Ladd-Franklin's mathematical interests ultimately led her to make important contributions to the field of psychology. In 1886, she became interested in the geometrical relationship between binocular vision and points in space and published a paper on this topic in the first volume of the American Journal of Psychology the following year. During the 1891-92 academic year, Ladd-Franklin took advantage of her husband's sabbatical leave from Johns Hopkins and traveled to Europe to conduct research in color vision in the laboratories of George Müller (1850-1934) in Göttingen, and Herman von Helmholtz (1821-1894) in Berlin, where she also attended lectures by Arthur König. In contrast to the prevailing three-color and opponent-color explanations of color vision, Ladd-Franklin developed an evolutionary theory that posited three stages in the development of color vision. Presenting her work at the International Congress of Psychology in London in 1892, she argued that black-white vision was the most primitive stage, since it occurs under the greatest variety of conditions, including under very low illumination and at the extreme edges of the visual field. The color white, she theorized, later became differentiated into blue and yellow, with yellow ultimately differentiated into red-green vision. Ladd-Franklin's theory was well-received and remained influential for some years, and its emphasis on evolution is still valid today.

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