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One day field worker George Cowan brought in a mountain goat covered with nearly a thousand engorged ticks. The researchers plucked the ticks off and decided to see what would happen when they ground them up and injected them into healthy guinea pigs. Every guinea pig got sick and died. The control group were guinea pigs that had been injected with ground-up unfed ticks; they did not get sick.

To be sure of the results, Spencer took some unfed ticks, attached them to a sick guinea pig to feed, ground up the ticks, and injected them into healthy guinea pigs. They all died. As Lucy Salamanca dramatically wrote:

“They had proved it was the meal of blood that had turned a harmless tick into an agent of death!”

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Ticks feed among the hair

Ticks feeding on guinea pig. Taken in 1931.

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Image: Office of NIH History and Stetten Museum, 1465-3

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Dr. Ralph Parker and his group at the Canyon Creek Schoolhouse laboratory became responsible for raising ticks and guinea pigs to feed them. The guinea pigs lived in cages swathed with white cotton as shown in this photo, which was taken in 1931 in Building One. The researchers studied the tick life cycle and fed them on many different animals to see which animals gave the RMSF bacteria to the ticks. They would carefully label the ticks by lot number.

Spencer took Lot 2351-B in a pillbox to the Hygienic Laboratory (precursor to the NIH) in Washington, D.C. to test them. These ticks were known to carry RMSF. After they were warmed up to get the pathogen active, they were fed on infected guinea pigs, so that they had been exposed to RMSF two times. They proved to be particularly virulent after they were fed, with more infectious material per weight than guinea pigs could produce.

Spencer had discovered that ticks were “a more efficient culture media than the guinea pig” if they went through incubation and feeding first.

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A man works at a desk in the animal area with a rack of cages covered in white cloth and a rack of uncovered cages.

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Image: Office of NIH History and Stetten Museum, 1490-1

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It was from a pan full of engorged, doubly-infected ticks like the one shown here that Spencer decided to try to make a vaccine by grinding the ticks with phenol (also known as carbolic acid, a strong disinfectant). He injected the ground-up ticks into healthy guinea pigs to vaccinate them. Then he infected both the vaccinated guinea pigs and unvaccinated guinea pigs with RMSF; the vaccinated guinea pigs did not get sick, while unvaccinated ones died.

“The feasibility of human vaccination also naturally arises,” he wrote in his 1924 paper describing these studies. And he adds that he tried the vaccine on one human, with no ill effects. The human was himself.

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A white enameled pan of engorged ticks

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Image: Office of NIH History and Stetten Museum, 1465-1

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This bottle of Rocky Mountain spotted fever vaccine from the early 1940s represents much scientific work and practical experimentation. There were no strict research protocols for vaccine development and testing in the early 19th century. There was no oversight or approvals from the Food and Drug Administration. The Hygienic Laboratory (NIH’s precursor) had regulatory authority, testing commercial vaccines for safety and effectiveness. Spencer worked at the Hygienic Laboratory and was certainly familiar with the tests required to prove that a vaccine worked safely and at what dose it should be given, as well as the standards for producing a safe vaccine. He knew proving that his RMSF vaccine worked would take more than inoculating himself with it.

After experimenting with different combinations of fed vs. unfed ticks and ticks in different stages of their life cycle to get the highest concentration of RMSF in the vaccine, Spencer and Parker were ready for the next step.  In February 1925, they conducted an experiment in 18 monkeys to see if the vaccine was effective and safe. None of the vaccinated monkeys died; all of the unvaccinated monkeys did.

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Image: Courtesy of Dr. Marshall Bloom

Next was to test the vaccine on people, and the Canyon Creek Schoolhouse laboratory staff became the participants in this early clinical trial. Thirty-four laboratory and field workers were vaccinated, and none had a severe reaction.

There were questions about the vaccine: what was the optimum dose? How long did immunity last? And how long did it take to gain immunity after being vaccinated? That last question was answered in April 1925, when a cattle-dipper for the Montana State Board of Entomology was vaccinated. He came down with RMSF a few days later but recovered. Four other people in the Bitterroot Valley who also got RMSF at the same time, but had not been vaccinated yet, all died. From this unplanned experience, Spencer and Parker learned the time required to gain immunity after vaccination: 10 days

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Vaccine Production Steps

In 1925, Drs. Roscoe Spencer and Ralph Parker described their method for creating RMSF vaccine. The method would become more streamlined and automated after they moved into the Building One laboratory in 1928 and got better space and equipment than the Canyon Creek Schoolhouse laboratory could provide. These photos include some taken at Building One after the laboratory moved from the schoolhouse.

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