It was in this emergency that the federal government appointed Oswaldo Cruz, who had recently arrived on a long-term internship in Paris, mainly at the Pasteur Institute, to, together with Adolpho Lutz and Vital Brazil, appointed by the government of São Paulo, verify the real etiology of the Santos epidemic. Officially confirmed that "the prevailing disease in Santos is the bubonic plague", the health authorities decided to establish laboratories for the production of vaccine and serum against the plague: Instituto Butantan, in São Paulo, and the Instituto Seroterapico Municipal in Rio de Janeiro.

The Serotherapy Institute was the result of a suggestion made by Barão de Pedro Affonso - a surgeon of recognized competence, founder of Instituto Vacínico, the first laboratory to produce smallpox vaccine in the country - to the Mayor of the Federal District, Cesário Alvim, who ceded the Farm of Manguinhos, conveniently located away from the urban centre. The Baron intended to hire a specialist from the Pasteur Institute for the technical direction, but on the recommendation of Émile Roux he offered the position to Oswaldo Cruz.

With the list of material to be acquired, organized by the new technical director, the Baron left for Europe. In Paris he managed to hire only the veterinarian Henri Carré, Yersin's collaborator in the production of the first anti-plague vaccine; is that the Brazilian government had only authorized him to offer unattractive contracts in addition to being inoperative, for a maximum period of six months.

Once the laboratories were installed, work began, without any ceremony, on May 25, 1900, under the weight of an enormous task to be fulfilled, in addition to the administrative and technical directors, by three professionals - Colonel-Doctor Ismael da Rocha, bacteriologist from the Army Health Service; physician Henrique de Figueiredo Vasconcellos, assistant at the Vaccine Institute; and veterinarian H. Carré - and a medical student, Ezequiel Caetano Dias. However, the Municipality soon found itself unable to continue maintaining the new institution, which was transferred to the Public Health Directorate of the Ministry of Justice and Interior Affairs, and officially opened on July 23 as the Federal Serotherapy Institute.

Shortly after, the initial team was short of two components: Ismael da Rocha, called back to the Army laboratory, and Carré, who was returning to France with health problems, according to some, or fear of yellow fever, according to others. But the competence of the rest was already proven, and it was deemed necessary only to hire a medical student, Antônio Cardoso Fontes, and some assistants.

None of the remaining five had any experience with a plague vaccine or serum. Only Oswaldo Cruz had visited the serum section of the Pasteur Institute, but his interest was in the preparation of diphtheria antitoxin. Both in relation to the vaccine and the serum, the data available in the scarce literature lacked precise details that would allow its preparation outside the producing laboratories.