[19] In 1969, he joined Donald Crothers’ laboratory as a National Institutes of Health (NIH) postdoctoral research fellow in the department of chemistry at Yale University.

DeLisi was subsequently appointed senior scientist (1975–1982) at the National Cancer Institute, NIH, and founding head of the Section on Theoretical Immunology (1982–1985), where he and his collaborators established one of the earliest protein and DNA sequence databases fully integrated with machine learning programs for functional inference[13] and developed a number of analytical methods that proved useful in cell biology.

[11][20][14] In 1986, as director of the U.S. Department of Energy's (DOE) Health and Environmental Research Programs, DeLisi and his advisors proposed the Human Genome Project to the White House Office of Management and Budget and the Congress.

The proposal created much controversy but received strong endorsement from Alvin Trivelpiece, who was chief of DOE's Office of Science, and William Flynn Martin, the Deputy Secretary of Energy.

Computer scientists, in particular, transformed the topic and created a record of discovery destined to provide much material for studying the sociology of late 20th and early 21st century science.