Lewis's research on race culminated in the 1942 publication of The Biology of the Negro, a lengthy text summarizing the scientific literature on the demographic, anatomical, physiological and biochemical characteristics of the black population.

In 1922, Lewis published a paper on the frequency of ABO blood types in African-Americans in the Journal of the American Medical Association.

[2][3] The Sprague Institute awarded him a grant in 1922 to research "pathology among Negroes in all countries",[4] and in 1926, he earned a Guggenheim Fellowship for immunology studies at the University of Basel.

[1][5] In 1942, Lewis published the culmination of the work he had begun 20 years ago: a 400-page volume titled The Biology of the Negro, drawing on medical and anthropological studies from more than 1,300 different researchers.

The book—"nothing more than an arranged assembly of the observed and reported facts concerning the biology, including the pathology, of the Negro", as Lewis described it—provided an extensive overview of the literature on racial differences, spending, for example, 35 pages on a discussion of black skin.

[3] A 1942 review in the Journal of the National Medical Association stated " [i]t is noteworthy that the author failed to discover any fundamental evidence to show that the Negro is biologically inferior to other groups".

[9] Lewis's position on sickle cell disease was later characterized by Keith Wailoo as "an endorsement and legitimation of cherished racial categories through blood analysis".

The next year, he asked the Sprague Institute to fund the establishment of a laboratory dedicated to the study of racial differences at the Provident Hospital.

The Institute agreed to finance the project, but the plans never materialized; the death of Lewis's wife that year may have played a role.