[2] Lushbaugh started his career in 1939 as a professor in the Department of Pathology at the University of Chicago, while he was working towards his Ph.D. His early medical research was directed by the onset of World War II, and resulted in the discovery of the chemotherapeutic potential of compounds being tested as chemical weapons.

After completing his medical degree from the school in 1948, he joined the Los Alamos National Laboratory as a pathologist, and began to develop expertise applying the science to victims of radiological accidents.

Lushbaugh identified an opportunity to analyze Kelley's remains to confirm or improve Los Alamos safety procedures concerning radiation exposure.

To this end, Lushbaugh extracted some of the irradiated organs and tissues from Kelley for analysis, eventuating the development of safer radiation exposure limits.

The propriety of the removal of Kelley's organs was eventually called into question, and his daughter filed a successful lawsuit against Lushbaugh and Los Alamos in 1996.

[5] Though the complication was originally described in 1926 by J. R. Meyer at the University of São Paulo, Lushbaugh and Steiner's 1941 report was considered a landmark publication that enabled widespread recognition of the diagnosis within the medical community.

[1][7] His thesis, titled The Effect of Alcoholic Intoxication Upon Acquired Resistance to Pneumococcal Infection in Rabbits, was published the following year in the Journal of Immunology.

Former research assistant John B. Storer recalled:[1] I worked part-time in Lush's laboratory while I was in medical school and returned full-time as a Fellow after my internship.

[2] On December 30, 1958, at the Los Alamos laboratory, 38-year-old chemical operator Cecil Kelley was involved in a criticality accident in which he absorbed 36 gray of ionizing radiation from a mixing tank containing highly concentrated plutonium-239.

As an employee of Los Alamos directly involved in the handling of radioactive materials, Kelley had given urine samples before he died, and now with his autopsy and the circumstances that preceded it, Lushbaugh identified a unique opportunity to confirm the validity of those tests and associated exposure limits, as well as ascertain the distribution of plutonium throughout the organs and skeleton.

[12] He also made this type of tissue removal part of the standard procedure for autopsies at Los Alamos, for both employees and non-employees, the latter of whom would act as a control group.

[9] To this end, when the next-of-kin was asked to authorize an autopsy at Los Alamos, a provision was included in the form to allow, at the discretion of the examining physician, the removal of tissues and other specimens for research purposes.

Starting in 1960 and continuing until 1974, around 89 patients who were admitted to the Medical and Health Sciences Division clinic for cancer treatment were directly exposed to high levels of ionizing radiation as human test subjects.

[2][13] After the conclusion of the experiments, an AEC review board questioned their propriety, empirical value, and actual benefit to the patients who unwittingly participated in the program.

[2][13] In a later interview Lushbaugh would propose several instances of positive outcomes from individuals in the programs, and a colleague said that the procedures under the purview of his experiments were still customized to the specific condition of each patient.

[2] He also later stated that he was not directly responsible for selecting which patients referred to the clinic would be placed in the experiment, though it was attested by several others that he was among the senior staff that formed the committee which made such decisions.

[15] The facility became a major resource for education and emergency response coordination concerning radiological accidents, and is a key consulting body for the National Nuclear Security Administration, part of the Department of Energy.

[18] Lushbaugh returned to academia in 1980, joining the faculty of the School of Public Health at the University of North Carolina at Chapel Hill as an adjunct professor of epidemiology.

[13][20] He would jokingly describe himself as a "cantankerous bastard",[4] and his nameplate from his desk at Oak Ridge National Laboratory read "HSOBIC" – Head Son-of-a-Bitch In Charge.

[21] Lushbaugh's first marriage to Mary Helen Chisolm in 1942 produced three children – William, who was a professor at the University of Mississippi, and Bob and Nancy, both of whom worked at Oak Ridge National Laboratory.