Blue spent his early years in the MHS at the front lines of turn-of-the-century public health, participating in the medical inspection of immigrants of the United States and battling outbreaks of epidemic disease.

[1] Upon arriving Blue was able to organize a conference between the federal, state, civil and business leaders of the area to discuss the sanitation conditions in Chinatown, where the majority of plague cases were aggregated within the city.

[1] Funding for these sanitation campaigns lasted from 1903 through 1905 at which time San Francisco was declared plague free due to a decrease in mortality rate within Chinatown and the lack of any new cases reported to officials.

[1] When he wasn't trapping rats and squirrels in California, Blue directed mosquito eradication efforts to control yellow fever in New Orleans (1905), at the Jamestown Exposition (1907), and in Honolulu (1911), to help Hawaii prepare for traffic to follow the opening of the new Panama Canal.

The Act stepped up Federal public health activities, most notably in response to repeated outbreaks of typhoid fever that tore through cities and towns that drew drinking water from increasingly contaminated supplies.

PHS received authority to initiate field research independently of county and state health departments and to extend campaigns against infectious disease toward the control of occupational and environmental threats.

Under Blue's leadership, physician researchers at PHS turned the new science of bacteriology and the age-old practices of sanitation and public education to effective use against diseases linked to poverty in both rural and urban areas.

In response, PHS established venereal disease control programs with funding from the Red Cross, provided industrial hygiene and health services for the thousands of workers laboring in war plants and the communities surrounding them, emptied swamps and sprayed for mosquitoes to prevent malaria, and built sanitary privies.

Blue's public health infrastructure was up and running by the time that Congressional support came, in the form of earmarked dollars and a statute covering the control and prevention of venereal disease (the Chamberlain Act of 1918).

Over the following year, PHS assembled a network of fourteen district offices and transformed war surplus facilities into hospitals and clinics, scrambling for staff and resources to stretch the $10.5 million given by Congress to fund the new program.

He resumed the rank of Assistant Surgeon General and was assigned to Paris, France, to oversee PHS operations in Europe and to serve as U.S. delegate to the Office International d’Hygiene Public (1920–1923) and subsequently to the League of Nations.