On June 24, President Truman signed the National Dental Research Act. The measure was inspired by revelations that more than 20 percent of wartime inductees could not meet baseline dental requirements and concerns about a postwar shortage of dentists. The act was supported by influential proponents in the American Dental Association and in Congress.

Trendley Dean was the 20th century's most influential dental scientist and administrator. In the 1930s, Dean was the first dental officer at NIH. In the 1940s his studies proved fluoridated water curbed dental caries. After becoming NIDR director in 1948, Dean put in place the structure prevailing today, although his focus was more on training and intramural research than extramural activities. Dean won the Lasker Award in 1952 and retired the next year.

Rachel Harris Larson was the first woman scientist in the NIDR intramural program. Larson began at the NIH Industrial Hygiene Laboratory in 1942 and was among the first 27 staff members hired by NIDR, earning M.S. and Ph.D. degrees in chemistry during off hours. Larson's research involved microbiological and genetic studies of dental caries in rats. Read the NIH Record story about Dr. Larson and her sister, “Dot” Murphy, a fellow long-time NIH employee.

Francis Arnold was Trendley Dean's assistant in the Grand Rapids fluoride study. Becoming NIDR director in 1953, Arnold continued Dean's emphasis on caries research and extended it into periodontal studies, genetics, and investigation of cleft lip and palate. Arnold expanded training and built up the intramural program, opening a dedicated lab in 1963. Arnold retired in 1966.

American Dental Association research fellow Edward Hampp was the first microbiologist at NIDR. In 1949 Hampp isolated the spirochete that caused acute necrotizing ulcerative gingivitis, or "trenchmouth," and laid the foundation for a strong periodontal disease program at NIDR.

Carl J. Witkop, Jr. was a specialist in inherited dental abnormalities. By 1956, studies of a tightly-knit Southern Maryland community convinced Witkop that dentinogenesis imperfecta was hereditary. In 1957 Witkop established the NIDR Section on Human Genetics, the first intramural genetics laboratory at NIH and edited the first textbook on dental genetics in 1962.

As inventors devised ever-faster dental drills, concerns grew about damage to dental pulp. In the mid-1950s, NIDR scientists Harold Stanley and Herbert Swerdlow evaluated different tools, speeds, and coolants and set guidelines enabling widespread adoption of high-speed drills. This "applied" research effort made NIDR a leader in studies of the nerves, blood vessels, and connective tissues in the dental pulp.