techniques, and activities carried on in association with the Fairport Biological Laboratory (Iowa) from about 1908 to 1932. While scientists developed sophisticated techniques and had success in mussel propagation, changing habitat conditions in the river (caused mainly by pollution and dam construction) meant limited success in rescuing mussel stocks, while the introduction of plastic and the growth of foreign sources of mussel shells influenced the decline of the button industry on the Mississippi River.