Canyon Creek Schoolhouse Laboratory 100^th Anniversary

Life cycle of ticks

Studying the life cycle of ticks provided important pieces of the RMSF puzzle. Knowing the life cycle meant that scientists could study questions such as: When did the ticks pick up the bacteria causing RMSF—was it when they were newly hatched? When they were adults? And was the infection passed on to a new generation of ticks through the eggs? The answers to these questions could be used in control efforts and in developing a new vaccine.

The life cycle of the tick: a fertilized female lays thousands of eggs on the ground. When they hatch as larvae, they attach to small animals and feed. Then they drop off to digest their meal, and molt (shed their old shell) to become nymphs. The first winter they spend as unfed nymphs.

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Constant collecting

As RMSF gave up its mysteries, researchers still had other tick-borne diseases to study. They constantly collected ticks where outbreaks of Rickettsial diseases occurred.

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In 1929, LeRoy Jones, Harley G. Sargent, Harry L. Sargent, and James Kerlee posed at the top of Blodgett Canyon in the Bitterroot Range. Each holds several white cloth bundles tied to a stick for specimen collection. James Kerlee’s brother, Arthur LeRoy Kerlee, had died the year before of RMSF that he had acquired in the laboratory.

Image: Office of NIH History and Stetten Museum, 1449

Diagnostic test

In a world filled with ticks and the diseases they carry—and diseases that have similar symptoms—being able to diagnose a disease quickly might be beneficial for treatment or for clues to how to control it. The classic feature of RMSF, the rash, appears days after the initial infection. The other symptoms can be confused with diseases such as typhus.

In 1916, the Weil-Felix reaction was developed to diagnose epidemic typhus. In 1928, LeRoy Kerlee and Dr. Roscoe Spencer did their own tests on guinea pigs, rabbits, and people at the Canyon Creek Schoolhouse laboratory. They reported that the Weil-Felix reaction could diagnose RMSF. The test became widely used to diagnose many Rickettsial diseases; although it has been replaced by newer diagnostic techniques such as indirect immunofluorescence, it can be useful in parts of the world without access to such technology.

Kerlee and Spencer’s results were published shortly after Kerlee died of Rocky Mountain spotted fever in 1928. Learn more about Kerlee [link to his bio].

“Rocky “Rocky Mountain Spotted Fever: A Preliminary Report on the Weil-Felix Reaction,” A. L. Kerlee and R. R. Spencer, Public Health Reports (1896-1970), Vol. 44, No. 4 (Jan. 25, 1929), pp. 179-182

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Overlooking Hamilton, Montana, where the Canyon Creek Schoolhouse laboratory was located. How many ticks were in that valley?

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The best way to deal with a deadly disease is to not get sick with it. But avoiding a disease can depend on how it’s spread, where you live or what you do for a living, and the possibility for a protective vaccine.

Control efforts

Because it was known that ticks carried RMSF, one way to eradicate the disease was to keep people from getting bitten by infected ticks. That could mean changing the way that ranchers, shepherds, woodsmen, and others did their jobs. Or it could mean eradicating the animal hosts of the tick in an area of heavy infection. Both methods were tried. 

There was another approach to tick control: eradicating the rodents and other small animals in an area where RMSF outbreaks occurred, often by using poison. The attempt to eradicate small animals in areas infested with RMSF failed; it wasn’t clear which animal or animals gave the infections to ticks, and new animals kept moving in.

Inventing the Vaccine

Dr. Roscoe Spencer came to the Canyon Creek Schoolhouse laboratory from Washington, D.C., in spring 1921, when the ticks were out. After the laboratory’s field workers collected ticks, Spencer would test the ticks for RMSF by taping them to a guinea pig; if the guinea pig came down with RMSF, the ticks were infected. But this process was messy and dangerous and slow, so he decided to grind up the ticks and inject them under the skin of the guinea pigs. Still, none of them got sick. Then he took samples from guinea pigs that were sick with RMSF. He injected the samples into guinea pigs that had been injected with ground-up ticks and into those guinea pigs that had not. The guinea pigs that had previously been injected with the ground-up ticks did not get sick.

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Dr. Roscoe Roy Spencer.

Image: National Library of Medicine, 101429481

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!”

(Quote from “Tick Conquered,” Lucy Salamanca, Washington Evening Star, March 28, 1937, page F-4.) (24 kB)

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Ticks feeding on guinea pig. Taken in 1931.

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

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.and feeding first.

(Quote: "Rocky Mountain Spotted Fever: Experimental Studies on Tick Virus" Roscoe R. Spencer and Ralph R. Parker, Public Health Reports, Vol. 39, No. 48, November 28, 1924, pp. 3027-2040) 1.3 MB(Quote: 1924 Experimental Studies.)

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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 with 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.

(Quote: "Rocky Mountain Spotted Fever: Experimental Studies on Tick Virus" Roscoe R. Spencer and Ralph R. Parker, 1924)Public Health Reports, Vol. 39, No. 48, November 28, 1924, pp. 3027-2040) 1.3 MB

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

The recipe for RMSF vaccine:

Because you use adult ticks, you have to start when the ticks are young the spring before to create a vaccine for the next spring.

1. Lab-reared adult ticks without RMSF are used. Feed female ticks to engorgement on rabbits and mate them.

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       2.  Put the females put in separate pill boxes, give the box a lot number, and place the box over moist sand so they can lay eggs.

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3.  After the eggs hatch, feed the whole group of larvae on infected rabbit. Do the same after they molt and become nymphs (as shown in the tubes) on a non-infected rabbit.

4.  After each feeding, inject a few ticks into a guinea pig’s abdomen to see if the guinea pig gets RMSF. Then you know the ticks are infected too.

5. After the ticks molt to become adults, keep them a month to let the RMSF infection grow in them.

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Image: Office of NIH History and Stetten Museum, 1486

10.  Let the mixture sit at room temperature for two or three days. A heavy precipitate is formed as seen in the photo, and extraneous organisms are killed as shown by anaerobic and aerobic sterility tests.

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12. Bottle the vaccine in a sterile environment.

The dosage is difficult to determine, but “Such irregularities are not surprising, however, when we recall that so little is known of the various factors affecting the process and mechanism of immunity.”

(1925, page 2160 Monkeys). Quote: "Rocky Mountain Spotted Fever: Vaccination of Monkeys and Man," Roscoe R. Spencer and Ralph R. Parker, Public Health Reports, Vol. 40, No. 41, October 9, 1925, pp. 2159-2167)  5.5 MB

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The residents of the Bitterroot Valley, Montana, where the most people died from RMSF, were also vaccinated. In the photo, families lined up outside a local school in Darby to be vaccinated. Dr. R. R. Hayward, a local physician (in a white lab coat), administered the vaccine to a man in his left arm. The town of Darby had lost Arthur Kerlee to the disease when he was working at the Canyon Creek Schoolhouse laboratory. 

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In this photo, vials of the Spencer-Parker RMSF vaccine sit on the letter or telegram requesting the vaccine from places all over the United States. The Canyon Creek Schoolhouse laboratory was producing as much of the vaccine as possible, but demand for the vaccine exceeded the supply, making the construction of a new building designed specifically for scientific research and vaccine production necessary—Building One of the Rocky Mountain Laboratories.

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