When the working gas of a negative ion source is changed from hydrogen to its isotope, deuterium, an 'isotope effect' is observed; namely, several plasma characteristics such as the electron energy distribution, the atomic fraction and the spectra of rovibrationally excited molecules change. The understanding of the effect becomes more important, as research and development aiming at ITER power level operation is being challenged with feeding deuterium to the ion sources. As a historical review of the effort to develop hydrogen/deuterium negative ion sources, several types of negative ion sources designed for the neutral beam plasma heating are described: double charge exchange sources, volume sources and surface-plasma sources. The early results with volume sources operated with and without cesium are introduced. The characteristics of the source charged with deuterium are compared to those of the source charged with hydrogen. The isotope effect did not appear pronounced as the negative ion density was measured in a small source but became more pronounced when the plasma source size was enlarged and the discharge power density was increased to higher values. Surface plasma sources were optimized for deuterium operation but could not achieve the same performance as a source operated with hydrogen at the same power and pressure. The lower velocity of negative deuterium ions leaving the low work function surface seemed to limit the production efficiency. Fundamental processes causing these differences in negative ion source operation are summarized. After explaining the current status of negative ion source research and development, the acquired knowledge is utilized to the development of large negative ion sources for nuclear fusion research and to the development of compact negative ion sources for neutron source applications.