He was one of the founding staff members of the University of Chicago Medical School, where he remained for the duration of his professional research career.

[1] Notable students of Professor Huggins included Howard Guy Williams-Ashman, Shutsung Liao, Paul Talalay and A. Hari Reddi.

However, he eventually felt this bone work was unlikely to lead to medical progress, and set it aside in favor of studying the male urogenital tract.

Through the 1930s, Huggins published work characterizing the constituents of semen and which organ (seminal vesicles or prostate) they derive from.

[8] In 1939, Huggins described a method for isolating prostate fluid from dogs, which served as the foundation for much of his subsequent work.

[1][8] In 1940 and 1941, Huggins – along with students Clarence V. Hodges and William Wallace Scott – published a series of three papers detailing his most famous finding: that counteracting androgen activity by orchiectomy (surgical removal of the testicles) or estrogen treatment shrank tumors in many men with metastatic prostate cancer.

These assays relied on chromogenic substrates (substances that change color in response to a given enzyme), a term Huggins coined, and a concept he pioneered.

[8] In the 1950s, Huggins went on to show an analogous relationship between sex hormones and breast cancer – tumor growth was stimulated by estrogens, and slowed by androgens.

His son, Charles E. Huggins, was also a surgeon, and directed the Massachusetts General Hospital blood bank until his death in 1990.