He was a professor at the University of Pennsylvania, wrote several editions of a textbook on medical problems in women, and was named a Fellow of the American Association for the Advancement of Science.

Penrose held two doctorates, which he earned concurrently: a medical degree from the University of Pennsylvania and a Ph.D. in physics from Harvard College.

He was interested in the idea of facilitating surgical site drainage in abdominal surgery patients, but he was concerned about the risks of the drains available in the late 19th century.

The family's proximity to the Delaware and Schuylkill Rivers allowed the Penrose brothers to enjoy fishing, ice skating, and swimming.

[3] Later, he and his brother Boies attended Episcopal Academy in Newtown Square, Pennsylvania, where they excelled academically with grade-point averages that fell within 0.1 percentage points of each other.

Penrose was 15 months younger than Boies, but they went off to Harvard College at the same time, living together in Boston in a house owned by an aunt.

[4][9][10] Penrose completed a physics degree at Harvard with highest honors in 1881, graduating at age 19, two months after his mother died of tuberculosis.

[14] While he was a resident, Penrose participated in research with Jacob Mendes Da Costa on the diuretic effects of injected cocaine.

The resulting article, "Observations on the diuretic influence of cocaine", was published in a local medical journal called The College and Clinical Record.

By early the next year, he had gained 20 pounds (9.1 kg)[13] Returning to Philadelphia, Penrose was hired as Professor of Gynecology for the medical school at the University of Pennsylvania in 1893, succeeding William Goodell.

[14] He authored the Text-Book on Diseases of Women (1897), which the Cincinnati Lancet-Clinic described as a concise text that was well-suited for medical students and general practitioners.

"[18] Along with Herbert Fox and Ellen Corson-White, Penrose established the study of zoo-based pathology in North America.

By 1924, as chairman of the hospital's board of directors, Penrose recommended that the facility be abandoned because it was only filled to ten percent of its capacity.

[32] While he was at the Cheyenne Club recovering from tuberculosis, Penrose agreed to serve as the surgeon on an invasion led by a group of cattlemen, the Wyoming Stock Growers Association (WSGA).

[13] Penrose was friends with the novelist Owen Wister, whose most well-known work was The Virginian, a fictionalized version of the events of the Johnson County War.

"[34] When two alleged cattle rustlers, Nate Champion and Nick Ray, were ambushed and killed by a group of the cattlemen, Penrose was among the suspects arrested.

Governor Barber, who had also been a longtime friend of the cattlemen, intervened; he had Penrose brought back to the Cheyenne Club by a U.S. marshal on a writ of habeas corpus.

Penrose parroted some of the myths that were widely held by the group, such as the thought that Cattle Kate needed to be killed in the interests of the country.

However, Penrose also expressed ideas that differed from those held by the men of the WSGA, such as the admission that the cattleman invaders had started north with the goal of targeting 70 specific people, including Nate Champion.

[13] Penrose, who stood six feet (183 cm) tall with an athletic build, was very physically active as a young man, having once traveled on horseback from Philadelphia to Niagara Falls and back.

[41] Penrose made what was supposed to be a brief trip back to Philadelphia to visit relatives, and he was accompanied by two nurses and a cousin named Sarah.